Kinase crystal structures

FIELD OF THE INVENTION

[0001] The present invention relates to the enzyme protein kinase B (PKB/Akt), and in particular its crystal structure and the use of this structure in drug discovery.

BACKGROUND TO THE INVENTION

[0002] Protein kinase B (PKB/Akt) is a component of an intracellular signalling pathway of fundamental importance that functions to exert the effects of growth and survival factors, and which mediates the response to insulin and inflammatory signals (Datta et al., 1999; Brazil and Hemmings, 2001). The enzyme is rapidly activated by phosphorylation following stimulation of phosphoinositide 3-kinase, and generation of the lipid second messenger phosphatidylinositol 3,4,5 trisphosphate [PtdIns(3,4,5) P3]. Activation of PKB occurs by a multi-step mechanism. PKB is first recruited to the membrane by association with PtdIns(3,4,5) P3 mediated by its N-terminal pleckstrin homology domain in a process that also induces a conformational change of the protein. In this state, PKB is a substrate for phosphorylation at two regulatory sites by membrane-localised kinases (Meier et al. 1997). PDK1 phosphorylates PKB on a Thr residue (Thr-308 of PKBα, Thr-309 of PKBβ, Thr-305 of PKBγ) within the activation segment, stimulating its activity by 30-fold (Alessi et al., 1996a; 1997). A distinct kinase activity, termed PDK2, phosphorylates PKB at a Ser residue of a C-terminal hydrophobic motif (Ser 473 of PKBα, Ser-474 of PKBβ, Ser-472 of PKBγ). Phosphorylation of Ser-474 promotes a 7-10-fold stimulation (Alessi et al., 1996a), which is synergistic with pThr-309 so that phosphorylation of both sites results in an ˜300-fold elevation of protein kinase activity. Whereas PDK1 is well characterised, the identity of PDK2 (also designated Ser-473 Kinase) remains controversial.

[0003] Activated PKB phosphorylates numerous cytosolic and nuclear proteins to regulate cell metabolism, growth and survival. In the insulin signalling pathway, PKB phosphorylates GSK-3, PFK2 and mTOR, inducing glycogenesis and protein synthesis, and regulates glucose uptake by promoting the translocation of Glut4 to the plasma membrane. Cell survival and transformation are controlled by phosphorylation of BAD, caspase-9, forkhead transcription factors and IκB kinase, promoting proliferation and suppressing cell apoptosis (Datta et al., 1999). A mechanism by which PKB stimulates cell cycle progression is by phosphorylation of the CDK inhibitors p21WAFl and p27KiP1, causing their retention in the cytoplasm (Zhou et al., 2001), whereas in contrast, PKB mediates nuclear localisation of mdm2 and subsequent regulation of the mdm2/p53 pathway (Mayo and Donner, 2001). In humans, the three isoforms of PKB are highly conserved, with a mean sequence identity of 73%, and share the same regulatory phosphorylation sites. However, a splice variant of PKBγ lacks the C-terminal regulatory phosphorylation site, and interestingly, the specific activity of this splice variant, isolated from stimulated cells, is ˜10-fold lower than the full length γ isoform, a value which is consistent with the role of the C-terminal phosphorylation site to stimulate PKB activity (Brodbeck et al., 2001). CTMP is a negative regulator of PKBα, which by binding to the C-terminal region of the protein, suppresses phosphorylation of Thr-308 and Ser-473 (Maira et al., 2001).

[0004] PKB plays an important role in the generation of human malignancy. The enzyme is the cellular homologue of v-Akt, an oncogene of the transforming murine leukaemia virus AKT8 isolated from a mouse lymphoma (Staal et al., 1977). Viral-Akt is a fusion of the viral Gag protein with the PKBα sequence (Bellacosa et al., 1991). Myristoylation of the Gag sequence targets v-Akt to the cell membrane, resulting in its constitutive phosphorylation. The genes for the α and β isoforms of PKB are over-expressed and amplified in ovarian, prostate, pancreatic, gastric, and breast tumours (Testa and Bellacosa, 2001). Compelling evidence linking PKB to oncogenesis stems from the elucidation of the mechanism of the PTEN tumour suppressor gene. PTEN is one of the most commonly mutated genes in human cancer and somatic deletions or mutations of PTEN have been identified in glioblastomas, melanoma and prostate cancers, and are associated with increased susceptibility to breast and thyroid tumours (Cantley and Neel, 1999). PTEN negatively regulates the PI-3 kinase/PKB pathway by dephosphorylating PtdIns(3,4,5)P3 on the D-3 position, and therefore loss of PTEN activity leads to a constitutive cell survival stimulus (Maehama and Dixon., 1998; Myers et al., 1998).

[0005] Protein kinase B is a member of the AGC-family of serine/threonine specific protein kinases that also includes PKA, PKC, PDK1 and the p70 and p90 S6-kinases (Coffer and Woodgett, 1991; Jones et al., 1991a). As well as being structurally related, AGC-protein kinases share numerous functional similarities such as activation in response to second messengers and dependence on phosphorylation for activity. Members of the family are phosphorylated on a conserved Thr-residue within their activation segment. In vitro PDK1 is capable of phosphorylating AGC-kinases on this position (Vanhaesebroeck and Alessi, 2000), although recent studies using PDK1 deficient ES cells suggest that PDK1 activity is only necessary for PKB and a subset of other AGC-kinases (Williams et al., 2000). The site of C-terminal regulatory phosphorylation of PKB (Ser-474) is within a hydrophobic activation sequence motif (F-x-x-F-[S/T]-Y), conserved within a large proportion of AGC-kinases (Keranen et al., 1995; Pearson et al., 1995). In PKB, substitution of Ser-474 with Asp mimics Ser-474 phosphorylation (Alessi et al., 1996a), and significantly, some a typical PKC isoforms and PRK2 (PKC related kinase-2) have Asp or Glu residues at this position. PKA requires phosphorylation of the activation segment Thr residue (Thr-197) for activity (Yonemoto et al., 1997), although this is a constitutive site of phosphorylation, and unlike other AGC-kinases, is resistant to dephosphorylation by protein phosphatases (Shoji et al., 1979). The hydrophobic motif of PKA is also unusual and comprises the sequence -Phe-Thr-Glu-Phe-350, with Phe-350 corresponding to the C-terminus of the PKA catalytic subunit, and therefore the enzyme lacks a site of regulatory phosphorylation. In the structure of PKA, the motif lies within a surface groove formed in the N-terminal lobe, with the side-chains of the two Phe-residues buried deep into the groove (Knighton et al., 1991a,b; Bossemeyer et al., 1993). Other AGC-kinases are likely to have an equivalent groove, and for PDK1, the groove is thought to allow recognition of specific target kinase substrates via their phosphorylated regulatory segment sequences, although this interaction has been suggested not to be essential for phosphorylation of PKB by PDK1 (Biondi et al., 2000; 2001).

[0006] In order to understand the mechanism of activation of PKB by phosphorylation, and as a framework for the rational development of modulators of PKB activity, knowledge of a PKB protein structure would be extremely valuable. Such knowledge would significantly assist the rational design of novel therapeutics for, e.g. the treatment of diabetes, cancer, neurodegeneration and erectile dysfunction, based on PKB modulators.

[0007] Definitions

[0008] In the following by “binding site” we mean a site (such as an atom, a functional group of an amino acid residue or a plurality of such atoms and/or groups) in a PKB binding cavity which may bind to an agent compound such as a candidate modulator (e.g. inhibitor). Depending on the particular molecule in the cavity, sites may exhibit attractive or repulsive binding interactions, brought about by charge, steric considerations and the like.

[0009] By “AGC kinase” is meant any protein kinase comprising a sequence which has a sequence identity of equal to or greater than 35% at the amino acid level with residues 37-350 of the catalytic subunit of PKA (Shoji et al., 1983). Determination of percentage sequence identity may be performed with the AMPS package as described by Barton (1994). AGC kinases are also described in detail by Hanks and Hunter, FASEB J. (1995) 9: 576, and Hardie, G. and Hanks, S. (eds) The Protein Kinase Facts Book—Protein-Serine Kinases (1995) Academic Press Ltd., London).

[0010] By “fitting”, is meant determining by manual, automatic, or semi-automatic means, interactions between one or more atoms of an agent molecule and one or more atoms or binding sites of the PKB, and calculating the extent to which such interactions are stable. Various computer-based methods for fitting are described further herein.

[0011] By “root mean square deviation” we mean the square root of the arithmetic mean of the squares of the deviations from the mean.

[0012] By a “computer system” we mean the hardware means, software means and data storage means used to analyse atomic coordinate data. The minimum hardware means of the computer-based systems of the present invention comprises a central processing unit (CPU), input means, output means and data storage means. Desirably a monitor is provided to visualise structure data. The data storage means may be RAM or means for accessing computer readable media of the invention. Examples of such systems are microcomputer workstations available from Silicon Graphics Incorporated and Sun Microsystems running Unix based, Windows NT or IBM OS/2 operating systems.

[0013] By “computer readable media” we mean any media which can be read and accessed directly by a computer e.g. so that the media is suitable for use in the above-mentioned computer system. Such media include, but are not limited to: magnetic storage media such as floppy discs, hard disc storage medium and magnetic tape; optical storage media such as optical discs or CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media.

DISCLOSURE OF THE INVENTION

[0014] The present invention is at least partly based on overcoming several technical hurdles: the present inventors have (i) produced PKBβ crystals of suitable quality for performing X-ray diffraction analyses, (ii) collected X-ray diffraction data from the crystals, (iii) determined the three-dimensional structure of PKBβ, and (iv) identified binding sites on the enzyme which are likely to be involved in the enzymatic reaction.

[0015] In order to understand the nature of the mechanism of regulation of PKB by PIP3, the N-terminal PH domain and phosphorylation of the regulatory Thr and Ser phosphorylation sites, the present inventors have generated Sf9/baculovirus expression systems for full length PKBα, PKBβ, PKBγ and PDK1 and also a number of modified forms of the three PKB isoforms. They have succeeded in generating crystal structures for both inactive and active conformations of the enzyme.

[0016] Limited trypsinolysis of full length PKBβ purified from Sf9 cells led to the identification of a protease resistant domain with an N-terminus at Lys-146, which we refer to as ΔPH-PKB. Lys-146 is located within the structurally diverse region linking the pleckstrin homology (PH) and kinase domains of PKB, close to the N-terminus of the corresponding β1-strand of PKA. During the course of the purification, partial cleavage of a C-terminal 3 kDa fragment was observed, suggesting conformational flexibility at the C-terminus of the protein. Human PKBα, PKBβ and PKBγ sequences are structurally diverse within a 12 residue region C-terminal to the conserved PP(D/E) motif (residues 452-454 of PKBP), preceding the C-terminal hydrophobic motif, and corresponding to the C-terminus of the PKBγ splice variant. Using this information, the present inventors constructed a number of new PKB baculovirus Fastbac entry vectors for the generation of PKB insect cell/baculovirus expression systems, and expressed the α and β-isoforms of PKB as the kinase domain, with an N-terminus at Lys-146 (i.e. lacking the PH domain), with and without the C-terminal 21 residues that includes the hydrophobic regulatory segment. These two kinase domains are termed ΔPH-PKB and ΔPH-PKB-ΔC, respectively.

[0017] Thus, using this limited proteolysis, the inventors have defined a stable, compact, crystallisable domain of PKB. The systems used express high levels of protein, that the inventors have purified to homogeneity. Moreover, the inventors have expressed PDK1 using the insect cell/baculovirus system and MAPKAPK2 in the E. coli expression system to enable phosphorylation of PKBβ on Thr309 and Ser474, respectively.

[0018] To prepare defined phosphorylated states of PKB, phosphorylation and dephosphorylation reactions were performed using PDK1(for pThr-309) and the non-specific λ-protein phosphatase, respectively. Distinct phosphorylated states of the protein were resolved using hydrophobic interaction chromatography.

[0019] The phosphorylation state of the protein was analysed by Western blots using phospho-specific antibodies, and the stoichiometry and sites of phosphorylation were quantitatively assessed by mass spectroscopic analysis of trypsin-generated peptides of the protein.

[0020] The inventors have succeeded in the expression, purification, crystallisation and structure determination of three forms of PKBβ in the inactive conformation, which differ in their state of phosphorylation.

[0021] The three crystal forms of human PKBβ are; (i) pΔPH-PKB-ΔC (residues 146 to 460, phosphorylated in vitro on Thr-309), (ii) ΔPH-PKB-ΔC(residues 146 to 460, not phosphorylated on Thr-309), and (iii) ΔPH-PKBβ (residues 146 to 481, dephosphorylated in vitro).

[0022] Two batches of crystals were prepared for crystal form (i), i.e. pΔPH-PKB-ΔC. Summaries of coordinate data, having different resolutions, are provided for each of these crystals (Table 1 below). Thus, data are provided for four crystals in total.

[0023] All four inactive crystals of PKB belong to the same space group and have similar cell dimensions. Summary data for the higher resolution pΔPH-PKB-ΔC crystal, as well as the ΔPH-PKB-ΔC and ΔPH-PKB crystals are shown in Table 1.

[0024] The two crystal preparations of pΔPH-PKB-ΔC diffract to 2.8 and 2.3 Å resolution, when exposed to synchrotron radiation, whereas ΔPH-PKB-ΔC and ΔPH-PKB diffract to 2.7 Å and 2.5 Å respectively.

[0025] The structure of PKB was solved by means of molecular replacement using the ternary complex of mouse PKA (Knighton et al., 1991) as a search object. During initial stages of the refinement, the relative orientations of the N- and C-terminal lobes of the kinase domain were refined, prior to atomic positional refinement (Table 1).

[0026] The resultant structures are believed to provide important insights into the structure activity relationships in the full length PKBβ and its highly homologous isoforms (see Brodbeck et al. 1999). For brevity, as used herein, unless the context demands otherwise, the term PKB is used to encompass full or part-length molecules of any of the three isoforms, which may not or may be phosphorylated e.g. ‘PKBβ’ encompasses the full length PKBβ molecule or a truncated form such as ΔPH-PKBβ (residues 146-481) or ΔPH-PKBβ-ΔC (residues 146-460).

[0027] The present inventors have also produced PKBβ crystals in which PKBβ has adopted an active conformation. This has been achieved by use of two PKBβ constructs based on ΔPH-PKB; one has a S to D mutation at position 474 (designated PKB S474D) while the other (designated PKB-PIF) is a fusion protein comprising residues 146 to 467 of human PKBβ fused to 15 residues from the C terminus of PRK2.

[0028] Each was crystallised as a ternary complex with the nucleotide analogue AMP-PNP and a substrate peptide.

[0029] In general aspects, the present invention is concerned with identifying or obtaining agent compounds for modulating PKB activity, and in preferred embodiments identifying or obtaining actual agent compounds which are inhibitors or activators. Where, methods of identifying or modelling inhibitors are described hereinafter, the skilled person will appreciate that the processes may be applied analogously to other modulators such as activators.

[0030] Crystal structure information presented herein is useful in designing potential modulators and modelling them or their potential interaction with PKB binding cavities, for example, the PKB substrate binding cavity, ATP binding site, or other region of interest (e.g. the hydrophobic motif, or regulatory phosphorylation sites), preferably the ATP binding site Potential modulators may be brought into contact with PKB to test for ability to interact with the PKB binding cavity. Actual modulators may be identified from among potential modulators synthesized following design and model work performed in silico. A modulator identified using the present invention may be formulated into a composition, for instance a composition comprising a pharmaceutically acceptable excipient, and may be used in the manufacture of a medicament for use in a method of treatment. These and other aspects and embodiments of the present invention are discussed below.

[0031] The present invention provides a crystal of PKBβ having a tetragonal space group P212121, and unit cell dimensions of a=44.94 Å, b=61.00 Å, c=131.32 Å, and more generally a=44.94±0.5 Å, b=61.00±0.5 Å, c=131.32±0.5 Å, preferably a=44.94±0.2 Å, b=61.00±0.2 Å, c=131.32±0.2 Å.

[0032] Alternatively, or additionally, the crystal may have the three dimensional atomic coordinates of Tables 6 or 7. An advantageous feature of the structural data according to Tables 6 and 7 are that they have a high resolution of about 1.6 Å and 1.7 Å respectively.

[0033] Indeed a further aspect of the invention includes within its scope a crystal of protein kinase Bβ (PKBβ) defined by structural data having a resolution of about 1.6 Å.

[0034] The crystallised PKBβ molecules may comprise a mutation corresponding to the mutation S474D in human PKBβ. Additionally or alternatively, the PKBβ may be a fusion protein having a C-terminal tail derived from another AGC kinase, preferably PRK-2. Preferably the C-terminal tail comprises the sequence EEQEMFRDFDYIADW.

[0035] The crystal may comprise the relevant enzyme molecules complexed with either a substrate or substrate analogue, or a nucleotide or nucleotide analogue, or both. The substrate or substrate analogue may be a peptide, for example the GSK-3 peptide described in the Examples below or any suitable substrate as described e.g. in Lawlor and Alessi (2001) (see particularly Table 1) or Manning et al. (2002). The nucleotide or analogue thereof will typically be ATP, or preferably a non-hydrolysable analogue thereof, such as AMP-PNP or ATP-gammaS.

[0036] The coordinates of Tables 6 and 7 provide a measure of atomic location in Angstroms. The coordinates are a relative set of positions that define a shape in three dimensions, so the skilled person would understand that an entirely different set of coordinates having a different origin and/or axes could define a similar or identical shape. Furthermore, the skilled person would understand that varying the relative atomic positions of the atoms of the structure so that the root mean square deviation of the residue backbone atoms (i.e. the nitrogen-carbon-carbon backbone atoms of the protein amino acid residues) is less than 1.5 Å (preferably less than 1.0 Å and more preferably less than 0.5 Å) when superimposed on the coordinates provided for the residue backbone atoms, will generally result in a structure which is substantially the same as the structure of Tables 6 and 7 in terms of both its structural characteristics and usefulness for structure-based analysis, including design of PKBβ modulators.

[0037] Likewise the skilled person would understand that changing the number and/or positions of the water molecules in these structures (where shown) will not generally affect the usefulness of the structure for structure-based analysis. Thus for the purposes described herein as being aspects of the present invention, it is within the scope of the invention if: the coordinates are transposed to a different origin and/or axes; the relative atomic positions of the atoms of the structure are varied so that the root mean square deviation of residue backbone atoms is less than 1.5 Å (preferably less than 1.0 Å and more preferably less than 0.5 Å) when superimposed on the coordinates provided in Tables 6 and 7 for the residue backbone atoms. Reference herein to the coordinate data of Tables 6 and 7 thus includes the coordinate data in which one or more individual values of the Tables are varied in this way.

[0038] Modifications in the native PKBβ crystal structure due to e.g mutations, additions, substitutions, and/or deletions of amino acid residues could lead to variations in the PKBβ atomic coordinates and where such modified forms of PKBβ are being investigated, atomic coordinate data of PKBβ modified so that a ligand that bound to one or more binding sites of PKBβ would be expected to bind to the corresponding binding sites of the modified PKBβ are, for the purposes described herein as being aspects of the present invention, also within the scope of the invention. Reference herein to the coordinates of Tables 6 and 7 thus includes the coordinates modified in this way. Preferably, the modified coordinate data define at least one PKBβ binding site.

[0039] In a further aspect, the invention provides a method for crystallizing a PKB derivative which comprises producing PKB by recombinant production in a host cell, recovering a PKB derivative from the host cell and growing one or more crystals from the recovered PKB derivative, wherein the PKB derivative is a stable protease-resistant form of PKB. The host cell may be of any suitable cell type, for example a eukaryotic cell host, such as a yeast cell, a mammalian cell, or an insect cell. In a preferred embodiment, the host cell is an insect cell, such as an Sf9 cell.

[0040] Typically the derivative lacks all or substantially all of the PH domain. Thus the derivative may be a truncated derivative e.g. truncated to positions 146-460 for PKBβ, or corresponding residues in other isoforms. The derivative may optionally include amino acid residues C-terminal of position 460 in PKBβ or its equivalent, e.g. the C-terminal 21 amino acids of PKBβ. In preferred embodiments the derivative comprises one or more mutations in the C terminal tail, corresponding to the C-terminal 21 amino acids of human PKBβ. Thus the derivative may comprise a mutation corresponding to the mutation S474D in human PKBβ. Additionally or alternatively the derivative may be expressed as a fusion protein with C-terminal residues derived from another AGC kinase such as PRK2 as descibed elsewhere herein.

[0041] The method may further comprise the steps of phosphorylating one or more phosphorylatable residues in vitro with a suitable kinase. For example, PDK1 can be used to phosphorylate Thr-309 in vitro. It has been suggested that MAPKAP 2 kinase can be used to phosphorylate Ser-474 of PKBP/Ser-473 of PKBα (Alessi et al. 1996a). For generation of kinases in the active conformation, the derivative will preferably be phosphorylated at a position corresponding to Thr-309 of human PKBβ.

[0042] Alternatively, the method may comprise the step of dephosphorylation in vitro, to ensure that any adventitious phosphorylation occurring during expression is removed. Numerous suitable enzymes will be known to the skilled person, e.g. the λ protein phosphatase.

[0043] The derivative may be encoded by a vector construct substantially similar to one disclosed herein. The method may include the further step of X-ray diffraction analysis of the obtained crystal.

[0044] Thus, the PKBβ produced by crystallising PKBβ (see the detailed description below) is provided as a crystallised protein suitable for X-ray diffraction analysis.

[0045] The crystal may be grown by any suitable method, e.g. the under oil batch methods as described in the Examples.

[0046] The present invention further provides a recombinant polypeptide comprising the catalytic domain of PKB, the N-terminus of said polypeptide corresponding to Lys-146 of human PKBβ. The polypeptide will typically comprise the full kinase domain which may correspond, for example to amino acid residues 144 to 439 of human PKBα, 146 to 440 of human PKBβ, or 143 to 436 of human PKBγ. In a preferred embodiment the polypeptide comprises amino acids 146 to 460 of human PKBβ, which corresponds to residues 145-459 of PKBα, and 143-456 of PKBγ. It may optionally further comprise the C-terminal region corresponding to amino acids 461 to 481 of human PKBβ or a portion thereof. The recombinant polypeptide may be a mutant or a fusion protein having a mutation equivalent to S474D in human PKBβ and/or be fused to a C-terminal sequence from another AGC kinase. In a preferred embodiment the derivative consists of residues 146 to 467 of human PKBβ fused to the sequence EEQEMFRDFDYIADW.

[0047] Reference to a PKB catalytic domain should be taken to include catalytic domains of mutant PKBs as described below (under ‘Homology Modelling’). The term ‘catalytic domain’ as used herein refers to the structural domain of the protein and should not be interpreted as requiring the polypeptide to have catalytic activity; for example it may contain a mutation which impairs or abrogates activity, e.g. at the active site, but which does not affect the gross structure of the domain.

[0048] The present invention further provides a crystallisable composition comprising a recombinant polypeptide as described above.

[0049] In a further aspect, the present invention provides nucleic acids encoding the polypeptides as described herein. Thus in these nucleic acids, the sequences encoding the catalytic domain are not contiguous with sequences encoding the PH domain of PKB, preferably not contiguous with sequences coding for any amino acids N-terminal of Lys-146.

[0050] The present invention also encompasses a method of making a polypeptide as disclosed, the method including the step of expressing said polypeptide or peptide from nucleic acid encoding it, which in most embodiments will be nucleic acid according to the present invention.

[0051] In another aspect, the invention provides a method of analysing a PKB-ligand complex comprising the step of employing (i) X-ray crystallographic diffraction data from the PKBβ-ligand complex and (ii) a three-dimensional structure of PKBβ to generate a difference Fourier electron density map of the complex, the three-dimensional structure being defined by atomic coordinate data according to Tables 6 and 7. If the PKBβ-ligand complex is crystallised in a different space group to the crystals described herein, molecular replacement methods may be used instead of difference Fourier methods.

[0052] Therefore, in the light of the present disclosure, PKBβ-ligand complexes can be crystallised and analysed using X-ray diffraction methods, e.g. according to the approach described by Greer et al., J. of Medicinal Chemistry, Vol. 37, (1994), 1035-1054, and difference Fourier electron density maps can be calculated based on X-ray diffraction patterns of soaked or co-crystallised PKBβ and the solved structure of un-complexed PKBβ. These maps can then be used to determine whether and where a particular ligand binds to PKBβ and/or changes the conformation of PKBβ.

[0053] Electron density maps can be calculated using programs such as those from the CCP4 computing package (Collaborative Computational Project 4. The CCP4 Suite: Programs for Protein Crystallography, Acta Crystallographica, D50, (1994), 760-763.). For map visualisation and model building programs such as 0 (Jones et al., Acta Crystallography, A47, (1991), 110-119) can be used.

[0054] In another aspect, the invention relates to methods of determining three dimensional structures of target kinases of unknown structure by utilising in whole or in part the structural coordinates provided for PKBβ in any one of the data sets provided herein (Tables 6 and 7).

[0055] The target kinase will typically be homologous to PKB, such as an AGC family kinase (e.g. SGK) (Hanks and Hunter (1995) FASEB J. 9: 576; Hardie, G. and Hanks, S. (eds) The Protein Kinase Facts Book—Protein-Serine Kinases (1995) Academic Press Ltd., London). In particular, it may be an isoform of PKB, such as PKBα or PKBγ. The data provided here relate to the inactive conformation of PKBβ, and so will be useful for determining the structure of the corresponding conformation of other kinases. However, the present invention also extends to the elucidation of the structure of alternative conformations such as active conformations of such target kinases, including PKB, and including the active conformation of PKBβ, or PKB-ligand complexes.

[0056] The primary ways in which the three-dimensional coordinate data of the present invention can be used to solve other target kinase structures are as follows:

[0057] The three-dimensional coordinate data provided herein for PKB may be aligned with an amino acid sequence of a target kinase to match homologous regions of the amino acid sequences, and a structure determined for the target kinase by homology modelling.

[0058] The three-dimensional coordinate data of the present invention may be used to assist in interpretation of a set of raw X-ray crystallographic data obtained for a target kinase, in order to establish a structure for the target kinase.

[0059] Typically, in each of these alternatives, the target structure will be established by the calculation of a set of three-dimensional coordinate data for some or all of the atoms in the target structure.

[0060] Homology Modelling

[0061] Thus the invention provides a method of homology modelling comprising the steps of:

[0062] (a) aligning a representation of an amino acid sequence of a target kinase of unknown structure with the amino acid sequence of PKBβ to match homologous regions of the amino acid sequences;

[0063] (b) modelling the structure of the matched homologous regions of the target kinase on the structure as defined by Tables 6 or 7 of the corresponding regions of PKBβ; and

[0064] (c) determining a conformation (e.g. so that favourable interactions are formed within the target kinase and/or so that a low energy conformation is formed) for the target kinase which substantially preserves the structure of said matched homologous regions.

[0065] The target kinase will typically be a PKB homologue, such as a member of the AGC kinase family. In particular, such a method may be used to determine the structure of the a isoform, γ isoform, or other isoforms of PKB or of related kinases such as the AGC kinase family.

[0066] The term “homologous regions” describes amino acid residues in two sequences that are identical or have similar (e.g. aliphatic, aromatic, polar, negatively charged, or positively charged) side-chain chemical groups. Identical and similar residues in homologous regions are sometimes described as being respectively “invariant” and “conserved” by those skilled in the art.

[0067] Preferably one or all of steps (a) to (c) are performed by computer modelling.

[0068] Homology modelling is a technique that is well known to those skilled in the art (see e.g. Greer, Science, Vol. 228, (1985), 1055, and Blundell et al., Eur. J. Biochem, Vol. 172, (1988), 513). By “homology modelling”, is meant the prediction of related kinase structures based either on x-ray crystallographic data or computer-assisted de novo prediction of structure, based upon manipulation of the coordinate data of Tables 6 or 7.

[0069] The various in silico modelling techniques described in this section and in the other sections of this application may utilize coordinates from any of the crystal data sets provided herein, or from any structure calculated by means of those data sets. To avoid unnecessary repetition, reference is made herein to the coordinate data of Tables 6 and 7.

[0070] “Homology modelling” extends to target kinases, in particular AGC kinases, which are analogues or homologues of the PKB protein whose structure has been determined in the accompanying examples. It also extends to mutants of PKB protein itself.

[0071] In general, comparison of amino acid sequences is accomplished by aligning the amino acid sequence of a polypeptide of a known structure with the amino acid sequence of the polypeptide of unknown structure. Amino acids in the sequences are then compared and groups of amino acids that are homologous are grouped together. This method detects conserved regions of the polypeptides and accounts for amino acid insertions or deletions.

[0072] Homology between amino acid sequences can be determined using commercially available algorithms. The programs BLAST, gapped BLAST, BLASTN, PSI-BLAST and BLAST 2 sequences (provided by the National Center for Biotechnology Information) are widely used in the art for this purpose, and can align homologous regions of two amino acid sequences. These may be used with default parameters to determine the degree of homology between the amino acid sequence of the protein of known structure and other target proteins which are to be modeled.

[0073] Analogues are defined as proteins with similar three-dimensional structures and/or functions and little evidence of a common ancestor at a sequence level.

[0074] Homologues are defined as proteins with evidence of a common ancestor i.e. likely to be the result of evolutionary divergence and are divided into remote, medium and close sub-divisions based on the degree (usually expressed as a percentage) of sequence identity.

[0075] A homologue is defined here as a protein with at least 15% sequence identity or which has at least one functional domain, which is characteristic of PKB, including polymorphic forms of PKB. Typically homologues of PKB will be AGC kinases.

[0076] There are two types of homologue: orthologues and paralogues. Orthologues are defined as homologous genes in different organisms, i.e. the genes share a common ancestor coincident with the speciation event that generated them. Paralogues are defined as homologous genes in the same organism derived from a gene/chromosome/genome duplication, i.e. the common ancestor of the genes occurred since the last speciation event.

[0077] A mutant is a kinase characterized by replacement or deletion of at least one amino acid from a wild type AGC kinase, e.g. PKB. Such a mutant may be prepared for example by site-specific mutagenesis, or incorporation of natural or unnatural amino acids.

[0078] The present invention contemplates “mutants”, and the application of the methods of the present invention to “mutants”, wherein a “mutant” refers to a polypeptide which is obtained by replacing at least one amino acid residue in a native or synthetic ACG kinase with a different amino acid residue and/or by adding and/or deleting amino acid residues within the native polypeptide or at the N- and/or C-terminus of a polypeptide corresponding to a wild-type kinase and which has substantially the same three-dimensional structure as the kinase from which it is derived. By having substantially the same three-dimensional structure is meant having a set of atomic structure co-ordinates that have a root mean square deviation (r.m.s.d.) of less than or equal to about 2.0 Å when superimposed with the atomic structure co-ordinates of the wild-type kinase from which the mutant is derived when at least about 50% to 100% of the Cα atoms of the kinase are included in the superposition. A mutant may have, but need not have, enzymatic or catalytic activity.

[0079] To produce homologues or mutants, amino acids present in the said protein can be replaced by other amino acids having similar properties, for example hydrophobicity, hydrophobic moment, antigenicity, propensity to form or break α-helical or β-sheet structures, and so. Substitutional variants of a protein are those in which at least one amino acid in the protein sequence has been removed and a different residue inserted in its place. Amino acid substitutions are typically of single residues but may be clustered depending on functional constraints e.g. at a crystal contact. Preferably amino acid substitutions will comprise conservative amino acid substitutions. Insertional amino acid variants are those in which one or more amino acids are introduced. This can be amino-terminal and/or carboxy-terminal fusion as well as intrasequence. Examples of amino-terminal and/or carboxy-terminal fusions are affinity tags, an MBP tag, and epitope tags.

[0080] Amino acid substitutions, deletions and additions which do not significantly interfere with the three-dimensional structure of the kinase will depend, in part, on the region of the molecule where the substitution, addition or deletion occurs. In highly variable regions of the molecule, non-conservative substitutions as well as conservative substitutions may be tolerated without significantly disrupting the three-dimensional structure of the molecule. In highly conserved regions, or regions containing significant secondary structure, conservative amino acid substitutions are preferred.

[0081] Conservative amino acid substitutions are well-known in the art, and include substitutions made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity and/or the amphipathic nature of the amino acid residues involved. For example, negatively charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and arginine; amino acids with uncharged polar head groups having similar hydrophilicity values include the following: leucine, isoleucine, valine; glycine, alanine; asparagine, glutamine; serine, threonine; phenylalanine, tyrosine. Other conservative amino acid substitutions are well known in the art.

[0082] In some instances, it may be particularly advantageous or convenient to substitute, delete and/or add amino acid residues to a particular binding site or catalytic residue, in order to provide convenient cloning sites in cDNA encoding the polypeptide, to aid in purification of the polypeptide, etc. Such substitutions, deletions and/or additions which do not substantially alter the three dimensional structure of the wild-type kinase will be apparent to those having skills in the art.

[0083] It should be noted that the mutants contemplated herein need not exhibit enzymatic activity. Indeed, amino acid substitutions, additions or deletions that interfere with the catalytic activity of the kinase but which do not significantly alter the three-dimensional structure of the catalytic region are specifically contemplated by the invention. Such crystalline polypeptides, or the atomic structure co-ordinates obtained therefrom, can be used to identify compounds that bind to the protein.

[0084] Once the amino acid sequences of the polypeptides with known and unknown structures are aligned, the structures of the conserved amino acids in a computer representation of the polypeptide with known structure are transferred to the corresponding amino acids of the polypeptide whose structure is unknown. For example, a tyrosine in the amino acid sequence of known structure may be replaced by a phenylalanine, the corresponding homologous amino acid in the amino acid sequence of unknown structure.

[0085] The structures of amino acids located in non-conserved regions may be assigned manually by using standard peptide geometries or by molecular simulation techniques, such as molecular dynamics. The final step in the process is accomplished by refining the entire structure using molecular dynamics and/or energy minimization.

[0086] Structure Solution

[0087] In a further aspect, the invention provides a method for determining the structure of a target kinase, which method comprises;

[0088] providing the co-ordinates of Tables 6 or 7, and positioning the co-ordinates in the crystal unit cell of said target kinase so as to provide a structure for said target kinase.

[0089] In a preferred aspect of this invention the co-ordinates are used to solve the structure of target kinases particularly homologues of PKB, such as AGC family kinases, including, without limitation, NDR, p70 S6K, p90, PKC, etc.

[0090] The structures of the human PKB provided can be used to solve the crystal structure of other target AGC kinases including other crystal forms of PKB, mutants, and co-complexes of PKB, where X-ray diffraction data of these target proteins has been generated and requires interpretation in order to provide the structure.

[0091] In the case of PKB, this protein may crystallize in more than one crystal form. The structure coordinates of PKB, or portions thereof, as provided by this invention are particularly useful to solve the structure of those other crystal forms of PKB, such as that of the active conformation. They may also be used to solve the structure of PKB mutants or co-complexes, or of the crystalline form of any other protein with significant amino acid sequence homology to any functional domain of PKB, such as an AGC kinase family member.

[0092] In the case of other target proteins, particularly the AGC kinases referred to above, the present invention allows the structures of such targets to be obtained more readily where raw X-ray diffraction data is generated.

[0093] Thus, where X-ray crystallographic or NMR spectroscopic data is provided for a target kinase of unknown three-dimensional structure, the structure of PKB as defined by Tables 6 and 7 may be used to interpret that data to provide a likely structure for the other kinase by techniques which are well known in the art, e.g. phasing in the case of X-ray crystallography and assisting peak assignments in NMR spectra.

[0094] One method that may be employed for these purposes is molecular replacement. In this method, the unknown crystal structure, whether it is another crystal form of PKB, a mutant or co-complex thereof, or the crystal of a target kinase with amino acid sequence homology to any functional domain of PKB, may be determined using any one of the data sets of PKB structure coordinates of this invention as provided herein. This method will provide an accurate structural form for the unknown crystal more quickly and efficiently than attempting to determine such information ab initio.

[0095] Examples of computer programs known in the art for performing molecular replacement are CNX (Brunger A. T.; Adams P. D.; Rice L. M., Current Opinion in Structural Biology, Volume 8, Issue 5, October 1998, Pages 606-611 (also commercially available from Accelerys San Diego, Calif.) or AMORE (Navaza, J. (1994). AMoRe: an automated package for molecular replacement. Acta Cryst. A50, 157-163).

[0096] The invention may also be used to assign peaks of NMR spectra of such proteins, by manipulation of the data provided herein.

[0097] Computer Systems

[0098] In another aspect, the present invention provides systems, particularly a computer system, intended to generate structures and/or perform rational drug design for PKBβ, PKBβ-ligand complexes or PKBβ homologues or mutants, the system containing either (a) atomic coordinate data according to Tables 6 or 7 recorded thereon, said data defining the three-dimensional structure of PKB, or at least selected coordinates thereof; (b) structure factor data for PKB recorded thereon, the structure factor data being derivable from the atomic coordinate data of Tables 6 or 7; (c) a Fourier transform of atomic coordinate data according to Tables 6 or 7, or at least selected coordinates thereof; (d) atomic coordinate data of a target kinase generated by homology modelling of the target based on the data of Tables 6 or 7; (e) atomic coordinate data of a target kinase generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Tables 6 or 7; or (f) structure factor data derivable from the atomic coordinate data of (d) or (e).

[0099] The invention also provides such systems containing atomic coordinate data of target kinases wherein such data has been generated according to the methods of the invention described herein based on the starting data provided by Tables 6 or 7.

[0100] Such data is useful for a number of purposes, including the generation of structures to analyze the mechanisms of action of kinases, and/or to perform rational drug design of compounds which interact with them, such as modulators of kinase activity, e.g. activators or inhibitors.

[0101] In a further aspect, the present invention provides computer readable media with either (a) atomic coordinate data according to either of Tables 6 or 7 recorded thereon, said data defining the three-dimensional structure of PKB, or at least selected coordinates thereof; (b) structure factor data for PKB recorded thereon, the structure factor data being derivable from the atomic coordinate data of Tables 6 or 7; (c) a Fourier transform of atomic coordinate data according to Tables 6 or 7, or at least selected coordinates thereof; (d) atomic coordinate data of a target kinase generated by homology modelling of the target based on the data of Tables 6 or 7; (e) atomic coordinate data of a target kinase generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Tables 6 or 7; or (f) structure factor data derivable from the atomic coordinate data of (d) or (e).

[0102] By providing such computer readable media, the atomic coordinate data can be routinely accessed to model PKB or selected coordinates thereof. For example, RASMOL (Sayle et al., TIBS, Vol. 20, (1995), 374) is a publicly available computer software package which allows access and analysis of atomic coordinate data for structure determination and/or rational drug design.

[0103] On the other hand, structure factor data, which are derivable from atomic coordinate data (see e.g. Blundell et al., in Protein Crystallography, Academic Press, New York, London and San Francisco, (1976)), are particularly useful for calculating e.g. difference Fourier electron density maps.

[0104] Uses of the Structures of the Invention

[0105] In another aspect, the present invention provides methods for modelling the interactions between PKB and modulators of PKB activity. Thus there is provided a method for modelling the interaction between PKB and an agent compound which modulates PKB activity, comprising the steps of:

[0106] (a) employing three-dimensional atomic coordinate data according to either of Tables 6 or 7 to characterise at least one PKBβ binding site;

[0107] (b) providing the structure of said agent compound; and

[0108] (c) fitting said agent compound to the binding site.

[0109] The agent compound may be any compound known to have an effect on PKB activity, such as the peptide activating agents, e.g. PIFtide, described below.

[0110] The present invention further provides a method for identifying an agent compound (e.g. an inhibitor) which modulates PKB (e.g. PKBβ) activity, comprising the steps of:

[0111] (a) employing three-dimensional atomic coordinate data according to Tables 6 or 7 to characterise at least one PKBβ binding site;

[0112] (b) providing the structure of a candidate agent compound;

[0113] (c) fitting the candidate agent compound to the binding sites; and

[0114] (d) selecting the candidate agent compound.

[0115] Preferably a plurality of binding sites are characterised; preferably sufficient binding sites are characterised to define a PKBβ binding cavity and/or the ATP binding site which forms part of the catalytic site.

[0116] For ease of reference, and to avoid unnecessary repetition, only the production of modulators of PKB activity is discussed here. However the present invention is considered to apply equally to the identification of modulators of any target enzyme whose structure has been determined by reference to the three-dimensional coordinate data for PKBβ provided herein. For example, the data provided herein may be used to calculate a structure for a related AGC family kinase, such as (without limitation) SGK, p70 S6K, p90 RSK, PKC, and NDR. Accordingly, the present invention extends to the use of such a structure for identification of modulators of that target enzyme.

[0117] In the inactive conformation of PKBβ, the adenine moiety of ATP is prevented from binding to the ATP binding site by Phe-294. The data presented here show details of the interaction between PKBβ and ATP. Since all known small molecule inhibitors of protein kinases are competitive with ATP, and therefore interact with the ATP binding site, an understanding of the PKB residues involved in the interaction with ATP allows the development of specific and potent inhibitors of this kinase. This information may thus be used to develop potent and specific small molecule inhibitors of PKB in a number of ways PKBβ may be co-crystallised, and/or existing PKBβ crystals may be soaked, for example with known inhibitors of PKB, such as staurosporine, or those discovered in high-throughput screening programmes known to the skilled person.

[0118] Alternatively, or additionally, rational drug design programmes may make full use of the crystallographic coordinates. These techniques are discussed in more detail below.

[0119] It may be desirable to compare the structures of the inactive and active conformations of the enzyme, in order to identify binding sites present on only one of said conformations. The three-dimensional coordinate data for such a site could then be used to identify a ligand capable of binding selectively to, and stabilising, that conformation.

[0120] A plurality (for example two, three or four) of spaced PKBβ binding sites may be characterised and a plurality of respective compounds designed or selected. The agent compound may then be formed by linking the respective compounds into a larger compound which maintains the relative positions and orientations of the respective compounds at the binding sites. The larger compound may be formed as a real molecule or by computer modelling.

[0121] In any event, the determination of the three-dimensional structure of PKBβ provides a basis for the identification of new and specific ligands for PKB e.g. PKBβ, and other members of the AGC family of kinases, e.g. NDR, p70 S6K, p90, PKC, etc., for instance by computer modelling.

[0122] As the structures of Tables 6 and 7 show coordinate data for ternary complexes of the active structures of PKBβ, they may enable the design of competitive inhibitors of PKB, or other AGC kinases, by modelling compounds which compete for the ATP binding site, or the substrate binding site of the kinase.

[0123] Thus the PKBβ binding site may comprise one or more residues implicated in interaction with ATP (or the non-hydrolysable ATP analogue in Tables 6 and 7) in the active conformation of the enzyme.

[0124] Residues making particularly close contacts with AMP-PNP in the structure defined by Table 6 include Val-166, Lys-181, Thr-213, Met-259, Ala-232, Glu-236, Lys-277, Glu-279, Met-282, Thr-292, Asp-293 (Table 3). Thus the binding site may comprise one or more of these residues, or their equivalents in other isoforms of PKB or other AGC kinases.

[0125] Some of these contacts are conserved in PKA, however, there are differences between PKA and PKB. Notably, Thr-213 and Ala-232 are Val in PKA, and Met-282 is Leu in PKA.

[0126] Thus the present invention enables the design of inhibitors of PKB which are selective for PKB over another AGC kinase (e.g. PKA), preferably over a plurality of AGC kinases. That is to say, the candidate agent compound is a better fit to the PKBβ binding site than to a corresponding binding site defined by the corresponding residues of the other kinase. Thus the method may involve the step of comparing the binding of the candidate agent compound to the PKB binding site, and to a corresponding binding site defined by the corresponding residues of the other kinase, e.g. PKA.

[0127] Likewise the structures provided enable the design of candidate agent compounds which are selective for other AGC kinases over PKB, by designing compounds which are a better fit to binding sites on those AGC kinases than to corresponding binding sites on PKB.

[0128] Alternatively, the method may involve the step of comparing the binding of the candidate agent compound to the PKB or AGC kinase binding site, and to a corresponding binding site of a mutant of the same kinase, in which significant residues are changed to those present in the corresponding positions in the other kinase.

[0129] For example, binding may be compared between a PKBβ binding site and a mutant PKBβ binding site having one or more amino acid changes corresponding to mutations T213V, A232V and M282L of human PKBβ.

[0130] The candidate agent compound may be modelled on the non-hydrolysable ATP analogue (AMP-PNP) shown in either of Tables 6 and 7.

[0131] An interaction between a candidate agent compound and a residue of the binding site is considered to mimic an interaction between AMP-PNP and that residue if atoms from the candidate agent compound make similar interactions with corresponding residues in the binding site, e.g. ionic bonds, and electrostatic interactions such as salt bridges, hydrogen bonds, and van der Waals interactions, as well as hydrophobic interactions.

[0132] Preferably the atoms from the candidate agent compound, when fitted to the binding site, lie at a similar distance from atoms of the relevant residue as atoms of AMP-PNP when fitted to the binding site. Distances between atoms of AMP-PNP and atoms of residues in the PKB ATP binding site are shown in Table 3. More generally, an interaction between the candidate agent compound and the binding site may be considered to mimic an interaction between the substrate and the binding site if the relevant atoms have the relevant separations shown in Table 3 +/−1 Å, preferably +/−0.5 Å, more preferably +/−0.2 Å.

[0133] The PKBβ binding site may comprise one or more residues implicated in interaction with the substrate or substrate analogue, e.g. the GSK-3 peptide shown in Tables 6 and 7 in the active configuration of the enzyme.

[0134] Residues making particularly close contacts with the GSK-3 peptide in the structure defined by Tables 6 and 7 include Glu-279, Tyr-316, Glu-342, Glu-236, Glu-279, Phe-310, Cys-311 and Leu-317.

[0135] The candidate binding agent may be modelled on the GSK-3 peptide shown in either of Tables 6 or 7.

[0136] When the candidate agent compound is fitted to the binding site, an interaction between the candidate agent compound and the binding site may mimic an interaction between one or more of the following sets of residues of Tables 6 and 7:

[0137] Arg-4 of GSK-3 and residues Glu-279, Tyr-316, Glu-342 of PKB-PIF;

[0138] Arg-6 of GSK-3 and residues Glu-236, Glu-279 of PKB-PIF;

[0139] Thr-7 of GSK-3 and residues Glu-279 of PKB-PIF;

[0140] Phe-10 of GSK-3 and residues Phe-310, Cys-311, Leu-317 of PKB-PIF;

[0141] Glu-12 of GSK-3 and residues Phe-310 of PKB-PIF.

[0142] An interaction between a candidate agent compound and a residue of the binding site is considered to mimic an interaction between the substrate peptide and that residue if atoms from the candidate agent compound make similar interactions with corresponding residues in the binding site, ionic bonds, and electrostatic interactions such as salt bridges, hydrogen bonds, and van der Waals interactions, as well as hydrophobic interactions.

[0143] Preferably the atoms from the candidate agent compound, when fitted to the binding site, lie at a similar distance from atoms of the relevant residue as atoms of the substrate when fitted to the binding site. Distances between atoms of the substrate and atoms of residues in the substrate binding site are shown in Table 4. More generally, an interaction between the candidate agent compound and the binding site may be considered to mimic an interaction between the substrate and the binding site if the relevant atoms have the relevant separations shown in Table 4 +/−1 Å, preferably +/−0.5 Å, more preferably +/−0.2 Å.

[0144] The structure shown in Table 6 further shows the interactions between the residues of PIFtide and the catalytic domain of PKB. This data may be used to design mimetics of PIFtide for activation of PKB.

[0145] Residues making particularly close contacts with the residues of the PRK-2 activation motif, i.e. the PIF residues in the structure defined by Table 6 include Val-194, Gln-220, Ile-188, Ile-189, Val-198, Arg-202, Gln-205, Ser-201, Ala-218, Leu-225, Phe-227, Arg-208, Leu-215 and Lys-216.

[0146] The candidate binding agent may be modelled on the PIF residues shown in Table 6, and preferably the residues of the activation motif.

[0147] When the candidate agent compound is fitted to the binding site, an interaction between the candidate agent compound and the binding site may mimic an interaction between one or more of the following sets of residues of PKB-PIF shown in Table 6:

[0148] Met-472 and Val-194, Gln-220;

[0149] Phe-473 and Ile-188, Ile-189, Val-194, Val-198;

[0150] Asp-475 and Arg-202, Gln-205;

[0151] Phe-476 and Ser-201, Ala-218, Leu-225, Phe-227;

[0152] Asp-477 and Gln-220;

[0153] Tyr-478 and Arg-208, Leu-215;

[0154] Ala-480 and Lys-216;

[0155] Asp-481 and Arg-208;

[0156] Trp-479 and Leu-215, Lys-216.

[0157] An interaction between a candidate agent compound and a residue of the binding site is considered to mimic an interaction between a PIF residue and that residue if atoms from the candidate agent compound make similar interactions with corresponding residues in the binding site, ionic bonds, and electrostatic interactions such as salt bridges, hydrogen bonds, and van der Waals interactions, as well as hydrophobic interactions.

[0158] Preferably the atoms from the candidate agent compound, when fitted to the binding site, lie at a similar distance from atoms of the relevant residue as atoms of PIF residues when fitted to the binding site. Distances between atoms of PIF residues and atoms of residues in the activation motif binding site are shown in Table 5. More generally, an interaction between the candidate agent compound and the binding site may be considered to mimic an interaction between PIF residues and the binding site if the relevant atoms have the relevant separations shown in Table 5 +/−1 Å, preferably +/−0.5 Å, more preferably +/−0.2 Å.

[0159] The data in Tables 3, 4 and 5 is provided for illustrative purposes only—similar data may be derived by the skilled person directly from the data of Tables 6 and 7. The similarity of the two structures shown in Tables 6 and 7 shows that PKB S474D makes essentially the same interactions with AMP-PNP and GSK-3 as PKB-PIF. The C-terminal tail of PKB S474D makes similar contacts with the catalytic domain as the corresponding residues of PKB-PIF make to the catalytic domain, except that there are no contacts to Met-469, Asp-472, Ile-476 and Trp-479. The skilled person will understand that precise details of the interactions between the C-terminal tail and the catalytic domain of PKB S474D may be derived from Table 7 and used in exactly the same way as the data of Table 5. The present invention encompasses use of all such derived data.

[0160] More specifically, a potential modulator of PKB activity can be examined through the use of computer modelling using a docking program such as GRAM, DOCK, or AUTODOCK (see Walters et al., Drug Discovery Today, Vol.3, No.4, (1998), 160-178, and Dunbrack et al., Folding and Design, 2, (1997), 27-42). This procedure can include computer fitting of candidate inhibitors to PKB to ascertain how well the shape and the chemical structure of the candidate inhibitor will bind to the enzyme.

[0161] Also computer-assisted, manual examination of the binding cavity structure of PKBβ may be performed. The use of programs such as GRID (Goodford, J. Med. Chem., 28, (1985), 849-857)—a program that determines probable interaction sites between molecules with various functional groups and the enzyme surface—may also be used to analyse the binding cavity to predict partial structures of inhibiting compounds.

[0162] Computer programs can be employed to estimate the attraction, repulsion, and steric hindrance of the two binding partners (e.g. the PKBβ and a candidate inhibitor). Generally the tighter the fit, the fewer the steric hindrances, and the greater the attractive forces, the more potent the potential modulator since these properties are consistent with a tighter binding constant. Furthermore, the more specificity in the design of a potential drug, the more likely it is that the drug will not interact with other proteins as well. This will tend to minimise potential side-effects due to unwanted interactions with other proteins

[0163] In one embodiment a plurality of candidate agent compounds are screened or interrogated for interaction with the binding sites. In one example, step (b) involves providing the structures of the candidate agent compounds, each of which is then fitted in step (c) to computationally screen a database of compounds (such as the Cambridge Structural Database) for interaction with the binding sites. In another example, a 3-D descriptor for the agent compound is derived, the descriptor including e.g geometric and functional constraints derived from the architecture and chemical nature of the binding cavity. The descriptor may then be used to interrogate the compound database, the identified agent compound being the compound which matches with the features of the descriptor. In effect, the descriptor is a type of virtual pharmacophore.

[0164] For example, the descriptor may be based on the AMP-PNP molecule which interacts with the ATP binding site, the substrate peptide which interacts with the substrate binding site, or the residues of the C-terminal tail of PKB-PIF, or PKB S474D, which interact with the catalytic domain.

[0165] Having designed or selected possible binding partners, these can then be screened for activity. Consequently, the method preferably comprises the further steps of:

[0166] (e) obtaining or synthesising the candidate agent compound; and

[0167] (f) contacting the candidate agent compound with PKBβ to determine the ability of the candidate agent compound to interact with PKBβ (or similarly with other homologous isoforms or AGC kinase family members).

[0168] In step (f) the candidate agent compound may be contacted with PKBβ in the presence of a substrate, and typically a buffer, to determine the ability of the candidate agent compound to inhibit PKBβ. The buffer will typically contain ATP. The substrate may be e.g. a peptide corresponding to the sequence GRPRTTSFAE, or salts thereof. So, for example, an assay mixture for PKB may be produced which comprises the candidate inhibitor, substrate and buffer

[0169] Instead of, or in addition to, performing e.g. a chemical assay, the method may comprise the further steps of:

[0170] (e) obtaining or synthesising the candidate agent compound;

[0171] (f) forming a complex of PKB and the candidate agent compound; and

[0172] (g) analysing (e.g. by the method of an earlier aspect of the invention) said complex by X-ray crystallography or NMR spectroscopy to determine the ability of the candidate agent compound to interact with PKB.

[0173] Detailed structural information can then be obtained about the binding of the agent compound to PKB, and in the light of this information adjustments can be made to the structure or functionality of the compound, e.g. to improve binding to the binding cavity. Steps (e) to (g) may be repeated and re-repeated as necessary. For X-ray crystallographic analysis, the complex may be formed by crystal soak-in methods or co-crystallisation.

[0174] Greer et al. describes an iterative approach to ligand design based on repeated sequences of computer modelling, protein-ligand complex formation and X-ray crystallographic or NMR spectroscopic analysis. Thus novel thymidylate synthase inhibitor series were designed de novo by Greer et al., and PKB inhibitors may also be designed in the this way. More specifically, using e.g. GRID on the solved 3D structure of PKBβ, a ligand (e.g. a potential inhibitor) for PKB may be designed that complements the functionalities of the PKB binding site(s). The ligand can then be synthesised, formed into a complex with PKB or other AGC family kinase, and the complex then analysed by X-ray crystallography to identify the actual position of the bound ligand. The structure and/or functional groups of the ligand can then be adjusted, if necessary, in view of the results of the X-ray analysis, and the synthesis and analysis sequence repeated until an optimised ligand is obtained. Related approaches to structure-based drug design are also discussed in Bohacek et al., Medicinal Research Reviews, Vol.16, (1996), 3-50.

[0175] As a result of the determination of the PKBβ 3D structure, more purely computational techniques for rational drug design may also be used to design PKB modulators, e.g. activators or inhibitors (for an overview of these techniques see e.g. Walters et al.). For example, automated ligand-receptor docking programs (discussed e.g. by Jones et al. in Current Opinion in Biotechnology, Vol.6, (1995), 652-656) which require accurate information on the atomic coordinates of target receptors may be used to design potential PKB modulators.

[0176] Linked-fragment approaches to drug design also require accurate information on the atomic coordinates of target receptors. The basic idea behind these approaches is to determine (computationally or experimentally) the binding locations of plural ligands to a target molecule, and then construct a molecular scaffold to connect the ligands together in such a way that their relative binding positions are preserved. The connected ligands thus form a potential lead compound that can be further refined using e.g. the iterative technique of Greer et al. For a virtual linked-fragment approach see Verlinde et al., J. of Computer-Aided Molecular Design, 6, (1992), 131-147, and for NMR and X-ray approaches see Shuker et al., Science, 274, (1996), 1531-1534 and Stout et al., Structure, 6, (1998), 839-848. The use of these approaches to design PKB inhibitors is made possible by the determination of the PKBβ structure.

[0177] Many of the techniques and approaches to structure-based drug design described above rely at some stage on X-ray analysis to identify the binding position of a ligand in a ligand-protein complex. A common way of doing this is to perform X-ray crystallography on the complex, produce a difference Fourier electron density map, and associate a particular pattern of electron density with the ligand. However, in order to produce the map (as explained e.g. by Blundell et al.) it is necessary to know beforehand the protein 3D structure (or at least the protein structure factors). Therefore, determination of the PKBβ structure also allows difference Fourier electron density maps of PKB-ligand complexes to be produced, which can greatly assist the process of rational drug design.

[0178] The approaches to structure-based drug design described above all require initial identification of possible compounds for interaction with the target bio-molecule (in this case PKB). Sometimes these compounds are known e.g. from the research literature.

[0179] Thus the present invention provides methods of identifying mimetics of known modulators of PKB activity. The methods may involve the identification of a binding site for the known modulator. Subsequently, candidate compounds may be fitted to the same binding site in order to identify a compound which will mimic the activity of the known modulator.

[0180] For example, the methods described above may be used to model the binding site at which PKB interacts with a known modulator, e.g. an activating agent such as PIFtide, as described elsewhere in this specification. A mimetic of the activating agent may then be designed by fitting candidate compounds to that binding site.

[0181] Thus the methods of the present invention for identifying agent compounds which modulate PKB activity may involve fitting a candidate agent compound to a PKB binding site, wherein the binding site has previously been determined to bind a known agent compound as described above.

[0182] When no suitable known starting compounds are known, or when novel compounds are wanted, a first stage of the drug design program may involve computer-based in silico screening of compound databases (such as the Cambridge Structural Database) with the aim of identifying compounds which interact with the binding site or sites of the target bio-molecule. Screening selection criteria may be based on pharmacokinetic properties such as metabolic stability and toxicity. However, determination of the PKBβ structure allows the architecture and chemical nature of each PKBβ binding site to be identified, which in turn allows the geometric and functional constraints of a descriptor for the potential inhibitor to be derived. The descriptor is, therefore, a type of virtual 3-D pharmacophore, which can also be used as selection criteria or filter for database screening.

[0183] In another aspect, the invention includes a compound which is identified as a modulator of PKB activity by the method of the earlier aspect.

[0184] Following identification of a suitable modulator compound, it may be manufactured and/or used in the preparation, i.e. manufacture or formulation, of a composition such as a medicament, pharmaceutical composition or drug. These may be administered to individuals for treatment of an appropriate condition, e.g. inhibitors for use in the treatment of cancers, or activators in the use of diabetes, erectile dysfunction or neurodegeneration.

[0185] Thus, the present invention extends in various aspects not only to a modulator as provided by the invention, but also a pharmaceutical composition, medicament, drug or other composition comprising such a modulator e.g. for treatment (which may include preventative treatment) of disease such as cancer; a method, comprising administration of such a composition to a patient, e.g. for treatment of disease such as cancer; use of such a modulator in the manufacture of a composition for administration, e.g. for treatment of disease such as cancer; and a method of making a pharmaceutical composition comprising admixing such a modulator with a pharmaceutically acceptable excipient, vehicle or carrier, and optionally other ingredients.

[0186] Although the examples relate to crystals of PKB mutants having an S474D mutation, and a chimera having a C terminus derived from PRK2, it will be clear that any of the peptide or non-peptide activating agents described below may be used to induce the catalytic domain of a kinase to adopt a catalytically active conformation, for crystallisation or for any other purposes. The activating agents may be covalently or non-covalently linked to the catalytic domain of the enzyme, as described below.

[0187] Activation of AGC kinases

[0188] The insights into the mechanism of kinase activation, which the crystal structure of PKB provides, enables the provision of novel methods for activating AGC kinases, and materials for use in those methods.

[0189] The present invention further provides a method of inducing a catalytic domain of an AGC kinase to adopt an active conformation, wherein the AGC kinase in its native form is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment distinct from said catalytic domain, said method comprising the steps of:

[0190] (a) providing a polypeptide comprising said catalytic domain, and

[0191] (b) forming a non-covalent complex between said polypeptide and an activating agent, wherein contact between said activating agent and said catalytic domain induces said catalytic domain to adopt an active conformation.

[0192] The activating agent does not catalyse covalent modification of the polypeptide; in particular, the activating agent is not a kinase and does not phosphorylate the polypeptide. Rather the activating agent interacts with the catalytic domain to induce ordering of the regions of the kinase corresponding to the αB and αC helices and activation segment of PKB. Full activity may also require phosphorylation of a residue in the activation segment corresponding to Thr-309 of human PKBβ. This disorder to order transition forms a hydrophobic surface groove in the N-terminal lobe of the catalytic domain which binds the activating agent. The interaction is believed to be stabilised further by electrostatic interactions between residues of the catalytic domain and one or more negative charges of the activating agent.

[0193] The catalytic domain may be that of any AGC kinase which, in its native form, is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment distinct from the catalytic domain. Such phosphorylation typically activates the kinase. Such kinases include, but are not limited to, PKB, PKC, NDR, SGK, and the p70 and p90 S6-kinases and include variants of these kinases which do not possess the regulatory phosphorylation site, such as the splice variant of PKBγ (Brodbeck et al., 2001). However, they do not include kinases which are not regulated by phosphorylation of this sort, such as PKA, PRK2, and PDK1.

[0194] By “AGC kinase” is meant any protein kinase which has a sequence identity of equal to or greater than 35% at the amino acid level with residues 37-350 of the catalytic subunit of PKA (Shoji et al., 1983). Determination of percentage sequence identity may be performed with the AMPS package as described by Barton (1994). AGC kinases are also described in detail by Hanks and Hunter FASEB J. (1995) 9: 576 and Hardie, G. and Hanks, S. (eds) The Protein Kinase Facts Book—Protein-Serine Kinases (1995) Academic Press Ltd., London).

[0195] Thus the kinases which can be activated by the methods of the present invention possess a regulatory segment distinct from the catalytic domain, which in PKB constitutes the portion of the protein C-terminal of the catalytic domain. Thus the term ‘C-terminal regulatory segment’ signifies only that this portion of the polypeptide is located C-terminal of the catalytic domain, and does not imply that any portion of the regulatory segment need form the C-terminus of the polypeptide. In a preferred embodiment, the C-terminal regulatory segment corresponds to amino acid residues 440 to 480 of PKBβ, 441 to 481 of PKBβ, 438 to 479 of PKBγ, or corresponding residues in other kinases.

[0196] The regulatory segment contains a hydrophobic motif at least four amino acids and typically six amino acid residues in length, which typically contains the sequence FXXF, e.g. FXXFXY/F, although the kinase NDR has the sequence FXXY at this position. Here, and throughout this specification, X represents any amino acid. The regulatory segment further comprises a regulatory phosphorylation site, which typically lies within the hydrophobic motif, e.g. Ser-473 of PKBα, Ser-474 of PKBβ, Ser 472 of PKBγ. For example, PKBα, β and γ all have the sequence FPQFSY within their regulatory segment.

[0197] The term ‘catalytic domain’ as used herein refers to a protein domain which when folded has a particular characteristic structure, and not necessarily to a domain having any particular catalytic activity. Thus the catalytic domain may contain a mutation which impairs or abrogates activity, e.g. substitution or deletion of one or more amino acid residues at the active site, but which does not affect the gross structure of the folded domain.

[0198] The minimum catalytic domain of a given kinase is the minimum polypeptide sequence from that kinase which will fold stably into the appropriate conformation when expressed independently, and may correspond, for example to amino acid residues 144 to 439 of human PKBα, 146 to 440 of human PKBβ, or 143 to 436 of human PKBγ (see

[0199]
FIG. 7—all references made herein to numbering of residues of PKBα or β refer to the human PKB sequences as shown in FIG. 7).

[0200] Catalytic domains of other target AGC kinases may be identified by alignment of the target sequences with that of PKBβ.

[0201] In general, comparison of amino acid sequences is accomplished by aligning the amino acid sequence of a polypeptide of a known structure with the amino acid sequence of the polypeptide of unknown structure. Amino acids in the sequences are then compared and groups of amino acids that are homologous are grouped together. This method detects conserved regions of the polypeptides and accounts for amino acid insertions or deletions.

[0202] Homology between amino acid sequences can be determined using commercially available algorithms. The programs BLAST, gapped BLAST, BLASTN, PSI-BLAST and BLAST 2 sequences (provided by the National Center for Biotechnology Information) are widely used in the art for this purpose, and can align homologous regions of two amino acid sequences. These may be used with default parameters to determine the degree of homology between the amino acid sequence of the protein of known structure and those of target proteins.

[0203] The polypeptide may consist solely or essentially of the catalytic domain in isolated form, e.g. a recombinant single domain. Alternatively the polypeptide may contain further domains of the AGC kinase, fusion partners, epitope tags, etc. For example, the catalytic domain may be contiguous with all or part of one or more further domains found in the native wild-type form of the enzyme, such as a pleckstrin homology (PH) domain or the C-terminal regulatory segment of PKB.

[0204] In preferred embodiments, the catalytic domain is from an isoform of PKB, e.g. from the α, β or γ isoforms of PKB.

[0205] The catalytic domain may be provided in phosphorylated form, e.g. in the activation segment of the catalytic domain. For example, in a preferred embodiment the catalytic domain is from PKB and is provided phosphorylated at Thr-308 (PKBα), Thr-309 (PKBβ) or Thr-305 (PKBγ). In alternative embodiments where the catalytic domain is derived from another AGC kinase, it may be phosphorylated at the corresponding position.

[0206] The methods of the present invention may further comprise the steps of phosphorylating one or more phosphorylatable residues of the catalytic domain in vitro with a suitable kinase. For example, PDK1 can be used to phosphorylate Thr-309 in vitro, while it has been suggested that MAPKAP 2 kinase can be used to phosphorylate Ser-474 (Alessi et al., 1996a).

[0207] Additionally or alternatively, the methods of the present invention may comprise the step of dephosphorylation in vitro, to ensure that any adventitious phosphorylation occurring during expression is removed. The skilled person will be aware of numerous suitable enzymes for this purpose, e.g. the λ protein phosphatase.

[0208] The activating agent may be a peptide. The peptide comprises an activation motif which is primarily responsible for mediating interaction with the catalytic domain. The activation motif may comprise a sequence derived from the native C-terminal regulatory segment of the same AGC kinase as the catalytic domain, or from the native C-terminal regulatory segment of a different AGC kinase, or may be a modified or mutated variant of either. Alternatively, the activation motif may be a synthetic sequence which does not occur naturally in an AGC kinase but which can activate the relevant catalytic domain in vitro, e.g. as described below.

[0209] The activation motif may comprise a hydrophobic motif. The hydrophobic motif is typically at least four amino acids in length, e.g. four, five or six amino acids in length, of which at least two amino acids, preferably at least three amino acids, are hydrophobic amino acids, preferably aromatic amino acids (e.g. phenylalanine, tyrosine). Preferably the hydrophobic motif comprises the sequence BXXB, where B represents an aromatic amino acid, e.g. tyrosine or phenylalanine and X is any amino acid. Thus in any sequence for an activating agent set out herein, it will be understood that phenylalanine can be replaced by tyrosine.

[0210] In a preferred embodiment, the hydrophobic motif comprises the sequence FXXF, YXXF, YXXY, FXXFX(Y/F), YXXFX(Y/F), or YXXYX(Y/F). In preferred embodiments, the hydrophobic motif comprises the sequence FXXFX(Y/F).

[0211] The activation motif preferably comprises an amino acid residue which carries a negative electrostatic charge at physiological pH. This amino acid may be located within, adjacent to or near (e.g. within one, two, three, four or five amino acids of) the hydrophobic motif, e.g. within the FXXF motif, or C-terminal of the FXXF motif, e.g. within one, two, three, four or five amino acids of the FXXF motif. The activation motif may comprise two such amino acids. In certain embodiments, one such amino acid may be located within the FXXF motif, and one may lie C terminal thereof, preferably one amino acid C-terminal thereof.

[0212] Preferably the activation motif comprises the sequence

[0213] FXXFX′, FXXFX′(F/Y), FXX′FX′, or FXX′FX′(F/Y);

[0214] YXXFX′, YXXFX′(F/Y), YXX′FX′, or YXX′FX′(F/Y);

[0215] FXXYX′, FXXYX′(F/Y), FXX′YX′, or FXX′YX′(F/Y);

[0216] YXXYX′, YXXYX′(F/Y), YXX′YX′, or YXX′YX′(F/Y);

[0217] where X′ represents an amino acid residue which carries a negative charge at physiological pH. This may be a naturally ionisable acidic amino acid, such as aspartic acid or glutamic acid. Alternatively, X′ may be charged as a result of chemical derivatisation or enzymatic modification, e.g. it may be a phosphorylated amino acid residue, such as phosphoserine or phosphothreonine. Thus, particularly when X′ is phosphoserine or phosphothreonine, X′ may carry more than one negative charge at physiological pH.

[0218] In preferred embodiments, the activation motif comprises the sequence FXXFX′, FXXFX′(F/Y), FXX′FX′, or FXX′FX′(F/Y).

[0219] In preferred embodiments the activation motif is derived from the regulatory segment of PKB or PRK2. Preferably the activation motif comprises the sequence FPQFpSY (where pS is phosphoserine), FPQFDY or FRDFDY. For example, the activating agent may comprise the whole or part of one of the sequences GLLELDQRTHFPQFpSYSASIRE, GLLELDQRTHFPQFDYSASIRE and REPRILSEEEQEMFRDFDYIADWC (PIFtide—Biondi et al., 2000).

[0220] Activation of an AGC kinase according to the present invention may be performed in vivo or in vitro.

[0221] When performed in vitro, the methods of the present invention may be used, inter alia, to generate an active conformation of an AGC kinase catalytic domain for the purposes of structural analysis. Thus the present invention further provides a method of determining a structure for an active conformation of a catalytic domain of an AGC kinase, wherein the AGC kinase in its native form is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment, said method comprising the steps of inducing the catalytic domain of the AGC kinase to adopt an active conformation by any of the methods described herein.

[0222] The method may further comprise the step of obtaining a data set for said active conformation from which a structure can be calculated, and may additionally involve the step of calculating a structure therefor.

[0223] In preferred embodiments, especially where the active conformation is to be crystallised, a stable protease-resistant form of the catalytic domain is used, preferably in recombinant form. The catalytic domain may be a PKB catalytic domain, which may lack all or substantially all of the PH domain, e.g. corresponding to residues 1 to 139, 1 to 140, 1 to 141, 1 to 142, 1 to 143, 1 to 144, or 1 to 145 of human PKBβ, or their corresponding residues in other isoforms. In a preferred embodiment, the catalytic domain lacks residues corresponding to residues 1 to 145 of human PKBβ.

[0224] Additionally or alternatively the catalytic domain may be truncated at the C-terminus, e.g. lacking amino acid residues C-terminal of position 440 in PKBβ or its equivalent. In one embodiment, the catalytic domain lacks amino acid residues C-terminal of position 460 in PKBβ or its equivalent e.g. the C-terminal 21 amino acids of PKBβ. Thus it may be a truncated derivative of PKB, e.g. truncated to positions 146-460 for PKBβ, or corresponding residues in other isoforms.

[0225] The structure may be determined by any suitable method, e.g. X-ray crystallography or NMR. Thus the method may further comprise the step of crystallising the catalytic domain of the kinase in its active conformation.

[0226] The method may include the further step of X-ray diffraction analysis of the obtained crystal.

[0227] Alternatively, the methods of the present invention may be applied in assays for assessing the ability of a candidate agent to modulating the activity of an AGC kinase.

[0228] Thus the present invention further provides a method of assessing the ability of a candidate compound to modulate the catalytic activity of an AGC kinase, which in its native form is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment, comprising the steps of

[0229] (a) providing a polypeptide comprising a catalytic domain of said kinase,

[0230] (b) forming a non-covalent complex between said polypeptide and an activating agent, wherein contact between said activating agent and said catalytic domain induces said catalytic domain to adopt an active conformation, and

[0231] (c) contacting said non-covalent complex with said candidate agent.

[0232] The method may further comprise the step of measuring the effect of the candidate agent on the AGC kinase activity.

[0233] Preferably, the AGC kinase is phosphorylated at a position corresponding to Thr-309 of human PKBβ.

[0234] The methods may be used to identify modulators, such as inhibitors or activators of AGC kinases. Suitable methods for measuring the effect of candidate compounds on AGC kinase activity will be well known to the skilled person. For example, the activity of PKB can be assayed by monitoring phosphorylation of an appropriate substrate, e.g. the peptide Crosstide, as described in the Examples.

[0235] In a further aspect, the present invention provides a non-covalent complex between a catalytic domain of an AGC kinase, which in its native form is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment, and an activating agent, wherein said catalytic domain is in an active conformation, i.e. the regions of the catalytic domain corresponding to the αB and αC helices and activation segment of PKB are in an ordered conformation.

[0236] It will be clear from the above disclosure that a catalytic domain of an AGC kinase may also be induced to adopt an active conformation if covalently linked to an activating agent such as those described above.

[0237] Thus, the present invention also provides a method of inducing a catalytic domain of an AGC kinase to adopt an active conformation, wherein the AGC kinase in its native form is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment distinct from said catalytic domain, said method comprising the steps of:

[0238] (a) providing a polypeptide comprising said catalytic domain, and

[0239] (b) covalently joining said polypeptide to an activating agent,

[0240] wherein contact between said activating agent and said catalytic domain induces said catalytic domain to adopt an active conformation.

[0241] Typically the polypeptide lacks some or all of a C-terminal regulatory domain prior to step (b). In preferred embodiments the polypeptide lacks the relevant regulatory phosphorylation site prior to step (b).

[0242] Preferably the activating agent is a peptide comprising an activation motif as described above, e.g. the peptide GLLELDQRTHFPQFDYSASIRE or REPRILSEEEQEMFRDFDYIADWC (PIFtide). Ligation of a peptide to a polypeptide may be achieved by native chemical ligation, by protein splicing, or may be catalysed by a heterologous enzyme. Methods for carrying out such ligations are reviewed in Cotton, G. J. and Muir, T. W. (1999) Chemistry and Biology 6(9): R247-R256. In some embodiments, as in all aspects of this invention, peptide mimetics, comprising non-natural amino acids, or having linkages other than peptide bonds, may advantageously be used.

[0243] In preferred embodiments a phosphopeptide derived from the C-terminal regulatory segment of an AGC kinase is ligated to the catalytic domain. Preferably, the phosphopeptide is derived from the same AGC kinase as the catalytic domain. Thus this technique enables the active phosphorylated form of the enzyme to be mimicked without needing to phosphorylate the whole enzyme. This may be particularly useful where the kinase responsible for phosphorylation in vivo has not been conclusively identified.

[0244] In a preferred embodiment a polypeptide comprising a PKB catalytic domain is ligated to a peptide comprising the whole or part of the sequence GLLELDQRTHFPQFPSYSASIRE.

[0245] In a yet further aspect, the present invention. provides a method of determining a structure for an active conformation of a catalytic domain of an AGC kinase, wherein the AGC kinase in its native form is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment distinct from said catalytic domain, said method comprising the steps of:

[0246] (a) providing a mutant AGC kinase protein comprising a catalytic domain and a C-terminal regulatory segment distinct from said catalytic domain, the protein further comprising a mutation which enhances the interaction between said regulatory segment and said catalytic domain relative to the wild type enzyme, such that an active conformation is induced in said catalytic domain, and

[0247] (b) obtaining a data set for said mutant protein from which a structure can be calculated.

[0248] The mutation enhances interaction between the regulatory segment (as described above) and the catalytic domain, such as to enable ordering of the regions of the kinase corresponding to the activation segment and αB and αC helices of PKB, without phosphorylation of a regulatory phosphorylation site in the C-terminal regulatory segment. The mutation may comprise one or more amino acid insertions, deletions or substitutions in the C-terminal regulatory segment, preferably in or around the hydrophobic motif, or in the catalytic domain, or in both C-terminal and catalytic domains. Alternatively, the mutation may involve the insertion or substitution of a number of contiguous residues of the C-terminal regulatory segment, e.g. with the corresponding residues from a second AGC kinase. Such a mutant AGC kinase may be considered to be a chimeric kinase.

[0249] Preferably, the C-terminal regulatory segment is mutated so that its interaction with the wild-type catalytic domain is enhanced. Preferably the mutation is made in or around the hydrohobic motif of the C-terminal regulatory segment, i.e. the region corresponding to the sequence FPQFSY of PKBβ (amino acid residues 470-475). The mutation may comprise substitution, deletion or insertion of one or more amino acids, e.g. 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, or 20 amino acids. In preferred embodiments the regulatory phosphorylation site is mutated.

[0250] In preferred embodiments, the mutation comprises the introduction into the C-terminal regulatory segment of a residue which carries an electrostatic charge at physiological pH, preferably a negative electrostatic charge, e.g. aspartic acid or glutamic acid.

[0251] In a preferred embodiment the amino acid residue which would be phosphorylated to activate the wild-type enzyme (e.g. the residue corresponding to Ser-474 of PKBβ) is mutated to a residue which carries a negative electrostatic charge at physiological pH, e.g. aspartic acid or glutamic acid. For example, where the AGC kinase is PKBβ, the mutation may involve alteration of the sequence FPQFSY to FPQFDY.

[0252] In other embodiments, the mutation may involve the substitution of a number of contiguous residues of the C-terminal regulatory segment, e.g. with the corresponding residues from a second AGC kinase. Thus the sequence FPQFSY of PKBβ may be replaced by the sequence FRDFDY from PRK2. The chimera may contain further sequences from the second kinase, e.g. one or more of the flanking residues in the sequence GLLELDQRTHFPQFDYSASIRE from PKBβ may be replaced by one or more corresponding residues of the sequence REPRILSEEEQEMFRDFDYIADWC from PRK2 (PIFtide).

[0253] Additionally or alternatively, the catalytic domain may be mutated to enhance its interaction with the wild-type C-terminal regulatory segment, or with a mutated C-terminal regulatory segment. Thus the catalytic domain may be mutated in or around the binding groove which interacts with the C terminal regulatory segment. For example, polar or charged residues (e.g. serine, threonine, aspartic acid, glutamic acid, lysine, etc.) may be mutated to more hydrophobic residues (e.g. phenylalanine, tyrosine, etc.), or hydrophobic residues replaced by more hydrophobic or larger hydrophobic residues, in order to enhance the interaction between the catalytic domain and the hydrophobic motif of the regulatory segment.

[0254] Possible target residues include V194 and V198 of PKBβ. These may, for example, be replaced by the corresponding residues of the hydrophobic groove from PKA. This is capable of binding the regulatory segment of PKA without phosphorylation, which implies that the hydrophobic interactions involved are stronger than are seen in PKB. Thus possible substitutions include V194I and V198L.

[0255] Additionally or alternatively, substitutions may be made which enhance the binding of the catalytic domain to a negative charge of the regulatory segment, e.g. incorporating further positive charges. A possible target residue is S201; therefore a possible substitution is S201K.

[0256] Alternatively, both catalytic domain and C-terminal regulatory segment may be mutated in order to enhance the affinity between them. Mutants may be prepared for example, by site-specific mutagenesis, or incorporation of natural or unnatural amino acids.

[0257] In preferred embodiments, especially where the mutant AGC kinase is to be crystallised, a stable protease-resistant form of the catalytic domain truncated at the N-terminus is used. The kinase may lack some or all of the wild-type residues upstream of the catalytic domain, e.g. corresponding to all or substantially all of the PH domain of PKB, e.g. corresponding to residues 1 to 139, 1 to 140, 1 to 141, 1 to 142, 1 to 143, 1 to 144, 1 to 145, 1 to 146, 1 to 147, 1 to 148, 1 to 149 or 1 to 150 of human PKBβ, or their corresponding residues in other isoforms. In a preferred embodiment the kinase lacks residues corresponding to residues 1 to 145 of PKBβ.

[0258] In a further aspect, the present invention provides a mutant AGC kinase protein, wherein the AGC kinase in its native form is regulated by phosphorylation of a regulatory phosphorylation site residue in a C-terminal regulatory segment, said mutant AGC kinase protein comprising a catalytic domain and a C-terminal regulatory segment distinct from said catalytic domain, and having an N-terminus corresponding to residue 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149 or 150 of PKBβ, or their corresponding residues in other isoforms, the mutant AGC kinase protein comprising a mutation which enhances the interaction between said regulatory segment and said catalytic domain relative to the wild type enzyme, such that an active conformation is induced in said catalytic domain.

[0259] The mutation enhances interaction between the regulatory segment and the catalytic domain, such as to enable ordering of the regions of the kinase corresponding to the activation segment and αB and αC helices of PKB, without phosphorylation of the regulatory segment, and may have any of the characteristics described above.

[0260] In a preferred embodiment the kinase has an N-terminus corresponding to residue 146 of PKBβ.

[0261] In a further aspect, the present invention provides nucleic acids encoding the mutant ACC kinase polypeptides as described herein.

[0262] Throughout this specification, where nucleic acids are referred to, they may be wholly or partially synthetic. In particular they may be recombinant in that nucleic acid sequences which are not found together in nature (do not run contiguously) have been ligated or otherwise combined artificially. Alternatively they may have been synthesised directly e.g. using an automated synthesiser.

[0263] Nucleic acid according to the present invention may be polynucleotides or oligonucleotides, and may include cDNA, RNA, genomic DNA (gDNA) and modified nucleic acids or nucleic acid analogs.

[0264] Where a nucleic acid (or nucleotide sequence) of the invention is referred to herein, the complement of that nucleic acid (or nucleotide sequence) will also be embraced by the invention. The ‘complement’ in each case is the same length as the reference, but is 100% complementary thereto whereby by each nucleotide is base paired to its counterpart i.e. G to C, and A to T or U.

[0265] The nucleic acids of the present invention may differ from any specific sequences recited or referred to herein by a change which is one or more of addition, insertion, deletion and substitution of one or more nucleotides of the sequences shown, e.g. 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 40, 50 or more nucleotides. Preferably the reading frame is maintained. Changes to a nucleotide sequence may result in an amino acid change at the protein level, or not, as determined by the degeneracy of the genetic code.

[0266] Nucleic acids of the present invention may be provided as part of a vector, and also provided by the present invention is a vector comprising nucleic acid as described herein, particularly vectors from which the polypeptide can be expressed under appropriate conditions, and a host cell containing any such vector or nucleic acid.

[0267] ‘Vector’ is defined to include, inter alia, any virus, plasmid, cosmid, or phage vector in double or single stranded linear or circular form which may or may not be self transmissible or mobilizable, and which can transform a prokaryotic or eukaryotic host either by integration into the cellular genome or exist extrachromosomally (e.g. autonomous replicating plasmid with an origin of replication).

[0268] Generally speaking, those skilled in the art are well able to construct vectors and design protocols for recombinant gene expression. Suitable vectors can be chosen or constructed, containing appropriate regulatory sequences, including promoter sequences, terminator fragments, polyadenylation sequences, enhancer sequences, marker genes and other sequences as appropriate. For further details see, for example, Molecular Cloning: a Laboratory Manual: 2nd edition, Sambrook et al, 1989, Cold Spring Harbor Laboratory Press or Current Protocols in Molecular Biology, Second Edition, Ausubel et al. eds., John Wiley & Sons, 1992.

[0269] Specifically included are shuttle vectors by which is meant a DNA vehicle capable, naturally or by design, of replication in two different host organisms, which may be selected from actinomycetes and related species, bacteria and eukaryotic (e.g. higher plant, mammalian, insect, yeast or fungal cells).

[0270] A vector including nucleic acid according to the present invention need not include a promoter or other regulatory sequence, particularly if the vector is to be used to introduce the nucleic acid into cells for recombination into the genome.

[0271] Preferably a nucleic acid sequence of the present invention in the vector is under the control of, and operably linked to, an appropriate promoter or other regulatory elements for transcription in a host cell such as a microbial, e.g. bacterial, or yeast cell, or an insect or mammalian cell. The vector may be a bifunctional expression vector which functions in multiple hosts. In the case of genomic DNA, this may contain its own promoter or other regulatory elements and in the case of cDNA this may be under the control of an appropriate promoter or other regulatory elements for expression in the host cell

[0272] By “promoter” is meant a sequence of nucleotides from which transcription may be initiated of DNA operably linked downstream (i.e. in the 3′ direction on the sense strand of double-stranded DNA).

[0273] “Operably linked” means joined as part of the same nucleic acid molecule, suitably positioned and oriented for transcription to be initiated from the promoter. DNA operably linked to a promoter is “under transcriptional initiation regulation” of the promoter.

[0274] In a preferred embodiment, the promoter is an inducible promoter. The term “inducible” as applied to a promoter is well understood by those skilled in the art. In essence, expression under the control of an inducible promoter is “switched on” or increased in response to an applied stimulus. The nature of the stimulus varies between promoters. Some inducible promoters cause little or undetectable levels of expression (or no expression) in the absence of the appropriate stimulus. Other inducible promoters cause detectable constitutive expression in the absence of the stimulus. Whatever the level of expression is in the absence of the stimulus, expression from any inducible promoter is increased in the presence of the correct stimulus.

[0275] Thus these aspects of the invention provide a gene construct, preferably a replicable vector, comprising a promoter (optionally inducible) operably linked to a nucleotide sequence provided by the present invention.

[0276] Preferably the vector is capable of providing expression in an insect cell, such as an Sf9 cell, especially where the expressed product is to be crystallised. The polypeptide may be encoded by a vector construct substantially similar to those disclosed herein.

[0277] The present invention also encompasses method of making peptides or polypeptides as disclosed, the method including the step of expressing said polypeptide or peptide from nucleic acid encoding it, which in most embodiments will be nucleic acid according to the present invention. This may conveniently be achieved by growing a host cell containing such a vector in culture under appropriate conditions which cause or allow expression of the polypeptide. Polypeptides and peptides may also be expressed in in vitro systems, such as reticulocyte lysates, as will be appreciated by the skilled person.

[0278] Systems for cloning and expression of a polypeptide in a variety of different host cells are well known. Suitable host cells include bacteria, eukaryotic cells such as mammalian and yeast, and baculovirus-based insect expression systems. Mammalian cell lines available in the art for expression of a heterologous polypeptide include Chinese hamster ovary cells, HeLa cells, baby hamster kidney cells, COS cells and many others.

[0279] Although certain specific amino acid sequences are referred to herein, e.g. in the context of peptides capable of activating AGC kinases, it will be appreciated that similar sequences having functionally insignificant changes are equally appropriate for practising the present invention. Therefore amino acids present in the said sequences can be replaced by other amino acids having similar properties, for example hydrophobicity, hydrophobic moment, antigenicity, propensity to form or break a-helical or β-sheet structures, and so. Substitutional variants of a protein are those in which at least one amino acid in the protein sequence has been removed and a different residue inserted in its place. Amino acid substitutions are typically of single residues but may be clustered depending on functional constraints e.g. at a crystal contact. Preferably amino acid substitutions will comprise conservative amino acid substitutions. Insertional amino acid variants are those in which one or more amino acids are introduced. This can be amino-terminal and/or carboxy-terminal fusion as well as intrasequence. Examples of amino-terminal and/or carboxy-terminal fusions are affinity tags, maltose binding protein (MBP) tags, and epitope tags.

[0280] Amino acid substitutions, deletions and additions which do not significantly interfere with three-dimensional structure will depend, in part, on the region of the molecule where the substitution, addition or deletion occurs. In highly variable regions of the molecule, non-conservative substitutions as well as conservative substitutions may be tolerated without significantly disrupting the three-dimensional structure of the molecule. In highly conserved regions, or regions containing significant secondary structure, conservative amino acid substitutions are preferred.

[0281] Conservative amino acid substitutions are well-known in the art, and include substitutions made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity and/or the amphipathic nature of the amino acid residues involved. For example, negatively charged amino acids include aspartic acid and glutamic acid; positively charged amino acids include lysine and arginine; amino acids with uncharged polar head groups having similar hydrophilicity values include the following: leucine, isoleucine, valine; glycine, alanine; asparagine, glutamine; serine, threonine; phenylalanine, tyrosine. Other conservative amino acid substitutions are well known in the art.

[0282] In some instances, it may be particularly advantageous or convenient to substitute, delete and/or add amino acid residues to a particular binding site or catalytic residue, in order to provide convenient cloning sites in cDNA encoding the polypeptide, to aid in purification of the polypeptide, etc. Such substitutions, deletions and/or additions which do not substantially alter the three dimensional structure of the wild-type kinase will be apparent to those having skills in the art.

[0283] Particular embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0284]
FIG. 1 shows a comparison of PKB and PKA structures, with ribbon representations of PKA (A) and PKB (B). PKA and PKB were superimposed onto their C-terminal lobes. Phe 294 of the DFG motif of PKB occupies a site equivalent to the adenine pocket of the nucleotide binding site of PKA. (C) Stereo view of a superimposition of PKA and PKB to show different relative orientations of their N- and C-terminal lobes. Conformational differences in C-lobe are localised to the activation segment and αF/αG loop Figure drawn using BOBSCRIPT (Esnouf, 1997) and RASTER3D (Merit and Murphy, 1994)

[0285]
FIG. 2 shows the structure of the N-terminal Lobe:

[0286] (A) Flexibility of αB- and αC-helices. 2Fo-Fc electron density map contoured at 1σ of a portion of the N-terminal lobe of pΔPH-PKB-ΔC (β3, β4, β5-strands, βB- and βC-helices). Electron density for the β-sheet is well resolved, whereas the αB- and αC-helices are disordered. The main-chain of the N-terminal lobe and hydrophobic motif of PKA is shown superimposed onto PKB.

[0287] (B and C) Role of hydrophobic motif to order the αB- and αC-helices and link to activation segment. (B) Interactions of hydrophobic motif of PKA with the β3, β, β5-strands and αB- and αC-helices of the N-terminal lobe. Phe 347 and Phe 350 are buried by hydrophobic residues. Glu 349 and C-terminal carboxylate form hydrogen bonds with basic residues of the αC-helix. (C) Disorder of the αB- and αC-helices of PKB is correlated with absence of bound hydrophobic motif. In (B) bracketed residues corresponds to PKB numbering.

[0288]
FIG. 3. Role of αC-helix to regulate conformation of PKA and PKB and structure of activation segment and DFG motif. (A) αC-helix stabilises an active state of PKA by interaction with pThr 197 of the activation segment via His 87, and Phe 185 of the DFG motif via Ile 93 and Leu 94. (B) In PKB, disorder of the αC-helix prevents His 196 from interacting with pThr 309. Loss of interactions with Phe 294 of the DFG motif binds within the nucleotide-binding site of ATP.

[0289]
FIG. 4 shows a multiple sequence alignment of the catalytic domains and C-terminal regulatory segments of various AGC-family protein kinases. Invariant residues are shown with dark shading and conserved residues with light shading. The position of critical functional residues are indicated with a dark arrow and numbered according to PKA residues. PKB Thr 309 and Ser 474 phosphorylation sites are indicated. The conserved AGC-kinase hydrophobic motif is shown and mutated residues of PKB that influence PIFtide activation (FIG. 7B) are indicated by light arrows. Figure drawn using ALSCRIPT (Barton, 1993).

[0290]
FIG. 5 illustrates the activation of PKB by hydrophobic motif peptides and complex formation between PKB and PIFtide.

[0291] (A) Dose response curve for the activation of ΔPH-PKB-ΔC by various synthetic 23 residue peptides derived from the PKB regulatory segment. &Circlesolid;: PKB HM-P has a phosphoserine residue at position 474; ▾: PKB HM-D has aspartate at position 474; o: has an unphosphorylated serine residue at position 474 and so corresponds to the wild type sequence.

[0292] (B) Dose response curve for the activation of (p)ΔPH-PKB-ΔC by PIFtide a synthetic 24 residue peptide encompassing the PRK2 HM motif. &Circlesolid;: PIFtide and pΔPH-PKB-ΔC, ▾: PIFtide and ΔPH-PKB-ΔC, ∘: mutant PIFtide(D>A) and pΔPH-PKB-ΔC. PIFtide can bind to ΔPH-PKB-ΔC but cannot activate it in the absence of Thr-309 phosphorylation.

[0293] (C) Isothermal titration calorimetry measurements of the binding of PIFtide to pΔPH-PKB-ΔC (left) and ΔPH-PKB-ΔC (right). Upper panel, raw data of the titration of PIFtide into pΔPH-PKB-ΔC. Lower panel, integrated heats of injections, corrected for the heat of dilution, with the solid line corresponding to the best fit of the data using the MicroCal software.

[0294]
FIG. 6 shows that conserved residues of the hydrophobic motif, and residues of the N-lobe of PKB, are required for PIFtide and PKB HM-peptide mediated stimulation of PKB kinase activity. Mutations of conserved hydrophobic motif residues of PIFtide and PKB HM-peptide reduce or eliminate their potential to activate ΔPH-PKB-ΔC phosphorylated on Thr 309.

[0295] Mutations of hydrophobic and electrostatic residues of the ΔPH-PKB-ΔC N-lobe hydrophobic groove reduces the stimulation of PKB activity by 130 pM PIFtide. The position of mutated residues on PKA and PKB (R202D, V194A-V198A and L225A) are shown in FIG. 4.

[0296]
FIG. 7 is a comparison of the amino acid sequences of human PKBα, PKBβ and PKBγ. The PH and catalytic domains are shown boxed, and are connected by the linker domain. The GXXGXG ATP binding site, the catalytic lysine residue, and the regulatory phosphorylation sites are shown in bold type.

[0297]
FIG. 8 shows ribbon diagrams of the structures obtained for PKB-PIF and PKB S474D, illustrating the positions of the AMP-PNP moiety and the GSK-3 substrate peptide.

DETAILED DESCRIPTION OF THE INVENTION

[0298] Inactive Structures of PKB

[0299] Limited trypsinolysis of full length PKBβ purified from Sf9 cells led the present inventors to the identification of a protease resistant domain with an N-terminus at Lys-146, referred to as ΔPH-PKB. Lys-146 is located within the structurally diverse region linking the pleckstrin homology (PH) and kinase domains of PKB, close to the N-terminus of the corresponding β1-strand of PKA.

[0300] During the course of the purification, partial cleavage of a C-terminal 3 kDa fragment was observed, suggesting conformational flexibility at the C-terminus of the protein. Human PKBα, PKBβ and PKBγ sequences are structurally diverse within a 12 residue region C-terminal to the conserved PP(D/E) motif (residues 452-454 of PKBβ), preceding the C-terminal hydrophobic motif, and corresponding to the C-terminus of the PKBβ splice variant.

[0301] Using this information, the present inventors constructed a number of new PKB baculovirus Fastbac entry vectors for the generation of PKB insect cell/baculovirus expression systems, and expressed the β and γ-isoforms of PKB as the kinase domain, with an N-terminus at Lys-146 (i.e. lacking the PH domain), with and without the C-terminal 21 residues that includes the hydrophobic regulatory segment. These two kinase domains are termed ΔPH-PKB and ΔPH-PKB-ΔC, respectively.

[0302] These expression systems express high levels of protein, which have been purified to homogeneity. Moreover, PDK1has been expressed using the insect cell/baculovirus system and MAPKAPK2 in the E. coli expression system to enable phosphorylation of PKBβ on Thr309 and Ser474, respectively.

[0303] To prepare defined phosphorylated states of PKB, phosphorylation and dephosphorylation reactions were performed using PDK1 (for pThr-309) and the non-specific λ-protein phosphatase, respectively.

[0304] Distinct phosphorylated states of the protein were resolved using hydrophobic interaction chromatography.

[0305] The phosphorylation state of the protein was analysed by Western blots using phospho-specific antibodies, and the stoichiometry and sites of phosphorylation were quantitatively assessed by mass spectroscopic analysis of trypsin-generated peptides of the protein.

[0306] Crystals were successfully obtained for the PKBβ derivatives, and structures determined for ΔPH-PKBβ-ΔC, pΔPH-PKBβ-ΔC and ΔPH-PKBβ by X-ray crystallographic techniques. High resolution structures were obtained, apparently showing the catalytic domain of PKBβ in the inactive conformation.

[0307] The phosphorylation state of the protein was analysed by Western blots using phospho-specific antibodies, and the stoichiometry and sites of phosphorylation were quantitatively assessed by mass spectroscopic analysis of trypsin-generated peptides of the protein. The three crystal forms of human PKBβ are; (i) pΔPH-PKB-ΔC, phosphorylated in vitro on Thr-309, (ii) ΔPH-PKBβ-ΔC, not phosphorylated on Thr-309, and (iii) ΔPH-PKBβ, dephosphorylated in vitro.

[0308] Two different batches of crystals, having different resolution, were produced for crystal form (i), i.e. pΔPH-PKB-ΔC.

[0309] Results

[0310] Each of the crystals belonged to the tetragonal space group P41212, and accommodated one molecule of PKB per asymmetric unit with cell parameters as follows:

[0311] pΔPH-PKB-ΔC (first batch): a=149.33 Å, b 149.33 Å, c=39.77 Å; pΔPH-PKB-ΔC (second batch): a 148.40 Å, b 148.40 Å, c 38.55 Å;

[0312] ΔPH-PKB-ΔC: a 149.70 Å, b=149.70 Å, c=39.19 Å;

[0313] ΔPH-PKB: a =149.52 Å, b=149.52 Å, c=39.06.

[0314] Resolution was determined to be 2.8 Å for the first batch and 2.3 Å for the second batch of PΔPH-PKB-ΔC crystals, 2.7 Å for ΔPH-PKB-ΔC and 2.5 Å for ΔPH-PKB.

[0315] The current refined R-factor:

[0316] (Σ|F0-Fc|/Σ|F0|, where F0=observed amplitude, and Fc=calculated amplitude) is as follows:

[0317] pΔPH-PKBβ-ΔC (second batch): 0.237 to 2.3 Å resolution.

[0318] ΔPH-PKBβ-ΔC: 0.238 to 2.7 Å resolution.

[0319] ΔPH-PKBβ: 0.254 to 2.5 Å resolution.

[0320] More detailed information about the data collection and refinement statistics are provided for all crystals except the first batch of pΔPH-PKB-ΔC is provided in Table 1 below.

1TABLE 1Crystallographic Data Collection and Refinement Statistics for InactiveCrystalsProteinpΔPH-PKBβ-ΔCΔPH-PKBβ-ΔCΔPH-PKBβAmino acid residues146-460146-460146-481PhosphorylationThr-309——Space group (Z)P41212 (1)P41212 (1)P41212 (1)Cell parameters a148.40149.70149.52(Å)c (Å)38.5539.1939.06X-ray sourceID14eh4 ESRFID14eh4 ESRFID14eh4 ESRFResolution (Å)2.32.72.5Observations (N)113 67750 87592 809Unique (N)18 90512 14716 090Completeness (%)96.194.299.7aRsym0.050 (0.243)0.065 (0.236)0.057 (0.255)I/σI21.018.014.8RefinementResolution range35-2.335-2.7535-2.6(Å)Reflections used (N)17 57610 32014 317Rfree set (N) (%)1398 (7.1)1199 (9.9)1598 (10.0)bRcryst/Rfree0.237/0.3090.238/0.300.254/0.314Protein atoms (N)2 1982 1982198Solvent atoms (N)15427125r.m.s.d. bond angles1.541.571.53(°)r.m.s.d. bond0.01050.01120.0104lengths (Å)

[0321] Values in parentheses are for the highest shell aRsym=ΣhΣj|<−I(h)j|/ΣhΣj<I(h)>, where <I(h)> is the mean intensity of symmetry-equivalent reflections. bRcryst/free=Σ∥Fobs|−|Fcalc∥/Σ|Fobs|, where Fobs and Fcalc are the observed and calculated structure factors, respectively. Root-mean-square deviations relate to the Engh and Huber parameters.

[0322] Overall Description of the Inactive Structure and Comparison with PKA

[0323] The structure of pΔPH-PKB-ΔC is essentially identical to those of ΔPH-PKB-ΔC and ΔPH-PKB (rms deviations of 0.3 Å and 0.4 Å, respectively), and this similarity to inactive forms of PKB, together with features of the structure, indicates that the crystallisation conditions favoured the inactive conformation of pΔPH-PKB-ΔC. Because of the higher resolution of the pΔPH-PKB-ΔC crystal structure, most of the discussion is focussed on this form.

[0324] The structure of pΔPH-PKBβ-ΔC (residues 146-460) resembles the catalytic domain of other protein kinases (reviewed by Johnson et al., 1996). In particular, it resembles that of the catalytic subunit of PKA (FIG. 1). The PKB molecule is organised into an N-terminal and C-terminal lobe, with the N-terminal lobe (residues 146-233) formed from a 5-membered P-sheet and flanking a-helix, αA (equivalent to αC of PKA). The C-terminal lobe (residues 234-450) is predominantly a-helical and is joined to the N-terminal lobe via a single polypeptide chain connection.

[0325] The catalytic site of PKB is situated at the interface of the N and C-terminal lobes and is formed from residues of the catalytic loop (residues 274-282), and the activation segment (residues 304-312) of the C-terminal lobe, together with the ATP binding site and the αA helix of the N-terminal lobe. The ATP binding site consists of a hydrophobic pocket formed by residues (Val158, Val166) that interact with the adenine ring of the nucleotide, and a more hydrophilic region that interacts with the ribose ring and phosphate groups. By analogy with other protein kinases (Hubbard, 1997), the activation segment provides the binding site for the peptide substrate, orientating the substrate amino acid towards the phosphates of the ATP.

[0326] The catalytic mechanism of all protein kinases is similar and involves a phosphoryl transfer reaction from the γ-phosphate group of the ATP onto the hydroxyl group of the substrate amino acid residue. The reaction commences with the nucleophilic attack by the hydroxyl group of the substrate amino acid residues onto the γ-phosphate of ATP. A catalytic base in PKBp, Asp265, facilitates this attack by increasing the nucleophilicity of the substrate hydroxyl group. The phosphate moieties of ATP are coordinated by the glycine rich loop and Lys1181 of the N-terminal lobe and by a Mg2+ ion that interacts with Asp293 of the protein kinase C-terminal lobe.

[0327] PKA and PKB share essentially the same secondary structure topology, except that in PKB there is no counterpart to the αA-helix of PKA, and some of the structural elements of PKB are disordered. The architecture of PKA consists of an N-terminal lobe based on a 5-stranded β-sheet, with two α-helices (the αB- and αC-helices), and a larger, mainly a-helical C-terminal lobe, containing the activation segment. The catalytic site for ATP is located at the interface of the two lobes, whereas the substrate peptide-binding site is within the C-lobe, centred on the activation segment.

[0328] The inactive state of PKB differs in structure from the catalytically active form of PKA in a number of respects that are important for the regulation of PKB by multi-site phosphorylation. These differences involve the overall juxtaposition of the N- and C-lobes of the kinase, and structural disorder of the αB- and αC-helices of the N-lobe, activation segment of the C-lobe, and C-terminal regulatory segment. When superimposed, equivalent Cα-atoms of PKB and the ternary complex of PKA differ by an rms deviation of 2.3 Å (FIG. 1C). This deviation is larger than the expected value of 1.2 Å for a pair of proteins with 43% sequence identity (Cothia and Lesk, 1986), and results from differences in the relative orientations of the N- and C-terminal lobes of PKA and PKB When superimposed individually, differences in conformation between the equivalent N- and C-lobes of PKA and PKB are seen to be localised to the β1-strand and αC-helix in the N-lobe, and DFG motif and αF/αG loop in the C-lobe.

[0329] PKA adopts open and closed conformational states resulting from relative rotations of the N- and C-lobes that are associated with various substrate-PKA complexes, with the ternary-PKA complex adopting a closed state, and the apo and binary complexes being more open. However, the relative position of the N- and C-lobes of PKB, do not resemble any of the various PKA-ligand complexes. Compared with the PKA-ternary complex, the N-lobe of PKB is rotated by 20° relative to its C-lobe, causing catalytic site residues from the two lobes to be misaligned.

[0330] Comparison of a number of activated protein kinase structures indicates that their N- and C-terminal lobes adopt similar relative configurations. For example, the Cα-Cα distance of two residues (Val-57 and Leu-173) that span the nucleotide-binding site in the PKA ternary complex is 12.9 Å, the same as that between equivalent residues of the phosphorylated insulin receptor kinase (Hubbard, 1997). In contrast, for PKB this distance is 15.2 Å.

[0331] Structural Disorder in PKB

[0332] In addition to variations in their overall bilobal configuration, the structures of PKB and PKA differ in other respects that are significant for the reduced catalytic activity of unphosphorylated and mono-phosphorylated forms of PKB. In the inactive PKB structures, three inter-related regions of the polypeptide chain are disordered; (i) the αB- and αC-helices of the N-terminal lobe, (ii) the activation segment between the invariant DFG and APE motifs, and (iii) the C-terminal regulatory segment in ΔPH-PKB. Concerted disorder to order transitions of these regions, linked to a conformational change of the activation segment DFG motif, and reorganisation of the N- and C-lobes, are required to generate a catalytically active protein kinase on phosphorylation of Thr-309 and Ser-474.

[0333] Although the structures of the three disordered regions are inter-dependent, each region is described in turn, before discussing the biological implications that these regions are disordered. This analysis is greatly assisted by the ability to compare the structural differences between an inactive PKB molecule with that of the related active PKA catalytic subunit, the latter serving as a model for an active phosphorylated form of PKB.

[0334] Flexibility of the αB- and αc-helices

[0335] Within the N-terminal lobe of PKB, the β-sheet is well ordered, however, residues Ala-189 to Thr-207, equivalent to the αB-helix and the majority of the αC-helix of PKA, are highly mobile, as judged by disorder in the weighted 2Fo-Fc electron density, and composite simulated annealing omit maps, and analysis of the atomic temperature-factors (FIG. 2A). Specifically, for all crystal forms, there is no visible electron density to account for residues Ala-189 to Thr-197, whose counterparts in PKA form the C-terminus and N-terminus of the αB- and αC-helices, respectively.

[0336] Electron density corresponding to the main-chain of the remaining residues of the αC-helix is fragmented, and the side-chains of these residues are disordered. The short αB-helix, which connects the αC-helix with the central β3-strand of the P-sheet, is unique to the AGC-protein kinases, and causes the N-terminus of the αC-helix to be displaced from the β4/β5-strands of the P-sheet (FIG. 1, 2). As a consequence, the αC-helix packs less tightly against the hydrophobic side-chains of the β-sheet, compared with other protein kinases, and, significantly a deep surface groove is created at the interface between the αB/αC-helices and P-sheet. In PKA this groove permits interactions between the N-terminal lobe and C-terminal hydrophobic motif.

[0337] The importance of the conserved αC-helix for both catalytic and regulatory functions has been demonstrated for many protein kinases. An invariant glutamate residue located near the N-terminus of the helix, (Glu-91 of PKA, Glu-200 of PKB), is responsible for its catalytic function by forming a hydrogen bond with an invariant lysine side-chain; Lys-72 of PKA (FIG. 3). Lys-72 in turn coordinates the P-phosphate of ATP in active protein kinases.

[0338] In addition, because the αC-helix is responsible for the major interfacial contacts between the N- and C-lobes, particularly via its interactions with the DFG motif of the activation segment, it plays a role both in aligning catalytic and substrate-peptide binding residues of the C-terminal lobe, and in governing the overall juxtaposition of the N- and C-lobes.

[0339] Motion of the αC-helix represents a general mechanism for the modulation of kinase catalytic activity, and the integration of diverse regulatory signals. For example, the position of the αC-helix of CDK2 is shifted to an active conformation on the association of the monomeric CDK2 subunit with cyclin A (Jeffrey et al., 1995), and similar changes in the αC-helix are observed on activation of the insulin receptor kinase and ERK2 on phosphorylation of their activation segments (Hubbard 1997; Canagarajah et al., 1997), and in the Src- and Eph-family tyrosine kinases (Sicheri et al., 1997, Xu et al., 1997; Wybenga-Groot et al., 2001). Significantly, in many protein kinases that are regulated by phosphorylation of the activation segment, the αC-helix provides a basic residue to contact the phosphate group of the phospho-amino acid, hence coordinating the relative positions of the αC-helix with the activation segment, and the N- and C-terminal lobes. In PKA, the basic residue is His-87 at the N-terminus of the αC-helix, which contacts pThr-197 of the activation segment (FIG. 2, 3). In the inactive state of PKB, His-196 and Glu-200 of the αC-helix (equivalent to His-87 and Glu-91 of PKA) are disordered, and contacts between Glu-200 and Lys-181 (Lys-72 of PKA), and those between His-196 and pThr-309, are not formed (FIG. 3).

[0340] Disorder of the αC-helix contributes to an inactive state of PKB for two reasons. First, the side-chain of Lys-181 is not properly positioned, and second, there are associated changes in the structure of the activation segment, and relative disposition of the N- and C-terminal lobes. As described below, disorder of the αB- and αC-helices of PKB is coupled to the disorder of its non-phosphorylated C-terminal regulatory segment.

[0341] Role of the C-terminal Regulatory Segment

[0342] A distinctive structural feature of PKA, not usually observed in other protein kinases, is the interaction of the extreme C-terminus of the protein with its N-terminal lobe. In PKA, the polypeptide chain emerges from the C-terminal lobe and extends along the entire length of the bi-lobal structure. At the tip of the N-lobe, the chain forms a reverse turn, allowing the extreme C-terminal eight residues of PKA to lie within an amphipathic/hydrophobic groove on the surface of the N-lobe (FIGS. 1A, 2B). Importantly, these interactions are mediated by residues of the C-terminal hydrophobic motif, which contact the surface groove formed by residues of the αB- and αC-helices, and the 5-strand of the N-lobe. The dominant interactions at the interface involve those between the side chains of the two phenylalanine residues of the hydrophobic motif, Phe-347 and Phe-350, which protrude into a pocket formed by hydrophobic residues of the N-lobe (FIG. 2). Specifically, the phenyl-ring of Phe-347 is extensively buried by the side-chains of five amino acids: Lys-76, Val-79 and Val-80 of the αB-helix, Ile-85 of the αC-helix, and Leu-116 of the P5-strand, whereas the side-chain of Phe-350 contacts Leu-89 and Lys-92 of the αC-helix, and Leu-116 and Met-118 of the β5-strand (FIG. 2B). At one end of the channel, two adjacent basic residues of the αC-helix form salt-bridge interactions with two carboxylate groups of the hydrophobic motif.

[0343] In all three inactive crystal structures of PKB, residues corresponding to the regions of the αB- and αC-helices of PKA that interact with the hydrophobic motif, are disordered, and this probably results from loss of interactions with the hydrophobic motif of PKB (FIG. 2A, C). In the crystal structures of ΔPH-PKB-ΔC, the 21 residues C-terminal to Ser-460 were removed from the expression construct, and therefore potential interactions between the hydrophobic motif and the N-lobe are not possible. Moreover, in these structures, electron density for residues C-terminal to Asp-441 is not visible, suggesting that they are conformational disordered. However, in the ΔPH-PKB structure, which contains a non-phosphorylated hydrophobic motif, and therefore retains the potential to interact with the N-lobe, we are also unable to detect visible electron density for residues C-terminal to Asp-441, indicating that the C-terminal 40 residues, including the hydrophobic motif, are mobile.

[0344] Conformation of the Activation Segment and Nucleotide Binding Site

[0345] The activation segment is central to the regulation and catalytic activity of protein kinases (Johnson et al., 1996). In the structure of active protein kinases, the activation segment contributes to the correct conformation of the catalytic site and ATP-binding residues, and participates in peptide-substrate recognition and specificity. By functioning as a link between the N- and C-lobes, conformational changes of the activation segment, resulting from regulatory phosphorylation, and/or modulator subunits, are coupled to global changes in kinase structure. In all three crystal forms of PKB, a contiguous region of the activation segment (residues 297 to 312) located between the invariant DFG and APE motifs, and including (p)Thr-309, is disordered. There is no electron density visible for these residues in either the 2Fo-Fc, or the simulated annealling omit maps. It was determined that pΔPH-PKB-ΔC was phosphorylated on Thr-309 by quantitative mass spectroscopic analysis of a tryptic digest of the protein. Moreover, it was confirmed that the protein forming the pΔPH-PKB-ΔC crystal was phosphorylated by Western blot analysis of a dissolved crystal using pThr-309-specific antibodies.

[0346] In the inactive PKB structures, residues of the DFG sequence are ordered, but adopt a different conformation from their counterparts in PKA, functioning to inhibit PKB by disrupting the nucleotide-binding site (FIG. 3). The DFG motif of activated protein kinases is important because its Asp residue (Asp-184 of PKA) coordinates the Mg2+ ion responsible for contacting the β- and γ-phosphates of ATP. In PKB, the side-chain of Asp-293 (equivalent to Asp-184 of PKA) is directed away from the ATP binding site (FIG. 3B). This structural change is accompanied by a shift in the positions of Phe-294 and Gly-295 of the DFG motif, and main-chain of Leu-296, towards the glycine-rich β1-β2 nucleotide-binding loop of the N-lobe. Motion of the DFG-motif residues is accommodated by a change in the relative orientation of the N- and C-lobes of PKB, compared with PKA, to avoid their clash with the β1-strand of the N-lobe. Relative to the conformation of the equivalent Phe-185 residue of PKA, the phenyl ring of Phe-294 is displaced by as much as 10 Å, and is situated within the hydrophobic adenine-binding pocket for ATP. This structural feature of PKB is similar to the inactive state of IRK where the Phe residue of the DFG motif blocks the nucleotide-binding site by mimicking the ATP adenine ring (Hubbard et al., 1994). Thus, in PKB, the ATP binding site is disrupted both because the Lys-181 and Asp-293, residues responsible for coordinating the phosphate groups, are displaced, and because ATP is sterically hindered from binding by Phe-294. In PKA, and in the structures of other activated protein kinases, Phe-185 of the DFG motif packs deep into the interface between the two lobes, and forms intimate contacts with hydrophobic residues of the αC-helix of the N-lobe. These interactions serve to stabilise the relative positions of the αC-helix and activation segment. The altered conformation of Phe-294 of PKB is correlated with the relative dispositions of its N- and C-lobes, and the disorder of the αC-helix.

[0347] Crystal structures of protein kinase-peptide substrate complexes indicate that a common function of the activation segment is to coordinate the peptide-substrate with the correct geometry to allow phosphorylation of the incoming hydroxyl-group of a Ser/Thr or Tyr residue (Knighton et al., 1991b, Bossemeyer, 1993, Hubbard, 1997; Lowe et al., 1997). In PKA, the P+1 region of the activation segment, immediately C-terminus to pThr-197, contributes to peptide binding. The conservation of the P+1 region amongst AGC-kinases, suggests that in the phosphorylated active state of a PKB-substrate complex, similar peptide-protein interactions will exist. Disorder of the activation segment of PKB in both the unphosphorylated and mono-phosphorylated (pThr-309) states will preclude interactions with protein substrates.

[0348] PKB Peptide Substrate Specificity

[0349] The substrate specificity of PKB is known from an analysis of physiological PKB phosphorylation sites, and from an oriented peptide library screen (Obata et al., 2000). PKB only phosphorylates peptides with an arginine at the P-3 position and also strongly prefers substrates with an Arg residue at P-5 and with large hydrophobic residues at P+1. The structural basis for this substrate specificity can be rationalised by comparing the ternary PKA complex with our structure of PKB including the activation segment modelled on that of PKA. Optimal peptide substrates of PKA are related, although not identical, to those of PKB and other AGC-kinases. In the ternary PKA structure, PKI has the sequence T-G-R-R-N-A-I-H, with Ala at P-0. Arg at P-3 forms a salt bridge to Glu-127 (Knighton et al., 1991b; Bossemeyer et al., 1993), and because this residue is also conserved in PKB and phosphorylase kinase (where it contacts an Arg at P-3, Lowe et al., 1997), it is likely that the equivalent interaction will be formed in PKB-peptide complexes. Interestingly, the side-chain of Tyr-330 of PKA that is directed towards the Arg P-3 residue is a glutamate in PKB, possibly enhancing the affinity for a peptide with an Arg at P-3. Unlike PKB, PKA does not have a preference for an Arg at P-5, and in the PKA structure, Arg-133 is in close proximity to the Thr side-chain at P-5 of PKI. In PKB, however, Arg-133 is replaced with a serine, and this less bulky residue would accommodate a potential interaction between the peptide Arg residue at P-5 and Glu-342 of PKB. Finally, PKB prefers bulky hydrophobic residues at P+1, in contrast to PKA which is only able to accommodate smaller aliphatic residues. This P+1 hydrophobic site is larger in PKB because the side-chain of Phe-359 lacks the hydroxyl group of the equivalent Tyr-247 residue of PKA.

[0350] Mechanism of PKB Activation by Phosphorylation

[0351] The crystal structures of PKB, combined with an analysis of the structural differences between PKB and an activated conformation of PKA, provides a framework for understanding the mechanism of activation of PKB by phosphorylation of Thr-309 and Ser-474. Central to the conversion to the activated state on phosphorylation, are concerted disorder to order transitions of the αB- and αC-helices, activation segment, and C-terminal regulatory segment, all of which are linked to conformational changes of the DFG motif and re-orientation of the N- and C-lobes to relieve steric hindrance to ATP binding, and to align catalytic site residues. Because the known structures of activated protein kinases all share the same overall features, including juxtaposition of catalytic site, and ATP and peptide binding residues, we can assume that phosphorylation of PKB converts the enzyme into a conformation similar to that of PKA phosphorylated on Thr-197. However, what distinguishes PKB from PKA, is the requirement for phosphorylation of both the C-terminal regulatory segment and the activation segment, to activate the kinase maximally. The role of Thr-309 phosphorylation will be similar to activation segment phosphorylation of PKA, CDK2 and ERK2, namely to coordinate contacts between the activation segment and other structural elements of the protein kinase, specifically, (i) the αC-helix of the N-lobe, (ii) a conserved arginine residue immediately preceding the catalytic Asp residue (Arg-165 and Asp-166, respectively of PKA), and (iii) a basic residue of the activation segment situated close to the Asp of the DFG motif (Lys-189 of PKA). Conservation of the three basic residues of PKA that contact the phosphate group of pThr-197 in all PKB-isoforms, suggests that the equivalent charge neutralisation observed in PKA will occur in the active state of PKB In all three crystal forms of PKB, which represent low and partially active forms of the enzyme, and includes pΔPH-PKB-ΔC phosphorylated on Thr-309, the activation segment is disordered, and the enzyme adopts an inactive conformation. Thus phosphorylation of Thr-309 alone is not sufficient to order the activation segment and promote an active state of the enzyme; additional phosphorylation of Ser-474 is required. The hydrophobic motif of PKA is not regulated by phosphorylation, and in the PKA crystal structure lies within a surface hydrophobic groove formed by residues whose counterparts in the αB- and αC-helices of the inactive states of PKB are disordered. The finding that the C-terminal regulatory segment, comprising the unphosphorylated hydrophobic motif of ΔPH-PKB was disordered, suggests that activation by Ser-474 phosphorylation is caused by the concomitant ordering of the regulatory segment and αB- and αC-helices mediated by the interaction of the motif with the induced N-terminal lobe surface groove. Ordering of the αC-helix will induce global changes in the PKB conformation by facilitating interactions between the residues of the αC-helix and critical regions of the molecule. These interactions include those between Lys-181 and Glu-200, and two αC-helix-activation segment interactions; His-196 and pThr-309, and hydrophobic contacts with Phe-294 of the DFG motif. Reconfiguration of the activation segment allows the correct alignment of catalytic site and substrate binding residues. Consistent with this model of activation by ordering of the regulatory segment induced by Ser-474 phosphorylation, previous studies of PKA suggested that an ordered hydrophobic motif is important for enzyme activity and stability. Replacing the conserved Phe residues of the motif with alanines, reduces catalytic activity to only 0.5% of the wild-type enzyme, and leads to decreased thermal stability (Etchebehere et al., 1997).

[0352] Allosteric Activation of pThr 309-PKB by Hydrophobic Motif Peptides

[0353] To test the model that Ser 474 phosphorylation promotes an interaction between the hydrophobic motif and the induced hydrophobic groove of the N-terminal lobe, thereby causing an allosteric activation of the kinase, the ability of peptides modelled on the hydrophobic motif of PKB to activate the enzyme via an intermolecular association with the N-terminal lobe was assessed.

[0354] First, it was shown that towards Crosstide, a peptide-substrate derived from the PKB phosphorylation site of GSK-3, the unphosphorylated form of ΔPH-PKB-ΔC has no significant catalytic activity, whereas its Thr 309 phosphorylated counterpart was active. Addition of a peptide modelled on the phosphorylated hydrophobic motif of PKBβ (HM-P, residues 460-481), activated pΔPH-PKB-ΔC, with the stimulation reaching a maximum of 4-fold at 0.6 mM, the highest concentration of HM-P peptide achievable in our assay (FIG. 5A). Significantly, this 4-fold stimulation of PKB by HM-P peptide is lower than the 7-10 fold stimulation of PKB by Ser 474 phosphorylation (Alessi et al., 1996a). Analysis of the concentration-dependent activation of PKB by HM-P (FIG. 5A) revealed that the binding sites for HM-P on ΔPH-PKB-ΔC were not fully titrated even at a peptide concentration of 0.6 mM, suggesting that higher concentrations of HM-P are necessary to fully stimulate PKB activity. The modest activation of PKB by HM-P peptide suggests a relatively low affinity of peptide for the PKB N-terminal lobe. An equivalent HM-peptide with an Asp substitution of Ser 474 was also capable of activating pΔPH-PKB-ΔC, consistent with studies showing that Asp mimics Ser 474 phosphorylation (Alessi et al., 1996a). However, the maximum activation by this peptide was only 3-fold because of the lower affinity towards ΔPH-PKB-ΔC than the HM-P peptide (FIG. 5A). Finally, the unphosphorylated HM-peptide did not stimulate PKB activity. It was also found that the phosphorylated HM-peptide did not further activate ΔPH-PKB phosphorylated on both Thr 309 and Ser 474. Furthermore, HM-P peptide was unable to activate ΔPH-PKB-ΔC with unphosphorylated Thr 309, in agreement with earlier findings that growth factor stimulation fails to activate T308A mutants of PKBa (Bellacosa et al., 1998) indicating an essential role of Thr 308/309 phosphorylation for PKB activity.

[0355] Phosphorylation of a Ser or Thr residue within the hydrophobic motif is a conserved feature of the activation of varied AGC-kinases, including PKC (Keranen et al., 1995) and the p70 and p90 S6-kinases (Pearson et al., 1995; Frodin et al., 2000). However, in some PKC isoforms, and in the PKC related kinase, PRK2, the site of Ser/Thr phosphorylation is replaced with either an Asp or Glu residue, suggesting that in these kinases, the hydrophobic motif will be constitutively activated, similarly to PKA, because of a permanent negative charge at this site. The C-terminal region of PRK2 that encompasses the carboxy-terminal hydrophobic motif was previously shown by Alessi and colleagues to interact tightly with the AGC-family kinase PDK1 (Balendran et al., 1999). PIFtide, a peptide representing the C-terminal 24 residues of PRK2, including its hydrophobic motif, was observed to stimulate PDK1 activity by four-fold (Biondi et al., 2000). Remarkably, PIFtide was found here to activate pΔPH-PKB-ΔC by 15-fold, substantially more strongly than the activation achieved by the phosphorylated HM-peptide. Analysis of the concentration dependence of pΔPH-PKB-ΔC activation by PIFtide, revealed that the peptide binds the kinase with high affinity, resulting in a maximum and saturable activation at 20 μM and a corresponding EC50 value of 3 μM (FIG. 5B). Significantly, the specific activity of pΔPH-PKB-ΔC maximally activated by PIFtide was 350 nmol/min/mg, essentially identical to the specific activity of ΔPH-PKB phosphorylated on both Thr 309 and Ser 474. These specific activity data indicate that the stimulation of pΔPH-PKB-ΔC by an intermolecular association with PIFtide is equivalent to Ser 474 phosphorylation and the resultant intramolecular association between the N-lobe of PKB and phosphorylated HM and furthermore suggests that an analysis of PKB-PIFtide interactions will provide insights concerning the mechanism of activation by Ser 474 phosphorylation. PIFtide promotes a 5-fold activation of ΔPH-PKB phosphorylated on Thr 309 to a specific activity similar to that of pΔPH-PKB-ΔC. The lower level of stimulation relative to the 15-fold observed for pΔPH-PKB-ΔC can be explained by the partial phosphorylation of Ser-474 on pΔPH-PKB purified from Sf9 cells.

[0356] Using isothermal titration calorimetry, the affinity between PIFtide and both pΔPH-PKB-ΔC and ΔPH-PKB-ΔC was determined (FIG. 5C). Firstly, we found that the equilibrium dissociation constant defining the interaction between PIFtide and PΔPH-PKB-ΔC was 6 μM, essentially identical to the EC50 value for the activation of pΔPH-PKB-ΔC by PIFtide (FIG. 5B). This result suggests that the association of PIFtide to PKB correlates with the activation of the kinase. Secondly, it was found that the interaction of PIFtide with ΔPH-PKB-ΔC is driven by a large negative enthalpy change (AH of −16.0 kcal.mol−1) that compensates the energetically unfavourable decrease in entropy (TAS of −9.2 kcal.mol−1). The observed large decrease in entropy is not generally typical of protein-peptide interactions, for example SH2-domain-phosphotyrosine peptide complexes (Ladbury et al., 1996), and is consistent with an ordering of both the protein, presumably the αB- and αC-helices of the N-lobe, and peptide on complex formation. Although PIFtide does not stimulate the activity of ΔPH-PKB-ΔC (FIG. 5B), ITC data revealing a dissociation constant of 5.5 μM indicated that PIFtide interacts with this form of the enzyme as strongly as it does to phosphorylated ΔPH-PKB-ΔC, further emphasising the crucial role of Thr 309 phosphorylation for PKB activity (FIG. 5C).

[0357] The finding that PIFtide interacts with PKB with high affinity provided a model system for testing the notion that the essential role of Ser 474 phosphorylation is to promote the association of the hydrophobic motif with the N-lobe of PKB. The residue of PIFtide equivalent to Ser 474 of PKB is an Asp, which presumably mimics a phosphorylated Ser 474 residue. To assess the importance of this residue for the ability of PIFtide to activate PKB, the concentration dependent activation of pΔPH-PKB-ΔC by PIFtide with an Ala residue substituting for the Asp was determined. Although higher concentrations of this mutant PIFtide(D−>A) are required to activate pΔPH-PKB-ΔC than wild type PIFtide, suggesting a lower affinity, the maximal activation of the kinase achieved by saturating concentrations of the mutant peptide is identical to that of the wild type peptide (FIG. 5B) The estimated EC50 value for PIFtide(D−>A) is 30 μM, indicating a 10-fold lower affinity than PIFtide. ITC experiments also revealed an approximately 25-fold lower affinity between PIFtide(D−>A) and pΔPH-PKB-ΔC relative to PIFtide. Thus, these experiments demonstrate an important concept that the PIFtide-induced conformational change of pΔPH-PKB-ΔC that results when PIFtide interacts with the kinase, and which leads to a maximal stimulation of the kinase activity, does not require a negatively charged residue at the equivalent of Ser 474 of the hydrophobic motif. The major role of a negative charge at this site is to increase the association of PIFtide with the PKB N-lobe, and that other residues, particularly the conserved Phe residues of the FxxF motif (see below), are more critical for promoting the conformational change of the protein.

[0358] Because of the low affinity between pΔPH-PKB-ΔC and the PKB HM peptides, it was not possible to determine a KD value defining their interaction with PKB using ITC. However, by assuming that the association between pΔPH-PKB-ΔC and the PKB HM-peptides is an equilibrium process and that at saturating concentrations of peptide, the activation of pΔPH-PKB-ΔC will be similar to that induced by PIFtide, the data in FIG. 5A were used to estimate the EC50 constants for the phosphorylated and S474D HM-peptides to be 2.3 mM and 3.6 mM, respectively, an affinity ˜1000-fold lower than for PIFtide.

[0359] Mutagenesis of the Hydrophobic Motif and N-lobe Hydrophobic Groove

[0360] By assessing the ability of modified PIFtide and HM peptides to activate pΔPH-PKB-ΔC, the role of conserved residues of the hydrophobic motif (HM) to induce the active conformation of PKB was delineated. These experiments used an 11-residue peptide encompassing the six-residue hydrophobic motif of PIFtide (PIFtide1, FIG. 6A) that essentially recapitulates the activation of pΔPH-PKB-ΔC observed for the 24-residue PIFtide. The slightly lower activation suggests that residues of PIFtide N-terminal to the HM cohtribute to high affinity PKB interactions. The PKB activities were determined at PIFtide concentrations ranging from 210-250 μM, where wild-type PIFtide fully activates PKB (FIGS. 5B, 6A). While all conserved residues of the HM motif contribute to PKB activation, significantly, the two phenylalanine residues of the motif are essential for HM-induced activation. Ala substitutions of these residues in both PIFtide and the phosphorylated PKB HM-peptide, completely eliminated the potential of these peptide to stimulate PKB, even at PKB HM-peptide concentrations of 1.2 mM (FIG. 6A). A similar essential role for the equivalent Phe residues has been proposed for PKA where Ala substitutions lower the thermal stability, and virtually abolishes the catalytic activity of the enzyme (Etchebehere et al., 1997). Mutation of either the conserved Tyr residue or of both Asp residues of the PTFtide motif showed that these residues also contribute to the stimulatory affect of PIFtide on PKB activity (FIG. 6A). PIFtide activates PKB by interacting with, and simultaneously stabilising the activated conformation of PKB. Therefore, the lower stimulatory effect of mutant PIFtide and PKB peptides most likely results from a reduced affinity for the activated conformation of PKB, however, because mutant PIFtide peptides have either low or no activity even at >200 μM, we were unable to determine EC50 values for their activation of PKB.

[0361] The crucial role of the conserved Phe residues of the hydrophobic motif to promote PIFtide and PKB HM-peptide mediated stimulation of PKB, and for the activity of PKA, suggests that they stabilise the active state of both PKB and PKA by a related structural mechanism. To test the notion that a hydrophobic groove is induced in PKB to engage the hydrophobic motif, and activate the kinase, a series of His tagged pΔPH-PKB-ΔC hydrophobic groove mutants was prepared and their responsiveness to PIFtide assessed. PKB mutants were transiently expressed in HEK cells, phosphorylated in vitro with PDK1, and purified using Ni-NTA agarose. SDS-PAGE and western blot analysis of the purified fractions revealed that wild type and mutant proteins were expressed to similar levels, and that the enzyme was quantitatively isolated in a phosphorylated state.

[0362] Moreover, the basal kinase activities of wild type and mutant proteins were similar, indicating that the mutations did not disrupt the overall structure of the protein. Wild type PKB prepared using this procedure was stimulated ˜5-fold by 130 μM PIFtide (FIG. 6B). The slightly lower activation probably results from incomplete Thr 309 phosphorylation, and consequently the PKB HM-peptide did not elicit measurable activation. The substitution of hydrophobic groove residues significantly reduced, but did not completely abolish the potential of PIFtide to stimulate PKB (FIG. 6B). Mutation of two αC-helix residues, Val 194 and Val 198 (Ile 85 and Leu 89 of PKA), reduced PIFtide activation to only 25% of wild type, whereas a Leu 225 mutant of the P-5 strand (Leu 116 of PKA) caused almost a complete loss of responsiveness to PIFtide (FIG. 2, 4, 6B)

[0363] Electrostatic interactions are important in defining high affinity PIFtide and PKB HM peptide associations with PKB (FIG. 5B), and form the basis for the increased affinity of the HM for the N-lobe and subsequent activation of PKB by Ser 474 phosphorylation. Examination of the PKA and PKB crystal structures suggests that Arg 202 of the αC-helix is likely to be important in mediating contacts to pSer 474 and the corresponding Asp residue of PIFtide. The equivalent residue of PKA, Arg 93, which is also conserved in PKC and PRK2, forms a water-mediated salt bridge to the carboxylate group of Glu 349 (FIG. 2). A charge reversal at this site (R202D) almost eliminates the ability of 130 pM PIFtide to activate PKB (FIG. 6B), consistent with the notion that Arg 202 forms electrostatic contacts with PIFtide. However, analogous to the finding that at high concentrations, the PIFtide(D−>A) mutant could activate PKB maximally (FIG. 5B), the R202D PKB mutant was more responsive to higher concentrations of the peptide.

[0364] Conservation of the Hydrophobic Motif Groove in AGC-Protein Kinases

[0365] The role of a phosphorylated hydrophobic motif to activate PKB that is described here, is probably applicable to other AGC-protein kinases that are regulated via dual phosphorylation of an activation segment residue and a hydrophobic motif residue, for example PKC, the p70 and p90 S6 kinases and SGK (Parekh et al., 2000; Pearson et al., 1995; Frodin et al., 2000; Kobayashi and Cohen, 1999). A disorder-order transition of PKC induced by phosphorylation is implied by the resistance of the fully phosphorylated, but not partially phosphorylated forms of PKC, to protein phosphatases, and their enhanced resistance to temperature-induced denaturation (Bornancin and Parker, 1997). Substitutions of the Phe residues of the hydrophobic motif of PKA lowers its thermal stability, and virtually abolishes its catalytic activity (Etchebehere et al., 1997). The conservation of the hydrophobic motif of AGC-kinases is correlated with the invariance of the residues equivalent to Lys-76 and Leu-116 of PKA that would be predicted to form the base of the hydrophobic groove in a number of diverse AGC-kinases, including PKA, PKB, PKC, p70-S6K, p90-S6K, SGK, NDR and PDK1. Alessi and colleagues have shown that the hydrophobic motif of PIFtide determines the ability of this peptide to bind to the N-lobe, hence activating PDK1(Balendran et al., 1999), and the presence of PIFtide greatly increases the thermal stability of PDK1(Biondi et al., 2000). By analogy to PKB, we suggest that the activation of PDK1by PIFtide involves a disorder-order transition of the αB- and αC-helices, and consequent global conformational changes.

[0366] Structure-Based Drug Design

[0367] Determination of the 3D structure of PKBβ provides important information about the binding sites of PKBβ, particularly when comparisons were made with similar enzymes. This information may then be used for rational design of PKBβ inhibitors, e.g. by computational techniques which identify possible binding ligands for the binding sites, by enabling linked-fragment approaches to drug design, and by enabling the identification and location of bound ligands using X-ray crystallographic analysis.

[0368] Since all known small molecule inhibitors of protein kinases are competitive with ATP, and therefore interact with the ATP binding site, an understanding of the PKB residues involved in the interaction with ATP enables the development of specific and potent inhibitors of this kinase. This information may thus be used to develop potent and specific small molecule inhibitors of PKB in a number of ways. PKBβ may be co-crystallised, and/or existing PKBβ crystals may be soaked, with known inhibitors of PKB, including staurosporin, and those discovered in high-throughput screening programmes known to the skilled person. Alternatively, or additionally, rational drug design programmes may make full use of the crystallographic coordinates.

[0369] Discussion and Implications for Other AGC Kinases

[0370] This study presents a model for the regulation of PKB by hydrophobic motif phosphorylation. The data indicates that the role of HM phosphorylation is to induce an ordered N-terminal lobe as a result of an increased affinity between the hydrophobic motif and the hydrophobic groove. Ordering of the αC-helix transmits a structural change to the activation segment and re-orients the N- and C-lobes. In the inactive PKB crystal structures residues of the αB- and αC-helices are disordered. Consistent with a disorder-to-order transition, the interaction of PIFtide with PKB is accompanied by a large negative entropy change. Mutation of key hydrophobic residues of the N-lobe groove and hydrophobic motif either reduce or eliminate the ability of PIFtide to activate PKB. Using PIFtide as a model system shows that the role of a negative charge within the HM (e.g. PKB Ser 474 phosphorylation) is to increase the affinity of the HM for the N-lobe. In the context of the PKB kinase domain, phosphorylation of Ser 474 will increase the ability of the HM to interact with the N-lobe via an intramolecular association. However, because PIFtide(D−>A) had only 10-fold lower affinity for PKB relative to PIFtide (FIG. 5B),-it is likely that the unphosphorylated HM of PKB will still retain a weak affinity for the N-lobe. It can therefore be rationalised why PKB mono-phosphorylated on Thr 309 has between 7-10-fold lower activity than doubly phosphorylated PKB.

[0371] Disorder to order transitions of the αC-helix as a result of phosphorylation represents a previously unrecognised mechanism for the stimulation of protein kinase activity. However, there is evidence that other AGC-kinases undergo similar transitions, modulated by the hydrophobic motif. For example, phosphorylation of the HM of PKC increases its resistance to temperature-induced denaturation (Bornancin and Parker, 1997) and the Phe residues of the PKA HM motif are critical for its stability and catalytic activity (Etchebehere et al., 1997). The conservation of the hydrophobic motif of AGC-kinases is correlated with the invariance of the residues equivalent to Lys 76 and Leu 116 of PKA predicted to form the base of the hydrophobic groove in a number of diverse ACC-kinases, (FIG. 4). Uniquely amongst AGC-kinases, PDK1 lacks a C-terminal hydrophobic motif, although its N-terminal lobe hydrophobic groove is proposed to interact with PIFtide (Biondi et al., 2000). Similarly to the findings with PKB, high affinity interactions between PIFtide and PDK1required the conserved aromatic and Asp residues of the hydrophobic motif of the peptide (Balendran et al., 1999), and were disrupted by substitutions of PDK1HM groove residues (Biondi et al., 2000).

[0372] The affinity of the HM-P peptide for PKB that is not phosphorylated on Ser 474 is −1000-fold lower than that of PIFtide, and is reminiscent of the low affinity of the tyrosine phosphorylated C-terminus of Src for its own SH2 domain, compared with optimal phosphotyrosine binding sequences (Bradshaw et al., 1998). The covalent attachment of the phosphorylated hydrophobic motif to the PKB kinase domain will greatly increase its effective concentrations presumably in excess of the EC50 value estimated for the activation of PKB by the HM-P peptide. However, a modest mutual affinity may be important for two reasons. First, in order for phosphorylation of the HM to be capable of modulating its affinity for the N-lobe, the affinity of the unphosphorylated HM for the N-lobe must be sufficiently low that it is not constitutively associated with the N-lobe. For example, a substitution of PIFtide(D−>A) for the PKB HM motif would render PKB fully active and therefore unresponsive to HM phosphorylation. Second, it allows modulator proteins to gain access either to the hydrophobic groove or the phosphorylated motif, or for protein phosphatases to dephosphorylate pSer 474. Whether the activation of PKB by PIFtide reflects a biologically significant regulatory mechanism for stimulation of PKB by a modulator protein that interacts with the N-lobe is unknown. However, the affinity of PIFtide for PKB may provide insight concerning the nature of the PDK2 enzyme responsible for phosphorylating Ser 474. A possible candidate for this enzyme is a kinase that interacts with the hydrophobic binding groove of PKB, perhaps via a sequence similar to the hydrophobic motif of PKB or PIFtide.

[0373] Active Structures of PKBβ

[0374] Using the principles set out above, the present inventors generated activated conformations of PKB for use in structural studies, firstly by replacing the PKB HM with the PRK2 HM sequence, and secondly by introducing the mutation S474D into ΔPH-PKB. The resultant proteins termed PKB-PIF and PKB S474D, were expressed in Sf9 cells and phosphorylated in vitro on Thr-309 using PDK1. The phosphorylated PKB-PIF protein, has a specific activity equivalent to bis-phosphorylated (i.e. pThr-309, pSer-474) PKB, confirming that the enzyme corresponds to an activated state of the kinase.

[0375] Here is described the crystal structure of a ternary complex of the activated PKB-PIF chimera associated with a GSK-3p peptide, the first identified PKB substrate (Cross et al., 1995), and the ATP analogue AMP-PNP. The structure explains the requirement for Thr-309 phosphorylation for activity and how the PIFtide HM (as a model for Ser-474 phosphorylation) promotes the activated PKB conformation via an allosteric mechanism. Analysis of the interactions between PKB and the GSK-3β peptide explains how PKB selects for protein substrates that are distinct from those of PKA. The crystal structure of the ternary PKB S474D-GSK-3/AMP-PNP complex was found to be essentially identical to the PKB-PIF structure, demonstrating the utility of the PIFtide HM for generating activated kinase domains of AGC-protein kinases, and so further discussion centres on the PKB-PIF structure.

[0376] Results

[0377] Detailed information about the crystals, and the data collection and refinement statistics are provided in Table 2 below.

2TABLE 2Crystallographic Data Collection and Refinement Statistics for ActiveCrystalsProteinPKBβ-PIFPKBβ-S474DAmino acid residues146-479146-481PhosphorylationThr-309Thr-309Space group (Z)P212121 (1)P212121 (1)Cell parameters a (Å)44.9444.91b (Å)61.0061.00c (Å)131.32129.41X-ray sourceID14eh2 ESRFID14eh4 ESRFResolution (Å)1.61.7Observations (N)150 113116 971Unique (N)42 77527 820Completeness (%)94.2 (88.7)82.4 (63.7)aRsym0.052 (0.198)0.078 (0.186)I/σI6.1 (3.4)6.0 (2.3)RefinementResolution range (Å)50-1.650-1.7Reflections used (N) (%)40 387 (83.2)30 601 (76.5)Rfree set (N) (%)2 132 (4.4)1 517 (3.8)bRcryst/Rfree0.197/0.2270.205/0.234Protein atoms (N)2 5872 590Solvent atoms (N)345280Ligand atoms (N)112112r.m.s.d. bond angles (°)1.501.47r.m.s.d. bond lengths (Å)0.01220.0124

[0378] Values in parentheses are for the highest shell 1.69-1.6 Å and 1.79-1.7 Å for PKB-PIF and PKB-S474D, respectively. aRsym=ΣhΣj|<I(h)j|/ΣhΣj<I(h)>, where <I(h)>is the mean intensity of symmetry-equivalent reflections. bRcryst/free −Σ∥Fobs|−|Fcalc∥/Σ|Fobs |, where Fobs and Fcalc are the observed and calculated structure factors, respectively. Root-mean-square deviations relate to the Engh and Huber parameters.

[0379] Coordinate data for the two active crystals is provided at the end of this specification as follows:

[0380] Table 6: PKB-PIF

[0381] Table 7: PKB S474D

[0382] Overall Structure of Active PKBβ Conformation, and Activation by PIFtide

[0383] The structure of the PKB-PIF ternary complex determined to 1.6 Å resolution, shown in FIG. 8, is virtually identical to the PKA ternary complex (Knighton et al., 1991b; Bossemeyer et al., 1993). Equivalent residues of the two kinases superimpose closely (r.m.s.d. 1.2 Å) with their N and C-lobes adopting similar relative orientations. The structural equivalence to the catalytic subunit of PKA, together with the presence of nucleotide and peptide substrates bound to PKB in a productive manner, indicates that the enzyme crystallised as an active enzyme-substrate complex. The activated PKB conformation differs markedly from the inactive state.

[0384] In the activated PKB-PIF structure, the αB and αC helices of the N-lobe are fully ordered, as is the activation segment and hydrophobic motif (FIG. 8). The αC helix of PKB-PIF adopts the same conformation to that seen in all other active protein kinases (Johnson et al., 1996), permitting the helix to fulfil its role to organise an active kinase structure by maintaining the nucleotide binding site and activation segment in a catalytically competent state. First, Glu-200 of the αC-helix forms a salt-bridge with Lys-181, positioning this residue to contact the β-phosphate of AMP-PNP. Second, the αC-helix contributes one of the residues (His-196) responsible for the charge neutralisation on the phosphate group of pThr-309 of the activation segment. As for the equivalent residues of PKA, pThr-309 also contacts Arg-274 of the catalytic loop and Lys-298 of the activation segment, thereby coordinating distinct regions of the structure important for configuring a kinase catalytic site (FIG. 9). Finally, the hydrophobic residues of the αC-helix interact with the aromatic side chain of Phe-294 of the DFG motif, positioning Phe-294 adjacent to the catalytic loop. The shift of conformation of Phe-294 relative to the inactive PKB state contributes to the formation of a nucleotide-binding site. In the inactive state, the altered conformation of the DFG motif causes Phe-294 to occupy the nucleotide-binding pocket, directly blocking nucleotide binding, whereas the shift in position of Asp-293 (Asp-184 of PKA), disrupts metal ion binding to the kinase catalytic site. Interactions between AMP-PNP/Mn2+ and the catalytic site of PKB-PIF are reminiscent of those between AMP-PNP/Mn2+ and PKA (FIG. 10). Specifically, the coordination of two Mn2+ ions and associated water molecules in the PKB structure is virtually identical to that seen in PKA. However, the adenine-binding pocket shows some differences between the two kinases, resulting in distinct protein interactions to the adenine ring and protein-bound water molecules. Such differences in protein structure will be crucial to the development of specific inhibitors of PKB.

[0385] By coordinating the phosphate group of pThr-309 via His-196, and inducing a shift in conformation of the DFG motif, the ordered αC-helix is responsible for creating a nucleotide binding site, and ordering the activation segment necessary for the generation of a catalytically competent protein kinase linked to formation of a substrate peptide binding site (see below). In the inactive conformer of mono-phosphorylated PKB, although Thr-309 is phosphorylated, disorder of the αC-helix causes a loss of contact to His-196, which together with a conformational change of the DFG motif, results in a disordered activation segment. Shifts in conformation of the αC-helix are known to be associated with the allosteric regulation of diverse kinases including CDK2 (Jeffrey et al., 1995), Src/Lck (Sicheri et al., 1997, Xu et al., 1997) and the Eph tyrosine kinase (Wybenga-Groot et al., 2001). However, the modulation of the PKB structure by a disorder to order transition of the αC helix, represents a novel mechanism for the regulation of protein kinase activity.

[0386] Hydrophobic motif peptides stimulate PKB allosterically, by promoting and stabilising the active conformation of the kinase domain characterised by ordered αB and αC helices, and activation segment. Introduction of a negative charge (either phosphoserine or an Asp amino acid) at residue 474 of the PKB HM increases its affinity for PKB. In the crystal structure of PKB-PIF, the HM of PIFtide associates within a groove in the N-lobe (FIG. 11). The groove is formed at the interface of the αB and αC helices with the β-4 and β-5 strands of the central β-sheet, and is induced by the ordered αB and αC helices. Extensive hydrophobic contacts between the invariant aromatic side-chains of Phe-470 and Phe-473 of the HM motif and hydrophobic residues of the αB and αC helices and β-5 strand, essentially equivalent to those observed in PKA (Phe-347 and Phe-350), function to stabilise the ordered αB and αC helices. The critical structural role the HM Phe residues perform to promote ordered αB and αC helices explains the finding that their replacement by Ala completely eliminates the ability of PIFtide and PKB HM peptides to stimulate PKB. Similarly, in PKA the equivalent Phe residues are also essential for its stability and catalytic activity (Etchebehere et al., 1997). The C-terminus of the HM of PKB extends relative to its counterpart in PKA where Phe-350 corresponds to the C-terminal residue of the catalytic subunit and probably contributes to a correctly positioned and ordered αC-helix. In PKB, residues Tyr-475 to Trp-479 pack against the C-terminus of the αC helix and form an edge P-strand of the central β-sheet. The aromatic side chain of the invariant Tyr-475 residue of the HM motif packs against Leu-215, whereas its hydroxyl group forms a hydrogen bond to the side chain of Arg-208. The conservation of these two αC-helix residues suggests that similar interactions will occur between the HM Tyr residue and αC-helix in other AGC kinases.

[0387] An Asp residue mimics the property of Ser-474 phosphorylation to activate PKB Substitution of Ala for Asp at the equivalent position of the HM of PIFtide reduced the affinity of the mutant PIFtide for PKB by 10-fold, suggesting that the role of a negative charge at this position (either phosphoserine or Asp) is to promote the association of the HM to the N-terminal lobe, concomitantly activating the kinase In the electron density map, the side chain for Asp-474 is well ordered, however, slightly contrary to our expectations, the Asp carboxylate group does not form salt bridges with basic residues of the protein. Three contacts with the protein are formed, however. First, a hydrogen bond (3.0 Å) is accepted from the amide side chain of Gln-220 of the β-4 strand. Second, a water-mediated contact is formed to the main-chain amide group of Gln 220. Thirdly, and intriguingly, a van der waals contact (3.5 Å) is made between the OD1 atom of Asp-474 and the edge hydrogen atom of the HM Phe-473 aromatic ring. The geometry of this interaction, where the OD1 atom of Asp-474 is in plane with the aromatic ring of Phe-473, suggests that this interaction would be energetically stable and may therefore contribute to the favourable interaction between the PIFtide HM and PKB by stabilising the appropriate conformation of the Phe-473 side chain allowing it to engage the N-lobe hydrophobic groove. PIFtide associates with PKB 1000-fold more tightly that the authentic PKB HM. One possible explanation is that Asp-472 of the PIF HM (Gln in PKB) forms a salt-bridge with Arg 202 of the αC-helix, similar to that between Glu-349 and Arg-93 of PKA, whereas Asp-478 accepts a hydrogen bond from Arg-208. In addition Trp-479 (Ile in PKB) forms extended hydrophobic contacts with Ala-214 and Lys-216 of the αC-helix (FIG. 11)

[0388] Protein-Peptide Interactions

[0389] The substrate specificity of PKB is known from an analysis of physiological PKB phosphorylation sites, and from an oriented peptide library screen (Alessi et al., 1996b; Obata et al., 2000). PKB only phosphorylates peptides with arginine residues at the P−3 and P−5 positions, and also strongly prefers substrates with a large hydrophobic residue at P+1 and a Thr at P−2. Optimal peptide substrates of PKB are related, although not identical, to other AGC-kinases. PKA for example, phosphorylates peptides with smaller aliphatic residues at P+1, and basic residues at P−3 and P−2 (Kennelly and Krebs, 1991). The structural basis for this substrate specificity can be rationalised by comparing the ternary PKA complex with our structure of PKB in complex with residues 3-12 of GSK-3β. Similarly to other protein kinases, the substrate peptide binding site is centred on the activation segment, with main-chain amide and carbonyl groups of residues P+1 to P+3 of the peptide forming a two-stranded anti-parallel β-sheet with residues of the P+1 site of the activation segment (Cys-311 and Gly-312). The side-chain of Arg at P-3 of the GSK-3 peptide forms a bidendate salt bridge to Glu-236 of PKB, identical to that seen in the PKA and phosphorylase kinase-peptide complexes. (Knighton et al., 1991b; Lowe et al., 1997). Also similar to PKA, Asp-440 accepts a long (4 Å) hydrogen bond from the quanidinium group of Arg at P−3. Unlike PKB however, PKA does not have a preference for an Arg at P−5, and in the PKA structure, Arg-133 is in close proximity to the Thr side-chain at P−5 of PKI, suggesting that a peptide with Arg at P−5 would be excluded. In contrast, the residue equivalent to Arg-133 is a serine in PKB and this less bulky residue allows the interaction of the peptide Arg residue at P−5 with Glu-279 and Glu-342. Interestingly, the guanidinium group of Arg at P−5 of the GSK-3 peptide bound to PKB adopts a similar position to the guanidinium group of an Arg at P−2 of the PKI peptide bound to PKA, suggesting that a peptide with Arg residues at both P−2 and P−5 could not bind to PKB. Thr (P−1) is solvent exposed, however the hydroxyl group of the Thr (P−2) side chain donates a hydrogen bond to the carboxylate group of Glu-279, which in turn contacts Arg at (P−5), explaining the preference of a peptide for Thr at P−2 (Alessi et al., 1996a, Obata et al., 2000). Finally, the bulky hydrophobic Phe residue at P+1 of the peptide is accommodated within an enlarged P+1 pocket resulting from the presence of a Phe at residue 359 compared with a Tyr in the equivalent position of PKA.

[0390] Interactions between the catalytic domain and the nucleotide analogue AMP-PNP, the substrate peptide GSK-3, and between the catalytic domain and PIFtide are detailed in the following Tables 3 to 5 respectively.

3TABLE 3List of contacts between PKB-PIF and AMP-PNPPKB-PIFatomsAMP-PNPatomsdistance ÅGly159ACAAMP-PNP500BO4*3.70Val166ACBAMP-PNP500BO4*3.52Val166ACG1AMP-PNP500BN93.81Val166ACG2AMP-PNP500BO5*3.35AMP-PNP500BC5*3.89AMP-PNP500BO4*3.37Ala179ACBAMP-PNP500BN63.78AMP-PNP500BC63.60AMP-PNP500BN13.50Lys181ACDAMP-PNP500BO1A3.58Lys181ACEAMP-PNP500BO2B3.81AMP-PNP500BO1A3.33AMP-PNP500BO3A3.67Lys181ANZAMP-PNP500BO2B3.01***AMP-PNP500BPB3.81AMP-PNP500BO1A2.83***AMP-PNP500BO3A3.57*AMP-PNP500BPA3.75Thr213ACG2AMP-PNP500BN63.63Met229ASDAMP-PNP500BN63.86Met229ACEAMP-PNP500BN73.48AMP-PNP500BN63.74Glu230AOAMP-PNP500BN63.01***Tyr231ACD1AMP-PNP500BC23.88Ala232ANAMP-PNP500BN13.20***AMP-PNP500BC23.75Ala232ACBAMP-PNP500BN13.76Glu236ACGAMP-PNP500BO2*3.31Glu236ACDAMP-PNP500BO2*3.33Glu236AOE2AMP-PNP500BC3*3.76AMP-PNP500BO3*2.94***AMP-PNP500BC2*3.63AMP-PNP500BO2*2.61***Asp275AOD2AMP-PNP500BO2G3.82*Lys277ACEAMP-PNP500BO2G3.12Lys277ANZAMP-PNP500BO2G2.89***Glu279ACAMP-PNP500BO3*3.76Glu279AOAMP-PNP500BC3*3.62AMP-PNP500BO3*2.78***Asn280AOD1AMP-PNP500BO2G3.70*AMP-PNP500BO2A3.42*Met282ASDAMP-PNP500BC2*3.84Met282ACEAMP-PNP500BC2*3.77AMP-PNP500BO2*3.90AMP-PNP500BC23.76AMP-PNP500BN33.31AMP-PNP500BC43.71Thr292ACBAMP-PNP500BN73.66Thr292AOG1AMP-PNP500BC83.65AMP-PNP500BN72.84***AMP-PNP500BC53.72AMP-PNP500BN63.84*Thr292ACG2AMP-PNP500BC83.70AMP-PNP500BN73.62Asp293ACAAMP-PNP500BO1A3.79Asp293ACBAMP-PNP500BO1A3.37AMP-PNP500BPA3.82AMP-PNP500BO2A3.29Asp293ACGAMP-PNP500BO2B3.18AMP-PNP500BO1A3.59AMP-PNP500BPA3.81AMP-PNP500BO2A3.31Asp293AOD1AMP-PNP500BO2B2.98***Asp293AOD2AMP-PNP500BO1G3.24***AMP-PNP500BO2B3.05***AMP-PNP500BPG3.47AMP-PNP500BN3B3.53*AMP-PNP500BO2G3.07***AMP-PNP500BPB3.79AMP-PNP500BPA3.86AMP-PNP500BO2A3.02***Phe439ACE2AMP-PNP500BN33.49Phe439ACZAMP-PNP500BC23.78AMP-PNP500BN33.75

[0391] Contacts listed if less than 3.9 Å between AMP-PNP and PKB-PIF

4TABLE 4List of contacts between PKB-PIF and GSK-3GSK-3atomsPKB-PIFatomsdistance ÅArg4CCDGlu342AOE23.50Phe238ACE13.77Arg4CNEGlu342AOE22.88***Arg4CCZTyr316AOH3.81Glu342AOE23.82Phe238ACE13.77Glu279AOE23.57Arg4CNH1Glu279ACD3.80Phe238ACD13.89Phe238ACE13.22Phe238ACZ3.37Glu279AOE22.95***Arg4CNH2Glu279ACD3.51Glu279AOE13.05***Tyr316ACE13.30Tyr316ACZ3.47Tyr316AOH2.78***Glu279AOE23.28***Arg4COPhe238ACZ3.44Pro5CCDTyr351AOH3.87Pro5CCGTyr351AOH3.75Arg6CCAGlu279AOE23.65Arg6CCGPhe238ACE23.72Arg6CCDPhe443ACE13.88Phe443ACZ3.65Arg6CNEPhe443ACZ3.77Arg6CCZGlu279ACG3.87Glu236AOE23.39Glu236AOE13.83Arg6CNH1Phe238ACD23.79Glu236ACD3.35Glu236AOE23.08***Glu236AOE12.86***Arg6CNH2Glu279ACB3.82Glu279ACG3.63Glu236ACD3.76Glu236AOE22.83***Arg6CCGlu279AOE23.72Thr7CNGlu279AOE22.84***Thr7CCAGlu279AOE23.70Thr7CCBGlu315AOE13.62Thr313ACG23.56Glu279AOE23.67Thr7COG1Lys277ACD3.64Glu279ACD3.34Glu279AOE13.27***Thr313ACG23.47Glu279AOE22.93***Thr7CCG2Glu315ACD3.68Glu315AOE13.41Thr7CCLys277ANZ3.69Thr7COLys277ANZ2.98***Glu279AOE23.83*Thr8CCALys277ANZ3.80Thr8CCThr313AOG13.89Lys277ANZ3.73Thr8COPro314ACD3.39Thr313AOG13.88*Thr313ACG23.72Ser9CNThr313AOG13.72*Lys277ANZ3.54*Ser9CCAGly312AO3.23Thr313AOG13.50Ser9CCBAsp275AOD23.65Gly312AO3.41Thr313AOG13.58Ser9CCGly312AO3.54Phe10C NGly312AO2.90***Phe10C CD2Pro314ACD3.75Gly312AC3.85Gly312AO3.14Phe10C CE1Phe310ACE13.85Phe310ACD13.84Phe310AO3.59Phe10C CE2Leu317ACD13.85Gly312AC3.83Gly312AO3.55Phe10C CZLeu317ACD13.78Phe10C OCys311ACA3.42Cys311ACB3.32Cys311AC3.86Gly312AN3.25***Leu296ACD13.70Gly312AO3.48*Ala11C CAPhe310A03.79Ala11C CBGlu193ACD3.84Glu193AOE13.48Glu193AOE23.71Ala11C CPhe310AO3.90Glu12C NPhe310AO3.05***Glu12C CBPhe310AO3.55Glu12C OE1Phe310ACB3.89Glu12C OE2Phe310ACD13.56

[0392] Contacts listed if less than 3.9 Å between GSK-3 peptide and PKB-PIF

5TABLE 5List of contacts between catalytic domain of PKB-PIF and PIFtidePIFtideatomsPKB-PIFatomsdistance ÅMet469ACGVal194ACG13.89Met469ACEIle189ACD13.75Phe470ACBGln220AOE13.60Gln220ANE23.64Phe470ACE1Val194ACG13.78Leu225ACD13.71Phe470AOGln220ANE22.92***Asp472AOGln205ANE23.03***Asp472AOD2Arg202ANH22.47***Phe473ACASer201AOG3.75Phe473ACD1Ser201ACB3.79Phe473ACE1Phe227ACE23.79Phe227ACZ3.60Phe473ACE2Phe219AO3.42Leu225ACD23.85Cys226AO3.73Phe473ACZLeu225ACD23.85Leu225ACB3.74Phe227ACE23.75Phe227ACZ3.66Phe473ACSer201AOG3.64Phe473AOSer201AOG2.77***Gln205ANE23.30***Ala218ACB3.38Asp474ACAAla218AO3.34Asp474ACGGln220ANE23.90Asp474AOD1Gln220ANE23.33*Gln220AN3.84*Gln220ACG3.64Phe219ACA3.69Ala218AO3.80*Asp474ACAla218AO3.63Tyr475ANAla218ACB3.82Ala218AO2.96***Tyr475ACBGln205ACG3.83Gln205ACD3.86Ala218ACB3.86Tyr475ACGGln205ACG3.67Tyr475ACD1Gln205ACG3.84Gln205AOE13.88Tyr475ACD2Leu215ACD23.66Tyr475ACE2Leu215AO3.56Tyr475AOHGln205AO3.66*Arg208ANH23.12***Arg208ACZ3.65Arg208ANH13.54*Tyr475AOTyr217ACA3.43Tyr217AC3.67Ala218AN2.97***Ala218AO3.34*Ile476ACLys216AO3.88Ala477ANLys216AO2.98***Ala477ACALys216AO3.71Ala477ACBLeu215AO3.67Lys216AO3.25Asp478AOD1Arg208ANH23.12***Trp479ACE2Leu215AO3.87Trp479ANE1Leu215AO3.70*Trp479ACZ2Leu215AC3.81Ala214ACB3.74Leu215AO3.50Trp479ACLys216ANZ3.60Trp479AOLys216ANZ3.73*Trp479AOXTLys216ACE3.82Lys216ANZ2.74***

[0393] Contacts listed if less than 3.9 Å between PIFtide and catalytic domain of PKB-PIF

[0394] Materials and Methods

[0395] The Genebank accession numbers for the PKB isoforms are as follows: α gi 190827 (m63167); β gi 178325 (m95936); γ gi 4757578 (af124141)

[0396] Expression of ΔPH-PKBβ-ΔC (residues 146-460) and ΔPH-PKBfl (residues 146-481)

[0397] Generation of recombinant baculovirus using the GIBCO/Life Sciences Bacmid system was performed using standard procedures.

[0398] For ΔPH-PKBβ-ΔC, 3 PCR reactions were set up as follows:

636.5μlH2O5μl10x pfu buffer5μldNTPs0.2 mM1.5μl5′ Primer 3611760 pmols1μl3′ Primer 3650860 pmols1μlPfastBacHTa ΔPH PKBβ 2851a(170 ng)50μltotal + 2.5 u pfu

[0399] Pfu polymerase and buffer were purchased from Promega (M7741). All PCR reactions were performed in a Perkin Elmer Geneamp PCR system 9700.

[0400] PCR conditions 60 s at 95° C.,

[0401] then 15 cycles:

[0402] 60 s at 95° C.

[0403] 120 s at annealing temperature 62° C.

[0404] 180 s at 72° C.

[0405] Primers were:

[0406] 36117: GCC ATG GAT CCG AAA GTG ACC ATG AAT GAC TTC (5′ BamHI)

[0407] 36508: GGG GGT ACC TCA CAG GCT GTC ATA GCG GTC AGG (3′ KpnI)

[0408] For ΔPH-PKBβ, 3 PCR reactions were set up as follows:

737μlH2O5μl10x pfu buffer5μldNTPs2.5 mM1μl5′ Primer 3611770 pmols1μl3′ Primer 2858554 pmols1μlpFastBacHTa.ΔPH PKBβ 2702b(200 ng)50μltotal + 2.5 u pfu

[0409] Pfu polymerase and buffer were purchased from Promega (M7741). All PCR reactions were performed in a Perkin Elmer Geneamp PCR system 9700

[0410] PCR conditions 60 s at 95° C.,

[0411] then 15 cycles:

[0412] 60 s at 95° C.

[0413] 120 s at annealing temperature 66° C.

[0414] 180 s at 72° C.

[0415] Primers were:

836117:GCC ATG GAT CCG AAA GTG ACC ATG AAT GAC TTC(5′ BamHI)28585:GGG GGT ACC TCA CTC GCG GAT GCT GGC CGA GTA GG(3′ KpnI)

[0416] All PCR fragments were pooled and purified using the Qiagen PCR purification kit (28106) and digested with the appropriate restriction enzymes and subcloned into the pFastBacHTa (10584-027) vector from Gibco BRL life technologies.

[0417] Ligation mixes were used to transform E. coli XLl blue (Stratagene) and colonies containing recombinant DNA were grown up for miniprep DNA analysis. Miniprep was prepared using Qiagen miniprep kit 27106. All expression constructs were fully sequenced on an Applied Biosystems 3700 automated sequencer.

[0418] Insect cells (density ˜2.0×106 cells/ml, total volume of 2.7 L; 5.4×109 Sf9 cells), grown in a culture of GIBCO/Life Sciences supplemented Sf9001I medium were infected at a moiety of infection of 2 and grown for 72 hours prior to harvesting.

[0419] Purification of ΔPH-PKBβ/-ΔC (residues 146-460) and ΔPH-PKBβ (residues 146-481)

[0420] All procedures were performed at 4° C.

[0421] 1. Cell lysis: Insect cells were lysed in a Q-sepharose buffer A (25 mM Tris.HCl, [pH 7.5], 25 mM NaCl, 25 mM NaF, 25 mM β-glycerophosphate, 0.1% (v/v) β-mercaptoethanol, 2 mM benzamidine, 0.2 mM PMSF, 10% (v/v) glycerol, 1 μg/ml of DNAase.

[0422] 2. Q-sepharose, anion exchange chromatography: The lysate was cleared by centrifugation and loaded onto a 50 mL Q-sepharose column equilibrated in buffer A. The column was washed in 200 mL of buffer A and PKB was eluted using 100 mL of buffer A+1 M NaCl.

[0423] 3. Ni-NTA affinity chromatography: The pH of the eluate was raised to 8.0 using a 1 M of Tris.HCl (pH 9.2) and this sample was loaded onto a Ni-NTA agarose column containing 10 mL of Ni-NTA agarose resin that had been pre-equilibrated in buffer B: 20 mM imidazole, 20 mM Tris.HCl (pH 8.0), 25 mM NaF, 25 mM β-glycerophosphate, 500 mM NaCl, 0.1% (v/v) P-mercaptoethanol, 2 mM benzamidine, 0.2 mM PMSF. The column was washed and the protein was eluted using buffer B+300 mM imidazole. EDTA and DTT to final concentrations of 0.5 mM and 2 mM, respectively, were added immediately to the eluted protein. Phosphorylation reactions (see below) were performed after this step.

[0424] 4. Phenyl TSK hydrophobic interaction chromatography: The protein was brought to the appropriate concentration of ammonium sulphate and loaded onto a phenyl TSK column equilibrated in buffer C: 50 mM Tris.HCl (pH 7.5), 100 mM NaCl, 2 mM DTT, 2 mM benzamidine, 0.2 mM PMSF, with the same concentration of ammonium sulphate as the protein solution. The column was washed and PKB was eluted using a linear gradient developed to a buffer D consisting of 50 mM Tris.HCl (pH 7.5), 100 mM NaCl, 15% (v/v) glycerol, 2 mM DTT, 2 mm benzamidine, 0.2 mM PMSF.

[0425] Concentrations of ammonium sulphate used were as follows:

9pΔPH-PKBβ-ΔC1.23 M ammonium sulphateΔPH-PKBβ-ΔC0.63-0.68 M ammonium sulphateΔPH-PKBβ0.82-0.86 M ammonium sulphate

[0426] Following this HIC step, those proteins which were to be dephosphorylated were treated with λ protein phosphatase, as described below.

[0427] 5. Tev protease cleavage. The 6×His affinity tag was removed by cleavage using Tev (tobacco etch virus) protease. Tev protease was added to PKB from step 4 and this solution was dialysed over 14 hr into buffer E: 50 mM Tris.HCl (pH 8.0), 100 mM NaCl, 5 mM DTT.

[0428] 6. To remove Tev protease (as well as PDK1 and λ protein phosphatase, where appropriate) from PKB after cleavage of the His-tag from PKB, the solution of Tev protease and PKB were dialysed into buffer B: 20 mM imidazole, 20 mM Tris.HCl (pH 8.0), 25 mM NaF, 25 mM β-glycerophosphate, 500 mM NaCl, 0.1% (v/v) β-mercaptoethanol, 2 mM benzamidine, 0.2 mM PMSF and loaded onto a Ni-NTA agarose column. Cleaved PKB was recovered in the flow through.

[0429] 7. Q-sepharose, anion exchange chromatography. The PKB collected in step 6 was dialysed into Q-sepharose buffer F: 25 mM Tris.HCl (pH 7.5), 25 mM NaCl, 5% (v/v) glycerol, 0.5 mM EDTA, 2 mM DTT, 0.2 mM PMSF. The column was washed in the above buffer and the protein was eluted by developing a shallow gradient to buffer F+0.5 M NaCl.

[0430] 8. Size exclusion chromatography. The protein from step 7 was concentrated to <2 mL and loaded onto an S75 gel filtration column equilibrated in buffer G: 10 mM Tris.HCl (pH 7.5), 100 mM NaCl, 2 mM DTT.

[0431] Expression of PDK1

[0432] Recombinant PDK1, for phosphorylation of ΔPH-PKβ-ΔC, was expressed from recombinant baculovirus generated by standard procedures.

[0433] 3 PCR reactions were set up as follows using pCMV5.myc PDK1fl-1 (Pullen et al., 1998) as a template:

1023μlH2O5μl10x Taq buffer10μlQ-solution (5x)5μldNTPs0.25 mM4μl5′ Primer 3066560 pmols1μl3′ Primer 2277760 pmols2μlpCMV5.myc PDK1 fl-1(200 ng)50μltotal + 2.5 u pfu

[0434] Taq polymerase, Q-solution and buffer were purchased from Qiagen 201203. All PCR reactions were performed in a Perkin Elmer Geneamp PCR system 9700

11PCR conditions60 s at 94° C.,Then 5 cycles:30 s at 94° C.4 min at 72° C.then 5 cycles:30s at 94° C.4 min at 70° C.then 20 cycles:30s at 94° C.4 min at 68° C.

[0435] Primers

1230665CCT GCT AGC ACG GCC ACG ACC ACC AGC CAG CTGTAT GAC NheI22777CCC GAA TTC TCA CTG CAC AGC GGC GTC CGG GTGGC EcoRI

[0436] All PCR fragments were pooled and purified using the Qiagen PCR purification kit (28106) and digested with the appropriate restriction enzymes and subcloned into the vectors indicated below. The PCR fragment was subcloned into pRSETA as a NheI/KpnI fragment, subsequently released as a NdeI/KpnI fragment and subcloned into pFastBac1 (10360-014 from Gibco BRL life technologies) between the BamHI and KpnI sites using a BamHI-NdeI linker.

[0437] All PCR fragments were pooled and purified using the Qiagen PCR purification kit (28106) and digested with the appropriate restriction enzymes and subcloned into pFastBacl (10360-014) from Gibco BRL life technologies to yield pFastbacl.His PDK1- c(full length aa 1-556).

[0438] Ligation mixes were used to transform E. coli XL1 blue (Stratagene) and colonies containing recombinant DNA were grown up for miniprep analysis.

[0439] Miniprep was prepared using Qiagen miniprep kit 27106. All expression constructs were fully sequenced on Applied Biosystems 3700.

[0440] Insect cells (density ˜2.0×106 cells/ml, total volume of 2.7 L; 5.4×109 Sf9 cells), grown in a culture of GIBCO/Life Sciences supplemented Sf9001I medium were infected at a moiety of infection of 2 and grown for 72 hours prior to harvesting.

[0441] Purification of PDK1

[0442] PDK1 was purified by following steps 1, 2, 3 5 and 6 described above, as for recombinant PKB.

[0443] Phosphorylation of ΔPH-PKBβ-ΔC (residues 146-460) and ΔPH-PKBβ (residues 146-481) on Thr309 Using PDK1

[0444] PKB from step 3 above was dialysed into a buffer containing 50 mM Tris.HCl (pH 7.5), 100 mM NaCl, 5 mM DTT. MgCl2 and ATP were added to a final concentration of 5 mM. PDK1was added and the mixture was incubated at 4° C. for 14 hrs and at 20° C. for 2 hrs. PDK1was removed from phosphorylated PKB by Ni-NTA agarose. The PKB-PDK1 solution was dialysed into buffer B (step 3) and loaded onto Ni-NTA agarose and eluted as described in step 3. The phosphorylated PKB was further purified using steps 4-8 above.

[0445] Dephosphorylation of ΔPH-PKBβ (residues 146-481) using λ Protein Phosphatase

[0446] ΔPH-PKBβ (residues 146-481) was dialysed into the following buffer: 50 mM Tris.HCl (pH 7.5), 150 mM NaCl, 2 mM MnCl2, 5 mM DTT, λ protein phosphatase was added at a ratio of 1 mg of λ protein phosphatase to 8 mg of ΔPH-PKBβ. ΔPH-PKBβ was incubated in these conditions at 20° C. for 2 h. Simultaneously, TEV protease was added to cleave the N-terminal His tag. After 2 h ΔPH-PKBβ was dialysed into buffer B (step 3) and loaded onto a Ni-NTA column to remove λ phosphatase and TEV. PKB was collected in the flow through. The protein was further purified using Q-sepharose and gel filtration chromatography (steps 7 and 8).

[0447] Crystallisation of pΔPH-PKBβ-ΔC (residues 146-460)—First Batch.

[0448] The protein was concentrated to 10 mg/ml and AMPPNP/MgCl2 was added to a final concentration of 5 mM. Crystals were grown using the under-oil batch method. A small volume of protein (3 μl) was mixed with an equal volume of crystallisation buffer: 30% (w/v) polyethylene glycol 4000, 0.2 M lithium sulphate, 0.1 M Tris.HCl (pH 7.5), 5 mM DTT, within individual wells of a 72 well polystyrene tray (Nunc) and immersed under 5 ml of silicone oil. The trays were incubated at 20° C. and crystals appeared within a few days and grew to a maximum size of 0.1 mm×0.1 mm×0.5 mm in a week. The crystals exhibited a rod-like rectangular morphology.

[0449] Crystallisation of PΔPH-PKB-ΔC (second batch), ΔPH-PKB-ΔC, and ΔPH-PKB.

[0450] The protein was concentrated to 10 mg/ml and AMP-PNP/MgCl2 was added to a final concentration of 5 mM. Crystals were grown using the under-oil batch method. A small volume of protein (1 μl) was mixed with an equal volume of crystallisation buffer: 30% (w/v) polyethylene glycol 4000, 0.2 M lithium sulphate, 0.1 M Tris.HCl (pH 8.5), 5 mM DTT, within individual wells of a 72 well polystyrene tray and immersed under silicone oil and incubated at 20° C.

[0451] Data Collection and Structure Determination

[0452] Preparation of Crystals for X-Ray Data Collection:

[0453] Crystals were harvested from the crystallisation trays and incubated in a cryoprotection buffer consisting of 18% (w/v) polyethylene glycol 4000, 120 mM lithium sulphate, 60 mM Tris.HCl (pH 7.5), 15% (v/v) polyethylene glycol 400, 5 mM AMPPNP/MgCl2 for 20 secs, prior to mounting the crystals in a ryan loop, and freezing in a nitrogen gas stream at 100 K. X-ray diffraction data were collected at the SRS, Daresbury, UK and at the European Synchrotron Radiation Facility, Grenoble, France.

[0454] Data were collected and these were analysed and processed using the HKL (Otwinowski and Minor, 1997) and CCP4 (CCP4, 1994) program suites. The structure was solved by means of molecular replacement using the coordinates of the ternary complex of the catalytic subunit of murine PKA as a search model (Knighton et al., 1991) with the program CNS (Brunger et al., 1998). The atomic structure was refined using rigid body and least squares refinement with CNS. Model building and analysis was done using 0 (Jones et al., 1991).

[0455] Protein Kinase B Assay

[0456] PKB was assayed essentially as described by Andjelkovic et al. (1999) with 30 μM Crosstide (GRPRTSSAEG) as substrate except the protein kinase A inhibitor peptide was not added to the reactions. For peptide stimulation experiments the various peptides were dissolved in water and added to the kinase assay mix prior to adding the PKB protein. Peptides were synthesized by Franz Fischer at the FMI or purchased from Neosystem, Strasburg, France.

[0457] Peptides Used Were:

13PKB HM-PGLLELDQRTHFPQFpSYSASIREPKB HM-DGLLELDQRTHFPQFDYSASIREPKB HM-SGLLELDQRTHFPQFSYSASIREPKB HM-PFGLLELDQRTHAPQApSYSASIREPIFtideREPRILSEEEQEMFRDFDYIADWPIFtide (D->A) REPRILSEEEQEMFRDFAYIADWPIFtide1 MFRDFDYIADWPIFtide2 MFRDFAYIADWPIFtide3 MFRAFAYIADWPIFtide4 MARDADYIADWPIFtide5 MFRDFDAIADW

[0458] pS is used to indicate phosphoserine.

[0459] All experiments were performed in either duplicate or triplicate.

[0460] Generation of PKBβ-PIF Chimera

[0461] A PKBβ kinase domain was generated with the PIFtide replacing the HM phosphorylation site (C-terminal sequence that encompasses residues 146 to 467 of the kinase attached to PIF as indicated below

14146KVTMNDF......GLLELDQR467 EEQEMFRDFDYIADW PKB PIF

[0462] To prepare the plasmid expression construct encoding the chimeric protein a 3′ oligonucleotide covering this region was synthesised with a Kpn1 site. The 5′ oligonucleotide used covered the region of PKB encoding 146 KVTMNDF region with a BamH1 site for subcloning into pFastBac HTa.

[0463] The sequence of the 5 prime oligonucleotide is:

[0464] gec atg gat ccg aaa ctg acc atg aat gac ttc (33mer ID36117).

[0465] The sequence of the 3 prime oligonucleotide is:

15ggg ggt acc tca cca gtc ggc gat gta gtc gaa gtcgcg gaa cat ctc ctg ctc ctc ccg ctg gtc cag ctccag taa gcc (81mer ID 38408).

[0466] For the PCR we carried 3 reactions with the following additions:

[0467] 1 μl 200 ng Template (pFastBac HTaAPH PKBβ 2851a)

[0468] 5 μl Qiagen Taq X10 buffer

[0469] 10 μl Q solution (for difficult templates)

[0470] 5 μl deoxynucleotide mixture (2.5 mM of dATP, dCTP, dGTP and TTP)

[0471] 24 μl ddH2O

[0472] 1 μl oligonucleotide 36117 (60 picomoles)

[0473] 4 μl oligonucleotide 38408 (60 picomoles)

[0474] 1 μl 2.5 U Taq polymerase (Qiagen) and 0.2U Pfu (Promega)

[0475] Touchdown PCR was performed as follows: 1 minute at 94° C.; 5 cycles of 94° C. for 30 sec. followed by 72° C. for 4 minutes; 5 cycles of 94° C. for 30 sec. followed by 4 minutes at 70° C.; 15 cycles of 94° C. for 30 sec. followed by 4 minutes at 68° C. After the final cycle the PCR reaction was incubated for 10 minutes at 68° C. and stored at 4° C.

[0476] The PCR products are purified on Qiagen Qiaquick PCR purification columns and eluted in 50 μl ddH2O. Purified PCR products are digested with BamHI (20 units) and KpnI (20 units) at 37° C. for 2 hrs. The digested PCR product is purified by electrophoresis using 1% Agarose gel run in Tris-Acetate buffer (TAE).

[0477] Purified DNA was isolated from the 1% Agarose gel using a Qiagen gel extraction kit following the manufacturers protocol and subcloned.

[0478] The vector pFastBac HTa (Gibco/Invitrogen) digested with BamHI/KpnI was used to subclone the PCR fragment. The sequence of the PCR product was determined using an Applied Biosystem DNA Analyzer 3700.

[0479] The pFastBac HTa.PKBP146-467/PIF plasmid used subsequently used to generate a virus for production of the chimeric protein.

[0480] Generation of PKB (146-481)S474D Mutant.

[0481] This mutant was generated by Quikchange mutagenesis of the pFastBacHTa PKBβ (146-481) plasmid.

[0482] Template pFastBacHTa.PKBP146-481/2851a

[0483] Quikchange according to the manufacturers specifications using the following oligo's:

[0484] PKBPS474D upper: cac ttc ccc cag ttc GAC tac tcg gcc agc atc

[0485] PKBPS474D lower: gat gct ggc cga gta GTC gaa ctg ggg gaagtg

[0486] The reaction contained the following:

[0487] 5 μl 10×Pfu reaction buffer

[0488] 1 μl DNA template 40 ng

[0489] 41 μl ddH2O

[0490] 1 μl upper strand oligonucleotide (30 picomoles)

[0491] 1 μl lower strand oligonucleotide (30 picomoles)

[0492] 1 μl Pfu (2.5 units from Stratagene)

[0493] The PCR cycling conditions were as follows:

[0494] 16 cycles of 30 sec. at 95° C., 60 sec. at 55° C. and 14 minutes at 68° C.

[0495] Following PCR the reaction was treated with 20 units of DpnI restriction enzyme for 4 hrs at 37° C. The treated DNA was used to transform XL-1 Blue (Stratagene) cells and bacteria were selected on ampicillin-agar plates. Plasmids DNA was prepared from transformed E. coli cultures using the Qiagen miniprep kit and sequenced on an Applied Biosystems 3700DNA analyzer.

[0496] Protein Expression and Purification

[0497] Expression of PKBβ-PIF

[0498] Generation of recombinant baculovirus using the GIBCO/Life Sciences Bacmid system was performed using standard procedures. Insect cells (density ˜2.0×106 cells/ml, total volume of 2.7 L; 5.4×109 Sf9 cells), grown in a culture of GIBCO/Life Sciences supplemented Sf900II medium were infected at a moiety of infection of 2 and grown for 72 hours prior to harvesting.

[0499] Purification of PKBβ-PIF

[0500] All procedures are performed at 4° C.

[0501] 1. Cell lysis: Insect cells are lysed in a Q-sepharose buffer A (25 mM Tris.HCl, [pH 7.5], 25 mM NaCl, 25 mM NaF, 25 mM β-glycerophosphate, 0.1% (v/v) P-mercaptoethanol, 2 mM benzamidine, 0.2 mM PMSF, 10% (v/v) glycerol, 1 μg/ml of DNAase, 2 μg/ml pepstatin, 2 μg/ml leupeptin, 2 μg/ml aprotinin A.

[0502] 2. Q-sepharose, anion exchange chromatography: The lysate is cleared by centrifugation and loaded onto a 50 mL Q-sepharose column equilibrated in buffer A. The column is washed in 300 mL of buffer A and PKB is eluted using 100 mL of buffer A+1 M NaCl.

[0503] 3. Ni-NTA affinity chromatography: The pH of the eluate is raised to 8.0 using a 1 M of Tris.HCl (pH 9.5) and this sample is loaded onto a Ni-NTA agarose column containing 10 mL of Ni-NTA agarose resin that had been pre-equilibrated in buffer B: 20 mM imidazole, 20 mM Tris.HCl (pH 8.0), 25 mM NaF, 25 mM β-glycerophosphate, 500 mM NaCl, 0.1% (v/v) β-mercaptoethanol, 2 mM benzamidine, 0.2 mM PMSF. The column is washed and the protein is eluted using a gradient to buffer B+300 mM imidazole. EDTA and DTT to final concentrations of 0.5 mM and 2 mM, respectively, are added immediately to the eluted protein.

[0504] 4. Tev protease cleavage. The 6×His affinity tag is removed by cleavage using Tev (tobacco etch virus) protease. Tev protease is added to PKB-PIF from step 3 (ratio of PKB-PIF:TEV of 15:1) and this solution is dialysed at 4° C. for 14 hr into buffer C: 50 mM Tris.HCl (pH 7.5), 150 mM NaCl, 5 mM DTT.

[0505] 5. Phosphorylation of PKB-PIF is carried out using PDK1purified in the inventors' laboratory. MgCl2/ATP are added PKB from step 4 to a final concentration of 5 mM. PDK1 is added (ratio of PKB-PIF:PDK1of 8:1). The mixture is incubated at 20° C. for 2 to 3 hrs and then at 4° C. for 14 hrs. To prepare a stock solution of 50 mM ATP/Mg2+: Solid ATP is added to a solution of 50 mM MgCl2 in 100 mM Tris.HCl (pH 9.5), 150, mM NaCl. ATP used is the magnesium salt: SIGMA catalogue code:A-9187. 9. To remove TEV and PDK1: Dialyse protein from step 5 into buffer B (from step 3) for 4 h at 4° C. in 4 L. This sample is loaded onto a Ni-NTA agarose column containing 10 mL of Ni-NTA agarose resin that had been pre-equilibrated in buffer B: 20 mM imidazole, 20 mM Tris.HCl (pH 8.0), 25 mM NaF, 25 mM β-glycerophosphate, 500 mM NaCl, 0.1% (v/v) β-mercaptoethanol, 2 mM benzamidine, 0.2 mM PMSF. PKB is collected in the flow through and first part of wash. EDTA and DTT to final concentrations of 0.5 mM and 2 mM, respectively, are added immediately to the eluted protein

[0506] 6. Phenyl TSK hydrophobic interaction chromatography: The protein from step 6 is brought to a concentration of ammonium sulphate in the range 1.5-1.7 M and loaded onto a phenyl TSK column equilibrated in buffer D: 50 mM Tris.HCl (pH 7.5), 1.5-1.7 M ammonium sulphate, 100 mM NaCl, 2 mM DTT, 0.5 mM EDTA, 2 mM benzamidine, 0.2 mM PMSF. The column is washed and PKB is eluted using a linear gradient developed to a buffer E consisting of 50 mM Tris.HCl (pH 7.5), 100 mM NaCl, 20% (v/v) glycerol, 2 mM DTT, 2 mM benzamidine, 0.5 mM EDTA, 0.2 mM PMSF.

[0507] 7. Mono-Q, anion exchange chromatography. The PKB-PIF collected in step 7 is dialysed into Mono-Q buffer F: 25 mM Tris.HCl (pH 7.5), 25 mM NaCl, 8% (v/v) glycerol, 0.5 mM EDTA, 2 mM DTT, 0.2 mM PMSF. The column is washed in the above buffer and the protein is eluted by developing a shallow gradient to buffer F+0.5 M NaCl.

[0508] 8. Size exclusion chromatography. The protein from step 8 is concentrated to <3 mL and loaded onto an S75 gel filtration column equilibrated in buffer G: 10 mM Tris.HCl (pH 7.5), 300 mM NaCl, 2 mM DTT.

[0509] Purification of PKB S474D

[0510] PKB S474D was purified as described above for PKB-PIF, except that:

[0511] 1. Phe-TSK column: 1.26 mM ammonium sulphate was used.

[0512] 2. Desalting was into MonoQ buffer F

[0513] 3. Protein concentration for crystallisation: 5 mg/ml, drop size: 3 ul+3 l.

[0514] Crystallisation of PKBβ-PIF

[0515] The protein from step 8 was concentrated to 10 mg/ml and AMPPNP/MnCl2 was added (from a stock solution of 50 mM [see below]) to a final concentration of 5 mM. A 10-residue GSK-3 peptide (GRPRTTSFAE) was added to the protein solution to give a final concentration of 0.6 mM. Crystals were grown using the under-oil batch method. A small volume of protein/AMP-PNP/GSK-3 (1 μl) was mixed with an equal volume of crystallisation buffer: 22% (w/v) polyethylene glycol 4000, 10%-14% (v/v) isopropanol, 0.1 M Hepes (pH 7.5), 5 mM DTT, within individual wells of a 72 well polystyrene tray (Nunc) and immersed under 5 ml of silicone oil. The trays were incubated at 22° C. and crystals grow to a maximum size of 0.05 mm×0.05 mm×1.0 mm within 18 hours and exhibit a needle-like morphology. To prepare a stock solution of 50 mM AMP-PNP/Mn2+: Solid AMP-PNP is added to a solution of 50 mM MnCl2 in 50 mM Tris.HCl (pH 7.5). AMP-PNP is lithium salt, SIGMA catalogue code: A-2647.

[0516] Data Collection and Structure Determination

[0517] Crystals were harvested from the crystallisation trays and incubated in a cryoprotection buffer consisting of 12% (w/v) polyethylene glycol 4000, 6% (v/v) isopropanol, 150 mM NaCl, 50 mM Tris.HCl (pH 7.5), 15% (v/v) methylpentane-diol, 0.5 mM AMPPNP/MnCl2, 0.3 mM GSK3 peptide for 20 sees, prior to mounting the crystals in a ryan loop, and freezing in a nitrogen gas stream at 100 K X-ray diffraction data were collected at the European Synchrotron Radiation Facility, Grenoble, France.

[0518] Data were collected and these were analysed and processed using the CCP4 program suite (CCP4, 1994). The structure was solved by means of molecular replacement using the coordinates of the catalytic subunit of PKA as a search model with the program CNS (Brunger et al., 1998). The atomic structure was refined using rigid body and least squares refinement with CNS. Model building and analysis was done using O (Jones et al., 1991). Crystallographic data statistics are given in Table 2.

[0519] While the invention has been described in conjunction with the exemplary embodiments described above, many equivalent modifications and variations will be apparent to those skilled in the art when given this disclosure Accordingly, the exemplary embodiments of the invention set forth are considered to be illustrative and not limiting. Various changes to the described embodiments may be made without departing from the spirit and scope of the invention. The references in the above text and listed below are incorporated by reference insofar as is required for the skilled person to carry out the invention.

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16TABLE 6Coordinate data for PKB-PIFREMARK Written by O version 8.0.5REMARK Wed Jul 10 19:14:27 2002CRYST144.93660.997131.31590.0090.0090.00ORIGX11.0000000.0000000.0000000.00000ORIGX20.0000001.0000000.0000000.00000ORIGX30.0000000.0000001.0000000.00000SCALE10.022254−0.000001 −0.000001 0.00000SCALE20.0000000.0163940.0000000.00000SCALE30.0000000.0000000.0076150.00000ATOM1CBLYSA14635.59846.50491.7261.0038.996ATOM2CGLYSA14635.64144.98991.4801.0039.596ATOM3CDLYSA14635.54644.67989.9951.0041.036ATOM4CELYSA14635.89043.22389.6971.0041.186ATOM5NZLYSA14635.86642.95388.2251.0040.707ATOM6CLYSA14637.33046.65693.5511.0037.526ATOM7OLYSA14638.25447.33293.0881.0038.038ATOM8NLYSA14635.57248.39693.3371.0037.087ATOM9CALYSA14635.87546.94593.1721.0037.176ATOM10NVALA14737.50845.65494.4131.0037.217ATOM11CAVALA14738.82645.22794.8871.0036.716ATOM12CBVALA14738.83344.98696.4341.0036.746ATOM13CG1VALA14740.24944.73096.9361.0037.526ATOM14CG2VALA14738.24046.18297.1751.0037.196ATOM15CVALA14739.20243.94194.1431.0036.206ATOM16OVALA14738.38543.02194.0271.0036.038ATOM17NTHRA14840.42143.91493.6021.0035.867ATOM18CATHRA14840.93242.76492.8511.0035.626ATOM19CBTHRA14841.36843.16091.4031.0035.706ATOM20OG1THRA14842.32744.22591.4541.0036.618ATOM21CG2THRA14840.17343.59390.5671.0037.016ATOM22CTHRA14842.10742.07193.5461.0034.676ATOM23OTHRA14842.66142.58594.5211.0034.138ATOM24NMETA14942.48040.91093.0051.0034.317ATOM25CAMETA14943.57940.07393.4951.0033.746ATOM26CBMETA14943.53938.72392.7641.0035.816ATOM27CGMETA14944.11437.54293.5251.0037.556ATOM28SDMETA14943.12737.08194.9631.0039.7716ATOM29CEMETA14942.24735.72094.3111.0039.136ATOM30CMETA14944.93840.75193.2651.0033.476ATOM31OMETA14945.85340.62094.0841.0031.648ATOM32NASNA15045.02441.52492.1811.0032.777ATOM33CAASNA15046.23842.24591.7861.0032.956ATOM34CBASNA15046.19042.57190.2871.0035.926ATOM35CGASNA15046.39341.34289.4171.0039.606ATOM36OD1ASNA15045.53240.46189.3511.0041.548ATOM37ND2ASNA15047.54241.27488.7491.0040.477ATOM38CASNA15046.56943.50892.5901.0031.476ATOM39OASNA15047.62444.11192.3891.0031.618ATOM40NASPA15145.68143.89093.5101.0029.837ATOM41CAASPA15145.88645.06794.3631.0028.236ATOM42CBASPA15144.54045.59894.8881.0030.096ATOM43CGASPA15143.62746.11993.7821.0032.086ATOM44OD1ASPA15144.13046.64892.7651.0034.408ATOM45OD2ASPA15142.39246.00893.9411.0033.268ATOM46CASPA15146.79544.74195.5551.0026.256ATOM47OASPA15147.16945.63396.3251.0025.268ATOM48NPHEA15247.13543.45795.6941.0024.407ATOM49CAPHEA15247.96542.95796.7921.0024.436ATOM50CBPHEA15247.14442.03197.7131.0022.346ATOM51CGPHEA15245.87442.64498.2421.0021.946ATOM52CD1PHEA15245.87043.34799.4601.0021.866ATOM53CD2PHEA15244.67042.52397.5211.0021.466ATOM54CE1PHEA15244.68043.93099.9601.0021.396ATOM55CE2PHEA15243.47043.09898.0041.0022.636ATOM56CZPHEA15243.47343.80599.2271.0021.836ATOM57CPHEA15249.20042.16996.3561.0024.576ATOM58OPHEA15249.23741.59595.2671.0024.798ATOM59NGLUA15350.19642.14597.2421.0024.317ATOM60CAGLUA15351.44141.39397.0631.0025.336ATOM61CBGLUA15352.65542.23397.4671.0027.506ATOM62CGGLUA15353.03843.30696.4661.0031.316ATOM63CDGLUA15353.95944.34797.0581.0034.616ATOM64OE1GLUA15355.16944.32596.7431.0038.598ATOM65OE2CLUA15353.47445.19197.8411.0037.318ATOM66CGLUA15351.29740.21298.0191.0025.656ATOM67OGLUA15350.87040.39699.1571.0023.898ATOM68NTYRA15451.61639.01097.5431.0025.477ATOM69CATYRA15451.50137.78298.3361.0025.806ATOM70CBTYRA15450.80936.68797.5051.0025.236ATOM71CGTYRA15449.42137.10297.0661.0024.776ATOM72CD1TYRA15449.23337.91295.9211.0023.176ATOM73CE1TYRA15447.95438.43995.5931.0023.316ATOM74CD2TYRA15448.29636.80897.8631.0023.336ATOM75CE2TYRA15447.01337.32797.5451.0022.636ATOM76CZTYRA15446.85738.14596.4161.0023.066ATOM77OHTYRA15445.63438.70196.1451.0023.288ATOM78CTYRA15452.87437.35698.8381.0026.256ATOM79OTYRA15453.70936.86198.0751.0026.408ATOM80NLEUA15553.08737.565100.1381.0026.027ATOM81CALEUA15554.36537.289100.7941.0026.196ATOM82CBLEUA15554.62238.343101.8751.0025.696ATOM83CGLEUA15554.46339.802101.4181.0027.246ATOM84CD1LEUA15554.49640.706102.6091.0029.076ATOM85CD2LEUA15555.52940.201100.3971.0028.006ATOM86CLEUA15554.59835.880101.3301.0026.376ATOM87OLEUA15555.49435.184100.8441.0028.068ATOM88NLYSA15653.85335.482102.3661.0025.397ATOM89CALYSA15653.98434.138102.9461.0025.086ATOM90CBLYSA15655.19834.012103.8881.0028.066ATOM91CGLYSA15655.48635.169104.8301.0029.466ATOM92CDLYSA15656.81434.912105.5211.0030.236ATOM93CELYSA15657.47736.199105.9421.0032.026ATOM94NZLYSA15658.71335.963106.7351.0031.987ATOM95CLYSA15652.73833.562103.6021.0023.606ATOM96OLYSA15651.84434.298104.0271.0023.618ATOM97NLEUA15752.69032.231103.6561.0020.167ATOM98CALEUA15751.57331.495104.2431.0019.096ATOM99CBLEUA15751.57930.041103.7461.0019.636ATOM100CGLEUA15750.40529.121104.1191.0018.376ATOM101CD1LEUA15749.15229.543103.3791.0018.246ATOM102CD2LEUA15750.74827.682103.7961.0019.546ATOM103CLEUA15751.61831.536105.7721.0019.086ATOM104OLEUA15752.63431.216106.3801.0019.148ATOM105NLEUA15850.50931.962106.3731.0017.837ATOM106CALEUA15850.38732.054107.8271.0016.376ATOM107CBLEUA15849.56533.286108.2071.0014.716ATOM108CGLEUA15850.11034.646107.7801.0014.556ATOM109CD1LEUA15849.07635.708108.0641.0014.276ATOM110CD2LEUA15851.42634.948108.4901.0015.526ATOM111CLEUA15849.71230.819108.3941.0015.856ATOM112OLEUA15850.08930.329109.4611.0016.438ATOM113NGLYA15948.71530.326107.6641.0016.937ATOM114CAGLYA15947.97229.159108.0991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ATOM227CBTHRA17447.64551.600102.0221.0025.776ATOM228OG1THRA17447.46950.180102.0961.0026.138ATOM229CG2THRA17446.36452.242101.4921.0026.336ATOM230CTHRA17450.12251.450101.8211.0024.306ATOM231OTHRA17450.62852.134102.7161.0024.188ATOM232NGLYA17550.61350.272101.4341.0023.347ATOM233CAGLYA17551.80349.701102.0491.0023.136ATOM234CGLYA17551.48548.985103.3541.0023.486ATOM235OGLYA17552.39248.510104.0441.0022.038ATOM236NARGA17650.19248.914103.6821.0024.067ATOM237CAARGA17649.70048.268104.9021.0023.496ATOM238CBARGA17648.36748.886105.3411.0026.596ATOM239CGARGA17648.48750.325105.8241.0030.976ATOM240CDARGA17647.13650.918106.1801.0035.946ATOM241NEARGA17647.23552.350106.4621.0041.427ATOM242CZARGA17646.25753.100106.9691.0043.796ATOM243NH1ARGA17645.07552.569107.2691.0045.627ATOM244NH2ARGA17646.46154.395107.1721.0044.857ATOM245CARGA17649.56946.756104.7521.0022.486ATOM246OARGA17649.19246.252103.6891.0020.688ATOM247NTYRA17749.88246.047105.8341.0019.607ATOM248CATYRA17749.84844.589105.8621.0020.496ATOM249CBTYRA17751.05944.046106.6211.0020.406ATOM250CGTYRA17752.38644.338105.9561.0022.096ATOM251CD1TYRA17752.96245.628106.0081.0022.396ATOM252CE1TYRA17754.22845.895105.4181.0024.166ATOM253CD2TYRA17753.09943.318105.2971.0023.496ATOM254CE2TYRA17754.36543.575104.7061.0025.396ATOM255CZTYRA17754.91844.859104.7731.0025.116ATOM256OHTYRA17756.14445.094104.1981.0027.138ATOM257CTYRA17748.56444.025106.4421.0018.106ATOM258OTYRA17748.01044.569107.4001.0019.848ATOM259NTYRA17848.06642.969105.7991.0016.417ATOM260CATYRA17846.83142.290106.1901.0015.686ATOM261CBTYRA17845.66542.743105.2941.0016.766ATOM262CGTYRA17845.33044.217105.3461.0018.566ATOM263CD1TYRA17845.67945.076104.2791.0018.906ATOM264CE1TYRA17845.40146.470104.3391.0019.666ATOM265CD2TYRA17844.69244.774106.4741.0018.886ATOM266CE2TYRA17844.41146.163106.5481.0020.276ATOM267CZTYRA17844.77047.000105.4771.0021.346ATOM268OHTYRA17844.50148.343105.5531.0022.688ATOM269CTYRA17846.97140.773106.0561.0015.156ATOM270OTYRA17847.95140.273105.5041.0016.388ATOM271NALAA17945.99840.048106.6011.0014.457ATOM272CAALAA17945.96338.593106.4971.0015.006ATOM273CBALAA17945.78937.960107.8641.0015.676ATOM274CALAA17944.77138.276105.6011.0016.106ATOM275OALAA17943.64138.670105.9041.0016.608ATOM276NMETA18045.03337.629104.4661.0015.477ATOM277CAMETA18043.96537.287103.5341.0015.016ATOM278CBMETA18044.33437.676102.0961.0016.406ATOM279CGMETA18043.15337.649101.1271.0017.986ATOM280SDMETA18043.63537.67499.3901.0020.7716ATOM281CEMETA18044.05939.34899.2021.0017.716ATOM282CMETA18043.59235.813103.5841.0014.046ATOM283OMETA18044.42634.952103.3181.0014.858ATOM284NLYSA18142.33235.540103.9301.0015.567ATOM285CALYSA18141.81534.176103.9831.0015.946ATOM286CBLYSA18140.78734.014105.1091.0016.206ATOM287CGLYSA18140.26432.592105.3001.0015.276ATOM288CDLYSA18139.37232.503106.5221.0015.796ATOM289CELYSA18138.86331.086106.7311.0015.366ATOM290NZLYSA18138.11430.981108.0171.0016.707ATOM291CLYSA18141.18133.906102.6221.0017.886ATOM292OLYSA18140.26034.615102.2021.0016.988ATOM293NILEA18241.73132.915101.9241.0018.707ATOM294CAILEA18241.27832.533100.5901.0020.086ATOM295CBILEA18242.47232.50499.5771.0020.316ATOM296CG2ILEA18241.97932.12498.1741.0021.676ATOM297CG1ILEA18243.15733.87899.5261.0021.096ATOM298CD1ILEA18244.44133.93698.7181.0023.196ATOM299CILEA18240.57331.177100.6221.0019.766ATOM300OILEA18241.12430.183101.1041.0019.958ATOM301NLEUA18339.33731.168100.1271.0020.477ATOM302CALEUA18338.51129.964100.0611.0021.626ATOM303CBLEUA18337.23930.136100.9051.0023.226ATOM304CGLEUA18337.26530.456102.4081.0024.406ATOM305CD1LEUA18335.85830.412102.9531.0025.406ATOM306CD2LEUA18338.12029.475103.1711.0027.446ATOM307CLEUA18338.13229.70198.6041.0022.116ATOM308OLEUA18337.91130.64097.8421.0021.498ATOM309NARGA18438.07628.42798.2221.0023.427ATOM310CAARGA18437.72428.03396.8521.0024.986ATOM311CBARGA18438.50926.78796.4341.0026.206ATOM312CGARGA18440.01526.97896.4201.0030.116ATOM313CDARGA18440.73025.71096.0061.0033.196ATOM314NEARGA18442.18125.88596.0271.0037.087ATOM315CZARGA18443.00325.54595.0361.0037.186ATOM316NH1ARGA18442.53124.99993.9201.0037.827ATOM317NH2ARGA18444.30625.75395.1621.0039.057ATOM318CARGA18436.22427.77896.7271.0025.206ATOM319OARGA18435.67126.94497.4491.0025.198ATOM320NLYSA18535.58128.48695.7951.0026.117ATOM321CALYSA18534.13428.37995.5531.0027.696ATOM322CBLYSA18533.69329.31694.4251.0028.306ATOM323CGLYSA18533.67630.77994.7901.0028.296ATOM324CDLYSA18533.08931.61193.6661.0029.316ATOM325CELYSA18533.08933.08494.0231.0030.136ATOM326NZLYSA18532.43433.92092.9831.0030.447ATOM327CLYSA18533.60926.97995.2551.0028.466ATOM328OLYSA18532.59326.58195.8171.0028.578ATOM329NGLUA18634.33626.22994.4231.0029.727ATOM330CAGLUA18633.95724.86894.0281.0030.936ATOM331CBGLUA18634.89824.35292.9291.0033.986ATOM332CGGLUA18634.36423.14292.1511.0038.416ATOM333CDGLUA18635.25622.73990.9941.0040.856ATOM334OE1GLUA18636.26722.04391.2321.0042.608ATOM335OE2GLUA18634.93823.11289.8441.0043.568ATOM336CGLUA18633.89323.87195.1951.0030.076ATOM337OGLUA18632.99823.02695.2361.0029.758ATOM338NVALA18734.80524.02396.1581.0029.337ATOM339CAVALA18734.88123.16297.3491.0028.736ATOM340CBVALA18736.24723.35898.0921.0028.626ATOM341CG1VALA18736.37622.42699.3001.0028.386ATOM342CG2VALA18737.40123.10697.1371.0029.336ATOM343CVALA18733.71423.45898.3071.0029.116ATOM344OVALA18733.12922.54398.8911.0028.948ATOM345NILEA18833.36524.73998.4121.0029.717ATOM346CAILEA18832.28625.22499.2751.0030.276ATOM347CBILEA18832.39926.76799.4361.0029.906ATOM348CG2ILEA18831.20727.354100.1821.0028.876ATOM349CG1ILEA18833.68227.096100.1981.0030.656ATOM350CD1ILEA18834.05128.532100.1471.0031.526ATOM351CILEA18830.89324.80698.7821.0031.156ATOM352OILEA18830.06424.35499.5801.0030.848ATOM353NILEA18930.66524.93397.4731.0032.147ATOM354CAILEA18929.38924.57596.8361.0033.046ATOM355CBILEA18929.32025.11995.3631.0033.406ATOM356CG2ILEA18928.00024.71494.6721.0033.206ATOM357CG1ILEA18929.41726.65195.3701.0032.936ATOM358CD1ILEA18929.84127.26394.0411.0032.116ATOM359CILEA18929.15423.05696.8751.0033.246ATOM360OILEA18928.04522.60897.1791.0033.538ATOM361NALAA19030.22122.28696.6401.0033.497ATOM362CAALAA19030.17420.81996.6351.0033.516ATOM363CBALAA19031.47820.25496.0851.0033.976ATOM364CALAA19029.87720.21098.0071.0034.086ATOM365OALAA19029.20619.18198.1031.0033.958ATOM366NLYSA19130.36620.86799.0581.0035.227ATOM367CALYSA19130.16320.413100.4341.0035.856ATOM368CBLYSA19131.45920.572101.2371.0037.796ATOM369CGLYSA19132.53419.584100.8031.0041.206ATOM370CDLYSA19133.89619.929101.3561.0043.636ATOM371CELYSA19134.95318.978100.8131.0045.496ATOM372NZLYSA19136.31919.306101.3071.0046.747ATOM373CLYSA19128.98121.091101.1301.0035.216ATOM374OLYSA19128.75020.875102.3241.0034.908ATOM375NASPA19228.22321.876100.3521.0034.347ATOM376CAASPA19227.02222.618100.7841.0034.646ATOM377CBASPA19225.84721.640101.0131.0036.566ATOM378CGASPA19224.48822.275100.7521.0038.946ATOM379OD1ASPA19223.76022.544101.7291.0041.278ATOM380OD2ASPA19224.14922.49899.5691.0041.238ATOM381CASPA19227.26123.529102.0051.0033.716ATOM382OASPA19226.47423.552102.9591.0034.098ATOM383NGLUA19328.36524.275101.9511.0031.637ATOM384CAGLUA19328.76625.179103.0281.0030.316ATOM385CBGLUA19330.19224.837103.4921.0030.386ATOM386CGGLUA19330.33023.520104.2621.0030.726ATOM387CDGLUA19329.59323.522105.5941.0031.986ATOM388OE1GLUA19329.90724.374106.4521.0032.638ATOM389OE2GLUA19328.70022.669105.7831.0032.378ATOM390CGLUA19328.66126.671102.6931.0029.346ATOM391OGLUA19329.34327.499103.3101.0029.548ATOM392NVALA19427.78827.010101.7411.0026.957ATOM393CAVALA19427.57328.397101.3031.0026.026ATOM394CBVALA19426.68328.457100.0141.0026.606ATOM395CG1VALA19426.41229.90599.5831.0026.046ATOM396CG2VALA19427.36727.71198.8751.0026.876ATOM397CVALA19426.99229.279102.4151.0024.836ATOM398OVALA19427.48830.384102.6431.0023.948ATOM399NALAA19526.00428.750103.1411.0024.477ATOM400CAALAA19525.33929.463104.2381.0023.926ATOM401CBALAA19524.21928.608104.8221.0024.426ATOM402CALAA19526.30729.894105.3421.0023.166ATOM403OALAA19526.25931.036105.7971.0023.248ATOM404NHISA19627.23229.001105.6961.0022.247ATOM405CAHISA19628.23529.265106.7281.0021.096ATOM406CBHISA19628.91027.962107.1751.0021.726ATOM407CGHISA19628.05227.098108.0511.0022.176ATOM408CD2HISA19627.02827.400108.8851.0023.836ATOM409ND1HISA19628.22025.733108.1331.0023.277ATOM410CE1HISA19627.33725.232108.9781.0023.896ATOM411NE2HISA19626.60126.222109.4481.0023.927ATOM412CHISA19629.29130.279106.2941.0020.956ATOM413OHISA19629.73831.095107.1031.0020.738ATOM414NTHRA19729.63830.250105.0051.0020.347ATOM415CATHRA19730.63131.158104.4221.0020.276ATOM416CBTHRA19731.09230.659103.0321.0021.836ATOM417OG1THRA19731.47329.281103.1271.0022.298ATOM418CG2THRA19732.29431.453102.5461.0023.086ATOM419CTHRA19730.08732.589104.3161.0019.656ATOM420OTHRA19730.82233.552104.5461.0019.148ATOM421NVALA19828.79632.711103.9961.0020.247ATOM422CAVALA19828.12734.012103.8851.0020.526ATOM423CBVALA19826.74533.888103.1531.0022.076ATOM424CG1VALA19826.00435.231103.1201.0024.566ATOM425CG2VALA19826.96133.415101.7231.0024.036ATOM426CVALA19827.97234.615105.2901.0019.886ATOM427OVALA19828.18435.816105.4751.0018.958ATOM428NTHRA19927.68933.756106.2751.0020.087ATOM429CATHRA19927.53834.165107.6761.0019.656ATOM430CBTHRA19926.97633.012108.5561.0020.556ATOM431OG1THRA19925.71032.593108.0331.0024.398ATOM432CG2THRA19926.76933.455110.0061.0022.786ATOM433CTHRA19928.89034.646108.2161.0018.066ATOM434OTHRA19928.94135.624108.9551.0018.638ATOM435NGLUA20029.97834.004107.7751.0017.087ATOM436CAGLUA20031.34034.375108.1851.0017.206ATOM437CBGLUA20032.37233.409107.5891.0017.186ATOM438CGGLUA20033.83133.711107.9751.0017.756ATOM439CDGLUA20034.81932.627107.5681.0018.916ATOM440OE1GLUA20034.42931.648106.8891.0019.308ATOM441OE2GLUA20035.99732.751107.9551.0018.688ATOM442CGLUA20031.63635.806107.7361.0017.746ATOM443OGLUA20032.16436.605108.5091.0017.908ATOM444NSERA20131.23036.131106.5071.0017.427ATOM445CASERA20131.42037.469105.9561.0019.196ATOM446CBSERA20131.12737.488104.4581.0020.046ATOM447OGSERA20131.46438.745103.8931.0024.228ATOM448CSERA20130.53538.481106.6721.0018.036ATOM449OSERA20131.02539.520107.0911.0019.228ATOM450NARGA20229.26538.123106.8851.0018.727ATOM451CAARGA20228.28538.985107.5621.0019.776ATOM452CBARGA20226.90138.336107.5661.0021.336ATOM453CGARGA20226.15338.409106.2441.0025.416ATOM454CDARGA20224.77337.749106.3491.0028.216ATOM455NEARGA20223.94738.331107.4121.0032.277ATOM456CZARGA20223.17439.410107.2821.0034.816ATOM457NH1ARGA20222.47539.847108.3221.0036.217ATOM458NH2ARGA20223.08840.051106.1211.0035.277ATOM459CARGA20228.67439.354108.9941.0019.146ATOM460OARGA20228.53040.510109.3961.0018.548ATOM461NVALA20329.21338.380109.7331.0018.467ATOM462CAVALA20329.65038.595111.1151.0018.506ATOM463CBVALA20329.95537.247111.8481.0017.926ATOM464CG1VALA20330.57037.487113.2281.0017.806ATOM465CG2VALA20328.66736.466112.0271.0017.416ATOM466CVALA20330.86039.529111.1231.0019.296ATOM467OVALA20330.89640.478111.8991.0020.878ATOM468NLEUA20431.79439.306110.1981.0018.777ATOM469CALEUA20432.99340.137110.0701.0019.466ATOM470CBLEUA20433.97239.500109.0841.0018.796ATOM471CGLEUA20434.97138.473109.6181.0018.356ATOM472CD1LEUA20435.50637.622108.4831.0018.916ATOM473CD2LEUA20436.10639.176110.3641.0019.886ATOM474CLEUA20432.65841.572109.6341.0021.486ATOM475OLEUA20433.33942.517110.0301.0023.728ATOM476NGLNA20531.57341.722108.8701.0021.947ATOM477CAGLNA20531.11143.028108.3861.0022.756ATOM478CBGLNA20530.11742.862107.2331.0023.216ATOM479CGGLNA20530.68242.303105.9541.0022.926ATOM480CDGLNA20529.62442.116104.8811.0023.616ATOM481OE1GLNA20528.78842.989104.6571.0024.788ATOM482NE2GLNA20529.66740.976104.2031.0023.687ATOM483CGLNA20530.39943.836109.4631.0023.716ATOM484OGLNA20530.56745.056109.5481.0026.358ATOM485NASNA20629.59943.141110.2721.0023.547ATOM486CAASNA20628.79143.768111.3141.0022.936ATOM487CBASNA20627.35643.228111.2411.0025.186ATOM488CGASNA20626.65943.597109.9381.0027.496ATOM489OD1ASNA20626.15844.713109.7821.0029.508ATOM490ND2ASNA20626.65042.668108.9881.0027.877ATOM491CASNA20629.30843.751112.7531.0022.846ATOM492OASNA20628.54144.009113.6901.0023.668ATOM493NTHRA20730.59043.434112.9361.0019.607ATOM494CATHRA20731.18843.431114.2761.0018.326ATOM495CBTHRA20731.69742.034114.7231.0017.826ATOM496OG1THRA20732.56141.476113.7241.0016.828ATOM497CG2THRA20730.53441.097115.0151.0017.666ATOM498CTHRA20732.32944.428114.4061.0017.606ATOM499OTHRA20733.11544.617113.4751.0018.468ATOM500NARGA20832.39145.072115.5691.0018.087ATOM501CAARGA20833.42346.055115.8831.0019.076ATOM502CBARGA20832.95547.472115.4921.0022.446ATOM503CGARGA20834.00748.319114.7591.0028.186ATOM504CDARGA20834.29147.822113.3341.0029.416ATOM505NEARGA20833.48648.497112.3111.0031.027ATOM506CZARGA20832.81347.884111.3361.0031.406ATOM507NH1ARGA20832.81846.559111.2261.0029.967ATOM508NH2ARGA20832.15148.607110.4401.0032.217ATOM509CARGA20833.71045.956117.3831.0017.636ATOM510OARGA20832.90546.383118.2141.0018.318ATOM511NHISA20934.84145.337117.7161.0015.817ATOM512CAHISA20935.25845.142119.1071.0015.056ATOM513CBHISA20934.62443.847119.6571.0015.476ATOM514CGHISA20934.79943.641121.1321.0015.166ATOM515CD2HISA20935.76242.999121.8331.0013.716ATOM516ND1HISA20933.91944.145122.0651.0017.117ATOM517CE1HISA20934.33743.826123.2771.0012.836ATOM518NE2HISA20935.45443.131123.1641.0017.367ATOM519CHISA20936.78745.044119.1321.0015.226ATOM520OHISA20937.38244.474118.2121.0014.488ATOM521NPROA21037.44545.591120.1841.0014.917ATOM522CDPROA21036.96246.482121.2581.0016.376ATOM523CAPROA21038.91145.512120.2411.0014.276ATOM524CBPROA21039.24946.304121.5131.0015.836ATOM525CGPROA21037.99646.263122.3131.0018.366ATOM526CPROA21039.53744.111120.2591.0012.156ATOM527OPROA21040.69643.955119.8821.0013.338ATOM528NPHEA21138.77043.095120.6651.0011.277ATOM529CAPHEA21139.29941.732120.7261.009.956ATOM530CBPHEA21139.13541.142122.1411.0010.986ATOM531CGPHEA21139.67042.042123.2291.009.846ATOM532CD1PHEA21140.95942.608123.1241.0012.376ATOM533CD2PHEA21138.85242.414124.3081.0013.846ATOM534CE1PHEA21141.42143.543124.0721.0011.666ATOM535CE2PHEA21139.30443.350125.2731.0013.036ATOM536CZPHEA21140.59143.916125.1491.0012.926ATOM537CPHEA21138.80240.786119.6451.0011.106ATOM538OPHEA21138.94839.566119.7531.0011.168ATOM539NLEUA21238.21241.369118.6041.0011.067ATOM540CALEUA21237.73840.617117.4481.0011.916ATOM541CBLEUA21236.23340.815117.2041.0012.236ATOM542CGLEUA21235.19140.292118.1991.0011.566ATOM543CD1LEUA21233.82740.576117.6411.0012.466ATOM544CD2LEUA21235.33338.813118.4701.0010.736ATOM545CLEUA21238.50241.150116.2491.0012.306ATOM546OLEUA21238.70242.366116.1221.0013.208ATOM547NTHRA21338.97440.235115.4031.0011.377ATOM548CATHRA21339.68940.586114.1761.0012.196ATOM549CBTHRA21340.19439.313113.4481.0013.416ATOM550OG1THRA21341.13338.632114.2841.0013.308ATOM551CG2THRA21340.87439.649112.1361.0013.026ATOM552CTHRA21338.70641.343113.2791.0012.716ATOM553OTHRA21337.58040.888113.0641.0014.898ATOM554NALAA21439.12042.527112.8311.0013.307ATOM555CAALAA21438.28343.360111.9751.0014.746ATOM556CBALAA21438.47744.821112.3151.0016.156ATOM557CALAA21438.55843.107110.4981.0014.136ATOM558OALAA21439.67742.739110.1161.0015.158ATOM559NLEUA21537.51443.276109.6871.0014.657ATOM560CALEUA21537.58243.070108.2421.0015.666ATOM561CBLEUA21536.30342.375107.7531.0017.506ATOM562CGLEUA21536.22441.855106.3091.0018.016ATOM563CD1LEUA21537.09040.625106.1411.0017.636ATOM564CD2LEUA21534.78841.519105.9621.0017.616ATOM565CLEUA21537.76544.389107.4941.0016.796ATOM566OLEUA21537.01345.346107.7061.0016.848ATOM567NLYSA21638.77244.425106.6241.0015.927ATOM568CALYSA21639.05945.604105.8121.0017.886ATOM569CBLYSA21640.56845.729105.5641.0018.116ATOM570CGLYSA21641.01546.979104.7991.0020.256ATOM571CDLYSA21640.86148.277105.5761.0023.746ATOM572CELYSA21641.32749.458104.7341.0023.616ATOM573NZLYSA21641.28950.736105.4921.0027.067ATOM574CLYSA21638.27745.484104.5001.0019.416ATOM575OLYSA21637.49946.375104.1551.0020.528ATOM576NTYRA21738.50144.393103.7671.0020.337ATOM577CATYRA21737.79544.151102.5041.0021.546ATOM578CBTYRA21738.67844.403101.2631.0022.416ATOM579CGTYRA21739.47045.689101.2051.0023.426ATOM580CD1TYRA21738.83146.946101.1191.0024.906ATOM581CE1TYRA21739.58748.147101.0331.0025.626ATOM582CD2TYRA21740.87845.654101.2031.0024.526ATOM583CE2TYRA21741.64546.844101.1141.0025.186ATOM584CZTYRA21740.99148.082101.0321.0025.166ATOM585OHTYRA21741.73349.235100.9661.0026.088ATOM586CTYRA21737.33542.705102.4201.0021.746ATOM587OTYRA21737.90241.815103.0521.0020.968ATOM588NALAA21836.30442.490101.6131.0022.247ATOM589CAALAA21835.75941.168101.3441.0023.856ATOM590CBALAA21834.52740.890102.1921.0025.666ATOM591CALAA21835.39741.23899.8691.0025.386ATOM592OALAA21834.61042.09699.4621.0026.618ATOM593NPHEA21936.07740.42799.0601.0025.937ATOM594CAPHEA21935.83140.39697.6221.0026.136ATOM595CBPHEA21936.82341.31196.8571.0026.716ATOM596CGPHEA21938.26440.83396.8571.0027.756ATOM597CD1PHEA21939.11541.10897.9461.0027.526ATOM598CD2PHEA21938.79140.14495.7411.0027.786ATOM599CE1PHEA21940.48240.70497.9251.0028.246ATOM600CE2PHEA21940.14939.73295.7051.0028.116ATOM601CZPHEA21941.00040.01496.8011.0027.676ATOM602CPHEA21935.83738.98397.0651.0026.636ATOM603OPHEA21936.22238.03297.7501.0026.358ATOM604NGLNA22035.44538.86595.7991.0027.677ATOM605CAGLNA22035.40637.57795.1271.0029.166ATOM606CBGLNA22034.01236.94095.2481.0029.396ATOM607CGGLNA22032.84937.76594.7011.0030.696ATOM608CDGLNA22031.50737.13294.9931.0030.686ATOM609OE1GLNA22031.18036.06794.4661.0031.498ATOM610NE2GLNA22030.72237.77895.8471.0030.597ATOM611CGLNA22035.83037.65293.6701.0030.496ATOM612OGLNA22035.77938.71793.0451.0030.468ATOM613NTHRA22136.33036.52293.1761.0031.947ATOM614CATHRA22136.75336.36791.7861.0034.306ATOM615CBTHRA22138.24135.92191.6701.0033.986ATOM616OG1THRA22138.43634.68792.3711.0033.818ATOM617CG2THRA22139.17936.98692.2291.0034.656ATOM618CTHRA22135.82035.30691.1901.0035.996ATOM619OTHRA22134.76535.02091.7661.0036.478ATOM620NHISA22236.21134.71090.0631.0037.937ATOM621CAHISA22235.40333.68589.3981.0039.376ATOM622CBHISA22235.83233.54087.9331.0042.246ATOM623CGHISA22235.60934.77487.1131.0045.276ATOM624CD2HISA22236.47535.56086.4311.0046.046ATOM625ND1HISA22234.36235.33686.9361.0046.167ATOM626CE1HISA22234.47036.41586.1801.0046.676ATOM627NE2HISA22235.74236.57385.8601.0046.667ATOM628CHISA22235.43632.32290.0961.0039.066ATOM629OHISA22234.48531.54389.9811.0040.158ATOM630NASPA22336.50032.06990.8611.0037.827ATOM631CAASPA22336.66530.79891.5691.0036.306ATOM632CBASPA22337.63629.87890.7941.0038.546ATOM633CGASPA22339.04430.47490.6251.0040.316ATOM634OD1ASPA22339.21731.71190.7081.0042.058ATOM635OD2ASPA22339.98629.68590.3951.0041.818ATOM636CASPA22337.08030.88893.0441.0034.416ATOM637OASPA22337.15029.86393.7281.0032.938ATOM638NARGA22437.34432.10293.5321.0032.317ATOM639CAARGA22437.77732.30394.9211.0030.756ATOM640CBARGA22439.27832.64494.9611.0033.006ATOM641CGARGA22440.21031.45494.7221.0035.746ATOM642CDARGA22441.61431.89694.3601.0040.626ATOM643NEARGA22442.53530.76594.2421.0043.587ATOM644CZARGA22443.84730.87194.0401.0044.596ATOM645NH1ARGA22444.42332.06393.9281.0044.537ATOM646NH2ARGA22444.59129.77593.9551.0045.527ATOM647CARGA22436.99433.33995.7301.0028.536ATOM648OARGA22436.37534.24695.1731.0027.318ATOM649NLEUA22536.99933.15097.0531.0026.167ATOM650CALEUA22536.34934.04098.0211.0022.966ATOM651CBLEUA22535.29733.28598.8421.0023.836ATOM652CGLEUA22533.98932.88198.1591.0023.246ATOM653CD1LEUA22533.24531.92699.0301.0024.996ATOM654CD2LEUA22533.12634.08597.8401.0023.776ATOM655CLEUA22537.46134.53498.9371.0021.316ATOM656OLEUA22538.18233.72399.5251.0020.598ATOM657NCYSA22637.59735.85399.0611.0020.167ATOM658CACYSA22638.66636.43599.8741.0019.266ATOM659CBCYSA22639.66637.15298.9681.0020.696ATOM660SGCYSA22640.22336.20997.5291.0023.9316ATOM661CCYSA22638.25537.384100.9951.0018.476ATOM662OCYSA22637.46938.309100.7851.0018.758ATOM663NPHEA22738.82237.151102.1791.0017.787ATOM664CAPHEA22738.58437.980103.3661.0016.656ATOM665CBPHEA22738.22337.134104.5961.0018.116ATOM666CGPHEA22737.03136.249104.4291.0019.386ATOM667CD1PHEA22737.18834.923103.9881.0022.416ATOM668CD2PHEA22735.75736.690104.8151.0021.366ATOM669CE1PHEA22736.09034.034103.9421.0022.756ATOM670CE2PHEA22734.64635.812104.7771.0021.476ATOM671CZPHEA22734.81434.478104.3411.0021.056ATOM672CPHEA22739.90538.672103.6951.0016.356ATOM673OPHEA22740.87438.000104.0401.0017.048ATOM674NVALA22839.94739.999103.5931.0014.847ATOM675CAVALA22841.15840.765103.9111.0015.406ATOM676CBVALA22841.39041.911102.8841.0015.786ATOM677CG1VALA22842.69842.615103.1331.0016.046ATOM678CG2VALA22841.37741.357101.4691.0017.876ATOM679CVALA22840.94741.292105.3351.0015.236ATOM680OVALA22840.20342.246105.5581.0015.678ATOM681NMETA22941.56640.596106.2861.0016.377ATOM682CAMETA22941.45940.888107.7201.0017.246ATOM683CBMETA22941.33239.573108.4891.0018.326ATOM684CGMETA22940.26938.609108.0261.0021.236ATOM685SDMETA22940.49437.062108.9161.0022.7616ATOM686CEMETA22941.84036.338107.9971.0022.296ATOM687CMETA22942.68941.587108.2751.0016.706ATOM688OMETA22943.76141.523107.6721.0016.748ATOM689NGLUA23042.55642.178109.4691.0016.427ATOM690CAGLUA23043.70442.817110.1081.0016.706ATOM691CBGLUA23043.30043.786111.2361.0022.166ATOM692CGGLUA23042.57743.199112.4331.0025.426ATOM693CDGLUA23042.07744.249113.4281.0025.886ATOM694OE1GLUA23042.54345.414113.4191.0026.118ATOM695OE2GLUA23041.19643.897114.2321.0024.208ATOM696CGLUA23044.63541.692110.5781.0015.646ATOM697OGLUA23044.17840.625111.0181.0014.938ATOM698NTYRA23145.92041.888110.3161.0013.707ATOM699CATYRA23146.96140.920110.6361.0013.556ATOM700CBTYRA23148.19241.204109.7531.0013.446ATOM701CGTYRA23149.44140.374110.0051.0014.196ATOM702CD1TYRA23149.38638.966110.1171.0014.556ATOM703CE1TYRA23150.55938.203110.3611.0015.676ATOM704CD2TYRA23150.69841.003110.1341.0015.116ATOM705CE2TYRA23151.87940.247110.3701.0016.616ATOM706CZTYRA23151.79738.853110.4851.0017.486ATOM707OHTYRA23152.92938.119110.7471.0018.788ATOM708CTYRA23147.33440.892112.1141.0012.316ATOM709OTYRA23147.70541.911112.6951.0014.178ATOM710NALAA23247.23439.699112.6951.0012.547ATOM711CAALAA23247.58939.482114.0911.0011.516ATOM712CBALAA23246.64838.477114.7141.0012.286ATOM713CALAA23249.04038.991114.1191.0011.286ATOM714OALAA23249.31337.794113.9901.0012.068ATOM715NASNA23349.96039.952114.2621.0011.067ATOM716CAASNA23351.41839.733114.2781.0013.606ATOM717CBASNA23352.16241.058114.5151.0016.456ATOM718CGASNA23351.89142.096113.4501.0020.276ATOM719OD1ASNA23352.75842.394112.6261.0021.968ATOM720ND2ASNA23350.69242.666113.4661.0019.967ATOM721CASNA23351.94238.742115.3081.0013.846ATOM722OASNA23352.96238.085115.0801.0014.158ATOM723NGLYA23451.22938.641116.4291.0011.747ATOM724CAGLYA23451.63837.770117.5151.0011.576ATOM725CGLYA23451.37136.286117.4241.0012.206ATOM726OGLYA23451.73035.561118.3431.0012.228ATOM727NGLYA23550.74735.834116.3381.0010.427ATOM728CAGLYA23550.46834.414116.1681.0012.476ATOM729CGLYA23549.35233.866117.0351.0010.956ATOM730OGLYA23548.65034.623117.7051.0011.788ATOM731NGLUA23649.17732.546116.9871.0010.957ATOM732CAGLUA23648.14431.852117.7581.0010.496ATOM733CBGLUA23647.92930.440117.2211.0012.706ATOM734CGGLUA23647.55630.319115.7721.0013.276ATOM735CDGLUA23647.60828.880115.2731.0013.936ATOM736OE1GLUA23648.17428.004115.9641.0015.468ATOM737OE2GLUA23647.07028.623114.1821.0014.908ATOM738CGLUA23648.53631.693119.2131.0012.346ATOM739OGLUA23649.71731.561119.5311.0010.748ATOM740NLEUA23747.52731.596120.0781.0011.557ATOM741CALEUA23747.74031.367121.5061.0013.296ATOM742CBLEUA23746.41931.508122.2701.0014.426ATOM743CGLEUA23746.43832.016123.7141.0018.606ATOM744CD1LEUA23747.16633.356123.8181.0016.356ATOM745CD2LEUA23745.00532.156124.2051.0016.856ATOM746CLEUA23748.29329.942121.6291.0012.926ATOM747OLEUA23749.07429.649122.5321.0014.018ATOM748NPHEA23847.96529.113120.6281.0011.907ATOM749CAPHEA23848.41927.724120.5181.0013.506ATOM750CBPHEA23847.74927.047119.3041.0014.416ATOM751CGPHEA23848.06725.572119.1451.0016.036ATOM752CD1PHEA23847.99624.678120.2401.0018.086ATOM753CD2PHEA23848.45325.070117.8871.0017.796ATOM754CE1PHEA23848.31223.304120.0791.0017.356ATOM755CE2PHEA23848.76823.696117.7121.0018.936ATOM756CZPHEA23848.69822.812118.8121.0017.356ATOM757CPHEA23849.94127.669120.3891.0012.666ATOM758OPHEA23850.57326.827121.0151.0012.968ATOM759NPHEA23950.51628.597119.6201.0012.537ATOM760CAPHEA23951.97028.666119.4221.0012.416ATOM761CBPHEA23952.31329.767118.3941.0012.066ATOM762CGPHEA23953.76829.796117.9771.0013.716ATOM763CD1PHEA23954.20829.031116.8801.0014.816ATOM764CD2PHEA23954.71530.559118.6981.0013.776ATOM765CE1PHEA23955.57729.016116.5031.0016.726ATOM766CE2PHEA23956.09030.554118.3371.0015.616ATOM767CZPHEA23956.52129.780117.2371.0017.176ATOM768CPHEA23952.70028.941120.7431.0011.846ATOM769OPHEA23953.67628.261121.0701.0013.118ATOM770NHISA24052.21129.942121.4761.0011.727ATOM771CAHISA24052.79030.372122.7471.0011.296ATOM772CBHISA24052.21031.722123.1561.0011.116ATOM773CGHISA24052.46032.796122.1491.0011.016ATOM774CD2HISA24051.63833.376121.2451.0012.506ATOM775ND1HISA24053.71233.325121.9271.0012.867ATOM776CE1HISA24053.64934.180120.9231.0013.246ATOM777NE2HISA24052.40234.228120.4911.0012.177ATOM778CHISA24052.63529.369123.8671.0012.956ATOM779OHISA24053.58329.128124.6161.0013.888ATOM780NLEUA24151.45428.756123.9481.0012.027ATOM781CALEUA24151.18327.758124.9721.0012.516ATOM782CBLEUA24149.68127.489125.0981.0011.916ATOM783CGLEUA24149.24826.637126.2961.0012.536ATOM784CD1LEUA24149.62127.298127.6091.0013.036ATOM785CD2LEUA24147.78326.412126.2271.0012.416ATOM786CLEUA24151.95026.466124.7161.0013.136ATOM787OLEUA24152.41725.843125.6611.0013.588ATOM788NSERA24252.11926.099123.4451.0014.037ATOM789CASERA24252.86824.889123.0841.0015.826ATOM790CBSERA24252.74924.585121.5921.0015.046ATOM791OGSERA24251.41824.242121.2521.0019.048ATOM792CSERA24254.34125.040123.4591.0016.866ATOM793OSERA24254.95224.096123.9571.0018.498ATOM794NARGA24354.86726.255123.2921.0015.487ATOM795CAARGA24356.25726.581123.6121.0016.346ATOM796CBARGA24356.64227.922122.9551.0016.886ATOM797CGARGA24358.09528.390123.1681.0018.936ATOM798CDARGA24358.29429.850122.7481.0019.476ATOM799NEARGA24357.53830.788123.5851.0022.917ATOM800CZARGA24356.67131.696123.1311.0023.626ATOM801NH1ARGA24356.42531.817121.8331.0023.767ATOM802NH2ARGA24356.02532.473123.9871.0024.687ATOM803CARGA24356.49426.647125.1261.0015.266ATOM804OARGA24357.42126.014125.6401.0016.988ATOM805NGLUA24455.62027.371125.8261.0014.287ATOM806CAGLUA24455.72427.572127.2711.0014.526ATOM807CBGLUA24455.10928.921127.6521.0017.016ATOM808CGGLUA24455.88630.116127.1041.0021.116ATOM809CDGLUA24455.34431.453127.5741.0024.366ATOM810OE1GLUA24454.92631.564128.7471.0027.608ATOM811OE2GLUA24455.35432.409126.7721.0027.598ATOM812CGLUA24455.15026.471128.1581.0012.966ATOM813OGLUA24455.41026.458129.3651.0013.388ATOM814NARGA24554.43425.525127.5341.0013.947ATOM815CAARGA24553.76324.360128.1631.0014.016ATOM816CBARGA24554.70623.493129.0361.0016.246ATOM817CGARGA24556.06023.080128.4361.0020.526ATOM818CDARGA24555.96622.358127.1071.0021.966ATOM819NEARGA24557.28621.861126.7171.0022.927ATOM820CZARGA24557.90022.123125.5661.0021.926ATOM821NH1ARGA24557.33222.894124.6471.0021.677ATOM822NH2ARGA24559.08121.575125.3211.0021.947ATOM823CARGA24552.53124.740128.9871.0014.876ATOM824OARGA24551.46824.127128.8481.0014.168ATOM825NVALA24652.68625.768129.8191.0013.227ATOM826CAVALA24651.63426.246130.7091.0013.496ATOM827CBVALA24651.64625.409132.0451.0013.876ATOM828CG1VALA24652.91325.677132.8721.0017.886ATOM829CG2VALA24650.38525.630132.8491.0014.926ATOM830CVALA24651.81727.747130.9851.0012.496ATOM831OVALA24652.92828.272130.8821.0014.568ATOM832NPHEA24750.70928.435131.2681.0012.157ATOM833CAPHEA24750.73429.856131.6031.0010.966ATOM834CBPHEA24749.62130.638130.8781.009.306ATOM835CGPHEA24749.81530.808129.3841.0010.756ATOM836CD1PHEA24751.08030.681128.7701.0011.596ATOM837CD2PHEA24748.70731.134128.5831.0010.236ATOM838CE1PHEA24751.23330.880127.3691.0013.016ATOM839CE2PHEA24748.83731.335127.1861.0010.256ATOM840CZPHEA24750.10831.209126.5741.0011.786ATOM841CPHEA24750.43829.956133.0891.0011.656ATOM842OPHEA24749.81929.055133.6691.0013.938ATOM843NTHRA24850.84131.072133.6971.0012.277ATOM844CATHRA24850.54731.327135.1101.0012.376ATOM845CBTHRA24851.32532.557135.6481.0014.866ATOM846OG1THRA24850.93933.729134.9181.0014.648ATOM847CG2THRA24852.83032.350135.5171.0015.186ATOM848CTHRA24849.04631.651135.1591.0013.216ATOM849OTHRA24848.44631.979134.1241.0012.838ATOM850NGLUA24948.44531.566136.3431.0012.567ATOM851CAGLUA24947.02231.864136.4961.0013.616ATOM852CBGLUA24946.54531.518137.8981.0013.496ATOM853CGGLUA24946.50930.020138.1551.0015.226ATOM854CDGLUA24945.81129.660139.4421.0016.836ATOM855OE1GLUA24944.94430.441139.8961.0018.718ATOM856OE2GLUA24946.11428.581139.9951.0016.068ATOM857CGLUA24946.68533.313136.1641.0012.756ATOM858OGLUA24945.62933.581135.5941.0012.678ATOM859NGLUA25047.63634.215136.4261.0012.457ATOM860CAGLUA25047.46735.641136.1521.0013.296ATOM861CBGLUA25048.53336.469136.8861.0017.166ATOM862CGGLUA25048.22337.970137.0021.0022.236ATOM863CDGLUA25047.03438.270137.9111.0024.686ATOM864OE1GLUA25047.18438.164139.1471.0031.368ATOM865OE2GLUA25045.95338.615137.3931.0026.068ATOM866CGLUA25047.50835.918134.6461.0011.946ATOM867OGLUA25046.73736.739134.1441.0013.218ATOM868NARGA25148.36435.189133.9281.0011.707ATOM869CAARGA25148.48235.342132.4761.0012.386ATOM870CBARGA25149.75534.666131.9491.0013.126ATOM871CGARGA25149.90834.762130.4441.0015.276ATOM872CDARGA25151.32534.733129.9701.0017.396ATOM873NEARGA25151.36534.932128.5241.0017.477ATOM874CZARGA25152.29234.426127.7171.0017.606ATOM875NH1ARGA25153.27433.690128.2091.0021.217ATOM876NH2ARGA25152.21334.625126.4101.0018.017ATOM877CARGA25147.23634.780131.7881.0011.766ATOM878OARGA25146.70735.395130.8561.0012.208ATOM879NALAA25246.74633.649132.2971.0011.067ATOM880CAALAA25245.54333.006131.7691.0010.456ATOM881CBALAA25245.37231.652132.3741.0011.176ATOM882CALAA25244.31633.868132.0551.0010.896ATOM883OALAA25243.39933.939131.2351.0011.648ATOM884NARGA25344.33934.562133.1971.0010.827ATOM885CAARGA25343.24935.460133.5891.0010.506ATOM886CBARGA25343.44635.960135.0231.0011.206ATOM887CGARGA25342.40836.983135.5251.0012.576ATOM888CDARGA25342.25336.983137.0461.0017.076ATOM889NEARGA25343.52336.861137.7531.0020.667ATOM890CZARGA25343.81535.901138.6291.0018.826ATOM891NH1ARGA25342.92634.964138.9391.0017.587ATOM892NH2ARGA25345.03735.830139.1251.0019.037ATOM893CARGA25343.16036.637132.6241.0010.056ATOM894OARGA25342.06337.023132.2401.009.548ATOM895NPHEA25444.31637.171132.2171.0010.687ATOM896CAPHEA25444.36538.294131.2761.0010.566ATOM897CBPHEA25445.81338.759131.0371.0011.016ATOM898CGPHEA25445.93039.938130.0911.0012.846ATOM899CD1PHEA25445.86641.253130.5831.0015.956ATOM900CD2PHEA25446.08139.738128.6941.0014.786ATOM901CE1PHEA25445.94542.363129.7011.0017.526ATOM902CE2PHEA25446.16240.834127.8001.0015.816ATOM903CZPHEA25446.09142.153128.3101.0016.736ATOM904CPHEA25443.70837.910129.9471.009.276ATOM905OPHEA25442.82738.623129.4651.009.858ATOM906NTYRA25544.14736.791129.3671.008.557ATOM907CATYRA25543.60536.311128.0941.008.186ATOM908CBTYRA25544.41635.127127.5531.008.206ATOM909CGTYRA25545.84635.466127.1821.009.186ATOM910CD1TYRA25546.17336.690126.5541.009.546ATOM911CE1TYRA25547.51937.024126.2461.009.526ATOM912CD2TYRA25546.89234.578127.4871.009.666ATOM913CE2TYRA25548.24034.899127.1771.0010.466ATOM914CZTYRA25548.54136.120126.5611.0010.836ATOM915OHTYRA25549.85236.426126.2731.0011.248ATOM916CTYRA25542.14335.929128.2271.008.296ATOM917OTYRA25541.32436.317127.3931.007.518ATOM918NGLYA25641.81935.279129.3471.008.207ATOM919CAGLYA25640.45734.859129.6371.008.206ATOM920CGLYA25639.49736.028129.7171.008.286ATOM921OGLYA25638.42135.970129.1321.008.778ATOM922NALAA25739.92937.118130.3571.008.227ATOM923CAALAA25739.11138.329130.4931.008.376ATOM924CBALAA25739.79939.341131.3941.009.126ATOM925CALAA25738.79938.961129.1411.009.176ATOM926OALAA25737.66839.385128.8851.009.038ATOM927NGLUA25839.79338.960128.2561.009.457ATOM928CAGLUA25839.62639.518126.9171.009.236ATOM929CBGLUA25840.98239.762126.2631.0010.326ATOM930CGGLUA25841.84240.737127.0631.0010.326ATOM931CDGLUA25842.97641.347126.2741.0012.976ATOM932OE1GLUA25843.48840.711125.3331.0012.518ATOM933OE2GLUA25843.35642.494126.5941.0013.098ATOM934CGLUA25838.70938.657126.0501.0010.116ATOM935OGLUA25837.88939.192125.2981.0010.138ATOM936NILEA25938.77337.333126.2311.0010.637ATOM937CAILEA25937.90336.410125.4881.009.016ATOM938CBILEA25938.36634.929125.6061.008.236ATOM939CG2ILEA25937.40333.993124.8331.009.956ATOM940CG1ILEA25939.76334.775125.0021.008.986ATOM941CD1ILEA25940.50833.536125.4871.009.306ATOM942CILEA25936.45436.560125.9881.008.436ATOM943OILEA25935.53036.577125.1771.0010.448ATOM944NVALA26036.27836.742127.3031.007.997ATOM945CAVALA26034.94636.924127.9001.007.716ATOM946CBVALA26034.99436.958129.4661.008.746ATOM947CG1VALA26033.63037.300130.0621.0010.316ATOM948CG2VALA26035.41935.625130.0111.0010.156ATOM949CVALA26034.32638.223127.3671.007.826ATOM950OVALA26033.15638.239126.9991.009.478ATOM951NSERA26135.13939.279127.2681.009.117ATOM952CASERA26134.68540.578126.7621.009.166ATOM953CBSERA26135.81741.609126.8461.0010.756ATOM954OGSERA26135.36842.898126.4521.0012.268ATOM955CSERA26134.19240.452125.3171.009.346ATOM956OSERA26133.10240.936124.9801.0010.408ATOM957NALAA26234.95139.707124.5081.009.967ATOM958CAALAA26234.61639.478123.1021.009.296ATOM959CBALAA26235.78438.842122.3831.009.416ATOM960CALAA26233.35638.626122.9351.0010.296ATOM961OALAA26232.51838.928122.0871.0010.488ATOM962NLEUA26333.21437.593123.7711.009.867ATOM963CALEUA26332.04836.706123.7231.0010.296ATOM964CBLEUA26332.30235.401124.4831.009.986ATOM965CGLEUA26333.23534.374123.8271.0010.036ATOM966CD1LEUA26333.51433.251124.8061.0011.526ATOM967CD2LEUA26332.64133.812122.5371.0012.886ATOM968CLEUA26330.77737.398124.2151.0011.306ATOM969OLEUA26329.69937.165123.6681.0011.308ATOM970NGLUA26430.92638.300125.1921.0011.157ATOM971CAGLUA26429.80739.087125.7281.0011.336ATOM972CBGLUA26430.27339.982126.8951.0013.746ATOM973CGGLUA26429.16040.738127.6681.0019.626ATOM974CDGLUA26428.79442.099127.0931.0025.176ATOM975OE1GLUA26427.58042.378126.9741.0028.228ATOM976OE2GLUA26429.71142.880126.7581.0029.468ATOM977CGLUA26429.29139.964124.5841.0010.826ATOM978OGLUA26428.08140.063124.3711.0011.308ATOM979NTYRA26530.22540.569123.8451.0012.377ATOM980CATYRA26529.88341.428122.7121.0011.806ATOM981CBTYRA26531.13242.124122.1431.0012.006ATOM982CGTYRA26530.88042.913120.8681.0014.176ATOM983CD1TYRA26530.25344.179120.9021.0015.206ATOM984CE1TYRA26529.94444.873119.6971.0015.026ATOM985CD2TYRA26531.20042.361119.6111.0013.356ATOM986CE2TYRA26530.89643.037118.4141.0014.776ATOM987CZTYRA26530.27044.283118.4631.0015.026ATOM988OHTYRA26529.95744.896117.2771.0016.508ATOM989CTYRA26529.16740.626121.6261.0011.736ATOM990OTYRA26528.12941.063121.1281.0012.828ATOM991NLEUA26629.73539.477121.2491.0011.977ATOM992CALEUA26629.12738.624120.2221.0012.056ATOM993CBLEUA26630.01037.409119.9131.0011.596ATOM994CGLEUA26631.26137.654119.0641.0011.696ATOM995CD1LEUA26632.12536.401119.0731.0013.186ATOM996CD2LEUA26630.89338.051117.6341.0013.086ATOM997CLEUA26627.71738.182120.6041.0011.876ATOM998OLEUA26626.79538.302119.7971.0011.498ATOM999NHISA26727.53337.786121.8671.0010.937ATOM1000CAHISA26726.22337.353122.3591.0011.186ATOM1001CBHISA26726.34636.670123.7261.0010.666ATOM1002CGHISA26726.99935.319123.6751.0010.636ATOM1003CD2HISA26727.61934.657122.6661.0011.096ATOM1004ND1HISA26727.06434.486124.7711.0012.067ATOM1005CE1HISA26727.69133.372124.4431.0010.446ATOM1006NE2HISA26728.03833.450123.1701.008.557ATOM1007CHISA26725.20838.497122.4061.0011.656ATOM1008OHISA26724.02138.280122.1461.0013.218ATOM1009NSERA26825.69539.720122.6401.0013.707ATOM1010CASERA26824.83740.913122.6821.0014.736ATOM1011CBSERA26825.56242.097123.3411.0015.256ATOM1012OGSERA26826.49542.711122.4691.0019.138ATOM1013CSERA26824.38041.286121.2621.0015.806ATOM1014OSERA26823.36941.971121.0871.0017.358ATOM1015NARGA26925.14140.820120.2671.0015.447ATOM1016CAARGA26924.84841.044118.8471.0015.626ATOM1017CBARGA26926.14541.312118.0651.0018.826ATOM1018CGARGA26926.87642.596118.4461.0022.506ATOM1019CDARGA26926.22143.847117.8751.0026.136ATOM1020NEARGA26926.82744.258116.6081.0029.687ATOM1021CZARGA26926.14944.529115.4941.0032.996ATOM1022NH1ARGA26924.82244.436115.4681.0035.147ATOM1023NH2ARGA26926.79944.896114.3981.0033.057ATOM1024CARGA26924.12439.826118.2531.0015.106ATOM1025OARGA26924.01939.692117.0281.0015.018ATOM1026NASPA27023.63138.951119.1381.0012.977ATOM1027CAASPA27022.90237.719118.7921.0013.076ATOM1028CBASPA27021.57138.029118.0671.0015.556ATOM1029CGASPA27020.62838.900118.8851.0018.496ATOM1030OD1ASPA27020.79639.022120.1191.0018.808ATOM1031OD2ASPA27019.69139.454118.2781.0019.668ATOM1032CASPA27023.72036.701117.9841.0012.416ATOM1033OASPA27023.18035.949117.1691.0012.298ATOM1034NVALA27125.03036.692118.2201.0011.567ATOM1035CAVALA27125.94135.786117.5241.0011.246ATOM1036CBVALA27127.08636.576116.7951.0011.076ATOM1037CG1VALA27128.04135.628116.0601.0012.566ATOM1038CG2VALA27126.50637.589115.8081.0012.976ATOM1039CVALA27126.57534.785118.4871.0011.136ATOM1040OVALA27127.05935.165119.5491.0013.728ATOM1041NVALA27226.52833.505118.1181.0010.757ATOM1042CAVALA27227.16332.436118.8971.009.536ATOM1043CBVALA27226.21131.241119.1471.009.396ATOM1044CG1VALA27226.88830.171119.9931.0010.606ATOM1045CG2VALA27225.00331.719119.8721.0011.646ATOM1046CVALA27228.34932.027118.0281.0010.466ATOM1047OVALA27228.19131.735116.8451.0011.348ATOM1048NTYRA27329.53032.008118.6381.0010.177ATOM1049CATYRA27330.78431.716117.9511.0010.406ATOM1050CBTYRA27331.92232.326118.7761.0010.326ATOM1051CGTYRA27333.27432.247118.1351.009.826ATOM1052CD1TYRA27333.59933.010116.9941.0011.786ATOM1053CE1TYRA27334.85232.854116.3601.0010.916ATOM1054CD2TYRA27334.22331.352118.6261.009.976ATOM1055CE2TYRA27335.45831.201118.0121.009.276ATOM1056CZTYRA27335.77131.931116.8901.0011.966ATOM1057OHTYRA27336.98131.665116.3191.0012.288ATOM1058CTYRA27331.04130.245117.5591.0011.406ATOM1059OTYRA27331.55029.976116.4631.0010.698ATOM1060NARGA27430.73929.325118.4811.0011.097ATOM1061CAARGA27430.85427.862118.3081.0011.216ATOM1062CBARGA27429.83227.352117.2691.0011.926ATOM1063CGARGA27428.38827.621117.6491.0012.166ATOM1064CDARGA27427.40426.886116.7651.0011.716ATOM1065NEARGA27427.39527.364115.3861.0011.257ATOM1066CZARGA27426.47027.037114.4871.0011.436ATOM1067NH1ARGA27425.47026.231114.8191.0012.817ATOM1068NH2ARGA27426.54627.513113.2511.0011.897ATOM1069CARGA27432.20527.183118.0551.0011.206ATOM1070OARGA27432.27425.946118.0531.0012.438ATOM1071NASPA27533.27427.961117.8801.0010.427ATOM1072CAASPA27534.58427.366117.6111.0010.316ATOM1073CBASPA27534.89427.441116.0981.0011.536ATOM1074CGASPA27535.93826.414115.6481.0011.036ATOM1075OD1ASPA27536.15925.421116.3681.0011.268ATOM1076OD2ASPA27536.54326.609114.5731.0011.218ATOM1077CASPA27535.74727.920118.4491.009.716ATOM1078OASPA27536.84728.132117.9261.0011.058ATOM1079NILEA27635.50828.192119.7381.0010.177ATOM1080CAILEA27636.57928.693120.6161.008.906ATOM1081CBILEA27636.07529.076122.0531.009.506ATOM1082CG2ILEA27637.26629.314123.0121.0010.366ATOM1083CG1ILEA27635.15930.308122.0211.0010.786ATOM1084CD1ILEA27635.87931.670121.8121.0011.936ATOM1085CILEA27637.63327.589120.7301.009.856ATOM1086OILEA27637.31326.440121.0451.0011.588ATOM1087NLYSA27738.84927.943120.3251.009.237ATOM1088CALYSA27740.00727.066120.3691.008.296ATOM1089CBLYSA27739.98125.985119.2761.009.246ATOM1090CGLYSA27739.97226.423117.8551.008.246ATOM1091CDLYSA27740.03525.187116.9941.009.506ATOM1092CELYSA27739.87125.524115.5421.0011.546ATOM1093NZLYSA27739.78524.276114.7361.0011.887ATOM1094CLYSA27741.28327.868120.3131.007.926ATOM1095OLYSA27741.28228.996119.8261.009.728ATOM1096NLEUA27842.37827.280120.7921.007.687ATOM1097CALEUA27843.66327.978120.8051.008.186ATOM1098CBLEUA27844.71427.140121.5221.008.716ATOM1099CGLEUA27844.58326.828123.0101.008.946ATOM1100CD1LEUA27845.70625.886123.3481.009.566ATOM1101CD2LEUA27844.65128.077123.8821.009.776ATOM1102CLEUA27844.17228.424119.4251.009.326ATOM1103OLEUA27844.84729.448119.3171.009.578ATOM1104NGLUA27943.79127.689118.3781.0010.177ATOM1105CAGLUA27944.19028.007117.0001.0010.116ATOM1106CBGLUA27943.99426.791116.0791.0010.416ATOM1107CGGLUA27944.88825.588116.3961.0012.006ATOM1108CDGLUA27944.25024.565117.3281.0015.396ATOM1109OE1GLUA27943.40624.937118.1711.0014.168ATOM1110OE2GLUA27944.62223.375117.2321.0016.188ATOM1111CGLUA27943.43829.209116.4221.0010.726ATOM1112OGLUA27943.89129.828115.4551.0010.078ATOM1113NASNA28042.29729.532117.0331.009.727ATOM1114CAASNA28041.45030.649116.6061.009.626ATOM1115CBASNA28039.97230.243116.6291.008.796ATOM1116CGASNA28039.60629.282115.5201.0010.796ATOM1117OD1ASNA28040.43128.950114.6651.009.208ATOM1118ND2ASNA28038.36128.820115.5321.009.717ATOM1119CASNA28041.62831.902117.4571.008.786ATOM1120OASNA28040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TOM1339O2PPTHA30923.15825.593113.3101.0015.008ATOM1340O3PPTHA30922.42925.765110.8291.0018.478ATOM1341NPHEA31025.39720.267113.7671.0015.097ATOM1342CAPHEA31026.42319.504114.4851.0014.346ATOM1343CBPHEA31026.22717.991114.2471.0014.106ATOM1344CGPHEA31027.22317.094114.9671.0016.326ATOM1345CD1PHEA31027.68915.925114.3351.0017.966ATOM1346CD2PHEA31027.67217.380116.2781.0016.416ATOM1347CE1PHEA31028.59015.042114.9921.0018.616ATOM1348CE2PHEA31028.57416.509116.9531.0016.196ATOM1349CZPHEA31029.03415.336116.3061.0018.266ATOM1350CPHEA31027.74520.012113.9031.0014.546ATOM1351OPHEA31028.13719.636112.7961.0014.238ATOM1352NCYSA31128.38220.925114.6381.0013.117ATOM1353CACYSA31129.63221.538114.1991.0013.416ATOM1354CBCYSA31129.33022.730113.2831.0013.506ATOM1355SGCYSA31128.51424.101114.1031.0013.3716ATOM1356CCYSA31130.50922.003115.3591.0013.006ATOM1357OCYSA31130.05522.078116.4991.0012.358ATOM1358NGLYA31231.74422.375115.0251.0012.887ATOM1359CAGLYA31232.71222.837116.0081.0012.866ATOM1360CGLYA31234.02222.129115.7341.0012.336ATOM1361OGLYA31234.29921.770114.5981.0013.158ATOM1362NTHRA31334.84321.966116.7631.0011.867ATOM1363CATHRA31336.11721.259116.6451.0010.146ATOM1364CBTHRA31337.30122.206116.9561.0010.446ATOM1365OG1THRA31337.43623.145115.8841.0010.808ATOM1366CG2THRA31338.58321.453117.0651.0011.086ATOM1367CTHRA31335.96820.114117.6511.0011.706ATOM1368OTHRA31335.64220.372118.8071.0010.748ATOM1369NPROA31436.20518.842117.2281.0011.547ATOM1370CDPROA31436.73618.435115.9091.0012.436ATOM1371CAPROA31436.07717.650118.0811.0012.236ATOM1372CBPROA31436.84016.591117.2941.0012.246ATOM1373CGPROA31436.50916.940115.9131.0012.536ATOM1374CPROA31436.49117.712119.5471.0011.906ATOM1375OPROA31435.67117.476120.4361.0012.588ATOM1376NGLUA31537.72618.139119.7901.0011.737ATOM1377CAGLUA31538.29418.232121.1391.0011.656ATOM1378CBGLUA31539.80518.469121.0281.0013.256ATOM1379CGGLUA31540.61617.282120.4591.0014.196ATOM1380CDGLUA31540.63817.168118.9311.0016.376ATOM1381OE1GLUA31540.04118.007118.2211.0014.238ATOM1382OE2GLUA31541.29016.225118.4331.0018.218ATOM1383CGLUA31537.66719.298122.0361.0010.256ATOM1384OGLUA31537.78619.235123.2641.0012.568ATOM1385NTYRA31636.95520.232121.4081.0011.117ATOM1386CATYRA31636.31621.359122.0811.0010.656ATOM1387CBTYRA31636.71722.655121.3711.0010.986ATOM1388CGTYRA31638.16023.037121.5671.0010.606ATOM1389CD1TYRA31639.18122.485120.7641.0010.056ATOM1390CE1TYRA31640.54222.844120.9621.009.966ATOM1391CD2TYRA31638.51623.949122.5661.0011.266ATOM1392CE2TYRA31639.86424.316122.7791.008.346ATOM1393CZTYRA31640.86523.767121.9681.009.906ATOM1394OHTYRA31642.14524.230122.1121.009.378ATOM1395CTYRA31634.79921.314122.1681.0011.136ATOM1396OTYRA31634.19422.219122.7461.0010.578ATOM1397NLEUA31734.18320.281121.5941.0010.047ATOM1398CALEUA31732.72620.161121.6031.0011.086ATOM1399CBLEUA31732.26618.970120.7611.0011.226ATOM1400CGLEUA31732.46719.008119.2531.0013.096ATOM1401CD1LEUA31731.97417.699118.6831.0014.176ATOM1402CD2LEUA31731.74820.176118.6171.0014.116ATOM1403CLEUA31732.12120.027122.9811.0010.036ATOM1404OLEUA31732.65719.324123.8361.009.848ATOM1405NALAA31831.02820.759123.1901.009.607ATOM1406CAALAA31830.27320.734124.4361.009.906ATOM1407CBALAA31829.37121.966124.5081.009.346ATOM1408CALAA31829.45119.441124.4721.0010.076ATOM1409OALAA31829.06018.947123.4151.0011.238ATOM1410NPROA31929.22418.847125.6711.0010.247ATOM1411CDPROA31929.70719.251126.9991.0011.916ATOM1412CAPROA31928.44517.607125.7981.0011.426ATOM1413CBPROA31928.31817.442127.3091.0013.436ATOM1414CGPROA31929.60117.967127.7841.0013.396ATOM1415CPROA31927.07617.640125.1321.0012.326ATOM1416OPROA31926.69216.672124.4811.0012.648ATOM1417NGLUA32026.38518.780125.2311.0012.717ATOM1418CAGLUA32025.05618.940124.6291.0011.426ATOM1419CBGLUA32024.35820.216125.1411.0011.326ATOM1420CGGLUA32025.01721.549124.7531.0011.276ATOM1421CDGLUA32026.02722.078125.7561.0014.016ATOM1422OE1GLUA32026.66621.289126.4931.0010.848ATOM1423OE2GLUA32026.20823.317125.7841.0013.578ATOM1424CGLUA32025.08418.882123.0911.0011.896ATOM1425OGLUA32024.11218.447122.4691.0011.848ATOM1426NVALA32126.22019.259122.4931.0010.097ATOM1427CAVALA32126.38619.222121.0321.009.776ATOM1428CBVALA32127.58220.115120.5541.0010.346ATOM1429CG1VALA32127.72020.112119.0221.0011.926ATOM1430CG2VALA32127.36621.540121.0201.0011.026ATOM1431CVALA32126.56417.763120.5861.0010.886ATOM1432OVALA32126.24517.412119.4521.0012.298ATOM1433NLEUA32227.00716.913121.5151.0010.497ATOM1434CALEUA32227.20015.486121.2481.0010.526ATOM1435CBLEUA32228.38014.958122.0541.0011.296ATOM1436CGLEUA32229.71915.466121.5341.0011.466ATOM1437CD1LEUA32230.79915.145122.5281.009.976ATOM1438CD2LEUA32229.99814.836120.1861.0011.906ATOM1439CLEUA32225.93714.670121.5181.0010.416ATOM1440OLEUA32225.95013.428121.5101.0011.218ATOM1441NGLUA32324.85115.393121.7691.0011.887ATOM1442CAGLUA32323.53714.809122.0041.0013.486ATOM1443CBGLUA32322.94915.291123.3311.0013.706ATOM1444CGGLUA32323.68514.788124.5641.0012.406ATOM1445CDGLUA32323.17415.399125.8511.0015.226ATOM1446OE1GLUA32322.62916.524125.8151.0015.128ATOM1447OE2GLUA32323.32614.753126.9091.0015.118ATOM1448CGLU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006ATOM1558CD2LEUA33635.21832.070129.3881.0011.206ATOM1559CLEUA33636.85628.274128.1751.008.426ATOM1560OLEUA33638.04028.422128.4761.008.708ATOM1561NGLYA33736.06027.359128.7301.008.617ATOM1562CAGLYA33736.53326.470129.7811.009.316ATOM1563CGLYA33737.65825.562129.3381.009.786ATOM1564OGLYA33738.61625.361130.0811.009.128ATOM1565NVALA33837.55725.053128.1091.007.997ATOM1566CAVALA33838.58824.173127.5541.008.616ATOM1567CBVALA33838.13223.492126.2451.007.046ATOM1568CG1VALA33839.17622.505125.7661.007.766ATOM1569CG2VALA33836.82822.739126.4511.009.226ATOM1570CVALA33839.89624.954127.3451.007.706ATOM1571OVALA33840.95324.480127.7631.008.428ATOM1572NVALA33939.82126.168126.7841.009.327ATOM1573CAVALA33941.04426.967126.5891.008.896ATOM1574CBVALA33940.91028.158125.5801.0011.166ATOM1575CG1VALA33940.54827.642124.2161.009.526ATOM1576CG2VALA33939.92829.205126.0351.0014.026ATOM1577CVALA33941.65727.434127.9081.008.656ATOM1578OVALA33942.87427.454128.0301.008.948ATOM1579NMETA34040.81727.743128.9041.009.447ATOM1580CAMETA34041.30728.162130.2241.008.926ATOM1581CBMETA34040.17728.715131.0981.0011.706ATOM1582CGMETA34039.64530.076130.6891.0013.056ATOM1583SDMETA34040.85831.386130.6941.0015.7316ATOM1584CEMETA34040.96131.748132.4091.0015.846ATOM1585CMETA34041.97826.977130.9241.008.246ATOM1586OMETA34042.99727.147131.6061.008.988ATOM1587NTYRA34141.43725.775130.6961.008.737ATOM1588CATYRA34141.99024.540131.2641.008.306ATOM1589CBTYRA34141.04823.338131.0251.008.536ATOM1590CGTYRA34141.45122.067131.7581.009.946ATOM1591CD1TYRA34142.49321.251131.2691.009.716ATOM1592CE1TYRA34142.93020.119131.9671.009.216ATOM1593CD2TYRA34140.84021.703132.9761.009.176ATOM1594CE2TYRA34141.27920.549133.6951.0010.706ATOM1595CZTYRA34142.32619.776133.1711.0010.866ATOM1596OHTYRA34142.78818.671133.8241.0013.118ATOM1597CTYRA34143.35424.298130.6251.008.676ATOM1598OTYRA34144.32023.996131.3241.009.198ATOM1599NGLUA34243.42824.433129.3011.007.617ATOM1600CAGLUA34244.69024.241128.5871.007.626ATOM1601CBGLUA34244.49024.394127.0911.006.736ATOM1602CGGLUA34243.75423.252126.4541.008.696ATOM1603CDGLUA34243.57823.471124.9871.009.656ATOM1604OE1GLUA34242.68324.256124.6221.0010.418ATOM1605OE2GLUA34244.34922.881124.1971.0010.208ATOM1606CGLUA34245.76025.223129.0441.009.356ATOM1607OGLUA34246.91424.843129.2261.009.348ATOM1608NMETA34345.35826.475129.2591.009.447ATOM1609CAMETA34346.28627.514129.6961.009.686ATOM1610CDMETA34345.65628.901129.5661.009.676ATOM1611CGMETA34345.45729.356128.1341.0010.766ATOM1612SDMETA34345.04331.114128.0131.0012.4716ATOM1613CEMETA34343.29131.044128.0011.0016.496ATOM1614CMETA34346.81227.325131.1151.0011.096ATOM1615OMETA34347.98027.587131.3771.0012.538ATOM1616NMETA34445.96026.829132.0131.009.997ATOM1617CAMETA34446.36126.644133.4081.0010.386ATOM1618CBMETA34445.26627.135134.3581.0011.176ATOM1619CGMETA34445.01228.613134.2321.0013.276ATOM1620SDMETA34443.86729.333135.4121.0013.1116ATOM1621CEMETA34442.32728.674134.8571.0013.346ATOM1622CMETA34446.82025.251133.8151.0010.466ATOM1623OMETA34447.54925.110134.8041.0011.068ATOM1624NCYSA34546.43624.234133.0461.0011.997ATOM1625CACYSA34546.81822.858133.3691.0011.036ATOM1626CBCYSA34545.57621.998133.5841.0010.846ATOM1627SGCYSA34544.37322.685134.7511.0013.2316ATOM1628CCYSA34547.76722.190132.3731.0011.636ATOM1629OCYSA34548.20521.059132.5981.0014.388ATOM1630NGLYA34648.06522.875131.2681.0011.837ATOM1631CAGLYA34648.99822.352130.2781.0012.506ATOM1632CGLYA34648.57521.212129.3681.0012.696ATOM1633OGLYA34649.42820.592128.7291.0015.898ATOM1634NARGA34747.27620.920129.3241.0011.557ATOM1635CAARGA34746.72719.860128.4721.0011.096ATOM1636CBARGA34746.95918.458129.0841.0010.996ATOM1637CCARGA34746.33418.210130.4711.0013.536ATOM1638CDARGA34746.27116.716130.7541.0013.476ATOM1639NEARGA34745.68516.370132.0501.0014.437ATOM1640CZARGA34744.39716.097132.2531.0014.076ATOM1641NH1ARGA34743.53116.151131.2501.0013.527ATOM1642NH2ARGA34743.99015.663133.4411.0012.667ATOM1643CARGA34745.23520.073128.2971.0011.676ATOM1644OARGA34744.63720.876129.0081.0010.218ATOM1645NLEUA34844.64519.346127.3481.0011.537ATOM1646CALEUA34843.20119.374127.1111.0010.756ATOM1647CBLEUA34842.86018.654125.8001.0011.506ATOM1648CGLEUA34842.98319.406124.4781.008.456ATOM1649CD1LUEA34842.93618.422123.3361.0011.456ATOM1650CD2LEUA34841.86020.408124.3271.0010.406ATOM1651CLEUA34842.56118.599128.2681.0010.746ATOM1652OLEUA34843.20217.706128.8341.0010.768ATOM1653NPROA34941.32818.966128.6811.009.417ATOM1654CDPROA34940.52120.142128.2991.0010.396ATOM1655CAPROA34940.68018.237129.7791.0010.536ATOM1656CBPROA34939.44019.086130.0711.0010.906ATOM1657CGPROA34939.15619.764128.7791.0010.536ATOM1658CPROA34940.34916.791129.4191.0011.316ATOM1659OPROA34940.37315.906130.2831.0013.758ATOM1660NPHEA35040.07816.570128.1321.0012.537ATOM1661CAPHEA35039.74615.250127.5861.0013.426ATOM1662CBPHEA35038.24115.128127.2921.0014.486ATOM1663CGPHEA35037.35515.549128.4241.0014.546ATOM1664CD1PHEA35037.23414.752129.5761.0016.306ATOM1665CD2PHEA35036.66216.774128.3601.0015.736ATOM1666CE1PHEA35036.43115.171130.6641.0018.066ATOM1667CE2PHEA35035.85717.208129.4371.0015.866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018.496ATOM1997CBLYSA39020.44624.240132.5951.0020.366ATOM1998CGLYSA39019.60824.313131.3281.0024.886ATOM1999CDLYSA39018.13824.030131.6031.0031.456ATOM2000CELYSA39017.28724.269130.3571.0034.466ATOM2001NZLYSA39017.32425.694129.8931.0036.887ATOM2002CLYSA39022.47625.116133.8181.0018.856ATOM2003OLYSA39022.14726.072134.5231.0021.718ATOM2004NGLNA39123.43624.253134.1551.0018.707ATOM2005CAGLNA39124.17824.319135.4231.0020.296ATOM2006CBGLNA39124.39422.908135.9941.0024.006ATOM2007CGGLNA39123.15522.182136.5361.0028.546ATOM2008CDGLNA39123.40120.689136.7931.0031.336ATOM2009OE1GLNA39124.48620.277137.2191.0033.698ATOM2010NE2GLNA39122.39119.870136.5101.0033.047ATOM2011CGLNA39125.54824.986135.2261.0018.566ATOM2012OGLNA39126.23825.306136.2021.0019.958ATOM2013NARGA39225.92125.204133.9631.0016.007ATOM2014CAARGA39227.20625.808133.5861.0013.806ATOM2015CBARGA39227.45725.592132.0841.0011.116ATOM2016CGARGA39228.84925.979131.5521.0010.426ATOM2017CDARGA39229.01425.631130.0851.009.756ATOM2018NEARGA39228.79124.203129.8611.009.177ATOM2019CZARGA39228.23723.675128.7761.009.486ATOM2020NH1ARGA39227.85524.445127.7611.0010.457ATOM2021NH2ARGA39227.93622.384128.7701.009.497ATOM2022CARGA39227.30327.292133.9111.0012.496ATOM2023OARGA39226.28927.996133.9201.0014.318ATOM2024NLEUA39328.52727.740134.2081.0012.227ATOM2025CALEUA39328.81829.144134.4881.0012.006ATOM2026CBLEUA39330.24129.291135.0321.0011.806ATOM2027CGLEUA39330.67830.635135.6121.0014.986ATOM2028CD1LEUA39330.00930.886136.9571.0014.606ATOM2029CD2LEUA39332.18130.638135.7621.0015.426ATOM2030CLEUA39328.68229.855133.1381.0012.326ATOM2031OLEUA39329.40629.548132.1851.0013.808ATOM2032NGLYA39427.68830.736133.0571.0013.897ATOM2033CAGLYA39427.39831.455131.8321.0013.916ATOM2034CGLYA39426.22330.818131.1091.0013.886ATOM2035OGLYA39425.75631.338130.0961.0014.388ATOM2036NGLYA39525.75129.690131.6421.0016.407ATOM2037CAGLYA39524.63728.959131.0561.0016.576ATOM2038CGLYA39523.26729.427131.5051.0017.446ATOM2039OGLYA39522.24528.979130.9721.0018.008ATOM2040NGLYA39623.25530.316132.4971.0017.837ATOM2041CAGLYA39622.01530.872133.0121.0018.396ATOM2042CGLYA39621.52632.023132.1421.0018.796ATOM2043OGLYA39622.21632.390131.1841.0019.298ATOM2044NPROA39720.35832.630132.4491.0019.857ATOM2045CDPROA39719.39632.200133.4831.0020.346ATOM2046CAPROA39719.79533.747131.6761.0019.636ATOM2047CBPROA39718.48334.034132.4101.0019.836ATOM2048CGPROA39718.09132.698132.9221.0021.566ATOM2049CPROA39720.66335.010131.5651.0018.556ATOM2050OPROA39720.55835.743130.5761.0020.038ATOM2051NSERA39821.54235.236132.5441.0017.137ATOM2052CASERA39822.40436.421132.5291.0016.536ATOM2053CBSERA39822.72036.911133.9471.0018.916ATOM2054OGSERA39823.57836.030134.6401.0020.938ATOM2055CSERA39823.67236.274131.6871.0016.046ATOM2056OSERA39824.45937.217131.5761.0015.488ATOM2057NASPA39923.86335.078131.1181.0014.877ATOM2058CAASPA39924.98334.755130.2211.0014.596ATOM2059CBASPA39924.66735.353128.8341.0014.176ATOM2060CGASPA39925.54434.805127.7201.0015.806ATOM2061OD1ASPA39925.62333.570127.5441.0016.418ATOM2062OD2ASPA39926.12435.639127.0001.0018.698ATOM2063CASPA39926.38635.146130.7401.0012.236ATOM2064OASPA39926.82234.633131.7691.0012.988ATOM2065NALAA40027.03936.103130.0761.0013.147ATOM2066CAALAA40028.38436.561130.4361.0012.176ATOM2067CBALAA40028.88037.550129.4291.0013.276ATOM2068CALAA40028.56937.123131.8281.0013.106ATOM2069OALAA40029.66637.033132.3811.0012.788ATOM2070NLYSA40127.49937.685132.3911.0012.577ATOM2071CALYSA40127.53138.265133.7361.0014.046ATOM2072CBLYSA40126.16838.854134.1171.0014.476ATOM2073CGLYSA40126.18239.648135.4191.0017.376ATOM2074CDLYSA40124.78939.992135.9091.0018.236ATOM2075CELYSA40124.85840.652137.2761.0020.096ATOM2076NZLYSA40123.51741.067137.7731.0022.397ATOM2077CLYSA40127.97237.238134.7781.0013.026ATOM2078OLYSA40128.78037.560135.6431.0014.288ATOM2079NGLUA40227.50835.993134.6341.0013.437ATOM2080CAGLUA40227.86634.906135.5571.0013.396ATOM2081CBGLUA40227.10633.619135.2211.0015.356ATOM2082CGGLUA40225.60833.694135.4651.0019.176ATOM2083CDGLUA40224.87832.375135.2491.0022.706ATOM2084OE1GLUA40225.39431.488134.5371.0021.798ATOM2085OE2GLUA40223.76832.224135.8001.0023.828ATOM2086CGLUA40229.36534.617135.5431.0012.956ATOM2087OGLUA40229.96734.405136.5961.0012.718ATOM2088NVALA40329.96234.673134.3491.0011.807ATOM2089CAVALA40331.39734.425134.1811.0011.796ATOM2090CBVALA40331.78034.132132.6971.0011.126ATOM2091CG1VALA40333.24833.709132.5931.0011.326ATOM2092CG2VALA40330.89233.036132.1251.009.796ATOM2093CVALA40332.19435.616134.7011.0011.206ATOM2094OVALA40333.16535.438135.4331.0011.218ATOM2095NMETA40431.72036.820134.3811.0011.167ATOM2096CAMETA40432.36538.061134.8031.0011.506ATOM2097CBMETA40431.68339.274134.1681.0011.896ATOM2098CGMETA40431.90639.399132.6801.0014.246ATOM2099SDMETA40431.44641.018132.0681.0017.6216ATOM2100CEMETA40429.83340.733131.5611.0020.496ATOM2101CMETA40432.40638.250136.3131.0012.356ATOM2102OMETA40433.39738.745136.8531.0013.208ATOM2103NGLUA40531.34837.794136.9811.0013.127ATOM2104CAGLUA40531.22637.916138.4281.0013.476ATOM2105CBGLUA40529.76438.168138.8261.0014.706ATOM2106CGGLUA40529.16339.480138.2861.0020.216ATOM2107CDGLUA40529.99640.715138.6171.0024.046ATOM2108OE1GLUA40530.10541.060139.8141.0027.018ATOM2109OE2GLUA40530.54941.334137.6771.0025.988ATOM2110CGLUA40531.81436.779139.2491.0012.996ATOM2111OGLUA40531.74636.808140.4821.0013.608ATOM2112NHISA40632.42535.798138.5811.0011.777ATOM2113CAHISA40633.04334.669139.2841.0012.706ATOM2114CBHISA40633.40833.549138.3051.0011.926ATOM2115CGHISA40633.88832.303138.9811.0012.886ATOM2116CD2HISA40633.23431.175139.3431.0012.346ATOM2117ND1HISA40635.18232.160139.4341.0013.217ATOM2118CE1HISA40635.30131.001140.0531.0013.576ATOM2119NE2HISA40634.13530.383140.0111.0011.877ATOM2120CHISA40634.29135.162140.0321.0012.026ATOM2121OHISA40635.02336.014139.5161.0012.478ATOM2122NARGA40734.52134.620141.2351.0012.757ATOM2123CAARGA40735.65135.003142.0961.0015.936ATOM2124CBARGA40735.63334.240143.4341.0018.496ATOM2125CGARGA40735.71932.723143.3451.0025.886ATOM2126CDARGA40735.84132.085144.7231.0030.526ATOM2127NEARGA40735.74330.625144.6621.0035.557ATOM2128CZARGA40736.29629.785145.5351.0037.676ATOM2129NH1ARGA40737.00730.240146.5621.0039.587ATOM2130NH2ARGA40736.12728.477145.3871.0039.547ATOM2131CARGA40737.04634.958141.4711.0014.356ATOM2132OARGA40737.94235.674141.9101.0016.128ATOM2133NPHEA40837.20634.154140.4181.0014.457ATOM2134CAPHEA40838.48234.049139.7001.0013.706ATOM2135CBPHEA40838.41032.940138.6331.0012.406ATOM2136CGPHEA40839.67432.783137.8161.0012.586ATOM2137CD1PHEA40840.78332.096138.3361.0014.906ATOM2138CD2PHEA40839.76133.335136.5261.0013.086ATOM2139CE1PHEA40841.97931.951137.5801.0014.826ATOM2140CE2PHEA40840.94133.203135.7571.0013.946ATOM2141CZPHEA40842.05732.508136.2851.0012.786ATOM2142CPHEA40838.80935.395139.0421.0013.426ATOM2143OPHEA40839.97735.760138.9231.0013.398ATOM2144NPHEA40937.76236.113138.6341.0013.107ATOM2145CAPHEA40937.90137.407137.9761.0013.416ATOM2146CBPHEA40936.95137.481136.7681.0013.846ATOM2147CGPHEA40937.34436.594135.6111.0012.156ATOM2148CD1PHEA40936.49635.552135.1981.0012.186ATOM2149CD2PHEA40938.54236.815134.9061.0011.876ATOM2150CE1PHEA40936.83134.728134.0861.0011.646ATOM2151CE2PHEA40938.89936.001133.7861.0012.096ATOM2152CZPHEA40938.04034.956133.3781.0010.576ATOM2153CPHEA40937.66738.618138.8951.0014.526ATOM2154OPHEA40937.42839.722138.4081.0014.198ATOM2155NLEUA41037.78738.421140.2111.0015.057ATOM2156CALEUA41037.57939.490141.2081.0018.506ATOM2157CBLEUA41037.76038.929142.6281.0021.406ATOM2158CGLEUA41037.29639.735143.8521.0025.186ATOM2159CD1LEUA41035.77339.743143.9351.0026.486ATOM2160CD2LEUA41037.88639.125145.1151.0027.656ATOM2161CLEUA41038.47840.726141.0171.0018.386ATOM2162OLEUA41038.02441.863141.1931.0019.408ATOM2163NSERA41139.71540.491140.5781.0017.427ATOM2164CASERA41140.70441.551140.3521.0018.356ATOM2165CBSERA41142.11740.956140.4001.0019.316ATOM2166OGSERA41142.33440.058139.3221.0020.748ATOM2167CSERA41140.51842.312139.0341.0017.946ATOM2168OSERA41141.20943.303138.7781.0020.078ATOM2169NILEA41239.58441.840138.2101.0017.117ATOM2170CAILEA41239.31542.434136.9051.0016.596ATOM2171CBILEA41238.93441.321135.8531.0016.816ATOM2172CG2ILEA41238.58241.918134.4951.0016.596ATOM2173CG1ILEA41240.06540.287135.7031.0017.736ATOM2174CD1ILEA41241.38940.816135.1301.0018.966ATOM2175CILEA41238.25343.540136.8971.0015.406ATOM2176OILEA41237.14943.375137.4221.0015.808ATOM2177NASNA41338.62944.671136.3041.0015.277ATOM2178CAASNA41337.73945.815136.1081.0015.146ATOM2179CBASNA41338.49147.136136.3511.0017.126ATOM2180CGASNA41337.63648.377136.0741.0019.496ATOM2181OD1ASNA41337.03048.513135.0101.0018.408ATOM2182ND2ASNA41337.62549.306137.0191.0021.927ATOM2183CASNA41337.39045.631134.6261.0013.676ATOM2184OASNA41338.25545.778133.7571.0014.068ATOM2185NTRPA41436.13045.295134.3581.0013.637ATOM2186CATRPA41435.64845.028133.0021.0012.976ATOM2187CBTRPA41434.30344.298133.0511.0012.806ATOM2188CGTRPA41434.46042.951133.6961.0013.876ATOM2189CD2TRPA41435.00041.772133.0881.0012.096ATOM2190CE2TRPA41435.13840.797134.1151.0011.466ATOM2191CE3TRPA41435.39341.441131.7741.0011.836ATOM2192CD1TRPA41434.27242.644135.0211.0013.166ATOM2193NE1TRPA41434.68541.359135.2791.0011.967ATOM2194CZ2TRPA41435.66039.508133.8691.0011.916ATOM2195CZ3TRPA41435.91140.159131.5271.0011.716ATOM2196CH2TRPA41436.03939.207132.5791.0010.396ATOM2197CTRPA41435.65646.159131.9891.0014.706ATOM2198OTRPA41435.72845.908130.7791.0013.368ATOM2199NGLNA41535.62547.398132.4781.0015.557ATOM2200CAGLNA41535.69048.554131.5941.0017.406ATOM2201CBGLNA41535.08149.802132.2441.0019.346ATOM2202CGGLNA41533.54849.789132.3191.0023.346ATOM2203CDGLNA41532.84749.801130.9511.0027.246ATOM2204OE1GLNA41533.36750.334129.9651.0028.768ATOM2205NE2GLNA41531.65149.219130.9001.0027.627ATOM2206CGLNA41537.13748.793131.1721.0017.706ATOM2207OGLNA41537.38849.190130.0361.0019.638ATOM2208NASPA41638.07948.458132.0601.0016.947ATOM2209CAASPA41639.51848.584131.7881.0016.836ATOM2210CBASPA41640.35048.351133.0541.0018.626ATOM2211CGASPA41640.37949.555133.9871.0019.846ATOM2212OD1ASPA41639.75750.595133.6831.0021.928ATOM2213OD2ASPA41641.02949.445135.0461.0021.808ATOM2214CASPA41639.94447.563130.7331.0017.256ATOM2215OASPA41640.85447.820129.9441.0018.228ATOM2216NVALA41739.26346.413130.7281.0017.397ATOM2217CAVALA41739.53045.331129.7721.0016.756ATOM2218CBVALA41738.76944.023130.1601.0017.266ATOM2219CG1VALA41738.91742.936129.0881.0016.256ATOM2220CG2VALA41739.31743.492131.4481.0016.176ATOM2221CVALA41739.17245.770128.3531.0017.996ATOM2222OVALA41740.05645.833127.5031.0018.758ATOM2223NVALA41837.90946.159128.1391.0018.287ATOM2224CAVALA41837.41846.587126.8221.0019.906ATOM2225CBVALA41835.84246.662126.7881.0019.646ATOM2226CG1VALA41835.30547.835127.6041.0019.846ATOM2227CG2VALA41835.32146.704125.3521.0020.166ATOM2228CVALA41838.07847.871126.2911.0019.906ATOM2229OVALA41838.19848.055125.0811.0021.008ATOM2230NGLNA41938.55348.719127.2021.0020.337ATOM2231CAGLNA41939.21349.967126.8171.0021.796ATOM2232CBGLNA41938.86651.088127.8081.0023.086ATOM2233CGGLNA41937.41751.577127.6931.0024.816ATOM2234CDGLNA41937.02452.558128.7871.0027.756ATOM2235OE1GLNA41936.12052.290129.5811.0029.198ATOM2236NE2GLNA41937.69053.706128.8221.0029.167ATOM2237CGLNA41940.72949.824126.6411.0022.346ATOM2238OGLNA41941.42350.816126.3991.0022.028ATOM2239NLYSA42041.22048.578126.7201.0022.057ATOM2240CALYSA42042.64548.215126.5671.0022.926ATOM2241CBLYSA42043.11648.414125.1121.0025.236ATOM2242CGLYSA42042.65147.388124.0951.0029.126ATOM2243CDLYSA42043.20347.780122.7331.0032.196ATOM2244CELYSA42043.09846.673121.7111.0036.006ATOM2245NZLYSA42043.59247.147120.3851.0038.117ATOM2246CLYSA42043.61148.936127.5251.0023.626ATOM2247OLYSA42044.76249.213127.1661.0022.558ATOM2248NLYSA42143.14549.212128.7441.0022.957ATOM2249CALYSA42143.94349.916129.7531.0023.806ATOM2250CBLYSA42143.03650.605130.7761.0024.286ATOM2251CGLYSA42142.20951.749130.2171.0025.046ATOM2252CDLYSA42141.41752.430131.3181.0026.696ATOM2253CELYSA42140.51953.508130.7541.0028.226ATOM2254NZLYSA42139.72054.179131.8151.0030.837ATOM2255CLYSA42144.96749.060130.4891.0024.936ATOM2256OLYSA42145.93149.589131.0481.0026.678ATOM2257NLEUA42244.76447.743130.4741.0025.517ATOM2258CALEUA42245.66446.813131.1521.0025.666ATOM2259CBLEUA42244.90145.556131.5851.0027.006ATOM2260CGLEUA42243.71045.738132.5391.0027.926ATOM2261CD1LEUA42242.97544.421132.6991.0028.256ATOM2262CD2LEUA42244.16646.266133.9001.0029.056ATOM2263CLEUA42246.89946.445130.3291.0025.156ATOM2264OLEUA42246.83046.339129.0991.0026.008ATOM2265NLEUA42348.02346.286131.0281.0024.137ATOM2266CALEUA42349.31945.941130.4341.0022.436ATOM2267CBLEUA42350.45846.327131.3991.0024.356ATOM2268CGLEUA42351.93746.016131.0901.0026.026ATOM2269CD1LEUA42352.46046.882129.9561.0027.116ATOM2270CD2LEUA42352.78246.231132.3361.0028.326ATOM2271CLEUA42349.41444.448130.0851.0020.236ATOM2272OLEUA42349.27443.595130.9721.0018.578ATOM2273NPROA42449.65344.114128.7921.0018.687ATOM2274CDPROA42449.66345.008127.6161.0017.866ATOM2275CAPROA42449.77042.714128.3551.0016.976ATOM2276CBPROA42449.94942.844126.8401.0016.816ATOM2277CGPROA42449.19144.092126.5211.0018.426ATOM2278CPROA42450.96242.001129.0091.0017.486ATOM2279OPROA42452.03042.594129.1551.0017.808ATOM2280NPROA42550.77640.739129.4601.0016.817ATOM2281CDPROA42549.51039.988129.4911.0017.806ATOM2282CAPROA42551.83539.955130.1041.0016.746ATOM2283CBPROA42551.06838.759130.6681.0017.346ATOM2284CGPROA42549.96038.578129.6911.0016.886ATOM2285CPROA42552.95039.524129.1541.0016.726ATOM2286OPROA42553.99739.042129.5871.0018.538ATOM2287NPHEA42652.70539.720127.8601.0016.037ATOM2288CAPHEA42653.64739.380126.8071.0016.866ATOM2289CBPHEA42653.47237.900126.3911.0018.586ATOM2290CGPHEA42654.36837.463125.2521.0021.116ATOM2291CD1PHEA42655.74937.280125.4561.0023.406ATOM2292CD2PHEA42653.83637.264123.9621.0022.086ATOM2293CE1PHEA42656.60436.905124.3851.0024.636ATOM2294CE2PHEA42654.67436.893122.8811.0023.506ATOM2295CZPHEA42656.06336.713123.0921.0023.306ATOM2296CPHEA42653.40040.287125.6081.0018.126ATOM2297OPHEA42652.26640.416125.1391.0017.878ATOM2298NLYSA42754.46840.914125.1241.0017.187ATOM2299CALYSA42754.37741.749123.9411.0018.166ATOM2300CBLYSA42754.89543.179124.1781.0021.736ATOM2301CGLYSA42754.64744.095122.9621.0023.526ATOM2302CDLYSA42755.22945.485123.0921.0027.956ATOM2303CELYSA42755.03046.241121.7841.0028.826ATOM2304NZLYSA42755.46247.660121.8531.0029.787ATOM2305CLYSA42755.21541.054122.8691.0017.626ATOM2306OLYSA42756.37940.711123.1151.0016.798ATOM2307NPROA42854.60740.752121.6981.0017.157ATOM2308CDPROA42853.16340.831121.4051.0017.036ATOM2309CAPROA42855.29940.097120.5861.0017.286ATOM2310CBPROA42854.23540.093119.4991.0017.516ATOM2311CGPROA42853.00839.854120.2821.0017.416ATOM2312CPROA42856.53740.882120.1571.0017.756ATOM2313OPROA42856.46742.095119.9461.0018.218ATOM2314NGLNA42957.67140.188120.0991.0018.767ATOM2315CAGLNA42958.94640.801119.7381.0021.296ATOM2316CBGLNA42960.09040.138120.5271.0022.566ATOM2317CGGLNA42959.98040.269122.0501.0025.446ATOM2318CDGLNA42960.06841.708122.5391.0027.926ATOM2319OE1GLNA42961.14742.301122.5741.0030.198ATOM2320NE2GLNA42958.93042.270122.9331.0028.127ATOM2321CGLNA42959.24740.828118.2381.0022.966ATOM2322OGLNA42960.34340.468117.8001.0023.758ATOM2323NVALA43058.27141.295117.4601.0023.887ATOM2324CAVALA43058.41041.406116.0081.0026.086ATOM2325CBVALA43057.02541.379115.2751.0026.036ATOM2326CG1VALA43056.45039.969115.3111.0025.786ATOM2327CG2VALA43056.03142.359115.9081.0026.266ATOM2328CVALA43059.21242.659115.6431.0027.986ATOM2329OVALA43058.98943.733116.2111.0028.958ATOM2330NTHRA43160.18142.489114.7441.0029.327ATOM2331CATHRA43161.06343.575114.3021.0031.976ATOM2332CBTHRA43162.50143.061114.0591.0032.026ATOM2333OG1THRA43162.46941.929113.1811.0032.458ATOM2334CG2THRA43163.16142.668115.3801.0032.426ATOM2335CTHRA43160.57144.322113.0601.0033.556ATOM2336OTHRA43161.07345.403112.7341.0034.028ATOM2337NSERA43259.60443.719112.3711.0034.537ATOM2338CASERA43258.99544.280111.1651.0035.566ATOM2339CBSERA43259.82543.930109.9191.0035.936ATOM2340OGSERA43259.97942.529109.7641.0036.588ATOM2341CSERA43257.58243.720111.0321.0035.976ATOM2342OSERA43257.20242.800111.7621.0036.118ATOM2343NGLUA43356.81444.269110.0921.0036.187ATOM2344CAGLUA43355.44143.824109.8481.0036.136ATOM2345CBGLUA43354.63344.944109.1861.0039.016ATOM2346CGGLUA43354.14446.052110.1241.0042.486ATOM2347CDGLUA43352.98645.619111.0201.0045.056ATOM2348OE1GLUA43351.96645.120110.4941.0045.278ATOM2349OE2GLUA43353.09645.786112.2541.0047.568ATOM2350CGLUA43355.37942.544109.0071.0034.716ATOM2351OGLUA43354.30841.961108.8281.0036.088ATOM2352NVALA43456.54442.104108.5301.0032.157ATOM2353CAVALA43456.68040.897107.7191.0029.736ATOM2354CBVALA43457.48541.211106.3971.0030.546ATOM2355CG1VALA43458.98441.409106.6701.0029.956ATOM2356CG2VALA43457.23440.155105.3341.0031.866ATOM2357CVALA43457.30739.751108.5471.0028.246ATOM2358OVALA43457.45738.627108.0671.0028.548ATOM2359NASPA43557.64040.052109.8051.0026.147ATOM2360CAASPA43558.24439.093110.7381.0023.406ATOM2361CBASPA43558.84639.864111.9281.0022.356ATOM2362CGASPA43559.67938.990112.8701.0022.386ATOM2363OD1ASPA43559.61037.744112.8131.0020.668ATOM2364OD2ASPA43560.40739.577113.6961.0023.008ATOM2365CASPA43557.17638.088111.2051.0021.896ATOM2366OASPA43556.24638.446111.9311.0022.648ATOM2367NTHRA43657.33436.834110.7771.0019.337ATOM2368CATHRA43656.39335.760111.1141.0017.476ATOM2369CBTHRA43655.86935.056109.8321.0017.566ATOM2370OG1THRA43656.97434.595109.0441.0019.378ATOM2371CG2THRA43655.01535.996109.0051.0018.196ATOM2372CTHRA43656.95634.709112.0831.0015.696ATOM2373OTHRA43656.56033.537112.0381.0014.918ATOM2374NARGA43757.81035.150113.0101.0015.427ATOM2375CAARGA43758.44434.264113.9981.0014.406ATOM2376CBARGA43759.49335.028114.8211.0014.856ATOM2377CGARGA43758.92036.112115.7231.0016.756ATOM2378CDARGA43759.97536.735116.5981.0017.366ATOM2379NEARGA43760.80837.670115.8541.0017.477ATOM2380CZARGA43762.00438.091116.2521.0016.946ATOM2381NH1ARGA43762.52737.656117.3911.0016.577ATOM2382NH2ARGA43762.65538.986115.5261.0020.397ATOM2383CARGA43757.46733.557114.9511.0013.966ATOM2384OARGA43757.83532.585115.6131.0015.318ATOM2385NTYRA43856.23634.062115.0171.0014.577ATOM2386CATYRA43855.22233.483115.8941.0013.556ATOM2387CBTYRA43854.52734.570116.7101.0013.946ATOM2388CGTYRA43855.46435.303117.6411.0012.646ATOM2389CD1TYRA43855.63036.692117.5371.0013.966ATOM2390CE1TYRA43856.52837.382118.3811.0014.916ATOM2391CD2TYRA43856.21534.608118.6171.0014.886ATOM2392CE2TYRA43857.11435.291119.4761.0014.086ATOM2393CZTYRA43857.26036.676119.3481.0014.786ATOM2394OHTYRA43858.10737.359120.1871.0015.818ATOM2395CTYRA43854.22532.572115.1961.0014.686ATOM2396OTYRA43853.16832.235115.7401.0012.738ATOM2397NPHEA43954.58032.189113.9731.0014.157ATOM2398CAPHEA43953.78731.275113.1631.0015.366ATOM2399CBPHEA43953.34931.944111.8571.0013.446ATOM2400CGPHEA43952.31333.011112.0481.0014.946ATOM2401CD1PHEA43952.69534.342112.3211.0014.256ATOM2402CD2PHEA43950.94432.690111.9831.0013.546ATOM2403CE1PHEA43951.72235.352112.5311.0014.396ATOM2404CE2PHEA43949.95133.685112.1891.0013.826ATOM2405CZPHEA43950.34335.022112.4651.0014.086ATOM2406CPHEA43954.67130.070112.9021.0015.296ATOM2407OPHEA43955.89130.210112.7751.0016.468ATOM2408NASPA44054.06428.883112.8861.0017.467ATOM2409CAASPA44054.79427.630112.6721.0019.376ATOM2410CBASPA44053.86726.425112.8561.0020.526ATOM2411CGASPA44053.38626.274114.2831.0025.246ATOM2412OD1ASPA44052.17026.432114.5161.0027.538ATOM2413OD2ASPA44054.22426.011115.1741.0026.158ATOM2414CASPA44055.49327.539111.3231.0020.616ATOM2415OASPA44054.94527.961110.2991.0019.758ATOM2416NASPA44156.71026.989111.3501.0022.107ATOM2417CAASPA44157.54826.804110.1601.0024.426ATOM2418CBASPA44158.93526.272110.5511.0027.706ATOM2419CGASPA44159.77727.300111.2971.0031.136ATOM2420OD1ASPA44159.75028.496110.9251.0033.158ATOM2421OD2ASPA44160.47926.907112.2571.0034.678ATOM2422CASPA44156.91025.886109.1171.0023.546ATOM2423OASPA44157.20625.999107.9311.0023.538ATOM2424NGLUA44255.98125.038109.5701.0022.837ATOM2425CAGLUA44255.24024.098108.7211.0024.276ATOM2426CBGLUA44254.27523.260109.5831.0026.346ATOM2427CGGLUA44253.65022.040108.8771.0032.646ATOM2428CDGLUA44252.46021.427109.6241.0035.156ATOM2429OE1GLUA44252.36221.565110.8661.0036.858ATOM2430OE2GLUA44251.61620.786108.9591.0037.078ATOM2431CGLUA44254.44324.870107.6591.0023.046ATOM2432OGLUA44254.27924.402106.5331.0023.838ATOM2433NPHEA44354.01026.078108.0241.0022.047ATOM2434CAPHEA44353.23126.940107.1401.0020.726ATOM2435CBPHEA44352.06827.577107.9131.0020.356ATOM2436CGPHEA44351.19826.573108.6161.0020.336ATOM2437CD1PHEA44351.17626.511110.0211.0021.786ATOM2438CD2PHEA44350.45525.630107.8771.0021.446ATOM2439CE1PHEA44350.43125.512110.6931.0021.606ATOM2440CE2PHEA44349.70324.623108.5251.0021.376ATOM2441CZPHEA44349.69124.560109.9351.0020.866ATOM2442CPHEA44354.03328.017106.4121.0020.986ATOM2443OPHEA44353.92228.139105.1931.0021.498ATOM2444NTHRA44454.87428.748107.1471.0021.527ATOM2445CATHRA44455.67629.844106.5831.0022.586ATOM2446CBTHRA44456.32230.718107.6831.0022.026ATOM2447OG1THRA44457.23929.934108.4561.0021.758ATOM2448CG2THRA44455.25431.305108.5951.0021.356ATOM2449CTHRA44456.74929.473105.5601.0024.726ATOM2450OTHRA44457.15330.319104.7571.0025.448ATOM2451NALAA44557.19028.216105.5901.0027.357ATOM2452CAALAA44558.21527.718104.6691.0029.676ATOM2453CBALAA44559.02126.608105.3291.0029.946ATOM2454CALAA44557.63927.235103.3351.0031.566ATOM2455OALAA44558.38627.037102.3731.0031.668ATOM2456NGLNA44656.31427.071103.2831.0033.187ATOM2457CAGLNA44655.61026.613102.0811.0034.776ATOM2458CBGLNA44654.18726.159102.4211.0034.246ATOM2459CGGLNA44654.09324.839103.1691.0034.086ATOM2460CDGLNA44652.65624.415103.4351.0033.296ATOM2461OE1GLNA44652.26924.175104.5781.0033.908ATOM2462NE2GLNA44651.85724.326102.3771.0033.087ATOM2463CGLNA44655.54527.674100.9881.0037.226ATOM2464OGLNA44655.37328.863101.2701.0036.658ATOM2465NSERA44755.68927.22499.7421.0039.807ATOM2466CASERA44755.65028.10198.5751.0043.006ATOM2467CBSERA44756.45727.49397.4201.0043.756ATOM2468OGSERA44756.00126.18897.0941.0045.508ATOM2469CSERA44754.21628.37498.1311.0044.416ATOM2470OSERA44753.36027.48398.1791.0045.148ATOM2471NILEA44853.95929.62497.7521.0046.017ATOM2472CAILEA44852.64330.06097.2851.0047.466ATOM2473CBILEA44852.03131.17598.2011.0047.296ATOM2474CG2ILEA44851.33730.53699.4061.0048.106ATOM2475CG1ILEA44853.10532.18198.6481.0047.366ATOM2476CD1ILEA44852.55633.47199.1911.0046.466ATOM2477CILEA44852.69630.50095.8141.0048.186ATOM2478OILEA44853.03131.64895.4961.0048.998ATOM2479NALAA44952.40429.55294.9241.0048.937ATOM2480CAALAA44952.41529.79093.4801.0049.146ATOM2481CBALAA44952.96528.56892.7521.0049.686ATOM2482CALAA44951.03330.15492.9401.0049.196ATOM2483OALAA44950.02629.56393.3281.0049.368ATOM2484NALAA46726.08537.48990.9281.0056.867ATOM2485CAALAA46726.40536.16991.4591.0056.706ATOM2486CBALAA46727.54636.27192.4691.0056.876ATOM2487CALAA46725.18335.50992.0991.0056.466ATOM2488OALAA46724.98634.29791.9531.0056.388ATOM2489NALAA46824.38736.31892.8121.0056.147ATOM2490CAALAA46823.15135.92493.5211.0055.796ATOM2491CBALAA46822.09435.36792.5421.0055.996ATOM2492CALAA46823.31434.98894.7251.0055.456ATOM2493OALAA46822.61135.13395.7321.0055.638ATOM2494NMETA46924.24534.04294.6111.0054.527ATOM2495CAMETA46924.54333.05995.6521.0054.016ATOM2496CBMETA46925.21231.83795.0021.0054.956ATOM2497CGMETA46925.42830.62795.9061.0056.406ATOM2498SDMETA46925.58429.04895.0221.0058.4816ATOM2499CEMETA46926.80129.44293.7471.0058.566ATOM2500CMETA46925.42933.67796.7461.0053.036ATOM2501OMETA46925.20833.44497.9391.0053.088ATOM2502NPHEA47026.40834.47896.3211.0051.147ATOM2503CAPHEA47027.33335.16797.2261.0049.716ATOM2504CBPHEA47028.79434.83996.8591.0048.676ATOM2505CGPHEA47029.14533.37496.9481.0047.866ATOM2506CD1PHEA47029.30432.74598.1991.0047.326ATOM2507CD2PHEA47029.33432.61695.7751.0047.256ATOM2508CE1PHEA47029.65031.36698.2881.0046.976ATOM2509CE2PHEA47029.68031.23695.8401.0046.766ATOM2510CZPHEA47029.83830.61097.1021.0046.816ATOM2511CPHEA47027.07736.68197.1251.0049.286ATOM2512OPHEA47028.00237.47896.9281.0049.598ATOM2513NALAA47125.80537.06097.2711.0048.797ATOM2514CAALAA47125.35738.45597.1871.0048.146ATOM2515CBALAA47123.85638.50496.9151.0048.356ATOM2516CALAA47125.69839.31898.4031.0047.446ATOM2517OALAA47126.03140.49898.2581.0047.418ATOM2518NASPA47225.62538.71999.5911.0046.107ATOM2519CAASPA47225.91239.418100.8461.0045.086ATOM2520CBASPA47224.94738.924101.9381.0047.056ATOM2521CGASPA47224.54140.021102.9131.0049.576ATOM2522OD1ASPA47225.42240.578103.6061.0051.078ATOM2523OD2ASPA47223.33140.319102.9921.0051.558ATOM2524CASPA47227.37639.233101.2871.0042.556ATOM2525OASPA47227.71439.448102.4561.0042.368ATOM2526NPHEA47328.24238.880100.3351.0039.707ATOM2527CAPHEA47329.66238.651100.6121.0036.816ATOM2528CBPHEA47330.23237.57899.6621.0035.116ATOM2529CGPHEA47331.54936.995100.1151.0032.536ATOM2530CD1PHEA47331.57435.931101.0351.0032.466ATOM2531CD2PHEA47332.77537.54599.6741.0031.946ATOM2532CE1PHEA47332.80135.422101.5221.0030.286ATOM2533CE2PHEA47334.01437.050100.1521.0031.336ATOM2534CZPHEA47334.02635.987101.0801.0030.076ATOM2535CPHEA47330.54739.904100.5791.0036.316ATOM2536OPHEA47331.30140.148101.5251.0036.198ATOM2537NASPA47430.67640.45499.6971.0034.657ATOM2538CAASPA47431.47341.66799.4591.0034.176ATOM2539CBASPA47431.23842.18498.0331.0035.206ATOM2540CGASPA47431.67041.18196.9561.0037.356ATOM2541OD1ASPA47432.09340.05097.2921.0036.568ATOM2542OD2ASPA47431.58541.52995.7611.0037.818ATOM2543CASPA47431.33942.805100.4791.0033.286ATOM2544OASPA47430.24343.070100.9851.0033.008ATOM2545NTYRA47532.33643.598100.6001.0032.507ATOM2546CATYRA47532.44344.665101.6071.0030.826ATOM2547CBTYRA47532.40344.028103.0111.0029.886ATOM2548CGTYRA47532.55344.941104.2221.0027.416ATOM2549CD1TYRA47531.51645.815104.6171.0027.876ATOM2550CE1TYRA47531.62846.597105.8061.0025.766ATOM2551CD2TYRA47533.70844.870105.0321.0027.776ATOM2552CE2TYRA47533.82945.642106.2161.0025.756ATOM2553CZTYRA47532.78746.497106.5931.0025.686ATOM2554OHTYRA47532.91247.239107.7441.0025.858ATOM2555CTYRA47533.71845.504101.4811.0030.766ATOM2556OTYRA47534.77744.998101.1061.0031.248ATOM2557NILEA47633.58246.790101.8091.0031.147ATOM2558CAILEA47634.67347.774101.8361.0031.206ATOM2559CBILEA47634.62748.784100.6281.0032.456ATOM2560CG2ILEA47635.68549.893100.8111.0032.136ATOM2561CG1ILEA47634.90348.06099.2991.0032.626ATOM2562CD1ILEA47634.56248.86298.0491.0034.466ATOM2563CILEA47634.43848.513103.1661.0031.576ATOM2564OILEA47633.34949.053103.3961.0030.478ATOM2565NALAA47735.45748.529104.0281.0032.707ATOM2566CAALAA47735.37549.166105.3491.0034.906ATOM2567CBALAA47736.49048.657106.2481.0034.366ATOM2568CALAA47735.32950.688105.3911.0036.496ATOM2569OALAA47735.83051.365104.4901.0036.958ATOM2570NASPA47834.72651.199106.4651.0038.847ATOM2571CAASPA47834.57552.633106.7171.0041.316ATOM2572CBASPA47833.31452.901107.5641.0042.946ATOM2573CGASPA47833.27952.091108.8621.0044.916ATOM2574OD1ASPA47833.18150.846108.7931.0046.078ATOM2575OD2ASPA47833.34052.704109.9491.0046.218ATOM2576CASPA47835.81853.249107.3761.0042.236ATOM2577OASPA47835.97754.474107.3981.0043.438ATOM2578NTRPA47936.68152.385107.9141.0042.387ATOM2579CATRPA47937.92452.797108.5701.0042.146ATOM2580CBTRPA47938.12452.045109.9051.0040.956ATOM2581CGTRPA47938.04250.527109.8341.0039.186ATOM2582CD2TRPA47939.13549.604109.6961.0038.786ATOM2583CE2TRPA47938.57748.296109.6721.0038.206ATOM2584CE3TRPA47940.53749.751109.5891.0038.366ATOM2585CD1TRPA47936.90549.764109.8911.0038.886ATOM2586NE1TRPA47937.21848.429109.7931.0037.917ATOM2587CZ2TRPA47939.37347.130109.5431.0037.406ATOM2588CZ3TRPA47941.33948.586109.4601.0038.316ATOM2589CH2TRPA47940.74447.292109.4391.0037.726ATOM2590CTRPA47939.13652.613107.6531.0042.816ATOM2591OTRPA47940.15353.307107.8701.0043.208ATOM2592OXTTRPA47939.05751.763106.7391.0042.868ATOM2593PGANPB50039.27725.675111.1201.0011.4715ATOM2594N3BANPB50040.22026.675110.2031.0012.927ATOM2595O1GANPB50037.82825.963110.7491.0012.028ATOM2596O2GANPB50039.68026.079112.4801.0011.218ATOM2597O3GANPB50039.64624.294110.8431.0011.948ATOM2598PBANPB50039.75027.681108.9481.0013.3615ATOM2599O1BANPB50039.86126.926107.7151.0016.598ATOM2600O2BANPB50038.43728.267109.2611.0014.328ATOM2601PAANPB50041.15230.005109.9781.0013.3715ATOM2602O1AANPB50040.37631.217109.7021.0012.088ATOM2603O2AANPB50041.09029.418111.3491.0012.138ATOM2604O3AANPB50040.84528.864108.8751.0013.968ATOM2605O5*ANPB50042.67930.329109.6031.0012.578ATOM2606C5*ANPB50043.68829.309109.7571.0011.886ATOM2607C4*ANPB50044.88429.865110.4931.0011.536ATOM2608O4*ANPB50045.35031.080109.8611.0012.108ATOM2609C3*ANPB50044.56630.261111.9261.0012.076ATOM2610O3*ANPB50044.52029.161112.8301.0012.828ATOM2611C2*ANPB50045.64031.288112.1911.0012.456ATOM2612O2*ANPB50046.87130.642112.5551.0013.198ATOM2613C1*ANPB50045.81532.006110.8631.0012.346ATOM2614N9ANPB50045.02133.246110.8351.0011.847ATOM2615C8ANPB50043.65233.406110.6561.0012.586ATOM2616N7ANPB50043.25034.638110.6891.0012.017ATOM2617C5ANPB50044.41135.359110.9031.0010.846ATOM2618C6ANPB50044.65936.746111.0431.0011.916ATOM2619N6ANPB50043.68337.652110.9771.0011.897ATOM2620N1ANPB50045.96437.150111.2541.0011.057ATOM2621C2ANPB50046.94236.227111.3171.0010.776ATOM2622N3ANPB50046.81734.892111.1981.0010.347ATOM2623C4ANPB50045.50534.525110.9921.0011.096ATOM2624MNMNB50140.35928.039112.6971.0011.366ATOM2625MNMNB50236.92127.830110.7221.0013.106ATOM2626CGLYC350.96918.410122.2001.0036.866ATOM2627OGLYC351.01619.584121.8171.0038.878ATOM2628NGLYC351.78117.163124.2161.0037.637ATOM2629CAGLYC352.15617.802122.9251.0037.926ATOM2630NARGC449.92017.598122.0121.0034.557ATOM2631CAARGC448.65717.957121.3361.0029.666ATOM2632CBARGC447.83618.940122.1941.0030.316ATOM2633CGARGC446.48919.447121.6261.0028.236ATOM2634CDARGC446.29820.867122.1341.0026.416ATOM2635NEARGC445.09621.613121.7391.0021.027ATOM2636CZARGC444.79122.028120.5091.0019.946ATOM2637NH1ARGC445.56221.747119.4681.0018.317ATOM2638NH2ARGC443.79522.884120.3451.0022.617ATOM2639CARGC448.79218.467119.8891.0027.386ATOM2640OARGC449.33519.553119.6511.0025.678ATOM2641NPROC548.33317.665118.9021.0023.857ATOM2642CDPROC547.95116.240118.9951.0024.256ATOM2643CAPROC548.41718.091117.4971.0021.436ATOM2644CBPROC548.19816.783116.7291.0023.456ATOM2645CGPROC547.34215.972117.6471.0024.546ATOM2646CPROC547.35619.146117.1531.0019.726ATOM2647OPROC546.43019.378117.9411.0017.728ATOM2648NARGC647.50919.786115.9931.0018.147ATOM2649CAARGC646.57120.807115.5141.0018.746ATOM2650CBARGC647.02421.393114.1811.0019.456ATOM2651CGARGC648.19422.325114.2721.0022.636ATOM2652CDARGC648.33823.129112.9921.0022.506ATOM2653NEARGC647.28024.125112.7901.0022.017ATOM2654CZARGC647.25125.335113.3541.0020.106ATOM2655NH1ARGC648.22225.728114.1721.0020.757ATOM2656NH2ARGC646.24626.160113.0971.0020.447ATOM2657CARGC645.17820.227115.3321.0018.256ATOM2658OARGC645.02219.090114.8811.0019.168ATOM2659NTHRC744.17821.010115.7191.0018.377ATOM2660CATHRC742.79020.587115.6281.0018.236ATOM2661CBTHRC742.07320.742116.9931.0018.366ATOM2662OG1THRC741.96922.129117.3461.0022.708ATOM2663CG2THRC742.81120.000118.0961.0018.616ATOM2664CTHRC742.03921.343114.5281.0018.626ATOM2665OTHRC742.19522.557114.3751.0019.258ATOM2666NTHRC841.23420.607113.7651.0018.247ATOM2667CATHRC840.45821.163112.6571.0017.386ATOM2668CBTHRC840.72420.389111.3351.0021.046ATOM2669OG1THRC840.47918.993111.5411.0025.518ATOM2670CG2THRC842.16320.580110.8661.0022.396ATOM2671CTHRC838.95921.117112.9371.0015.746ATOM2672OTHRC838.47020.188113.5861.0014.438ATOM2673NSERC938.23222.101112.4121.0014.117ATOM2674CASERC936.78622.161112.5891.0015.026ATOM2675CBSERC936.27523.606112.5191.0014.756ATOM2676OGSERC936.12524.060111.1821.0016.198ATOM2677CSERC936.04821.291111.5721.0015.896ATOM2678OSERC936.64720.803110.6051.0017.628ATOM2679NPHEC1034.75821.080111.8261.0016.187ATOM2680CAPHEC1033.89020.298110.9461.0016.486ATOM2681CBPHEC1033.87818.796111.3411.0015.786ATOM2682CGPHEC1033.08818.479112.5951.0016.586ATOM2683CD1PHEC1031.78617.932112.5071.0016.686ATOM2684CD2PHEC1033.61418.772113.8661.0016.846ATOM2685CE1PHEC1031.01517.691113.6721.0017.056ATOM2686CE2PHEC1032.85818.536115.0451.0016.946ATOM2687CZPHEC1031.55617.997114.9461.0016.526ATOM2688CPHEC1032.47820.878110.9871.0017.206ATOM2689OPHEC1032.13621.647111.8901.0015.118ATOM2690NALAC1131.65920.440110.0361.0018.607ATOM2691CAALAC1130.26220.835109.9201.0021.476ATOM2692CBALAC1130.12322.153109.1511.0020.506ATOM2693CALAC1129.56119.709109.1811.0023.326ATOM2694OALAC1129.98619.320108.0901.0025.508ATOM2695NGLUC1228.52719.152109.8101.0025.807ATOM2696CAGLUC1227.74318.057109.2351.0029.126ATOM2697CBGLUC1226.93917.360110.3401.0030.626ATOM2698CGGLUC1226.28116.038109.9461.0034.196ATOM2699CDGLUC1225.51815.406111.0951.0035.676ATOM2700OE1GLUC1224.45715.948111.4831.0037.038ATOM2701OE2GLUC1225.98414.368111.6151.0037.508ATOM2702CGLUC1226.81118.584108.1371.0030.906ATOM2703OGLUC1226.16019.629108.3631.0032.728ATOM2704OXTGLUC1226.77217.958107.0561.0032.948ATOM2705OH2TIPS150.88030.829115.3541.0012.378ATOM2706OH2TIPS239.10718.395125.6711.0013.748ATOM2707OH2TIPS350.06739.054125.7441.0014.468ATOM2708OH2TIPS433.21417.947132.3461.0014.318ATOM2709OH2TIPS533.87023.765119.0661.0012.758ATOM2710OH2TIPS655.05836.723114.0471.0014.058ATOM2711OH2TIPS735.34219.387124.8111.0010.528ATOM2712OH2TIPS822.14327.022128.8851.0015.758ATOM2713OH2TIPS935.36927.593112.4091.0018.448ATOM2714OH2TIPS1034.52538.856139.3891.0014.388ATOM2715OH2TIPS1150.59523.028126.4831.0021.638ATOM2716OH2TIPS1250.10930.822138.6501.0018.518ATOM2717OH2TIPS1348.95728.883111.4501.0015.578ATOM2718OH2TIPS1436.46244.242115.3821.0016.528ATOM2719OH2TIPS1539.81533.856109.9021.0017.168ATOM2720OH2TIPS1635.19541.517138.1991.0015.868ATOM2721OH2TIPS1735.20242.427113.6161.0019.428ATOM2722OH2TIPS1833.37630.532114.1961.0016.908ATOM2723OH2TIPS1922.79238.265114.8731.0015.628ATOM2724OH2TIPS2043.56740.244113.9181.0016.938ATOM2725OH2TIPS2120.81030.568123.5001.0017.328ATOM2726OH2TIPS2241.06037.798140.3351.0014.568ATOM2727OH2TIPS2335.17746.194109.3461.0021.198ATOM2728OH2TIPS2429.44718.326135.2281.0016.888ATOM2729OH2TIPS2530.56122.975121.2681.0016.648ATOM2730OH2TIPS2622.41318.170127.9551.0014.888ATOM2731OH2TIPS2746.21417.759125.3151.0019.368ATOM2732OH2TIPS2819.32220.943134.5181.0022.038ATOM2733OH2TIPS2944.09632.795140.6201.0023.668ATOM2734OH2TIPS3030.20623.891118.7271.0016.838ATOM2735OH2TIPS3132.93627.738121.2441.0015.408ATOM2736OH2TIPS3258.83131.975120.3941.0018.838ATOM2737OH2TIPS3348.56643.482115.1941.0023.928ATOM2738OH2TIPS3440.84415.752133.0431.0016.618ATOM2739OH2TIPS3535.07043.968111.1201.0017.048ATOM2740OH2TIPS3625.25915.523128.6771.0017.498ATOM2741OH2TIPS3728.85233.859139.0171.0021.638ATOM2742OH2TIPS3852.81332.605131.9821.0017.258ATOM2743OH2TIPS3943.3499.991135.6661.0016.468ATOM2744OH2TIPS4048.64427.596135.8721.0018.698ATOM2745OH2TIPS4151.75746.157124.7411.0019.068ATOM2746OH2TIPS4216.34218.660124.0211.0025.318ATOM2747OH2TIPS4335.92529.248107.0061.0018.948ATOM2748OH2TIPS4426.60513.506129.5901.0020.838ATOM2749OH2TIPS4546.52644.521109.6241.0021.148ATOM2750OH2TIPS4659.86225.385124.3981.0021.248ATOM2751OH2TIPS4736.43124.738118.9441.0012.458ATOM2752OH2TIPS4824.27525.017125.1901.0016.828ATOM2753OH2TIPS4926.54918.879134.7651.0017.158ATOM2754OH2TIPS5046.91022.255124.8921.0019.188ATOM2755OH2TIPS5123.04812.045127.6421.0015.858ATOM2756OH2TIPS5246.27946.528120.5761.0026.098ATOM2757OH2TIPS5348.08819.125134.3291.0019.718ATOM2758OH2TIPS5441.20115.894140.1671.0019.378ATOM2759OH2TIPS5532.53232.821142.3991.0018.798ATOM2760OH2TIPS5641.00513.422118.5261.0022.948ATOM2761OH2TIPS5745.42342.293114.8491.0021.918ATOM2762OH2TIPS5834.17145.681136.5331.0018.228ATOM2763OH2TIPS5959.54936.211122.0421.0021.688ATOM2764OH2TIPS6041.71523.526109.5971.0026.868ATOM2765OH2TIPS6159.40832.626117.7551.0022.588ATOM2766OH2TIPS6228.36312.355132.6251.0021.098ATOM2767OH2TIPS6348.57027.462139.4961.0040.678ATOM2768OH2TIPS6414.67933.201125.0481.0028.708ATOM2769OH2TIPS6536.6436.730125.8861.0028.648ATOM2770OH2TIPS6651.05528.844113.3261.0015.468ATOM2771OH2TIPS6732.93524.342121.6691.0022.648ATOM2772OH2TIPS6841.62612.464128.4841.0019.348ATOM2773OH2TIPS6923.32132.418110.8201.0023.938ATOM2774OH2TIPS7036.94234.509109.7171.0016.368ATOM2775OH2TIPS7120.53626.082113.6181.0019.588ATOM2776OH2TIPS7244.16340.980137.4331.0026.238ATOM2777OH2TIPS7322.94135.738122.5351.0021.618ATOM2778OH2TIPS7440.47818.154115.4391.0020.648ATOM2779OH2TIPS7532.17843.404125.5781.0027.418ATOM2780OH2TIPS7621.32038.314122.7811.0034.218ATOM2781OH2TIPS7743.73515.060128.3171.0020.408ATOM2782OH2TIPS7847.44526.751110.1231.0020.458ATOM2783OH2TIPS7921.78724.231125.5221.0022.058ATOM2784OH2TIPS8041.67044.807136.1371.0023.578ATOM2785OH2TIPS8158.36630.315114.3161.0020.068ATOM2786OH2TIPS8229.6739.405133.8961.0031.618ATOM2787OH2TIPS8324.77517.987129.0361.0025.028ATOM2788OH2TIPS8446.61413.440131.1861.0026.068ATOM2789OH2TIPS8523.99339.811112.7901.0034.348ATOM2790OH2TIPS8647.30347.864126.6791.0024.998ATOM2791OH2TIPS8753.96643.943128.0121.0028.558ATOM2792OH2TIPS8847.85823.095127.0991.0022.718ATOM2793OH2TIPS8957.78630.944110.8971.0026.758ATOM2794OH2TIPS9039.82035.599143.7811.0031.448ATOM2795OH2TIPS9149.59733.870138.6711.0022.658ATOM2796OH2TIPS9226.76322.386107.8161.0029.298ATOM2797OH2TIPS9342.79325.932109.4531.0024.898ATOM2798OH2TIPS9438.53011.440135.9021.0027.548ATOM2799OH2TIPS9550.00419.487126.4321.0023.318ATOM2800OH2TIPS9643.4498.768137.9251.0025.258ATOM2801OH2TIPS9724.08436.713137.2401.0032.638ATOM2802OH2TIPS9852.16936.019135.5561.0025.648ATOM2803OH2TIPS9954.39730.590131.4741.0025.348ATOM2804OH2TIPS10042.19047.366136.5551.0028.238ATOM2805OH2TIPS10146.58248.34796.0821.0026.238ATOM2806OH2TIPS10228.87847.284117.2431.0029.188ATOM2807OH2TIPS10341.8414.408123.4181.0038.418ATOM2808OH2TIPS10419.59029.610130.5551.0028.078ATOM2809OH2TIPS10537.55925.439144.5751.0023.588ATOM2810OH2TIPS10652.35147.830122.7931.0026.718ATOM2811OH2TIPS10727.77211.423120.7291.0027.598ATOM2812OH2TIPS10837.30417.824112.2841.0029.318ATOM2813OH2TIPS10925.89640.003125.9641.0044.528ATOM2814OH2TIPS11055.25530.966102.8431.0022.198ATOM2815OH2TIPS11154.12025.349117.8521.0030.548ATOM2816OH2TIPS11231.4108.275120.6851.0024.198ATOM2817OH2TIPS11333.43916.859134.9081.0023.688ATOM2818OH2TIPS11526.44026.129105.3001.0030.808ATOM2819OH2TIPS11655.44326.741119.6631.0022.098ATOM2820OH2TIPS11754.49445.04993.8661.0042.518ATOM2821OH2TIPS11840.75752.771134.9501.0037.878ATOM2822OH2TIPS11941.1657.640126.4301.0023.768ATOM2823OH2TIPS12065.21439.814115.0571.0029.228ATOM2824OH2TIPS12150.39447.451108.3081.0030.198ATOM2825OH2TIPS12233.73923.776109.5591.0028.488ATOM2826OH2TIPS12333.20019.214107.7111.0032.658ATOM2827OH2TIPS12416.77432.211116.3251.0023.248ATOM2828OH2TIPS12549.65418.866114.3131.0034.588ATOM2829OH2TIPS12619.54222.338128.4361.0025.458ATOM2830OH2TIPS12743.18315.839106.1951.0048.468ATOM2831OH2TIPS12843.97216.480117.9301.0037.248ATOM2832OH2TIPS12932.26425.802140.3111.0031.728ATOM2833OH2TIPS13058.40939.864124.9991.0027.798ATOM2834OH2TIPS13150.71727.447116.3981.0028.188ATOM2835OH2TIPS13254.52434.273124.9611.0027.628ATOM2836OH2TIPS13344.9428.806122.0761.0023.218ATOM2837OH2TIPS13445.01949.937103.5491.0035.778ATOM2838OH2TIPS13513.93935.763126.6011.0028.798ATOM2839OH2TIPS13647.69745.857133.9701.0031.828ATOM2840OH2TIPS13742.9515.634120.8101.0040.748ATOM2841OH2TIPS13824.81125.975102.7691.0042.308ATOM2842OH2TIPS13919.40427.466134.1481.0035.788ATOM2843OH2TIPS14019.72216.378115.9531.0038.318ATOM2844OH2TIPS14133.16526.435108.7611.0025.718ATOM2845OH2TIPS14223.99432.686105.7861.0032.488ATOM2846OH2TIPS14356.73131.921100.6371.0044.838ATOM2847OH2TIPS14423.40839.422130.5541.0036.148ATOM2848OH2TIPS14516.40427.543125.2681.0023.358ATOM2849OH2TIPS14621.91333.905135.0581.0026.198ATOM2850OH2TIPS14724.03819.019111.4971.0022.278ATOM2851OH2TIPS14845.06011.433142.5031.0023.888ATOM2852OH2TIPS14941.06315.170115.9131.0031.288ATOM2853OH2TIPS15021.75218.570116.2111.0024.208ATOM2854OH2TIPS15159.50133.631122.3581.0046.238ATOM2855OH2TIPS15258.12627.185113.9441.0036.358ATOM2856OH2TIPS15320.93813.871115.6071.0046.268ATOM2857OH2TIPS15429.63744.495124.5701.0036.628ATOM2858OH2TIPS15543.36624.704113.0481.0025.368ATOM2859OH2TIPS15635.45216.596138.4031.0042.248ATOM2860OH2TIPS15748.29723.939137.0601.0036.418ATOM2861OH2TIPS15819.30328.323114.8011.0026.838ATOM2862OH2TIPS15963.48240.278122.1011.0035.378ATOM2863OH2TIPS16014.10024.011122.1381.0036.608ATOM2864OH2TIPS16132.52120.362136.3501.0028.698ATOM2865OH2TIPS16254.33138.297132.2531.0040.298ATOM2866OH2TIPS16333.28630.321143.3481.0043.868ATOM2867OH2TIPS16414.83320.433122.7031.0048.238ATOM2868OH2TIPS16517.10925.312116.5821.0048.748ATOM2869OH2TIPS16636.83727.15393.1191.0030.298ATOM2870OH2TIPS16723.60631.494128.4161.0020.968ATOM2871OH2TIPS16842.29712.908116.2411.0026.128ATOM2872OH2TIPS16938.98847.32590.1051.0056.338ATOM2873OH2TIPS17049.90740.41292.8211.0038.058ATOM2874OH2TIPS17142.72543.422129.0531.0027.818ATOM2875OH2TIPS17225.85945.309121.5441.0032.718ATOM2876OH2TIPS17343.65716.641114.7191.0037.518ATOM2877OH2TIPS17457.56127.727130.4741.0042.178ATOM2878OH2TIPS17525.85244.022101.1931.0052.158ATOM2879OH2TIPS17617.88941.128118.9151.0031.818ATOM2880OH2TIPS17754.91744.291118.3121.0033.018ATOM2881OH2TIPS17845.75732.304144.4421.0038.198ATOM2882OH2TIPS17945.11345.502117.3341.0033.868ATOM2883OH2TIPS18059.49231.846104.5201.0047.268ATOM2884OH2TIPS18125.26025.416100.1171.0033.588ATOM2885OH2TIPS18238.60714.869139.6081.0034.718ATOM2886OH2TIPS18322.59126.885126.2611.0033.318ATOM2887OH2TIPS18459.02133.013110.0181.0028.538ATOM2888OH2TIPS18543.03845.888128.8621.0040.368ATOM2889OH2TIPS18647.94112.202119.3381.0037.778ATOM2890OH2TIPS18743.23443.410120.4371.0036.298ATOM2891OH2TIPS18839.22554.856126.7471.0044.078ATOM2892OH2TIPS18955.04940.893112.0161.0027.708ATOM2893OH2TIPS19042.25723.718146.3691.0039.058ATOM2894OH2TIPS19153.94321.613124.1801.0049.228ATOM2895OH2TIPS19256.22433.47696.5991.0053.688ATOM2896OH2TIPS19330.82412.457134.4621.0032.588ATOM2897OH2TIPS19423.55429.013108.9131.0038.738ATOM2898OH2TIPS19544.44314.105117.0311.0035.658ATOM2899OH2TIPS19659.97336.155109.5021.0031.578ATOM2900OH2TIPS19741.01155.319134.0601.0036.628ATOM2901OH2TIPS19845.29548.877108.4031.0038.368ATOM2902OH2TIPS19947.41643.146132.9461.0031.648ATOM2903OH2TIPS20024.05128.088135.5561.0043.178ATOM2904OH2TIPS20116.83122.525127.4921.0048.228ATOM2905OH2TIPS20248.28444.483111.5831.0036.568ATOM2906OH2TIPS20360.72547.338110.3081.0049.828ATOM2907OH2TIPS20443.10052.688126.8651.0031.418ATOM2908OH2TIPS20550.32122.195105.5821.0038.958ATOM2909OH2TIPS20642.60141.435130.8111.0022.018ATOM2910OH2TIPS20751.14442.594132.9111.0036.018ATOM2911OH2TIPS20844.03624.667101.8321.0033.338ATOM2912OH2TIPS20942.69327.656107.0801.0039.358ATOM2913OH2TIPS21042.39927.193113.0331.0012.718ATOM2914OH2TIPS21143.78417.104135.4391.0069.388ATOM2915OH2TIPS21335.38627.677109.1831.0013.108ATOM2916OH2TIPS21456.95540.837126.9191.0019.438ATOM2917OH2TIPS21547.94614.090128.8961.0018.548ATOM2918OH2TIPS21653.84646.419126.5771.0023.308ATOM2919OH2TIPS21719.95220.857130.5131.0019.788ATOM2920OH2TIPS21840.23813.147133.2571.0019.078ATOM2921OH2TIPS21956.39543.468127.5461.0021.048ATOM2922OH2TIPS22020.55818.224129.8751.0026.188ATOM2923OH2TIPS22120.42225.115127.6851.0021.858ATOM2924OH2TIPS22214.18431.110126.4271.0028.268ATOM2925OH2TIPS22325.55330.355110.0191.0031.918ATOM2926OH2TIPS22447.96719.947125.1341.0032.198ATOM2927OH2TIPS22534.50843.980128.8631.0022.018ATOM2928OH2TIPS22627.52114.466134.0841.0027.118ATOM2929OH2TIPS22721.41332.875128.5111.0033.828ATOM2930OH2TIPS22845.96414.452127.0831.0022.848ATOM2931OH2TIPS22938.58723.359108.6671.0029.488ATOM2932OH2TIPS23020.26929.207125.9131.0023.248ATOM2933OH2TIPS23139.82312.495130.4971.0025.208ATOM2934OH2TIPS23249.95047.945125.5181.0027.818ATOM2935OH2TIPS23332.24125.732106.3031.0029.228ATOM2936OH2TIPS23433.10940.481141.2261.0029.308ATOM2937OH2TIPS23559.83133.318107.2411.0034.808ATOM2938OH2TIPS23628.59329.974110.0141.0032.068ATOM2939OH2TIPS23738.8669.581114.5981.0033.348ATOM2940OH2TIPS23830.61742.655135.2421.0025.008ATOM2941OH2TIPS23959.58029.369119.1571.0027.418ATOM2942OH2TIPS24059.26325.840127.9941.0025.258ATOM2943OH2TIPS24152.94538.82695.1221.0027.008ATOM2944OH2TIPS24255.23748.817124.2171.0026.928ATOM2945OH2TIPS24343.72913.168130.2731.0032.028ATOM2946OH2TIPS24430.12332.187140.9391.0025.608ATOM2947OH2TIPS24540.02624.418106.8791.0032.078ATOM2948OH2TIPS24644.98626.182110.6021.0036.488ATOM2949OH2TIPS24743.97442.983135.7751.0027.668ATOM2950OH2TIPS24832.47629.429106.8221.0022.508ATOM2951OH2TIPS24949.29723.815123.8851.0033.228ATOM2952OH2TIPS25031.55514.849135.5541.0024.458ATOM2953OH2TIPS25121.16441.884123.0131.0035.988ATOM2954OH2TIPS25230.84347.804101.5811.0040.378ATOM2955OH2TIPS25348.84624.693139.4601.0038.738ATOM2956OH2TIPS25436.03145.307139.2751.0041.578ATOM2957OH2TIPS25549.28717.017125.9601.0037.898ATOM2958OH2TIPS25628.70211.672117.9121.0030.338ATOM2959OH2TIPS25751.74820.975140.5971.0027.038ATOM2960OH2TIPS25846.40648.92593.5001.0032.898ATOM2961OH2TIPS25926.93131.784138.8671.0035.588ATOM2962OH2TIPS26023.14738.768125.2951.0034.848ATOM2963OH2TIPS26121.97138.619128.5091.0034.678ATOM2964OH2TIPS26234.13941.17794.5191.0037.528ATOM2965OH2TIPS26324.53635.76399.9361.0040.698ATOM2966OH2TIPS26446.64834.643140.8951.0036.628ATOM2967OH2TIPS26556.67343.421102.0421.0043.178ATOM2968OH2TIPS26616.60434.485118.4291.0041.388ATOM2969OH2TIPS26716.84911.405119.3531.0034.228ATOM2970OH2TIPS26832.54926.181143.0731.0044.938ATOM2971OH2TIPS26922.59329.195127.1731.0032.068ATOM2972OH2TIPS27018.52729.991113.0971.0037.888ATOM2973OH2TIPS27156.38124.501120.7431.0027.288ATOM2974OH2TIPS27232.30945.003127.5701.0029.328ATOM2975OH2TIPS27337.89727.898105.9981.0033.928ATOM2976OH2TIPS27451.64924.974118.3981.0032.108ATOM2977OH2TIPS27543.7355.648125.1681.0044.938ATOM2978OH2TIPS27629.34847.316108.7101.0036.218ATOM2979OH2TIPS27730.68849.378107.4561.0043.408ATOM2980OH2TIPS27844.19041.312133.4461.0037.198ATOM2981OH2TIPS27945.68239.402134.6691.0033.118ATOM2982OH2TIPS28027.61345.102127.6151.0032.738ATOM2983OH2TIPS28158.13226.991119.9621.0029.418ATOM2984OH2TIPS28245.72042.763139.5131.0040.708ATOM2985OH2TIPS28339.57649.576123.1481.0035.958ATOM2986OH2TIPS28430.96922.69592.9321.0043.048ATOM2987OH2TIPS28546.91918.071112.7221.0039.358ATOM2988OH2TIPS28647.79822.226107.1181.0030.088ATOM2989OH2TIPS28755.89243.63799.4921.0048.198ATOM2990OH2TIPS28844.81813.801149.0411.0034.648ATOM2991OH2TIPS28945.69024.705145.5881.0039.198ATOM2992OH2TIPS29029.17615.761135.6751.0034.518ATOM2993OH2TIPS29142.82517.643112.3041.0037.928ATOM2994OH2TIPS29256.70634.093129.1811.0046.188ATOM2995OH2TIPS29337.23247.010115.3241.0034.688ATOM2996OH2TIPS29453.67547.47793.9141.0032.388ATOM2997OH2TIPS29519.76334.206136.8261.0038.338ATOM2998OH2TIPS29648.09021.156109.8061.0035.728ATOM2999OH2TIPS29754.40149.12799.5041.0053.528ATOM3000OH2TIPS29839.33916.696113.4761.0034.628ATOM3001OH2TIPS29946.36325.74592.9921.0043.728ATOM3002OH2TIPS30044.03549.13696.8481.0038.908ATOM3003OH2TIPS30149.75927.583142.8591.0042.948ATOM3004OH2TIPS30239.04823.411145.5751.0032.228ATOM3005OH2TIPS30324.97921.235139.7421.0047.178ATOM3006OH2TIPS30438.43956.154107.3911.0053.308ATOM3007OH2TIPS30534.70219.403138.5101.0032.498ATOM3008OH2TIPS30632.19535.83690.8211.0042.848ATOM3009OH2TIPS30763.62944.256123.5891.0052.838ATOM3010OH2TIPS30821.49642.773118.8061.0045.138ATOM3011OH2TIPS30951.15738.180134.4101.0039.128ATOM3012OH2TIPS31055.56136.748129.2541.0040.558ATOM3013OH2TIPS31147.48647.348108.6191.0039.398ATOM3014OH2TIPS31242.39228.47799.2811.0030.058ATOM3015OH2TIPS31334.98155.570128.3801.0038.288ATOM3016OH2TIPS31455.89946.231113.4301.0041.358ATOM3017OH2TIPS31543.37052.122103.4061.0047.318ATOM3018OH2TIPS31626.98447.057119.6911.0043.808ATOM3019OH2TIPS31752.39629.647138.7061.0043.398ATOM3020OH2TIPS31856.61923.277112.3701.0041.038ATOM3021OH2TIPS31955.76222.376105.5321.0037.468ATOM3022OH2TIPS32028.14840.281141.5921.0042.508ATOM3023OH2TIPS32118.61343.026120.5561.0045.128ATOM3024OH2TIPS32258.93525.48999.9791.0035.778ATOM3025OH2TIPS32340.57150.534137.6621.0041.608ATOM3026OH2TIPS32452.01420.946125.6581.0042.858ATOM3027OH2TIPS32542.71625.82999.6831.0039.828ATOM3028OH2TIPS32619.89324.784110.6671.0035.828ATOM3029OH2TIPS32720.96018.912112.9501.0035.828ATOM3030OH2TIPS32851.94535.676138.4411.0041.148ATOM3031OH2TIPS32937.77552.025132.4071.0040.298ATOM3032OH2TIPS33030.4935.711121.3901.0032.588ATOM3033OH2TIPS33116.94522.758124.4901.0046.508ATOM3034OH2TIPS33249.82620.361111.6041.0043.198ATOM3035OH2TIPS33361.14033.733111.4681.0031.348ATOM3036OH2TIPS33447.69941.062134.4991.0043.668ATOM3037OH2TIPS33533.75541.73391.6911.0053.228ATOM3038OH2TIPS33626.36436.964138.6561.0034.778ATOM3039OH2TIPS33752.19519.821118.0031.0049.798ATOM3040OH2TIPS33845.37839.208140.9281.0044.248ATOM3041OH2TIPS33930.96448.467118.8381.0040.618ATOM3042OH2TIPS34041.46053.913110.2501.0044.098ATOM3043OH2TIPS34146.78821.233147.3481.0041.728ATOM3044OH2TIPS34222.26238.333138.4181.0049.158ATOM3045OH2TIPS34318.93628.397110.1491.0045.058ATOM3046OH2TIPS34441.3593.502120.4301.0039.498ATOM3047OH2TIPS34542.63837.542142.4791.0038.828ATOM3048OH2TIPS34619.38132.382112.6201.0037.758ATOM3049OH2TIPS34735.54324.103143.3371.0038.258ATOM3050OH2TIPS34817.91420.835132.0161.0031.748ATOM3051OH2TIPS34950.85824.159114.7171.0030.338ATOM3052OH2TIPS35025.66338.315127.7291.0033.908ATOM3053OH2TIPS35162.53033.961113.5301.0039.168ATOM3054OH2TIPS35249.86855.18996.9371.0036.358ATOM3055OH2TIPS35333.17027.813104.9691.0032.288ATOM3056OH2TIPS35427.77519.637104.4631.0040.738ATOM3057OH2TIPS35541.68254.782127.4821.0036.108ATOM3058OH2TIPS35616.59529.666117.0691.0030.628ATOM3059OH2TIPS35759.68028.085115.8251.0037.778ATOM3060OH2TIPS35832.83642.032129.4321.0040.028ATOM3061OH2TIPS35941.35738.82390.2911.0043.928ATOM3062OH2TIPS36030.97129.187141.0431.0036.548ATOM3063OH2TIPS36119.71330.822128.2401.0045.668ATOM3064OH2TIPS36253.17447.82291.3931.0040.028ATOM3065OH2TIPS36322.47329.992136.6451.0044.498ATOM3066OH2TIPS36423.37326.355108.3481.0042.188ATOM3067OH2TIPS36527.22945.249105.9881.0038.328ATOM3068OH2TIPS36648.84839.125133.2581.0037.048ATOM3069OH2TIPS36744.85846.631109.9781.0042.078ATOM3070OH2TIPS36833.89137.87390.3311.0039.108ATOM3071OH2TIPS36929.1878.473124.5591.0037.638ATOM3072OH2TIPS37046.36717.893147.7461.0040.658ATOM3073OH2TIPS37115.3779.348119.4811.0042.478ATOM3074OH2TIPS37236.32525.547107.3621.0036.438ATOM3075OH2TIPS37361.87836.279112.1691.0036.008ATOM3076OH2TIPS37443.86529.24996.8711.0037.518ATOM3077OH2TIPS37556.79025.252115.3341.0036.468ATOM3078OH2TIPS37626.07542.793105.9911.0039.928ATOM3079OH2TIPS37739.0405.988126.9421.0049.708ATOM3080OH2TIPS37860.59930.306112.7741.0042.518ATOM3081OH2TIPS37919.97629.184136.5401.0039.698ATOM3082OH2TIPS38033.86723.699105.0071.0039.728ATOM3083OH2TIPS38144.04247.505112.3541.0037.268ATOM3084OH2TIPS38239.88257.673134.1871.0049.208ATOM3085OH2TIPS38325.01426.001138.9811.0037.958ATOM3086OH2TIPS38431.57747.522127.0341.0043.688ATOM3087OH2TIPS38530.55223.935139.6121.0043.848ATOM3088OH2TIPS38631.2708.957117.7821.0041.308ATOM3089OH2TIPS38727.52242.58699.6041.0036.818ATOM3090OH2TIPS38853.39335.796132.4751.0045.128ATOM3091OH2TIPS38926.11139.132140.3831.0036.688ATOM3092OH2TIPS39041.14933.93591.1971.0044.118ATOM3093OH2TIPS39138.7269.903111.9351.0048.668ATOM3094OH2TIPS39244.03720.151107.7911.0047.158ATOM3095OH2TIPS39324.89624.586106.7291.0042.318ATOM3096OH2TIPS39448.69242.557136.5451.0047.738ATOM3097OH2TIPS39521.80910.675116.0471.0044.038ATOM3098OH2TIPS39642.92451.84999.8181.0045.408ATOM3099OH2TIPS39722.28625.894103.8081.0039.778ATOM3100OH2TIPS39843.20644.710140.0381.0046.928ATOM3101OH2TIPS39934.25012.341113.4571.0042.738ATOM3102OH2TIPS40038.61529.176148.8561.0040.998ATOM3103OH2TIPS40151.55637.24593.3041.0040.248ATOM3104OH2TIPS40236.30322.463141.3921.0039.998ATOM3105OH2TIPS40330.84549.960104.8461.0049.778ATOM3106OH2TIPS40447.70848.566134.2151.0048.938ATOM3107OH2TIPS40546.51945.968113.0881.0050.748ATOM3108OH2TIPS40630.3626.706116.5251.0046.938ATOM3109OH2TIPS40752.03449.065118.5681.0040.348ATOM3110OH2TIPS40836.64317.245109.7151.0049.938ATOM3111OH2TIPS40922.07831.213107.0311.0044.788ATOM3112OH2TIPS41058.65341.437102.1071.0040.488ATOM3113OH2TIPS41132.35047.045120.8661.0048.988ATOM3114OH2TIPS41259.39833.349102.3281.0047.568ATOM3115OH2TIPS41357.46238.698128.5631.0048.988ATOM3116OH2TIPS41434.29420.012141.0971.0037.728ATOM3117OH2TIPS41543.34050.963135.7741.0044.078ATOM3118OH2TIPS41629.81036.408142.5401.0041.108ATOM3119OH2TIPS41746.86248.645122.7751.0047.518ENDATOM2796OH2TIPS9442.06723.372209.1001.0027.04SATOM2797OH2TIPS9526.92713.464192.0941.0017.75SATOM2798OH2TIPS9623.65531.513191.3451.0025.01SATOM2799OH2TIPS9744.31549.513160.2721.0036.39SATOM2800OH2TIPS9857.83330.994173.6831.0026.75SATOM2801OH2TIPS9926.80022.613170.6881.0025.00SATOM2802OH2TIPS10022.68027.785189.1841.0022.86SATOM2803OH2TIPS10125.62530.635172.9091.0023.36SATOM2804OH2TIPS10238.64611.391198.7401.0025.76SATOM2805OH2TIPS10354.55230.397194.0091.0019.46SATOM2806OH2TIPS10438.65114.663202.5221.0033.79SATOM2807OH2TIPS10559.93933.390170.1611.0040.87SATOM2808OH2TIPS10656.54724.130162.5781.0030.87SATOM2809OH2TIPS10759.12332.997172.9271.0023.82SATOM2810OH2TIPS10816.25827.458188.1501.0024.41SATOM2811OH2TIPS10919.96625.088173.7941.0029.67SATOM2812OH2TIPS11021.40238.440185.8331.0038.67SATOM2813OH2TIPS11128.42935.246163.1551.0071.86SATOM2814OH2TIPS11238.4036.830197.3691.0032.52SATOM2815OH2TIPS11330.22843.749202.5481.0029.22SATOM2816OH2TIPS11439.60124.423170.5561.0053.39SATOM2817OH2TIPS11542.64013.003178.9581.0029.22SATOM2818OH2TIPS11622.55529.731199.1671.0038.31SATOM2819OH2TIPS11714.33924.524184.6571.0031.37SATOM2820OH2TIPS11843.83516.827178.1051.0033.90SATOM2821OH2TIPS11925.21543.521198.7531.0027.12SATOM2822OH2TIPS12041.27637.770203.2561.0024.26SATOM2823OH2TIPS12158.61139.813187.8191.0034.65SATOM2824OH2TIPS12240.53918.220177.9411.0023.96SATOM2825OH2TIPS12350.76522.768189.3291.0034.68SATOM2826OH2TIPS12446.45746.638183.4641.0026.39SATOM2827OH2TIPS12556.91232.719163.7741.0034.48SATOM2828OH2TIPS12631.6388.254183.3421.0020.78SATOM2829OH2TIPS12758.56630.181177.1261.0019.66SATOM2830OH2TIPS12821.21221.887187.6961.0022.94SATOM2831OH2TIPS12943.39343.606183.4691.0037.28SATOM2832OH2TIPS13041.63645.401198.9801.0029.59SATOM2833OH2TIPS13124.19718.989174.2101.0022.41SATOM2834OH2TIPS13255.46749.014187.1341.0034.28SATOM2835OH2TIPS13342.64341.055153.0001.0037.84SATOM2836OH2TIPS13419.68629.647193.3741.0031.62SATOM2837OH2TIPS13516.61129.520179.8181.0022.23SATOM2838OH2TIPS13657.17327.973193.5331.0034.16SATOM2839OH2TIPS13746.67313.556194.3971.0035.31SATOM2840OH2TIPS13831.56948.735164.6621.0042.74SATOM2841OH2TIPS13953.87621.633187.4561.0035.40SATOM2842OH2TIPS14052.13220.711203.8051.0030.39SATOM2843OH2TIPS14151.32042.885195.7591.0028.93SATOM2844OH2TIPS14244.38732.976203.3571.0030.89SATOM2845OH2TIPS14338.62322.478171.7641.0032.42SATOM2846OH2TIPS14425.59238.833189.5071.0041.27SATOM2847OH2TIPS14523.35226.633170.9251.0035.02SATOM2848OH2TIPS14646.78534.483203.7771.0039.25SATOM2849OH2TIPS14728.91830.213172.8631.0032.61SATOM2850OH2TIPS14852.47635.831198.4101.0030.47SATOM2851OH2TIPS14928.52440.341159.7911.0037.22SATOM2852OH2TIPS15024.74626.566165.6631.0031.73SATOM2853OH2TIPS15221.31832.655191.3581.0028.87S

[0622]

17

TABLE 7

Coordinate data for PKB S474D

REMARK coordinates from restrained individual B-factor refinement

REMARK refinement resolution: 500.0-1.6 A

REMARK starting r = 0.2057 free_r = 0.2340

REMARK final r = 0.2049 free_r = 0.2345

REMARK B rmsd for bonded mainchain atoms = 1.267 target = 1.5

REMARK B rmsd for bonded sidechain atoms = 1.886 target = 2.0

REMARK B rmsd for angle mainchain atoms = 2.013 target = 2.0

REMARK B rmsd for angle sidechain atoms = 2.871 target = 2.5

REMARK rweight = 0.1000 (with wa = 1.01586)

REMARK target = mlf steps = 30

REMARK sg = P2 (1) 2 (1) 2 (1) a = 44.906 b = 60.998 c = 129.410 alpha = 90 beta = 90

gamma = 90

REMARK parameter file 1: protein.param

REMARK parameter file 2: anp.par

REMARK parameter file 3: CNS_TOPPAR: ion.param

REMARK parameter file 4: CNS_TOPPAR: water_rep.param

REMARK molecular structure file: generate_easy.mtf

REMARK input coordinates: minimize.pdb

REMARK reflection file = pkb-s474d-free.hkl

REMARK ncs = none

REMARK B-correction resolution: 6.0-1.6

REMARK initial B-factor correction applied to fobs:

REMARK B11 = 4.041 B22 = 3.016 B33 = −7.057

REMARK B12 = 0.000 B13 = 0.000 B23 = 0.000

REMARK B-factor correction applied to coordinate array B: −0.072

REMARK bulk solvent: density level = 0.337514 e/A{circumflex over ( )}3, B-factor = 17.3248 A{circumflex over ( )}2

REMARK reflections with |Fobs|/sigma_F < 0.0 rejected

REMARK reflections with |Fobs| > 10000 * rms (Fobs) rejected

REMARK theoretical total number of refl. in resol. range: 47803 (100.0%)

REMARK number of unobserved reflections (no entry or |F|=0): 17202 (36.0%)

REMARK number of reflections rejected: 0 (0.0%)

REMARK total number of reflections used: 30601 (64.0%)

REMARK number of reflections in working set: 29084 (60.8%)

REMARK number of reflections in test set: 1517 (3.2%)

CRYST1 44.906 60.998 129.410 90.00 90.00 90.00 P 21 21 21

REMARK FILENAME=“bindividual.pdb”

REMARK DATE: 10-Jul-02 12:01:24 created by user: dbarford

REMARK VERSION: 1.1

ATOM
1
CB
LYS
A
146
35.991
47.970
155.511
1.00
46.78
A

ATOM
2
CG
LYS
A
146
35.552
46.519
155.327
1.00
48.24
A

ATOM
3
CD
LYS
A
146
35.012
46.271
153.930
1.00
49.40
A

ATOM
4
CE
LYS
A
146
34.523
44.840
153.779
1.00
49.88
A

ATOM
5
NZ
LYS
A
146
33.881
44.612
152.453
1.00
50.89
A

ATOM
6
C
LYS
A
146
37.792
47.796
157.271
1.00
44.89
A

ATOM
7
O
LYS
A
146
38.804
48.458
157.011
1.00
45.12
A

ATOM
8
N
LYS
A
146
36.358
49.816
157.132
1.00
45.98
A

ATOM
9
CA
LYS
A
146
36.396
48.335
156.947
1.00
45.62
A

ATOM
10
N
VAL
A
147
37.827
46.598
157.859
1.00
42.77
A

ATOM
11
CA
VAL
A
147
39.074
45.936
158.259
1.00
40.74
A

ATOM
12
CB
VAL
A
147
39.056
45.539
159.772
1.00
40.55
A

ATOM
13
CG1
VAL
A
147
40.474
45.391
160.300
1.00
39.85
A

ATOM
14
CG2
VAL
A
147
38.283
46.556
160.605
1.00
40.90
A

ATOM
15
C
VAL
A
147
39.307
44.670
157.424
1.00
38.88
A

ATOM
16
O
VAL
A
147
38.397
43.851
157.259
1.00
38.52
A

ATOM
17
N
THR
A
148
40.528
44.525
156.904
1.00
37.71
A

ATOM
18
CA
THR
A
148
40.915
43.370
156.084
1.00
37.31
A

ATOM
19
CB
THR
A
148
41.229
43.776
154.611
1.00
37.93
A

ATOM
20
OG1
THR
A
148
42.165
44.860
154.591
1.00
39.40
A

ATOM
21
CG2
THR
A
148
39.959
44.175
153.862
1.00
37.85
A

ATOM
22
C
THR
A
148
42.116
42.611
156.662
1.00
35.95
A

ATOM
23
O
THR
A
148
42.756
43.070
157.613
1.00
35.13
A

ATOM
24
N
MET
A
149
42.417
41.459
156.061
1.00
35.36
A

ATOM
25
CA
MET
A
149
43.520
40.577
156.462
1.00
34.92
A

ATOM
26
CB
MET
A
149
43.414
39.255
155.691
1.00
36.33
A

ATOM
27
CG
MET
A
149
43.998
38.040
156.391
1.00
38.13
A

ATOM
28
SD
MET
A
149
43.030
37.531
157.828
1.00
40.90
A

ATOM
29
CE
MET
A
149
42.120
36.200
157.139
1.00
38.85
A

ATOM
30
C
MET
A
149
44.907
41.197
156.230
1.00
33.99
A

ATOM
31
O
MET
A
149
45.818
41.014
157.043
1.00
32.97
A

ATOM
32
N
ASN
A
150
45.032
41.964
155.146
1.00
33.65
A

ATOM
33
CA
ASN
A
150
46.287
42.620
154.761
1.00
33.79
A

ATOM
34
CB
ASN
A
150
46.310
42.887
153.242
1.00
37.25
A

ATOM
35
CG
ASN
A
150
45.099
43.676
152.756
1.00
39.85
A

ATOM
36
OD1
ASN
A
150
44.990
44.882
152.990
1.00
42.32
A

ATOM
37
ND2
ASN
A
150
44.191
42.996
152.066
1.00
41.41
A

ATOM
38
C
ASN
A
150
46.680
43.885
155.543
1.00
31.77
A

ATOM
39
O
ASN
A
150
47.716
44.494
155.261
1.00
32.40
A

ATOM
40
N
ASP
A
151
45.857
44.272
156.518
1.00
29.24
A

ATOM
41
CA
ASP
A
151
46.121
45.449
157.357
1.00
27.13
A

ATOM
42
CB
ASP
A
151
44.805
46.053
157.876
1.00
28.08
A

ATOM
43
CG
ASP
A
151
43.957
46.667
156.775
1.00
30.02
A

ATOM
44
OD1
ASP
A
151
44.517
47.317
155.864
1.00
31.91
A

ATOM
45
OD2
ASP
A
151
42.720
46.509
156.833
1.00
30.02
A

ATOM
46
C
ASP
A
151
47.005
45.083
158.551
1.00
25.59
A

ATOM
47
O
ASP
A
151
47.368
45.944
159.361
1.00
24.48
A

ATOM
48
N
PHE
A
152
47.331
43.793
158.652
1.00
24.32
A

ATOM
49
CA
PHE
A
152
48.139
43.255
159.745
1.00
23.75
A

ATOM
50
CB
PHE
A
152
47.290
42.314
160.624
1.00
22.47
A

ATOM
51
CG
PHE
A
152
46.049
42.951
161.191
1.00
22.06
A

ATOM
52
CD1
PHE
A
152
46.090
43.627
162.424
1.00
22.19
A

ATOM
53
CD2
PHE
A
152
44.835
42.908
160.477
1.00
21.35
A

ATOM
54
CE1
PHE
A
152
44.932
44.265
162.947
1.00
21.99
A

ATOM
55
CE2
PHE
A
152
43.670
43.537
160.981
1.00
20.95
A

ATOM
56
CZ
PHE
A
152
43.719
44.219
162.220
1.00
21.29
A

ATOM
57
C
PHE
A
152
49.380
42.492
159.296
1.00
23.26
A

ATOM
58
O
PHE
A
152
49.446
41.981
158.173
1.00
23.87
A

ATOM
59
N
GLU
A
153
50.355
42.430
160.202
1.00
23.42
A

ATOM
60
CA
GLU
A
153
51.610
41.700
160.015
1.00
23.74
A

ATOM
61
CB
GLU
A
153
52.808
42.571
160.394
1.00
26.53
A

ATOM
62
CG
GLU
A
153
53.159
43.619
159.359
1.00
31.28
A

ATOM
63
CD
GLU
A
153
54.006
44.732
159.923
1.00
34.15
A

ATOM
64
OE1
GLU
A
153
55.220
44.768
159.627
1.00
38.38
A

ATOM
65
OE2
GLU
A
153
53.458
45.575
160.666
1.00
36.09
A

ATOM
66
C
GLU
A
153
51.506
40.512
160.966
1.00
23.22
A

ATOM
67
O
GLU
A
153
51.255
40.695
162.155
1.00
22.59
A

ATOM
68
N
TYR
A
154
51.656
39.304
160.427
1.00
22.72
A

ATOM
69
CA
TYR
A
154
51.552
38.063
161.200
1.00
22.21
A

ATOM
70
CB
TYR
A
154
50.833
36.991
160.362
1.00
22.82
A

ATOM
71
CG
TYR
A
154
49.442
37.436
159.938
1.00
21.25
A

ATOM
72
CD1
TYR
A
154
49.261
38.289
158.821
1.00
21.61
A

ATOM
73
CE1
TYR
A
154
47.985
38.830
158.502
1.00
22.05
A

ATOM
74
CD2
TYR
A
154
48.310
37.115
160.717
1.00
21.58
A

ATOM
75
CE2
TYR
A
154
47.024
37.650
160.407
1.00
22.01
A

ATOM
76
CZ
TYR
A
154
46.878
38.511
159.304
1.00
21.58
A

ATOM
77
OH
TYR
A
154
45.660
39.090
159.037
1.00
20.58
A

ATOM
78
C
TYR
A
154
52.928
37.617
161.686
1.00
22.76
A

ATOM
79
O
TYR
A
154
53.755
37.127
160.913
1.00
22.34
A

ATOM
80
N
LEU
A
155
53.156
37.815
162.984
1.00
22.84
A

ATOM
81
CA
LEU
A
155
54.436
37.517
163.631
1.00
23.49
A

ATOM
82
CB
LEU
A
155
54.709
38.548
164.732
1.00
22.23
A

ATOM
83
CG
LEU
A
155
54.516
40.018
164.322
1.00
23.82
A

ATOM
84
CD1
LEU
A
155
54.699
40.891
165.524
1.00
25.47
A

ATOM
85
CD2
LEU
A
155
55.470
40.434
163.196
1.00
24.24
A

ATOM
86
C
LEU
A
155
54.654
36.095
164.140
1.00
23.77
A

ATOM
87
O
LEU
A
155
55.531
35.394
163.627
1.00
25.45
A

ATOM
88
N
LYS
A
156
53.899
35.681
165.161
1.00
23.72
A

ATOM
89
CA
LYS
A
156
54.022
34.324
165.713
1.00
23.83
A

ATOM
90
CB
LYS
A
156
55.243
34.177
166.642
1.00
26.51
A

ATOM
91
CG
LYS
A
156
55.446
35.236
167.710
1.00
28.39
A

ATOM
92
CD
LYS
A
156
56.739
34.935
168.446
1.00
30.20
A

ATOM
93
CE
LYS
A
156
57.547
36.187
168.697
1.00
31.27
A

ATOM
94
NZ
LYS
A
156
58.763
35.906
169.507
1.00
30.91
A

ATOM
95
C
LYS
A
156
52.778
33.759
166.381
1.00
22.12
A

ATOM
96
O
LYS
A
156
51.905
34.503
166.832
1.00
20.31
A

ATOM
97
N
LEU
A
157
52.713
32.427
166.427
1.00
20.31
A

ATOM
98
CA
LEU
A
157
51.596
31.698
167.025
1.00
17.99
A

ATOM
99
CB
LEU
A
157
51.590
30.244
166.529
1.00
18.27
A

ATOM
100
CG
LEU
A
157
50.460
29.295
166.950
1.00
17.24
A

ATOM
101
CD1
LEU
A
157
49.163
29.686
166.272
1.00
18.35
A

ATOM
102
CD2
LEU
A
157
50.828
27.874
166.586
1.00
17.81
A

ATOM
103
C
LEU
A
157
51.663
31.740
168.551
1.00
17.21
A

ATOM
104
O
LEU
A
157
52.695
31.428
169.147
1.00
16.26
A

ATOM
105
N
LEU
A
158
50.559
32.157
169.164
1.00
16.20
A

ATOM
106
CA
LEU
A
158
50.453
32.247
170.620
1.00
15.54
A

ATOM
107
CB
LEU
A
158
49.637
33.476
171.017
1.00
14.60
A

ATOM
108
CG
LEU
A
158
50.188
34.849
170.645
1.00
14.10
A

ATOM
109
CD1
LEU
A
158
49.148
35.897
170.959
1.00
14.40
A

ATOM
110
CD2
LEU
A
158
51.503
35.133
171.371
1.00
13.46
A

ATOM
111
C
LEU
A
158
49.793
31.007
171.200
1.00
15.73
A

ATOM
112
O
LEU
A
158
50.201
30.514
172.253
1.00
15.26
A

ATOM
113
N
GLY
A
159
48.777
30.512
170.497
1.00
16.92
A

ATOM
114
CA
GLY
A
159
48.054
29.339
170.948
1.00
19.04
A

ATOM
115
C
GLY
A
159
47.246
28.690
169.848
1.00
22.76
A

ATOM
116
O
GLY
A
159
46.961
29.312
168.821
1.00
20.44
A

ATOM
117
N
LYS
A
160
46.856
27.441
170.084
1.00
26.41
A

ATOM
118
CA
LYS
A
160
46.080
26.670
169.120
1.00
31.69
A

ATOM
119
CB
LYS
A
160
47.021
25.810
168.263
1.00
33.56
A

ATOM
120
CG
LYS
A
160
46.474
25.406
166.902
1.00
37.49
A

ATOM
121
CD
LYS
A
160
47.561
24.765
166.051
1.00
39.02
A

ATOM
122
CE
LYS
A
160
47.085
24.532
164.623
1.00
40.97
A

ATOM
123
NZ
LYS
A
160
48.162
23.969
163.761
1.00
42.36
A

ATOM
124
C
LYS
A
160
45.072
25.784
169.841
1.00
34.91
A

ATOM
125
O
LYS
A
160
45.374
25.197
170.885
1.00
35.09
A

ATOM
126
N
GLY
A
161
43.865
25.733
169.287
1.00
37.41
A

ATOM
127
CA
GLY
A
161
42.804
24.908
169.835
1.00
40.92
A

ATOM
128
C
GLY
A
161
42.480
23.808
168.842
1.00
42.89
A

ATOM
129
O
GLY
A
161
43.197
23.628
167.849
1.00
43.97
A

ATOM
130
N
THR
A
162
41.399
23.077
169.101
1.00
44.70
A

ATOM
131
CA
THR
A
162
40.957
21.988
168.226
1.00
45.93
A

ATOM
132
CB
THR
A
162
40.212
20.882
169.044
1.00
46.60
A

ATOM
133
OG1
THR
A
162
40.875
20.686
170.301
1.00
46.54
A

ATOM
134
CG2
THR
A
162
40.223
19.546
168.298
1.00
46.54
A

ATOM
135
C
THR
A
162
40.044
22.560
167.123
1.00
46.32
A

ATOM
136
O
THR
A
162
39.621
21.839
166.215
1.00
47.55
A

ATOM
137
N
PHE
A
163
39.763
23.864
167.210
1.00
46.08
A

ATOM
138
CA
PHE
A
163
38.908
24.567
166.249
1.00
45.94
A

ATOM
139
CB
PHE
A
163
37.654
25.139
166.941
1.00
48.60
A

ATOM
140
CG
PHE
A
163
36.868
24.129
167.749
1.00
50.85
A

ATOM
141
CD1
PHE
A
163
36.739
24.285
169.144
1.00
51.89
A

ATOM
142
CD2
PHE
A
163
36.253
23.019
167.128
1.00
52.06
A

ATOM
143
CE1
PHE
A
163
36.006
23.345
169.928
1.00
53.11
A

ATOM
144
CE2
PHE
A
163
35.515
22.065
167.892
1.00
52.93
A

ATOM
145
CZ
PHE
A
163
35.391
22.230
169.297
1.00
53.36
A

ATOM
146
C
PHE
A
163
39.639
25.704
165.522
1.00
44.28
A

ATOM
147
O
PHE
A
163
39.503
25.844
164.300
1.00
44.95
A

ATOM
148
N
GLY
A
164
40.402
26.506
166.272
1.00
41.78
A

ATOM
149
CA
GLY
A
164
41.128
27.628
165.686
1.00
37.51
A

ATOM
150
C
GLY
A
164
42.459
28.002
166.319
1.00
34.67
A

ATOM
151
O
GLY
A
164
42.857
27.432
167.340
1.00
34.02
A

ATOM
152
N
LYS
A
165
43.128
28.989
165.718
1.00
30.49
A

ATOM
153
CA
LYS
A
165
44.437
29.464
166.175
1.00
26.36
A

ATOM
154
CB
LYS
A
165
45.507
29.144
165.119
1.00
28.07
A

ATOM
155
CG
LYS
A
165
45.213
29.664
163.712
1.00
29.66
A

ATOM
156
CD
LYS
A
165
46.250
29.187
162.712
1.00
31.90
A

ATOM
157
CE
LYS
A
165
45.887
29.629
161.304
1.00
34.12
A

ATOM
158
NZ
LYS
A
165
46.866
29.140
160.292
1.00
36.61
A

ATOM
159
C
LYS
A
165
44.494
30.949
166.553
1.00
23.30
A

ATOM
160
O
LYS
A
165
43.719
31.758
166.041
1.00
22.11
A

ATOM
161
N
VAL
A
166
45.405
31.285
167.473
1.00
18.51
A

ATOM
162
CA
VAL
A
166
45.605
32.664
167.946
1.00
16.12
A

ATOM
163
CB
VAL
A
166
45.335
32.813
169.478
1.00
14.80
A

ATOM
164
CG1
VAL
A
166
45.444
34.284
169.914
1.00
13.52
A

ATOM
165
CG2
VAL
A
166
43.945
32.289
169.823
1.00
14.78
A

ATOM
166
C
VAL
A
166
47.033
33.096
167.602
1.00
14.71
A

ATOM
167
O
VAL
A
166
48.002
32.486
168.051
1.00
13.66
A

ATOM
168
N
ILE
A
167
47.135
34.146
166.789
1.00
14.33
A

ATOM
169
CA
ILE
A
167
48.413
34.683
166.311
1.00
13.86
A

ATOM
170
CB
ILE
A
167
48.456
34.630
164.725
1.00
15.99
A

ATOM
171
CG2
ILE
A
167
49.737
35.282
164.164
1.00
15.76
A

ATOM
172
CG1
ILE
A
167
48.376
33.172
164.237
1.00
17.11
A

ATOM
173
CD1
ILE
A
167
48.112
33.004
162.746
1.00
19.50
A

ATOM
174
C
ILE
A
167
48.660
36.123
166.789
1.00
12.81
A

ATOM
175
O
ILE
A
167
47.738
36.939
166.818
1.00
13.42
A

ATOM
176
N
LEU
A
168
49.912
36.421
167.153
1.00
13.57
A

ATOM
177
CA
LEU
A
168
50.321
37.769
167.568
1.00
13.34
A

ATOM
178
CB
LEU
A
168
51.657
37.741
168.331
1.00
13.85
A

ATOM
179
CG
LEU
A
168
52.360
39.064
168.686
1.00
14.31
A

ATOM
180
CD1
LEU
A
168
51.474
39.963
169.534
1.00
15.36
A

ATOM
181
CD2
LEU
A
168
53.660
38.775
169.396
1.00
15.22
A

ATOM
182
C
LEU
A
168
50.480
38.586
166.288
1.00
13.78
A

ATOM
183
O
LEU
A
168
51.263
38.219
165.405
1.00
13.96
A

ATOM
184
N
VAL
A
169
49.693
39.656
166.188
1.00
13.83
A

ATOM
185
CA
VAL
A
169
49.705
40.532
165.020
1.00
16.50
A

ATOM
186
CB
VAL
A
169
48.338
40.496
164.242
1.00
15.39
A

ATOM
187
CG1
VAL
A
169
48.027
39.095
163.770
1.00
16.18
A

ATOM
188
CG2
VAL
A
169
47.183
41.021
165.095
1.00
15.89
A

ATOM
189
C
VAL
A
169
50.062
41.980
165.348
1.00
17.03
A

ATOM
190
O
VAL
A
169
49.970
42.410
166.497
1.00
16.28
A

ATOM
191
N
ARG
A
170
50.493
42.710
164.323
1.00
18.98
A

ATOM
192
CA
ARG
A
170
50.835
44.120
164.449
1.00
20.17
A

ATOM
193
CB
ARG
A
170
52.344
44.340
164.249
1.00
21.99
A

ATOM
194
CG
ARG
A
170
52.798
45.811
164.246
1.00
24.54
A

ATOM
195
CD
ARG
A
170
54.319
45.972
164.189
1.00
26.69
A

ATOM
196
NE
ARG
A
170
54.944
45.240
163.086
1.00
30.34
A

ATOM
197
CZ
ARG
A
170
56.024
44.466
163.202
1.00
31.30
A

ATOM
198
NH1
ARG
A
170
56.622
44.305
164.377
1.00
31.59
A

ATOM
199
NH2
ARG
A
170
56.503
43.840
162.134
1.00
33.00
A

ATOM
200
C
ARG
A
170
50.032
44.846
163.379
1.00
20.88
A

ATOM
201
O
ARG
A
170
50.069
44.463
162.207
1.00
21.21
A

ATOM
202
N
GLU
A
171
49.264
45.851
163.800
1.00
20.64
A

ATOM
203
CA
GLU
A
171
48.459
46.658
162.884
1.00
22.06
A

ATOM
204
CB
GLU
A
171
47.360
47.405
163.650
1.00
22.82
A

ATOM
205
CG
GLU
A
171
46.315
48.084
162.753
1.00
24.90
A

ATOM
206
CD
GLU
A
171
45.188
48.772
163.516
1.00
26.38
A

ATOM
207
OE1
GLU
A
171
45.287
48.974
164.748
1.00
28.56
A

ATOM
208
OE2
GLU
A
171
44.186
49.126
162.864
1.00
29.84
A

ATOM
209
C
GLU
A
171
49.417
47.632
162.196
1.00
22.37
A

ATOM
210
O
GLU
A
171
50.087
48.419
162.864
1.00
22.45
A

ATOM
211
N
LYS
A
172
49.508
47.525
160.871
1.00
23.08
A

ATOM
212
CA
LYS
A
172
50.400
48.350
160.045
1.00
25.36
A

ATOM
213
CB
LYS
A
172
50.238
47.985
158.567
1.00
24.67
A

ATOM
214
CG
LYS
A
172
50.701
46.585
158.206
1.00
25.16
A

ATOM
215
CD
LYS
A
172
50.441
46.283
156.741
1.00
26.03
A

ATOM
216
CE
LYS
A
172
50.894
44.882
156.373
1.00
27.30
A

ATOM
217
NZ
LYS
A
172
50.627
44.564
154.941
1.00
28.64
A

ATOM
218
C
LYS
A
172
50.278
49.865
160.206
1.00
25.97
A

ATOM
219
O
LYS
A
172
51.289
50.555
160.371
1.00
27.02
A

ATOM
220
N
ALA
A
173
49.039
50.358
160.221
1.00
27.17
A

ATOM
221
CA
ALA
A
173
48.744
51.788
160.340
1.00
27.54
A

ATOM
222
CB
ALA
A
173
47.296
52.054
159.941
1.00
28.28
A

ATOM
223
C
ALA
A
173
49.044
52.437
161.689
1.00
28.27
A

ATOM
224
O
ALA
A
173
49.482
53.589
161.734
1.00
29.02
A

ATOM
225
N
THR
A
174
48.838
51.687
162.774
1.00
28.12
A

ATOM
226
CA
THR
A
174
49.053
52.193
164.133
1.00
26.80
A

ATOM
227
CB
THR
A
174
47.841
51.887
165.045
1.00
27.59
A

ATOM
228
OG1
THR
A
174
47.652
50.469
165.132
1.00
25.96
A

ATOM
229
CG2
THR
A
174
46.568
52.542
164.511
1.00
25.92
A

ATOM
230
C
THR
A
174
50.319
51.694
164.839
1.00
27.09
A

ATOM
231
O
THR
A
174
50.823
52.356
165.755
1.00
26.75
A

ATOM
232
N
GLY
A
175
50.816
50.528
164.425
1.00
26.61
A

ATOM
233
CA
GLY
A
175
52.006
49.947
165.034
1.00
27.34
A

ATOM
234
C
GLY
A
175
51.710
49.208
166.331
1.00
27.13
A

ATOM
235
O
GLY
A
175
52.626
48.705
166.987
1.00
27.15
A

ATOM
236
N
ARG
A
176
50.426
49.146
166.690
1.00
26.58
A

ATOM
237
CA
ARG
A
176
49.963
48.480
167.909
1.00
25.46
A

ATOM
238
CB
ARG
A
176
48.637
49.082
168.377
1.00
28.67
A

ATOM
239
CG
ARG
A
176
48.748
50.519
168.855
1.00
32.16
A

ATOM
240
CD
ARG
A
176
47.390
51.087
169.205
1.00
35.83
A

ATOM
241
NE
ARG
A
176
47.473
52.504
169.554
1.00
40.39
A

ATOM
242
CZ
ARG
A
176
46.468
53.372
169.450
1.00
42.09
A

ATOM
243
NH1
ARG
A
176
45.279
52.984
169.001
1.00
43.47
A

ATOM
244
NH2
ARG
A
176
46.654
54.638
169.796
1.00
43.14
A

ATOM
245
C
ARG
A
176
49.828
46.973
167.728
1.00
24.01
A

ATOM
246
O
ARG
A
176
49.442
46.495
166.656
1.00
23.61
A

ATOM
247
N
TYR
A
177
50.155
46.237
168.790
1.00
21.65
A

ATOM
248
CA
TYR
A
177
50.114
44.779
168.787
1.00
20.54
A

ATOM
249
CB
TYR
A
177
51.336
44.212
169.514
1.00
20.61
A

ATOM
250
CG
TYR
A
177
52.662
44.516
168.843
1.00
22.82
A

ATOM
251
CD1
TYR
A
177
53.195
45.828
168.833
1.00
24.24
A

ATOM
252
CE1
TYR
A
177
54.457
46.110
168.237
1.00
25.32
A

ATOM
253
CD2
TYR
A
177
53.415
43.490
168.241
1.00
23.65
A

ATOM
254
CE2
TYR
A
177
54.679
43.761
167.644
1.00
26.72
A

ATOM
255
CZ
TYR
A
177
55.187
45.069
167.648
1.00
26.11
A

ATOM
256
OH
TYR
A
177
56.406
45.327
167.061
1.00
28.14
A

ATOM
257
C
TYR
A
177
48.833
44.211
169.377
1.00
19.07
A

ATOM
258
O
TYR
A
177
48.320
44.715
170.379
1.00
19.67
A

ATOM
259
N
TYR
A
178
48.297
43.189
168.709
1.00
17.60
A

ATOM
260
CA
TYR
A
178
47.057
42.529
169.116
1.00
17.11
A

ATOM
261
CB
TYR
A
178
45.877
43.019
168.261
1.00
17.47
A

ATOM
262
CG
TYR
A
178
45.579
44.507
168.316
1.00
19.26
A

ATOM
263
CD1
TYR
A
178
45.920
45.349
167.234
1.00
19.57
A

ATOM
264
CE1
TYR
A
178
45.670
46.749
167.283
1.00
21.58
A

ATOM
265
CD2
TYR
A
178
44.977
45.089
169.452
1.00
19.12
A

ATOM
266
CE2
TYR
A
178
44.723
46.489
169.516
1.00
22.32
A

ATOM
267
CZ
TYR
A
178
45.075
47.307
168.427
1.00
22.02
A

ATOM
268
OH
TYR
A
178
44.845
48.660
168.483
1.00
26.18
A

ATOM
269
C
TYR
A
178
47.155
41.012
168.964
1.00
15.27
A

ATOM
270
O
TYR
A
178
48.116
40.493
168.396
1.00
15.12
A

ATOM
271
N
ALA
A
179
46.167
40.307
169.510
1.00
13.73
A

ATOM
272
CA
ALA
A
179
46.093
38.856
169.401
1.00
12.88
A

ATOM
273
CB
ALA
A
179
45.920
38.224
170.770
1.00
13.44
A

ATOM
274
C
ALA
A
179
44.891
38.556
168.513
1.00
12.57
A

ATOM
275
O
ALA
A
179
43.766
38.952
168.830
1.00
11.35
A

ATOM
276
N
MET
A
180
45.141
37.912
167.376
1.00
12.14
A

ATOM
277
CA
MET
A
180
44.070
37.577
166.444
1.00
12.46
A

ATOM
278
CB
MET
A
180
44.448
37.959
165.006
1.00
13.41
A

ATOM
279
CG
MET
A
180
43.265
37.956
164.032
1.00
16.23
A

ATOM
280
SD
MET
A
180
43.740
38.002
162.294
1.00
18.09
A

ATOM
281
CE
MET
A
180
44.079
39.712
162.118
1.00
18.60
A

ATOM
282
C
MET
A
180
43.656
36.113
166.488
1.00
12.76
A

ATOM
283
O
MET
A
180
44.453
35.229
166.180
1.00
11.58
A

ATOM
284
N
LYS
A
181
42.404
35.870
166.877
1.00
12.35
A

ATOM
285
CA
LYS
A
181
41.858
34.520
166.909
1.00
13.81
A

ATOM
286
CB
LYS
A
181
40.824
34.352
168.031
1.00
13.00
A

ATOM
287
CG
LYS
A
181
40.321
32.921
168.189
1.00
14.36
A

ATOM
288
CD
LYS
A
181
39.412
32.758
169.383
1.00
12.64
A

ATOM
289
CE
LYS
A
181
38.950
31.313
169.497
1.00
14.72
A

ATOM
290
NZ
LYS
A
181
38.167
31.096
170.745
1.00
13.62
A

ATOM
291
C
LYS
A
181
41.219
34.277
165.541
1.00
15.58
A

ATOM
292
O
LYS
A
181
40.275
34.975
165.150
1.00
15.91
A

ATOM
293
N
ILE
A
182
41.793
33.329
164.804
1.00
16.92
A

ATOM
294
CA
ILE
A
182
41.332
32.963
163.467
1.00
18.77
A

ATOM
295
CB
ILE
A
182
42.521
32.887
162.455
1.00
18.33
A

ATOM
296
CG2
ILE
A
182
42.015
32.506
161.055
1.00
19.77
A

ATOM
297
CG1
ILE
A
182
43.251
34.237
162.391
1.00
18.27
A

ATOM
298
CD1
ILE
A
182
44.575
34.219
161.643
1.00
19.42
A

ATOM
299
C
ILE
A
182
40.587
31.627
163.502
1.00
19.51
A

ATOM
300
O
ILE
A
182
41.125
30.611
163.955
1.00
20.62
A

ATOM
301
N
LEU
A
183
39.341
31.656
163.035
1.00
19.80
A

ATOM
302
CA
LEU
A
183
38.482
30.475
162.980
1.00
20.88
A

ATOM
303
CB
LEU
A
183
37.231
30.684
163.846
1.00
22.23
A

ATOM
304
CG
LEU
A
183
37.343
30.798
165.375
1.00
22.62
A

ATOM
305
CD1
LEU
A
183
36.011
31.217
165.953
1.00
25.26
A

ATOM
306
CD2
LEU
A
183
37.779
29.481
165.990
1.00
24.84
A

ATOM
307
C
LEU
A
183
38.079
30.193
161.530
1.00
20.98
A

ATOM
308
O
LEU
A
183
37.784
31.116
160.770
1.00
20.81
A

ATOM
309
N
ARG
A
184
38.100
28.917
161.151
1.00
22.37
A

ATOM
310
CA
ARG
A
184
37.745
28.490
159.795
1.00
24.46
A

ATOM
311
CB
ARG
A
184
38.528
27.230
159.413
1.00
26.64
A

ATOM
312
CG
ARG
A
184
40.037
27.412
159.350
1.00
31.44
A

ATOM
313
CD
ARG
A
184
40.737
26.100
159.025
1.00
34.87
A

ATOM
314
NE
ARG
A
184
42.175
26.286
158.834
1.00
39.41
A

ATOM
315
CZ
ARG
A
184
42.825
26.078
157.689
1.00
40.55
A

ATOM
316
NH1
ARG
A
184
42.177
25.665
156.604
1.00
40.86
A

ATOM
317
NH2
ARG
A
184
44.131
26.306
157.623
1.00
41.12
A

ATOM
318
C
ARG
A
184
36.242
28.236
159.673
1.00
23.47
A

ATOM
319
O
ARG
A
184
35.684
27.423
160.418
1.00
23.44
A

ATOM
320
N
LYS
A
185
35.605
28.926
158.723
1.00
23.71
A

ATOM
321
CA
LYS
A
185
34.159
28.824
158.472
1.00
25.34
A

ATOM
322
CB
LYS
A
185
33.729
29.765
157.342
1.00
25.67
A

ATOM
323
CG
LYS
A
185
33.756
31.234
157.681
1.00
26.84
A

ATOM
324
CD
LYS
A
185
33.158
32.059
156.551
1.00
27.13
A

ATOM
325
CE
LYS
A
185
33.152
33.535
156.886
1.00
27.10
A

ATOM
326
NZ
LYS
A
185
32.548
34.353
155.795
1.00
27.64
A

ATOM
327
C
LYS
A
185
33.636
27.428
158.151
1.00
25.95
A

ATOM
328
O
LYS
A
185
32.611
27.017
158.694
1.00
26.63
A

ATOM
329
N
GLU
A
186
34.369
26.695
157.310
1.00
27.17
A

ATOM
330
CA
GLU
A
186
33.989
25.345
156.878
1.00
28.65
A

ATOM
331
CB
GLU
A
186
34.952
24.856
155.789
1.00
32.27
A

ATOM
332
CG
GLU
A
186
34.361
23.808
154.845
1.00
38.31
A

ATOM
333
CD
GLU
A
186
35.222
23.568
153.617
1.00
41.05
A

ATOM
334
OE1
GLU
A
186
35.835
22.481
153.523
1.00
43.72
A

ATOM
335
OE2
GLU
A
186
35.279
24.463
152.743
1.00
42.30
A

ATOM
336
C
GLU
A
186
33.876
24.317
158.011
1.00
27.71
A

ATOM
337
O
GLU
A
186
32.985
23.466
157.990
1.00
27.55
A

ATOM
338
N
VAL
A
187
34.733
24.456
159.024
1.00
26.87
A

ATOM
339
CA
VAL
A
187
34.760
23.567
160.196
1.00
26.83
A

ATOM
340
CB
VAL
A
187
36.095
23.724
160.993
1.00
26.78
A

ATOM
341
CG1
VAL
A
187
36.257
22.610
162.027
1.00
27.09
A

ATOM
342
CG2
VAL
A
187
37.271
23.717
160.050
1.00
27.39
A

ATOM
343
C
VAL
A
187
33.585
23.870
161.133
1.00
25.64
A

ATOM
344
O
VAL
A
187
32.925
22.956
161.631
1.00
26.32
A

ATOM
345
N
ILE
A
188
33.320
25.163
161.325
1.00
25.47
A

ATOM
346
CA
ILE
A
188
32.245
25.663
162.186
1.00
25.33
A

ATOM
347
CB
ILE
A
188
32.421
27.197
162.416
1.00
25.89
A

ATOM
348
CG2
ILE
A
188
31.205
27.820
163.117
1.00
25.29
A

ATOM
349
CG1
ILE
A
188
33.682
27.431
163.254
1.00
26.99
A

ATOM
350
CD1
ILE
A
188
34.062
28.868
163.415
1.00
28.36
A

ATOM
351
C
ILE
A
188
30.843
25.308
161.668
1.00
25.57
A

ATOM
352
O
ILE
A
188
29.974
24.911
162.452
1.00
24.31
A

ATOM
353
N
ILE
A
189
30.649
25.418
160.353
1.00
25.77
A

ATOM
354
CA
ILE
A
189
29.370
25.099
159.708
1.00
26.71
A

ATOM
355
CB
ILE
A
189
29.313
25.675
158.244
1.00
27.02
A

ATOM
356
CG2
ILE
A
189
28.009
25.260
157.526
1.00
26.65
A

ATOM
357
CG1
ILE
A
189
29.386
27.209
158.291
1.00
25.94
A

ATOM
358
CD1
ILE
A
189
29.688
27.880
156.957
1.00
27.91
A

ATOM
359
C
ILE
A
189
29.115
23.580
159.730
1.00
27.66
A

ATOM
360
O
ILE
A
189
27.996
23.146
160.016
1.00
28.08
A

ATOM
361
N
ALA
A
190
30.175
22.795
159.510
1.00
28.63
A

ATOM
362
CA
ALA
A
190
30.106
21.328
159.494
1.00
29.95
A

ATOM
363
CB
ALA
A
190
31.395
20.745
158.928
1.00
30.58
A

ATOM
364
C
ALA
A
190
29.807
20.713
160.863
1.00
30.97
A

ATOM
365
O
ALA
A
190
29.134
19.683
160.953
1.00
31.74
A

ATOM
366
N
LYS
A
191
30.296
21.363
161.920
1.00
31.94
A

ATOM
367
CA
LYS
A
191
30.088
20.907
163.295
1.00
32.19
A

ATOM
368
CB
LYS
A
191
31.335
21.188
164.143
1.00
34.20
A

ATOM
369
CG
LYS
A
191
32.515
20.271
163.839
1.00
37.34
A

ATOM
370
CD
LYS
A
191
33.738
20.646
164.663
1.00
40.00
A

ATOM
371
CE
LYS
A
191
34.896
19.688
164.411
1.00
41.29
A

ATOM
372
NZ
LYS
A
191
36.125
20.078
165.167
1.00
42.38
A

ATOM
373
C
LYS
A
191
28.845
21.523
163.948
1.00
31.73
A

ATOM
374
O
LYS
A
191
28.551
21.239
165.115
1.00
31.84
A

ATOM
375
N
ASP
A
192
28.116
22.341
163.173
1.00
30.78
A

ATOM
376
CA
ASP
A
192
26.884
23.046
163.584
1.00
30.80
A

ATOM
377
CB
ASP
A
192
25.731
22.038
163.812
1.00
33.11
A

ATOM
378
CG
ASP
A
192
24.352
22.670
163.677
1.00
36.31
A

ATOM
379
OD1
ASP
A
192
23.725
22.955
164.719
1.00
39.17
A

ATOM
380
OD2
ASP
A
192
23.893
22.874
162.531
1.00
38.75
A

ATOM
381
C
ASP
A
192
27.126
23.952
164.811
1.00
29.85
A

ATOM
382
O
ASP
A
192
26.313
24.018
165.745
1.00
30.07
A

ATOM
383
N
GLU
A
193
28.267
24.643
164.781
1.00
27.44
A

ATOM
384
CA
GLU
A
193
28.694
25.538
165.858
1.00
25.61
A

ATOM
385
CB
GLU
A
193
30.135
25.197
166.272
1.00
26.55
A

ATOM
386
CG
GLU
A
193
30.288
23.902
167.071
1.00
27.57
A

ATOM
387
CD
GLU
A
193
29.638
23.968
168.446
1.00
29.06
A

ATOM
388
OE1
GLU
A
193
30.037
24.835
169.254
1.00
29.31
A

ATOM
389
OE2
GLU
A
193
28.728
23.152
168.713
1.00
29.35
A

ATOM
390
C
GLU
A
193
28.577
27.032
165.541
1.00
24.30
A

ATOM
391
O
GLU
A
193
29.275
27.858
166.141
1.00
23.23
A

ATOM
392
N
VAL
A
194
27.667
27.376
164.627
1.00
22.03
A

ATOM
393
CA
VAL
A
194
27.438
28.764
164.204
1.00
21.39
A

ATOM
394
CB
VAL
A
194
26.471
28.827
162.972
1.00
21.56
A

ATOM
395
CG1
VAL
A
194
26.205
30.276
162.532
1.00
22.36
A

ATOM
396
CG2
VAL
A
194
27.062
28.043
161.806
1.00
20.88
A

ATOM
397
C
VAL
A
194
26.924
29.656
165.343
1.00
19.90
A

ATOM
398
O
VAL
A
194
27.477
30.731
165.573
1.00
18.23
A

ATOM
399
N
ALA
A
195
25.932
29.160
166.087
1.00
20.46
A

ATOM
400
CA
ALA
A
195
25.311
29.881
167.206
1.00
19.76
A

ATOM
401
CB
ALA
A
195
24.161
29.060
167.784
1.00
22.18
A

ATOM
402
C
ALA
A
195
26.297
30.270
168.311
1.00
19.00
A

ATOM
403
O
ALA
A
195
26.265
31.397
168.804
1.00
18.06
A

ATOM
404
N
HIS
A
196
27.208
29.352
168.635
1.00
18.31
A

ATOM
405
CA
HIS
A
196
28.232
29.574
169.655
1.00
17.97
A

ATOM
406
CB
HIS
A
196
28.915
28.251
170.029
1.00
19.85
A

ATOM
407
CG
HIS
A
196
28.093
27.368
170.920
1.00
21.21
A

ATOM
408
CD2
HIS
A
196
27.071
27.647
171.765
1.00
22.11
A

ATOM
409
ND1
HIS
A
196
28.305
26.010
171.015
1.00
23.75
A

ATOM
410
CE1
HIS
A
196
27.450
25.490
171.878
1.00
23.78
A

ATOM
411
NE2
HIS
A
196
26.690
26.463
172.347
1.00
22.56
A

ATOM
412
C
HIS
A
196
29.279
30.608
169.226
1.00
16.92
A

ATOM
413
O
HIS
A
196
29.736
31.409
170.046
1.00
16.75
A

ATOM
414
N
THR
A
197
29.601
30.614
167.932
1.00
16.78
A

ATOM
415
CA
THR
A
197
30.578
31.541
167.353
1.00
16.32
A

ATOM
416
CB
THR
A
197
31.074
31.041
165.966
1.00
18.12
A

ATOM
417
OG1
THR
A
197
31.510
29.679
166.084
1.00
19.61
A

ATOM
418
CG2
THR
A
197
32.252
31.874
165.472
1.00
18.32
A

ATOM
419
C
THR
A
197
30.006
32.967
167.262
1.00
15.64
A

ATOM
420
O
THR
A
197
30.734
33.939
167.478
1.00
13.77
A

ATOM
421
N
VAL
A
198
28.701
33.075
166.985
1.00
15.52
A

ATOM
422
CA
VAL
A
198
28.006
34.372
166.908
1.00
16.32
A

ATOM
423
CB
VAL
A
198
26.556
34.239
166.307
1.00
16.75
A

ATOM
424
CG1
VAL
A
198
25.839
35.597
166.262
1.00
18.00
A

ATOM
425
CG2
VAL
A
198
26.614
33.669
164.904
1.00
18.78
A

ATOM
426
C
VAL
A
198
27.933
34.950
168.330
1.00
15.21
A

ATOM
427
O
VAL
A
198
28.151
36.145
168.527
1.00
14.31
A

ATOM
428
N
THR
A
199
27.704
34.075
169.314
1.00
14.72
A

ATOM
429
CA
THR
A
199
27.630
34.471
170.724
1.00
15.19
A

ATOM
430
CB
THR
A
199
27.100
33.314
171.614
1.00
16.75
A

ATOM
431
OG1
THR
A
199
25.810
32.914
171.141
1.00
20.05
A

ATOM
432
CG2
THR
A
199
26.974
33.741
173.077
1.00
15.91
A

ATOM
433
C
THR
A
199
29.003
34.953
171.204
1.00
13.44
A

ATOM
434
O
THR
A
199
29.086
35.970
171.889
1.00
13.34
A

ATOM
435
N
GLU
A
200
30.071
34.281
170.758
1.00
14.14
A

ATOM
436
CA
GLU
A
200
31.450
34.655
171.116
1.00
14.99
A

ATOM
437
CB
GLU
A
200
32.462
33.672
170.512
1.00
15.69
A

ATOM
438
CG
GLU
A
200
33.935
33.968
170.866
1.00
16.14
A

ATOM
439
CD
GLU
A
200
34.906
32.871
170.452
1.00
17.37
A

ATOM
440
OE1
GLU
A
200
34.503
31.916
169.748
1.00
19.02
A

ATOM
441
OE2
GLU
A
200
36.088
32.962
170.847
1.00
18.72
A

ATOM
442
C
GLU
A
200
31.742
36.074
170.630
1.00
15.64
A

ATOM
443
O
GLU
A
200
32.346
36.868
171.353
1.00
14.99
A

ATOM
444
N
SER
A
201
31.230
36.393
169.439
1.00
14.72
A

ATOM
445
CA
SER
A
201
31.393
37.714
168.836
1.00
17.30
A

ATOM
446
CB
SER
A
201
30.965
37.695
167.366
1.00
17.20
A

ATOM
447
OG
SER
A
201
31.340
38.901
166.721
1.00
19.79
A

ATOM
448
C
SER
A
201
30.589
38.763
169.586
1.00
15.73
A

ATOM
449
O
SER
A
201
31.126
39.807
169.948
1.00
16.20
A

ATOM
450
N
ARG
A
202
29.329
38.435
169.879
1.00
16.69
A

ATOM
451
CA
ARG
A
202
28.413
39.326
170.595
1.00
15.65
A

ATOM
452
CB
ARG
A
202
27.017
38.714
170.647
1.00
17.87
A

ATOM
453
CG
ARG
A
202
26.242
38.775
169.337
1.00
19.27
A

ATOM
454
CD
ARG
A
202
24.906
38.038
169.458
1.00
23.09
A

ATOM
455
NE
ARG
A
202
24.133
38.461
170.629
1.00
23.59
A

ATOM
456
CZ
ARG
A
202
23.279
39.484
170.666
1.00
25.15
A

ATOM
457
NH1
ARG
A
202
22.645
39.769
171.794
1.00
25.80
A

ATOM
458
NH2
ARG
A
202
23.048
40.217
169.586
1.00
26.28
A

ATOM
459
C
ARG
A
202
28.883
39.659
172.009
1.00
15.85
A

ATOM
460
O
ARG
A
202
28.764
40.804
172.445
1.00
15.35
A

ATOM
461
N
VAL
A
203
29.448
38.665
172.701
1.00
14.75
A

ATOM
462
CA
VAL
A
203
29.960
38.856
174.061
1.00
15.03
A

ATOM
463
CB
VAL
A
203
30.202
37.490
174.797
1.00
13.67
A

ATOM
464
CG1
VAL
A
203
30.819
37.705
176.183
1.00
13.44
A

ATOM
465
CG2
VAL
A
203
28.877
36.761
174.969
1.00
12.74
A

ATOM
466
C
VAL
A
203
31.225
39.723
174.015
1.00
15.83
A

ATOM
467
O
VAL
A
203
31.351
40.651
174.802
1.00
16.91
A

ATOM
468
N
LEU
A
204
32.100
39.478
173.037
1.00
16.93
A

ATOM
469
CA
LEU
A
204
33.333
40.261
172.874
1.00
17.63
A

ATOM
470
CB
LEU
A
204
34.250
39.622
171.825
1.00
17.49
A

ATOM
471
CG
LEU
A
204
35.279
38.588
172.296
1.00
16.87
A

ATOM
472
CD1
LEU
A
204
35.779
37.765
171.125
1.00
16.98
A

ATOM
473
CD2
LEU
A
204
36.441
39.277
173.012
1.00
18.10
A

ATOM
474
C
LEU
A
204
33.055
41.726
172.507
1.00
19.08
A

ATOM
475
O
LEU
A
204
33.753
42.625
172.977
1.00
20.76
A

ATOM
476
N
GLN
A
205
31.985
41.950
171.741
1.00
20.36
A

ATOM
477
CA
GLN
A
205
31.571
43.289
171.301
1.00
23.06
A

ATOM
478
CB
GLN
A
205
30.597
43.197
170.120
1.00
22.83
A

ATOM
479
CG
GLN
A
205
31.162
42.674
168.821
1.00
23.09
A

ATOM
480
CD
GLN
A
205
30.102
42.558
167.739
1.00
24.54
A

ATOM
481
OE1
GLN
A
205
29.446
43.541
167.386
1.00
25.94
A

ATOM
482
NE2
GLN
A
205
29.927
41.356
167.209
1.00
24.19
A

ATOM
483
C
GLN
A
205
30.873
44.114
172.383
1.00
23.68
A

ATOM
484
O
GLN
A
205
31.144
45.309
172.532
1.00
25.54
A

ATOM
485
N
ASN
A
206
29.976
43.463
173.123
1.00
24.00
A

ATOM
486
CA
ASN
A
206
29.167
44.117
174.151
1.00
24.37
A

ATOM
487
CB
ASN
A
206
27.723
43.603
174.068
1.00
25.24
A

ATOM
488
CG
ASN
A
206
27.047
43.979
172.761
1.00
26.73
A

ATOM
489
OD1
ASN
A
206
26.544
45.092
172.608
1.00
27.81
A

ATOM
490
ND2
ASN
A
206
27.054
43.058
171.804
1.00
25.36
A

ATOM
491
C
ASN
A
206
29.643
44.134
175.604
1.00
24.23
A

ATOM
492
O
ASN
A
206
28.905
44.593
176.485
1.00
25.66
A

ATOM
493
N
THR
A
207
30.851
43.635
175.867
1.00
22.36
A

ATOM
494
CA
THR
A
207
31.385
43.649
177.231
1.00
20.05
A

ATOM
495
CB
THR
A
207
31.894
42.264
177.710
1.00
19.98
A

ATOM
496
OG1
THR
A
207
32.833
41.725
176.772
1.00
18.18
A

ATOM
497
CG2
THR
A
207
30.729
41.296
177.923
1.00
19.16
A

ATOM
498
C
THR
A
207
32.497
44.672
177.415
1.00
19.67
A

ATOM
499
O
THR
A
207
33.321
44.881
176.521
1.00
19.51
A

ATOM
500
N
ARG
A
208
32.497
45.306
178.585
1.00
19.92
A

ATOM
501
CA
ARG
A
208
33.489
46.311
178.945
1.00
20.83
A

ATOM
502
CB
ARG
A
208
32.966
47.721
178.614
1.00
24.67
A

ATOM
503
CG
ARG
A
208
34.001
48.651
177.973
1.00
28.29
A

ATOM
504
CD
ARG
A
208
34.286
48.295
176.510
1.00
31.05
A

ATOM
505
NE
ARG
A
208
33.255
48.783
175.589
1.00
32.75
A

ATOM
506
CZ
ARG
A
208
32.748
48.089
174.569
1.00
33.94
A

ATOM
507
NH1
ARG
A
208
33.157
46.849
174.317
1.00
33.38
A

ATOM
508
NH2
ARG
A
208
31.851
48.652
173.770
1.00
34.03
A

ATOM
509
C
ARG
A
208
33.794
46.167
180.439
1.00
19.33
A

ATOM
510
O
ARG
A
208
33.010
46.589
181.292
1.00
19.36
A

ATOM
511
N
HIS
A
209
34.923
45.525
180.738
1.00
17.75
A

ATOM
512
CA
HIS
A
209
35.372
45.283
182.112
1.00
15.71
A

ATOM
513
CB
HIS
A
209
34.744
43.975
182.634
1.00
13.97
A

ATOM
514
CG
HIS
A
209
34.881
43.768
184.113
1.00
14.51
A

ATOM
515
CD2
HIS
A
209
35.808
43.099
184.838
1.00
13.07
A

ATOM
516
ND1
HIS
A
209
33.986
44.286
185.023
1.00
13.80
A

ATOM
517
CE1
HIS
A
209
34.356
43.945
186.244
1.00
13.80
A

ATOM
518
NE2
HIS
A
209
35.458
43.225
186.160
1.00
15.21
A

ATOM
519
C
HIS
A
209
36.903
45.167
182.096
1.00
15.32
A

ATOM
520
O
HIS
A
209
37.466
44.597
181.159
1.00
14.32
A

ATOM
521
N
PRO
A
210
37.597
45.700
183.133
1.00
14.63
A

ATOM
522
CD
PRO
A
210
37.135
46.571
184.232
1.00
15.85
A

ATOM
523
CA
PRO
A
210
39.063
45.611
183.164
1.00
14.76
A

ATOM
524
CB
PRO
A
210
39.427
46.386
184.434
1.00
15.04
A

ATOM
525
CG
PRO
A
210
38.190
46.335
185.263
1.00
14.72
A

ATOM
526
C
PRO
A
210
39.679
44.206
183.164
1.00
12.44
A

ATOM
527
O
PRO
A
210
40.830
44.046
182.768
1.00
13.93
A

ATOM
528
N
PHE
A
211
38.915
43.199
183.597
1.00
11.98
A

ATOM
529
CA
PHE
A
211
39.423
41.826
183.649
1.00
11.07
A

ATOM
530
CB
PHE
A
211
39.250
41.226
185.056
1.00
10.17
A

ATOM
531
CG
PHE
A
211
39.810
42.097
186.148
1.00
10.42
A

ATOM
532
CD1
PHE
A
211
41.098
42.665
186.024
1.00
10.66
A

ATOM
533
CD2
PHE
A
211
39.013
42.455
187.247
1.00
11.11
A

ATOM
534
CE1
PHE
A
211
41.580
43.593
186.972
1.00
13.04
A

ATOM
535
CE2
PHE
A
211
39.482
43.380
188.210
1.00
10.99
A

ATOM
536
CZ
PHE
A
211
40.770
43.953
188.068
1.00
11.66
A

ATOM
537
C
PHE
A
211
38.922
40.892
182.558
1.00
10.95
A

ATOM
538
O
PHE
A
211
39.043
39.670
182.663
1.00
11.34
A

ATOM
539
N
LEU
A
212
38.344
41.483
181.515
1.00
10.29
A

ATOM
540
CA
LEU
A
212
37.868
40.733
180.359
1.00
10.76
A

ATOM
541
CB
LEU
A
212
36.357
40.910
180.141
1.00
11.36
A

ATOM
542
CG
LEU
A
212
35.335
40.364
181.145
1.00
12.18
A

ATOM
543
CD1
LEU
A
212
33.963
40.658
180.631
1.00
12.06
A

ATOM
544
CD2
LEU
A
212
35.481
38.879
181.377
1.00
12.41
A

ATOM
545
C
LEU
A
212
38.618
41.292
179.163
1.00
11.97
A

ATOM
546
O
LEU
A
212
38.778
42.514
179.040
1.00
12.62
A

ATOM
547
N
THR
A
213
39.090
40.394
178.298
1.00
11.57
A

ATOM
548
CA
THR
A
213
39.811
40.763
177.082
1.00
12.05
A

ATOM
549
CB
THR
A
213
40.289
39.491
176.332
1.00
13.16
A

ATOM
550
OG1
THR
A
213
41.159
38.743
177.188
1.00
13.29
A

ATOM
551
CG2
THR
A
213
41.043
39.832
175.066
1.00
13.95
A

ATOM
552
C
THR
A
213
38.880
41.601
176.196
1.00
11.62
A

ATOM
553
O
THR
A
213
37.741
41.209
175.940
1.00
12.81
A

ATOM
554
N
ALA
A
214
39.348
42.797
175.841
1.00
13.78
A

ATOM
555
CA
ALA
A
214
38.590
43.724
175.004
1.00
15.27
A

ATOM
556
CB
ALA
A
214
38.952
45.164
175.345
1.00
16.32
A

ATOM
557
C
ALA
A
214
38.832
43.456
173.525
1.00
15.97
A

ATOM
558
O
ALA
A
214
39.939
43.082
173.127
1.00
15.74
A

ATOM
559
N
LEU
A
215
37.783
43.643
172.727
1.00
15.59
A

ATOM
560
CA
LEU
A
215
37.845
43.438
171.284
1.00
16.64
A

ATOM
561
CB
LEU
A
215
36.554
42.775
170.787
1.00
16.49
A

ATOM
562
CG
LEU
A
215
36.474
42.292
169.329
1.00
16.97
A

ATOM
563
CD1
LEU
A
215
37.284
41.017
169.148
1.00
15.18
A

ATOM
564
CD2
LEU
A
215
35.032
42.040
168.954
1.00
17.56
A

ATOM
565
C
LEU
A
215
38.042
44.769
170.566
1.00
16.85
A

ATOM
566
O
LEU
A
215
37.384
45.762
170.883
1.00
18.00
A

ATOM
567
N
LYS
A
216
38.967
44.780
169.611
1.00
17.92
A

ATOM
568
CA
LYS
A
216
39.248
45.969
168.816
1.00
19.21
A

ATOM
569
CB
LYS
A
216
40.758
46.093
168.545
1.00
20.77
A

ATOM
570
CG
LYS
A
216
41.204
47.365
167.805
1.00
24.04
A

ATOM
571
CD
LYS
A
216
40.977
48.646
168.600
1.00
28.27
A

ATOM
572
CE
LYS
A
216
41.317
49.872
167.762
1.00
30.49
A

ATOM
573
NZ
LYS
A
216
40.984
51.133
168.484
1.00
34.56
A

ATOM
574
C
LYS
A
216
38.447
45.856
167.518
1.00
19.24
A

ATOM
575
O
LYS
A
216
37.678
46.759
167.180
1.00
20.53
A

ATOM
576
N
TYR
A
217
38.638
44.750
166.796
1.00
19.17
A

ATOM
577
CA
TYR
A
217
37.932
44.498
165.537
1.00
20.98
A

ATOM
578
CB
TYR
A
217
38.835
44.717
164.306
1.00
21.08
A

ATOM
579
CG
TYR
A
217
39.583
46.026
164.212
1.00
22.21
A

ATOM
580
CD1
TYR
A
217
38.897
47.258
164.131
1.00
22.98
A

ATOM
581
CE1
TYR
A
217
39.601
48.484
164.005
1.00
25.26
A

ATOM
582
CD2
TYR
A
217
40.992
46.040
164.166
1.00
23.39
A

ATOM
583
CE2
TYR
A
217
41.710
47.258
164.038
1.00
25.07
A

ATOM
584
CZ
TYR
A
217
41.005
48.472
163.959
1.00
24.80
A

ATOM
585
OH
TYR
A
217
41.691
49.656
163.845
1.00
26.66
A

ATOM
586
C
TYR
A
217
37.424
43.065
165.441
1.00
21.24
A

ATOM
587
O
TYR
A
217
38.001
42.140
166.012
1.00
21.28
A

ATOM
588
N
ALA
A
218
36.329
42.906
164.709
1.00
21.97
A

ATOM
589
CA
ALA
A
218
35.730
41.610
164.427
1.00
22.98
A

ATOM
590
CB
ALA
A
218
34.458
41.393
165.240
1.00
22.40
A

ATOM
591
C
ALA
A
218
35.405
41.712
162.946
1.00
23.21
A

ATOM
592
O
ALA
A
218
34.700
42.628
162.537
1.00
23.57
A

ATOM
593
N
PHE
A
219
36.026
40.860
162.135
1.00
24.15
A

ATOM
594
CA
PHE
A
219
35.778
40.867
160.695
1.00
24.49
A

ATOM
595
CB
PHE
A
219
36.751
41.821
159.947
1.00
24.79
A

ATOM
596
CG
PHE
A
219
38.203
41.375
159.928
1.00
23.54
A

ATOM
597
CD1
PHE
A
219
39.064
41.680
161.000
1.00
23.92
A

ATOM
598
CD2
PHE
A
219
38.725
40.681
158.814
1.00
24.61
A

ATOM
599
CE1
PHE
A
219
40.438
41.299
160.964
1.00
22.90
A

ATOM
600
CE2
PHE
A
219
40.090
40.292
158.762
1.00
23.27
A

ATOM
601
CZ
PHE
A
219
40.950
40.604
159.842
1.00
22.95
A

ATOM
602
C
PHE
A
219
35.797
39.463
160.113
1.00
25.30
A

ATOM
603
O
PHE
A
219
36.140
38.499
160.803
1.00
24.04
A

ATOM
604
N
GLN
A
220
35.426
39.361
158.840
1.00
25.71
A

ATOM
605
CA
GLN
A
220
35.403
38.085
158.142
1.00
28.27
A

ATOM
606
CB
GLN
A
220
34.011
37.437
158.228
1.00
27.42
A

ATOM
607
CG
GLN
A
220
32.856
38.245
157.636
1.00
27.25
A

ATOM
608
CD
GLN
A
220
31.509
37.614
157.907
1.00
26.81
A

ATOM
609
OE1
GLN
A
220
31.233
36.495
157.475
1.00
25.70
A

ATOM
610
NE2
GLN
A
220
30.659
38.331
158.633
1.00
28.24
A

ATOM
611
C
GLN
A
220
35.841
38.211
156.690
1.00
30.28
A

ATOM
612
O
GLN
A
220
35.776
39.292
156.098
1.00
30.47
A

ATOM
613
N
THR
A
221
36.359
37.105
156.161
1.00
32.45
A

ATOM
614
CA
THR
A
221
36.799
37.008
154.772
1.00
34.77
A

ATOM
615
CB
THR
A
221
38.307
36.634
154.660
1.00
34.88
A

ATOM
616
OG1
THR
A
221
38.574
35.454
155.425
1.00
34.21
A

ATOM
617
CG2
THR
A
221
39.198
37.779
155.140
1.00
34.18
A

ATOM
618
C
THR
A
221
35.920
35.932
154.121
1.00
36.77
A

ATOM
619
O
THR
A
221
34.880
35.565
154.680
1.00
37.62
A

ATOM
620
N
HIS
A
222
36.343
35.410
152.970
1.00
38.37
A

ATOM
621
CA
HIS
A
222
35.589
34.383
152.242
1.00
39.93
A

ATOM
622
CB
HIS
A
222
36.071
34.305
150.788
1.00
42.29
A

ATOM
623
CG
HIS
A
222
35.834
35.559
150.004
1.00
44.96
A

ATOM
624
CD2
HIS
A
222
36.684
36.348
149.304
1.00
46.37
A

ATOM
625
ND1
HIS
A
222
34.588
36.137
149.881
1.00
45.74
A

ATOM
626
CE1
HIS
A
222
34.681
37.227
149.140
1.00
47.02
A

ATOM
627
NE2
HIS
A
222
35.943
37.378
148.777
1.00
47.37
A

ATOM
628
C
HIS
A
222
35.600
32.987
152.875
1.00
39.47
A

ATOM
629
O
HIS
A
222
34.708
32.177
152.605
1.00
41.05
A

ATOM
630
N
ASP
A
223
36.581
32.726
153.741
1.00
37.88
A

ATOM
631
CA
ASP
A
223
36.710
31.425
154.403
1.00
36.41
A

ATOM
632
CB
ASP
A
223
37.702
30.530
153.628
1.00
38.42
A

ATOM
633
CG
ASP
A
223
39.125
31.093
153.601
1.00
41.14
A

ATOM
634
OD1
ASP
A
223
39.302
32.292
153.290
1.00
43.06
A

ATOM
635
OD2
ASP
A
223
40.067
30.327
153.899
1.00
42.28
A

ATOM
636
C
ASP
A
223
37.098
31.474
155.888
1.00
34.14
A

ATOM
637
O
ASP
A
223
37.108
30.436
156.560
1.00
33.12
A

ATOM
638
N
ARG
A
224
37.426
32.665
156.393
1.00
31.65
A

ATOM
639
CA
ARG
A
224
37.845
32.828
157.792
1.00
29.25
A

ATOM
640
CB
ARG
A
224
39.353
33.133
157.862
1.00
31.08
A

ATOM
641
CG
ARG
A
224
40.268
31.957
157.497
1.00
35.01
A

ATOM
642
CD
ARG
A
224
41.699
32.401
157.243
1.00
38.26
A

ATOM
643
NE
ARG
A
224
42.568
31.285
156.869
1.00
41.99
A

ATOM
644
CZ
ARG
A
224
43.894
31.274
157.001
1.00
43.44
A

ATOM
645
NH1
ARG
A
224
44.537
32.324
157.504
1.00
44.06
A

ATOM
646
NH2
ARG
A
224
44.585
30.204
156.628
1.00
44.49
A

ATOM
647
C
ARG
A
224
37.073
33.872
158.605
1.00
27.60
A

ATOM
648
O
ARG
A
224
36.478
34.798
158.051
1.00
25.75
A

ATOM
649
N
LEU
A
225
37.047
33.659
159.924
1.00
24.26
A

ATOM
650
CA
LEU
A
225
36.403
34.551
160.897
1.00
21.38
A

ATOM
651
CB
LEU
A
225
35.360
33.801
161.733
1.00
21.18
A

ATOM
652
CG
LEU
A
225
34.088
33.324
161.040
1.00
21.51
A

ATOM
653
CD1
LEU
A
225
33.358
32.344
161.918
1.00
22.54
A

ATOM
654
CD2
LEU
A
225
33.212
34.501
160.686
1.00
21.44
A

ATOM
655
C
LEU
A
225
37.523
35.027
161.808
1.00
20.15
A

ATOM
656
O
LEU
A
225
38.254
34.205
162.367
1.00
20.04
A

ATOM
657
N
CYS
A
226
37.644
36.343
161.974
1.00
19.07
A

ATOM
658
CA
CYS
A
226
38.716
36.905
162.790
1.00
19.51
A

ATOM
659
CB
CYS
A
226
39.722
37.632
161.896
1.00
19.55
A

ATOM
660
SG
CYS
A
226
40.281
36.700
160.448
1.00
23.57
A

ATOM
661
C
CYS
A
226
38.306
37.828
163.929
1.00
18.57
A

ATOM
662
O
CYS
A
226
37.440
38.692
163.772
1.00
18.39
A

ATOM
663
N
PHE
A
227
38.958
37.627
165.074
1.00
17.25
A

ATOM
664
CA
PHE
A
227
38.752
38.423
166.283
1.00
16.14
A

ATOM
665
CB
PHE
A
227
38.369
37.541
167.480
1.00
17.32
A

ATOM
666
CG
PHE
A
227
37.025
36.905
167.380
1.00
17.71
A

ATOM
667
CD1
PHE
A
227
36.894
35.513
167.524
1.00
17.96
A

ATOM
668
CD2
PHE
A
227
35.873
37.685
167.186
1.00
18.00
A

ATOM
669
CE1
PHE
A
227
35.621
34.892
167.483
1.00
19.19
A

ATOM
670
CE2
PHE
A
227
34.605
37.084
167.144
1.00
19.33
A

ATOM
671
CZ
PHE
A
227
34.472
35.680
167.295
1.00
18.55
A

ATOM
672
C
PHE
A
227
40.074
39.090
166.627
1.00
15.62
A

ATOM
673
O
PHE
A
227
41.033
38.405
166.973
1.00
15.83
A

ATOM
674
N
VAL
A
228
40.127
40.415
166.533
1.00
15.49
A

ATOM
675
CA
VAL
A
228
41.340
41.165
166.863
1.00
15.30
A

ATOM
676
CB
VAL
A
228
41.592
42.323
165.850
1.00
15.49
A

ATOM
677
CG1
VAL
A
228
42.885
43.040
166.151
1.00
14.57
A

ATOM
678
CG2
VAL
A
228
41.640
41.785
164.435
1.00
18.30
A

ATOM
679
C
VAL
A
228
41.131
41.670
168.294
1.00
14.86
A

ATOM
680
O
VAL
A
228
40.414
42.644
168.538
1.00
14.24
A

ATOM
681
N
MET
A
229
41.705
40.927
169.236
1.00
15.11
A

ATOM
682
CA
MET
A
229
41.594
41.212
170.666
1.00
15.13
A

ATOM
683
CB
MET
A
229
41.430
39.902
171.437
1.00
14.74
A

ATOM
684
CG
MET
A
229
40.387
38.940
170.934
1.00
17.80
A

ATOM
685
SD
MET
A
229
40.569
37.400
171.834
1.00
19.60
A

ATOM
686
CE
MET
A
229
41.938
36.649
170.952
1.00
16.89
A

ATOM
687
C
MET
A
229
42.846
41.873
171.212
1.00
15.65
A

ATOM
688
O
MET
A
229
43.904
41.805
170.589
1.00
16.17
A

ATOM
689
N
GLU
A
230
42.740
42.450
172.413
1.00
15.75
A

ATOM
690
CA
GLU
A
230
43.900
43.052
173.067
1.00
17.42
A

ATOM
691
CB
GLU
A
230
43.504
43.950
174.256
1.00
20.56
A

ATOM
692
CG
GLU
A
230
42.870
43.263
175.453
1.00
24.89
A

ATOM
693
CD
GLU
A
230
42.589
44.204
176.615
1.00
26.43
A

ATOM
694
OE1
GLU
A
230
43.444
45.060
176.940
1.00
29.81
A

ATOM
695
OE2
GLU
A
230
41.510
44.069
177.224
1.00
22.46
A

ATOM
696
C
GLU
A
230
44.825
41.896
173.489
1.00
16.10
A

ATOM
697
O
GLU
A
230
44.360
40.816
173.891
1.00
15.53
A

ATOM
698
N
TYR
A
231
46.116
42.099
173.269
1.00
14.61
A

ATOM
699
CA
TYR
A
231
47.143
41.109
173.562
1.00
14.63
A

ATOM
700
CB
TYR
A
231
48.372
41.399
172.679
1.00
15.21
A

ATOM
701
CG
TYR
A
231
49.619
40.562
172.903
1.00
15.22
A

ATOM
702
CD1
TYR
A
231
49.560
39.151
172.979
1.00
15.64
A

ATOM
703
CE1
TYR
A
231
50.734
38.378
173.188
1.00
17.96
A

ATOM
704
CD2
TYR
A
231
50.877
41.182
173.033
1.00
15.49
A

ATOM
705
CE2
TYR
A
231
52.060
40.415
173.236
1.00
16.52
A

ATOM
706
CZ
TYR
A
231
51.976
39.020
173.314
1.00
16.37
A

ATOM
707
OH
TYR
A
231
53.110
38.274
173.527
1.00
18.34
A

ATOM
708
C
TYR
A
231
47.515
41.041
175.042
1.00
14.32
A

ATOM
709
O
TYR
A
231
47.859
42.051
175.657
1.00
15.12
A

ATOM
710
N
ALA
A
232
47.433
39.829
175.592
1.00
13.08
A

ATOM
711
CA
ALA
A
232
47.788
39.572
176.982
1.00
12.20
A

ATOM
712
CB
ALA
A
232
46.844
38.556
177.582
1.00
11.96
A

ATOM
713
C
ALA
A
232
49.237
39.067
177.007
1.00
13.00
A

ATOM
714
O
ALA
A
232
49.496
37.863
176.882
1.00
11.98
A

ATOM
715
N
ASN
A
233
50.163
40.018
177.172
1.00
12.50
A

ATOM
716
CA
ASN
A
233
51.619
39.793
177.193
1.00
14.35
A

ATOM
717
CB
ASN
A
233
52.365
41.114
177.438
1.00
14.72
A

ATOM
718
CG
ASN
A
233
52.082
42.164
176.387
1.00
18.13
A

ATOM
719
OD1
ASN
A
233
52.952
42.495
175.577
1.00
18.88
A

ATOM
720
ND2
ASN
A
233
50.868
42.705
176.398
1.00
17.15
A

ATOM
721
C
ASN
A
233
52.124
38.794
178.225
1.00
12.73
A

ATOM
722
O
ASN
A
233
53.154
38.139
178.019
1.00
13.87
A

ATOM
723
N
GLY
A
234
51.392
38.695
179.332
1.00
12.52
A

ATOM
724
CA
GLY
A
234
51.768
37.812
180.420
1.00
11.86
A

ATOM
725
C
GLY
A
234
51.504
36.332
180.298
1.00
11.18
A

ATOM
726
O
GLY
A
234
51.895
35.584
181.188
1.00
12.45
A

ATOM
727
N
GLY
A
235
50.850
35.902
179.221
1.00
11.65
A

ATOM
728
CA
GLY
A
235
50.576
34.484
179.034
1.00
12.03
A

ATOM
729
C
GLY
A
235
49.470
33.931
179.914
1.00
11.49
A

ATOM
730
O
GLY
A
235
48.814
34.674
180.647
1.00
12.06
A

ATOM
731
N
GLU
A
236
49.279
32.616
179.840
1.00
10.95
A

ATOM
732
CA
GLU
A
236
48.244
31.914
180.598
1.00
10.55
A

ATOM
733
CB
GLU
A
236
48.008
30.521
180.019
1.00
11.33
A

ATOM
734
CG
GLU
A
236
47.733
30.443
178.540
1.00
12.01
A

ATOM
735
CD
GLU
A
236
47.744
29.013
178.016
1.00
13.60
A

ATOM
736
OE1
GLU
A
236
48.240
28.101
178.715
1.00
13.29
A

ATOM
737
OE2
GLU
A
236
47.244
28.792
176.898
1.00
13.08
A

ATOM
738
C
GLU
A
236
48.638
31.718
182.046
1.00
9.40
A

ATOM
739
O
GLU
A
236
49.820
31.612
182.367
1.00
9.30
A

ATOM
740
N
LEU
A
237
47.631
31.581
182.908
1.00
10.59
A

ATOM
741
CA
LEU
A
237
47.860
31.324
184.326
1.00
12.01
A

ATOM
742
CB
LEU
A
237
46.546
31.464
185.102
1.00
13.34
A

ATOM
743
CG
LEU
A
237
46.561
32.014
186.534
1.00
17.84
A

ATOM
744
CD1
LEU
A
237
47.318
33.336
186.615
1.00
17.25
A

ATOM
745
CD2
LEU
A
237
45.121
32.199
187.007
1.00
14.63
A

ATOM
746
C
LEU
A
237
48.421
29.897
184.417
1.00
10.85
A

ATOM
747
O
LEU
A
237
49.205
29.584
185.310
1.00
11.83
A

ATOM
748
N
PHE
A
238
48.093
29.092
183.399
1.00
10.15
A

ATOM
749
CA
PHE
A
238
48.553
27.706
183.250
1.00
10.40
A

ATOM
750
CB
PHE
A
238
47.860
27.054
182.035
1.00
11.19
A

ATOM
751
CG
PHE
A
238
48.218
25.600
181.811
1.00
15.22
A

ATOM
752
CD1
PHE
A
238
48.063
24.641
182.836
1.00
17.28
A

ATOM
753
CD2
PHE
A
238
48.736
25.188
180.569
1.00
15.71
A

ATOM
754
CE1
PHE
A
238
48.428
23.283
182.624
1.00
17.50
A

ATOM
755
CE2
PHE
A
238
49.103
23.834
180.340
1.00
17.73
A

ATOM
756
CZ
PHE
A
238
48.949
22.880
181.373
1.00
17.04
A

ATOM
757
C
PHE
A
238
50.076
27.643
183.100
1.00
10.74
A

ATOM
758
O
PHE
A
238
50.711
26.766
183.685
1.00
10.07
A

ATOM
759
N
PHE
A
239
50.652
28.589
182.353
1.00
9.77
A

ATOM
760
CA
PHE
A
239
52.104
28.647
182.147
1.00
10.45
A

ATOM
761
CB
PHE
A
239
52.469
29.757
181.134
1.00
11.60
A

ATOM
762
CG
PHE
A
239
53.926
29.757
180.719
1.00
12.43
A

ATOM
763
CD1
PHE
A
239
54.367
28.925
179.673
1.00
12.74
A

ATOM
764
CD2
PHE
A
239
54.877
30.545
181.410
1.00
10.98
A

ATOM
765
CE1
PHE
A
239
55.745
28.866
179.315
1.00
16.02
A

ATOM
766
CE2
PHE
A
239
56.259
30.496
181.068
1.00
14.21
A

ATOM
767
CZ
PHE
A
239
56.691
29.654
180.019
1.00
14.99
A

ATOM
768
C
PHE
A
239
52.824
28.899
183.475
1.00
10.20
A

ATOM
769
O
PHE
A
239
53.789
28.202
183.810
1.00
9.58
A

ATOM
770
N
HIS
A
240
52.329
29.888
184.219
1.00
9.88
A

ATOM
771
CA
HIS
A
240
52.901
30.290
185.503
1.00
11.98
A

ATOM
772
CB
HIS
A
240
52.319
31.632
185.944
1.00
12.15
A

ATOM
773
CG
HIS
A
240
52.584
32.736
184.974
1.00
12.41
A

ATOM
774
CD2
HIS
A
240
51.770
33.362
184.094
1.00
12.25
A

ATOM
775
ND1
HIS
A
240
53.836
33.282
184.796
1.00
12.84
A

ATOM
776
CE1
HIS
A
240
53.780
34.196
183.844
1.00
13.59
A

ATOM
777
NE2
HIS
A
240
52.539
34.264
183.402
1.00
12.96
A

ATOM
778
C
HIS
A
240
52.751
29.254
186.599
1.00
11.94
A

ATOM
779
O
HIS
A
240
53.708
28.989
187.327
1.00
13.30
A

ATOM
780
N
LEU
A
241
51.571
28.634
186.676
1.00
13.96
A

ATOM
781
CA
LEU
A
241
51.308
27.608
187.681
1.00
12.92
A

ATOM
782
CB
LEU
A
241
49.805
27.335
187.818
1.00
14.05
A

ATOM
783
CG
LEU
A
241
49.351
26.532
189.043
1.00
13.77
A

ATOM
784
CD1
LEU
A
241
49.746
27.213
190.344
1.00
14.38
A

ATOM
785
CD2
LEU
A
241
47.874
26.374
188.981
1.00
13.17
A

ATOM
786
C
LEU
A
241
52.080
26.318
187.414
1.00
14.44
A

ATOM
787
O
LEU
A
241
52.565
25.698
188.356
1.00
14.08
A

ATOM
788
N
SER
A
242
52.242
25.956
186.138
1.00
13.96
A

ATOM
789
CA
SER
A
242
52.996
24.756
185.753
1.00
15.59
A

ATOM
790
CB
SER
A
242
52.880
24.489
184.249
1.00
16.20
A

ATOM
791
OG
SER
A
242
51.543
24.187
183.880
1.00
18.65
A

ATOM
792
C
SER
A
242
54.472
24.907
186.131
1.00
16.05
A

ATOM
793
O
SER
A
242
55.104
23.946
186.561
1.00
17.31
A

ATOM
794
N
ARG
A
243
54.980
26.137
186.017
1.00
14.31
A

ATOM
795
CA
ARG
A
243
56.369
26.481
186.344
1.00
14.86
A

ATOM
796
CB
ARG
A
243
56.729
27.836
185.700
1.00
15.08
A

ATOM
797
CG
ARG
A
243
58.152
28.360
185.968
1.00
16.55
A

ATOM
798
CD
ARG
A
243
58.311
29.821
185.540
1.00
17.96
A

ATOM
799
NE
ARG
A
243
57.546
30.745
186.384
1.00
21.78
A

ATOM
800
CZ
ARG
A
243
56.771
31.731
185.929
1.00
22.92
A

ATOM
801
NH1
ARG
A
243
56.638
31.947
184.626
1.00
23.68
A

ATOM
802
NH2
ARG
A
243
56.112
32.501
186.785
1.00
24.74
A

ATOM
803
C
ARG
A
243
56.608
26.545
187.860
1.00
14.72
A

ATOM
804
O
ARG
A
243
57.531
25.907
188.378
1.00
14.26
A

ATOM
805
N
GLU
A
244
55.755
27.296
188.556
1.00
12.67
A

ATOM
806
CA
GLU
A
244
55.861
27.497
190.002
1.00
13.25
A

ATOM
807
CB
GLU
A
244
55.263
28.853
190.383
1.00
15.29
A

ATOM
808
CG
GLU
A
244
55.997
30.046
189.774
1.00
20.11
A

ATOM
809
CD
GLU
A
244
55.456
31.381
190.245
1.00
22.00
A

ATOM
810
OE1
GLU
A
244
55.241
31.553
191.465
1.00
25.13
A

ATOM
811
OE2
GLU
A
244
55.258
32.273
189.395
1.00
26.82
A

ATOM
812
C
GLU
A
244
55.262
26.403
190.889
1.00
12.35
A

ATOM
813
O
GLU
A
244
55.461
26.426
192.106
1.00
12.06
A

ATOM
814
N
ARG
A
245
54.592
25.424
190.263
1.00
12.65
A

ATOM
815
CA
ARG
A
245
53.913
24.267
190.905
1.00
12.33
A

ATOM
816
CB
ARG
A
245
54.856
23.388
191.767
1.00
15.96
A

ATOM
817
CG
ARG
A
245
56.232
23.022
191.185
1.00
17.57
A

ATOM
818
CD
ARG
A
245
56.190
22.359
189.828
1.00
19.78
A

ATOM
819
NE
ARG
A
245
57.537
21.940
189.445
1.00
21.49
A

ATOM
820
CZ
ARG
A
245
58.108
22.172
188.266
1.00
22.07
A

ATOM
821
NH1
ARG
A
245
57.464
22.834
187.314
1.00
21.19
A

ATOM
822
NH2
ARG
A
245
59.326
21.705
188.031
1.00
23.54
A

ATOM
823
C
ARG
A
245
52.689
24.634
191.750
1.00
12.77
A

ATOM
824
O
ARG
A
245
51.650
23.970
191.667
1.00
11.62
A

ATOM
825
N
VAL
A
246
52.830
25.678
192.566
1.00
10.78
A

ATOM
826
CA
VAL
A
246
51.777
26.148
193.467
1.00
11.80
A

ATOM
827
CB
VAL
A
246
51.771
25.295
194.799
1.00
12.61
A

ATOM
828
CG1
VAL
A
246
53.016
25.563
195.654
1.00
12.86
A

ATOM
829
CG2
VAL
A
246
50.494
25.503
195.587
1.00
12.03
A

ATOM
830
C
VAL
A
246
51.968
27.641
193.774
1.00
11.54
A

ATOM
831
O
VAL
A
246
53.090
28.150
193.727
1.00
11.04
A

ATOM
832
N
PHE
A
247
50.862
28.337
194.046
1.00
11.44
A

ATOM
833
CA
PHE
A
247
50.897
29.758
194.394
1.00
11.43
A

ATOM
834
CB
PHE
A
247
49.806
30.559
193.654
1.00
10.98
A

ATOM
835
CG
PHE
A
247
50.010
30.702
192.162
1.00
10.69
A

ATOM
836
CD1
PHE
A
247
51.282
30.578
191.558
1.00
9.91
A

ATOM
837
CD2
PHE
A
247
48.903
31.004
191.345
1.00
10.05
A

ATOM
838
CE1
PHE
A
247
51.448
30.757
190.152
1.00
10.67
A

ATOM
839
CE2
PHE
A
247
49.047
31.184
189.940
1.00
10.23
A

ATOM
840
CZ
PHE
A
247
50.325
31.061
189.343
1.00
9.00
A

ATOM
841
C
PHE
A
247
50.600
29.876
195.880
1.00
11.50
A

ATOM
842
O
PHE
A
247
49.991
28.978
196.473
1.00
11.11
A

ATOM
843
N
THR
A
248
51.008
30.998
196.477
1.00
12.66
A

ATOM
844
CA
THR
A
248
50.719
31.261
197.888
1.00
12.42
A

ATOM
845
CB
THR
A
248
51.525
32.465
198.439
1.00
12.30
A

ATOM
846
OG1
THR
A
248
51.186
33.650
197.709
1.00
13.52
A

ATOM
847
CG2
THR
A
248
53.025
32.209
198.329
1.00
14.93
A

ATOM
848
C
THR
A
248
49.229
31.607
197.950
1.00
12.03
A

ATOM
849
O
THR
A
248
48.615
31.915
196.917
1.00
13.38
A

ATOM
850
N
GLU
A
249
48.655
31.563
199.146
1.00
12.55
A

ATOM
851
CA
GLU
A
249
47.241
31.874
199.327
1.00
12.92
A

ATOM
852
CB
GLU
A
249
46.794
31.513
200.734
1.00
13.33
A

ATOM
853
CG
GLU
A
249
46.767
30.009
200.966
1.00
15.98
A

ATOM
854
CD
GLU
A
249
46.055
29.624
202.235
1.00
15.69
A

ATOM
855
OE1
GLU
A
249
45.152
30.378
202.665
1.00
15.93
A

ATOM
856
OE2
GLU
A
249
46.390
28.559
202.801
1.00
13.53
A

ATOM
857
C
GLU
A
249
46.895
33.323
199.000
1.00
12.47
A

ATOM
858
O
GLU
A
249
45.829
33.590
198.451
1.00
11.25
A

ATOM
859
N
GLU
A
250
47.844
34.231
199.245
1.00
13.16
A

ATOM
860
CA
GLU
A
250
47.657
35.654
198.969
1.00
14.49
A

ATOM
861
CB
GLU
A
250
48.710
36.500
199.705
1.00
19.43
A

ATOM
862
CG
GLU
A
250
48.371
37.999
199.834
1.00
26.02
A

ATOM
863
CD
GLU
A
250
47.109
38.267
200.658
1.00
28.19
A

ATOM
864
OE1
GLU
A
250
47.137
38.051
201.889
1.00
33.54
A

ATOM
865
OE2
GLU
A
250
46.091
38.692
200.072
1.00
28.94
A

ATOM
866
C
GLU
A
250
47.698
35.924
197.463
1.00
13.59
A

ATOM
867
O
GLU
A
250
46.941
36.762
196.958
1.00
12.85
A

ATOM
868
N
ARG
A
251
48.542
35.173
196.750
1.00
12.93
A

ATOM
869
CA
ARG
A
251
48.669
35.315
195.299
1.00
11.46
A

ATOM
870
CB
ARG
A
251
49.937
34.628
194.778
1.00
13.58
A

ATOM
871
CG
ARG
A
251
50.109
34.767
193.274
1.00
14.49
A

ATOM
872
CD
ARG
A
251
51.522
34.658
192.796
1.00
18.51
A

ATOM
873
NE
ARG
A
251
51.563
34.773
191.340
1.00
19.55
A

ATOM
874
CZ
ARG
A
251
52.558
34.333
190.578
1.00
20.55
A

ATOM
875
NH1
ARG
A
251
53.611
33.749
191.128
1.00
23.76
A

ATOM
876
NH2
ARG
A
251
52.490
34.459
189.260
1.00
22.77
A

ATOM
877
C
ARG
A
251
47.418
34.755
194.615
1.00
10.01
A

ATOM
878
O
ARG
A
251
46.904
35.352
193.666
1.00
10.64
A

ATOM
879
N
ALA
A
252
46.908
33.647
195.150
1.00
10.04
A

ATOM
880
CA
ALA
A
252
45.698
33.010
194.632
1.00
10.06
A

ATOM
881
CB
ALA
A
252
45.517
31.660
195.252
1.00
12.46
A

ATOM
882
C
ALA
A
252
44.480
33.889
194.907
1.00
10.61
A

ATOM
883
O
ALA
A
252
43.577
33.976
194.071
1.00
8.88
A

ATOM
884
N
ARG
A
253
44.505
34.594
196.046
1.00
9.47
A

ATOM
885
CA
ARG
A
253
43.428
35.507
196.446
1.00
10.22
A

ATOM
886
CB
ARG
A
253
43.654
36.009
197.880
1.00
11.58
A

ATOM
887
CG
ARG
A
253
42.640
37.044
198.395
1.00
15.79
A

ATOM
888
CD
ARG
A
253
42.515
37.073
199.916
1.00
18.19
A

ATOM
889
NE
ARG
A
253
43.780
36.884
200.615
1.00
21.67
A

ATOM
890
CZ
ARG
A
253
44.006
35.940
201.527
1.00
21.38
A

ATOM
891
NH1
ARG
A
253
43.048
35.086
201.874
1.00
22.53
A

ATOM
892
NH2
ARG
A
253
45.215
35.814
202.044
1.00
24.22
A

ATOM
893
C
ARG
A
253
43.319
36.685
195.481
1.00
9.40
A

ATOM
894
O
ARG
A
253
42.215
37.081
195.109
1.00
8.31
A

ATOM
895
N
PHE
A
254
44.471
37.194
195.044
1.00
9.39
A

ATOM
896
CA
PHE
A
254
44.526
38.311
194.103
1.00
9.66
A

ATOM
897
CB
PHE
A
254
45.977
38.773
193.879
1.00
9.36
A

ATOM
898
CG
PHE
A
254
46.108
39.931
192.911
1.00
11.36
A

ATOM
899
CD1
PHE
A
254
45.963
41.255
193.362
1.00
15.23
A

ATOM
900
CD2
PHE
A
254
46.339
39.700
191.531
1.00
15.03
A

ATOM
901
CE1
PHE
A
254
46.040
42.345
192.454
1.00
16.82
A

ATOM
902
CE2
PHE
A
254
46.418
40.776
190.609
1.00
15.10
A

ATOM
903
CZ
PHE
A
254
46.266
42.103
191.078
1.00
16.06
A

ATOM
904
C
PHE
A
254
43.878
37.921
192.770
1.00
8.48
A

ATOM
905
O
PHE
A
254
43.020
38.643
192.272
1.00
8.74
A

ATOM
906
N
TYR
A
255
44.311
36.793
192.202
1.00
8.89
A

ATOM
907
CA
TYR
A
255
43.774
36.306
190.928
1.00
9.03
A

ATOM
908
CB
TYR
A
255
44.590
35.121
190.396
1.00
9.19
A

ATOM
909
CG
TYR
A
255
46.029
35.450
190.040
1.00
9.91
A

ATOM
910
CD1
TYR
A
255
46.377
36.685
189.445
1.00
9.09
A

ATOM
911
CE1
TYR
A
255
47.731
37.000
189.129
1.00
9.66
A

ATOM
912
CD2
TYR
A
255
47.061
34.531
190.309
1.00
9.65
A

ATOM
913
CE2
TYR
A
255
48.421
34.834
189.988
1.00
9.49
A

ATOM
914
CZ
TYR
A
255
48.740
36.069
189.403
1.00
11.34
A

ATOM
915
OH
TYR
A
255
50.052
36.368
189.105
1.00
11.59
A

ATOM
916
C
TYR
A
255
42.308
35.925
191.055
1.00
7.99
A

ATOM
917
O
TYR
A
255
41.498
36.312
190.218
1.00
7.50
A

ATOM
918
N
GLY
A
256
41.975
35.259
192.163
1.00
8.47
A

ATOM
919
CA
GLY
A
256
40.608
34.845
192.440
1.00
7.94
A

ATOM
920
C
GLY
A
256
39.651
36.017
192.548
1.00
7.98
A

ATOM
921
O
GLY
A
256
38.563
35.969
191.977
1.00
7.43
A

ATOM
922
N
ALA
A
257
40.102
37.101
193.190
1.00
8.64
A

ATOM
923
CA
ALA
A
257
39.296
38.316
193.354
1.00
9.93
A

ATOM
924
CB
ALA
A
257
39.993
39.306
194.276
1.00
10.11
A

ATOM
925
C
ALA
A
257
38.985
38.977
192.015
1.00
10.56
A

ATOM
926
O
ALA
A
257
37.859
39.420
191.773
1.00
10.25
A

ATOM
927
N
GLU
A
258
39.971
38.971
191.121
1.00
10.39
A

ATOM
928
CA
GLU
A
258
39.794
39.558
189.800
1.00
11.25
A

ATOM
929
CB
GLU
A
258
41.146
39.820
189.138
1.00
11.50
A

ATOM
930
CG
GLU
A
258
42.025
40.767
189.944
1.00
10.66
A

ATOM
931
CD
GLU
A
258
43.165
41.375
189.153
1.00
14.47
A

ATOM
932
OE1
GLU
A
258
43.711
40.715
188.252
1.00
13.36
A

ATOM
933
OE2
GLU
A
258
43.517
42.542
189.431
1.00
15.92
A

ATOM
934
C
GLU
A
258
38.863
38.722
188.914
1.00
10.08
A

ATOM
935
O
GLU
A
258
38.052
39.285
188.174
1.00
9.82
A

ATOM
936
N
ILE
A
259
38.904
37.393
189.082
1.00
10.00
A

ATOM
937
CA
ILE
A
259
38.040
36.468
188.326
1.00
9.66
A

ATOM
938
CB
ILE
A
259
38.498
34.977
188.450
1.00
9.87
A

ATOM
939
CG2
ILE
A
259
37.526
34.033
187.700
1.00
8.88
A

ATOM
940
CG1
ILE
A
259
39.893
34.803
187.839
1.00
11.12
A

ATOM
941
CD1
ILE
A
259
40.627
33.550
188.318
1.00
12.02
A

ATOM
942
C
ILE
A
259
36.594
36.615
188.819
1.00
9.65
A

ATOM
943
O
ILE
A
259
35.672
36.645
188.003
1.00
9.15
A

ATOM
944
N
VAL
A
260
36.417
36.759
190.139
1.00
8.61
A

ATOM
945
CA
VAL
A
260
35.087
36.934
190.754
1.00
8.52
A

ATOM
946
CB
VAL
A
260
35.161
36.963
192.314
1.00
7.63
A

ATOM
947
CG1
VAL
A
260
33.801
37.292
192.931
1.00
8.09
A

ATOM
948
CG2
VAL
A
260
35.615
35.622
192.847
1.00
7.58
A

ATOM
949
C
VAL
A
260
34.451
38.232
190.242
1.00
9.95
A

ATOM
950
O
VAL
A
260
33.272
38.247
189.887
1.00
9.77
A

ATOM
951
N
SER
A
261
35.259
39.292
190.165
1.00
10.95
A

ATOM
952
CA
SER
A
261
34.818
40.605
189.680
1.00
10.64
A

ATOM
953
CB
SER
A
261
35.967
41.614
189.793
1.00
12.26
A

ATOM
954
OG
SER
A
261
35.595
42.886
189.298
1.00
13.27
A

ATOM
955
C
SER
A
261
34.333
40.505
188.228
1.00
10.64
A

ATOM
956
O
SER
A
261
33.264
41.018
187.889
1.00
10.21
A

ATOM
957
N
ALA
A
262
35.082
39.757
187.416
1.00
9.57
A

ATOM
958
CA
ALA
A
262
34.764
39.533
186.005
1.00
10.66
A

ATOM
959
CB
ALA
A
262
35.937
38.891
185.309
1.00
9.52
A

ATOM
960
C
ALA
A
262
33.512
38.672
185.834
1.00
10.95
A

ATOM
961
O
ALA
A
262
32.673
38.958
184.978
1.00
11.45
A

ATOM
962
N
LEU
A
263
33.378
37.647
186.678
1.00
10.72
A

ATOM
963
CA
LEU
A
263
32.221
36.746
186.643
1.00
8.95
A

ATOM
964
CB
LEU
A
263
32.505
35.456
187.419
1.00
9.12
A

ATOM
965
CG
LEU
A
263
33.369
34.389
186.731
1.00
8.06
A

ATOM
966
CD1
LEU
A
263
33.638
33.255
187.709
1.00
7.97
A

ATOM
967
CD2
LEU
A
263
32.689
33.851
185.479
1.00
8.44
A

ATOM
968
C
LEU
A
263
30.942
37.421
187.139
1.00
10.52
A

ATOM
969
O
LEU
A
263
29.859
37.151
186.615
1.00
9.90
A

ATOM
970
N
GLU
A
264
31.091
38.349
188.091
1.00
10.31
A

ATOM
971
CA
GLU
A
264
29.973
39.131
188.646
1.00
11.96
A

ATOM
972
CB
GLU
A
264
30.466
40.041
189.793
1.00
14.48
A

ATOM
973
CG
GLU
A
264
29.376
40.752
190.653
1.00
20.37
A

ATOM
974
CD
GLU
A
264
28.795
42.031
190.049
1.00
24.02
A

ATOM
975
OE1
GLU
A
264
27.588
42.287
190.257
1.00
26.91
A

ATOM
976
OE2
GLU
A
264
29.532
42.771
189.363
1.00
26.95
A

ATOM
977
C
GLU
A
264
29.425
39.997
187.515
1.00
11.34
A

ATOM
978
O
GLU
A
264
28.211
40.066
187.316
1.00
10.55
A

ATOM
979
N
TYR
A
265
30.341
40.645
186.790
1.00
11.64
A

ATOM
980
CA
TYR
A
265
29.999
41.514
185.667
1.00
11.05
A

ATOM
981
CB
TYR
A
265
31.252
42.212
185.108
1.00
12.33
A

ATOM
982
CG
TYR
A
265
31.010
43.028
183.843
1.00
12.95
A

ATOM
983
CD1
TYR
A
265
30.414
44.310
183.902
1.00
13.79
A

ATOM
984
CE1
TYR
A
265
30.107
45.029
182.711
1.00
13.88
A

ATOM
985
CD2
TYR
A
265
31.300
42.485
182.573
1.00
12.24
A

ATOM
986
CE2
TYR
A
265
30.997
43.189
181.385
1.00
14.47
A

ATOM
987
CZ
TYR
A
265
30.402
44.453
181.462
1.00
15.05
A

ATOM
988
OH
TYR
A
265
30.102
45.110
180.294
1.00
15.45
A

ATOM
989
C
TYR
A
265
29.278
40.734
184.565
1.00
10.82
A

ATOM
990
O
TYR
A
265
28.272
41.206
184.046
1.00
12.32
A

ATOM
991
N
LEU
A
266
29.816
39.566
184.207
1.00
11.18
A

ATOM
992
CA
LEU
A
266
29.221
38.716
183.170
1.00
10.85
A

ATOM
993
CB
LEU
A
266
30.115
37.510
182.867
1.00
11.40
A

ATOM
994
CG
LEU
A
266
31.366
37.737
182.007
1.00
10.46
A

ATOM
995
CD1
LEU
A
266
32.222
36.476
182.001
1.00
11.44
A

ATOM
996
CD2
LEU
A
266
30.983
38.117
180.577
1.00
12.01
A

ATOM
997
C
LEU
A
266
27.813
38.256
183.548
1.00
10.96
A

ATOM
998
O
LEU
A
266
26.889
38.385
182.746
1.00
9.27
A

ATOM
999
N
HIS
A
267
27.644
37.807
184.794
1.00
9.75
A

ATOM
1000
CA
HIS
A
267
26.345
37.350
185.292
1.00
10.52
A

ATOM
1001
CB
HIS
A
267
26.488
36.649
186.652
1.00
10.88
A

ATOM
1002
CG
HIS
A
267
27.144
35.298
186.585
1.00
9.28
A

ATOM
1003
CD2
HIS
A
267
27.781
34.655
185.575
1.00
9.90
A

ATOM
1004
ND1
HIS
A
267
27.185
34.441
187.664
1.00
10.19
A

ATOM
1005
CE1
HIS
A
267
27.814
33.332
187.324
1.00
10.55
A

ATOM
1006
NE2
HIS
A
267
28.186
33.436
186.062
1.00
10.79
A

ATOM
1007
C
HIS
A
267
25.315
38.484
185.371
1.00
11.93
A

ATOM
1008
O
HIS
A
267
24.127
38.247
185.155
1.00
14.31
A

ATOM
1009
N
SER
A
268
25.793
39.715
185.586
1.00
12.99
A

ATOM
1010
CA
SER
A
268
24.932
40.906
185.666
1.00
16.08
A

ATOM
1011
CB
SER
A
268
25.654
42.063
186.377
1.00
14.97
A

ATOM
1012
OG
SER
A
268
26.632
42.678
185.554
1.00
19.70
A

ATOM
1013
C
SER
A
268
24.454
41.343
184.271
1.00
17.40
A

ATOM
1014
O
SER
A
268
23.441
42.034
184.138
1.00
19.73
A

ATOM
1015
N
ARG
A
269
25.196
40.914
183.246
1.00
17.18
A

ATOM
1016
CA
ARG
A
269
24.888
41.193
181.841
1.00
17.62
A

ATOM
1017
CB
ARG
A
269
26.177
41.498
181.060
1.00
21.11
A

ATOM
1018
CG
ARG
A
269
26.888
42.795
181.454
1.00
25.38
A

ATOM
1019
CD
ARG
A
269
26.203
44.039
180.904
1.00
27.78
A

ATOM
1020
NE
ARG
A
269
26.350
44.157
179.453
1.00
32.09
A

ATOM
1021
CZ
ARG
A
269
25.748
45.076
178.699
1.00
33.70
A

ATOM
1022
NH1
ARG
A
269
24.939
45.979
179.244
1.00
34.89
A

ATOM
1023
NH2
ARG
A
269
25.963
45.097
177.391
1.00
33.61
A

ATOM
1024
C
ARG
A
269
24.175
39.977
181.227
1.00
16.92
A

ATOM
1025
O
ARG
A
269
24.036
39.872
180.000
1.00
16.31
A

ATOM
1026
N
ASP
A
270
23.724
39.074
182.107
1.00
14.40
A

ATOM
1027
CA
ASP
A
270
23.005
37.830
181.778
1.00
13.46
A

ATOM
1028
CB
ASP
A
270
21.650
38.124
181.092
1.00
14.60
A

ATOM
1029
CG
ASP
A
270
20.732
39.018
181.925
1.00
18.26
A

ATOM
1030
OD1
ASP
A
270
20.919
39.132
183.158
1.00
18.04
A

ATOM
1031
OD2
ASP
A
270
19.802
39.605
181.331
1.00
21.02
A

ATOM
1032
C
ASP
A
270
23.815
36.808
180.964
1.00
11.78
A

ATOM
1033
O
ASP
A
270
23.257
36.012
180.199
1.00
10.83
A

ATOM
1034
N
VAL
A
271
25.131
36.817
181.167
1.00
10.42
A

ATOM
1035
CA
VAL
A
271
26.043
35.920
180.457
1.00
9.27
A

ATOM
1036
CB
VAL
A
271
27.173
36.721
179.713
1.00
10.84
A

ATOM
1037
CG1
VAL
A
271
28.106
35.785
178.950
1.00
11.06
A

ATOM
1038
CG2
VAL
A
271
26.575
37.749
178.751
1.00
10.78
A

ATOM
1039
C
VAL
A
271
26.700
34.919
181.408
1.00
9.33
A

ATOM
1040
O
VAL
A
271
27.217
35.297
182.457
1.00
10.42
A

ATOM
1041
N
VAL
A
272
26.643
33.641
181.033
1.00
7.94
A

ATOM
1042
CA
VAL
A
272
27.279
32.561
181.790
1.00
6.49
A

ATOM
1043
CB
VAL
A
272
26.308
31.377
182.034
1.00
6.42
A

ATOM
1044
CG1
VAL
A
272
26.991
30.243
182.811
1.00
8.22
A

ATOM
1045
CG2
VAL
A
272
25.153
31.861
182.833
1.00
6.79
A

ATOM
1046
C
VAL
A
272
28.463
32.152
180.915
1.00
7.17
A

ATOM
1047
O
VAL
A
272
28.299
31.860
179.728
1.00
8.47
A

ATOM
1048
N
TYR
A
273
29.646
32.132
181.522
1.00
6.61
A

ATOM
1049
CA
TYR
A
273
30.895
31.827
180.830
1.00
8.02
A

ATOM
1050
CB
TYR
A
273
32.048
32.422
181.648
1.00
7.65
A

ATOM
1051
CG
TYR
A
273
33.395
32.332
181.000
1.00
7.99
A

ATOM
1052
CD1
TYR
A
273
33.727
33.105
179.865
1.00
7.18
A

ATOM
1053
CE1
TYR
A
273
34.985
32.949
179.229
1.00
6.85
A

ATOM
1054
CD2
TYR
A
273
34.338
31.430
181.485
1.00
7.03
A

ATOM
1055
CE2
TYR
A
273
35.576
31.280
180.871
1.00
8.23
A

ATOM
1056
CZ
TYR
A
273
35.896
32.020
179.755
1.00
6.72
A

ATOM
1057
OH
TYR
A
273
37.112
31.765
179.196
1.00
8.95
A

ATOM
1058
C
TYR
A
273
31.125
30.351
180.437
1.00
9.03
A

ATOM
1059
O
TYR
A
273
31.582
30.077
179.322
1.00
8.84
A

ATOM
1060
N
ARG
A
274
30.864
29.428
181.369
1.00
8.63
A

ATOM
1061
CA
ARG
A
274
30.977
27.967
181.173
1.00
9.18
A

ATOM
1062
CB
ARG
A
274
29.961
27.463
180.122
1.00
9.26
A

ATOM
1063
CG
ARG
A
274
28.505
27.591
180.537
1.00
10.03
A

ATOM
1064
CD
ARG
A
274
27.570
26.835
179.606
1.00
10.31
A

ATOM
1065
NE
ARG
A
274
27.509
27.402
178.258
1.00
10.13
A

ATOM
1066
CZ
ARG
A
274
26.604
27.069
177.337
1.00
10.15
A

ATOM
1067
NH1
ARG
A
274
25.670
26.164
177.602
1.00
10.43
A

ATOM
1068
NH2
ARG
A
274
26.623
27.660
176.151
1.00
8.58
A

ATOM
1069
C
ARG
A
274
32.331
27.292
180.912
1.00
9.34
A

ATOM
1070
O
ARG
A
274
32.408
26.059
180.946
1.00
11.86
A

ATOM
1071
N
ASP
A
275
33.390
28.066
180.679
1.00
8.02
A

ATOM
1072
CA
ASP
A
275
34.693
27.459
180.402
1.00
8.04
A

ATOM
1073
CB
ASP
A
275
34.995
27.532
178.886
1.00
9.80
A

ATOM
1074
CG
ASP
A
275
36.035
26.501
178.433
1.00
7.91
A

ATOM
1075
OD1
ASP
A
275
36.271
25.518
179.166
1.00
8.81
A

ATOM
1076
OD2
ASP
A
275
36.623
26.680
177.346
1.00
8.43
A

ATOM
1077
C
ASP
A
275
35.866
28.002
181.234
1.00
7.00
A

ATOM
1078
O
ASP
A
275
36.957
28.240
180.693
1.00
7.47
A

ATOM
1079
N
ILE
A
276
35.634
28.252
182.529
1.00
6.51
A

ATOM
1080
CA
ILE
A
276
36.699
28.744
183.421
1.00
6.60
A

ATOM
1081
CB
ILE
A
276
36.190
29.097
184.868
1.00
7.25
A

ATOM
1082
CG2
ILE
A
276
37.383
29.332
185.831
1.00
7.34
A

ATOM
1083
CG1
ILE
A
276
35.267
30.326
184.871
1.00
9.05
A

ATOM
1084
CD1
ILE
A
276
35.970
31.697
184.676
1.00
12.14
A

ATOM
1085
C
ILE
A
276
37.759
27.650
183.522
1.00
8.47
A

ATOM
1086
O
ILE
A
276
37.451
26.495
183.833
1.00
8.65
A

ATOM
1087
N
LYS
A
277
38.976
28.025
183.142
1.00
7.22
A

ATOM
1088
CA
LYS
A
277
40.139
27.152
183.179
1.00
6.80
A

ATOM
1089
CB
LYS
A
277
40.106
26.077
182.078
1.00
8.00
A

ATOM
1090
CG
LYS
A
277
40.140
26.534
180.648
1.00
6.57
A

ATOM
1091
CD
LYS
A
277
40.157
25.310
179.770
1.00
9.85
A

ATOM
1092
CE
LYS
A
277
40.085
25.671
178.319
1.00
10.08
A

ATOM
1093
NZ
LYS
A
277
39.993
24.460
177.450
1.00
12.92
A

ATOM
1094
C
LYS
A
277
41.406
27.968
183.104
1.00
7.80
A

ATOM
1095
O
LYS
A
277
41.392
29.091
182.603
1.00
9.59
A

ATOM
1096
N
LEU
A
278
42.507
27.392
183.583
1.00
9.89
A

ATOM
1097
CA
LEU
A
278
43.797
28.078
183.591
1.00
8.36
A

ATOM
1098
CB
LEU
A
278
44.840
27.221
184.295
1.00
8.17
A

ATOM
1099
CG
LEU
A
278
44.707
26.894
185.782
1.00
8.04
A

ATOM
1100
CD1
LEU
A
278
45.802
25.911
186.112
1.00
8.41
A

ATOM
1101
CD2
LEU
A
278
44.818
28.136
186.659
1.00
10.25
A

ATOM
1102
C
LEU
A
278
44.309
28.515
182.212
1.00
8.63
A

ATOM
1103
O
LEU
A
278
45.001
29.522
182.108
1.00
9.02
A

ATOM
1104
N
GLU
A
279
43.920
27.785
181.162
1.00
8.79
A

ATOM
1105
CA
GLU
A
279
44.316
28.109
179.784
1.00
8.25
A

ATOM
1106
CB
GLU
A
279
44.097
26.910
178.844
1.00
9.40
A

ATOM
1107
CG
GLU
A
279
45.007
25.704
179.102
1.00
12.77
A

ATOM
1108
CD
GLU
A
279
44.418
24.672
180.057
1.00
13.04
A

ATOM
1109
OE1
GLU
A
279
43.599
25.029
180.934
1.00
13.44
A

ATOM
1110
OE2
GLU
A
279
44.791
23.486
179.934
1.00
13.66
A

ATOM
1111
C
GLU
A
279
43.570
29.326
179.232
1.00
8.31
A

ATOM
1112
O
GLU
A
279
44.039
29.970
178.286
1.00
8.54
A

ATOM
1113
N
ASN
A
280
42.419
29.632
179.836
1.00
6.31
A

ATOM
1114
CA
ASN
A
280
41.575
30.767
179.440
1.00
7.33
A

ATOM
1115
CB
ASN
A
280
40.096
30.368
179.453
1.00
6.01
A

ATOM
1116
CG
ASN
A
280
39.725
29.456
178.304
1.00
8.77
A

ATOM
1117
OD1
ASN
A
280
40.528
29.223
177.402
1.00
8.00
A

ATOM
1118
ND2
ASN
A
280
38.495
28.942
178.325
1.00
7.13
A

ATOM
1119
C
ASN
A
280
41.755
32.013
180.303
1.00
6.80
A

ATOM
1120
O
ASN
A
280
41.158
33.056
180.024
1.00
10.46
A

ATOM
1121
N
LEU
A
281
42.545
31.886
181.370
1.00
7.47
A

ATOM
1122
CA
LEU
A
281
42.817
32.998
182.287
1.00
8.41
A

ATOM
1123
CB
LEU
A
281
42.674
32.534
183.744
1.00
8.16
A

ATOM
1124
CG
LEU
A
281
41.296
31.986
184.143
1.00
8.45
A

ATOM
1125
CD1
LEU
A
281
41.389
31.184
185.432
1.00
9.90
A

ATOM
1126
CD2
LEU
A
281
40.265
33.095
184.246
1.00
11.76
A

ATOM
1127
C
LEU
A
281
44.222
33.526
182.001
1.00
9.46
A

ATOM
1128
O
LEU
A
281
45.219
32.868
182.292
1.00
10.14
A

ATOM
1129
N
MET
A
282
44.281
34.707
181.392
1.00
9.92
A

ATOM
1130
CA
MET
A
282
45.548
35.332
181.010
1.00
9.92
A

ATOM
1131
CB
MET
A
282
45.442
35.936
179.604
1.00
9.90
A

ATOM
1132
CG
MET
A
282
44.780
35.093
178.531
1.00
13.02
A

ATOM
1133
SD
MET
A
282
45.649
33.583
178.146
1.00
15.90
A

ATOM
1134
CE
MET
A
282
47.048
34.238
177.267
1.00
13.84
A

ATOM
1135
C
MET
A
282
45.971
36.464
181.930
1.00
10.24
A

ATOM
1136
O
MET
A
282
45.190
36.940
182.745
1.00
11.10
A

ATOM
1137
N
LEU
A
283
47.224
36.889
181.777
1.00
9.57
A

ATOM
1138
CA
LEU
A
283
47.762
38.018
182.530
1.00
9.80
A

ATOM
1139
CB
LEU
A
283
48.981
37.617
183.376
1.00
11.37
A

ATOM
1140
CG
LEU
A
283
48.810
36.691
184.587
1.00
11.11
A

ATOM
1141
CD1
LEU
A
283
50.123
36.609
185.358
1.00
12.01
A

ATOM
1142
CD2
LEU
A
283
47.711
37.212
185.497
1.00
12.37
A

ATOM
1143
C
LEU
A
283
48.171
39.075
181.515
1.00
10.80
A

ATOM
1144
O
LEU
A
283
48.740
38.735
180.475
1.00
10.89
A

ATOM
1145
N
ASP
A
284
47.818
40.338
181.767
1.00
12.21
A

ATOM
1146
CA
ASP
A
284
48.218
41.426
180.862
1.00
12.15
A

ATOM
1147
CB
ASP
A
284
47.216
42.610
180.872
1.00
12.94
A

ATOM
1148
CG
ASP
A
284
47.055
43.295
182.242
1.00
15.18
A

ATOM
1149
OD1
ASP
A
284
47.848
43.064
183.177
1.00
12.85
A

ATOM
1150
OD2
ASP
A
284
46.106
44.099
182.371
1.00
15.48
A

ATOM
1151
C
ASP
A
284
49.651
41.858
181.209
1.00
13.96
A

ATOM
1152
O
ASP
A
284
50.250
41.285
182.123
1.00
12.43
A

ATOM
1153
N
LYS
A
285
50.174
42.880
180.525
1.00
15.26
A

ATOM
1154
CA
LYS
A
285
51.541
43.372
180.764
1.00
18.56
A

ATOM
1155
CB
LYS
A
285
51.929
44.434
179.721
1.00
21.83
A

ATOM
1156
CG
LYS
A
285
50.982
45.626
179.604
1.00
26.06
A

ATOM
1157
CD
LYS
A
285
51.481
46.619
178.557
1.00
29.53
A

ATOM
1158
CE
LYS
A
285
50.449
47.704
178.275
1.00
31.29
A

ATOM
1159
NZ
LYS
A
285
49.206
47.152
177.657
1.00
33.75
A

ATOM
1160
C
LYS
A
285
51.828
43.890
182.181
1.00
16.68
A

ATOM
1161
O
LYS
A
285
52.987
43.955
182.595
1.00
18.17
A

ATOM
1162
N
ASP
A
286
50.765
44.209
182.919
1.00
16.70
A

ATOM
1163
CA
ASP
A
286
50.872
44.718
184.290
1.00
15.22
A

ATOM
1164
CB
ASP
A
286
49.838
45.829
184.529
1.00
15.56
A

ATOM
1165
CG
ASP
A
286
50.035
47.032
183.613
1.00
19.79
A

ATOM
1166
OD1
ASP
A
286
51.161
47.570
183.547
1.00
21.62
A

ATOM
1167
OD2
ASP
A
286
49.055
47.444
182.957
1.00
22.25
A

ATOM
1168
C
ASP
A
286
50.715
43.626
185.356
1.00
14.92
A

ATOM
1169
O
ASP
A
286
51.060
43.842
186.521
1.00
16.19
A

ATOM
1170
N
GLY
A
287
50.191
42.466
184.957
1.00
13.57
A

ATOM
1171
CA
GLY
A
287
49.999
41.359
185.887
1.00
11.70
A

ATOM
1172
C
GLY
A
287
48.574
41.120
186.350
1.00
11.64
A

ATOM
1173
O
GLY
A
287
48.339
40.316
187.258
1.00
11.78
A

ATOM
1174
N
HIS
A
288
47.629
41.834
185.743
1.00
9.91
A

ATOM
1175
CA
HIS
A
288
46.207
41.697
186.066
1.00
11.23
A

ATOM
1176
CB
HIS
A
288
45.471
43.017
185.834
1.00
13.28
A

ATOM
1177
CG
HIS
A
288
45.808
44.088
186.822
1.00
14.63
A

ATOM
1178
CD2
HIS
A
288
46.526
45.228
186.691
1.00
16.43
A

ATOM
1179
ND1
HIS
A
288
45.356
44.068
188.123
1.00
15.31
A

ATOM
1180
CE1
HIS
A
288
45.779
45.150
188.752
1.00
16.81
A

ATOM
1181
NE2
HIS
A
288
46.492
45.871
187.904
1.00
17.87
A

ATOM
1182
C
HIS
A
288
45.576
40.628
185.179
1.00
10.60
A

ATOM
1183
O
HIS
A
288
46.028
40.410
184.055
1.00
11.22
A

ATOM
1184
N
ILE
A
289
44.519
39.991
185.686
1.00
10.82
A

ATOM
1185
CA
ILE
A
289
43.774
38.947
184.971
1.00
10.21
A

ATOM
1186
CB
ILE
A
289
42.739
38.227
185.933
1.00
9.51
A

ATOM
1187
CG2
ILE
A
289
41.618
37.445
185.165
1.00
7.93
A

ATOM
1188
CG1
ILE
A
289
43.473
37.322
186.929
1.00
11.18
A

ATOM
1189
CD1
ILE
A
289
44.069
36.033
186.354
1.00
13.48
A

ATOM
1190
C
ILE
A
289
43.032
39.488
183.748
1.00
10.59
A

ATOM
1191
O
ILE
A
289
42.554
40.621
183.746
1.00
11.51
A

ATOM
1192
N
LYS
A
290
43.036
38.685
182.688
1.00
11.77
A

ATOM
1193
CA
LYS
A
290
42.324
38.979
181.455
1.00
11.00
A

ATOM
1194
CB
LYS
A
290
43.252
39.492
180.341
1.00
13.10
A

ATOM
1195
CG
LYS
A
290
43.686
40.953
180.447
1.00
14.99
A

ATOM
1196
CD
LYS
A
290
42.529
41.930
180.290
1.00
18.52
A

ATOM
1197
CE
LYS
A
290
43.034
43.364
180.295
1.00
22.11
A

ATOM
1198
NZ
LYS
A
290
41.922
44.337
180.126
1.00
26.55
A

ATOM
1199
C
LYS
A
290
41.695
37.664
181.035
1.00
11.30
A

ATOM
1200
O
LYS
A
290
42.397
36.735
180.631
1.00
12.04
A

ATOM
1201
N
ILE
A
291
40.385
37.542
181.229
1.00
9.93
A

ATOM
1202
CA
ILE
A
291
39.682
36.332
180.811
1.00
9.56
A

ATOM
1203
CB
ILE
A
291
38.279
36.183
181.477
1.00
10.13
A

ATOM
1204
CG2
ILE
A
291
37.582
34.918
180.959
1.00
10.54
A

ATOM
1205
CG1
ILE
A
291
38.399
36.142
183.006
1.00
11.61
A

ATOM
1206
CD1
ILE
A
291
37.094
35.832
183.747
1.00
12.24
A

ATOM
1207
C
ILE
A
291
39.510
36.439
179.294
1.00
9.16
A

ATOM
1208
O
ILE
A
291
39.099
37.482
178.788
1.00
10.60
A

ATOM
1209
N
THR
A
292
39.902
35.382
178.590
1.00
8.25
A

ATOM
1210
CA
THR
A
292
39.777
35.311
177.142
1.00
9.83
A

ATOM
1211
CB
THR
A
292
41.179
35.209
176.452
1.00
11.15
A

ATOM
1212
OG1
THR
A
292
41.037
35.449
175.048
1.00
12.68
A

ATOM
1213
CG2
THR
A
292
41.833
33.831
176.672
1.00
10.76
A

ATOM
1214
C
THR
A
292
38.899
34.098
176.828
1.00
9.68
A

ATOM
1215
O
THR
A
292
38.379
33.467
177.753
1.00
10.43
A

ATOM
1216
N
ASP
A
293
38.721
33.799
175.537
1.00
9.17
A

ATOM
1217
CA
ASP
A
293
37.931
32.655
175.053
1.00
10.04
A

ATOM
1218
CB
ASP
A
293
38.658
31.336
175.377
1.00
9.36
A

ATOM
1219
CG
ASP
A
293
37.989
30.109
174.770
1.00
10.66
A

ATOM
1220
OD1
ASP
A
293
37.099
30.252
173.899
1.00
10.21
A

ATOM
1221
OD2
ASP
A
293
38.361
28.988
175.171
1.00
10.02
A

ATOM
1222
C
ASP
A
293
36.473
32.625
175.536
1.00
9.58
A

ATOM
1223
O
ASP
A
293
36.118
31.901
176.475
1.00
10.78
A

ATOM
1224
N
PHE
A
294
35.634
33.371
174.833
1.00
9.42
A

ATOM
1225
CA
PHE
A
294
34.216
33.457
175.151
1.00
10.65
A

ATOM
1226
CB
PHE
A
294
33.765
34.919
175.027
1.00
8.98
A

ATOM
1227
CG
PHE
A
294
34.492
35.850
175.965
1.00
10.40
A

ATOM
1228
CD1
PHE
A
294
35.657
36.524
175.545
1.00
10.44
A

ATOM
1229
CD2
PHE
A
294
34.037
36.034
177.284
1.00
10.22
A

ATOM
1230
CE1
PHE
A
294
36.372
37.377
176.429
1.00
10.90
A

ATOM
1231
CE2
PHE
A
294
34.734
36.880
178.186
1.00
10.17
A

ATOM
1232
CZ
PHE
A
294
35.912
37.556
177.753
1.00
9.39
A

ATOM
1233
C
PHE
A
294
33.401
32.528
174.243
1.00
10.59
A

ATOM
1234
O
PHE
A
294
32.197
32.718
174.062
1.00
11.98
A

ATOM
1235
N
GLY
A
295
34.074
31.490
173.735
1.00
9.82
A

ATOM
1236
CA
GLY
A
295
33.481
30.518
172.823
1.00
10.01
A

ATOM
1237
C
GLY
A
295
32.307
29.675
173.272
1.00
11.65
A

ATOM
1238
O
GLY
A
295
31.543
29.186
172.434
1.00
12.48
A

ATOM
1239
N
LEU
A
296
32.188
29.469
174.582
1.00
10.57
A

ATOM
1240
CA
LEU
A
296
31.105
28.666
175.139
1.00
11.63
A

ATOM
1241
CB
LEU
A
296
31.663
27.439
175.874
1.00
10.26
A

ATOM
1242
CG
LEU
A
296
32.185
26.311
174.973
1.00
13.35
A

ATOM
1243
CD1
LEU
A
296
32.808
25.234
175.818
1.00
11.29
A

ATOM
1244
CD2
LEU
A
296
31.069
25.737
174.094
1.00
12.10
A

ATOM
1245
C
LEU
A
296
30.147
29.452
176.022
1.00
10.80
A

ATOM
1246
O
LEU
A
296
29.403
28.874
176.817
1.00
12.17
A

ATOM
1247
N
CYS
A
297
30.139
30.773
175.845
1.00
10.80
A

ATOM
1248
CA
CYS
A
297
29.254
31.652
176.603
1.00
13.22
A

ATOM
1249
CB
CYS
A
297
29.650
33.120
176.428
1.00
13.44
A

ATOM
1250
SG
CYS
A
297
31.066
33.657
177.396
1.00
13.71
A

ATOM
1251
C
CYS
A
297
27.807
31.491
176.152
1.00
14.72
A

ATOM
1252
O
CYS
A
297
27.541
31.040
175.037
1.00
15.60
A

ATOM
1253
N
LYS
A
298
26.883
31.807
177.053
1.00
14.15
A

ATOM
1254
CA
LYS
A
298
25.461
31.753
176.750
1.00
13.85
A

ATOM
1255
CB
LYS
A
298
24.778
30.562
177.435
1.00
15.15
A

ATOM
1256
CG
LYS
A
298
23.365
30.255
176.908
1.00
15.78
A

ATOM
1257
CD
LYS
A
298
23.368
29.620
175.525
1.00
16.76
A

ATOM
1258
CE
LYS
A
298
21.948
29.414
175.021
1.00
17.84
A

ATOM
1259
NZ
LYS
A
298
21.915
28.831
173.647
1.00
19.96
A

ATOM
1260
C
LYS
A
298
24.862
33.058
177.241
1.00
14.64
A

ATOM
1261
O
LYS
A
298
25.089
33.463
178.386
1.00
11.66
A

ATOM
1262
N
GLU
A
299
24.146
33.733
176.343
1.00
14.33
A

ATOM
1263
CA
GLU
A
299
23.482
35.003
176.637
1.00
16.11
A

ATOM
1264
CB
GLU
A
299
23.466
35.897
175.395
1.00
17.68
A

ATOM
1265
CG
GLU
A
299
24.812
36.408
174.942
1.00
19.12
A

ATOM
1266
CD
GLU
A
299
24.710
37.162
173.631
1.00
21.04
A

ATOM
1267
OE1
GLU
A
299
24.554
38.400
173.663
1.00
24.87
A

ATOM
1268
OE2
GLU
A
299
24.763
36.510
172.569
1.00
22.96
A

ATOM
1269
C
GLU
A
299
22.039
34.780
177.075
1.00
15.92
A

ATOM
1270
O
GLU
A
299
21.492
33.688
176.902
1.00
14.96
A

ATOM
1271
N
GLY
A
300
21.446
35.826
177.653
1.00
15.75
A

ATOM
1272
CA
GLY
A
300
20.060
35.794
178.099
1.00
17.47
A

ATOM
1273
C
GLY
A
300
19.732
34.960
179.322
1.00
17.70
A

ATOM
1274
O
GLY
A
300
18.566
34.623
179.545
1.00
20.16
A

ATOM
1275
N
ILE
A
301
20.755
34.633
180.114
1.00
17.12
A

ATOM
1276
CA
ILE
A
301
20.582
33.826
181.321
1.00
17.87
A

ATOM
1277
CB
ILE
A
301
21.690
32.723
181.437
1.00
16.61
A

ATOM
1278
CG2
ILE
A
301
21.438
31.802
182.641
1.00
17.26
A

ATOM
1279
CG1
ILE
A
301
21.796
31.902
180.138
1.00
16.71
A

ATOM
1280
CD1
ILE
A
301
20.506
31.195
179.667
1.00
15.02
A

ATOM
1281
C
ILE
A
301
20.545
34.713
182.571
1.00
18.46
A

ATOM
1282
O
ILE
A
301
21.584
35.030
183.164
1.00
17.14
A

ATOM
1283
N
SER
A
302
19.332
35.132
182.928
1.00
20.13
A

ATOM
1284
CA
SER
A
302
19.077
35.983
184.090
1.00
22.53
A

ATOM
1285
CB
SER
A
302
18.073
37.083
183.727
1.00
23.18
A

ATOM
1286
OG
SER
A
302
16.908
36.542
183.122
1.00
25.28
A

ATOM
1287
C
SER
A
302
18.524
35.159
185.245
1.00
23.86
A

ATOM
1288
O
SER
A
302
17.776
34.208
185.020
1.00
23.97
A

ATOM
1289
N
ASP
A
303
18.886
35.547
186.472
1.00
26.08
A

ATOM
1290
CA
ASP
A
303
18.456
34.896
187.721
1.00
27.31
A

ATOM
1291
CB
ASP
A
303
17.005
35.281
188.076
1.00
30.01
A

ATOM
1292
CG
ASP
A
303
16.838
36.766
188.352
1.00
32.98
A

ATOM
1293
OD1
ASP
A
303
16.891
37.163
189.536
1.00
34.13
A

ATOM
1294
OD2
ASP
A
303
16.644
37.534
187.385
1.00
36.20
A

ATOM
1295
C
ASP
A
303
18.652
33.370
187.737
1.00
26.42
A

ATOM
1296
O
ASP
A
303
19.787
32.892
187.664
1.00
27.68
A

ATOM
1297
N
GLY
A
304
17.544
32.628
187.755
1.00
24.67
A

ATOM
1298
CA
GLY
A
304
17.595
31.177
187.772
1.00
22.31
A

ATOM
1299
C
GLY
A
304
17.347
30.513
186.429
1.00
21.41
A

ATOM
1300
O
GLY
A
304
16.949
29.346
186.398
1.00
22.36
A

ATOM
1301
N
ALA
A
305
17.588
31.234
185.326
1.00
19.38
A

ATOM
1302
CA
ALA
A
305
17.400
30.692
183.974
1.00
16.23
A

ATOM
1303
CB
ALA
A
305
17.534
31.784
182.923
1.00
18.12
A

ATOM
1304
C
ALA
A
305
18.412
29.576
183.723
1.00
15.49
A

ATOM
1305
O
ALA
A
305
19.523
29.604
184.259
1.00
16.41
A

ATOM
1306
N
THR
A
306
18.008
28.582
182.939
1.00
14.64
A

ATOM
1307
CA
THR
A
306
18.857
27.423
182.679
1.00
14.69
A

ATOM
1308
CB
THR
A
306
18.147
26.135
183.143
1.00
14.73
A

ATOM
1309
OG1
THR
A
306
16.953
25.939
182.373
1.00
14.38
A

ATOM
1310
CG2
THR
A
306
17.801
26.183
184.639
1.00
15.77
A

ATOM
1311
C
THR
A
306
19.374
27.222
181.249
1.00
13.86
A

ATOM
1312
O
THR
A
306
18.902
27.858
180.305
1.00
13.55
A

ATOM
1313
N
MET
A
307
20.379
26.348
181.126
1.00
12.76
A

ATOM
1314
CA
MET
A
307
21.030
25.989
179.858
1.00
13.15
A

ATOM
1315
CB
MET
A
307
22.487
26.452
179.848
1.00
14.43
A

ATOM
1316
CG
MET
A
307
22.665
27.950
179.895
1.00
17.96
A

ATOM
1317
SD
MET
A
307
24.155
28.447
180.732
1.00
15.06
A

ATOM
1318
CE
MET
A
307
23.609
28.298
182.407
1.00
16.64
A

ATOM
1319
C
MET
A
307
20.997
24.475
179.689
1.00
14.21
A

ATOM
1320
O
MET
A
307
21.014
23.740
180.679
1.00
13.98
A

ATOM
1321
N
LYS
A
308
21.002
24.012
178.438
1.00
13.94
A

ATOM
1322
CA
LYS
A
308
20.933
22.579
178.138
1.00
16.40
A

ATOM
1323
CB
LYS
A
308
19.650
22.275
177.345
1.00
20.02
A

ATOM
1324
CG
LYS
A
308
18.356
22.428
178.138
1.00
26.06
A

ATOM
1325
CD
LYS
A
308
17.131
22.272
177.254
1.00
29.32
A

ATOM
1326
CE
LYS
A
308
15.855
22.516
178.049
1.00
31.48
A

ATOM
1327
NZ
LYS
A
308
14.645
22.478
177.180
1.00
34.34
A

ATOM
1328
C
LYS
A
308
22.121
21.939
177.414
1.00
14.91
A

ATOM
1329
O
LYS
A
308
22.251
20.714
177.428
1.00
15.41
A

ATOM
1330
N
PTH
A
309
22.995
22.753
176.816
1.00
14.40
A

ATOM
1331
CA
PTH
A
309
24.145
22.248
176.051
1.00
12.21
A

ATOM
1332
CB
PTH
A
309
24.836
23.392
175.261
1.00
13.59
A

ATOM
1333
OG1
PTH
A
309
23.864
24.142
174.505
1.00
13.57
A

ATOM
1334
CG2
PTH
A
309
25.863
22.833
174.267
1.00
11.34
A

ATOM
1335
C
PTH
A
309
25.200
21.515
176.902
1.00
13.43
A

ATOM
1336
O
PTH
A
309
25.651
22.046
177.914
1.00
12.16
A

ATOM
1337
P
PTH
A
309
23.695
25.504
174.704
1.00
15.40
A

ATOM
1338
O1P
PTH
A
309
24.865
26.333
174.283
1.00
15.17
A

ATOM
1339
O2P
PTH
A
309
23.252
25.585
176.140
1.00
15.51
A

ATOM
1340
O3P
PTH
A
309
22.569
25.829
173.656
1.00
15.33
A

ATOM
1341
N
PHE
A
310
25.565
20.297
176.498
1.00
11.60
A

ATOM
1342
CA
PHE
A
310
26.607
19.533
177.193
1.00
11.72
A

ATOM
1343
CB
PHE
A
310
26.439
18.021
176.927
1.00
12.18
A

ATOM
1344
CG
PHE
A
310
27.425
17.127
177.668
1.00
11.43
A

ATOM
1345
CD1
PHE
A
310
27.917
15.962
177.046
1.00
14.94
A

ATOM
1346
CD2
PHE
A
310
27.840
17.415
178.992
1.00
11.04
A

ATOM
1347
CE1
PHE
A
310
28.810
15.083
177.728
1.00
13.98
A

ATOM
1348
CE2
PHE
A
310
28.729
16.553
179.688
1.00
11.48
A

ATOM
1349
CZ
PHE
A
310
29.216
15.379
179.053
1.00
13.60
A

ATOM
1350
C
PHE
A
310
27.919
20.069
176.600
1.00
11.28
A

ATOM
1351
O
PHE
A
310
28.305
19.708
175.484
1.00
11.72
A

ATOM
1352
N
CYS
A
311
28.550
20.983
177.338
1.00
10.71
A

ATOM
1353
CA
CYS
A
311
29.790
21.617
176.905
1.00
11.00
A

ATOM
1354
CB
CYS
A
311
29.476
22.836
176.030
1.00
11.91
A

ATOM
1355
SG
CYS
A
311
28.629
24.175
176.875
1.00
12.31
A

ATOM
1356
C
CYS
A
311
30.689
22.042
178.063
1.00
10.60
A

ATOM
1357
O
CYS
A
311
30.269
22.039
179.220
1.00
8.91
A

ATOM
1358
N
GLY
A
312
31.911
22.447
177.719
1.00
11.10
A

ATOM
1359
CA
GLY
A
312
32.893
22.878
178.705
1.00
11.36
A

ATOM
1360
C
GLY
A
312
34.201
22.154
178.454
1.00
10.56
A

ATOM
1361
O
GLY
A
312
34.472
21.741
177.329
1.00
11.29
A

ATOM
1362
N
THR
A
313
35.017
22.018
179.495
1.00
9.91
A

ATOM
1363
CA
THR
A
313
36.294
21.314
179.420
1.00
9.63
A

ATOM
1364
CB
THR
A
313
37.469
22.273
179.754
1.00
8.21
A

ATOM
1365
OG1
THR
A
313
37.591
23.245
178.710
1.00
8.40
A

ATOM
1366
CG2
THR
A
313
38.767
21.538
179.842
1.00
9.49
A

ATOM
1367
C
THR
A
313
36.150
20.163
180.427
1.00
10.10
A

ATOM
1368
O
THR
A
313
35.793
20.414
181.583
1.00
9.15
A

ATOM
1369
N
PRO
A
314
36.419
18.897
180.003
1.00
10.35
A

ATOM
1370
CD
PRO
A
314
36.972
18.514
178.683
1.00
12.20
A

ATOM
1371
CA
PRO
A
314
36.309
17.692
180.842
1.00
10.55
A

ATOM
1372
CB
PRO
A
314
37.131
16.667
180.064
1.00
11.31
A

ATOM
1373
CG
PRO
A
314
36.807
17.012
178.677
1.00
11.44
A

ATOM
1374
C
PRO
A
314
36.693
17.750
182.321
1.00
9.90
A

ATOM
1375
O
PRO
A
314
35.857
17.489
183.190
1.00
10.46
A

ATOM
1376
N
GLU
A
315
37.925
18.169
182.595
1.00
10.50
A

ATOM
1377
CA
GLU
A
315
38.462
18.264
183.956
1.00
9.77
A

ATOM
1378
CB
GLU
A
315
39.981
18.492
183.890
1.00
11.68
A

ATOM
1379
CG
GLU
A
315
40.800
17.322
183.303
1.00
12.07
A

ATOM
1380
CD
GLU
A
315
40.854
17.269
181.773
1.00
15.42
A

ATOM
1381
OE1
GLU
A
315
40.240
18.114
181.084
1.00
14.43
A

ATOM
1382
OE2
GLU
A
315
41.543
16.370
181.250
1.00
18.17
A

ATOM
1383
C
GLU
A
315
37.821
19.352
184.820
1.00
9.08
A

ATOM
1384
O
GLU
A
315
37.923
19.310
186.049
1.00
10.42
A

ATOM
1385
N
TYR
A
316
37.125
20.284
184.167
1.00
7.79
A

ATOM
1386
CA
TYR
A
316
36.479
21.420
184.824
1.00
8.92
A

ATOM
1387
CB
TYR
A
316
36.898
22.718
184.127
1.00
9.19
A

ATOM
1388
CG
TYR
A
316
38.344
23.088
184.339
1.00
8.52
A

ATOM
1389
CD1
TYR
A
316
39.367
22.514
183.555
1.00
9.47
A

ATOM
1390
CE1
TYR
A
316
40.724
22.849
183.762
1.00
9.76
A

ATOM
1391
CD2
TYR
A
316
38.706
24.005
185.337
1.00
10.20
A

ATOM
1392
CE2
TYR
A
316
40.062
24.348
185.560
1.00
8.85
A

ATOM
1393
CZ
TYR
A
316
41.059
23.775
184.765
1.00
9.50
A

ATOM
1394
OH
TYR
A
316
42.351
24.203
184.909
1.00
12.63
A

ATOM
1395
C
TYR
A
316
34.958
21.371
184.902
1.00
9.80
A

ATOM
1396
O
TYR
A
316
34.339
22.274
185.477
1.00
10.39
A

ATOM
1397
N
LEU
A
317
34.359
20.325
184.331
1.00
8.92
A

ATOM
1398
CA
LEU
A
317
32.905
20.175
184.327
1.00
9.94
A

ATOM
1399
CB
LEU
A
317
32.477
18.977
183.478
1.00
9.39
A

ATOM
1400
CG
LEU
A
317
32.619
19.044
181.963
1.00
10.78
A

ATOM
1401
CD1
LEU
A
317
32.104
17.748
181.394
1.00
11.21
A

ATOM
1402
CD2
LEU
A
317
31.866
20.222
181.373
1.00
9.97
A

ATOM
1403
C
LEU
A
317
32.284
20.030
185.704
1.00
8.12
A

ATOM
1404
O
LEU
A
317
32.814
19.324
186.564
1.00
8.69
A

ATOM
1405
N
ALA
A
318
31.175
20.740
185.903
1.00
10.04
A

ATOM
1406
CA
ALA
A
318
30.412
20.701
187.148
1.00
9.46
A

ATOM
1407
CB
ALA
A
318
29.508
21.928
187.236
1.00
10.35
A

ATOM
1408
C
ALA
A
318
29.595
19.405
187.170
1.00
8.52
A

ATOM
1409
O
ALA
A
318
29.194
18.929
186.107
1.00
9.09
A

ATOM
1410
N
PRO
A
319
29.366
18.797
188.365
1.00
9.01
A

ATOM
1411
CD
PRO
A
319
29.815
19.202
189.707
1.00
10.61
A

ATOM
1412
CA
PRO
A
319
28.594
17.548
188.466
1.00
8.90
A

ATOM
1413
CB
PRO
A
319
28.510
17.315
189.973
1.00
9.23
A

ATOM
1414
CG
PRO
A
319
29.769
17.906
190.466
1.00
10.30
A

ATOM
1415
C
PRO
A
319
27.208
17.605
187.844
1.00
8.12
A

ATOM
1416
O
PRO
A
319
26.760
16.625
187.253
1.00
10.13
A

ATOM
1417
N
GLU
A
320
26.556
18.767
187.941
1.00
9.41
A

ATOM
1418
CA
GLU
A
320
25.215
18.952
187.372
1.00
9.08
A

ATOM
1419
CB
GLU
A
320
24.556
20.240
187.895
1.00
10.40
A

ATOM
1420
CG
GLU
A
320
25.240
21.552
187.504
1.00
10.56
A

ATOM
1421
CD
GLU
A
320
26.171
22.108
188.563
1.00
11.83
A

ATOM
1422
OE1
GLU
A
320
26.765
21.329
189.337
1.00
10.20
A

ATOM
1423
OE2
GLU
A
320
26.326
23.348
188.600
1.00
10.61
A

ATOM
1424
C
GLU
A
320
25.197
18.896
185.837
1.00
10.94
A

ATOM
1425
O
GLU
A
320
24.207
18.464
185.245
1.00
10.55
A

ATOM
1426
N
VAL
A
321
26.311
19.288
185.209
1.00
9.07
A

ATOM
1427
CA
VAL
A
321
26.454
19.255
183.744
1.00
10.14
A

ATOM
1428
CB
VAL
A
321
27.662
20.132
183.255
1.00
8.06
A

ATOM
1429
CG1
VAL
A
321
27.740
20.181
181.718
1.00
10.09
A

ATOM
1430
CG2
VAL
A
321
27.528
21.545
183.784
1.00
9.95
A

ATOM
1431
C
VAL
A
321
26.639
17.789
183.313
1.00
10.09
A

ATOM
1432
O
VAL
A
321
26.296
17.414
182.190
1.00
10.46
A

ATOM
1433
N
LEU
A
322
27.136
16.964
184.238
1.00
10.76
A

ATOM
1434
CA
LEU
A
322
27.346
15.534
183.999
1.00
10.24
A

ATOM
1435
CB
LEU
A
322
28.532
15.021
184.815
1.00
10.24
A

ATOM
1436
CG
LEU
A
322
29.875
15.467
184.246
1.00
11.13
A

ATOM
1437
CD1
LEU
A
322
30.975
15.144
185.229
1.00
10.25
A

ATOM
1438
CD2
LEU
A
322
30.106
14.781
182.906
1.00
10.66
A

ATOM
1439
C
LEU
A
322
26.093
14.703
184.261
1.00
9.62
A

ATOM
1440
O
LEU
A
322
26.117
13.466
184.215
1.00
9.76
A

ATOM
1441
N
GLU
A
323
25.003
15.411
184.536
1.00
11.36
A

ATOM
1442
CA
GLU
A
323
23.695
14.819
184.765
1.00
12.36
A

ATOM
1443
CB
GLU
A
323
23.092
15.307
186.086
1.00
12.59
A

ATOM
1444
CG
GLU
A
323
23.833
14.842
187.337
1.00
12.32
A

ATOM
1445
CD
GLU
A
323
23.263
15.415
188.628
1.00
14.18
A

ATOM
1446
OE1
GLU
A
323
22.733
16.546
188.612
1.00
13.47
A

ATOM
1447
OE2
GLU
A
323
23.353
14.733
189.671
1.00
14.44
A

ATOM
1448
C
GLU
A
323
22.811
15.244
183.596
1.00
14.58
A

ATOM
1449
O
GLU
A
323
23.160
16.174
182.864
1.00
15.03
A

ATOM
1450
N
ASP
A
324
21.690
14.549
183.399
1.00
15.81
A

ATOM
1451
CA
ASP
A
324
20.753
14.878
182.322
1.00
18.79
A

ATOM
1452
CB
ASP
A
324
19.741
13.747
182.104
1.00
20.75
A

ATOM
1453
CG
ASP
A
324
20.371
12.482
181.558
1.00
23.45
A

ATOM
1454
OD1
ASP
A
324
21.223
12.558
180.644
1.00
24.22
A

ATOM
1455
OD2
ASP
A
324
19.981
11.399
182.032
1.00
24.40
A

ATOM
1456
C
ASP
A
324
19.992
16.175
182.608
1.00
19.31
A

ATOM
1457
O
ASP
A
324
20.058
16.716
183.715
1.00
18.94
A

ATOM
1458
N
ASN
A
325
19.278
16.653
181.587
1.00
22.17
A

ATOM
1459
CA
ASN
A
325
18.462
17.874
181.618
1.00
23.16
A

ATOM
1460
CB
ASN
A
325
17.340
17.785
182.688
1.00
26.60
A

ATOM
1461
CG
ASN
A
325
16.054
18.515
182.278
1.00
29.66
A

ATOM
1462
OD1
ASN
A
325
15.296
18.973
183.133
1.00
31.41
A

ATOM
1463
ND2
ASN
A
325
15.802
18.610
180.973
1.00
33.05
A

ATOM
1464
C
ASN
A
325
19.261
19.189
181.691
1.00
23.60
A

ATOM
1465
O
ASN
A
325
20.353
19.283
181.119
1.00
25.24
A

ATOM
1466
N
ASP
A
326
18.748
20.167
182.434
1.00
20.49
A

ATOM
1467
CA
ASP
A
326
19.349
21.496
182.516
1.00
17.99
A

ATOM
1468
CB
ASP
A
326
18.260
22.535
182.202
1.00
18.89
A

ATOM
1469
CG
ASP
A
326
17.047
22.458
183.142
1.00
23.31
A

ATOM
1470
OD1
ASP
A
326
17.079
21.724
184.155
1.00
26.82
A

ATOM
1471
OD2
ASP
A
326
16.055
23.172
182.868
1.00
25.35
A

ATOM
1472
C
ASP
A
326
20.168
21.916
183.744
1.00
16.92
A

ATOM
1473
O
ASP
A
326
20.117
21.271
184.787
1.00
16.41
A

ATOM
1474
N
TYR
A
327
20.902
23.023
183.602
1.00
14.26
A

ATOM
1475
CA
TYR
A
327
21.745
23.568
184.673
1.00
12.93
A

ATOM
1476
CB
TYR
A
327
23.176
22.999
184.580
1.00
10.53
A

ATOM
1477
CG
TYR
A
327
23.885
23.243
183.259
1.00
9.84
A

ATOM
1478
CD1
TYR
A
327
24.635
24.423
183.043
1.00
9.94
A

ATOM
1479
CE1
TYR
A
327
25.262
24.679
181.809
1.00
9.67
A

ATOM
1480
CD2
TYR
A
327
23.784
22.315
182.198
1.00
9.05
A

ATOM
1481
CE2
TYR
A
327
24.407
22.562
180.953
1.00
8.79
A

ATOM
1482
CZ
TYR
A
327
25.141
23.752
180.771
1.00
9.34
A

ATOM
1483
OH
TYR
A
327
25.713
24.039
179.558
1.00
11.63
A

ATOM
1484
C
TYR
A
327
21.765
25.100
184.689
1.00
11.84
A

ATOM
1485
O
TYR
A
327
21.590
25.735
183.646
1.00
13.50
A

ATOM
1486
N
GLY
A
328
22.049
25.671
185.860
1.00
13.42
A

ATOM
1487
CA
GLY
A
328
22.086
27.117
186.028
1.00
12.25
A

ATOM
1488
C
GLY
A
328
23.457
27.768
185.989
1.00
10.86
A

ATOM
1489
O
GLY
A
328
24.462
27.117
185.671
1.00
12.06
A

ATOM
1490
N
ARG
A
329
23.492
29.060
186.325
1.00
10.44
A

ATOM
1491
CA
ARG
A
329
24.719
29.872
186.321
1.00
11.12
A

ATOM
1492
CB
ARG
A
329
24.385
31.369
186.466
1.00
13.08
A

ATOM
1493
CG
ARG
A
329
23.730
31.787
187.773
1.00
13.12
A

ATOM
1494
CD
ARG
A
329
23.319
33.241
187.706
1.00
17.93
A

ATOM
1495
NE
ARG
A
329
22.595
33.662
188.903
1.00
22.88
A

ATOM
1496
CZ
ARG
A
329
22.070
34.873
189.082
1.00
25.02
A

ATOM
1497
NH1
ARG
A
329
22.180
35.806
188.143
1.00
27.77
A

ATOM
1498
NH2
ARG
A
329
21.426
35.150
190.207
1.00
27.77
A

ATOM
1499
C
ARG
A
329
25.812
29.488
187.318
1.00
11.17
A

ATOM
1500
O
ARG
A
329
26.962
29.906
187.158
1.00
9.66
A

ATOM
1501
N
ALA
A
330
25.458
28.653
188.299
1.00
10.24
A

ATOM
1502
CA
ALA
A
330
26.382
28.195
189.340
1.00
10.50
A

ATOM
1503
CB
ALA
A
330
25.633
27.407
190.407
1.00
9.00
A

ATOM
1504
C
ALA
A
330
27.575
27.383
188.831
1.00
8.85
A

ATOM
1505
O
ALA
A
330
28.532
27.165
189.576
1.00
8.15
A

ATOM
1506
N
VAL
A
331
27.525
26.967
187.561
1.00
8.42
A

ATOM
1507
CA
VAL
A
331
28.614
26.202
186.939
1.00
8.41
A

ATOM
1508
CB
VAL
A
331
28.253
25.700
185.510
1.00
9.21
A

ATOM
1509
CG1
VAL
A
331
27.118
24.714
185.601
1.00
9.28
A

ATOM
1510
CG2
VAL
A
331
27.874
26.864
184.575
1.00
12.35
A

ATOM
1511
C
VAL
A
331
29.920
27.000
186.901
1.00
6.92
A

ATOM
1512
O
VAL
A
331
31.002
26.426
186.998
1.00
7.72
A

ATOM
1513
N
ASP
A
332
29.794
28.329
186.829
1.00
8.72
A

ATOM
1514
CA
ASP
A
332
30.949
29.230
186.808
1.00
8.42
A

ATOM
1515
CB
ASP
A
332
30.543
30.648
186.390
1.00
9.09
A

ATOM
1516
CG
ASP
A
332
30.297
30.779
184.891
1.00
10.81
A

ATOM
1517
OD1
ASP
A
332
30.726
29.897
184.116
1.00
8.54
A

ATOM
1518
OD2
ASP
A
332
29.686
31.788
184.483
1.00
10.71
A

ATOM
1519
C
ASP
A
332
31.663
29.279
188.156
1.00
8.16
A

ATOM
1520
O
ASP
A
332
32.877
29.489
188.205
1.00
9.32
A

ATOM
1521
N
TRP
A
333
30.914
29.049
189.240
1.00
7.97
A

ATOM
1522
CA
TRP
A
333
31.499
29.055
190.582
1.00
7.70
A

ATOM
1523
CB
TRP
A
333
30.460
29.418
191.655
1.00
7.03
A

ATOM
1524
CG
TRP
A
333
29.794
30.749
191.372
1.00
8.05
A

ATOM
1525
CD2
TRP
A
333
30.429
32.035
191.199
1.00
9.02
A

ATOM
1526
CE2
TRP
A
333
29.413
32.950
190.820
1.00
9.48
A

ATOM
1527
CE3
TRP
A
333
31.759
32.506
191.320
1.00
8.07
A

ATOM
1528
CD1
TRP
A
333
28.470
30.948
191.117
1.00
8.00
A

ATOM
1529
NE1
TRP
A
333
28.232
32.257
190.782
1.00
10.50
A

ATOM
1530
CZ2
TRP
A
333
29.679
34.312
190.554
1.00
10.90
A

ATOM
1531
CZ3
TRP
A
333
32.028
33.870
191.058
1.00
10.17
A

ATOM
1532
CH2
TRP
A
333
30.985
34.753
190.678
1.00
10.71
A

ATOM
1533
C
TRP
A
333
32.249
27.764
190.870
1.00
7.92
A

ATOM
1534
O
TRP
A
333
33.278
27.782
191.556
1.00
9.29
A

ATOM
1535
N
TRP
A
334
31.792
26.669
190.252
1.00
8.16
A

ATOM
1536
CA
TRP
A
334
32.473
25.374
190.367
1.00
6.51
A

ATOM
1537
CB
TRP
A
334
31.663
24.248
189.698
1.00
7.58
A

ATOM
1538
CG
TRP
A
334
32.431
22.936
189.535
1.00
7.77
A

ATOM
1539
CD2
TRP
A
334
32.484
21.843
190.458
1.00
6.79
A

ATOM
1540
CE2
TRP
A
334
33.375
20.873
189.906
1.00
6.34
A

ATOM
1541
CE3
TRP
A
334
31.872
21.579
191.701
1.00
8.55
A

ATOM
1542
CD1
TRP
A
334
33.258
22.585
188.484
1.00
6.61
A

ATOM
1543
NE1
TRP
A
334
33.824
21.361
188.708
1.00
7.06
A

ATOM
1544
CZ2
TRP
A
334
33.673
19.655
190.557
1.00
6.77
A

ATOM
1545
CZ3
TRP
A
334
32.170
20.349
192.358
1.00
7.71
A

ATOM
1546
CH2
TRP
A
334
33.066
19.410
191.775
1.00
8.15
A

ATOM
1547
C
TRP
A
334
33.820
25.538
189.647
1.00
7.38
A

ATOM
1548
O
TRP
A
334
34.846
25.086
190.148
1.00
8.42
A

ATOM
1549
N
GLY
A
335
33.773
26.146
188.455
1.00
7.12
A

ATOM
1550
CA
GLY
A
335
34.967
26.385
187.650
1.00
6.28
A

ATOM
1551
C
GLY
A
335
35.979
27.232
188.394
1.00
6.84
A

ATOM
1552
O
GLY
A
335
37.180
26.946
188.365
1.00
6.62
A

ATOM
1553
N
LEU
A
336
35.478
28.256
189.092
1.00
6.68
A

ATOM
1554
CA
LEU
A
336
36.317
29.136
189.908
1.00
4.47
A

ATOM
1555
CB
LEU
A
336
35.503
30.281
190.524
1.00
5.67
A

ATOM
1556
CG
LEU
A
336
36.249
31.165
191.542
1.00
6.85
A

ATOM
1557
CD1
LEU
A
336
37.319
32.015
190.873
1.00
9.49
A

ATOM
1558
CD2
LEU
A
336
35.274
32.026
192.298
1.00
9.90
A

ATOM
1559
C
LEU
A
336
36.945
28.277
191.008
1.00
5.28
A

ATOM
1560
O
LEU
A
336
38.136
28.389
191.284
1.00
4.65
A

ATOM
1561
N
GLY
A
337
36.152
27.351
191.546
1.00
5.39
A

ATOM
1562
CA
GLY
A
337
36.630
26.446
192.582
1.00
5.35
A

ATOM
1563
C
GLY
A
337
37.768
25.555
192.137
1.00
6.46
A

ATOM
1564
O
GLY
A
337
38.736
25.374
192.878
1.00
6.24
A

ATOM
1565
N
VAL
A
338
37.678
25.054
190.904
1.00
5.24
A

ATOM
1566
CA
VAL
A
338
38.715
24.181
190.356
1.00
5.90
A

ATOM
1567
CB
VAL
A
338
38.269
23.482
189.043
1.00
5.33
A

ATOM
1568
CG1
VAL
A
338
39.352
22.537
188.548
1.00
5.96
A

ATOM
1569
CG2
VAL
A
338
37.000
22.684
189.262
1.00
8.01
A

ATOM
1570
C
VAL
A
338
40.033
24.940
190.151
1.00
6.00
A

ATOM
1571
O
VAL
A
338
41.090
24.430
190.534
1.00
5.44
A

ATOM
1572
N
VAL
A
339
39.970
26.163
189.611
1.00
6.37
A

ATOM
1573
CA
VAL
A
339
41.197
26.950
189.404
1.00
6.09
A

ATOM
1574
CB
VAL
A
339
41.043
28.145
188.402
1.00
6.11
A

ATOM
1575
CG1
VAL
A
339
40.624
27.634
187.045
1.00
8.57
A

ATOM
1576
CG2
VAL
A
339
40.086
29.206
188.899
1.00
11.74
A

ATOM
1577
C
VAL
A
339
41.821
27.414
190.719
1.00
5.30
A

ATOM
1578
O
VAL
A
339
43.038
27.415
190.853
1.00
6.78
A

ATOM
1579
N
MET
A
340
40.978
27.735
191.704
1.00
7.84
A

ATOM
1580
CA
MET
A
340
41.455
28.154
193.021
1.00
7.60
A

ATOM
1581
CB
MET
A
340
40.314
28.718
193.873
1.00
9.80
A

ATOM
1582
CG
MET
A
340
39.808
30.088
193.440
1.00
12.08
A

ATOM
1583
SD
MET
A
340
41.050
31.377
193.499
1.00
15.52
A

ATOM
1584
CE
MET
A
340
41.018
31.824
195.212
1.00
13.99
A

ATOM
1585
C
MET
A
340
42.125
26.968
193.722
1.00
7.55
A

ATOM
1586
O
MET
A
340
43.148
27.142
194.389
1.00
7.33
A

ATOM
1587
N
TYR
A
341
41.591
25.762
193.486
1.00
7.78
A

ATOM
1588
CA
TYR
A
341
42.139
24.525
194.050
1.00
7.21
A

ATOM
1589
CB
TYR
A
341
41.183
23.327
193.830
1.00
7.22
A

ATOM
1590
CG
TYR
A
341
41.578
22.049
194.561
1.00
7.96
A

ATOM
1591
CD1
TYR
A
341
42.624
21.231
194.079
1.00
7.01
A

ATOM
1592
CE1
TYR
A
341
43.029
20.068
194.756
1.00
8.21
A

ATOM
1593
CD2
TYR
A
341
40.933
21.661
195.750
1.00
7.56
A

ATOM
1594
CE2
TYR
A
341
41.331
20.478
196.447
1.00
7.60
A

ATOM
1595
CZ
TYR
A
341
42.385
19.697
195.934
1.00
8.92
A

ATOM
1596
OH
TYR
A
341
42.825
18.569
196.576
1.00
10.99
A

ATOM
1597
C
TYR
A
341
43.509
24.272
193.417
1.00
6.78
A

ATOM
1598
O
TYR
A
341
44.469
24.003
194.129
1.00
7.58
A

ATOM
1599
N
GLU
A
342
43.596
24.390
192.091
1.00
6.47
A

ATOM
1600
CA
GLU
A
342
44.858
24.197
191.375
1.00
7.82
A

ATOM
1601
CB
GLU
A
342
44.659
24.355
189.876
1.00
6.70
A

ATOM
1602
CG
GLU
A
342
43.909
23.227
189.232
1.00
8.49
A

ATOM
1603
CD
GLU
A
342
43.719
23.466
187.763
1.00
10.87
A

ATOM
1604
OE1
GLU
A
342
42.866
24.302
187.416
1.00
8.48
A

ATOM
1605
OE2
GLU
A
342
44.435
22.842
186.954
1.00
10.15
A

ATOM
1606
C
GLU
A
342
45.925
25.181
191.835
1.00
7.08
A

ATOM
1607
O
GLU
A
342
47.084
24.805
192.023
1.00
7.82
A

ATOM
1608
N
MET
A
343
45.515
26.434
192.040
1.00
9.08
A

ATOM
1609
CA
MET
A
343
46.429
27.486
192.487
1.00
8.94
A

ATOM
1610
CB
MET
A
343
45.786
28.872
192.360
1.00
9.73
A

ATOM
1611
CG
MET
A
343
45.561
29.331
190.926
1.00
11.44
A

ATOM
1612
SD
MET
A
343
45.208
31.100
190.816
1.00
13.16
A

ATOM
1613
CE
MET
A
343
43.432
31.110
190.813
1.00
15.26
A

ATOM
1614
C
MET
A
343
46.951
27.291
193.910
1.00
9.79
A

ATOM
1615
O
MET
A
343
48.130
27.521
194.168
1.00
9.24
A

ATOM
1616
N
MET
A
344
46.091
26.812
194.812
1.00
8.11
A

ATOM
1617
CA
MET
A
344
46.486
26.626
196.213
1.00
9.92
A

ATOM
1618
CB
MET
A
344
45.378
27.107
197.152
1.00
10.64
A

ATOM
1619
CG
MET
A
344
45.118
28.579
197.021
1.00
11.26
A

ATOM
1620
SD
MET
A
344
44.052
29.333
198.240
1.00
12.53
A

ATOM
1621
CE
MET
A
344
42.443
28.833
197.665
1.00
14.60
A

ATOM
1622
C
MET
A
344
46.951
25.242
196.629
1.00
10.10
A

ATOM
1623
O
MET
A
344
47.716
25.113
197.594
1.00
11.04
A

ATOM
1624
N
CYS
A
345
46.537
24.219
195.884
1.00
10.86
A

ATOM
1625
CA
CYS
A
345
46.907
22.840
196.200
1.00
9.73
A

ATOM
1626
CB
CYS
A
345
45.655
21.982
196.381
1.00
11.24
A

ATOM
1627
SG
CYS
A
345
44.441
22.623
197.568
1.00
11.81
A

ATOM
1628
C
CYS
A
345
47.864
22.195
195.193
1.00
9.70
A

ATOM
1629
O
CYS
A
345
48.332
21.079
195.414
1.00
11.96
A

ATOM
1630
N
GLY
A
346
48.140
22.893
194.090
1.00
10.45
A

ATOM
1631
CA
GLY
A
346
49.078
22.401
193.085
1.00
10.92
A

ATOM
1632
C
GLY
A
346
48.691
21.245
192.179
1.00
10.71
A

ATOM
1633
O
GLY
A
346
49.561
20.638
191.549
1.00
13.43
A

ATOM
1634
N
ARG
A
347
47.400
20.929
192.130
1.00
9.02
A

ATOM
1635
CA
ARG
A
347
46.867
19.852
191.294
1.00
9.41
A

ATOM
1636
CB
ARG
A
347
47.137
18.464
191.922
1.00
10.70
A

ATOM
1637
CG
ARG
A
347
46.513
18.208
193.305
1.00
11.11
A

ATOM
1638
CD
ARG
A
347
46.485
16.712
193.606
1.00
13.31
A

ATOM
1639
NE
ARG
A
347
45.844
16.367
194.878
1.00
13.84
A

ATOM
1640
CZ
ARG
A
347
44.553
16.069
195.031
1.00
16.02
A

ATOM
1641
NH1
ARG
A
347
43.723
16.087
193.993
1.00
16.77
A

ATOM
1642
NH2
ARG
A
347
44.098
15.692
196.221
1.00
15.24
A

ATOM
1643
C
ARG
A
347
45.366
20.038
191.118
1.00
9.80
A

ATOM
1644
O
ARG
A
347
44.742
20.818
191.839
1.00
7.76
A

ATOM
1645
N
LEU
A
348
44.790
19.299
190.170
1.00
8.76
A

ATOM
1646
CA
LEU
A
348
43.347
19.322
189.932
1.00
7.77
A

ATOM
1647
CB
LEU
A
348
43.016
18.607
188.618
1.00
7.94
A

ATOM
1648
CG
LEU
A
348
43.179
19.366
187.307
1.00
4.37
A

ATOM
1649
CD1
LEU
A
348
43.207
18.384
186.184
1.00
8.30
A

ATOM
1650
CD2
LEU
A
348
42.024
20.348
187.117
1.00
5.26
A

ATOM
1651
C
LEU
A
348
42.691
18.556
191.080
1.00
8.12
A

ATOM
1652
O
LEU
A
348
43.339
17.691
191.679
1.00
7.63
A

ATOM
1653
N
PRO
A
349
41.445
18.918
191.467
1.00
6.62
A

ATOM
1654
CD
PRO
A
349
40.641
20.102
191.103
1.00
7.65
A

ATOM
1655
CA
PRO
A
349
40.799
18.176
192.562
1.00
8.62
A

ATOM
1656
CB
PRO
A
349
39.548
19.012
192.863
1.00
8.60
A

ATOM
1657
CG
PRO
A
349
39.268
19.720
191.564
1.00
6.96
A

ATOM
1658
C
PRO
A
349
40.468
16.735
192.180
1.00
10.52
A

ATOM
1659
O
PRO
A
349
40.465
15.844
193.035
1.00
12.38
A

ATOM
1660
N
PHE
A
350
40.215
16.530
190.886
1.00
11.12
A

ATOM
1661
CA
PHE
A
350
39.881
15.224
190.312
1.00
11.86
A

ATOM
1662
CB
PHE
A
350
38.369
15.104
190.034
1.00
12.02
A

ATOM
1663
CG
PHE
A
350
37.494
15.491
191.191
1.00
13.00
A

ATOM
1664
CD1
PHE
A
350
37.412
14.675
192.335
1.00
13.23
A

ATOM
1665
CD2
PHE
A
350
36.772
16.702
191.162
1.00
14.04
A

ATOM
1666
CE1
PHE
A
350
36.622
15.060
193.447
1.00
14.82
A

ATOM
1667
CE2
PHE
A
350
35.974
17.101
192.268
1.00
12.10
A

ATOM
1668
CZ
PHE
A
350
35.902
16.274
193.412
1.00
13.30
A

ATOM
1669
C
PHE
A
350
40.612
15.063
188.987
1.00
11.79
A

ATOM
1670
O
PHE
A
350
40.535
15.948
188.125
1.00
10.18
A

ATOM
1671
N
TYR
A
351
41.318
13.941
188.823
1.00
12.02
A

ATOM
1672
CA
TYR
A
351
42.031
13.660
187.577
1.00
11.41
A

ATOM
1673
CB
TYR
A
351
43.395
14.398
187.496
1.00
12.73
A

ATOM
1674
CG
TYR
A
351
44.077
14.267
186.132
1.00
15.09
A

ATOM
1675
CD1
TYR
A
351
43.525
14.882
184.983
1.00
16.36
A

ATOM
1676
CE1
TYR
A
351
44.075
14.661
183.688
1.00
17.90
A

ATOM
1677
CD2
TYR
A
351
45.206
13.432
185.961
1.00
16.94
A

ATOM
1678
CE2
TYR
A
351
45.763
13.197
184.671
1.00
17.10
A

ATOM
1679
CZ
TYR
A
351
45.189
13.813
183.545
1.00
18.68
A

ATOM
1680
OH
TYR
A
351
45.705
13.567
182.296
1.00
19.38
A

ATOM
1681
C
TYR
A
351
42.235
12.183
187.258
1.00
10.65
A

ATOM
1682
O
TYR
A
351
42.535
11.370
188.133
1.00
9.83
A

ATOM
1683
N
ASN
A
352
42.097
11.894
185.964
1.00
13.33
A

ATOM
1684
CA
ASN
A
352
42.306
10.589
185.337
1.00
15.06
A

ATOM
1685
CB
ASN
A
352
41.179
9.591
185.650
1.00
15.24
A

ATOM
1686
CG
ASN
A
352
41.552
8.153
185.284
1.00
16.92
A

ATOM
1687
OD1
ASN
A
352
41.586
7.788
184.108
1.00
14.81
A

ATOM
1688
ND2
ASN
A
352
41.817
7.334
186.292
1.00
15.78
A

ATOM
1689
C
ASN
A
352
42.358
10.881
183.833
1.00
16.14
A

ATOM
1690
O
ASN
A
352
41.558
11.677
183.326
1.00
16.48
A

ATOM
1691
N
GLN
A
353
43.292
10.233
183.130
1.00
18.24
A

ATOM
1692
CA
GLN
A
353
43.475
10.398
181.678
1.00
20.68
A

ATOM
1693
CB
GLN
A
353
44.721
9.636
181.194
1.00
23.71
A

ATOM
1694
CG
GLN
A
353
44.775
8.154
181.584
1.00
29.95
A

ATOM
1695
CD
GLN
A
353
45.429
7.286
180.527
1.00
33.80
A

ATOM
1696
OE1
GLN
A
353
46.598
7.473
180.183
1.00
37.41
A

ATOM
1697
NE2
GLN
A
353
44.672
6.326
180.003
1.00
34.96
A

ATOM
1698
C
GLN
A
353
42.256
9.980
180.845
1.00
20.32
A

ATOM
1699
O
GLN
A
353
42.007
10.530
179.769
1.00
21.84
A

ATOM
1700
N
ASP
A
354
41.511
9.004
181.361
1.00
20.74
A

ATOM
1701
CA
ASP
A
354
40.304
8.489
180.721
1.00
21.34
A

ATOM
1702
CB
ASP
A
354
40.100
7.018
181.116
1.00
23.31
A

ATOM
1703
CG
ASP
A
354
38.885
6.389
180.456
1.00
28.32
A

ATOM
1704
OD1
ASP
A
354
37.856
6.242
181.144
1.00
30.76
A

ATOM
1705
OD2
ASP
A
354
38.957
6.044
179.258
1.00
30.43
A

ATOM
1706
C
ASP
A
354
39.139
9.360
181.198
1.00
19.72
A

ATOM
1707
O
ASP
A
354
38.920
9.498
182.406
1.00
19.08
A

ATOM
1708
N
HIS
A
355
38.411
9.944
180.245
1.00
19.58
A

ATOM
1709
CA
HIS
A
355
37.271
10.820
180.536
1.00
19.39
A

ATOM
1710
CB
HIS
A
355
36.764
11.511
179.263
1.00
19.77
A

ATOM
1711
CG
HIS
A
355
37.698
12.551
178.715
1.00
19.38
A

ATOM
1712
CD2
HIS
A
355
38.764
13.182
179.265
1.00
17.83
A

ATOM
1713
ND1
HIS
A
355
37.578
13.052
177.436
1.00
21.90
A

ATOM
1714
CE1
HIS
A
355
38.529
13.944
177.222
1.00
21.76
A

ATOM
1715
NE2
HIS
A
355
39.262
14.042
178.316
1.00
20.76
A

ATOM
1716
C
HIS
A
355
36.115
10.166
181.291
1.00
20.04
A

ATOM
1717
O
HIS
A
355
35.514
10.805
182.154
1.00
18.52
A

ATOM
1718
N
GLU
A
356
35.853
8.885
181.012
1.00
20.65
A

ATOM
1719
CA
GLU
A
356
34.785
8.129
181.683
1.00
20.99
A

ATOM
1720
CB
GLU
A
356
34.607
6.744
181.053
1.00
25.74
A

ATOM
1721
CG
GLU
A
356
34.065
6.752
179.632
1.00
32.46
A

ATOM
1722
CD
GLU
A
356
33.852
5.350
179.087
1.00
36.08
A

ATOM
1723
OE1
GLU
A
356
34.635
4.928
178.209
1.00
38.52
A

ATOM
1724
OE2
GLU
A
356
32.905
4.670
179.540
1.00
38.42
A

ATOM
1725
C
GLU
A
356
35.060
7.975
183.181
1.00
18.43
A

ATOM
1726
O
GLU
A
356
34.157
8.155
183.999
1.00
18.67
A

ATOM
1727
N
ARG
A
357
36.322
7.704
183.527
1.00
15.83
A

ATOM
1728
CA
ARG
A
357
36.748
7.552
184.923
1.00
15.71
A

ATOM
1729
CB
ARG
A
357
38.129
6.894
185.014
1.00
16.68
A

ATOM
1730
CG
ARG
A
357
38.264
5.485
184.432
1.00
19.52
A

ATOM
1731
CD
ARG
A
357
37.563
4.407
185.263
1.00
23.41
A

ATOM
1732
NE
ARG
A
357
36.140
4.264
184.944
1.00
28.97
A

ATOM
1733
CZ
ARG
A
357
35.651
3.612
183.889
1.00
30.77
A

ATOM
1734
NH1
ARG
A
357
34.339
3.551
183.706
1.00
32.39
A

ATOM
1735
NH2
ARG
A
357
36.462
3.022
183.015
1.00
30.71
A

ATOM
1736
C
ARG
A
357
36.791
8.913
185.618
1.00
11.47
A

ATOM
1737
O
ARG
A
357
36.442
9.019
186.791
1.00
10.69
A

ATOM
1738
N
LEU
A
358
37.172
9.948
184.862
1.00
11.53
A

ATOM
1739
CA
LEU
A
358
37.248
11.334
185.356
1.00
10.03
A

ATOM
1740
CB
LEU
A
358
37.860
12.243
184.278
1.00
10.92
A

ATOM
1741
CG
LEU
A
358
37.811
13.775
184.369
1.00
10.43
A

ATOM
1742
CD1
LEU
A
358
38.723
14.289
185.482
1.00
11.85
A

ATOM
1743
CD2
LEU
A
358
38.202
14.353
183.034
1.00
12.77
A

ATOM
1744
C
LEU
A
358
35.857
11.849
185.743
1.00
9.95
A

ATOM
1745
O
LEU
A
358
35.699
12.506
186.771
1.00
8.78
A

ATOM
1746
N
PHE
A
359
34.862
11.524
184.917
1.00
11.15
A

ATOM
1747
CA
PHE
A
359
33.478
11.937
185.148
1.00
11.12
A

ATOM
1748
CB
PHE
A
359
32.613
11.674
183.908
1.00
12.11
A

ATOM
1749
CG
PHE
A
359
32.970
12.534
182.711
1.00
12.91
A

ATOM
1750
CD1
PHE
A
359
32.520
12.172
181.426
1.00
13.76
A

ATOM
1751
CD2
PHE
A
359
33.742
13.715
182.854
1.00
12.49
A

ATOM
1752
CE1
PHE
A
359
32.827
12.968
180.290
1.00
15.22
A

ATOM
1753
CE2
PHE
A
359
34.060
14.523
181.732
1.00
14.08
A

ATOM
1754
CZ
PHE
A
359
33.601
14.150
180.443
1.00
15.66
A

ATOM
1755
C
PHE
A
359
32.892
11.279
186.386
1.00
11.66
A

ATOM
1756
O
PHE
A
359
32.102
11.898
187.099
1.00
12.57
A

ATOM
1757
N
GLU
A
360
33.357
10.059
186.673
1.00
13.41
A

ATOM
1758
CA
GLU
A
360
32.941
9.302
187.857
1.00
13.36
A

ATOM
1759
CB
GLU
A
360
33.412
7.847
187.773
1.00
15.74
A

ATOM
1760
CG
GLU
A
360
32.655
7.001
186.751
1.00
20.96
A

ATOM
1761
CD
GLU
A
360
33.291
5.637
186.480
1.00
23.89
A

ATOM
1762
OE1
GLU
A
360
34.370
5.328
187.034
1.00
23.51
A

ATOM
1763
OE2
GLU
A
360
32.701
4.868
185.691
1.00
27.47
A

ATOM
1764
C
GLU
A
360
33.539
9.970
189.095
1.00
12.15
A

ATOM
1765
O
GLU
A
360
32.872
10.098
190.109
1.00
11.69
A

ATOM
1766
N
LEU
A
361
34.772
10.462
188.971
1.00
10.17
A

ATOM
1767
CA
LEU
A
361
35.449
11.148
190.076
1.00
9.58
A

ATOM
1768
CB
LEU
A
361
36.927
11.391
189.747
1.00
9.91
A

ATOM
1769
CG
LEU
A
361
37.869
10.187
189.621
1.00
11.80
A

ATOM
1770
CD1
LEU
A
361
39.220
10.671
189.133
1.00
12.73
A

ATOM
1771
CD2
LEU
A
361
38.015
9.450
190.951
1.00
12.04
A

ATOM
1772
C
LEU
A
361
34.763
12.471
190.430
1.00
8.52
A

ATOM
1773
O
LEU
A
361
34.522
12.745
191.601
1.00
9.51
A

ATOM
1774
N
ILE
A
362
34.390
13.247
189.408
1.00
8.48
A

ATOM
1775
CA
ILE
A
362
33.715
14.542
189.593
1.00
8.08
A

ATOM
1776
CB
ILE
A
362
33.573
15.305
188.231
1.00
7.37
A

ATOM
1777
CG2
ILE
A
362
32.714
16.567
188.379
1.00
8.25
A

ATOM
1778
CG1
ILE
A
362
34.960
15.696
187.703
1.00
8.55
A

ATOM
1779
CD1
ILE
A
362
34.981
16.199
186.255
1.00
9.49
A

ATOM
1780
C
ILE
A
362
32.340
14.370
190.264
1.00
7.15
A

ATOM
1781
O
ILE
A
362
31.966
15.149
191.142
1.00
7.87
A

ATOM
1782
N
LEU
A
363
31.629
13.320
189.870
1.00
8.80
A

ATOM
1783
CA
LEU
A
363
30.311
13.028
190.416
1.00
9.50
A

ATOM
1784
CB
LEU
A
363
29.511
12.163
189.433
1.00
10.23
A

ATOM
1785
CG
LEU
A
363
28.866
12.756
188.183
1.00
11.66
A

ATOM
1786
CD1
LEU
A
363
28.563
11.635
187.201
1.00
12.67
A

ATOM
1787
CD2
LEU
A
363
27.597
13.511
188.547
1.00
11.57
A

ATOM
1788
C
LEU
A
363
30.306
12.325
191.769
1.00
9.37
A

ATOM
1789
O
LEU
A
363
29.470
12.638
192.611
1.00
9.29
A

ATOM
1790
N
MET
A
364
31.270
11.424
191.991
1.00
12.17
A

ATOM
1791
CA
MET
A
364
31.306
10.594
193.205
1.00
11.00
A

ATOM
1792
CB
MET
A
364
31.343
9.103
192.817
1.00
12.91
A

ATOM
1793
CG
MET
A
364
30.464
8.668
191.649
1.00
15.64
A

ATOM
1794
SD
MET
A
364
28.732
8.949
191.931
1.00
17.28
A

ATOM
1795
CE
MET
A
364
28.046
8.535
190.264
1.00
12.45
A

ATOM
1796
C
MET
A
364
32.386
10.786
194.265
1.00
11.80
A

ATOM
1797
O
MET
A
364
32.139
10.503
195.437
1.00
12.72
A

ATOM
1798
N
GLU
A
365
33.586
11.193
193.858
1.00
9.97
A

ATOM
1799
CA
GLU
A
365
34.700
11.343
194.802
1.00
11.91
A

ATOM
1800
CB
GLU
A
365
36.043
11.191
194.062
1.00
11.49
A

ATOM
1801
CG
GLU
A
365
37.295
11.013
194.941
1.00
16.42
A

ATOM
1802
CD
GLU
A
365
37.255
9.748
195.789
1.00
18.10
A

ATOM
1803
OE1
GLU
A
365
37.645
8.678
195.278
1.00
21.84
A

ATOM
1804
OE2
GLU
A
365
36.827
9.828
196.961
1.00
19.20
A

ATOM
1805
C
GLU
A
365
34.686
12.622
195.633
1.00
13.09
A

ATOM
1806
O
GLU
A
365
34.324
13.687
195.141
1.00
12.98
A

ATOM
1807
N
GLU
A
366
35.074
12.505
196.903
1.00
13.82
A

ATOM
1808
CA
GLU
A
366
35.132
13.675
197.769
1.00
17.11
A

ATOM
1809
CB
GLU
A
366
34.663
13.370
199.199
1.00
21.86
A

ATOM
1810
CG
GLU
A
366
35.242
12.138
199.864
1.00
27.09
A

ATOM
1811
CD
GLU
A
366
34.590
11.863
201.211
1.00
31.54
A

ATOM
1812
OE1
GLU
A
366
33.555
11.158
201.244
1.00
34.18
A

ATOM
1813
OE2
GLU
A
366
35.105
12.362
202.236
1.00
33.66
A

ATOM
1814
C
GLU
A
366
36.511
14.327
197.736
1.00
16.12
A

ATOM
1815
O
GLU
A
366
37.535
13.649
197.578
1.00
15.84
A

ATOM
1816
N
ILE
A
367
36.503
15.657
197.786
1.00
16.03
A

ATOM
1817
CA
ILE
A
367
37.711
16.482
197.759
1.00
16.93
A

ATOM
1818
CB
ILE
A
367
37.386
17.986
197.547
1.00
18.85
A

ATOM
1819
CG2
ILE
A
367
37.265
18.290
196.058
1.00
19.99
A

ATOM
1820
CG1
ILE
A
367
36.154
18.392
198.376
1.00
22.24
A

ATOM
1821
CD1
ILE
A
367
35.726
19.831
198.234
1.00
26.50
A

ATOM
1822
C
ILE
A
367
38.569
16.353
199.010
1.00
16.24
A

ATOM
1823
O
ILE
A
367
38.057
16.146
200.114
1.00
16.79
A

ATOM
1824
N
ARG
A
368
39.881
16.417
198.797
1.00
14.71
A

ATOM
1825
CA
ARG
A
368
40.867
16.333
199.868
1.00
14.98
A

ATOM
1826
CB
ARG
A
368
41.783
15.129
199.657
1.00
15.28
A

ATOM
1827
CG
ARG
A
368
41.061
13.796
199.810
1.00
16.96
A

ATOM
1828
CD
ARG
A
368
41.968
12.615
199.551
1.00
15.72
A

ATOM
1829
NE
ARG
A
368
43.020
12.464
200.558
1.00
13.71
A

ATOM
1830
CZ
ARG
A
368
42.860
11.897
201.753
1.00
14.25
A

ATOM
1831
NH1
ARG
A
368
41.674
11.425
202.130
1.00
12.11
A

ATOM
1832
NH2
ARG
A
368
43.910
11.730
202.548
1.00
13.19
A

ATOM
1833
C
ARG
A
368
41.667
17.626
199.887
1.00
13.16
A

ATOM
1834
O
ARG
A
368
41.797
18.288
198.859
1.00
14.99
A

ATOM
1835
N
PHE
A
369
42.154
18.009
201.065
1.00
11.72
A

ATOM
1836
CA
PHE
A
369
42.919
19.247
201.232
1.00
12.56
A

ATOM
1837
CB
PHE
A
369
42.124
20.266
202.075
1.00
14.44
A

ATOM
1838
CG
PHE
A
369
40.806
20.660
201.492
1.00
16.74
A

ATOM
1839
CD1
PHE
A
369
40.740
21.329
200.255
1.00
16.87
A

ATOM
1840
CD2
PHE
A
369
39.615
20.357
202.175
1.00
18.15
A

ATOM
1841
CE1
PHE
A
369
39.497
21.691
199.700
1.00
17.51
A

ATOM
1842
CE2
PHE
A
369
38.355
20.715
201.635
1.00
17.80
A

ATOM
1843
CZ
PHE
A
369
38.298
21.385
200.391
1.00
18.34
A

ATOM
1844
C
PHE
A
369
44.214
19.014
201.988
1.00
10.89
A

ATOM
1845
O
PHE
A
369
44.244
18.175
202.892
1.00
9.62
A

ATOM
1846
N
PRO
A
370
45.297
19.767
201.654
1.00
11.55
A

ATOM
1847
CD
PRO
A
370
45.486
20.615
200.458
1.00
9.99
A

ATOM
1848
CA
PRO
A
370
46.577
19.614
202.364
1.00
11.45
A

ATOM
1849
CB
PRO
A
370
47.493
20.586
201.619
1.00
13.59
A

ATOM
1850
CG
PRO
A
370
46.972
20.535
200.234
1.00
12.44
A

ATOM
1851
C
PRO
A
370
46.351
20.084
203.810
1.00
13.02
A

ATOM
1852
O
PRO
A
370
45.597
21.036
204.030
1.00
11.71
A

ATOM
1853
N
ARG
A
371
46.941
19.389
204.787
1.00
12.92
A

ATOM
1854
CA
ARG
A
371
46.782
19.735
206.213
1.00
15.39
A

ATOM
1855
CB
ARG
A
371
47.612
18.794
207.093
1.00
15.08
A

ATOM
1856
CG
ARG
A
371
47.102
17.378
207.153
1.00
17.29
A

ATOM
1857
CD
ARG
A
371
48.043
16.473
207.934
1.00
18.11
A

ATOM
1858
NE
ARG
A
371
47.703
15.060
207.764
1.00
19.41
A

ATOM
1859
CZ
ARG
A
371
46.831
14.385
208.512
1.00
21.94
A

ATOM
1860
NH1
ARG
A
371
46.185
14.978
209.509
1.00
23.13
A

ATOM
1861
NH2
ARG
A
371
46.603
13.103
208.258
1.00
21.92
A

ATOM
1862
C
ARG
A
371
47.138
21.175
206.581
1.00
16.98
A

ATOM
1863
O
ARG
A
371
46.508
21.774
207.465
1.00
17.84
A

ATOM
1864
N
THR
A
372
48.110
21.726
205.853
1.00
16.72
A

ATOM
1865
CA
THR
A
372
48.626
23.078
206.065
1.00
19.70
A

ATOM
1866
CB
THR
A
372
50.095
23.187
205.598
1.00
20.96
A

ATOM
1867
OG1
THR
A
372
50.191
22.808
204.218
1.00
23.21
A

ATOM
1868
CG2
THR
A
372
50.990
22.289
206.443
1.00
23.38
A

ATOM
1869
C
THR
A
372
47.828
24.221
205.441
1.00
18.26
A

ATOM
1870
O
THR
A
372
48.093
25.391
205.739
1.00
20.19
A

ATOM
1871
N
LEU
A
373
46.867
23.887
204.575
1.00
16.85
A

ATOM
1872
CA
LEU
A
373
46.012
24.889
203.923
1.00
14.74
A

ATOM
1873
CB
LEU
A
373
45.106
24.214
202.880
1.00
15.58
A

ATOM
1874
CG
LEU
A
373
44.364
25.061
201.836
1.00
15.64
A

ATOM
1875
CD1
LEU
A
373
45.348
25.795
200.934
1.00
14.61
A

ATOM
1876
CD2
LEU
A
373
43.437
24.181
201.004
1.00
13.80
A

ATOM
1877
C
LEU
A
373
45.182
25.570
205.023
1.00
14.73
A

ATOM
1878
O
LEU
A
373
44.702
24.905
205.944
1.00
15.24
A

ATOM
1879
N
SER
A
374
45.093
26.897
204.968
1.00
14.03
A

ATOM
1880
CA
SER
A
374
44.361
27.677
205.970
1.00
13.90
A

ATOM
1881
CB
SER
A
374
44.510
29.174
205.682
1.00
15.68
A

ATOM
1882
OG
SER
A
374
43.662
29.580
204.620
1.00
14.80
A

ATOM
1883
C
SER
A
374
42.877
27.295
206.038
1.00
14.54
A

ATOM
1884
O
SER
A
374
42.316
26.860
205.022
1.00
12.11
A

ATOM
1885
N
PRO
A
375
42.240
27.391
207.236
1.00
13.75
A

ATOM
1886
CD
PRO
A
375
42.799
27.643
208.581
1.00
16.61
A

ATOM
1887
CA
PRO
A
375
40.817
27.039
207.346
1.00
14.78
A

ATOM
1888
CB
PRO
A
375
40.517
27.242
208.841
1.00
15.76
A

ATOM
1889
CG
PRO
A
375
41.608
28.168
209.316
1.00
17.77
A

ATOM
1890
C
PRO
A
375
39.888
27.848
206.438
1.00
13.92
A

ATOM
1891
O
PRO
A
375
38.910
27.307
205.921
1.00
13.54
A

ATOM
1892
N
GLU
A
376
40.252
29.109
206.182
1.00
14.21
A

ATOM
1893
CA
GLU
A
376
39.459
29.983
205.312
1.00
15.69
A

ATOM
1894
CB
GLU
A
376
39.838
31.467
205.490
1.00
16.80
A

ATOM
1895
CG
GLU
A
376
41.287
31.862
205.168
1.00
18.90
A

ATOM
1896
CD
GLU
A
376
42.206
31.939
206.388
1.00
21.53
A

ATOM
1897
OE1
GLU
A
376
41.923
31.296
207.429
1.00
18.38
A

ATOM
1898
OE2
GLU
A
376
43.248
32.631
206.282
1.00
20.98
A

ATOM
1899
C
GLU
A
376
39.544
29.551
203.841
1.00
14.26
A

ATOM
1900
O
GLU
A
376
38.574
29.698
203.096
1.00
13.81
A

ATOM
1901
N
ALA
A
377
40.687
28.976
203.456
1.00
13.24
A

ATOM
1902
CA
ALA
A
377
40.898
28.485
202.092
1.00
12.78
A

ATOM
1903
CB
ALA
A
377
42.373
28.352
201.781
1.00
12.35
A

ATOM
1904
C
ALA
A
377
40.179
27.158
201.911
1.00
11.93
A

ATOM
1905
O
ALA
A
377
39.515
26.962
200.901
1.00
10.02
A

ATOM
1906
N
LYS
A
378
40.246
26.295
202.932
1.00
11.91
A

ATOM
1907
CA
LYS
A
378
39.566
24.992
202.919
1.00
12.33
A

ATOM
1908
CB
LYS
A
378
39.853
24.199
204.198
1.00
12.06
A

ATOM
1909
CG
LYS
A
378
41.248
23.631
204.286
1.00
15.67
A

ATOM
1910
CD
LYS
A
378
41.458
22.874
205.584
1.00
17.02
A

ATOM
1911
CE
LYS
A
378
42.851
22.276
205.633
1.00
16.73
A

ATOM
1912
NZ
LYS
A
378
43.160
21.642
206.940
1.00
21.03
A

ATOM
1913
C
LYS
A
378
38.060
25.195
202.798
1.00
12.05
A

ATOM
1914
O
LYS
A
378
37.397
24.477
202.052
1.00
11.83
A

ATOM
1915
N
SER
A
379
37.556
26.224
203.490
1.00
11.10
A

ATOM
1916
CA
SER
A
379
36.134
26.582
203.490
1.00
11.67
A

ATOM
1917
CB
SER
A
379
35.828
27.582
204.611
1.00
12.32
A

ATOM
1918
OG
SER
A
379
34.457
27.948
204.619
1.00
13.54
A

ATOM
1919
C
SER
A
379
35.686
27.149
202.142
1.00
10.66
A

ATOM
1920
O
SER
A
379
34.587
26.833
201.677
1.00
9.95
A

ATOM
1921
N
LEU
A
380
36.546
27.958
201.515
1.00
11.69
A

ATOM
1922
CA
LEU
A
380
36.244
28.549
200.203
1.00
9.61
A

ATOM
1923
CB
LEU
A
380
37.325
29.546
199.767
1.00
11.07
A

ATOM
1924
CG
LEU
A
380
37.030
30.229
198.419
1.00
10.92
A

ATOM
1925
CD1
LEU
A
380
36.093
31.405
198.603
1.00
13.48
A

ATOM
1926
CD2
LEU
A
380
38.301
30.646
197.733
1.00
10.36
A

ATOM
1927
C
LEU
A
380
36.132
27.446
199.159
1.00
9.94
A

ATOM
1928
O
LEU
A
380
35.135
27.369
198.440
1.00
10.00
A

ATOM
1929
N
LEU
A
381
37.136
26.569
199.142
1.00
9.86
A

ATOM
1930
CA
LEU
A
381
37.191
25.456
198.202
1.00
9.46
A

ATOM
1931
CB
LEU
A
381
38.570
24.799
198.221
1.00
9.84
A

ATOM
1932
CG
LEU
A
381
39.744
25.697
197.831
1.00
9.17
A

ATOM
1933
CD1
LEU
A
381
41.052
24.948
197.958
1.00
9.01
A

ATOM
1934
CD2
LEU
A
381
39.548
26.208
196.420
1.00
11.76
A

ATOM
1935
C
LEU
A
381
36.089
24.436
198.415
1.00
10.95
A

ATOM
1936
O
LEU
A
381
35.477
24.006
197.449
1.00
10.54
A

ATOM
1937
N
ALA
A
382
35.775
24.129
199.677
1.00
11.73
A

ATOM
1938
CA
ALA
A
382
34.698
23.183
200.007
1.00
12.27
A

ATOM
1939
CB
ALA
A
382
34.693
22.870
201.498
1.00
12.71
A

ATOM
1940
C
ALA
A
382
33.342
23.749
199.579
1.00
12.03
A

ATOM
1941
O
ALA
A
382
32.472
23.007
199.117
1.00
12.69
A

ATOM
1942
N
GLY
A
383
33.222
25.078
199.658
1.00
10.59
A

ATOM
1943
CA
GLY
A
383
32.001
25.772
199.280
1.00
10.18
A

ATOM
1944
C
GLY
A
383
31.814
25.873
197.775
1.00
8.45
A

ATOM
1945
O
GLY
A
383
30.723
25.612
197.272
1.00
10.40
A

ATOM
1946
N
LEU
A
384
32.876
26.254
197.062
1.00
7.94
A

ATOM
1947
CA
LEU
A
384
32.837
26.384
195.604
1.00
8.03
A

ATOM
1948
CB
LEU
A
384
34.056
27.159
195.096
1.00
5.65
A

ATOM
1949
CG
LEU
A
384
34.172
28.658
195.399
1.00
7.76
A

ATOM
1950
CD1
LEU
A
384
35.550
29.149
195.002
1.00
6.46
A

ATOM
1951
CD2
LEU
A
384
33.102
29.457
194.674
1.00
6.17
A

ATOM
1952
C
LEU
A
384
32.764
25.013
194.933
1.00
8.59
A

ATOM
1953
O
LEU
A
384
32.134
24.863
193.884
1.00
9.89
A

ATOM
1954
N
LEU
A
385
33.365
24.013
195.578
1.00
8.39
A

ATOM
1955
CA
LEU
A
385
33.369
22.650
195.061
1.00
9.22
A

ATOM
1956
CB
LEU
A
385
34.774
22.025
195.118
1.00
9.16
A

ATOM
1957
CG
LEU
A
385
35.851
22.686
194.247
1.00
9.77
A

ATOM
1958
CD1
LEU
A
385
37.221
22.141
194.588
1.00
9.20
A

ATOM
1959
CD2
LEU
A
385
35.543
22.492
192.770
1.00
10.49
A

ATOM
1960
C
LEU
A
385
32.306
21.712
195.640
1.00
9.48
A

ATOM
1961
O
LEU
A
385
32.472
20.490
195.649
1.00
9.86
A

ATOM
1962
N
LYS
A
386
31.188
22.287
196.079
1.00
10.56
A

ATOM
1963
CA
LYS
A
386
30.071
21.493
196.591
1.00
11.38
A

ATOM
1964
CB
LYS
A
386
29.109
22.372
197.388
1.00
14.55
A

ATOM
1965
CG
LYS
A
386
28.256
21.629
198.398
1.00
20.84
A

ATOM
1966
CD
LYS
A
386
28.988
21.414
199.715
1.00
22.83
A

ATOM
1967
CE
LYS
A
386
28.062
20.811
200.756
1.00
27.84
A

ATOM
1968
NZ
LYS
A
386
28.721
20.676
202.085
1.00
29.09
A

ATOM
1969
C
LYS
A
386
29.389
20.955
195.330
1.00
10.45
A

ATOM
1970
O
LYS
A
386
29.172
21.711
194.373
1.00
9.32
A

ATOM
1971
N
LYS
A
387
29.093
19.655
195.320
1.00
10.89
A

ATOM
1972
CA
LYS
A
387
28.487
18.999
194.159
1.00
12.50
A

ATOM
1973
CB
LYS
A
387
28.544
17.477
194.306
1.00
12.97
A

ATOM
1974
CG
LYS
A
387
29.971
16.958
194.448
1.00
13.15
A

ATOM
1975
CD
LYS
A
387
30.063
15.475
194.194
1.00
12.93
A

ATOM
1976
CE
LYS
A
387
31.405
14.919
194.638
1.00
11.17
A

ATOM
1977
NZ
LYS
A
387
32.570
15.446
193.861
1.00
12.25
A

ATOM
1978
C
LYS
A
387
27.095
19.470
193.759
1.00
13.09
A

ATOM
1979
O
LYS
A
387
26.813
19.609
192.568
1.00
12.47
A

ATOM
1980
N
ASP
A
388
26.258
19.762
194.754
1.00
12.54
A

ATOM
1981
CA
ASP
A
388
24.898
20.257
194.532
1.00
13.42
A

ATOM
1982
CB
ASP
A
388
24.025
19.933
195.765
1.00
16.51
A

ATOM
1983
CG
ASP
A
388
22.566
20.410
195.637
1.00
18.40
A

ATOM
1984
OD1
ASP
A
388
22.161
20.968
194.596
1.00
17.40
A

ATOM
1985
OD2
ASP
A
388
21.814
20.229
196.614
1.00
18.24
A

ATOM
1986
C
ASP
A
388
24.991
21.778
194.298
1.00
13.09
A

ATOM
1987
O
ASP
A
388
25.468
22.507
195.176
1.00
11.21
A

ATOM
1988
N
PRO
A
389
24.549
22.268
193.109
1.00
13.98
A

ATOM
1989
CD
PRO
A
389
24.071
21.528
191.924
1.00
13.65
A

ATOM
1990
CA
PRO
A
389
24.602
23.708
192.813
1.00
14.34
A

ATOM
1991
CB
PRO
A
389
24.052
23.802
191.384
1.00
14.48
A

ATOM
1992
CG
PRO
A
389
23.236
22.563
191.219
1.00
14.86
A

ATOM
1993
C
PRO
A
389
23.830
24.586
193.797
1.00
14.54
A

ATOM
1994
O
PRO
A
389
24.250
25.703
194.076
1.00
15.08
A

ATOM
1995
N
LYS
A
390
22.772
24.030
194.391
1.00
16.14
A

ATOM
1996
CA
LYS
A
390
21.954
24.748
195.371
1.00
19.29
A

ATOM
1997
CB
LYS
A
390
20.614
24.041
195.577
1.00
20.74
A

ATOM
1998
CG
LYS
A
390
19.617
24.294
194.464
1.00
25.04
A

ATOM
1999
CD
LYS
A
390
18.218
23.864
194.877
1.00
30.99
A

ATOM
2000
CE
LYS
A
390
17.159
24.495
193.984
1.00
33.33
A

ATOM
2001
NZ
LYS
A
390
17.119
25.984
194.123
1.00
35.42
A

ATOM
2002
C
LYS
A
390
22.652
24.955
196.721
1.00
18.60
A

ATOM
2003
O
LYS
A
390
22.353
25.915
197.435
1.00
21.49
A

ATOM
2004
N
GLN
A
391
23.586
24.060
197.050
1.00
18.57
A

ATOM
2005
CA
GLN
A
391
24.353
24.123
198.300
1.00
19.12
A

ATOM
2006
CB
GLN
A
391
24.591
22.709
198.856
1.00
20.95
A

ATOM
2007
CG
GLN
A
391
23.347
21.934
199.310
1.00
25.46
A

ATOM
2008
CD
GLN
A
391
23.656
20.476
199.664
1.00
28.32
A

ATOM
2009
OE1
GLN
A
391
24.492
20.193
200.526
1.00
31.25
A

ATOM
2010
NE2
GLN
A
391
22.977
19.547
198.996
1.00
28.41
A

ATOM
2011
C
GLN
A
391
25.712
24.816
198.084
1.00
16.92
A

ATOM
2012
O
GLN
A
391
26.411
25.145
199.046
1.00
17.18
A

ATOM
2013
N
ARG
A
392
26.061
25.054
196.817
1.00
14.27
A

ATOM
2014
CA
ARG
A
392
27.332
25.685
196.435
1.00
11.83
A

ATOM
2015
CB
ARG
A
392
27.594
25.446
194.939
1.00
10.55
A

ATOM
2016
CG
ARG
A
392
28.962
25.900
194.406
1.00
9.50
A

ATOM
2017
CD
ARG
A
392
29.137
25.565
192.933
1.00
8.08
A

ATOM
2018
NE
ARG
A
392
28.943
24.135
192.703
1.00
8.88
A

ATOM
2019
CZ
ARG
A
392
28.373
23.609
191.625
1.00
8.90
A

ATOM
2020
NH1
ARG
A
392
27.947
24.387
190.638
1.00
9.41
A

ATOM
2021
NH2
ARG
A
392
28.133
22.304
191.586
1.00
9.77
A

ATOM
2022
C
ARG
A
392
27.419
27.175
196.748
1.00
10.82
A

ATOM
2023
O
ARG
A
392
26.407
27.881
196.711
1.00
11.58
A

ATOM
2024
N
LEU
A
393
28.635
27.630
197.073
1.00
10.59
A

ATOM
2025
CA
LEU
A
393
28.919
29.035
197.361
1.00
11.25
A

ATOM
2026
CB
LEU
A
393
30.336
29.191
197.918
1.00
12.85
A

ATOM
2027
CG
LEU
A
393
30.767
30.542
198.479
1.00
13.61
A

ATOM
2028
CD1
LEU
A
393
30.120
30.783
199.841
1.00
14.74
A

ATOM
2029
CD2
LEU
A
393
32.276
30.576
198.592
1.00
13.30
A

ATOM
2030
C
LEU
A
393
28.784
29.779
196.033
1.00
13.13
A

ATOM
2031
O
LEU
A
393
29.526
29.519
195.077
1.00
13.97
A

ATOM
2032
N
GLY
A
394
27.768
30.631
195.967
1.00
12.66
A

ATOM
2033
CA
GLY
A
394
27.484
31.381
194.760
1.00
12.06
A

ATOM
2034
C
GLY
A
394
26.319
30.763
194.013
1.00
12.94
A

ATOM
2035
O
GLY
A
394
25.881
31.299
192.994
1.00
14.02
A

ATOM
2036
N
GLY
A
395
25.828
29.635
194.529
1.00
15.17
A

ATOM
2037
CA
GLY
A
395
24.720
28.915
193.919
1.00
16.80
A

ATOM
2038
C
GLY
A
395
23.344
29.380
194.350
1.00
17.44
A

ATOM
2039
O
GLY
A
395
22.337
28.932
193.798
1.00
18.42
A

ATOM
2040
N
GLY
A
396
23.311
30.280
195.334
1.00
18.62
A

ATOM
2041
CA
GLY
A
396
22.061
30.829
195.836
1.00
18.72
A

ATOM
2042
C
GLY
A
396
21.583
31.999
194.987
1.00
20.09
A

ATOM
2043
O
GLY
A
396
22.287
32.380
194.044
1.00
19.22
A

ATOM
2044
N
PRO
A
397
20.409
32.604
195.288
1.00
21.16
A

ATOM
2045
CD
PRO
A
397
19.443
32.168
196.317
1.00
22.25
A

ATOM
2046
CA
PRO
A
397
19.856
33.739
194.531
1.00
21.11
A

ATOM
2047
CB
PRO
A
397
18.560
34.045
195.282
1.00
21.67
A

ATOM
2048
CG
PRO
A
397
18.142
32.708
195.781
1.00
23.33
A

ATOM
2049
C
PRO
A
397
20.739
34.989
194.413
1.00
20.15
A

ATOM
2050
O
PRO
A
397
20.646
35.720
193.420
1.00
19.90
A

ATOM
2051
N
SER
A
398
21.609
35.215
195.402
1.00
19.97
A

ATOM
2052
CA
SER
A
398
22.497
36.384
195.395
1.00
17.27
A

ATOM
2053
CB
SER
A
398
22.865
36.807
196.820
1.00
19.31
A

ATOM
2054
OG
SER
A
398
23.582
35.796
197.497
1.00
24.32
A

ATOM
2055
C
SER
A
398
23.747
36.231
194.522
1.00
16.60
A

ATOM
2056
O
SER
A
398
24.508
37.187
194.351
1.00
15.27
A

ATOM
2057
N
ASP
A
399
23.946
35.022
193.986
1.00
16.68
A

ATOM
2058
CA
ASP
A
399
25.052
34.685
193.078
1.00
14.61
A

ATOM
2059
CB
ASP
A
399
24.739
35.277
191.685
1.00
15.21
A

ATOM
2060
CG
ASP
A
399
25.636
34.738
190.580
1.00
17.81
A

ATOM
2061
OD1
ASP
A
399
25.662
33.511
190.348
1.00
15.72
A

ATOM
2062
OD2
ASP
A
399
26.295
35.569
189.929
1.00
19.60
A

ATOM
2063
C
ASP
A
399
26.459
35.068
193.592
1.00
13.28
A

ATOM
2064
O
ASP
A
399
26.909
34.534
194.602
1.00
12.10
A

ATOM
2065
N
ALA
A
400
27.098
36.045
192.946
1.00
14.41
A

ATOM
2066
CA
ALA
A
400
28.443
36.501
193.297
1.00
12.16
A

ATOM
2067
CB
ALA
A
400
28.916
37.510
192.298
1.00
12.22
A

ATOM
2068
C
ALA
A
400
28.636
37.042
194.702
1.00
12.25
A

ATOM
2069
O
ALA
A
400
29.732
36.926
195.252
1.00
10.75
A

ATOM
2070
N
LYS
A
401
27.566
37.592
195.284
1.00
11.70
A

ATOM
2071
CA
LYS
A
401
27.602
38.157
196.634
1.00
13.89
A

ATOM
2072
CB
LYS
A
401
26.241
38.751
197.017
1.00
16.12
A

ATOM
2073
CG
LYS
A
401
26.271
39.596
198.286
1.00
19.60
A

ATOM
2074
CD
LYS
A
401
24.880
39.905
198.794
1.00
20.68
A

ATOM
2075
CE
LYS
A
401
24.950
40.615
200.133
1.00
22.34
A

ATOM
2076
NZ
LYS
A
401
23.598
40.943
200.648
1.00
25.16
A

ATOM
2077
C
LYS
A
401
28.053
37.138
197.680
1.00
14.23
A

ATOM
2078
O
LYS
A
401
28.843
37.475
198.559
1.00
14.96
A

ATOM
2079
N
GLU
A
402
27.611
35.886
197.528
1.00
13.34
A

ATOM
2080
CA
GLU
A
402
27.979
34.802
198.448
1.00
15.47
A

ATOM
2081
CB
GLU
A
402
27.203
33.525
198.123
1.00
16.98
A

ATOM
2082
CG
GLU
A
402
25.721
33.597
198.471
1.00
22.80
A

ATOM
2083
CD
GLU
A
402
24.948
32.320
198.157
1.00
26.41
A

ATOM
2084
OE1
GLU
A
402
25.359
31.553
197.259
1.00
26.03
A

ATOM
2085
OE2
GLU
A
402
23.905
32.091
198.809
1.00
27.43
A

ATOM
2086
C
GLU
A
402
29.484
34.519
198.430
1.00
14.42
A

ATOM
2087
O
GLU
A
402
30.088
34.282
199.480
1.00
13.65
A

ATOM
2088
N
VAL
A
403
30.082
34.607
197.239
1.00
13.01
A

ATOM
2089
CA
VAL
A
403
31.518
34.385
197.053
1.00
11.76
A

ATOM
2090
CB
VAL
A
403
31.876
34.137
195.560
1.00
11.44
A

ATOM
2091
CG1
VAL
A
403
33.369
33.820
195.403
1.00
9.58
A

ATOM
2092
CG2
VAL
A
403
31.043
32.986
195.005
1.00
11.72
A

ATOM
2093
C
VAL
A
403
32.303
35.588
197.576
1.00
11.84
A

ATOM
2094
O
VAL
A
403
33.286
35.420
198.298
1.00
10.47
A

ATOM
2095
N
MET
A
404
31.830
36.787
197.232
1.00
11.80
A

ATOM
2096
CA
MET
A
404
32.457
38.045
197.641
1.00
13.26
A

ATOM
2097
CB
MET
A
404
31.750
39.244
196.994
1.00
15.05
A

ATOM
2098
CG
MET
A
404
31.958
39.354
195.494
1.00
16.33
A

ATOM
2099
SD
MET
A
404
31.462
40.933
194.791
1.00
18.23
A

ATOM
2100
CE
MET
A
404
29.757
40.696
194.547
1.00
21.53
A

ATOM
2101
C
MET
A
404
32.516
38.250
199.151
1.00
13.67
A

ATOM
2102
O
MET
A
404
33.516
38.754
199.671
1.00
13.54
A

ATOM
2103
N
GLU
A
405
31.466
37.801
199.840
1.00
14.50
A

ATOM
2104
CA
GLU
A
405
31.359
37.928
201.291
1.00
14.98
A

ATOM
2105
CB
GLU
A
405
29.903
38.193
201.706
1.00
17.47
A

ATOM
2106
CG
GLU
A
405
29.295
39.491
201.149
1.00
23.07
A

ATOM
2107
CD
GLU
A
405
30.138
40.735
201.417
1.00
27.01
A

ATOM
2108
OE1
GLU
A
405
30.342
41.086
202.601
1.00
30.41
A

ATOM
2109
OE2
GLU
A
405
30.600
41.358
200.436
1.00
29.99
A

ATOM
2110
C
GLU
A
405
31.954
36.790
202.119
1.00
13.80
A

ATOM
2111
O
GLU
A
405
31.878
36.817
203.349
1.00
14.06
A

ATOM
2112
N
HIS
A
406
32.587
35.819
201.455
1.00
11.75
A

ATOM
2113
CA
HIS
A
406
33.219
34.694
202.155
1.00
11.72
A

ATOM
2114
CB
HIS
A
406
33.585
33.576
201.166
1.00
11.05
A

ATOM
2115
CG
HIS
A
406
34.070
32.324
201.828
1.00
11.80
A

ATOM
2116
CD2
HIS
A
406
33.421
31.187
202.176
1.00
11.83
A

ATOM
2117
ND1
HIS
A
406
35.361
32.184
202.289
1.00
11.13
A

ATOM
2118
CE1
HIS
A
406
35.484
31.021
202.901
1.00
12.32
A

ATOM
2119
NE2
HIS
A
406
34.321
30.396
202.846
1.00
10.29
A

ATOM
2120
C
HIS
A
406
34.466
35.203
202.902
1.00
11.51
A

ATOM
2121
O
HIS
A
406
35.166
36.089
202.404
1.00
11.68
A

ATOM
2122
N
ARG
A
407
34.731
34.636
204.084
1.00
13.02
A

ATOM
2123
CA
ARG
A
407
35.868
35.036
204.933
1.00
14.27
A

ATOM
2124
CB
ARG
A
407
35.863
34.286
206.275
1.00
16.28
A

ATOM
2125
CG
ARG
A
407
35.775
32.776
206.190
1.00
22.36
A

ATOM
2126
CD
ARG
A
407
35.703
32.149
207.573
1.00
26.72
A

ATOM
2127
NE
ARG
A
407
35.227
30.767
207.515
1.00
31.71
A

ATOM
2128
CZ
ARG
A
407
35.868
29.715
208.020
1.00
33.50
A

ATOM
2129
NH1
ARG
A
407
37.038
29.859
208.635
1.00
35.91
A

ATOM
2130
NH2
ARG
A
407
35.326
28.509
207.922
1.00
34.67
A

ATOM
2131
C
ARG
A
407
37.259
35.005
204.297
1.00
12.73
A

ATOM
2132
O
ARG
A
407
38.146
35.746
204.718
1.00
13.98
A

ATOM
2133
N
PHE
A
408
37.424
34.196
203.248
1.00
12.68
A

ATOM
2134
CA
PHE
A
408
38.694
34.107
202.521
1.00
12.92
A

ATOM
2135
CB
PHE
A
408
38.625
32.985
201.467
1.00
10.80
A

ATOM
2136
CG
PHE
A
408
39.886
32.820
200.656
1.00
13.01
A

ATOM
2137
CD1
PHE
A
408
40.999
32.147
201.191
1.00
13.20
A

ATOM
2138
CD2
PHE
A
408
39.973
33.352
199.356
1.00
12.18
A

ATOM
2139
CE1
PHE
A
408
42.199
32.001
200.441
1.00
13.70
A

ATOM
2140
CE2
PHE
A
408
41.159
33.217
198.594
1.00
14.00
A

ATOM
2141
CZ
PHE
A
408
42.277
32.540
199.137
1.00
13.44
A

ATOM
2142
C
PHE
A
408
39.002
35.455
201.853
1.00
11.74
A

ATOM
2143
O
PHE
A
408
40.166
35.818
201.692
1.00
13.32
A

ATOM
2144
N
PHE
A
409
37.945
36.180
201.486
1.00
11.79
A

ATOM
2145
CA
PHE
A
409
38.060
37.477
200.826
1.00
11.95
A

ATOM
2146
CB
PHE
A
409
37.098
37.537
199.629
1.00
12.23
A

ATOM
2147
CG
PHE
A
409
37.473
36.630
198.481
1.00
10.69
A

ATOM
2148
CD1
PHE
A
409
36.592
35.616
198.066
1.00
10.42
A

ATOM
2149
CD2
PHE
A
409
38.687
36.806
197.782
1.00
11.00
A

ATOM
2150
CE1
PHE
A
409
36.909
34.776
196.957
1.00
10.74
A

ATOM
2151
CE2
PHE
A
409
39.023
35.976
196.670
1.00
10.99
A

ATOM
2152
CZ
PHE
A
409
38.128
34.959
196.258
1.00
9.34
A

ATOM
2153
C
PHE
A
409
37.804
38.682
201.745
1.00
13.98
A

ATOM
2154
O
PHE
A
409
37.555
39.786
201.255
1.00
13.33
A

ATOM
2155
N
LEU
A
410
37.906
38.482
203.063
1.00
13.39
A

ATOM
2156
CA
LEU
A
410
37.678
39.547
204.058
1.00
16.53
A

ATOM
2157
CB
LEU
A
410
37.848
38.989
205.482
1.00
20.16
A

ATOM
2158
CG
LEU
A
410
37.432
39.810
206.716
1.00
23.30
A

ATOM
2159
CD1
LEU
A
410
35.917
39.992
206.765
1.00
25.76
A

ATOM
2160
CD2
LEU
A
410
37.913
39.103
207.973
1.00
26.00
A

ATOM
2161
C
LEU
A
410
38.561
40.796
203.871
1.00
17.65
A

ATOM
2162
O
LEU
A
410
38.076
41.926
203.997
1.00
19.37
A

ATOM
2163
N
SER
A
411
39.820
40.577
203.484
1.00
18.04
A

ATOM
2164
CA
SER
A
411
40.798
41.652
203.269
1.00
19.59
A

ATOM
2165
CB
SER
A
411
42.221
41.105
203.458
1.00
21.68
A

ATOM
2166
OG
SER
A
411
42.528
40.102
202.496
1.00
23.38
A

ATOM
2167
C
SER
A
411
40.689
42.353
201.907
1.00
19.99
A

ATOM
2168
O
SER
A
411
41.476
43.254
201.598
1.00
21.28
A

ATOM
2169
N
ILE
A
412
39.704
41.945
201.111
1.00
18.60
A

ATOM
2170
CA
ILE
A
412
39.493
42.500
199.777
1.00
18.28
A

ATOM
2171
CB
ILE
A
412
39.151
41.357
198.742
1.00
18.49
A

ATOM
2172
CG2
ILE
A
412
38.813
41.920
197.364
1.00
18.91
A

ATOM
2173
CG1
ILE
A
412
40.297
40.335
198.643
1.00
18.27
A

ATOM
2174
CD1
ILE
A
412
41.629
40.866
198.097
1.00
19.98
A

ATOM
2175
C
ILE
A
412
38.413
43.588
199.720
1.00
17.05
A

ATOM
2176
O
ILE
A
412
37.298
43.410
200.214
1.00
18.27
A

ATOM
2177
N
ASN
A
413
38.780
44.714
199.113
1.00
17.73
A

ATOM
2178
CA
ASN
A
413
37.869
45.830
198.891
1.00
17.76
A

ATOM
2179
CB
ASN
A
413
38.570
47.173
199.155
1.00
19.37
A

ATOM
2180
CG
ASN
A
413
37.665
48.384
198.906
1.00
21.20
A

ATOM
2181
OD1
ASN
A
413
37.098
48.549
197.828
1.00
21.10
A

ATOM
2182
ND2
ASN
A
413
37.573
49.257
199.893
1.00
21.56
A

ATOM
2183
C
ASN
A
413
37.520
45.653
197.410
1.00
16.29
A

ATOM
2184
O
ASN
A
413
38.367
45.845
196.532
1.00
14.73
A

ATOM
2185
N
TRP
A
414
36.264
45.293
197.156
1.00
15.91
A

ATOM
2186
CA
TRP
A
414
35.763
45.034
195.807
1.00
16.45
A

ATOM
2187
CB
TRP
A
414
34.415
44.311
195.880
1.00
13.45
A

ATOM
2188
CG
TRP
A
414
34.584
42.970
196.530
1.00
14.40
A

ATOM
2189
CD2
TRP
A
414
35.140
41.795
195.927
1.00
11.06
A

ATOM
2190
CE2
TRP
A
414
35.255
40.816
196.950
1.00
12.17
A

ATOM
2191
CE3
TRP
A
414
35.563
41.471
194.620
1.00
11.86
A

ATOM
2192
CD1
TRP
A
414
34.372
42.661
197.850
1.00
12.42
A

ATOM
2193
NE1
TRP
A
414
34.781
41.373
198.108
1.00
13.10
A

ATOM
2194
CZ2
TRP
A
414
35.781
39.527
196.709
1.00
11.22
A

ATOM
2195
CZ3
TRP
A
414
36.087
40.188
194.376
1.00
10.37
A

ATOM
2196
CH2
TRP
A
414
36.190
39.230
195.424
1.00
11.11
A

ATOM
2197
C
TRP
A
414
35.751
46.181
194.812
1.00
17.39
A

ATOM
2198
O
TRP
A
414
35.760
45.951
193.597
1.00
17.89
A

ATOM
2199
N
GLN
A
415
35.782
47.409
195.326
1.00
18.71
A

ATOM
2200
CA
GLN
A
415
35.829
48.590
194.473
1.00
20.74
A

ATOM
2201
CB
GLN
A
415
35.189
49.804
195.152
1.00
24.69
A

ATOM
2202
CG
GLN
A
415
33.661
49.752
195.198
1.00
29.88
A

ATOM
2203
CD
GLN
A
415
33.001
49.730
193.817
1.00
34.21
A

ATOM
2204
OE1
GLN
A
415
33.336
50.527
192.935
1.00
37.63
A

ATOM
2205
NE2
GLN
A
415
32.051
48.816
193.633
1.00
35.32
A

ATOM
2206
C
GLN
A
415
37.274
48.873
194.071
1.00
21.49
A

ATOM
2207
O
GLN
A
415
37.524
49.369
192.975
1.00
22.13
A

ATOM
2208
N
ASP
A
416
38.216
48.486
194.937
1.00
21.58
A

ATOM
2209
CA
ASP
A
416
39.653
48.651
194.681
1.00
21.45
A

ATOM
2210
CB
ASP
A
416
40.474
48.432
195.956
1.00
21.37
A

ATOM
2211
CG
ASP
A
416
40.464
49.636
196.897
1.00
24.16
A

ATOM
2212
OD1
ASP
A
416
39.787
50.653
196.619
1.00
25.95
A

ATOM
2213
OD2
ASP
A
416
41.144
49.548
197.939
1.00
23.18
A

ATOM
2214
C
ASP
A
416
40.115
47.647
193.621
1.00
21.58
A

ATOM
2215
O
ASP
A
416
41.055
47.917
192.868
1.00
21.69
A

ATOM
2216
N
VAL
A
417
39.430
46.500
193.571
1.00
20.41
A

ATOM
2217
CA
VAL
A
417
39.720
45.429
192.614
1.00
19.94
A

ATOM
2218
CB
VAL
A
417
38.987
44.101
192.996
1.00
19.93
A

ATOM
2219
CG1
VAL
A
417
39.178
43.016
191.926
1.00
17.42
A

ATOM
2220
CG2
VAL
A
417
39.528
43.584
194.297
1.00
17.75
A

ATOM
2221
C
VAL
A
417
39.344
45.869
191.199
1.00
20.99
A

ATOM
2222
O
VAL
A
417
40.213
45.922
190.334
1.00
21.45
A

ATOM
2223
N
VAL
A
418
38.082
46.270
191.006
1.00
20.67
A

ATOM
2224
CA
VAL
A
418
37.575
46.703
189.697
1.00
23.32
A

ATOM
2225
CB
VAL
A
418
36.002
46.789
189.694
1.00
23.10
A

ATOM
2226
CG1
VAL
A
418
35.492
47.986
190.497
1.00
23.90
A

ATOM
2227
CG2
VAL
A
418
35.458
46.805
188.270
1.00
24.63
A

ATOM
2228
C
VAL
A
418
38.234
47.988
189.154
1.00
23.66
A

ATOM
2229
O
VAL
A
418
38.341
48.170
187.942
1.00
24.79
A

ATOM
2230
N
GLN
A
419
38.717
48.839
190.058
1.00
24.64
A

ATOM
2231
CA
GLN
A
419
39.381
50.087
189.677
1.00
26.12
A

ATOM
2232
CB
GLN
A
419
39.044
51.203
190.678
1.00
27.13
A

ATOM
2233
CG
GLN
A
419
37.590
51.677
190.619
1.00
29.70
A

ATOM
2234
CD
GLN
A
419
37.243
52.666
191.720
1.00
31.46
A

ATOM
2235
OE1
GLN
A
419
36.443
52.370
192.607
1.00
32.13
A

ATOM
2236
NE2
GLN
A
419
37.837
53.853
191.660
1.00
31.64
A

ATOM
2237
C
GLN
A
419
40.900
49.935
189.518
1.00
26.30
A

ATOM
2238
O
GLN
A
419
41.603
50.924
189.285
1.00
25.43
A

ATOM
2239
N
LYS
A
420
41.383
48.688
189.623
1.00
26.79
A

ATOM
2240
CA
LYS
A
420
42.806
48.305
189.494
1.00
28.25
A

ATOM
2241
CB
LYS
A
420
43.297
48.489
188.045
1.00
29.48
A

ATOM
2242
CG
LYS
A
420
42.849
47.437
187.052
1.00
31.95
A

ATOM
2243
CD
LYS
A
420
43.363
47.799
185.670
1.00
33.87
A

ATOM
2244
CE
LYS
A
420
43.263
46.639
184.705
1.00
36.54
A

ATOM
2245
NZ
LYS
A
420
43.670
47.044
183.331
1.00
37.53
A

ATOM
2246
C
LYS
A
420
43.781
48.989
190.467
1.00
28.96
A

ATOM
2247
O
LYS
A
420
44.945
49.226
190.128
1.00
29.26
A

ATOM
2248
N
LYS
A
421
43.311
49.262
191.684
1.00
29.05
A

ATOM
2249
CA
LYS
A
421
44.118
49.927
192.712
1.00
30.32
A

ATOM
2250
CB
LYS
A
421
43.219
50.633
193.731
1.00
30.17
A

ATOM
2251
CG
LYS
A
421
42.369
51.755
193.156
1.00
29.79
A

ATOM
2252
CD
LYS
A
421
41.592
52.450
194.257
1.00
30.47
A

ATOM
2253
CE
LYS
A
421
40.647
53.491
193.701
1.00
31.51
A

ATOM
2254
NZ
LYS
A
421
39.903
54.178
194.792
1.00
31.93
A

ATOM
2255
C
LYS
A
421
45.096
49.013
193.445
1.00
31.69
A

ATOM
2256
O
LYS
A
421
46.060
49.493
194.050
1.00
33.59
A

ATOM
2257
N
LEU
A
422
44.854
47.704
193.381
1.00
32.62
A

ATOM
2258
CA
LEU
A
422
45.712
46.721
194.041
1.00
32.37
A

ATOM
2259
CB
LEU
A
422
44.920
45.452
194.382
1.00
33.90
A

ATOM
2260
CG
LEU
A
422
43.839
45.531
195.469
1.00
34.03
A

ATOM
2261
CD1
LEU
A
422
43.122
44.198
195.558
1.00
33.87
A

ATOM
2262
CD2
LEU
A
422
44.444
45.895
196.823
1.00
35.38
A

ATOM
2263
C
LEU
A
422
46.958
46.372
193.232
1.00
31.85
A

ATOM
2264
O
LEU
A
422
46.887
46.188
192.013
1.00
32.31
A

ATOM
2265
N
LEU
A
423
48.094
46.313
193.929
1.00
30.37
A

ATOM
2266
CA
LEU
A
423
49.399
45.998
193.340
1.00
29.21
A

ATOM
2267
CB
LEU
A
423
50.524
46.430
194.304
1.00
30.06
A

ATOM
2268
CG
LEU
A
423
52.018
46.171
194.021
1.00
31.99
A

ATOM
2269
CD1
LEU
A
423
52.507
46.964
192.813
1.00
31.88
A

ATOM
2270
CD2
LEU
A
423
52.837
46.539
195.250
1.00
31.74
A

ATOM
2271
C
LEU
A
423
49.521
44.501
193.008
1.00
26.95
A

ATOM
2272
O
LEU
A
423
49.266
43.656
193.871
1.00
27.20
A

ATOM
2273
N
PRO
A
424
49.844
44.159
191.735
1.00
25.86
A

ATOM
2274
CD
PRO
A
424
49.831
45.042
190.550
1.00
23.71
A

ATOM
2275
CA
PRO
A
424
49.996
42.759
191.311
1.00
23.59
A

ATOM
2276
CB
PRO
A
424
50.170
42.880
189.794
1.00
23.55
A

ATOM
2277
CG
PRO
A
424
49.393
44.103
189.464
1.00
25.21
A

ATOM
2278
C
PRO
A
424
51.201
42.057
191.958
1.00
22.61
A

ATOM
2279
O
PRO
A
424
52.268
42.658
192.085
1.00
22.14
A

ATOM
2280
N
PRO
A
425
51.032
40.792
192.412
1.00
21.49
A

ATOM
2281
CD
PRO
A
425
49.751
40.070
192.518
1.00
22.31
A

ATOM
2282
CA
PRO
A
425
52.097
40.005
193.047
1.00
21.27
A

ATOM
2283
CB
PRO
A
425
51.326
38.855
193.696
1.00
20.79
A

ATOM
2284
CG
PRO
A
425
50.179
38.658
192.775
1.00
19.95
A

ATOM
2285
C
PRO
A
425
53.160
39.504
192.065
1.00
20.52
A

ATOM
2286
O
PRO
A
425
54.187
38.959
192.473
1.00
20.46
A

ATOM
2287
N
PHE
A
426
52.893
39.705
190.775
1.00
20.11
A

ATOM
2288
CA
PHE
A
426
53.796
39.313
189.701
1.00
20.51
A

ATOM
2289
CB
PHE
A
426
53.572
37.837
189.305
1.00
21.57
A

ATOM
2290
CG
PHE
A
426
54.572
37.310
188.298
1.00
23.74
A

ATOM
2291
CD1
PHE
A
426
55.909
37.066
188.673
1.00
26.85
A

ATOM
2292
CD2
PHE
A
426
54.191
37.092
186.959
1.00
26.11
A

ATOM
2293
CE1
PHE
A
426
56.865
36.613
187.723
1.00
27.97
A

ATOM
2294
CE2
PHE
A
426
55.132
36.641
185.996
1.00
26.89
A

ATOM
2295
CZ
PHE
A
426
56.474
36.401
186.380
1.00
27.49
A

ATOM
2296
C
PHE
A
426
53.575
40.216
188.492
1.00
19.87
A

ATOM
2297
O
PHE
A
426
52.450
40.350
188.003
1.00
19.07
A

ATOM
2298
N
LYS
A
427
54.653
40.843
188.031
1.00
20.11
A

ATOM
2299
CA
LYS
A
427
54.586
41.690
186.851
1.00
19.92
A

ATOM
2300
CB
LYS
A
427
55.129
43.110
187.104
1.00
23.46
A

ATOM
2301
CG
LYS
A
427
54.904
44.050
185.898
1.00
26.03
A

ATOM
2302
CD
LYS
A
427
55.558
45.414
186.026
1.00
29.53
A

ATOM
2303
CE
LYS
A
427
55.402
46.181
184.717
1.00
31.56
A

ATOM
2304
NZ
LYS
A
427
55.924
47.576
184.777
1.00
33.40
A

ATOM
2305
C
LYS
A
427
55.407
40.998
185.764
1.00
19.78
A

ATOM
2306
O
LYS
A
427
56.554
40.613
186.005
1.00
17.85
A

ATOM
2307
N
PRO
A
428
54.795
40.744
184.586
1.00
19.63
A

ATOM
2308
CD
PRO
A
428
53.357
40.865
184.285
1.00
19.37
A

ATOM
2309
CA
PRO
A
428
55.479
40.097
183.462
1.00
19.43
A

ATOM
2310
CB
PRO
A
428
54.403
40.107
182.380
1.00
18.78
A

ATOM
2311
CG
PRO
A
428
53.177
39.887
183.175
1.00
20.13
A

ATOM
2312
C
PRO
A
428
56.708
40.902
183.039
1.00
19.52
A

ATOM
2313
O
PRO
A
428
56.621
42.119
182.843
1.00
18.89
A

ATOM
2314
N
GLN
A
429
57.852
40.223
182.988
1.00
20.38
A

ATOM
2315
CA
GLN
A
429
59.130
40.841
182.632
1.00
23.68
A

ATOM
2316
CB
GLN
A
429
60.277
40.166
183.405
1.00
24.40
A

ATOM
2317
CG
GLN
A
429
60.268
40.410
184.915
1.00
28.23
A

ATOM
2318
CD
GLN
A
429
60.626
41.840
185.292
1.00
29.68
A

ATOM
2319
OE1
GLN
A
429
61.800
42.209
185.331
1.00
33.85
A

ATOM
2320
NE2
GLN
A
429
59.611
42.648
185.582
1.00
31.72
A

ATOM
2321
C
GLN
A
429
59.430
40.884
181.132
1.00
24.80
A

ATOM
2322
O
GLN
A
429
60.529
40.532
180.692
1.00
24.99
A

ATOM
2323
N
VAL
A
430
58.453
41.355
180.360
1.00
25.32
A

ATOM
2324
CA
VAL
A
430
58.585
41.480
178.908
1.00
26.94
A

ATOM
2325
CB
VAL
A
430
57.196
41.446
178.189
1.00
25.86
A

ATOM
2326
CG1
VAL
A
430
56.643
40.031
178.201
1.00
26.31
A

ATOM
2327
CG2
VAL
A
430
56.197
42.403
178.850
1.00
26.32
A

ATOM
2328
C
VAL
A
430
59.374
42.739
178.526
1.00
28.11
A

ATOM
2329
O
VAL
A
430
59.141
43.819
179.079
1.00
28.91
A

ATOM
2330
N
THR
A
431
60.335
42.572
177.617
1.00
28.63
A

ATOM
2331
CA
THR
A
431
61.196
43.664
177.151
1.00
30.71
A

ATOM
2332
CB
THR
A
431
62.589
43.141
176.737
1.00
31.07
A

ATOM
2333
OG1
THR
A
431
62.442
42.057
175.811
1.00
32.95
A

ATOM
2334
CG2
THR
A
431
63.369
42.672
177.959
1.00
31.57
A

ATOM
2335
C
THR
A
431
60.595
44.457
175.990
1.00
31.23
A

ATOM
2336
O
THR
A
431
60.789
45.671
175.888
1.00
32.41
A

ATOM
2337
N
SER
A
432
59.886
43.748
175.116
1.00
31.42
A

ATOM
2338
CA
SER
A
432
59.227
44.338
173.954
1.00
31.65
A

ATOM
2339
CB
SER
A
432
60.023
44.038
172.676
1.00
32.10
A

ATOM
2340
OG
SER
A
432
60.171
42.643
172.462
1.00
30.64
A

ATOM
2341
C
SER
A
432
57.816
43.765
173.844
1.00
31.86
A

ATOM
2342
O
SER
A
432
57.450
42.851
174.587
1.00
31.28
A

ATOM
2343
N
GLU
A
433
57.033
44.296
172.909
1.00
32.49
A

ATOM
2344
CA
GLU
A
433
55.663
43.836
172.685
1.00
33.34
A

ATOM
2345
CB
GLU
A
433
54.854
44.928
171.980
1.00
35.90
A

ATOM
2346
CG
GLU
A
433
54.521
46.158
172.830
1.00
39.92
A

ATOM
2347
CD
GLU
A
433
53.369
45.924
173.801
1.00
42.93
A

ATOM
2348
OE1
GLU
A
433
52.204
45.874
173.346
1.00
44.52
A

ATOM
2349
OE2
GLU
A
433
53.628
45.796
175.018
1.00
45.85
A

ATOM
2350
C
GLU
A
433
55.618
42.526
171.884
1.00
32.35
A

ATOM
2351
O
GLU
A
433
54.568
41.888
171.779
1.00
34.04
A

ATOM
2352
N
VAL
A
434
56.776
42.126
171.357
1.00
29.34
A

ATOM
2353
CA
VAL
A
434
56.923
40.902
170.570
1.00
27.57
A

ATOM
2354
CB
VAL
A
434
57.732
41.198
169.247
1.00
28.24
A

ATOM
2355
CG1
VAL
A
434
59.233
41.366
169.516
1.00
27.69
A

ATOM
2356
CG2
VAL
A
434
57.455
40.146
168.184
1.00
29.67
A

ATOM
2357
C
VAL
A
434
57.544
39.763
171.419
1.00
25.80
A

ATOM
2358
O
VAL
A
434
57.710
38.635
170.947
1.00
26.50
A

ATOM
2359
N
ASP
A
435
57.854
40.078
172.679
1.00
22.61
A

ATOM
2360
CA
ASP
A
435
58.442
39.139
173.640
1.00
20.42
A

ATOM
2361
CB
ASP
A
435
59.008
39.931
174.832
1.00
20.57
A

ATOM
2362
CG
ASP
A
435
59.900
39.101
175.758
1.00
21.84
A

ATOM
2363
OD1
ASP
A
435
59.839
37.852
175.753
1.00
21.41
A

ATOM
2364
OD2
ASP
A
435
60.669
39.727
176.517
1.00
22.72
A

ATOM
2365
C
ASP
A
435
57.355
38.156
174.103
1.00
19.53
A

ATOM
2366
O
ASP
A
435
56.418
38.537
174.810
1.00
19.91
A

ATOM
2367
N
THR
A
436
57.490
36.900
173.678
1.00
16.13
A

ATOM
2368
CA
THR
A
436
56.529
35.845
174.009
1.00
14.69
A

ATOM
2369
CB
THR
A
436
55.988
35.164
172.719
1.00
15.23
A

ATOM
2370
OG1
THR
A
436
57.083
34.673
171.934
1.00
17.12
A

ATOM
2371
CG2
THR
A
436
55.166
36.139
171.889
1.00
14.36
A

ATOM
2372
C
THR
A
436
57.098
34.776
174.957
1.00
13.23
A

ATOM
2373
O
THR
A
436
56.737
33.595
174.862
1.00
13.45
A

ATOM
2374
N
ARG
A
437
57.940
35.204
175.903
1.00
11.51
A

ATOM
2375
CA
ARG
A
437
58.581
34.301
176.872
1.00
12.26
A

ATOM
2376
CB
ARG
A
437
59.638
35.049
177.696
1.00
13.67
A

ATOM
2377
CG
ARG
A
437
59.081
36.111
178.628
1.00
13.51
A

ATOM
2378
CD
ARG
A
437
60.154
36.732
179.486
1.00
15.66
A

ATOM
2379
NE
ARG
A
437
60.964
37.681
178.733
1.00
17.26
A

ATOM
2380
CZ
ARG
A
437
62.110
38.195
179.163
1.00
16.07
A

ATOM
2381
NH1
ARG
A
437
62.595
37.852
180.349
1.00
17.27
A

ATOM
2382
NH2
ARG
A
437
62.767
39.062
178.407
1.00
19.67
A

ATOM
2383
C
ARG
A
437
57.606
33.579
177.813
1.00
11.96
A

ATOM
2384
O
ARG
A
437
57.958
32.571
178.432
1.00
12.52
A

ATOM
2385
N
TYR
A
438
56.385
34.102
177.901
1.00
12.10
A

ATOM
2386
CA
TYR
A
438
55.362
33.520
178.760
1.00
10.77
A

ATOM
2387
CB
TYR
A
438
54.675
34.607
179.583
1.00
11.18
A

ATOM
2388
CG
TYR
A
438
55.614
35.336
180.515
1.00
11.04
A

ATOM
2389
CD1
TYR
A
438
55.794
36.724
180.407
1.00
12.49
A

ATOM
2390
CE1
TYR
A
438
56.690
37.408
181.254
1.00
14.41
A

ATOM
2391
CD2
TYR
A
438
56.352
34.638
181.500
1.00
13.83
A

ATOM
2392
CE2
TYR
A
438
57.250
35.318
182.364
1.00
12.87
A

ATOM
2393
CZ
TYR
A
438
57.409
36.701
182.230
1.00
14.15
A

ATOM
2394
OH
TYR
A
438
58.259
37.379
183.065
1.00
16.58
A

ATOM
2395
C
TYR
A
438
54.359
32.630
178.038
1.00
10.95
A

ATOM
2396
O
TYR
A
438
53.292
32.298
178.568
1.00
12.70
A

ATOM
2397
N
PHE
A
439
54.726
32.251
176.819
1.00
11.45
A

ATOM
2398
CA
PHE
A
439
53.935
31.359
175.983
1.00
12.49
A

ATOM
2399
CB
PHE
A
439
53.525
32.055
174.684
1.00
11.92
A

ATOM
2400
CG
PHE
A
439
52.465
33.099
174.873
1.00
11.02
A

ATOM
2401
CD1
PHE
A
439
52.814
34.431
175.176
1.00
9.95
A

ATOM
2402
CD2
PHE
A
439
51.105
32.752
174.779
1.00
10.65
A

ATOM
2403
CE1
PHE
A
439
51.820
35.417
175.386
1.00
8.73
A

ATOM
2404
CE2
PHE
A
439
50.090
33.727
174.987
1.00
11.34
A

ATOM
2405
CZ
PHE
A
439
50.452
35.063
175.291
1.00
10.88
A

ATOM
2406
C
PHE
A
439
54.799
30.137
175.703
1.00
13.60
A

ATOM
2407
O
PHE
A
439
56.030
30.245
175.626
1.00
13.99
A

ATOM
2408
N
ASP
A
440
54.157
28.974
175.595
1.00
16.16
A

ATOM
2409
CA
ASP
A
440
54.857
27.708
175.349
1.00
19.82
A

ATOM
2410
CB
ASP
A
440
53.894
26.524
175.465
1.00
22.10
A

ATOM
2411
CG
ASP
A
440
53.392
26.317
176.875
1.00
27.42
A

ATOM
2412
OD1
ASP
A
440
52.186
26.540
177.109
1.00
30.82
A

ATOM
2413
OD2
ASP
A
440
54.201
25.935
177.750
1.00
30.42
A

ATOM
2414
C
ASP
A
440
55.574
27.657
174.005
1.00
19.98
A

ATOM
2415
O
ASP
A
440
55.037
28.118
172.993
1.00
19.33
A

ATOM
2416
N
ASP
A
441
56.791
27.104
174.022
1.00
21.03
A

ATOM
2417
CA
ASP
A
441
57.644
26.954
172.834
1.00
23.44
A

ATOM
2418
CB
ASP
A
441
59.019
26.389
173.217
1.00
26.45
A

ATOM
2419
CG
ASP
A
441
59.864
27.370
174.011
1.00
28.97
A

ATOM
2420
OD1
ASP
A
441
59.811
28.590
173.734
1.00
30.64
A

ATOM
2421
OD2
ASP
A
441
60.595
26.912
174.915
1.00
32.82
A

ATOM
2422
C
ASP
A
441
57.011
26.056
171.774
1.00
22.99
A

ATOM
2423
O
ASP
A
441
57.314
26.180
170.588
1.00
23.08
A

ATOM
2424
N
GLU
A
442
56.095
25.194
172.222
1.00
21.93
A

ATOM
2425
CA
GLU
A
442
55.349
24.258
171.374
1.00
24.14
A

ATOM
2426
CB
GLU
A
442
54.434
23.394
172.259
1.00
27.03
A

ATOM
2427
CG
GLU
A
442
53.712
22.238
171.555
1.00
32.34
A

ATOM
2428
CD
GLU
A
442
52.816
21.443
172.493
1.00
35.35
A

ATOM
2429
OE1
GLU
A
442
51.940
22.046
173.154
1.00
35.80
A

ATOM
2430
OE2
GLU
A
442
52.989
20.207
172.567
1.00
38.32
A

ATOM
2431
C
GLU
A
442
54.516
25.031
170.341
1.00
22.89
A

ATOM
2432
O
GLU
A
442
54.305
24.557
169.222
1.00
23.30
A

ATOM
2433
N
PHE
A
443
54.109
26.245
170.717
1.00
21.55
A

ATOM
2434
CA
PHE
A
443
53.312
27.117
169.862
1.00
19.42
A

ATOM
2435
CB
PHE
A
443
52.178
27.769
170.663
1.00
19.65
A

ATOM
2436
CG
PHE
A
443
51.247
26.786
171.309
1.00
19.62
A

ATOM
2437
CD1
PHE
A
443
51.178
26.694
172.711
1.00
21.07
A

ATOM
2438
CD2
PHE
A
443
50.453
25.925
170.525
1.00
21.15
A

ATOM
2439
CE1
PHE
A
443
50.328
25.747
173.338
1.00
21.41
A

ATOM
2440
CE2
PHE
A
443
49.597
24.971
171.130
1.00
21.45
A

ATOM
2441
CZ
PHE
A
443
49.535
24.881
172.540
1.00
22.37
A

ATOM
2442
C
PHE
A
443
54.111
28.204
169.150
1.00
18.78
A

ATOM
2443
O
PHE
A
443
53.990
28.352
167.938
1.00
19.73
A

ATOM
2444
N
THR
A
444
54.945
28.933
169.896
1.00
18.79
A

ATOM
2445
CA
THR
A
444
55.741
30.042
169.343
1.00
20.20
A

ATOM
2446
CB
THR
A
444
56.357
30.926
170.449
1.00
18.90
A

ATOM
2447
OG1
THR
A
444
57.288
30.163
171.223
1.00
18.55
A

ATOM
2448
CG2
THR
A
444
55.269
31.479
171.354
1.00
18.16
A

ATOM
2449
C
THR
A
444
56.830
29.696
168.329
1.00
21.39
A

ATOM
2450
O
THR
A
444
57.235
30.556
167.542
1.00
22.19
A

ATOM
2451
N
ALA
A
445
57.293
28.446
168.351
1.00
23.41
A

ATOM
2452
CA
ALA
A
445
58.332
27.980
167.429
1.00
25.34
A

ATOM
2453
CB
ALA
A
445
59.168
26.886
168.081
1.00
25.22
A

ATOM
2454
C
ALA
A
445
57.761
27.493
166.095
1.00
27.29
A

ATOM
2455
O
ALA
A
445
58.512
27.273
165.139
1.00
26.93
A

ATOM
2456
N
GLN
A
446
56.434
27.351
166.034
1.00
28.39
A

ATOM
2457
CA
GLN
A
446
55.735
26.898
164.829
1.00
30.40
A

ATOM
2458
CB
GLN
A
446
54.319
26.422
165.164
1.00
31.32
A

ATOM
2459
CG
GLN
A
446
54.240
25.068
165.848
1.00
32.45
A

ATOM
2460
CD
GLN
A
446
52.807
24.610
166.067
1.00
33.93
A

ATOM
2461
OE1
GLN
A
446
52.348
24.488
167.203
1.00
34.49
A

ATOM
2462
NE2
GLN
A
446
52.090
24.361
164.975
1.00
34.58
A

ATOM
2463
C
GLN
A
446
55.654
27.981
163.761
1.00
32.00
A

ATOM
2464
O
GLN
A
446
55.357
29.140
164.059
1.00
31.38
A

ATOM
2465
N
SER
A
447
55.934
27.590
162.519
1.00
34.38
A

ATOM
2466
CA
SER
A
447
55.891
28.503
161.378
1.00
36.87
A

ATOM
2467
CB
SER
A
447
56.785
27.989
160.242
1.00
37.47
A

ATOM
2468
OG
SER
A
447
56.482
26.646
159.902
1.00
37.47
A

ATOM
2469
C
SER
A
447
54.453
28.680
160.897
1.00
38.40
A

ATOM
2470
O
SER
A
447
53.683
27.716
160.848
1.00
39.25
A

ATOM
2471
N
ILE
A
448
54.090
29.927
160.604
1.00
40.49
A

ATOM
2472
CA
ILE
A
448
52.749
30.274
160.131
1.00
42.86
A

ATOM
2473
CB
ILE
A
448
52.111
31.412
160.988
1.00
42.99
A

ATOM
2474
CG2
ILE
A
448
51.539
30.826
162.281
1.00
43.72
A

ATOM
2475
CG1
ILE
A
448
53.133
32.524
161.278
1.00
42.57
A

ATOM
2476
CD1
ILE
A
448
52.548
33.770
161.891
1.00
42.57
A

ATOM
2477
C
ILE
A
448
52.717
30.634
158.642
1.00
43.59
A

ATOM
2478
O
ILE
A
448
53.473
31.497
158.181
1.00
44.55
A

ATOM
2479
N
ALA
A
449
51.859
29.936
157.897
1.00
44.86
A

ATOM
2480
CA
ALA
A
449
51.699
30.146
156.456
1.00
45.55
A

ATOM
2481
CB
ALA
A
449
52.668
29.253
155.677
1.00
45.40
A

ATOM
2482
C
ALA
A
449
50.263
29.874
156.017
1.00
46.17
A

ATOM
2483
O
ALA
A
449
49.668
28.858
156.386
1.00
47.08
A

ATOM
2484
N
ALA
A
466
26.345
36.321
148.790
1.00
55.65
A

ATOM
2485
CA
ALA
A
466
26.716
36.093
150.182
1.00
55.32
A

ATOM
2486
CB
ALA
A
466
26.650
37.403
150.968
1.00
55.16
A

ATOM
2487
C
ALA
A
466
25.826
35.026
150.825
1.00
55.28
A

ATOM
2488
O
ALA
A
466
24.699
35.306
151.250
1.00
55.63
A

ATOM
2489
N
ALA
A
467
26.341
33.798
150.861
1.00
54.91
A

ATOM
2490
CA
ALA
A
467
25.638
32.654
151.442
1.00
54.32
A

ATOM
2491
CB
ALA
A
467
25.428
31.575
150.384
1.00
54.96
A

ATOM
2492
C
ALA
A
467
26.403
32.088
152.638
1.00
53.99
A

ATOM
2493
O
ALA
A
467
25.829
31.391
153.480
1.00
53.96
A

ATOM
2494
N
THR
A
468
27.698
32.400
152.700
1.00
52.91
A

ATOM
2495
CA
THR
A
468
28.586
31.953
153.777
1.00
51.02
A

ATOM
2496
CB
THR
A
468
29.896
31.331
153.187
1.00
51.53
A

ATOM
2497
OG1
THR
A
468
30.720
30.827
154.246
1.00
52.59
A

ATOM
2498
CG2
THR
A
468
30.684
32.352
152.351
1.00
51.69
A

ATOM
2499
C
THR
A
468
28.884
33.110
154.754
1.00
49.54
A

ATOM
2500
O
THR
A
468
29.800
33.031
155.581
1.00
48.58
A

ATOM
2501
N
HIS
A
469
28.068
34.163
154.663
1.00
48.00
A

ATOM
2502
CA
HIS
A
469
28.188
35.363
155.495
1.00
46.23
A

ATOM
2503
CB
HIS
A
469
27.474
36.541
154.810
1.00
46.08
A

ATOM
2504
CG
HIS
A
469
27.777
37.879
155.412
1.00
45.97
A

ATOM
2505
CD2
HIS
A
469
27.023
38.708
156.174
1.00
45.86
A

ATOM
2506
ND1
HIS
A
469
28.988
38.515
155.238
1.00
46.38
A

ATOM
2507
CE1
HIS
A
469
28.966
39.677
155.866
1.00
46.15
A

ATOM
2508
NE2
HIS
A
469
27.786
39.818
156.442
1.00
46.02
A

ATOM
2509
C
HIS
A
469
27.625
35.146
156.903
1.00
45.32
A

ATOM
2510
O
HIS
A
469
26.439
34.841
157.074
1.00
45.07
A

ATOM
2511
N
PHE
A
470
28.491
35.327
157.899
1.00
44.14
A

ATOM
2512
CA
PHE
A
470
28.132
35.177
159.310
1.00
43.02
A

ATOM
2513
CB
PHE
A
470
29.369
34.797
160.134
1.00
41.68
A

ATOM
2514
CG
PHE
A
470
29.591
33.315
160.263
1.00
40.48
A

ATOM
2515
CD1
PHE
A
470
29.477
32.688
161.519
1.00
39.62
A

ATOM
2516
CD2
PHE
A
470
29.937
32.535
159.141
1.00
40.21
A

ATOM
2517
CE1
PHE
A
470
29.708
31.293
161.665
1.00
39.55
A

ATOM
2518
CE2
PHE
A
470
30.171
31.139
159.266
1.00
39.57
A

ATOM
2519
CZ
PHE
A
470
30.057
30.517
160.533
1.00
39.80
A

ATOM
2520
C
PHE
A
470
27.510
36.462
159.867
1.00
43.39
A

ATOM
2521
O
PHE
A
470
28.119
37.536
159.773
1.00
42.56
A

ATOM
2522
N
PRO
A
471
26.281
36.375
160.428
1.00
44.34
A

ATOM
2523
CD
PRO
A
471
25.366
35.213
160.446
1.00
45.04
A

ATOM
2524
CA
PRO
A
471
25.615
37.559
160.988
1.00
45.42
A

ATOM
2525
CB
PRO
A
471
24.175
37.083
161.177
1.00
45.46
A

ATOM
2526
CG
PRO
A
471
24.333
35.622
161.467
1.00
45.63
A

ATOM
2527
C
PRO
A
471
26.223
38.074
162.295
1.00
46.03
A

ATOM
2528
O
PRO
A
471
26.943
37.349
162.993
1.00
46.15
A

ATOM
2529
N
GLN
A
472
25.926
39.340
162.590
1.00
46.33
A

ATOM
2530
CA
GLN
A
472
26.381
40.069
163.781
1.00
46.54
A

ATOM
2531
CB
GLN
A
472
25.639
39.600
165.042
1.00
47.23
A

ATOM
2532
CG
GLN
A
472
24.141
39.861
164.977
1.00
49.30
A

ATOM
2533
CD
GLN
A
472
23.496
39.887
166.336
1.00
50.05
A

ATOM
2534
OE1
GLN
A
472
23.577
40.886
167.050
1.00
50.50
A

ATOM
2535
NE2
GLN
A
472
22.851
38.787
166.709
1.00
50.49
A

ATOM
2536
C
GLN
A
472
27.896
40.181
164.002
1.00
45.51
A

ATOM
2537
O
GLN
A
472
28.380
40.245
165.136
1.00
45.91
A

ATOM
2538
N
PHE
A
473
28.630
40.205
162.890
1.00
44.75
A

ATOM
2539
CA
PHE
A
473
30.086
40.364
162.890
1.00
43.02
A

ATOM
2540
CB
PHE
A
473
30.744
39.336
161.957
1.00
41.34
A

ATOM
2541
CG
PHE
A
473
31.470
38.232
162.679
1.00
39.89
A

ATOM
2542
CD1
PHE
A
473
30.765
37.134
163.211
1.00
38.04
A

ATOM
2543
CD2
PHE
A
473
32.869
38.275
162.822
1.00
38.61
A

ATOM
2544
CE1
PHE
A
473
31.446
36.077
163.883
1.00
37.36
A

ATOM
2545
CE2
PHE
A
473
33.572
37.230
163.490
1.00
37.42
A

ATOM
2546
CZ
PHE
A
473
32.854
36.127
164.022
1.00
37.19
A

ATOM
2547
C
PHE
A
473
30.343
41.802
162.411
1.00
43.73
A

ATOM
2548
O
PHE
A
473
29.480
42.671
162.602
1.00
45.51
A

ATOM
2549
N
ASP
A
474
31.504
42.050
161.794
1.00
42.35
A

ATOM
2550
CA
ASP
A
474
31.906
43.371
161.268
1.00
42.24
A

ATOM
2551
CB
ASP
A
474
31.165
43.685
159.955
1.00
45.28
A

ATOM
2552
CG
ASP
A
474
31.574
42.757
158.813
1.00
47.74
A

ATOM
2553
OD1
ASP
A
474
31.190
41.565
158.835
1.00
48.55
A

ATOM
2554
OD2
ASP
A
474
32.282
43.223
157.891
1.00
49.47
A

ATOM
2555
C
ASP
A
474
31.819
44.527
162.288
1.00
40.00
A

ATOM
2556
O
ASP
A
474
30.980
45.429
162.177
1.00
40.94
A

ATOM
2557
N
TYR
A
475
32.704
44.465
163.282
1.00
36.44
A

ATOM
2558
CA
TYR
A
475
32.779
45.442
164.370
1.00
33.09
A

ATOM
2559
CB
TYR
A
475
32.573
44.700
165.706
1.00
30.04
A

ATOM
2560
CG
TYR
A
475
32.771
45.478
167.006
1.00
24.95
A

ATOM
2561
CD1
TYR
A
475
31.737
46.274
167.546
1.00
23.36
A

ATOM
2562
CE1
TYR
A
475
31.896
46.933
168.802
1.00
22.57
A

ATOM
2563
CD2
TYR
A
475
33.973
45.359
167.741
1.00
22.85
A

ATOM
2564
CE2
TYR
A
475
34.144
46.011
168.993
1.00
21.48
A

ATOM
2565
CZ
TYR
A
475
33.104
46.791
169.514
1.00
20.48
A

ATOM
2566
OH
TYR
A
475
33.272
47.411
170.729
1.00
22.52
A

ATOM
2567
C
TYR
A
475
34.101
46.216
164.380
1.00
33.06
A

ATOM
2568
O
TYR
A
475
35.139
45.712
163.949
1.00
32.18
A

ATOM
2569
N
SER
A
476
34.032
47.430
164.927
1.00
32.88
A

ATOM
2570
CA
SER
A
476
35.161
48.347
165.087
1.00
34.71
A

ATOM
2571
CB
SER
A
476
35.261
49.314
163.898
1.00
34.88
A

ATOM
2572
OG
SER
A
476
35.573
48.628
162.695
1.00
34.52
A

ATOM
2573
C
SER
A
476
34.898
49.124
166.376
1.00
35.91
A

ATOM
2574
O
SER
A
476
33.831
49.729
166.532
1.00
36.10
A

ATOM
2575
N
ALA
A
477
35.857
49.078
167.302
1.00
37.38
A

ATOM
2576
CA
ALA
A
477
35.745
49.754
168.599
1.00
40.37
A

ATOM
2577
CB
ALA
A
477
36.753
49.175
169.586
1.00
39.82
A

ATOM
2578
C
ALA
A
477
35.883
51.271
168.536
1.00
42.21
A

ATOM
2579
O
ALA
A
477
36.699
51.802
167.777
1.00
42.18
A

ATOM
2580
N
SER
A
478
35.063
51.947
169.340
1.00
45.14
A

ATOM
2581
CA
SER
A
478
35.035
53.407
169.431
1.00
47.33
A

ATOM
2582
CB
SER
A
478
33.630
53.885
169.813
1.00
49.73
A

ATOM
2583
OG
SER
A
478
32.676
53.498
168.837
1.00
50.82
A

ATOM
2584
C
SER
A
478
36.063
53.955
170.424
1.00
48.10
A

ATOM
2585
O
SER
A
478
36.592
55.053
170.228
1.00
47.74
A

ATOM
2586
N
ALA
A
479
36.342
53.180
171.475
1.00
48.79
A

ATOM
2587
CA
ALA
A
479
37.302
53.556
172.517
1.00
50.13
A

ATOM
2588
CB
ALA
A
479
36.887
52.957
173.857
1.00
50.04
A

ATOM
2589
C
ALA
A
479
38.724
53.124
172.160
1.00
50.67
A

ATOM
2590
O
ALA
A
479
39.673
53.902
172.284
1.00
51.60
A

ATOM
2591
PG
ANP
A
500
39.417
25.847
173.896
1.00
9.41
A

ATOM
2592
N3B
ANP
A
500
40.344
26.913
173.019
1.00
10.38
A

ATOM
2593
O1G
ANP
A
500
37.969
26.073
173.474
1.00
9.65
A

ATOM
2594
O2G
ANP
A
500
39.744
26.245
175.274
1.00
8.04
A

ATOM
2595
O3G
ANP
A
500
39.850
24.489
173.609
1.00
10.48
A

ATOM
2596
PB
ANP
A
500
39.861
27.891
171.746
1.00
11.17
A

ATOM
2597
O1B
ANP
A
500
39.952
27.125
170.525
1.00
13.09
A

ATOM
2598
O2B
ANP
A
500
38.541
28.477
172.062
1.00
12.20
A

ATOM
2599
PA
ANP
A
500
41.239
30.219
172.776
1.00
9.68
A

ATOM
2600
O1A
ANP
A
500
40.479
31.439
172.504
1.00
9.02
A

ATOM
2601
O2A
ANP
A
500
41.174
29.615
174.136
1.00
7.76
A

ATOM
2602
O3A
ANP
A
500
40.938
29.083
171.660
1.00
11.08
A

ATOM
2603
O5*
ANP
A
500
42.774
30.527
172.425
1.00
8.07
A

ATOM
2604
C5*
ANP
A
500
43.761
29.488
172.580
1.00
9.46
A

ATOM
2605
C4*
ANP
A
500
44.980
30.030
173.294
1.00
9.67
A

ATOM
2606
O4*
ANP
A
500
45.424
31.254
172.662
1.00
11.95
A

ATOM
2607
C3*
ANP
A
500
44.701
30.400
174.743
1.00
10.39
A

ATOM
2608
O3*
ANP
A
500
44.708
29.285
175.636
1.00
10.49
A

ATOM
2609
C2*
ANP
A
500
45.759
31.445
174.994
1.00
10.98
A

ATOM
2610
O2*
ANP
A
500
47.007
30.817
175.342
1.00
10.67
A

ATOM
2611
C1*
ANP
A
500
45.905
32.171
173.663
1.00
9.49
A

ATOM
2612
N9
ANP
A
500
45.115
33.414
173.660
1.00
10.60
A

ATOM
2613
C8
ANP
A
500
43.752
33.584
173.478
1.00
10.97
A

ATOM
2614
N7
ANP
A
500
43.357
34.811
173.540
1.00
11.38
A

ATOM
2615
C5
ANP
A
500
44.524
35.523
173.778
1.00
12.24
A

ATOM
2616
C6
ANP
A
500
44.777
36.902
173.952
1.00
11.76
A

ATOM
2617
N6
ANP
A
500
43.802
37.813
173.903
1.00
11.24
A

ATOM
2618
N1
ANP
A
500
46.084
37.297
174.178
1.00
13.39
A

ATOM
2619
C2
ANP
A
500
47.059
36.370
174.224
1.00
12.04
A

ATOM
2620
N3
ANP
A
500
46.929
35.038
174.075
1.00
10.58
A

ATOM
2621
C4
ANP
A
500
45.610
34.683
173.851
1.00
10.86
A

ATOM
2622
MN
MN
A
501
40.473
28.238
175.472
1.00
9.43
A

ATOM
2623
MN
MN
A
502
37.013
28.007
173.523
1.00
11.07
A

ATOM
2624
C
GLY
B
3
50.740
18.235
185.265
1.00
34.68
B

ATOM
2625
O
GLY
B
3
50.818
19.442
185.025
1.00
37.14
B

ATOM
2626
N
GLY
B
3
51.802
17.798
187.495
1.00
36.33
B

ATOM
2627
CA
GLY
B
3
51.851
17.538
186.029
1.00
35.97
B

ATOM
2628
N
ARG
B
4
49.716
17.461
184.886
1.00
32.14
B

ATOM
2629
CA
ARG
B
4
48.527
17.908
184.134
1.00
26.40
B

ATOM
2630
CB
ARG
B
4
47.671
18.879
184.976
1.00
26.58
B

ATOM
2631
CG
ARG
B
4
46.437
19.516
184.310
1.00
24.76
B

ATOM
2632
CD
ARG
B
4
46.316
20.936
184.844
1.00
23.33
B

ATOM
2633
NE
ARG
B
4
45.172
21.756
184.419
1.00
19.93
B

ATOM
2634
CZ
ARG
B
4
44.915
22.175
183.179
1.00
18.01
B

ATOM
2635
NH1
ARG
B
4
45.685
21.832
182.155
1.00
14.82
B

ATOM
2636
NH2
ARG
B
4
43.992
23.104
182.990
1.00
18.10
B

ATOM
2637
C
ARG
B
4
48.797
18.478
182.730
1.00
24.18
B

ATOM
2638
O
ARG
B
4
49.389
19.557
182.591
1.00
22.33
B

ATOM
2639
N
PRO
B
5
48.387
17.742
181.670
1.00
21.51
B

ATOM
2640
CD
PRO
B
5
47.890
16.348
181.678
1.00
22.02
B

ATOM
2641
CA
PRO
B
5
48.591
18.212
180.293
1.00
18.98
B

ATOM
2642
CB
PRO
B
5
48.413
16.933
179.469
1.00
20.54
B

ATOM
2643
CG
PRO
B
5
47.409
16.153
180.256
1.00
21.49
B

ATOM
2644
C
PRO
B
5
47.553
19.275
179.913
1.00
18.20
B

ATOM
2645
O
PRO
B
5
46.621
19.539
180.687
1.00
14.64
B

ATOM
2646
N
ARG
B
6
47.716
19.865
178.727
1.00
17.95
B

ATOM
2647
CA
ARG
B
6
46.792
20.883
178.214
1.00
17.65
B

ATOM
2648
CB
ARG
B
6
47.255
21.430
176.868
1.00
20.26
B

ATOM
2649
CG
ARG
B
6
48.392
22.398
176.947
1.00
23.07
B

ATOM
2650
CD
ARG
B
6
48.511
23.194
175.656
1.00
22.64
B

ATOM
2651
NE
ARG
B
6
47.416
24.148
175.441
1.00
22.34
B

ATOM
2652
CZ
ARG
B
6
47.322
25.350
176.016
1.00
19.82
B

ATOM
2653
NH1
ARG
B
6
48.251
25.771
176.865
1.00
18.72
B

ATOM
2654
NH2
ARG
B
6
46.307
26.148
175.720
1.00
19.88
B

ATOM
2655
C
ARG
B
6
45.403
20.299
178.036
1.00
16.97
B

ATOM
2656
O
ARG
B
6
45.254
19.164
177.581
1.00
15.89
B

ATOM
2657
N
THR
B
7
44.396
21.072
178.431
1.00
15.56
B

ATOM
2658
CA
THR
B
7
43.010
20.635
178.336
1.00
17.45
B

ATOM
2659
CB
THR
B
7
42.294
20.722
179.713
1.00
17.68
B

ATOM
2660
OG1
THR
B
7
42.156
22.093
180.107
1.00
21.53
B

ATOM
2661
CG2
THR
B
7
43.057
19.973
180.789
1.00
18.88
B

ATOM
2662
C
THR
B
7
42.253
21.468
177.303
1.00
17.25
B

ATOM
2663
O
THR
B
7
42.388
22.697
177.268
1.00
19.69
B

ATOM
2664
N
THR
B
8
41.481
20.791
176.454
1.00
16.02
B

ATOM
2665
CA
THR
B
8
40.697
21.455
175.409
1.00
15.55
B

ATOM
2666
CB
THR
B
8
41.025
20.895
173.996
1.00
18.90
B

ATOM
2667
OG1
THR
B
8
40.925
19.465
174.006
1.00
21.52
B

ATOM
2668
CG2
THR
B
8
42.426
21.303
173.560
1.00
21.36
B

ATOM
2669
C
THR
B
8
39.198
21.324
175.671
1.00
13.80
B

ATOM
2670
O
THR
B
8
38.754
20.392
176.349
1.00
13.33
B

ATOM
2671
N
SER
B
9
38.422
22.260
175.129
1.00
12.68
B

ATOM
2672
CA
SER
B
9
36.973
22.249
175.307
1.00
12.47
B

ATOM
2673
CB
SER
B
9
36.405
23.674
175.249
1.00
14.21
B

ATOM
2674
OG
SER
B
9
36.285
24.142
173.911
1.00
14.37
B

ATOM
2675
C
SER
B
9
36.245
21.361
174.296
1.00
12.76
B

ATOM
2676
O
SER
B
9
36.841
20.887
173.323
1.00
14.55
B

ATOM
2677
N
PHE
B
10
34.962
21.126
174.561
1.00
13.76
B

ATOM
2678
CA
PHE
B
10
34.100
20.333
173.688
1.00
13.46
B

ATOM
2679
CB
PHE
B
10
34.083
18.836
174.100
1.00
16.28
B

ATOM
2680
CG
PHE
B
10
33.284
18.538
175.355
1.00
14.94
B

ATOM
2681
CD1
PHE
B
10
31.961
18.045
175.265
1.00
16.82
B

ATOM
2682
CD2
PHE
B
10
33.828
18.789
176.625
1.00
17.22
B

ATOM
2683
CE1
PHE
B
10
31.186
17.816
176.429
1.00
15.52
B

ATOM
2684
CE2
PHE
B
10
33.067
18.564
177.805
1.00
14.78
B

ATOM
2685
CZ
PHE
B
10
31.741
18.078
177.702
1.00
15.44
B

ATOM
2686
C
PHE
B
10
32.693
20.926
173.732
1.00
13.91
B

ATOM
2687
O
PHE
B
10
32.360
21.692
174.642
1.00
11.85
B

ATOM
2688
N
ALA
B
11
31.867
20.510
172.776
1.00
14.09
B

ATOM
2689
CA
ALA
B
11
30.476
20.930
172.671
1.00
16.39
B

ATOM
2690
CB
ALA
B
11
30.357
22.277
171.951
1.00
15.47
B

ATOM
2691
C
ALA
B
11
29.748
19.839
171.899
1.00
19.04
B

ATOM
2692
O
ALA
B
11
30.139
19.501
170.776
1.00
19.18
B

ATOM
2693
N
GLU
B
12
28.740
19.248
172.542
1.00
21.65
B

ATOM
2694
CA
GLU
B
12
27.927
18.180
171.951
1.00
26.02
B

ATOM
2695
CB
GLU
B
12
27.165
17.433
173.055
1.00
28.33
B

ATOM
2696
CG
GLU
B
12
26.435
16.157
172.618
1.00
32.22
B

ATOM
2697
CD
GLU
B
12
25.643
15.520
173.751
1.00
34.95
B

ATOM
2698
OE1
GLU
B
12
24.628
16.115
174.182
1.00
36.56
B

ATOM
2699
OE2
GLU
B
12
26.036
14.425
174.211
1.00
36.85
B

ATOM
2700
C
GLU
B
12
26.948
18.750
170.917
1.00
27.72
B

ATOM
2701
O
GLU
B
12
26.264
19.748
171.238
1.00
27.95
B

ATOM
2702
OXT
GLU
B
12
26.890
18.194
169.798
1.00
29.77
B

ATOM
2703
OH2
TIP
S
1
35.513
19.462
187.609
1.00
8.68
S

ATOM
2704
OH2
TIP
S
2
34.119
23.788
181.779
1.00
8.79
S

ATOM
2705
OH2
TIP
S
3
50.965
30.957
178.095
1.00
11.42
S

ATOM
2706
OH2
TIP
S
4
39.194
18.375
188.406
1.00
7.91
S

ATOM
2707
OH2
TIP
S
5
33.495
30.603
176.993
1.00
12.70
S

ATOM
2708
OH2
TIP
S
6
33.279
17.866
195.059
1.00
11.14
S

ATOM
2709
OH2
TIP
S
7
49.067
29.203
174.198
1.00
16.63
S

ATOM
2710
OH2
TIP
S
8
30.715
23.037
184.039
1.00
14.80
S

ATOM
2711
OH2
TIP
S
9
46.349
17.630
188.194
1.00
15.87
S

ATOM
2712
OH2
TIP
S
10
22.572
18.305
190.665
1.00
16.99
S

ATOM
2713
OH2
TIP
S
11
36.637
44.504
178.296
1.00
10.61
S

ATOM
2714
OH2
TIP
S
12
20.954
30.509
186.356
1.00
13.91
S

ATOM
2715
OH2
TIP
S
13
35.546
27.646
175.192
1.00
15.04
S

ATOM
2716
OH2
TIP
S
14
50.275
38.942
188.553
1.00
13.53
S

ATOM
2717
OH2
TIP
S
15
35.330
42.723
176.495
1.00
13.11
S

ATOM
2718
OH2
TIP
S
16
55.177
36.700
176.903
1.00
11.19
S

ATOM
2719
OH2
TIP
S
17
55.266
31.109
165.695
1.00
18.50
S

ATOM
2720
OH2
TIP
S
18
41.312
16.013
203.045
1.00
20.46
S

ATOM
2721
OH2
TIP
S
19
50.201
30.584
201.352
1.00
16.58
S

ATOM
2722
OH2
TIP
S
20
36.996
34.711
172.597
1.00
15.08
S

ATOM
2723
OH2
TIP
S
21
29.676
18.119
197.893
1.00
13.47
S

ATOM
2724
OH2
TIP
S
22
40.919
15.924
195.875
1.00
15.77
S

ATOM
2725
OH2
TIP
S
23
23.000
12.106
190.288
1.00
14.25
S

ATOM
2726
OH2
TIP
S
24
52.949
32.525
194.744
1.00
13.76
S

ATOM
2727
OH2
TIP
S
25
33.009
27.747
184.065
1.00
15.77
S

ATOM
2728
OH2
TIP
S
26
22.253
26.995
191.698
1.00
16.31
S

ATOM
2729
OH2
TIP
S
27
58.929
31.921
183.099
1.00
17.72
S

ATOM
2730
OH2
TIP
S
28
22.864
38.421
177.895
1.00
13.50
S

ATOM
2731
OH2
TIP
S
29
48.171
19.107
197.167
1.00
17.80
S

ATOM
2732
OH2
TIP
S
30
23.481
32.542
173.772
1.00
17.19
S

ATOM
2733
OH2
TIP
S
31
59.971
25.389
187.105
1.00
14.41
S

ATOM
2734
OH2
TIP
S
32
36.493
24.796
181.760
1.00
13.84
S

ATOM
2735
OH2
TIP
S
33
35.916
29.549
169.844
1.00
19.69
S

ATOM
2736
OH2
TIP
S
34
26.760
18.671
197.567
1.00
13.32
S

ATOM
2737
OH2
TIP
S
35
51.205
29.093
176.132
1.00
11.39
S

ATOM
2738
OH2
TIP
S
36
35.408
41.548
201.022
1.00
14.63
S

ATOM
2739
OH2
TIP
S
37
48.677
43.513
177.997
1.00
22.26
S

ATOM
2740
OH2
TIP
S
38
55.545
26.769
182.425
1.00
20.34
S

ATOM
2741
OH2
TIP
S
39
51.976
46.164
187.557
1.00
20.17
S

ATOM
2742
OH2
TIP
S
40
47.037
22.259
187.710
1.00
20.21
S

ATOM
2743
OH2
TIP
S
41
34.633
38.852
202.253
1.00
14.95
S

ATOM
2744
OH2
TIP
S
42
30.505
23.971
181.497
1.00
14.52
S

ATOM
2745
OH2
TIP
S
43
40.037
34.151
172.734
1.00
15.01
S

ATOM
2746
OH2
TIP
S
44
24.388
25.120
188.049
1.00
20.05
S

ATOM
2747
OH2
TIP
S
45
32.659
32.730
205.273
1.00
18.75
S

ATOM
2748
OH2
TIP
S
46
59.518
32.651
180.652
1.00
19.23
S

ATOM
2749
OH2
TIP
S
47
20.673
26.102
176.394
1.00
15.77
S

ATOM
2750
OH2
TIP
S
48
26.440
26.553
168.049
1.00
18.31
S

ATOM
2751
OH2
TIP
S
49
25.405
15.362
191.412
1.00
18.80
S

ATOM
2752
OH2
TIP
S
50
35.319
44.324
174.147
1.00
19.55
S

ATOM
2753
OH2
TIP
S
51
55.207
40.912
175.135
1.00
20.88
S

ATOM
2754
OH2
TIP
S
52
56.981
40.770
189.703
1.00
18.54
S

ATOM
2755
OH2
TIP
S
53
48.076
23.195
189.959
1.00
19.55
S

ATOM
2756
OH2
TIP
S
54
48.774
27.766
198.643
1.00
14.67
S

ATOM
2757
OH2
TIP
S
55
32.106
43.138
189.021
1.00
22.66
S

ATOM
2758
OH2
TIP
S
56
24.074
39.850
175.826
1.00
28.15
S

ATOM
2759
OH2
TIP
S
57
21.973
33.790
197.949
1.00
34.40
S

ATOM
2760
OH2
TIP
S
58
22.026
24.203
188.263
1.00
21.34
S

ATOM
2761
OH2
TIP
S
59
33.453
16.616
197.704
1.00
23.05
S

ATOM
2762
OH2
TIP
S
60
50.801
27.570
178.959
1.00
28.34
S

ATOM
2763
OH2
TIP
S
61
52.902
39.224
157.977
1.00
23.75
S

ATOM
2764
OH2
TIP
S
62
41.488
7.599
189.155
1.00
19.38
S

ATOM
2765
OH2
TIP
S
63
38.845
11.799
201.454
1.00
27.38
S

ATOM
2766
OH2
TIP
S
64
19.536
28.443
177.717
1.00
18.22
S

ATOM
2767
OH2
TIP
S
65
28.303
12.355
195.234
1.00
22.19
S

ATOM
2768
OH2
TIP
S
66
21.973
18.597
178.917
1.00
25.36
S

ATOM
2769
OH2
TIP
S
67
37.673
25.400
207.417
1.00
21.23
S

ATOM
2770
OH2
TIP
S
68
25.125
17.966
191.418
1.00
22.23
S

ATOM
2771
OH2
TIP
S
69
41.253
13.685
181.348
1.00
22.30
S

ATOM
2772
OH2
TIP
S
70
35.350
46.611
172.452
1.00
22.34
S

ATOM
2773
OH2
TIP
S
71
28.913
47.422
180.499
1.00
21.84
S

ATOM
2774
OH2
TIP
S
72
43.694
40.374
176.847
1.00
16.46
S

ATOM
2775
OH2
TIP
S
73
22.932
35.810
185.514
1.00
25.69
S

ATOM
2776
OH2
TIP
S
74
27.757
11.435
183.289
1.00
28.99
S

ATOM
2777
OH2
TIP
S
75
14.735
36.062
184.933
1.00
22.70
S

ATOM
2778
OH2
TIP
S
76
46.773
44.790
172.601
1.00
25.80
S

ATOM
2779
OH2
TIP
S
77
41.994
12.598
191.334
1.00
18.04
S

ATOM
2780
OH2
TIP
S
78
45.286
8.859
184.781
1.00
22.73
S

ATOM
2781
OH2
TIP
S
79
34.459
45.849
199.248
1.00
23.78
S

ATOM
2782
OH2
TIP
S
80
49.997
33.952
201.347
1.00
23.16
S

ATOM
2783
OH2
TIP
S
81
47.050
26.998
172.932
1.00
26.45
S

ATOM
2784
OH2
TIP
S
82
50.437
19.716
177.733
1.00
27.06
S

ATOM
2785
OH2
TIP
S
83
34.063
47.953
197.860
1.00
23.39
S

ATOM
2786
OH2
TIP
S
84
44.020
15.103
191.224
1.00
18.68
S

ATOM
2787
OH2
TIP
S
85
33.015
24.574
184.481
1.00
25.62
S

ATOM
2788
OH2
TIP
S
86
17.099
25.296
179.596
1.00
36.31
S

ATOM
2789
OH2
TIP
S
87
28.989
34.198
201.808
1.00
24.10
S

ATOM
2790
OH2
TIP
S
88
19.471
20.951
197.413
1.00
26.73
S

ATOM
2791
OH2
TIP
S
89
33.503
19.254
170.465
1.00
21.21
S

ATOM
2792
OH2
TIP
S
90
14.410
32.374
188.444
1.00
35.55
S

ATOM
2793
OH2
TIP
S
91
50.036
19.368
189.222
1.00
19.75
S

ATOM
2794
OH2
TIP
S
92
19.777
20.806
193.508
1.00
29.16
S

ATOM
2795
OH2
TIP
S
93
42.821
5.486
183.252
1.00
29.85
S

ATOM
2854
OH2
TIP
S
153
59.037
25.695
190.823
1.00
23.41
S

ATOM
2855
OH2
TIP
S
154
32.478
25.593
203.042
1.00
25.66
S

ATOM
2856
OH2
TIP
S
155
45.821
42.754
177.669
1.00
34.32
S

ATOM
2857
OH2
TIP
S
156
28.989
44.834
187.660
1.00
38.53
S

ATOM
2858
OH2
TIP
S
157
60.167
36.196
172.532
1.00
29.39
S

ATOM
2859
OH2
TIP
S
158
50.004
40.728
155.773
1.00
34.95
S

ATOM
2860
OH2
TIP
S
159
58.989
35.289
189.746
1.00
44.53
S

ATOM
2861
OH2
TIP
S
160
16.930
32.266
179.235
1.00
26.96
S

ATOM
2862
OH2
TIP
S
161
37.722
17.742
175.393
1.00
33.58
S

ATOM
2863
OH2
TIP
S
162
37.001
27.551
156.174
1.00
34.38
S

ATOM
2864
OH2
TIP
S
163
56.216
22.358
168.570
1.00
52.08
S

ATOM
2865
OH2
TIP
S
164
43.307
24.924
175.719
1.00
30.97
S

ATOM
2866
OH2
TIP
S
165
31.555
50.258
162.429
1.00
40.07
S

ATOM
2867
OH2
TIP
S
166
62.303
47.418
173.584
1.00
45.59
S

ATOM
2868
OH2
TIP
S
167
47.109
17.914
210.912
1.00
42.78
S

ATOM
2869
OH2
TIP
S
168
23.879
33.048
168.898
1.00
34.23
S

ATOM
2870
OH2
TIP
S
169
40.895
34.331
154.310
1.00
34.53
S

ATOM
2871
OH2
TIP
S
170
31.937
50.261
170.310
1.00
40.40
S

ATOM
2872
OH2
TIP
S
171
32.516
26.022
169.042
1.00
25.90
S

ATOM
2873
OH2
TIP
S
172
51.018
47.685
171.259
1.00
32.99
S

ATOM
2874
OH2
TIP
S
173
50.051
54.453
167.264
1.00
46.29
S

ATOM
2875
OH2
TIP
S
174
58.984
45.818
186.069
1.00
38.72
S

ATOM
2876
OH2
TIP
S
175
58.195
26.946
176.789
1.00
32.90
S

ATOM
2877
OH2
TIP
S
176
52.285
20.827
191.417
1.00
41.48
S

ATOM
2878
OH2
TIP
S
177
32.590
29.707
169.779
1.00
26.14
S

ATOM
2879
OH2
TIP
S
178
36.480
19.235
153.519
1.00
41.40
S

ATOM
2880
OH2
TIP
S
179
43.010
44.995
190.927
1.00
44.14
S

ATOM
2881
OH2
TIP
S
180
44.742
21.757
166.449
1.00
49.28
S

ATOM
2882
OH2
TIP
S
181
42.091
4.325
185.720
1.00
35.81
S

ATOM
2883
OH2
TIP
S
182
43.744
24.461
165.023
1.00
37.22
S

ATOM
2884
OH2
TIP
S
183
23.778
20.893
171.557
1.00
50.83
S

ATOM
2885
OH2
TIP
S
184
47.952
45.789
196.708
1.00
38.69
S

ATOM
2886
OH2
TIP
S
185
32.513
3.008
181.727
1.00
41.23
S

ATOM
2887
OH2
TIP
S
186
17.997
41.636
181.572
1.00
44.78
S

ATOM
2888
OH2
TIP
S
187
40.259
35.881
206.400
1.00
37.81
S

ATOM
2889
OH2
TIP
S
188
65.479
40.015
178.254
1.00
32.75
S

ATOM
2890
OH2
TIP
S
189
49.440
16.871
189.100
1.00
33.81
S

ATOM
2891
OH2
TIP
S
190
44.412
41.390
200.479
1.00
35.02
S

ATOM
2892
OH2
TIP
S
191
47.677
33.628
158.523
1.00
41.63
S

ATOM
2893
OH2
TIP
S
192
44.004
13.331
193.278
1.00
37.83
S

ATOM
2894
OH2
TIP
S
193
34.579
44.061
191.774
1.00
25.71
S

ATOM
2895
OH2
TIP
S
194
35.914
3.269
188.382
1.00
36.75
S

ATOM
2896
OH2
TIP
S
195
45.275
23.850
173.309
1.00
35.54
S

ATOM
2897
OH2
TIP
S
196
59.521
32.119
167.352
1.00
44.76
S

ATOM
2898
OH2
TIP

210
42.509
27.406
175.671
1.00
7.70

ATOM
2899
OH2
TIP

213
35.527
27.997
171.928
1.00
12.93

ATOM
2900
OH2
TIP
S
197
25.667
16.315
196.524
1.00
14.31
S

ATOM
2901
OH2
TIP
S
198
20.985
20.487
189.856
1.00
19.24
S

ATOM
2902
OH2
TIP
S
199
47.877
19.863
187.919
1.00
37.55
S

ATOM
2903
OH2
TIP
S
200
33.409
40.577
203.909
1.00
21.10
S

ATOM
2904
OH2
TIP
S
201
51.083
24.139
177.423
1.00
29.24
S

ATOM
2905
OH2
TIP
S
202
40.108
12.526
193.310
1.00
24.57
S

ATOM
2906
OH2
TIP
S
203
46.204
14.480
189.797
1.00
20.39
S

ATOM
2907
OH2
TIP
S
204
59.725
29.306
182.130
1.00
24.53
S

ATOM
2908
OH2
TIP
S
205
19.660
22.585
191.338
1.00
20.78
S

ATOM
2909
OH2
TIP
S
206
20.366
29.151
188.684
1.00
24.25
S

ATOM
2910
OH2
TIP
S
207
18.552
29.962
175.953
1.00
24.46
S

ATOM
2911
OH2
TIP
S
208
40.246
13.296
196.148
1.00
27.69
S

ATOM
2912
OH2
TIP
S
209
39.384
9.796
177.359
1.00
30.25
S

ATOM
2913
OH2
TIP
S
210
42.901
12.306
195.542
1.00
25.85
S

ATOM
2914
OH2
TIP
S
211
46.745
48.676
159.158
1.00
28.61
S

ATOM
2915
OH2
TIP
S
212
25.057
24.931
169.591
1.00
35.99
S

ATOM
2916
OH2
TIP
S
213
51.729
21.198
183.094
1.00
38.05
S

ATOM
2917
OH2
TIP
S
214
54.190
46.635
189.239
1.00
26.46
S

ATOM
2918
OH2
TIP
S
215
41.358
15.872
178.575
1.00
28.40
S

ATOM
2919
OH2
TIP
S
216
30.758
5.815
183.937
1.00
30.68
S

ATOM
2920
OH2
TIP
S
217
44.499
17.166
181.580
1.00
45.83
S

ATOM
2921
OH2
TIP
S
218
50.193
16.047
191.422
1.00
25.35
S

ATOM
2922
OH2
TIP
S
219
18.578
26.839
189.735
1.00
35.25
S

ATOM
2923
OH2
TIP
S
220
30.442
32.389
203.918
1.00
33.23
S

ATOM
2924
OH2
TIP
S
221
48.189
12.146
182.335
1.00
27.32
S

ATOM
2925
OH2
TIP
S
222
22.870
19.047
182.621
1.00
26.54
S

ATOM
2926
OH2
TIP
S
223
15.038
20.644
185.432
1.00
35.64
S

ATOM
2927
OH2
TIP
S
224
19.574
30.830
191.004
1.00
36.66
S

ATOM
2928
OH2
TIP
S
225
25.386
23.543
159.436
1.00
32.20
S

ATOM
2929
OH2
TIP
S
226
35.762
27.555
167.952
1.00
39.91
S

ATOM
2930
OH2
TIP
S
227
56.362
24.244
183.451
1.00
30.98
S

ATOM
2931
OH2
TIP
S
228
43.983
43.413
198.979
1.00
35.86
S

ATOM
2932
OH2
TIP
S
229
58.148
27.235
182.659
1.00
25.52
S

ATOM
2933
OH2
TIP
S
230
57.231
38.376
191.705
1.00
29.97
S

ATOM
2934
OH2
TIP
S
231
20.438
25.071
190.325
1.00
27.05
S

ATOM
2935
OH2
TIP
S
232
49.374
23.256
186.582
1.00
32.24
S

ATOM
2936
OH2
TIP
S
233
31.653
47.356
197.435
1.00
39.51
S

ATOM
2937
OH2
TIP
S
234
32.871
26.291
206.215
1.00
41.69
S

ATOM
2938
OH2
TIP
S
235
56.963
48.017
166.922
1.00
41.33
S

ATOM
2939
OH2
TIP
S
236
55.551
36.207
192.111
1.00
35.03
S

ATOM
2940
OH2
TIP
S
237
39.593
45.654
179.152
1.00
45.66
S

ATOM
2941
OH2
TIP
S
238
54.494
25.491
180.488
1.00
32.50
S

ATOM
2942
OH2
TIP
S
239
22.686
42.000
174.825
1.00
34.96
S

ATOM
2943
OH2
TIP
S
240
30.458
42.567
198.012
1.00
42.30
S

ATOM
2944
OH2
TIP
S
241
32.588
20.101
199.129
1.00
40.13
S

ATOM
2945
OH2
TIP
S
242
36.814
6.726
188.574
1.00
30.03
S

ATOM
2946
OH2
TIP
S
243
31.557
14.729
198.380
1.00
36.65
S

ATOM
2947
OH2
TIP
S
244
61.873
24.000
188.309
1.00
46.44
S

ATOM
2948
OH2
TIP
S
245
19.147
23.741
187.058
1.00
41.94
S

ATOM
2949
OH2
TIP
S
246
33.080
28.203
167.770
1.00
40.37
S

ATOM
2950
OH2
TIP
S
247
33.047
26.649
171.502
1.00
29.73
S

ATOM
2951
OH2
TIP
S
248
61.443
33.660
174.498
1.00
37.78
S

ATOM
2952
OH2
TIP
S
249
22.270
31.262
170.291
1.00
32.69
S

ATOM
2953
OH2
TIP
S
250
45.722
39.480
203.974
1.00
41.52
S

ATOM
2954
OH2
TIP
S
251
51.506
37.660
196.901
1.00
38.39
S

ATOM
2955
OH2
TIP
S
252
58.939
25.420
162.339
1.00
38.51
S

ATOM
2956
OH2
TIP
S
253
27.598
43.470
199.877
1.00
40.65
S

ATOM
2957
OH2
TIP
S
254
31.256
8.994
180.108
1.00
36.78
S

ATOM
2958
OH2
TIP
S
255
21.276
41.879
185.920
1.00
34.18
S

ATOM
2959
OH2
TIP
S
256
19.869
38.072
188.104
1.00
36.71
S

ATOM
2960
OH2
TIP
S
257
62.029
36.228
175.092
1.00
40.06
S

ATOM
2961
OH2
TIP
S
258
51.861
21.808
178.461
1.00
44.11
S

ATOM
2962
OH2
TIP
S
259
32.933
42.026
192.309
1.00
40.66
S

ATOM
2963
OH2
TIP
S
260
40.922
46.243
202.382
1.00
47.61
S

ATOM
2964
OH2
TIP
S
261
54.008
34.812
195.671
1.00
38.51
S

ATOM
2965
OH2
TIP
S
262
31.023
12.231
197.309
1.00
36.92
S

ATOM
2966
OH2
TIP
S
263
46.934
46.192
175.930
1.00
35.59
S

ATOM
2967
OH2
TIP
S
264
51.061
24.166
201.555
1.00
41.56
S

ATOM
2968
OH2
TIP
S
265
19.412
32.509
175.612
1.00
39.41
S

ATOM
2969
OH2
TIP
S
266
22.420
33.009
166.350
1.00
38.16
S

ATOM
2970
OH2
TIP
S
267
45.672
24.498
208.627
1.00
42.67
S

ATOM
2971
OH2
TIP
S
268
45.405
47.077
173.230
1.00
35.95
S

ATOM
2972
OH2
TIP
S
269
28.182
36.091
146.589
1.00
35.22
S

ATOM
2973
OH2
TIP
S
270
58.022
37.298
163.226
1.00
32.86
S

ATOM
2974
OH2
TIP
S
271
49.386
49.478
192.687
1.00
35.65
S

ATOM
2975
OH2
TIP
S
272
27.643
18.836
166.258
1.00
45.49
S

ATOM
2976
OH2
TIP
S
273
46.091
39.730
197.476
1.00
36.53
S

ATOM
2977
OH2
TIP
S
274
52.146
35.742
201.214
1.00
36.20
S

ATOM
2978
OH2
TIP
S
275
48.834
44.782
174.633
1.00
40.19
S

ATOM
2979
OH2
TIP
S
276
51.922
25.202
180.996
1.00
45.09
S

ATOM
2980
OH2
TIP
S
277
30.932
23.368
155.743
1.00
32.13
S

ATOM
2981
OH2
TIP
S
278
18.988
40.249
185.025
1.00
39.74
S

ATOM
2982
OH2
TIP
S
279
34.632
9.705
203.624
1.00
43.63
S

ATOM
2983
OH2
TIP
S
280
42.646
41.610
193.545
1.00
33.68
S

END

Number	Date	Country
0119860.5	Aug 2001	GB
0209985.1	May 2002	GB
0216215.4	Jul 2002	GB

Kinase crystal structures

Information

Publication Number

Date Filed

Date Published

Inventors

Original Assignees

CPC

US Classifications

International Classifications

Abstract

Description

Claims

Priority Claims (3)