CRYSTAL STRUCTURE OF THE INFLUENZA VIRUS POLYMERASE PAC-PB1N COMPLEX AND USES THEREOF

Abstract

Provided are the expression method of influenza virus polymerase PAc-PB1N complex, the co-crystallization method of the complex and the three-dimendional structure of the crystal of PAc-PB1N complex. Also provided are the compounds binding to the influenza virus polymerase PAc and the expression method of influenza virus polymerase PAN. The three-dimensional structure of the crystal of PAc-PB1N complex can be used for screening and designing the drug for the treatment of influenza.

Description

TECHNICAL FIELD

The present invention relates to a method for expression of influenza virus PA and PB1 N-terminal polypeptide in bacteria, purification and crystallization. It also relates to the crystal three-dimensional structure of complex of C-terminal of PA and N-terminal polypeptide of PB1 and its application in drug design.

BACKGROUND ART

Influenza virus have already brought great disaster to human beings (Taubenberger and Morens 2007). Due to lacking enough treating means and frequent variation of the virus itself, the virus remains a threat to human beings. In recent years, frequent and severe avian influenza epidemic situation as well as transmission of avian influenza in human beings has constituted a great threat to health and economics of human beings, so investigation directed to this kind of virus is of great value to protect human health. Avian influenza virus belongs to influenza virus A type, which are all Orthomyxoviridae family members. The virus genome consists of 8 negatively charged single-stranded RNA. Through comparison and analysis of genes of Avian influenza virus origin and other influenza A viruses, it is found that there are sporadic mutations in primary struture, and these mutations result in differential pathogenicity of different influenza viruses. Now, it is considered that influenza virus can encode 11 proteins, wherein the replication of influenza virus genome RNA and mRNA transcription were completed by the RNA polymerase carried by that virus itself, and thus the polymerase has become a potentially important drug target. Recent research suggested that the high pathogenicity of some influenza viruses is directly correlated with the polymerase mutations (Hulse-Post, Franks et al. 2007; Munster, de Wit et 20 al. 2007), further illustrating the necessity of designing drugs aming at this complex. Investigation into this complex is of great significance to reveal the molecular mechanism underlying virus replication and to design drugs aming at this complex. The RNA polymerase is a complex composed of PB1, PB2 and PA subunits, wherein PB1 is a subunit with catalytic activity, PB2 is responsible for acquiring cellular mRNA cap (CAP structure) through a snatching mode as primers of virus mRNA transcription, but PB1 acts as an endonuclease in this process. A temperature sensitive mutant ts53 suggests that PA takes part in the replication process of virus genome, but its specific function is still unclear (Sugiura, Ueda et al. 1975; Kawaguchi, Naito et al. 2005). The polymerase has three kind of RNA activity which is needed in virus synthesis, i.e. mRNA, cRNA and vRNA, respectively. The mRNA synthesis starts from capped oligonucleotide primer and ends at the 15-17 nucleotides from vRNA terminal and a polyA tail is added. Polymerase can synthesize cRNA intermediate of the full-length virus de novo and further synthesize full-length vRNA. Respective subunits of the polymerase can be exprssed by insect cell expression system, thus forming three different complexes, wherein one is a ternary complex containg the three subunits PB1/PB2/PA of polymerase, and the other two are binary complexes: PB1/PB2 and PB1/PA binary complex respectively, but they can not form PB2/PA complex (Honda, Mizumoto et al. 2002). Wherein, 25 amino acids of PB1 N-terminal are sufficient to interact with PA C-terminal, whereas PB1 C-terminal is responsible for the interaction with PB2 N-terminal. A synthetical competive small peptide of PB1 N-terminal can significantly inhibit the activity of virus polymerase. RNA synthesis experiments using dinucleotide ApG as primers indicated that PB1/PA complex can effectively initiate the replication of virus genome RNA, and PB1/PB2 can synthesize virus mRNA in vitro (Honda, Mizumoto et al. 2002), but the recombinant polymerase which was expressed and purified using 293 cell revealed that the three subuits are all necessary for replication and transcription (Deng, Sharps et al. 2006). The idea that PA principally participates the replication process of virus RNA is derived from a finding that a tempreture sensitive mutant (L226P) can result in replication disorder of virus genome under non-permissible temperatures without affecting transcription activity (Kawaguchi, Naito et al. 2005); whereas PB2 is involved in virus mRNA transcription. Further studies found that PA can extensively take part in processes such as transcription, replication and virus stability (Hara, Schmidt et al. 2006). PB1/PA complex can bind the 5′ terminal virus promoter, but only PB1 fails to bind that promoter. Cross-linking experiments indicate that PA can bind vRNA and cRNA promoters (Fodor, Pritlove et al. 1994; Deng, Sharps et al. 2005; Hara, Schmidt et al. 2006)(Fodor 1994, Gonzalez 1999, Jung 2006, Hara 2006), but the specific binding sites are not clear. PA was found to have similar protease activity as chymotrypsins. Sanz-Ezquerro et al. (1996) found that about 250 amino acids at N-terminal are the active region of that protease (Sanz-Ezquerro, Zurcher et al. 1996). But subsequently the studies by Hara et al. (2001) showed that the Serine at position 624 of C-terminal was the active site of PA protease, and the mutation at that site resulted in loss of protease activity, therefore Ser624 may also consiste an active region of that protease (Hara, Shiota et al. 2001). There is still controversy about the effect of PA protease activity on polymerase function. Hara et al. (2006) reported that purified recombinant PA protein can be degraded into two fragments with molecular weight of ˜25 kDa and ˜55 kDa through trypsin hydrolysis (Hara, Schmidt et al. 2006). It is known that three-dimensional structure of protein is of great help to perform rational drug design, so revealing three-dimensional structure of PA is of important value to perform drug design and function studies. In addition, previous studies have not reported the expression and purification of influenza virus protein PA in bacteria, so expression and purification of proteins in bacteria is of important benefit to further explore the function of PA and to perform drug screening, thus saving much time and greatly decreasing job cost and labour intensity.

SUMMARY OF THE INVENTION

The present invention provides a method of separating the wild type or mutant protein of influenza virus polymerase complex subunit PA into N-terminal and C-terminal, and then cloning and expressing them respectively; and a method of expressing, purifying and crystallizating N-terminal of PA; and a method of expressing N-terminal short peptide of wild type or mutant protein of influenza virus polymerase subunit PB1; and a method of co-purification of PA C-terminal and PB1 N-terminal short peptides. The method of expressing and co-purifying the complex of the former 256 amino acids of the N-terminal of PA as well as 257-716 amino acids of C-terminal of PA and the 25 peptides of N-terminal of PB1 according to the invention, crystallization method of the protein complex of PA C-terminal and PB1 N-terminal peptide as well as crystal three-dimensional structure of the resulting complex.

In one aspect, the present invention provides a method of dividing the wild type or mutant protein of influenza virus polymerase complex subunit PA into N-terminal part and C-terminal part as well as cloning and expressing them respectively; and a method of expressing, purifying and crystalling N-terminal of PA; and a method of expressing N-terminal polypeptide of wild type or mutant protein of influenza virus polymerase subunit PB1 and co-purifying the complex of PA C-terminal and PB1 N-terminal short peptides for crystallization. The present invention preferably use prokaryotic cell expression system of E. coli (but other expression systems are not exclued, for example, expression can also be performed in other bacteria or other eukaryotic cells) to express the above-mentioned polypeptide as GST (glutathione-5-transferase) fusion protein, and mix two kind of expression bacteria which express PA C-terminal and PB1 N-terminal short peptide, and further co-purify the protein complex containing above-mentioned PA C-terminal and PB1 N-terminal short peptides from the bacteria, for use in crystallization of protein. According to the expression method of obtaining the former 256 amino acids of N-terminal of influenza virus polymerase subunit PA and 257-716 amino acids of C-terminal of influenza virus polymerase subunit PA through expression in E. coli and the method of obtaining microbial population of E. coli that express the polypeptide within 25 or 48 amino acids of N-terminal of influenza virus protein PB1 that are described in the invention, the methods can express the GST (glutathione-5-transferase)-fused fusion proteins by cloning corresponding genes into pGEX-6p vector.

In another aspect, the present invention provides a method of purifying the complex of PA C-terminal (PAc) and PB1_N peptides, comprising: the microbial population expressing the 257-716 amino acids of C-terminal of influenza virus PA and the microbial population expressing a short peptide within 25 or 48 amino acids of the N-terminal of influenza virus PB1 were suspended with buffers respectively, and these two expression bacteria are mixed proportionally to reach a certain molar ratio between the total protein content of GST-PAc and GST-PB1_N, thus expressing the protein mixture of these two proteins; the protein mixture was purified by affinity column and then cleaved by PreScission protease to cut GST fusion protein; and the complex of PA and PB1 N-terminal peptide through such methods as gel filtration and ion exchange chromatography; and the protein purity is determined by gel electrophoresis.

In another aspect, the present invention provides a method of crystallizing the complex of PAc and PB1_N peptide obtained as described above, comprising: the complex of PAc and PB1_N peptide is condensed to a concentration of 5-30 mg/ml; the crystal growth condition is screened by gas hanging drop at 4-30° C.; and crystal of the protein complex is obtained.

In another aspect, the present invention provides the crystal of the complex of PAc and PB1_N peptides.

In another aspect, the present invention provides crystal three-dimensional structure of the complex of PAc and PB1_N peptide, the structure describes interaction mode between PAc and PB1_N and corresponding interaction sites, and also describes the composition of secondary structure, peptide chain direction and three-dimensional molecular structure of polypeptide in the complex, wherein X-ray crystal diffraction was performed based on the crystal of the complex of PAc and PB1_N peptide to obtain the diffraction data from the protein crystal of the complex of PAc and PB1 N-terminal peptide, and then three-dimensional structure model of the complex of PAc and PB1_N peptide was constructed by further performing a structure analysis process with the diffraction data from the protein crystal.

In one embodiment, the present invention provides crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein the C-terminal of the influenza virus polymerase subunit PA-PAc is amino acids from amino acid positions about 201˜about 301 to about 650˜terminal, the N-terminal of influenza virus polymerase subunit PB1-PB1_N is a short peptide within the 48 amino acids of the N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein atoms of the crystal three-dimensional structure of the complex have at least part of atomic coordinates listed in table 1, or any structure that has average root mean square deviation (RMSD) smaller than or equal to 1.7 Angstrom with atomic coordinates of main chain carbon backbone of at least 40% amino acids in the crystal three-dimensional structure of complex.

Preferably, the crystal of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N has space group of P4(1)2(1)2, and the lattice parameters are about: a=b=122 Angstrom, c=133 Angstrom, α=β=γ=90°.

In one embodiment, the influenza virus is selected from influenza virus A, B and C type, preferably influenza virus A type: A/goose/Guangdong/1/96, A/Brevig Mission/1/1918; influenza virus B type: B/Ann Arbor/1/1966 or influenza virus C type: C/JJ/1950.

In one embodiment, the C-terminal of influenza virus A polymerase subunit PA-PAc consists of the first portion (i.e. it constitutes the mouth section of the crystal structure, as shown in FIG. 4) and the second portion (i.e. it constitutes the head section of the crystal structure, as shown in FIG. 4), wherein the first portion consists of α helix 4, i.e. amino acids fragment of 406-414 positions, α helix 5, i.e. amino acids fragment of 440-450 positions, α helix 8, i.e. amino acids fragment of 583-603 positions, α helix 9, i.e. amino acids fragment of 608-613 positions, α helix 10, i.e. amino acids fragment of 633-649 positions, α helix 11, i.e. amino acids fragment of 653-673 positions, α helix 12, i.e. amino acids fragment of 683-691 positions, α helix 13, i.e. amino acids fragment of 698-714 positions, β sheet 8, i.e. amino acids fragment of 619-623 positions and β sheet 9, i.e. amino acids fragment of 628-631 positions; wherein the second portion mainly consists of β sheet 1, i.e. amino acids fragment of 290-292 positions, β sheet 2, i.e. amino acids fragment of 317-324 positions, β sheet 3, i.e. amino acids fragment of 480-491 positions, β sheet 4, i.e. amino acids fragment of 496-506 positions, β sheet 5, i.e. amino acids fragment of 517-526 positions, β sheet 6, i.e. amino acids fragment of 541-550 positions and β sheet 7, i.e. amino acids fragment of 557-571 positions; wherein the β sheets of the second portion of the C-terminal of PA-PAc is surrounded by α helix 1, i.e. amino acids fragment of 303-311 positions, α helix 2, i.e. amino acids fragment of 331-349 positions, α helix 3, i.e. amino acids fragment of 364-369 positions, α helix 6, i.e. amino acids fragment of 454-475 positions and α helix 7, i.e. amino acids fragment of 572-578 positions, wherein fragments of influenza virus B and C type corresponding to α helixes and β sheets of influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, the C-terminal of influenza virus type A polymerase subunit PA-PAc interacts with N-terminal of PB1-PB1_N mainly through α helix 8, α helix 10, α helix 11 and α helix 13, preferably through at least one amino acid selected from a group consisting of Leu666 of α helix 11, Phe710 of α helix 13, Val636 of α helix 10, Leu640 of α helix 10, Trp706 of α helix 13 and Gln670 of α helix 11, wherein fragments of influenza virus B and C type corresponding to α helixes of influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIG. 10A, FIG. 10B respectively.

In one embodiment, wherein at least one amino acid selected from the group consisting of Ile621, Gly622, Glu623, Thr618 and Pro620 interacts with the influenza virus polymerase subunit PB1, the Ile621, Gly622, Glu623, Thr618 and Pro620 is in the ring peptide between α helix 9 and α helix 10 of C-terminal of influenza virus A polymerase subunit PA-PAc, wherein fragments of influenza virus B and C type corresponding to α helixes of influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, wherein at least one amino acid selected from the group consisting of Asn647, Gln408, Cys584, Gln587, Gln591, Lys643, Asn647, Ser659, Lys663, Trp699 and Asn703 of the C-terminal of influenza virus A polymerase subunit PA-PAc constitutes “pocket-shape” amino acid sites which bind the influenza virus polymerase subunit PB1_N, wherein fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, wherein at least one amino acid selected from the group consisting of Trp406, Glu410, Lys461, Glu524, Phe525, Ser526, Lys536, Lys539, Tyr540, Leu563, Tyr564, Arg566 and Lys574 of the C-terminal of influenza virus A polymerase subunit PA-PAc constitutes “big groove” and “channel” structures which bind nucleotide, RNA or other small molecules or proteins, wherein fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, amino acid residues of 370˜405 positions of the C-terminal of PA-PAc constitutes a big ring, wherein corresponding fragments of influenza virus B and C type to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, α helix 12 and α helix 13 interact with other proteins, preferably at least one amino acid selected from the group consisting of Ile690, Glu691, Glu692, Cys693 and Asn696 of the α helix 12 and α helix 13 interacts with other proteins.

In one embodiment, at least one amino acid selected from the group consisting of Lys506, Gly507, Arg508, Ser509, His510, Leu511, Arg512, Asn513 and Asp514 interacts with other proteins, wherein His510 constitutes a portion of the polymerase complex RNAse, wherein fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, which binds to at least one member selected from the group consisting of α helix 8, α helix 10, α helix 11 and α helix 13 of C-terminal of influenza virus subunit PA-PAc, preferably binds to the member selected from the group consisting of Leu666 in α helix 11, Phe710 in α helix 13, Val636 and Leu640 in α helix 10, Trp706 in α helix 13, Gln670 in α helix 11 of N-terminal of influenza virus subunit PA-PAc, wherein fragments of influenza virus B and C type corresponding to influenza virus A are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate binding to at least one member selected from the group consisting of Ile621, Gly622, Glu623, Thr618 and Pro620 located at the circle peptide between α helix 9 and α helix 10 of the C-terminal of influenza virus polymerase subunit PA-PAc, wherein fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate binding to at least one amino acid selected from the group consisting of Asn647, Gln408, Cys584, Gln587, Gln591, Lys643, Asn647, Ser659, Lys663, Trp699 and Asn703 of the C-terminal of influenza virus A polymerase subunit PA-PAc, wherein fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate binding to at least one amino acid selected from the group consisting of Trp406, Glu410, Lys461, Glu524, Phe525, Ser526, Lys536, Lys539, Tyr540, Leu563, Tyr564, Arg566 and Lys574 of the C-terminal of influenza virus A polymerase subunit PA-PAc, wherein fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate binding to amino acids position 370˜405 of the C-terminal of influenza virus A polymerase subunit PA-PAc, wherein fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate binding to helix 12 and α helix 13 of the C-terminal of influenza virus A polymerase subunit PA-PAc, preferably to at least one amino acid selected from the group consisting of Ile690, Glu691, Glu692, Cys693 and Asn696 in α helix 12 and α helix 13, wherein corresponding fragments of influenza virus B and C type to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate binding to at least one amino acid selected from the group consisting of Lys506, Gly507, Arg508, Ser509, His510, Leu511, Arg512, Asn513 and Asp514 located at ring region between sheet β 4 and sheet β 5 in the C-terminal of influenza virus A polymerase subunit PA-PAc, wherein fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate which competes with influenza virus polymerase subunit PB1 for binding PAc, wherein fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, the present invention provides an interaction with PAc through the hydrophobic core constituted by the α helix 8, α helix 11, α helix 13 and α helix 10, preferably interaction with PAc through Met595 in α helix 8, Leu666 in α helix 11, Trp706 and Phe710 in α helix 13, Val636 and Val640 in α helix 10, wherein fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In one embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate which competes with influenza virus polymerase subunit PB1 for binding PAc, wherein the amino acid sequence of the polypeptide, protein, antibody or immune conjugate comprises at least three amino acids which are identical to amino acids of corresponding position in short PTLLFL motif of the short helix domain constituted by the 5th˜10th residues Pro5, Thr6, Leu7, Leu8, Phe9 and Leu 10 of N-terminal of wild influenza virus polymerase subunit PB1-PB1_N, when the polypeptide or protein is aligned with the PTLLFL motif.

In one embodiment, the present invention provides a composition comprising above-mentioned polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate.

In one embodiment, the present invention provides use of the above-mentioned composition in manufacturing the medicament used in the treatment of diseases caused by influenza virus.

In one embodiment, the present invention provides a method of expressing and purifying the complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, comprising: (a) construct a vector of gene sequence encoding amino acid positions about 201˜about 301 to about 650˜terminal of the C-terminal of influenza virus polymerase subunit PA-PAc, with a tag protein fused or not fused to the vector, prokaryotic cells or eukaryotic cells are transformed with said vector in order to express the PAc with the tag protein; (b) a method similar with that of expressing PAc was used to express the PB1_N with or without a tag protein; (c) Proportionally mix the cell expressing influenza virus polymerase subunit PAc obtained from step (a) and the cell expressing amino acids within the 48 amino acids of the N-terminal of influenza virus polymerase subunit PB1 obtained from step (b), the resulting protein is separated through the specifically recognizing by the specific tag, the tag protein is removed from the protein through enzymolysis, the complex of PAc and PB1_N is separated, and the concentration of the complex is determined;

The atoms of the Crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N has at least 40% atomic coordinates listed in table 1, or atomic coordinates of main chain carbon backbone of at least 40% amino acids in the crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N has average root mean square deviation smaller than or equal to 1.7 Angstrom with respect to the atomic coordinates listed in table 1.

In one embodiment, the present invention provides a method of expressing and purifying the complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein the tag protein is selected from GST, Flag-tag, Myc-tag, MBP-tag, specific antibodies; the vector comprises selective marker gene, the proportional mixing in step (c) means that molar ratio of tag protein-PAc and tag protein-PB1_N is 0.1:1˜1:0.1, preferably the molar ratio of tag protein-PAc and tag protein-PB1_N is 0.5:1˜1:0.5, more preferably the molar ratio of tag protein-PAc and tag protein-PB1_N is nearly 1:1; preferably the tag protein is GST, the method recognizing the specific tag is performed through affinity column, the method of removing tag is preformed by enzymolysis with proteinases, the method of separating the complex of PAc and PB1_N is preformed through gel filtration or ion-exchange chromatography, the protein concentration is determined through gel electrophoresis.

In one embodiment, the present invention provides a method of expressing and purifying the complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein the vector is pGEX-6p plasmid vector, and said selective marker gene is penicillin resistance gene, and the proteinase used in step (c) is ProScission proteinase; the restriction site in primers that is employed by the vector is a restriction site selected from a group consisting of SalI and NotI; the restriction site used where gene fragment is inserted is a restriction site selected from a group consisting of SalI and NotI; said gene fragment of C-terminal of influenza virus polymerase subunit PA-PAc is obtained from the genome of influenza virus A type: A/goose/Guangdong/1/96 by polymerase chain reaction (PCR) method; said vector and said inserted gene fragment are treated by corresponding DNA restriction enzyme respectively, such as those selected from a group consisting of BamHI and XhoI, and then the inserted gene and the vector is liagated by T4 DNA ligase, thus transfroming prokaryotic cells such as E. coli to obtain cloned plasimds. The cloned plasmid as described above is transformed into E. coli BL21, the resulting transformed bacteria are cultured and induced by using IPTG, wherein the preferred concentration of IPTG is 0.1 mM to 1 mM, and the cultured bacteria are centrifuged to obtain the microbial population that express said fusion protein.

In one embodiment, the present invention provides a method of co-crystallizing the complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, comprising: the protein concentration of the purified complex of PAc and PB1_N is condensed to 5-30 mg/ml; the crystal growth condition is screened by gas sitting drop and hanging drop; and crystal of the complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N is obtained.

In one embodiment, the present invention provides a method of expressing wild type or mutant protein of N-terminal of PA-PA_N, wherein PA_N is amino acids from positions 1˜ about 50 to about 200˜ about 300, the method comprising: construct a expression vector of gene sequence encoding amino acid positions 1˜ about 50 to about 200˜ about 300 of the N-terminal of influenza virus polymerase subunit PA-PA_N, with a gene of tag protein fused to the vector, and cells are transformed with the expression vector in order to express the PA_N with the maker protein, wherein the N-terminal of PA-PA_N has at least 40% sequence identity with the amino acids listed in FIG. 1C.

In one embodiment, the present invention provides a method of expressing wild type or mutant protein of N-terminal of PA-PA_N, wherein the gene sequence of N-terminal of polymerase subunit PA-PA_N is cloned into plasmind vectors for example, a series of pGEX vectors such as pGEX-6p, pGEX-4 T (Amersham Pharmacia), a series of pET vectors (Novagen) and a series of pMAL-c2 (Invitrogen) to express a fusion protein GST-PA_N which N-terminal of PA_N is fused with GST; the plasmid vector comprises the penicillin resistance gene and the restriction site that is employed by vector when cloning the polypeptide gene of N-terminal of PA-PA_N is a restriction site selected from a group consisting of BamHI and XhoI from multiple cloning sites in pGEX-6p; the restriction site used in PA_N gene cloning fragment is BamHI and XhoI; gene fragment of PA_N protein is amplified from the genome of influenza virus A type: A/goose/Guangdong/1/96 by polymerase chain reaction (PCR) method; the vector and the inserted gene fragment are treated by corresponding DNA restriction enzyme respectively, such as those selected from a group consisting of BamHI and XhoI, and then the inserted gene and the vector is liagated by T4 DNA ligase, thus transfroming E. coli to obtain cloned plasimds. The cloned plasmid as described above is transformed into E. coli BL21, the resulting transformed bacteria are cultured and induced by using 0.1 mM to 1 mM IPTG, and the cultured bacteria are centrifuged to obtain the microbial population that express said fusion protein.

In one embodiment, the present invention provides a method of screening candidate compounds which compete with PB1_N for binding PAc, the method comprising: (a) combine PAc to surface of the fixed support; (b) contact the excess tagged PB1_N with the fixed PAc; (c) thoroughly elute with eluent in order to remove unbound PB1_N; (d) contact the candidate compound solutions to be detected with the fixed PAc binding to the PB1_N in step (b); (e) thoroughly elute with the eluent in order to obtain solution to be detected; (f) measure concentration of free tagged PB1_N in the solution to be detected; (g) calculate the binding capability of the candidate compound to be detected with PAc according to the concentration of free tagged PB1_N in the solution.

In one embodiment, the present invention provides a method of screening candidate compounds which compete with PB1_N for binding PAc, wherein combining PAc to surface of the fixed support in step (a) is accomplished through covalently crosslinking or through binding PAc with affinity matrix, wherein there is a binding group of affinity matrix on the surface of the fixed support.

In one embodiment, the present invention provides a method of screening candidate compounds which compete with PB1_N for binding PAc, wherein the affinity matrix can be other polypeptides such as GST, Flag-tag, Myc-tag, MBP-tag and specific antibody, whereas there is corresponding binding group on the surface of the fixed support.

In one embodiment, the present invention provides a method of screening candidate compounds compete with PB1_N for binding PAc, wherein the tagged PB1_N polypeptide is selected from the protein tagged with isotope or the protein tagged with other chemical molecule, preferably, the other chemical molecular tag is green fluorescent protein or various fusion polypeptides, eg. binding peroxidase, phosphohydrolase, protien kinase, various group transferase.

In one embodiment, the present invention provides a method of screening candidate compounds which compete with PB1_N for binding PAc, wherein the fixed surface can be affinity chromatography columns

In one embodiment, the present invention provides use of the crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N in designing and screening polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate used in the treatment of diseases caused by the influenza virus infection.

Drug screening can be performed based on the above method of expressing and purifying PAc protein; the above method of expressing and purifying the complex of PAc and PB1_N polypeptide and the above method of obtaining protein crystal, and drug design can be performed based on the three-dimensional structure of PAc and PB1_N.

In one embodiment, the present invention provides use of the crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N in designing and screening polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate used in the treatment of diseases caused by the influenza virus infection, comprising:

design polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate binding to specific portion through computer simulation technology according to coordinates of three-dimensional structure of protein;

search for potential polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate binding to specific portion through computer simulation technology according to coordinates of three-dimensional structure of the protein;

the designed or searched polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate according to coordinates of three-dimensional structure of the protein bind to any subtype of influenza virus polymerase protein which have at least 50% sequence identity with the PAc and the PB1_N sequence, binding information is then analyzed;

the designed or searched polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate according to coordinates of three-dimensional structure of the protein bind to any subtype of influenza virus polymerase protein which have at least 50% sequence identity with the PAc and the PB1_N sequence, and then crystallization is preformed, the binding information of polypeptide or compound molecule to protein is analyzed through crystal diffraction method;

wherein the polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate that bind to any subtype of influenza virus polymerase protein which had at least 50% sequence identity with the PAc and the PB1_N sequence are candidate compounds.

To reveal the role of PA in polymerase and its fine three-dimensional structure, the inventors analyzed the crystal structure with a resolution of 2.9 Angstrom of the complex of a fragment of 257-716 residue in the C-terminal of PA (PAC) and 25 peptides in the N-terminal of PB1 (PB1N). This structure clearly indicates the interaction mode between the C-terminal of PA and N-terminal of PB1 as well as the composition of amino acid residues that participate in the interaction and their relative spatial position; reveals the three-dimensional structure model of the complex of C-terminal of PA and N-terminal of PB1, the composition of secondary structure in that protein, the binding sites of nucleic acid in PA protein molecule, small-molecule channel in PA protein molecule and the charge distribution of PA protein surface, providing structure basis for investigating the role of PA in the complex of virus RNA polymerase, and providing protein crystal platform and three-dimensional platform for designing drugs aming at interaction between PA and PB1 as well as interaction between PA and RNA and other proteins to inhibit the activity of influenza virus polymerase.

It should be noted that the amino acid sequence of corresponding fragments in influenza virus B and C type to α helixes and β sheets of influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively, which is not listed in detail.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A and 1B: Sequence of C-terminal of PA and protein sequence of PB1_N from three type of influenza virus. FIG. 1A. Sequence alignment of PA protein from three type of influenza virus, wherein A_OURS is sequence of C-terminal of PA protein from influenza virus A type: A/goose/Guangdong/1/96; A_—1918 is sequence of PA protein from influenza virus A type: A/Brevig Mission/1/1918, which is the cause of widespread influenza outbreak and a great death event in Europe in 1918; B_—1966 is sequence of PA protein from influenza virus B type: B/Ann Arbor/1/1966; C_—1950 is sequence of PA protein from influenza virus C type: C/JJ/1950; this result indicates that protein of influenza virus polymerase subunit PA has highly conservative amino acid residues. FIG. 1B. Sequence alignment of PB1_N protein from four type of influenza virus, wherein A_OURS, A_—1918, B_—1966, C_—1950 are as described above. In figures, . . . is used to indicate amino acid deletion in corresponding fragments. Specific amino acid positions in specification and claims are illustrated by the example of A_OURS.

FIG. 1C: Sequence of N-terminal of PA protein from three type of influenza virus. In figures, . . . is used to indicate amino acid deletion in corresponding fragments. Specific amino acid positions in specification and claims are illustrated by the example of A_OURS.

FIG. 2: Purification of a polypeptide fragment of the former 256 amino acid in PA N-terminal of influenza virus A type: A/goose/Guangdong/1/96, wherein A shows the peak of purified protein during gel filtration chromatography Superdex-200(Amersham Pharmacia Inc.). B represents electrophoresis result from PA N-terminal of corresponding peak. C is the finally purified protein of PA N-terminal.

FIG. 3: Protein crystallization and diffraction obtained from purified protein of PA N-terminal (1-256 residues), wherein A and B are crystals obtained under different crystallization conditions; and C and D show X-ray diffraction pattern of two protein crystals from PA N-terminal.

FIG. 4: PAc and GST-PB1_N protein expressed and purified in E. coli, and interaction experiment between PAc and PB1 N-terminal peptide, and ribbon image of structure of the complex between purified PAc and PB1_N polypeptide. A. purified PAc protein, and in vitro interaction experiment between purified PAc and PB1 N-terminal peptide. B. Diagram of three-dimensional structure of the complex between PAc and PB1_N polypeptide, which shows a overall structure of chewing wolf's head.

FIG. 5: Overall structure of the complex of C-terminal of PA and N-terminal of PB1, wherein: A. side view of overall structure of the complex of PAc and PB1_N, to clearly show the direction of protein chain; B. Image in FIG. 5(A) is rotated by 180°, wherein secondary structure is marked, and the two ends of PB1 N-terminal peptide and PAc is indicated by arrows.

FIG. 6: Interaction between PAc and PB1_N polypeptide, wherein: A. surface image of PA protein molecule; N-terminal polypeptide of PB1 is illustrated by ribbon image, whereas PA molecule is illustrated by surface charge distribution. B. zoomed to observe that interaction between PA and PB1 is mainly through hydrophobic interaction.

FIG. 7: Surface charge pattern of PA protein molecule, wherein A and B are consistent with the direction of A and B in FIG. 5 respectively.

FIG. 8: Schematic diagrams of big groove and channel present in molecular structure of PAc/PB1_N complex. A illustrates the big groove, and some alkaline amino acids residues are marked. B and C are drawings of channel observed from the two sides respectively (rotate 180° about X axis). Some reserved amino acids in or around the channel are marked.

FIG. 9: Illustration of interaction between PA-C and PB1-N, wherein: A. ribbon image of three-dimensional structure of the complex molecule between PA-C and PB1-N polypeptide; B. A surface image of PA protein molecule. N-terminal polypeptide of PB1 is illustrated by ribbon image, whereas PA molecule is illustrated by surface charge distribution. C. part of the complex is zoomed to observe that helix 8, 10, 11 and 13 of PA molecule interac with PB1 polypeptide. D. zoomed to observe interaction between PA and PB1. N-terminal polypeptide of PB1 is illustrated by ribbon image, whereas PA molecule is illustrated by surface charge distribution. The two polypeptides bind mainly through hydrophobic interaction.

FIG. 10: As describded in FIGS. 1A and 1B: Sequence of C-terminal of PA and protein sequence of PB1_N from three type of influenza virus. A. Sequence alignment of PA protein from three type of influenza virus, wherein A_OURS is sequence of C-terminal of PA protein from influenza virus A type: A/goose/Guangdong/1/96; A_—1918 is sequence of PA protein from influenza virus A type: A/Brevig Mission/1/1918, which is the cause of widespread influenza outbreak and a great death event in Europe in 1918; B_—1966 is sequence of PA protein from influenza virus B type: B/Ann Arbor/1/1966; C_—1950 is sequence of PA protein from influenza virus C type: C/JJ/1950; this result indicates that protein of influenza virus polymerase subunit PA has highly conservative amino acid residues. B. Sequence alignment of PB1_N protein from four type of influenza virus, wherein A_OURS, A_—1918, B_—1966, C_—1950 are as described above. In figures, . . . is used to indicate amino acid deletion in corresponding fragments. Specific amino acid positions in specification and claims are illustrated by the example of A_OURS. The box noted with “Round Loop” indicates big-ring region in the structure, and the other box (unmarked) is a possible nucleic acid binding region. Arrows indicate amino acid residues in PA that participate in binding with PB1 short peptide. Specific amino acid positions in specification and claims are illustrated by the example of A_OURS.

EMBODIMENTS

The present invention provides a method of expressing fragments of wild type or mutant protein of influenza virus polymerase subunit PA, wherein N-terminal part and C-terminal part are expressed and purified in E. coli respectively, including: a method of only using N-terminal of PA for crystallization experiment; a method of expressing and purifying a fragment containing the 257-716 residue in the C-terminal of the PA as well as the wild type and mutant protein of the N-terminal of influenza virus subunit PB1 in E. coli respectively. It also provides a method of crystallizating the complex of C-terminal of PA and N-terminal peptide of PB1, and the crystal structure of complex of PAc/PB1_N short peptide obtained therefrom, and drug screening based on these crystallization methods as well as drug design based on these crystal structures.

In one embodiment, the present invention provides crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein the C-terminal of the influenza virus polymerase subunit PA-PAc is amino acids from amino acid positions about 201˜ about 301 to about 650˜ terminal, the N-terminal of influenza virus polymerase subunit PB1-PB1_N is a short peptide within the 48 amino acids of the N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein atoms of the crystal three-dimensional structure has at least 40% atomic coordinates listed in table 1, or atomic coordinates of main chain carbon backbone of at least 40% amino acids in the crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N has an average root mean square deviation smaller than or equal to 1.7 Angstrom with respect to the atomic coordinates listed in table 1.

In one embodiment, the present invention provides crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein the influenza virus is selected from influenza virus A, B and C type, preferably influenza virus A type: A/goose/Guangdong/1/96, A/Brevig Mission/1/1918; influenza virus B type: B/Ann Arbor/1/1966 or influenza virus C type: C/JJ/1950.

In a preferred embodiment, the present invention provides crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein the crystal of the complex has space group of P4(1)2(1)2, and the lattice parameters are about: a=b=122 Angstrom, c=133 Angstrom, α=β=γ=90°.

In a preferred embodiment, the present invention provides crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein the C-terminal of influenza virus A polymerase subunit PA-PAc consists of the first portion and the second portion, wherein the first portion consists of α helix 4, i.e. amino acids fragment of 406-414 positions, α helix 5, i.e. amino acids fragment of 440-450 positions, α helix 8, i.e. amino acids fragment of 583-603 positions, α helix 9, i.e. amino acids fragment of 608-613 positions, α helix 10, i.e. amino acids fragment of 633-649 positions, α helix 11, i.e. amino acids fragment of 653-673 positions, α helix 12, i.e. amino acids fragment of 683-691 positions, α helix 13, i.e. amino acids fragment of 698-714 positions, β sheet 8, i.e. amino acids fragment of 619-623 positions and β sheet 9, i.e. amino acids fragment of 628-631 positions; wherein the second portion mainly consists of β sheet 1, i.e. amino acids fragment of 290-292 positions, β sheet 2, i.e. amino acids fragment of 317-324 positions, β sheet 3, i.e. amino acids fragment of 480-491 positions, β sheet 4, i.e. amino acids fragment of 496-506 positions, β sheet 5, i.e. amino acids fragment of 517-526 positions, β sheet 6, i.e. amino acids fragment of 541-550 positions and β sheet 7, i.e. amino acids fragment of 557-571 positions; wherein the β sheets of the second portion of the C-terminal of influenza virus polymerase A polymerase subunit PA-PAc is surrounded by α helix 1, i.e. amino acids fragment of 303-311 positions, α helix 2, i.e. amino acids fragment of 331-349 positions, α helix 3, i.e. amino acids fragment of 364-369 positions, α helix 6, i.e. amino acids fragment of 454-475 positions and α helix 7, i.e. amino acids fragment of 572-578 positions, wherein amino acids of fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In a preferred embodiment, the present invention provides crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein the C-terminal of influenza virus A polymerase subunit PA-PAc interacts with N-terminal of PB1-PB1_N mainly through α helix 8, α helix 10, α helix 11 and α helix 13, preferably through at least one amino acid selected from a group consisting of Leu666 of α helix 11, Phe710 of α helix 13, Val636 of α helix 10, Leu640 of α helix 10, Trp706 of α helix 13 and Gln670 of α helix 11, wherein amino acids of fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In a preferred embodiment, the present invention provides crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein at least one amino acid selected from the group consisting of Ile621, Gly622, Glu623, Thr618 and Pro620 interacts with the influenza virus polymerase subunit PB1, the Ile621, Gly622, Glu623, Thr618 and Pro620 is in the ring peptide between α helix 9 and α helix 10 of C-terminal of influenza virus A polymerase subunit PA-PAc, wherein amino acids of fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In a preferred embodiment, the present invention provides crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein at least one amino acid selected from the group consisting of Asn647, Gln408, Cys584, Gln587, Gln591, Lys643, Asn647, Ser659, Lys663, Trp699 and Asn703 of the C-terminal of influenza virus A polymerase subunit PA-PAc constitutes “pocket” amino acid sites which bind the influenza virus polymerase subunit PB1_N, wherein amino acids of fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In a preferred embodiment, the present invention provides crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein at least one amino acid selected from the group consisting of Trp406, Glu410, Lys461, Glu524, Phe525, Ser526, Lys536, Lys539, Tyr540, Leu563, Tyr564, Arg566 and Lys574 of the C-terminal of influenza virus A polymerase subunit PA-PAc constitutes “big groove” and “channel” structures which bind nucleotide, RNA or other small molecules or proteins, wherein amino acids of fragments of influenza virus B and C type corresponding to the influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In a preferred embodiment, the present invention provides crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein amino acid residues of 370-405 positions of the C-terminal of influenza virus A polymerase subunit PA-PAc constitutes a big ring, wherein amino acids of fragments of influenza virus B and C type corresponding to the influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In a preferred embodiment, the present invention provides crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein α helix 12 and α helix 13 of C-terminal of influenza virus polymerase subunit PA-PAc interact with other proteins, preferably at least one amino acid selected from the group consisting of Ile690, Glu691, Glu692, Cys693 and Asn696 of the α helix 12 and α helix 13 interacts with other proteins, and amino acids of fragments of influenza virus B and C type corresponding to the influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In a preferred embodiment, the present invention provides crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, wherein at least one amino acid of C-terminal of influenza virus polymerase subunit PA-PAc that is selected from the group consisting of Lys506, Gly507, Arg508, Ser509, His510, Leu511, Arg512, Asn513 and Asp514 interacts with other proteins, wherein His510 constitutes a portion of the polymerase complex RNAse, and amino acids of fragments of influenza virus B and C type corresponding to the influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In another embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound binding to at least one member selected from the group consisting of α helix 8, α helix 10, α helix 11 and α helix 13 of C-terminal of influenza virus polymerase subunit PA-PAc, wherein the influenza virus is selected from influenza virus A, B and C type, preferably influenza virus A type: A/goose/Guangdong/1/96, A/Brevig Mission/1/1918; influenza virus B type: B/Ann Arbor/1/1966 or influenza virus C type: C/JJ/1950; wherein the polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate preferably bind to the member selected from the group consisting of Leu666 in α helix 11, Phe710 in α helix 13, Val636 and Leu640 in α helix 10, Trp706 in α helix 13, Gln670 in α helix 11 of C-terminal of influenza virus polymerase subunit PA-PAc, wherein amino acids of fragments of influenza virus B and C type corresponding to the influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In another embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate binding to at least one member selected from the group consisting of Ile621, Gly622, Glu623, Thr618 and Pro620 located at the circle peptide between α helix 9 and α helix 10 of the C-terminal of influenza virus polymerase subunit PA-PAc, wherein amino acids of fragments of influenza virus B and C type corresponding to the influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In another embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate binding to at least one amino acid selected from the group consisting of Asn647, Gln408, Cys584, Gln587, Gln591, Lys643, Asn647, Ser659, Lys663, Trp699 and Asn703 of the C-terminal of influenza virus A polymerase subunit PA-PAc, wherein amino acids of fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In another embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate binding to at least one amino acid selected from the group consisting of Trp406, Glu410, Lys461, Glu524, Phe525, Ser526, Lys536, Lys539, Tyr540, Leu563, Tyr564, Arg566 and Lys574 of the C-terminal of influenza virus A polymerase subunit PA-PAc, wherein amino acids of fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In another embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate binding to amino acids position 370˜405 of the C-terminal of influenza virus A polymerase subunit PA-PAc, wherein amino acids of fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In another embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate binding to helix 12 and a helix 13 of the C-terminal of influenza virus A polymerase subunit PA-Pac, preferably to at least one amino acid selected from the group consisting of Ile690, Glu691, Glu692, Cys693 and Asn696 in α helix 12 and α helix 13, wherein amino acids of fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In another embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate binding to at least one amino acid selected from the group consisting of Lys506, Gly507, Arg508, Ser509, His510, Leu511, Arg512, Asn513 and Asp514 located at ring region between β sheet 4 and β sheet 5 in the C-terminal of influenza virus A polymerase subunit PA-PAc, wherein amino acids of fragments of influenza virus B and C type corresponding to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In another embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate which competes with influenza virus polymerase subunit PB1 for binding PAc.

In a preferred embodiment, the present invention provides the polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate which competes with influenza virus polymerase subunit PB1 for binding PAc predominantly by an interaction with PAc through the hydrophobic core constituted by the α helix 8, α helix 11, α helix 13 and α helix 10, preferably interaction with PAc through Met595 in α helix 8, Leu666 in α helix 11, Trp706 and Phe710 in α helix 13, Val636 and Val640 in α helix 10, wherein amino acids of corresponding fragments of influenza virus B and C type to influenza virus A type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, 10B respectively.

In a preferred embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate which competes with influenza virus polymerase subunit PB1 for binding PAc, wherein the amino acid sequence of the polypeptide or protein comprises at least three amino acids which are identical to amino acids of corresponding position of short PTLLFL motif of the short helix domain constituted by the 5th-10th residues Pro5, Thr6, Leu7, Leu8, Phe9 and Leu10 of N-terminal of wild influenza virus polymerase subunit PB1-PB1_N, when the polypeptide or protein is aligned with the PTLLFL motif

In another embodiment, the present invention provides a composition comprising above-mentioned polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates, and optionally comprising an carrier and an excipient.

In another embodiment, the present invention provides use of the composition in manufacturing medicaments used in the treatment of diseases caused by influenza virus.

In another embodiment, the present invention provides a method of expressing and purifying the complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, comprising:

(a) Construct a vector of gene sequence encoding amino acid positions about 201˜ about 301 to about 650˜ terminal of the C-terminal of influenza virus polymerase subunit PA-PAc, with a tag protein fused or not fused to the vector, prokaryotic cells or eukaryotic cells are transformed with said vector in order to express the PAc with the tag protein;

(b) A method similar with that of expressing PAc was used to express the PB1_N with or without a tag;

(c) Proportionally mix cells expressing the influenza virus PAc obtained from step (a) and cells expressing amino acids sequence within the 48 amino acids of the N-terminal of influenza virus PB1 obtained from step (b), the resulting protein is separated through the specifically recognizing the specific tag, the tag protein is removed from the protein through enzymolysis, the complex of PAc and PB1_N is separated, the concentration of the complex is determined;

Wherein the atoms of the crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N has at least 40% atomic coordinates listed in table 1, or atomic coordinates of main chain carbon backbone of at least 40% amino acids in the crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N has average root mean square deviation smaller than or equal to 1.7 Angstrom with respect to the atomic coordinates listed in table 1.

In a preferred embodiment, wherein the tag protein is selected from GST, Flag-tag, Myc-tag, MBP-tag, specific antibodies; the vector comprises selective marker gene, the Proportional mixing in step (c) means that molar ratio of tag protein-PAc and tag protein-PB1_N is 0.1:1˜1:0.1, preferably the molar ratio of tag protein-PAc and tag protein-PB1_N is 0.5:1˜1:0.5, more preferably the molar ratio of tag protein-PAc and tag protein-PB1_N is nearly 1:1; more preferably the tag protein is GST, the method of recognizing the specific tag is performed through affinity column, the method of removing tag is preformed with a protease, the method of separating the complex of PAc and PB1_N is preformed through gel filtration or ion-exchange chromatography, the protein concentration is determined through gel electrophoresis.

In a more preferable embodiment, wherein the procaryotic cell is E coli.

In another embodiment, the present invention provides a method of cocrystallizing the complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N, comprising:

the protein concentration of the purified complex of PAc and PB1_N is condensed to 5-30 mg/ml;

the crystal growth condition is screened by gas sitting drop and hanging drop;

crystal of the complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N is obtained.

In another embodiment, the present invention provides a method of expressing wild type or mutant protein of N-terminal of PA-PA_N, wherein PA_N is amino acids from positions 1˜ about 50 to about 200˜ about 300, the method comprising: construct an expression vector of gene sequence encoding amino acid positions 1˜ about 50 to about 200˜ about 300 of the N-terminal of influenza virus polymerase subunit PA-PA_N, with a gene of tag protein fused or not fused to the vector, and eukaryotic cells or prokaryotic cell are transformed with the vector in order to express the PA_N with or without the tag protein, wherein the amino acid sequence of the N-terminal of PA-PA_N has at least 40% sequence identity with the amino acids listed in FIG. 1C.

In a preferred embodiment, the procaryotic cell is E coli.

In another embodiment, the present invention provides a method of screening candidate compounds which compete with PB1_N for binding PAc, the method comprising:

(a) combine PAc to surface of the fixed support;

(b) contact the excess tagged PB1_N with the combined PAc;

(c) thoroughly elute with eluent in order to remove unbound PB1_N;

(d) contact the candidate compound solutions to be detected with the fixed PAc binding to the PB1_N;

(e) thoroughly elute with the eluent in order to obtain solution to be detected;

(f) measure concentration of free tagged PB1_N in the solution to be detected;

(g) calculate the binding capability of the candidate compound to be detected with PAc according to the concentration of free tagged PB1_N in the solution.

In a preferred embodiment, combining PAc to surface of the fixed support in step (a) is accomplished through covalently crosslinking or through binding PAc with affinity matrix, wherein there is a binding group of affinity matrix on the surface of the fixed support.

Preferably, the affinity matrix can be selected from GST, Flag-tag, Myc-tag, MBP-tag and specific antibody, whereas there is corresponding binding group of the affinity matrix on the surface of the fixed support.

Preferably, the tagged PB1_N polypeptide is selected from the protein tagged with isotope or the protein tagged with other chemical molecule, preferably, the other chemical molecular tag is green fluorescent protein or various fusion polypeptides.

Preferably, the fixed surface can be affinity chromatography columns

In one embodiment, the present invention provides use of the crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N in designing and screening polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates used in the treatment of diseases caused by the influenza virus infection, comprising:

design polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates binding to specific portion through computer simulation technology according to coordinates of three-dimensional structure of protein;

search for potential polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates binding to specific portion through computer simulation technology according to coordinates of three-dimensional structure of the protein;

the designed or searched polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates according to coordinates of three-dimensional structure of the protein bind to any subtype of influenza virus polymerase protein which have at least 50% sequence identity with the PAc and the PB1_N sequence, binding information is then analyzed;

the designed or searched polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates according to coordinates of three-dimensional structure of the protein bind to any subtype of influenza virus polymerase protein which have at least 50% sequence identity with the PAc and the PB1_N sequence, and then crystallization is preformed, the binding information of polypeptide or compound molecule to protein is analyzed through crystal diffraction method;

wherein the polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates that bind to any subtype of influenza virus polymerase protein which had at least 50% sequence identity with the PAc and the PB1_N sequence are candidate compounds.

In one embodiment, the present invention provides structure of the three subunits i.e. PA, PB1, PB2 of any subtype of influenza virus polymerase or the complex of PA, PB1 and PB2, wherein a protein contained in it or a fragment thereof has 40% identical sequence with the PAc protein.

In one embodiment, the present invention provides three-dimensional stereochemical structure of the three subunits i.e. PA, PB1, PB2 of any subtype of influenza virus polymerase or that of the complex of PA, PB1 and PB2, wherein the coordinates of three-dimensional structure in main chain of a protein contained in it or a fragment thereof has an average root mean square deviation smaller than or equal to 1.7 Angstrom with respect to three-dimensional atomic coordinates of a main chain carbon backbone having at least 40% amino acid residues of the PAc protein sequence.

In one embodiment, the present invention provides structure of subunit PA, PB1, PB2 or that of the complex of subunit PA, PB1 and PB2 from any subtype of influenza virus, wherein a protein fragment contained in it has 20% sequcne homology with the fragment of amnio acid 1-11 in the PB1_N polypeptide, preferably 40% sequence homology.

In one embodiment, the present invention provides a polypeptide or a small molecule, characterized in that it interacts with any amino acid of the influenza virus subunit PA.

In one embodiment, the present invention provides use of the crystal three-dimensional structure in drug screening and drug design.

In one embodiment, the present invention provides a method of screening a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate which binds to the protein based on crystal three-dimensional structure of PAc and PB1_N protein, comprising: obtaining PAc-containing crystal by protein crystallization method, or obtaining the coordinates of crystal three-dimensional structure of the protein complex containing PAc and PB1_N; wherein the three-dimensional structure contains any structure that has an average root mean square deviation smaller than or equal to 1.7 Angstrom with respect to three-dimensional coordinates of a main chain carbon backbone having at least 40% amino acid residues of the coordinates.

In one embodiment, the present invention provides a method of expressing and purifying the influenza virus subunit PA through expressing PA fragments in bacteria and eukaryotic cell expression systems.

In one embodiment, the present invention provides a polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugate that interacts with amino-acid residues on a protein, wherein the protein has at least 40% identical amino acids with any fragment of α helix 8, 10, 11 and 13 in complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1_N.

It should be noted that the fragments in influenza virus B and C type corresponding to α helix and β sheet of influenza virus A are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, FIGS. 10B respectively, which will not be listed in detail. The alignment methods of protein or polypeptide sequence that can be used is for example: CLUSTALW (http://www.ebi.ac.uk/Tools/clustalw2/index.html).

Expression and Purification Methods of Influenza Virus PA and PB1 Protein:

The protein sequences encoded by virus gene derived from Avian influenza virus A/goose/Guangdong/1/96 are respectively as follows:

(1) Protein sequence of PA:

MEDFVRQCFNPMIVELAEKAMKEYGEDPKIETNKFAAICTHLEVCFMYS
DNIFIDERGESTIIESGDPNALLKHRFEIIEGRDRTMAWTVVNSICNTT
GVEKPKFLPDLYDYKENRFIEIGVTRREVHTYYLEKANKIKSEKTHIHI
FSFTGEEMATKADYTLDEESRARIKTRLFTIRQEMASRGLWDSFRQSER
GEETIEERFEITGTMCRLADQSLPPNFSSLEKFRAYVDGEEPNGCIEGK
LSQMSKEVNARIEPFLKTTPRPLRLPDGPPCSQRSKFLLMDALKLSIED
PSHEGEGIPLYDAIKCMKTFFGWKEPNIVKPHEKGINPNYLLAWKQVLA
ELQDIENEEKIPKTKNMRKTSQLKWALGENMAPEKVDFEDCKDVSDLRQ
YDSDEPKPRSLASWIQSEFNKACELTDSSWIELDEIGEDVAPIEHIASM
RRNYFTAEVSHCRATEYIMKGVYINTALLNASCAAMDDFQLIPMISKCR
TKEGRRKTNLYGFIIKGRSHLRNDTDVVNFVSNIEFSLTDPRLEPHKWE
KYCVLEIGDMLLRTAIGQVSRPMFLYVRTNGTSKIKMKWGMEMRRCLLQ
SLQQIESMIEAESSVKEKDMTKEFFENKSETWPIGESPKGMEEGSIGKV
CRTLLAKSVFNSLYASPQLEGFSAESRKLLLIVQALRDNLEPGTFDLGG
LYEAIEECLINDPWVLLNASWFNSFLTHALK; i.e.,
( SEQ ID NO: 1 )
Met Glu Asp Phe Val Arg Gln Cys Phe Asn Pro Met
Ile Val Glu Leu Ala Glu Lys Ala Met Lys Glu Tyr
Gly Glu Asp Pro Lys Ile Glu Thr Asn Lys Phe Ala
Ala Ile Cys Thr His Leu Glu Val Cys Phe Met Tyr
Ser Asp Phe His Phe Ile Asp Glu Arg Gly Glu Ser
Thr Ile Ile Glu Ser Gly Asp Pro Asn Ala Leu Leu
Lys His Arg Phe Glu Ile Ile Glu Gly Arg Asp Arg
Thr Met Ala Trp Thr Val Val Asn Ser Ile Cys Asn
Thr Thr Gly Val Glu Lys Pro Lys Phe Leu Pro Asp
Leu Tyr Asp Tyr Lys Glu Asn Arg Phe Ile Glu Ile
Gly Val Thr Arg Arg Glu Val His Thr Tyr Tyr Leu
Glu Lys Ala Asn Lys Ile Lys Ser Glu Lys Thr His
Ile His Ile Phe Ser Phe Thr Gly Glu Glu Met Ala
Thr Lys Ala Asp Tyr Thr Leu Asp Glu Glu Ser Arg
Ala Arg Ile Lys Thr Arg Leu Phe Thr Ile Arg Gln
Glu Met Ala Ser Arg Gly Leu Trp Asp Ser Phe Arg
Gln Ser Glu Arg Gly Glu Glu Thr Ile Glu Glu Arg
Phe Glu Ile Thr Gly Thr Met Cys Arg Leu Ala Asp
Gln Ser Leu Pro Pro Asn Phe Ser Ser Leu Glu Lys
Phe Arg Ala Tyr Val Asp Gly Phe Glu Pro Asn Gly
Cys Ile Glu Gly Lys Leu Ser Gln Met Ser Lys Glu
Val Asn Ala Arg Ile Glu Pro Phe Leu Lys Thr Thr
Pro Arg Pro Leu Arg Leu Pro Asp Gly Pro Pro Cys
Ser Gln Arg Ser Lys Phe Leu Leu Met Asp Ala Leu
Lys Leu Ser Ile Glu Asp Pro Ser His Glu Gly Glu
Gly Ile Pro Leu Tyr Asp Ala Ile Lys Cys Met Lys
Thr Phe Phe Gly Trp Lys Glu Pro Asn Ile Val Lys
Pro His Glu Lys Gly Ile Asn Pro Asn Tyr Leu Leu
Ala Trp Lys Gln Val Leu Ala Glu Leu Gln Asp Ile
Glu Asn Glu Glu Lys Ile Pro Lys Thr Lys Asn Met
Arg Lys Thr Ser Gln Leu Lys Trp Ala Leu Gly Glu
Asn Met Ala Pro Glu Lys Val Asp Phe Glu Asp Cys
Lys Asp Val Ser Asp Leu Arg Gln Tyr Asp Ser Asp
Glu Pro Lys Pro Arg Ser Leu Ala Ser Trp Ile Gln
Ser Glu Phe Asn Lys Ala Cys Glu Leu Thr Asp Ser
Ser Trp Ile Glu Leu Asp Glu Ile Gly Glu Asp Val
Ala Pro Ile Glu His Ile Ala Ser Met Arg Arg Asn
Tyr Phe Thr Ala Glu Val Ser His Cys Arg Ala Thr
Glu Tyr Ile Met Lys Gly Val Tyr Ile Asn Thr Ala
Leu Leu Asn Ala Ser Cys Ala Ala Met Asp Asp Phe
Gln Leu Ile Pro Met Ile Ser Lys Cys Arg Thr Lys
Glu Gly Arg Arg Lys Thr Asn Leu Tyr Gly Phe Ile
Ile Lys Gly Arg Ser His Leu Arg Asn Asp Thr Asp
Val Val Asn Phe Val Ser Met Glu Phe Ser Leu Thr
Asp Pro Arg Leu Glu Pro His Lys Trp Glu Lys Tyr
Cys Val Leu Glu Ile Gly Asp Met Leu Leu Arg Thr
Ala Ile Gly Gln Val Ser Arg Pro Met Phe Leu Tyr
Val Arg Thr Asn Gly Thr Ser Lys Ile Lys Met Lys
Trp Gly Met Glu Met Arg Arg Cys Leu Leu Gln Ser
Leu Gln Gln Ile Glu Ser Met Ile Glu Ala Glu Ser
Ser Val Lys Glu Lys Asp Met Thr Lys Glu Phe Phe
Glu Asn Lys Ser Glu Thr Trp Pro Ile Gly Glu Ser
Pro Lys Gly Met Glu Glu Gly Ser Ile Gly Lys Val
Cys Arg Thr Leu Leu Ala Lys Ser Val Phe Asn Ser
Leu Tyr Ala Ser Pro Gln Leu Glu Gly Phe Ser Ala
Glu Ser Arg Lys Leu Leu Leu Ile Val Gln Ala Leu
Arg Asp Asn Leu Glu Pro Gly Thr Phe Asp Leu Gly
Gly Leu Tyr Glu Ala Ile Glu Glu Cys Leu Ile Asn
Asp Pro Trp Val Leu Leu Asn Ala Ser Trp Phe Asn
Ser Phe Leu Thr His Ala Leu Lys.

(2) Protein sequence of PB1:

MDVNPTLLFLKVPAQNAISTTFPYTGDPPYSHGTGTGYTMDTVNRTHQY
SEKGKWTTNTETGAPQLNPIDGPLPEDNEPSGYAQTDCVLEAMAFLEKS
HPGIFENSCLETMEIVQQTRVDKLTQGRQTYDWTLNRNQPAATALANTI
EVFRSNGLTANESGRLIDFLKDVMESMDKGEMEIITHFQRKRRVRDNMT
KKMVTQRTIGKKKQRLNKRSYLIRALTLNTMTKDAERGKLKRRAIATPG
MQIRGFVYFVETLARSICEKLEQSGLPVGGNEKKAKLANVVRKMMTNSQ
DTELSFTITGDNTKWNENQNPRMFLAMITYITRNQPEWFRNVLSIAPIM
FSNKMARLGKGYMFESKSMKLRTQIPAEMLASIDLKYFNESTRKKIEKI
RPLLIDGTASLSPGNIMMGMFNMLSTVLGVSILNLGQKRYTKTTYWWDG
LQSSDDFALIVNAPNHEGIQAGVDRFYRTCKLVGINMSKKKSYINRTGT
EEFTSFFYRYGFVANFSMELPSFGVSGINESADMSIGVTVIKNNMINND
LGPATAQMALQLFIKDYRYTYRCHRGDTQIQTRRSEELKKLWEQTRSKA
GLLVSDGGPNLYNIRNLHIPEVCLKWELMDEDYQGRLCNPLNPFVSHKE
IESVNNAVVMPAHGPAKSMEYDAVATTHSWIPKRNRSILNTSQRGILED
EQMYQKCCNLFEKFFPSSSYRRPVGISSMVEAMVSRARIDARIDFESGR
IKKEEFAEIMKICSTIEELRRQK; i.e.,
( SEQ ID NO: 2 )
Met Asp Val Asn Pro Thr Leu Leu Phe Leu Lys Val
Pro Ala Gln Asn Ala Ile Ser Thr Thr Phe Pro Tyr
Thr Gly Asp Pro Pro Tyr Ser His Gly Thr Gly Thr
Gly Tyr Thr Met Asp Thr Val Asn Arg Thr His Gln
Tyr Ser Glu Lys Gly Lys Trp Thr Thr Asn Thr Glu
Thr Gly Ala Pro Gln Leu Asn Pro Ile Asp Gly Pro
Leu Pro Glu Asp Asn Glu Pro Ser Gly Tyr Ala Gln
Thr Asp Cys Val Leu Glu Ala Met Ala Phe Leu Glu
Lys Ser His Pro Gly Ile Phe Glu Asn Ser Cys Leu
Glu Thr Met Glu Ile Val Gln Gln Thr Arg Val Asp
Lys Leu Thr Gln Gly Arg Gln Thr Tyr Asp Trp Thr
Leu Asn Arg Asn Gln Pro Ala Ala Thr Ala Leu Ala
Asn Thr Ile Glu Val Phe Arg Ser Asn Gly Leu Thr
Ala Asn Glu Ser Gly Arg Leu Ile Asp Phe Leu Lys
Asp Val Met Glu Ser Met Asp Lys Gly Glu Met Glu
Ile Ile Thr His Phe Gln Arg Lys Arg Arg Val Arg
Asp Asn Met Thr Lys Lys Met Val Thr Gln Arg Thr
Ile Gly Lys Lys Lys Gln Arg Leu Asn Lys Arg Ser
Tyr Leu Ile Arg Ala Leu Thr Leu Asn Thr Met Thr
Lys Asp Ala Glu Arg Gly Lys Leu Lys Arg Arg Ala
Ile Ala Thr Pro Gly Met Gln Ile Arg Gly Phe Val
Tyr Phe Val Glu Thr Leu Ala Arg Ser Ile Cys Glu
Lys Leu Glu Gln Ser Gly Leu Pro Val Gly Gly Asn
Glu Lys Lys Ala Lys Leu Ala Asn Val Val Arg Lys
Met Met Thr Asn Ser Gln Asp Thr Glu Leu Ser Phe
Thr Ile Thr Gly Asp Asn Thr Lys Trp Asn Glu Asn
Gln Asn Pro Arg Met Phe Leu Ala Met Ile Thr Tyr
Ile Thr Arg Asn Gln Pro Glu Trp Phe Arg Asn Val
Leu Ser Ile Ala Pro Ile Met Phe Ser Asn Lys Met
Ala Arg Leu Gly Lys Gly Tyr Met Phe Glu Ser Lys
Ser Met Lys Leu Arg Thr Gln Ile Pro Ala Glu Met
Leu Ala Ser Ile Asp Leu Lys Tyr Phe Asn Glu Ser
Thr Arg Lys Lys Ile Glu Lys Ile Arg Pro Leu Leu
Ile Asp Gly Thr Ala Ser Leu Ser Pro Gly Met Met
Met Gly Met Phe Asn Met Leu Ser Thr Val Leu Gly
Val Ser Ile Leu Asn Leu Gly Gln Lys Arg Tyr Thr
Lys Thr Thr Tyr Trp Trp Asp Gly Leu Gln Ser Ser
Asp Asp Phe Ala Leu Ile Val Asn Ala Pro Asn His
Glu Gly Ile Gln Ala Gly Val Asp Arg Phe Tyr Arg
Thr Cys Lys Leu Val Gly Ile Asn Met Ser Lys Lys
Lys Ser Tyr Ile Asn Arg Thr Gly Thr Phe Glu Phe
Thr Ser Phe Phe Tyr Arg Tyr Gly Phe Val Ala Asn
Phe Ser Met Glu Leu Pro Ser Phe Gly Val Ser Gly
Ile Asn Glu Ser Ala Asp Met Ser Ile Gly Val Thr
Val Ile Lys Asn Asn Met Ile Asn Asn Asp Leu Gly
Pro Ala Thr Ala Gln Met Ala Leu Gln Leu Phe Ile
Lys Asp Tyr Arg Tyr Thr Tyr Arg Cys His Arg Gly
Asp Thr Gln Ile Gln Thr Arg Arg Ser Phe Glu Leu
Lys Lys Leu Trp Glu Gln Thr Arg Ser Lys Ala Gly
Leu Leu Val Ser Asp Gly Gly Pro Asn Leu Tyr Asn
Ile Arg Asn Leu His Ile Pro Glu Val Cys Leu Lys
Trp Glu Leu Met Asp Glu Asp Tyr Gln Gly Arg Leu
Cys Asn Pro Leu Asn Pro Phe Val Ser His Lys Glu
Ile Glu Ser Val Asn Asn Ala Val Val Met Pro Ala
His Gly Pro Ala Lys Ser Met Glu Tyr Asp Ala Val
Ala Thr Thr His Ser Trp Ile Pro Lys Arg Asn Arg
Ser Ile Leu Asn Thr Ser Gln Arg Gly Ile Leu Glu
Asp Glu Gln Met Tyr Gln Lys Cys Cys Asn Leu Phe
Glu Lys Phe Phe Pro Ser Ser Ser Tyr Arg Arg Pro
Val Gly Ile Ser Ser Met Val Glu Ala Met Val Ser
Arg Ala Arg Ile Asp Ala Arg Ile Asp Phe Glu Ser
Gly Arg Ile Lys Lys Glu Glu Phe Ala Glu Ile Met
Lys Ile Cys Ser Thr Ile Glu Glu Leu Arg Arg Gln
Lys

The gene of influenza virus subunit PA was separated into C-terminal part and N-terminal part, and then the C-terminal part and the N-terminal part were cloned by molecular cloning techniques, wherein the N-terminal part contains the first 256 amino acids and the C-terminal part contains 257-716 amino acids. The two parts were cloned into pGEX-6p vector (from Amersham Pharmacia Inc.) respectively so as to express fusion proteins of N-terminal fused with GST (GST-PA_N and GST-PAc). The cloned plasmids were transformed into E. coli BL21 respectively, and E. coli are induced by using 0.1 to 1 mM IPTG(isopropyl-β-thiogalactoside) in BL21 to express these two proteins respectively, thus obtaining respectively expressing bacteria of these two protein, for details see Example 1.

The gene encoding within 48 amino acids of N-terminal of PB1 (including the former 25 amino acids peptide) was also cloned into pGEX-6p vector, so as to express fusion protein of fused GST-PB1 peptide.

Likewise, the short peptide of GST fused the former 25 amino acids or former 48 amino acids of PB1_N was expressed respectively. The vectors were transformed into E. coli BL21 in the same way. E. coli were induced by using 0.1 to 1 mM IPTG in BL21 to express proteins, thus obtaining expression bacteria of the protein.

The bacteria that express GST-PA-N were suspended with buffer, lysed and centrifuged to obtain supernatant. Then affinity chromatographic column was used to purify GST-PA-N fusion protein from the supernatant.

The GST-PAc expressing bacteria and the GST-PB1 expressing bacteria were suspended with a buffer (which contains about 20 mM Tris-HCl (pH8.0) and 250 mM NaCl) respectively and mixed with a molar ratio between the protein content of GST-PAc and GST-PB1_N is 0.1:1˜1:0.1, preferably the molar ratio between the protein content of GST-PAc and GST-PB1_N is 0.5:1˜1:0.5, more preferably the molar ratio between the protein content of GST-PAc and GST-PB1_N is near 1:1.

Subsequently, Glutathione-Sepharose affinity column (from Amersham Pharmacia Inc.) was used to purify the GST fusion protein. After enzymolysis with PreScission protease (from Amersham Pharmacia Inc.), the complex of PAc/PB1 short peptide was separated and purified through such methods as gel filtration Superdex-200 and ion exchange chromatography (Q sepharose), wherein complex can be used for further crystallization experiment after determining the protein concentration by SDS-PAGE gel electrophoresis.

Crystallization and Optimization of Protein:

The complex that has been expressed and purified through above methods was condensed to a concentration of 5-30 mg/ml, and crystal growth condition is screened with crystallization reagents (from Hampton Research) by gas hanging drop so as to obtain original crystals under conditions of multiple crystallization reagents.

Through further optimization, crystals with good appearance were obtained in solution containing about 1M sodium acetate with different buffer conditions under pH 4-9, wherein larger triangle-cone crystal was obtained in solution containing about 1-1.3M sodium acetate (Sigma) with different buffers under pH 4-9, and the resolution of said crystal is about 4 Angstrom.

When collecting X-ray diffraction data, the crystal required by diffraction was transferred from hanging drops to about 10 μl corresponding crystallization buffer containing 1.4 M sodium acetate and 10% glycerol (Sigma). After the fluid drops are left open for air dehydration for more than one hour, parent crystal and selenium-containing crystal with a resolution of about 3 Angstrom as well as corresponding X-ray diffraction data were obtained.

Collection of Crystal Data and Structure Analysis:

A set data of parent crystal with a resolution of 2.9 Angstrom from the complex crystal of PA-PB1 N-terminal (this PB1 N-terminal contains 25 amino acids) was first collected by using FR-E X-ray diffractometer (Rigaku) under a wave length 1.5418 Angstrom. Then under wave length of 0.9783 and 0.9785 Angstrom, two sets of data from derivative crystal of selenium atom were collected, i.e. peak and edge, using synchrotron radiometer located at APS, Chicago, USA (station number: SBC 19ID; detection screen: ADSC Q315), the resolution of said crystal is about 3.3 Angstrom. The three sets of data were treated by HKL2000 (Otwinowski 1997) and found to have spacegroup of P4(1)2(1)2. Phase was calculated by multi-wavelength anomalous scattering (Hendrickson 1991), and sas file resulted from treatment was searched for selenium atoms by SHELXD (Sheldrick 1998). The protein itself has 14 methionines, and the inventors found 14 selenium atoms in all. Coordinates of selenium atoms and two sets of data (i.e. Peak and Edge) were input into Program autoSHARP (Vonrhein, Blanc et al. 2007) to calculate phase and to modify the electron density map, and several secondary structures (including α helixes and (β sheets) can be clearly found from the calculated electron density map. Then phase can be expanded by Program CAD, and the phase was expanded to 2.9 Angstrom by collected parent data so as to construct a structure model, wherein the Programs used to construt model are ARP/wARP (Perrakis, Morris et al. 1999) and Phenix (Adams, Grosse-Kunstleve et al. 2002). Automatic model construction performed by these two programs can amount to 60% of the whole structure, and the rest is manually constructed through Program COOT (Emsley and Cowtan 2004).

Finally, the resulting model was modified by Program CNS (Brunger, Adams et al. 1998) and REFMAC5(Murshudov, Vagin et al. 1997) to achieve the protein structure analysis, and the final factor R and factor R-free for modify structure are 0.22 and 0.26 respectively.

Atomic coordinates in crystal structure of protein complex of PAc/PB1_N short peptide, see Table 1.

Example 1

Method for Expressing Influenza Virus PA and PB1 Polypeptides

In one embodiment of the present invention, PA was divided into two fragments so as to express former 256 amino acid residues fragments and 257-716 amino acid residues fragments of the PA, respectively, and two gene fragments encoding these two protein polypeptides were cloned into an Escherichia coli expression vector, respectively so as to expressing proteins in a bacteria. The PA N-terminal polypeptides were purified from a PA N-terminal (1-256 amino acids) expressing bacteria and used for protein crystallization. C-terminal of PA expressing bacteria was centrifugally collected for later use so as to be co-purified with the N-terminal of PB1 polypeptides.

Polypeptide containing former 25 or no more than 48 amino acids of the N-terminal of PB1 (not containing first-position methionine) was expressed in the form of GST fusion protein in a bacteria. The influenza virus polymerase protein subunit PA was expressed by fragments in a bacteria or other eukaryotic cells such that at least 50% fragments were part of amino acid fragments of positions 257-716 of the PA protein.

Expression and Purification of N-Terminal of Influenza Virus PA in Escherichia coli

The N-terminal of the influenza virus PA (amino acids 1-256) was cloned into a pGEX-6p vector (from Amersham Pharmacia Inc.) via a molecular cloning technique, the cloning sites thereof being BamHI and XhoI. Expression plasmids with a PA N-terminal gene, obtained by cloning, were transformed into Escherichia coli BL21 for protein expression, such that the bacteria could express the N-terminal (amino terminal) of the PA protein which was connected with the GST fusion protein and has protease cleavage sites cleaved by ProScission protease to further separate a GST protein tag from the target protein-PA polypeptide. IPTG with a final concentration of about 0.1-1 mM was used in the cultured Escherichia coli BL21 cells to induce Escherichia coli in order to obtain the expressing bacteria of said protein. The used vector contained an ampicillin-resistance gene. After the cloning-constructed expression plasmids of the fusion protein were transformed into Escherichia coli such as BL21 (Novagen), bacterium were cultured overnight using bacteria culture media such as LB and so on at 37, and after about 12 hours transferred to a mass culture medium in a proportion of about 1:100, and cultured in a shake flask at 37 until OD is approximately 1.0, and then added 0.1-1 mM IPTG for inducing expression. After about 3 to 6 hours, the bacterium were collected centrifugally, and the collected precipitated bacterium could be stored at −20 to −80 in a refrigerator for later use or be used directly for purification of the PA N-terminal protein.

Expression and Purification of Complex of C-Terminal of Influenza Virus PA and PB1 Polypeptide

The C-terminal (amino acids 257-716) of the influenza virus PA was cloned into a pGEX-6p vector (from Amersham Pharmacia Inc.) via a molecular cloning technique, the cloning sites thereof being BamHI and NhoI. Expression plasmids with a PA C-terminal gene, obtained by cloning, were transformed into Escherichia coli BL21 for protein expression, such that the bacteria could express the N-terminal (amino terminal) of the protein which was connected with the GST fusion protein and has protease cleavage sites cleaved by ProScission protease to further separate a GST protein tag from the target protein-PA polypeptide. IPTG with a final concentration of about 0.1-1 mM was used in the cultured Escherichia coli BL21 cells to induce Escherichia coli in order to obtain the expressing bacteria of said protein. The used vector contained an ampicillin-resistance gene. After the cloning-constructed expression plasmids of the fusion protein were transformed into Escherichia coli such as BL21 (Novagen), bacterium were cultured overnight using bacteria culture media such as LB and so on at 37, and after about 12 hours transferred to a mass culture medium in a proportion of about 1:100, and cultured in a shake flask at 37 until OD is approximately 1.0, and then added 0.1-1 mM IPTG for inducing expression after the culture temperature is lowered to 16. After about 12 to 24 hours, the bacterium were collected centrifugally, and the collected precipitated bacterium could be stored at −20 to −80 in a refrigerator for later use or be used directly for purification.

The gene of the N-terminal of PB1 with no more than 48 amino acids (the inventor had expressed the former 48-amino acid polypeptide and the former 25-amino acid polypeptide of the N-terminal of PB1) was likewise cloned into multiple cloning sites of the pGEX-6p vector, wherein the used cloning sites were BamHI and XhoI, such that the bacteria could express a fusion protein containing GST, there is protease cleavage sites cleaved by ProScission protease in the fusion protein in order to further separate a GST protein tag from the target protein of PB1 polypeptide. The fusion protein of a GST-PB1_N peptide was expressed in Escherichia coli BL21 in the same way as the PA fusion protein was expressed above. The resistance gene was ampicillin-resistance gene. The protein expression was carried out at 37° C., and the used inducer was IPTG. Finally, the expressing bacterium were collected centrifugally, used directly for protein purification and could be stored temporarily at −20° C. to −80° C. in a refrigerator.

The centrifugally collected expressing bacteria expressing the GST-PA N-terminal polypeptide was suspended using a buffer solution containing 20 mM Tris-HCl (pH8.0) and 250 mM NaCl or a buffer solution of 1×PBS (pH7.4) phosphoric acid. An ultrasonic breaker was used to break cells. The insoluble precipitation was centrifugally separated and removed in order to collect soluble supernatant. A Glutathione affinity chromatographic column was used to purify the GST-PA-N-terminal polypeptide, and the ProScission protease was further used to enzymolyze the fusion protein into two fragments of GST (glutathione S-transferase) and PA-N. Ion exchange chromatography and gel exclusion chromatography were then used to purify the PA-N protein polypeptide. The protein was concentrated to 5-30 mg/mL for crystal growth.

The expressing bacteria expressing the GST-PA_C C-terminal polypeptide and the expressing bacteria expressing the GST-PB1_N short peptide were suspended using a buffer solution containing 20 mM Tris-HCl (pH8.0) and 250 mM NaCl or a buffer solution of 1×PBS (pH7.4) phosphoric acid, and then mixed in proportion, such that the molar ratio of the total protein of GST-PA to GST-PB1 was 0.1:1 to 1:0.1, preferably 0.5:1 to 1:0.5, most preferably close to 1:1.

The cell in the mixed bacterial suspension was lysed using ultrasonic wave or other cell lysing methods. An insoluble portion and a soluble portion of the bacterial lysates were centrifugally separated. The supernatant obtained by high speed centrifugation (about 20,000 g) was preliminarily separated using a Glutathione-Sepharose affinity column (from Amersham Pharmacia Inc.) to purify such mixed protein. The protein containing a GST tag could bind to the Glutathione-Sepharose affinity column, while other proteins could not bind to said affinity column. The above mentioned bacterial suspension buffer solution was used to rinse impurity after the protein bound to the affinity column. A suitable amount of ProScission protease (from Amersham Pharmacia Inc.) was used to enzymolyze the mixed GST fusion protein of the affinity column. This process generally needs about 24 hours. Then, the enzymatically cleaved PA_C and PB1_N proteins were further separated using methods of gel filtration superdex-200 (from Amersham Pharmacia Inc.), Q sepharose ion exchange chromatography (from Amersham Pharmacia Inc.) and so on to purify the PA_C/PB1_N short peptide complex (the chromatography column comes from Amersham Pharmacia Inc.). The protein purity was determined via SDS-PAGE gel electrophoresis, and the purity generally reached more than 90%. The protein purified by the above steps was concentrated to about 5-30 mg/mL using an evaporating pipe (coming from Millipore Inc.) for a further crystallization experiment.

The person skilled in the art would know that, the N-terminal of influenza virus PA-PA_N and the C-terminal of influenza virus PA-PA_C as well as the N-terminal of PB1-PB_N could be expressed not only in the prokaryotic cell such as Escherichia coli described hereinabove but also in an eukaryotic cell such as insect cells; any other endonuclease, protease cleavage site, and ligase could be used; the target polypeptide to be purified may be fused with other tags such as GST, and the corresponding separating and purifying method was then selected for purification, and finally the tag fused into the target polypeptide was removed. Various change and modification of the present invention as described above fall within the scope of protection of the present invention.

It shall be noted that, the fragments of an α helix and a β sheet of type B or type C influenza corresponding to type A influenza virus are as shown in FIGS. 1A, 1B and 1C as well as FIGS. 10A and 10B, respectively. Herein, the description thereof is omitted.

Example 2

Crystallization of PA_C/PB1_N Short Peptide Complex

The complex of the PA and PB1 polypeptides expressed and purified with the above method was concentrated to about 5 to 30 mg/mL. A crystallization reagent (from reagent kits such as Screen Kit I/II, Index, and so on from Hampton Research incorporation, etc.) was used in gas sitting drop to screen crystal growth conditions. Upon preliminary screening, the inventor could obtain an original crystal with multiple different crystallization reagents.

Upon further optimization, a crystal with a fairly good appearance was obtained using a solution containing about 1M of sodium acetate in cases of using buffer solutions with different PH values (PH 4-9). A relatively larger triangle-cone crystal was obtained in a sodium acetate buffer solution (PH4-9) with a concentration of 1 to 1.3 M (from Sigma Inc.), the resolution being about 4 Angstrom.

When X-ray diffraction was performed to collect data, crystal needed for the diffraction was transferred from suspension drops to a 10 microliter corresponding crystal buffer solution containing 1.4M sodium acetate and 10% glycerol (from Sigma). The liquid drops were placed in the air for dehydration for more than one hour to obtain a protein crystal with a high resolution, and the resolution of parental and selenium-containing (selenium substituted) protein crystal could reach more than 2.9 Angstrom.

It shall be noted that, the fragments of an α helix and a β sheet of type B or type C influenza corresponding to type A influenza virus are as shown in FIGS. 1A, 1B and 1C as well as FIGS. 10A and 10B, respectively. Herein, the description thereof is omitted.

Example 3

Crystal Structure of PA_C/PB1_N Short Peptide Complex

A set data of parent crystal with a resolution of 2.9 Angstrom from the complex crystal of PA-PB1 N-terminal (this PB1 N-terminal contains 25 amino acids) was first collected by using FR-E X-ray diffractometer (Rigaku) under a wave length 1.5418 Angstrom. Then under wave length of 0.9783 and 0.9785 Angstrom, two sets of data from derivative crystal of selenium atom were collected, i.e. peak and edge, using synchrotron radiometer located at APS, Chicago, USA (station number: SBC 19ID; detection screen: ADSC Q315), the resolution of said crystal is about 3.3 Angstrom. The three sets of data were treated by HKL2000 (Otwinowski 1997) and found to have spacegroup of P4(1)2(1)2. Phase was calculated by multi-wavelength anomalous scattering (Hendrickson 1991), and sas file resulted from treatment was searched for selenium atoms by SHELXD (Sheldrick 1998). The protein itself has 14 methionines, and the inventors found 14 selenium atoms in all. Coordinates of selenium atoms and two sets of data (i.e. Peak and Edge) were input into Program autoSHARP (Vonrhein, Blanc et al. 2007) to calculate phase and to modify the electron density map, and several secondary structures (including α helixes and β sheets) can be clearly found from the calculated electron density map. Then phase can be expanded by Program CAD, and the phase was expanded to 2.9 Angstrom by collected parent data so as to construct a structure model, wherein the Programs used to construt model are ARP/wARP (Perrakis, Morris et al. 1999) and Phenix (Adams, Grosse-Kunstleve et al. 2002). Automatic model construction performed by these two programs can amount to 60% of the whole structure, and the rest is manually constructed through Program COOT (Emsley and Cowtan 2004).

Finally, the resulting model was modified by Program CNS (Brunger, Adams et al. 1998) and REFMAC5(Murshudov, Vagin et al. 1997) to achieve the protein structure analysis, and the final factor R and factor R-free for modify structure are 0.23 and 0.26 respectively.

Example 4

Crystallization of N-Terminal of PA

The PA N-terminal polypeptide complex expressed and purified by the above method was concentrated to about 5 to 30 mg/mL. A crystal agent (kits such as Screen Kit I/II, Index, and so on from Hampton Research Incorporation, etc.) was used in gas sitting drop to screen crystal growth conditions. Upon preliminary screening, the inventor obtained an original crystal with different crystal agents.

For further optimization, a crystal well diffracted by an X-ray was obtained from a solution containing about 20% PEG 8000 or 20% PEG 3350 and 0.1 M magnesium chloride or 0.1 M magnesium acetate in a case of using a MES buffer solution with PH 6.5 (all the used regents came from Sigma Inc.) (see A and B crystal pictures and C and D diffraction pictures in FIG. 3). The X-ray diffracting resolution of the obtained crystal is about 2 to 4 Angstrom.

Example 5

Method for Screening Small Molecules Competing with PB1_N for Binding to PA_C

During a process of screening a small molecular medicament capable of disintegrating the PA_C/PB1_N short peptide complex, the PB1_N short peptide gene was fused with a gene expressing GFP (green fluorescent protein). The PB1_N short peptide protein fused with GFP was expressed as an indicator molecule during a small molecular compound disintegrating a protein complex. The PB1 short peptide gene fragment was connected to the GFP gene fragment using a molecular cloning method so as to express PB1 small peptide fusion protein of which one N-terminal or C-terminal was connected with GFP.

Method 1: a complex of PA C-terminal fusion protein with the N-terminal fused GST, viz. GST-PA_C fusion protein, and GFP-PB1_N short peptide fusion protein was expressed with the above method of expressing and purifying the C-terminal of PA and the PB1 short peptide.

The complex of the GST-PA_C fusion protein and the GFP-PB1_N short peptide fusion protein flew through and bound to the Glutathione affinity column Since said complex contained the GFP protein, the GFP-PB1_N fusion protein binding to GST-PA_C enabled the affinity column to show a green color after GST-PA_C bound to the affinity column. The affinity column binding with the complex protein of GST-PA_C and GFP-PB1_N was rinsed sufficiently with a buffer solution to thoroughly elute and remove unbound proteins. Then, a mixture of small molecular compounds to be screened flew through the affinity column (said mixture should not contain Glutathione or other eluted compounds for detaching GST from the affinity column). If the mixture contained small molecules substituted for the PB1_N polypeptide to bind to the PA_C, part of the GFP-PB1_N polypeptide fusion protein binding to PAc was replaced and eluted. The eluted solution flowing out showed a green color due to containing said GFP fusion protein when observed under a fixed wavelength fluorescent microscope. The small molecules were further sequentially separated and purified from the mixture, and the components substituted for the PB1_N polypeptide were traced by the above green GFP protein tracing method to finally determine a small molecular compound interfering with the binding of PA to the PB1 small peptide. In the above method, besides using GST as an affinity matrix, other polypeptides such as Flag-tag, Myc-tag, MBP (Maltose binding protein)-tag, specific antibody, etc. could be used as combining groups of affinity matrix. Correspondingly, the affinity chromatographic column needs a corresponding affinity matrix, for example, if the Flag-tag was used, an antibody against the Flag-tag (e.g. an anti-flag monoclonal antibody from Sigma Inc.) was used to be fixed to the affinity chromatographic column as a gel medium binding to the Flag. The compound molecules binding to PA and replacing a PB1 small peptide (specific structure) could be determined via methods such as mass spectrometry, etc.

Method 2: PA_C was purified separately (fusion protein or non-fusion protein) and covalently crosslinked to a gel medium by chemical crosslinking, but protein was not denatured. GFP-PB1_N flew through the covalently binding gel column GFP-PB1_N bound to the PA_C protein such that the gel column presents a green fluorescent light of GFP. The solution of the small molecular mixture flew through the gel column, if a compound substituted for GFP-PB1_N to bind to PA_C was present, the GFP-PB1_N fusion protein was eluted. The eluent showed a green color by stimulation of a specific-wavelength light, and the compound molecules substituted for GFP-PB1_N bound to the PA_C molecules of the gel column. A buffer solution was used to elute the gel column to remove impurities, and urea and the like was then used to denature PA_C in order that the small molecules binding thereto were eluted. Methods of mass spectrometry and the like were used to analyze small molecules binding to PA to obtain structural information of the small molecules. The compound may be a small molecular medicament capable of disintegrating the PA_C/PB1_N short peptide complex.

Example 6

Method of Using Crystal Three-Dimensional Structure of PA_C/PB1_N Complex to Design and Screen Various Polypeptides, Proteins, or Inorganic or Organic Compounds for Treating Diseases Caused by Influenza Virus Infection

A crystal three-dimensional structure of a complex of the C-terminal of influenza virus polymerase subunit PA-PA_C and the N-terminal of influenza virus polymerase subunit PB1-PB1_N was used to design and screen various polypeptides, proteins, or inorganic or organic compounds for treating diseases caused by influenza virus infection. The specific steps are as follows: polypeptides and compound molecules binding to specific portion were designed through computer stimulation technology according to coordinates of three-dimensional structure of protein; potential polypeptides and compound molecules binding to specific portion were searched for through computer stimulation technology according to coordinates of three-dimensional structure of protein; the polypeptides and compound molecules designed or searched according to the coordinates of three-dimensional structure of protein bound to any type of influenza virus polymerase protein which has at least 50% sequence identity with the PA_C and PB1_N sequences, and binding information was then analysed; the polypeptides and compound molecules designed or searched according to the coordinates of three-dimensional structure of protein bound to any type of influenza virus polymerase protein which has at least 50% sequence identity with the PA_C and the PB1_N sequences, and then crystallized; and the binding information of the polypeptides or compound molecules to protein is analyzed through a crystal diffraction method.

Example 7

Designing and Screening Small Peptides Using Crystal Three-Dimensional Structure of PA_C/PB1_N for Treating Diseases Caused by Influenza Virus Infection

Upon verification by experiment, a short peptide containing M1, D2, V3, N4, P5, T6, L7, L8, F9, L10, and K11 bound to the C-terminal of PA. The inventors cloned gene encoding PB1_N polypeptide containing the first-position M1 to the eleventh-position K11 into a pFEX-6p vector, purified said GST-PB1_N fusion protein, and used the fusion protein fixed to the affinity chromatographic gel column to bind to PA-C in a solution through an in vitro binding experiment. The inventors found that said fusion protein maintained the PB1_N's capability of binding to PA-C.

Using the same experimental method, the inventors found that a fusion protein containing M1, D2, V3, N4, P5, T6, L7, L8, F9, L10, K11, V12 and p13 also maintained the PB1_N's capability of binding to PA-C. Thus, these two short peptides had a capacity of binding to PA-C to make themselves potential polypeptide medicaments interfering with influenza virus polymerase activity or models for further medicament design.

Likewise, the selected polypeptide having at least three amino acid sequence alignment identical with the above polypeptide might be a potential polypeptide medicament interfering with influenza virus polymerase activity.

The structure of subunits PA, PB1, PB2 or the complex of PA, PB1 and PB2 of any type of influenza virus polymerase contains one protein or one fragment thereof having at least 40% sequences identical with those of the PA_C protein.

In the structure of subunits PA, PB1, PB2 or the complex of PA, PB1 and PB2 of any type of influenza virus polymerase, at least 40% coordinates of main chain carbon backbone of three-dimensional structure of one protein or one fragment thereof has average root mean square deviation smaller than or equal to 1.7 Angstrom with respect to the atomic coordinates of PA_C.

In the structure of subunit PA, PB1, PB2 or the complex of PA, PB1 and PB2 of any type of influenza virus polymerase, the protein fragment has 40% sequence identity of 2-12 amino acid fragments of the PB1_N polypeptide.

Any polypeptide or small molecule that interacts with key amino acids of the influenza virus subunit PA is included in the invention.

The structure is used in medicament screening and medicament designing.

A method for screening a compound or polypeptide binding to a protein based on the three-dimensional structure of the PA_C and PB1_N comprises: obtaining a crystal of the complex of PA_C and PB1_N proteins by protein crystallization, wherein the crystal of the complex protein has a spacegroup of P4(1)2(1)2, and the crystal cell parameters are: a=b=122 Angstrom, c=133 Angstrom, and α=β=γ=90°; obtaining the coordinate of the three-dimensional structure of the complex of the PA_C and PB1_N proteins by an X-ray diffracting crystal technique, wherein any structure containing at least 40% amino acid residues of which coordinates of main chain carbon backbone have average root mean square deviation smaller than or equal to 1.7 Angstrom with respect to said coordinate is included.

A method of expressing and purifying influenza virus subunit PA comprises expressing PA in segments in a bacteria or a eukaryotic expressing system, and the method is used to express and purify any protein fragments which has 40% sequence identity with PA.

In a preferred embodiment, the PA_C/PB1_N complex is used in designing and screening polypeptides, proteins, compounds, or medicaments in the treatment of diseases caused by influenza virus infection.

In a preferred embodiment, polypeptides for treating diseases caused by the influenza virus infection comprises polypeptides interacting with the above complex, at least one of the α helix or β sheet, and at least one amino acid site.

In a preferred embodiment, proteins for treating diseases caused by the influenza virus infection comprises proteins interacting with the above complex, at least one of the α helix or β sheet, and at least one amino acid site.

In a preferred embodiment, compounds for treating diseases caused by the influenza virus infection comprises compounds interacting with the above complex, at least one of the α helix or β sheet, and at least one amino acid site.

In a preferred embodiment, a pharmaceutical composition comprises the above polypeptides, proteins, or compounds.

The pharmaceutical composition of the present invention generally includes one carrier or excipient. An antibody and/or immune conjugate are dissolved in a pharmaceutically acceptable carrier, wherein an aqueous carrier is preferred. Many types of aqueous carriers can be applied, e.g. buffer saline, etc. These solutions are sterilized and generally free from undesired substances. These components can be disinfected through a conventional, well-known disinfecting technique. These components may include auxiliary substances required by physiological conditions, such as a buffering agent adjusting PH, toxicity regulator, sodium acetate, sodium chloride, potassium chloride, calcium chloride, sodium lactate, etc. The fusion proteins of these components vary greatly in concentration mainly depending on the selected administration manner, the liquid amount and viscosity required by a patient, body weight, etc.

Therefore, about 1.2 to 1200 μg of one typical pharmaceutical immunotoxin component in the present invention shall be applied daily for brain administration. One typical component for treating neoplasms of breast, ovary and lung via intravenous administration shall be applied to one patient 0.1 to 10 mg per day. The dosage of 0.1 to 100 mg per day for one person may be allowed, especially in a case that the medicament is administrated to a closed position without entering blood circulation or a lymphatic system, for example, it is administrated to a body cavity or an organ lacuna. The actual procedures for preparing applicable medical components are understood or acquired by the person skilled in the art and are described in detail in some publications, e.g. Remington's PHARMACETUTICAL SCIENCE, 19^th ed., Mack Publishing Company, Easton, Pa. (1995).

The components of the present invention can be used for a treatment. In treatment application, the components are applied to a patient suffering from a certain disease (for example, glioblastoma, breast cancer, ovarian cancer, and lung cancer), the dosage of which shall be enough to at least alleviate or partially control said disease and the complications thereof. The dosage enough to complete these tasks is called as “therapeutically effective dosage”. The applied effective dosage depends on illness severity and patient's general health conditions. The effective dosage of the component can achieve subjectively-recognized alleviation of a certain symptom or objective improvement recorded by a clinician or other qualified observer.

Whether to be administrate once only or for several times depends on desired and tolerated dose and frequency by a patient. Nevertheless, an adequate amount of the immunotoxin shall be provided to treat a patient effectively. Preferably, the medical dosage might be administrated only once or administrated periodically until a certain therapy efficacy or an adverse reaction inhibits continuation of the treatment. Generally, these dosages are enough to treat or improve disease conditions without incurring unbearable toxicity for a patient.

The immune conjugates of the present invention can be prepared into gastrointestinal sustained release formulations (e.g. an implant, an oil injection, or a microparticle system). A protein delivery system can be fully understood by referring to Banga, A. J., THERAPEUTIC PEPTIDES AND PROTEINS: FORMULATION, PROCESSING, AND DELIVERY SYSTEMS, Technomic Publishing Company, Inc., Lancaster, Pa., (1995). The microparticle system includes microspheres, particles, microcapsules, nano-microcapsules, nano-microspheres, and nano-particles. The microcapsule uses therapeutic protein as a core. In globules, therapeutic substances are dispersed in the particles. Particles, microspheres, and microcapsues which are smaller than about 1 μm are generally called as nano-microparticles, nano-spheres, and nano-microcapsules. Capillary vessels are about 5 μm in diameter. Therefore, only nano-particles are intravenously administrated. The microparticles are about 100 μm in diameter and are intravenously and intramuscularly administrated. Examples are Kreuter, J., COLLOIDAL DRUG DELIVERY SYSTEMS, J. Kreuter, ed., Marcel Dekker, Inc., New York, N.Y., pp. 219-342 (1994); and Tice&Tabibi, TREATISE ON CONTROLLED DRUG DELIVERY, A. Kydonieus, ed., Marcel Dekker, Inc. New York, N.Y., pp. 315-339, (1992), both of which are cited herein.

Polymers can be used for ion controlled release of immune conjugate components in the present invention. Multiple degradable and nondegradable polymers for drug controlled release are well-known in the art (Langer, R., Accounts Chem. Res. 26:537-542 (1993)), for example, a retarding polymer polaxamer 407 is viscous and flowable at low temperature, but is formed as a semisolid gel at body temperature, and is proved to be an effective carrier for forming and delivering continuously recombinant interleukin-2 and urease (Johnston etc., Pharm. Res. 9:425-434 (1992)) and Pec etc., J. Parent. Sci. Tech. 44(2):58-65 (1990)). Likewise, hydroxyapatite can be used as a microcarrier for protein controlled release (Ijntema etc., Int. J. Pharm. 112:215-224 (1994)), while liposome is used for controlled release and targeting transport processes of a liplid-coated medicament (Betageri, etc., LIPOSOME DRUG DELIVERY SYSTEMS, Technomic Publishing Co., Inc., Lancaster, Pa. (1993)). Many other therapeutic protein controlled release systems have been known, for example, U.S. Pat. Nos. 5,055,303, 5,188,837, 4,235,871, 4,501,728, 4,837,028, 4,957,735, 5,019,369, 5,055,303, 5,514,670, 5,413,797, 5,268,164, 5,004,697, 4,902,505, 5,506,206, 5,271,961, 5,254,342, and 5,534,496, any of which is cited herein.

Experimental Results

The atomic coordinate of the structure of the complex of PA_C and PB1_N is shown in the following Table 1.

TABLE 1
Remark DATE 2008-01-29 TIME 15:31:51 CST +0800 (1201591911.23 s)
Remark	3	HIGH RESOLUTION SCOPE (angstrom): 2.899
Remark	3	LOW RESOLUTION SCOPE (angstrom): 45.184
Remark	3	INTEGRITY OF DATA (%): 99.29
Remark	3	NUMBER OF REFLECTIONS: 22964
Remark	3	R VALUE  (WORKING + TEST SET): 0.2329
Remark	3	R VALUE   (WORKING SET): 0.2313
Remark	3	FREE R VALUE     :0.2621
Remark	3	FREE R VALUE TEST SET SIZE  (%):5.12
Remark	3	Data Number used by the FREE R   :1176
Remark	3	ERROR ESTIMATES
Remark	3	COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED) 0.36
Remark	3	PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) 26.77
Remark	3	element	count	occupies
Remark	3	C	2316	2316.00
Remark	3	S	28	28.00
Remark	3	O	729	728.50
Remark	3	N	609	609.00
Remark	3	TOTAL	3682	3681.50
Remark	3
Remark	3	ERROR with ideal coordinate
Remark	3		RMSD	MAX	COUNT
Remark	3	BOND   :	0.003	0.046	3703
Remark	3	ANGLE :	0.746	8.143	4994
Remark	3	CHIRALITY:	0.059	0.437	551
Remark	3	PLANARITY:	0.003	0.025	635
Remark	3	DIHEDRAL:	18.490	84.485	1412
Remark	3	The least non-bond distance: 2.355
				occupies
	X	Y	Z	factortemp	Atom
Atom	1	N	ILE	A	257	91.537	8.970	33.916	1.00	120.40	N
Atom	2	CA	ILE	A	257	90.592	8.158	34.672	1.00	128.69	C
Atom	3	CB	ILE	A	257	90.300	6.814	33.966	1.00	130.96	C
Atom	4	CG1	ILE	A	257	89.450	7.047	32.712	1.00	123.59	C
Atom	5	CD1	ILE	A	257	88.942	5.776	32.059	1.00	118.76	C
Atom	6	CG2	ILE	A	257	89.601	5.847	34.914	1.00	122.29	C
Atom	7	C	ILE	A	257	91.090	7.920	36.099	1.00	117.70	C
Atom	8	O	ILE	A	257	90.293	7.804	37.031	1.00	115.24	O
Atom	9	N	GLU	A	258	92.409	7.859	36.266	1.00	116.30	N
Atom	10	CA	GLU	A	258	93.009	7.761	37.595	1.00	123.54	C
Atom	11	CB	GLU	A	258	94.530	7.892	37.498	1.00	119.91	C
Atom	12	CG	GLU	A	258	95.178	6.762	36.703	1.00	112.24	C
Atom	13	CD	GLU	A	258	96.441	7.191	35.978	1.00	112.51	C
Atom	14	OE1	GLU	A	258	96.533	6.950	34.756	1.00	102.19	O
Atom	15	OE2	GLU	A	258	97.337	7.775	36.624	1.00	102.43	O
Atom	16	C	GLU	A	258	92.393	8.812	38.525	1.00	121.13	C
Atom	17	O	GLU	A	258	92.644	10.007	38.377	1.00	119.88	O
Atom	18	N	PRO	A	259	91.585	8.349	39.493	1.00	114.15	N
Atom	19	CA	PRO	A	259	90.548	9.104	40.206	1.00	110.56	C
Atom	20	CB	PRO	A	259	89.519	8.015	40.557	1.00	117.90	C
Atom	21	CG	PRO	A	259	90.143	6.678	40.122	1.00	108.56	C
Atom	22	CD	PRO	A	259	91.590	6.939	39.906	1.00	107.70	C
Atom	23	C	PRO	A	259	90.959	9.796	41.508	1.00	109.05	C
Atom	24	O	PRO	A	259	90.207	10.646	41.985	1.00	101.59	O
Atom	25	N	PHE	A	260	92.115	9.440	42.061	1.00	112.64	N
Atom	26	CA	PHE	A	260	92.461	9.740	43.459	1.00	110.07	C
Atom	27	CB	PHE	A	260	93.825	9.126	43.796	1.00	118.03	C
Atom	28	CG	PHE	A	260	94.761	9.054	42.623	1.00	117.55	C
Atom	29	CD1	PHE	A	260	94.893	7.880	41.899	1.00	110.10	C
Atom	30	CE1	PHE	A	260	95.749	7.808	40.819	1.00	118.42	C
Atom	31	CZ	PHE	A	260	96.485	8.918	40.447	1.00	119.59	C
Atom	32	CE2	PHE	A	260	96.361	10.095	41.157	1.00	109.72	C
Atom	33	CD2	PHE	A	260	95.501	10.161	42.239	1.00	117.37	C
Atom	34	C	PHE	A	260	92.434	11.207	43.924	1.00	101.28	C
Atom	35	O	PHE	A	260	93.404	11.679	44.523	1.00	99.58	O
Atom	36	N	LEU	A	261	91.332	11.918	43.693	1.00	110.37	N
Atom	37	CA	LEU	A	261	91.197	13.265	44.260	1.00	110.86	C
Atom	38	CB	LEU	A	261	91.310	14.373	43.206	1.00	83.41	C
Atom	39	CG	LEU	A	261	92.630	15.117	43.435	1.00	75.60	C
Atom	40	CD1	LEU	A	261	92.957	16.095	42.325	1.00	74.55	C
Atom	41	CD2	LEU	A	261	92.605	15.826	44.785	1.00	73.35	C
Atom	42	C	LEU	A	261	90.035	13.487	45.239	1.00	106.98	C
Atom	43	O	LEU	A	261	89.563	14.609	45.422	1.00	100.30	O
Atom	44	N	LYS	A	262	89.581	12.396	45.847	1.00	106.50	N
Atom	45	CA	LYS	A	262	89.099	12.431	47.225	1.00	99.64	C
Atom	46	CB	LYS	A	262	90.200	13.043	48.102	1.00	87.94	C
Atom	47	CG	LYS	A	262	91.600	12.580	47.736	1.00	84.96	C
Atom	48	CD	LYS	A	262	92.638	13.623	48.095	1.00	83.60	C
Atom	49	CE	LYS	A	262	92.770	13.777	49.602	1.00	75.13	C
Atom	50	NZ	LYS	A	262	93.106	12.475	50.253	1.00	78.69	N
Atom	51	C	LYS	A	262	87.785	13.153	47.523	1.00	100.82	C
Atom	52	O	LYS	A	262	87.001	13.488	46.632	1.00	94.80	O
Atom	53	N	THR	A	263	87.573	13.366	48.819	1.00	99.01	N
Atom	54	CA	THR	A	263	86.483	14.167	49.342	1.00	84.52	C
Atom	55	CB	THR	A	263	86.065	13.675	50.739	1.00	92.19	C
Atom	56	OG1	THR	A	263	87.201	13.707	51.614	1.00	89.70	O
Atom	57	CG2	THR	A	263	85.530	12.248	50.673	1.00	93.60	C
Atom	58	C	THR	A	263	86.993	15.597	49.467	1.00	88.22	C
Atom	59	O	THR	A	263	86.826	16.244	50.500	1.00	87.38	O
Atom	60	N	THR	A	264	87.640	16.076	48.411	1.00	91.46	N
Atom	61	CA	THR	A	264	88.228	17.413	48.398	1.00	85.52	C
Atom	62	CB	THR	A	264	89.071	17.635	47.127	1.00	83.35	C
Atom	63	OG1	THR	A	264	90.110	16.653	47.069	1.00	86.29	O
Atom	64	CG2	THR	A	264	89.691	19.022	47.130	1.00	75.97	C
Atom	65	C	THR	A	264	87.197	18.539	48.541	1.00	81.66	C
Atom	66	O	THR	A	264	87.427	19.494	49.289	1.00	75.55	O
Atom	67	N	PRO	A	265	86.066	18.437	47.817	1.00	74.49	N
Atom	68	CA	PRO	A	265	85.014	19.454	47.924	1.00	74.11	C
Atom	69	CB	PRO	A	265	83.877	18.861	47.093	1.00	71.63	C
Atom	70	CG	PRO	A	265	84.569	18.028	46.077	1.00	74.33	C
Atom	71	CD	PRO	A	265	85.759	17.440	46.776	1.00	69.08	C
Atom	72	C	PRO	A	265	84.557	19.668	49.362	1.00	73.62	C
Atom	73	O	PRO	A	265	84.188	18.709	50.037	1.00	73.69	O
Atom	74	N	ARG	A	266	84.594	20.917	49.815	1.00	71.81	N
Atom	75	CA	ARG	A	266	84.154	21.279	51.156	1.00	69.16	C
Atom	76	CB	ARG	A	266	85.153	22.245	51.794	1.00	66.29	C
Atom	77	CG	ARG	A	266	85.305	23.551	51.034	1.00	64.77	C
Atom	78	CD	ARG	A	266	86.031	24.593	51.861	1.00	63.22	C
Atom	79	NE	ARG	A	266	86.266	25.811	51.092	1.00	68.05	N
Atom	80	CZ	ARG	A	266	85.398	26.814	50.994	1.00	71.11	C
Atom	81	NH1	ARG	A	266	84.230	26.744	51.617	1.00	72.62	N
Atom	82	NH2	ARG	A	266	85.697	27.885	50.273	1.00	63.93	N
Atom	83	C	ARG	A	266	82.785	21.943	51.081	1.00	75.68	C
Atom	84	O	ARG	A	266	82.339	22.329	50.000	1.00	73.21	O
Atom	85	N	PRO	A	267	82.112	22.087	52.232	1.00	77.49	N
Atom	86	CA	PRO	A	267	80.838	22.811	52.230	1.00	74.00	C
Atom	87	CB	PRO	A	267	80.375	22.712	53.688	1.00	72.07	C
Atom	88	CG	PRO	A	267	81.104	21.529	54.246	1.00	70.88	C
Atom	89	CD	PRO	A	267	82.433	21.527	53.556	1.00	74.87	C
Atom	90	C	PRO	A	267	81.041	24.273	51.846	1.00	70.24	C
Atom	91	O	PRO	A	267	82.057	24.869	52.205	1.00	72.02	O
Atom	92	N	LEU	A	268	80.091	24.837	51.109	1.00	68.84	N
Atom	93	CA	LEU	A	268	80.122	26.258	50.803	1.00	66.24	C
Atom	94	CB	LEU	A	268	79.014	26.621	49.816	1.00	62.15	C
Atom	95	CG	LEU	A	268	78.992	25.877	48.482	1.00	59.79	C
Atom	96	CD1	LEU	A	268	77.667	26.099	47.763	1.00	64.25	C
Atom	97	CD2	LEU	A	268	80.149	26.314	47.613	1.00	63.20	C
Atom	98	C	LEU	A	268	79.951	27.039	52.099	1.00	66.63	C
Atom	99	O	LEU	A	268	79.316	26.565	53.038	1.00	69.53	O
Atom	100	N	ARG	A	269	80.526	28.234	52.153	1.00	67.41	N
Atom	101	CA	ARG	A	269	80.440	29.054	53.353	1.00	69.87	C
Atom	102	CB	ARG	A	269	81.817	29.608	53.727	1.00	66.44	C
Atom	103	CG	ARG	A	269	82.745	28.549	54.299	1.00	77.44	C
Atom	104	CD	ARG	A	269	84.209	28.931	54.176	1.00	86.20	C
Atom	105	NE	ARG	A	269	85.080	27.820	54.557	1.00	93.54	N
Atom	106	CZ	ARG	A	269	86.393	27.792	54.359	1.00	87.58	C
Atom	107	NH1	ARG	A	269	87.001	28.818	53.780	1.00	84.19	N
Atom	108	NH2	ARG	A	269	87.098	26.735	54.740	1.00	76.10	N
Atom	109	C	ARG	A	269	79.417	30.172	53.196	1.00	69.09	C
Atom	110	O	ARG	A	269	79.525	31.014	52.302	1.00	66.44	O
Atom	111	N	LEU	A	270	78.415	30.161	54.068	1.00	64.18	N
Atom	112	CA	LEU	A	270	77.352	31.159	54.028	1.00	68.05	C
Atom	113	CB	LEU	A	270	75.995	30.518	54.344	1.00	62.77	C
Atom	114	CG	LEU	A	270	75.332	29.702	53.229	1.00	60.46	C
Atom	115	CD1	LEU	A	270	76.223	28.561	52.763	1.00	59.74	C
Atom	116	CD2	LEU	A	270	73.983	29.168	53.687	1.00	61.40	C
Atom	117	C	LEU	A	270	77.641	32.324	54.977	1.00	65.51	C
Atom	118	O	LEU	A	270	78.282	32.144	56.013	1.00	62.64	O
Atom	119	N	PRO	A	271	77.163	33.525	54.617	1.00	66.71	N
Atom	120	CA	PRO	A	271	77.402	34.771	55.357	1.00	64.01	C
Atom	121	CB	PRO	A	271	76.628	35.813	54.544	1.00	64.36	C
Atom	122	CG	PRO	A	271	76.475	35.222	53.192	1.00	63.59	C
Atom	123	CD	PRO	A	271	76.362	33.747	53.402	1.00	68.19	C
Atom	124	C	PRO	A	271	76.849	34.757	56.776	1.00	67.61	C
Atom	125	O	PRO	A	271	75.874	34.060	57.056	1.00	71.15	O
Atom	126	N	ASP	A	272	77.477	35.528	57.658	1.00	72.04	N
Atom	127	CA	ASP	A	272	76.918	35.821	58.970	1.00	71.75	C
Atom	128	CB	ASP	A	272	78.031	36.028	59.997	1.00	89.42	C
Atom	129	CG	ASP	A	272	78.540	34.723	60.577	1.00	100.84	C
Atom	130	OD1	ASP	A	272	77.717	33.806	60.794	1.00	94.50	O
Atom	131	OD2	ASP	A	272	79.762	34.619	60.822	1.00	108.66	O
Atom	132	C	ASP	A	272	76.096	37.093	58.843	1.00	76.85	C
Atom	133	O	ASP	A	272	76.172	37.784	57.827	1.00	80.23	O
Atom	134	N	GLY	A	273	75.317	37.409	59.871	1.00	80.11	N
Atom	135	CA	GLY	A	273	74.535	38.633	59.873	1.00	79.17	C
Atom	136	C	GLY	A	273	73.094	38.407	60.282	1.00	78.11	C
Atom	137	O	GLY	A	273	72.708	37.286	60.608	1.00	78.88	O
Atom	138	N	PRO	A	274	72.286	39.477	60.269	1.00	75.96	N
Atom	139	CA	PRO	A	274	70.856	39.354	60.564	1.00	74.11	C
Atom	140	CB	PRO	A	274	70.318	40.767	60.300	1.00	71.18	C
Atom	141	CG	PRO	A	274	71.505	41.661	60.373	1.00	72.28	C
Atom	142	CD	PRO	A	274	72.657	40.846	59.878	1.00	74.52	C
Atom	143	C	PRO	A	274	70.221	38.364	59.598	1.00	78.24	C
Atom	144	O	PRO	A	274	70.748	38.171	58.499	1.00	76.47	O
Atom	145	N	PRO	A	275	69.107	37.735	60.000	1.00	79.44	N
Atom	146	CA	PRO	A	275	68.408	36.789	59.124	1.00	71.22	C
Atom	147	CB	PRO	A	275	67.212	36.340	59.973	1.00	71.46	C
Atom	148	CG	PRO	A	275	67.600	36.655	61.385	1.00	69.92	C
Atom	149	CD	PRO	A	275	68.434	37.887	61.300	1.00	72.01	C
Atom	150	C	PRO	A	275	67.923	37.483	57.856	1.00	66.65	C
Atom	151	O	PRO	A	275	67.565	38.661	57.902	1.00	66.44	O
Atom	152	N	CYS	A	276	67.928	36.765	56.738	1.00	61.03	N
Atom	153	CA	CYS	A	276	67.427	37.307	55.481	1.00	64.32	C
Atom	154	CB	CYS	A	276	67.692	36.330	54.337	1.00	63.67	C
Atom	155	SG	CYS	A	276	66.977	34.690	54.596	1.00	65.48	S
Atom	156	C	CYS	A	276	65.934	37.603	55.586	1.00	64.10	C
Atom	157	O	CYS	A	276	65.242	37.060	56.449	1.00	62.47	O
Atom	158	N	SER	A	277	65.439	38.458	54.699	1.00	63.64	N
Atom	159	CA	SER	A	277	64.046	38.879	54.753	1.00	60.63	C
Atom	160	CB	SER	A	277	63.959	40.351	55.147	1.00	60.71	C
Atom	161	OG	SER	A	277	64.595	41.161	54.176	1.00	60.49	O
Atom	162	C	SER	A	277	63.331	38.665	53.423	1.00	63.02	C
Atom	163	O	SER	A	277	63.963	38.580	52.368	1.00	65.56	O
Atom	164	N	GLN	A	278	62.005	38.585	53.488	1.00	63.80	N
Atom	165	CA	GLN	A	278	61.174	38.420	52.303	1.00	57.94	C
Atom	166	CB	GLN	A	278	59.697	38.355	52.697	1.00	57.85	C
Atom	167	CG	GLN	A	278	58.735	38.136	51.536	1.00	59.11	C
Atom	168	CD	GLN	A	278	59.004	36.843	50.789	1.00	62.32	C
Atom	169	OE1	GLN	A	278	58.254	35.875	50.912	1.00	61.13	O
Atom	170	NE2	GLN	A	278	60.087	36.817	50.018	1.00	61.31	N
Atom	171	C	GLN	A	278	61.403	39.574	51.337	1.00	56.85	C
Atom	172	O	GLN	A	278	61.604	40.713	51.758	1.00	57.72	O
Atom	173	N	ARG	A	279	61.381	39.276	50.042	1.00	59.21	N
Atom	174	CA	ARG	A	279	61.580	40.300	49.019	1.00	63.43	C
Atom	175	CB	ARG	A	279	63.068	40.498	48.741	1.00	58.78	C
Atom	176	CG	ARG	A	279	63.714	39.337	48.021	1.00	55.98	C
Atom	177	CD	ARG	A	279	65.047	39.744	47.438	1.00	58.76	C
Atom	178	NE	ARG	A	279	65.402	38.891	46.311	1.00	68.48	N
Atom	179	CZ	ARG	A	279	65.122	39.176	45.044	1.00	65.33	C
Atom	180	NH1	ARG	A	279	64.483	40.299	44.738	1.00	56.96	N
Atom	181	NH2	ARG	A	279	65.484	38.339	44.080	1.00	60.65	N
Atom	182	C	ARG	A	279	60.851	39.955	47.724	1.00	61.68	C
Atom	183	O	ARG	A	279	61.148	40.508	46.664	1.00	53.66	O
Atom	184	N	SER	A	280	59.907	39.025	47.813	1.00	58.43	N
Atom	185	CA	SER	A	280	59.081	38.678	46.669	1.00	53.89	C
Atom	186	CB	SER	A	280	58.317	37.384	46.932	1.00	58.53	C
Atom	187	OG	SER	A	280	57.534	37.491	48.108	1.00	66.07	O
Atom	188	C	SER	A	280	58.113	39.823	46.405	1.00	56.48	C
Atom	189	O	SER	A	280	57.879	40.653	47.283	1.00	59.54	O
Atom	190	N	LYS	A	281	57.567	39.880	45.195	1.00	59.61	N
Atom	191	CA	LYS	A	281	56.658	40.959	44.815	1.00	58.47	C
Atom	192	CB	LYS	A	281	56.296	40.855	43.335	1.00	63.40	C
Atom	193	CG	LYS	A	281	55.346	41.934	42.855	1.00	68.09	C
Atom	194	CD	LYS	A	281	54.826	41.618	41.464	1.00	74.78	C
Atom	195	CE	LYS	A	281	54.082	42.798	40.868	1.00	78.19	C
Atom	196	NZ	LYS	A	281	54.957	43.995	40.730	1.00	87.89	N
Atom	197	C	LYS	A	281	55.390	40.934	45.662	1.00	64.74	C
Atom	198	O	LYS	A	281	54.975	41.953	46.214	1.00	61.14	O
Atom	199	N	PHE	A	282	54.774	39.760	45.748	1.00	62.08	N
Atom	200	CA	PHE	A	282	53.606	39.566	46.595	1.00	58.02	C
Atom	201	CB	PHE	A	282	52.376	39.212	45.754	1.00	55.39	C
Atom	202	CG	PHE	A	282	52.650	38.209	44.668	1.00	58.20	C
Atom	203	CD1	PHE	A	282	52.772	38.612	43.349	1.00	62.35	C
Atom	204	CE1	PHE	A	282	53.026	37.692	42.348	1.00	62.43	C
Atom	205	CZ	PHE	A	282	53.163	36.352	42.662	1.00	63.79	C
Atom	206	CE2	PHE	A	282	53.047	35.941	43.975	1.00	58.77	C
Atom	207	CD2	PHE	A	282	52.792	36.867	44.969	1.00	56.46	C
Atom	208	C	PHE	A	282	53.883	38.485	47.632	1.00	57.85	C
Atom	209	O	PHE	A	282	54.906	37.803	47.572	1.00	56.07	O
Atom	210	N	LEU	A	283	52.980	38.346	48.595	1.00	54.72	N
Atom	211	CA	LEU	A	283	53.120	37.326	49.624	1.00	52.75	C
Atom	212	CB	LEU	A	283	52.069	37.516	50.720	1.00	55.49	C
Atom	213	CG	LEU	A	283	52.121	38.824	51.511	1.00	55.91	C
Atom	214	CD1	LEU	A	283	51.019	38.844	52.557	1.00	53.24	C
Atom	215	CD2	LEU	A	283	53.484	39.007	52.163	1.00	50.75	C
Atom	216	C	LEU	A	283	52.978	35.953	48.988	1.00	55.54	C
Atom	217	O	LEU	A	283	52.348	35.811	47.941	1.00	53.96	O
Atom	218	N	LEU	A	284	53.568	34.944	49.619	1.00	58.94	N
Atom	219	CA	LEU	A	284	53.520	33.586	49.092	1.00	52.63	C
Atom	220	CB	LEU	A	284	54.933	33.031	48.918	1.00	53.20	C
Atom	221	CG	LEU	A	284	55.799	33.855	47.961	1.00	57.03	C
Atom	222	CD1	LEU	A	284	57.176	33.231	47.771	1.00	50.50	C
Atom	223	CD2	LEU	A	284	55.091	34.041	46.621	1.00	54.76	C
Atom	224	C	LEU	A	284	52.681	32.677	49.988	1.00	55.51	C
Atom	225	O	LEU	A	284	51.463	32.618	49.848	1.00	58.23	O
Atom	226	N	MET	A	285	53.327	31.982	50.916	1.00	55.47	N
Atom	227	CA	MET	A	285	52.614	31.073	51.810	1.00	53.47	C
Atom	228	CB	MET	A	285	53.599	30.197	52.582	1.00	58.57	C
Atom	229	CG	MET	A	285	54.464	30.957	53.575	1.00	55.03	C
Atom	230	SD	MET	A	285	55.677	29.887	54.378	1.00	64.78	S
Atom	231	CE	MET	A	285	54.618	28.823	55.360	1.00	58.58	C
Atom	232	C	MET	A	285	51.724	31.823	52.791	1.00	57.38	C
Atom	233	O	MET	A	285	50.812	31.247	53.383	1.00	65.33	O
Atom	234	N	ASP	A	286	52.000	33.111	52.961	1.00	59.98	N
Atom	235	CA	ASP	A	286	51.288	33.925	53.933	1.00	51.26	C
Atom	236	CB	ASP	A	286	52.240	34.943	54.552	1.00	54.72	C
Atom	237	CG	ASP	A	286	53.502	34.302	55.089	1.00	57.96	C
Atom	238	OD1	ASP	A	286	53.437	33.659	56.159	1.00	57.26	O
Atom	239	OD2	ASP	A	286	54.562	34.445	54.443	1.00	56.96	O
Atom	240	C	ASP	A	286	50.100	34.639	53.307	1.00	56.00	C
Atom	241	O	ASP	A	286	49.349	35.327	53.999	1.00	59.93	O
Atom	242	N	ALA	A	287	49.930	34.476	51.997	1.00	57.81	N
Atom	243	CA	ALA	A	287	48.835	35.127	51.280	1.00	56.63	C
Atom	244	CB	ALA	A	287	48.961	34.879	49.786	1.00	52.92	C
Atom	245	C	ALA	A	287	47.478	34.650	51.791	1.00	57.56	C
Atom	246	O	ALA	A	287	47.338	33.512	52.230	1.00	63.14	O
Atom	247	N	LEU	A	288	46.484	35.529	51.741	1.00	57.00	N
Atom	248	CA	LEU	A	288	45.125	35.170	52.122	1.00	55.42	C
Atom	249	CB	LEU	A	288	44.749	35.813	53.455	1.00	62.57	C
Atom	250	CG	LEU	A	288	43.303	35.603	53.921	1.00	58.43	C
Atom	251	CD1	LEU	A	288	43.108	34.184	54.414	1.00	49.90	C
Atom	252	CD2	LEU	A	288	42.942	36.599	55.008	1.00	58.53	C
Atom	253	C	LEU	A	288	44.158	35.641	51.052	1.00	56.81	C
Atom	254	O	LEU	A	288	44.185	36.805	50.654	1.00	58.00	O
Atom	255	N	LYS	A	289	43.300	34.736	50.593	1.00	59.73	N
Atom	256	CA	LYS	A	289	42.341	35.058	49.543	1.00	56.64	C
Atom	257	CB	LYS	A	289	42.313	33.950	48.486	1.00	54.20	C
Atom	258	CG	LYS	A	289	43.673	33.599	47.909	1.00	57.79	C
Atom	259	CD	LYS	A	289	43.554	32.571	46.793	1.00	56.56	C
Atom	260	CE	LYS	A	289	43.268	31.183	47.338	1.00	63.87	C
Atom	261	NZ	LYS	A	289	44.463	30.585	47.998	1.00	66.79	N
Atom	262	C	LYS	A	289	40.932	35.258	50.095	1.00	58.06	C
Atom	263	O	LYS	A	289	40.454	34.470	50.911	1.00	61.12	O
Atom	264	N	LEU	A	290	40.279	36.324	49.648	1.00	57.12	N
Atom	265	CA	LEU	A	290	38.844	36.484	49.823	1.00	56.50	C
Atom	266	CB	LEU	A	290	38.513	37.904	50.274	1.00	54.88	C
Atom	267	CG	LEU	A	290	39.082	38.345	51.623	1.00	55.95	C
Atom	268	CD1	LEU	A	290	38.807	39.822	51.853	1.00	53.24	C
Atom	269	CD2	LEU	A	290	38.519	37.504	52.759	1.00	52.12	C
Atom	270	C	LEU	A	290	38.212	36.195	48.468	1.00	63.90	C
Atom	271	O	LEU	A	290	38.527	36.859	47.483	1.00	70.79	O
Atom	272	N	SER	A	291	37.336	35.198	48.403	1.00	66.46	N
Atom	273	CA	SER	A	291	36.862	34.731	47.101	1.00	73.98	C
Atom	274	CB	SER	A	291	37.495	33.380	46.753	1.00	69.69	C
Atom	275	OG	SER	A	291	37.218	32.413	47.749	1.00	82.37	O
Atom	276	C	SER	A	291	35.346	34.648	46.933	1.00	71.81	C
Atom	277	O	SER	A	291	34.590	34.642	47.903	1.00	65.73	O
Atom	278	N	ILE	A	292	34.926	34.591	45.673	1.00	77.20	N
Atom	279	CA	ILE	A	292	33.527	34.445	45.302	1.00	77.17	C
Atom	280	CB	ILE	A	292	32.901	35.809	44.972	1.00	66.61	C
Atom	281	CG1	ILE	A	292	33.663	36.480	43.828	1.00	69.00	C
Atom	282	CD1	ILE	A	292	33.195	37.898	43.525	1.00	76.10	C
Atom	283	CG2	ILE	A	292	32.894	36.703	46.197	1.00	63.22	C
Atom	284	C	ILE	A	292	33.433	33.545	44.071	1.00	84.27	C
Atom	285	O	ILE	A	292	34.417	32.907	43.687	1.00	82.37	O
Atom	286	N	GLU	A	293	32.254	33.500	43.453	1.00	96.02	N
Atom	287	CA	GLU	A	293	32.063	32.758	42.205	1.00	93.08	C
Atom	288	CB	GLU	A	293	30.810	31.886	42.291	1.00	88.37	C
Atom	289	CG	GLU	A	293	30.595	31.220	43.648	1.00	100.57	C
Atom	290	CD	GLU	A	293	31.694	30.231	44.029	1.00	111.87	C
Atom	291	OE1	GLU	A	293	31.366	29.049	44.275	1.00	126.15	O
Atom	292	OE2	GLU	A	293	32.879	30.630	44.093	1.00	103.21	O
Atom	293	C	GLU	A	293	31.974	33.686	40.986	1.00	90.56	C
Atom	294	O	GLU	A	293	32.410	33.341	39.883	1.00	89.86	O
Atom	295	N	ILE	A	302	35.653	43.080	35.367	1.00	86.17	N
Atom	296	CA	ILE	A	302	35.821	44.327	36.107	1.00	97.26	C
Atom	297	CB	ILE	A	302	34.501	45.112	36.211	1.00	97.26	C
Atom	298	CG1	ILE	A	302	33.835	45.227	34.837	1.00	93.64	C
Atom	299	CD1	ILE	A	302	32.498	45.942	34.862	1.00	96.26	C
Atom	300	CG2	ILE	A	302	34.752	46.490	36.810	1.00	93.36	C
Atom	301	C	ILE	A	302	36.355	44.062	37.509	1.00	92.13	C
Atom	302	O	ILE	A	302	35.581	43.829	38.440	1.00	88.17	O
Atom	303	N	PRO	A	303	37.688	44.105	37.659	1.00	90.36	N
Atom	304	CA	PRO	A	303	38.402	43.801	38.903	1.00	84.21	C
Atom	305	CB	PRO	A	303	39.795	44.373	38.647	1.00	83.95	C
Atom	306	CG	PRO	A	303	39.968	44.254	37.173	1.00	86.75	C
Atom	307	CD	PRO	A	303	38.610	44.493	36.576	1.00	88.05	C
Atom	308	C	PRO	A	303	37.789	44.451	40.140	1.00	81.80	C
Atom	309	O	PRO	A	303	37.493	43.749	41.104	1.00	84.37	O
Atom	310	N	LEU	A	304	37.610	45.767	40.116	1.00	79.27	N
Atom	311	CA	LEU	A	304	37.071	46.479	41.271	1.00	84.47	C
Atom	312	CB	LEU	A	304	36.983	47.976	40.991	1.00	87.18	C
Atom	313	CG	LEU	A	304	38.265	48.766	41.234	1.00	87.84	C
Atom	314	CD1	LEU	A	304	37.985	50.237	41.039	1.00	95.99	C
Atom	315	CD2	LEU	A	304	38.799	48.500	42.633	1.00	83.86	C
Atom	316	C	LEU	A	304	35.707	45.950	41.691	1.00	86.61	C
Atom	317	O	LEU	A	304	35.432	45.794	42.881	1.00	84.35	O
Atom	318	N	TYR	A	305	34.850	45.685	40.712	1.00	86.70	N
Atom	319	CA	TYR	A	305	33.539	45.124	40.998	1.00	89.33	C
Atom	320	CB	TYR	A	305	32.743	44.921	39.706	1.00	94.36	C
Atom	321	CG	TYR	A	305	31.411	44.238	39.917	1.00	97.01	C
Atom	322	CD1	TYR	A	305	30.366	44.895	40.556	1.00	94.75	C
Atom	323	CE1	TYR	A	305	29.149	44.274	40.754	1.00	99.89	C
Atom	324	CZ	TYR	A	305	28.963	42.980	40.309	1.00	107.94	C
Atom	325	OH	TYR	A	305	27.751	42.354	40.501	1.00	112.22	O
Atom	326	CE2	TYR	A	305	29.984	42.307	39.671	1.00	104.17	C
Atom	327	CD2	TYR	A	305	31.198	42.936	39.478	1.00	100.81	C
Atom	328	C	TYR	A	305	33.698	43.804	41.745	1.00	85.14	C
Atom	329	O	TYR	A	305	33.054	43.571	42.768	1.00	86.38	O
Atom	330	N	ASP	A	306	34.575	42.949	41.235	1.00	79.13	N
Atom	331	CA	ASP	A	306	34.838	41.663	41.865	1.00	81.52	C
Atom	332	CB	ASP	A	306	35.673	40.780	40.937	1.00	83.26	C
Atom	333	CG	ASP	A	306	34.933	40.408	39.664	1.00	87.46	C
Atom	334	OD1	ASP	A	306	33.799	40.896	39.464	1.00	91.24	O
Atom	335	OD2	ASP	A	306	35.486	39.624	38.863	1.00	89.32	O
Atom	336	C	ASP	A	306	35.545	41.840	43.205	1.00	80.16	C
Atom	337	O	ASP	A	306	35.298	41.095	44.155	1.00	81.79	O
Atom	338	N	ALA	A	307	36.429	42.829	43.274	1.00	76.33	N
Atom	339	CA	ALA	A	307	37.161	43.117	44.499	1.00	74.77	C
Atom	340	CB	ALA	A	307	38.102	44.300	44.295	1.00	72.36	C
Atom	341	C	ALA	A	307	36.191	43.395	45.641	1.00	71.76	C
Atom	342	O	ALA	A	307	36.313	42.826	46.726	1.00	69.25	O
Atom	343	N	ILE	A	308	35.223	44.267	45.384	1.00	72.91	N
Atom	344	CA	ILE	A	308	34.237	44.635	46.390	1.00	76.02	C
Atom	345	CB	ILE	A	308	33.356	45.798	45.905	1.00	81.11	C
Atom	346	CG1	ILE	A	308	34.196	47.071	45.779	1.00	72.28	C
Atom	347	CD1	ILE	A	308	33.495	48.199	45.064	1.00	86.00	C
Atom	348	CG2	ILE	A	308	32.184	46.015	46.854	1.00	72.78	C
Atom	349	C	ILE	A	308	33.366	43.445	46.791	1.00	73.57	C
Atom	350	O	ILE	A	308	33.099	43.235	47.972	1.00	72.60	O
Atom	351	N	LYS	A	309	32.929	42.661	45.812	1.00	69.57	N
Atom	352	CA	LYS	A	309	32.133	41.476	46.115	1.00	74.77	C
Atom	353	CB	LYS	A	309	31.599	40.820	44.839	1.00	78.28	C
Atom	354	CG	LYS	A	309	30.575	41.672	44.105	1.00	85.98	C
Atom	355	CD	LYS	A	309	29.443	40.831	43.521	1.00	100.58	C
Atom	356	CE	LYS	A	309	29.946	39.804	42.512	1.00	113.59	C
Atom	357	NZ	LYS	A	309	28.821	39.020	41.914	1.00	107.16	N
Atom	358	C	LYS	A	309	32.920	40.470	46.949	1.00	69.11	C
Atom	359	O	LYS	A	309	32.348	39.749	47.771	1.00	68.26	O
Atom	360	N	CYS	A	310	34.231	40.424	46.734	1.00	72.90	N
Atom	361	CA	CYS	A	310	35.102	39.552	47.514	1.00	67.98	C
Atom	362	CB	CYS	A	310	36.477	39.429	46.856	1.00	62.27	C
Atom	363	SG	CYS	A	310	36.528	38.310	45.444	1.00	65.00	S
Atom	364	C	CYS	A	310	35.242	40.056	48.946	1.00	66.63	C
Atom	365	O	CYS	A	310	35.174	39.281	49.898	1.00	59.77	O
Atom	366	N	MET	A	311	35.438	41.361	49.092	1.00	60.90	N
Atom	367	CA	MET	A	311	35.581	41.955	50.412	1.00	62.78	C
Atom	368	CB	MET	A	311	35.983	43.428	50.309	1.00	64.52	C
Atom	369	CG	MET	A	311	37.326	43.653	49.638	1.00	66.16	C
Atom	370	SD	MET	A	311	37.827	45.382	49.638	1.00	70.15	S
Atom	371	CE	MET	A	311	38.294	45.600	51.353	1.00	63.04	C
Atom	372	C	MET	A	311	34.283	41.810	51.192	1.00	62.65	C
Atom	373	O	MET	A	311	34.296	41.707	52.420	1.00	61.94	O
Atom	374	N	LYS	A	312	33.164	41.796	50.475	1.00	65.90	N
Atom	375	CA	LYS	A	312	31.858	41.672	51.114	1.00	69.11	C
Atom	376	CB	LYS	A	312	30.729	41.965	50.122	1.00	70.01	C
Atom	377	CG	LYS	A	312	30.544	43.437	49.780	1.00	65.98	C
Atom	378	CD	LYS	A	312	29.065	43.762	49.618	1.00	80.79	C
Atom	379	CE	LYS	A	312	28.835	45.139	49.006	1.00	84.10	C
Atom	380	NZ	LYS	A	312	28.820	45.085	47.514	1.00	83.82	N
Atom	381	C	LYS	A	312	31.657	40.294	51.746	1.00	64.33	C
Atom	382	O	LYS	A	312	30.772	40.112	52.582	1.00	63.96	O
Atom	383	N	THR	A	313	32.473	39.323	51.347	1.00	59.73	N
Atom	384	CA	THR	A	313	32.388	37.989	51.932	1.00	58.55	C
Atom	385	CB	THR	A	313	32.955	36.907	51.000	1.00	57.93	C
Atom	386	OG1	THR	A	313	34.387	36.975	50.992	1.00	61.30	O
Atom	387	CG2	THR	A	313	32.425	37.092	49.584	1.00	55.25	C
Atom	388	C	THR	A	313	33.132	37.937	53.262	1.00	56.81	C
Atom	389	O	THR	A	313	33.223	36.885	53.893	1.00	56.45	O
Atom	390	N	PHE	A	314	33.668	39.078	53.683	1.00	57.09	N
Atom	391	CA	PHE	A	314	34.343	39.173	54.972	1.00	56.18	C
Atom	392	CB	PHE	A	314	35.785	39.644	54.797	1.00	59.26	C
Atom	393	CG	PHE	A	314	36.531	39.816	56.092	1.00	61.68	C
Atom	394	CD1	PHE	A	314	36.908	38.714	56.842	1.00	58.65	C
Atom	395	CE1	PHE	A	314	37.599	38.866	58.031	1.00	54.45	C
Atom	396	CZ	PHE	A	314	37.929	40.131	58.478	1.00	54.85	C
Atom	397	CE2	PHE	A	314	37.563	41.235	57.738	1.00	59.88	C
Atom	398	CD2	PHE	A	314	36.869	41.077	56.551	1.00	61.49	C
Atom	399	C	PHE	A	314	33.576	40.142	55.849	1.00	58.40	C
Atom	400	O	PHE	A	314	33.185	41.216	55.399	1.00	66.31	O
Atom	401	N	PHE	A	315	33.351	39.757	57.100	1.00	60.42	N
Atom	402	CA	PHE	A	315	32.509	40.542	57.992	1.00	60.60	C
Atom	403	CB	PHE	A	315	31.183	39.818	58.251	1.00	59.04	C
Atom	404	CG	PHE	A	315	30.051	40.738	58.618	1.00	65.15	C
Atom	405	CD1	PHE	A	315	29.554	41.644	57.695	1.00	68.73	C
Atom	406	CE1	PHE	A	315	28.514	42.492	58.025	1.00	69.14	C
Atom	407	CZ	PHE	A	315	27.953	42.438	59.283	1.00	70.04	C
Atom	408	CE2	PHE	A	315	28.433	41.535	60.212	1.00	69.11	C
Atom	409	CD2	PHE	A	315	29.475	40.690	59.878	1.00	65.85	C
Atom	410	C	PHE	A	315	33.223	40.836	59.307	1.00	63.39	C
Atom	411	O	PHE	A	315	32.600	40.867	60.367	1.00	67.11	O
Atom	412	N	GLY	A	316	34.534	41.050	59.230	1.00	58.15	N
Atom	413	CA	GLY	A	316	35.336	41.322	60.409	1.00	59.36	C
Atom	414	C	GLY	A	316	36.209	42.561	60.293	1.00	58.93	C
Atom	415	O	GLY	A	316	37.117	42.764	61.098	1.00	60.49	O
Atom	416	N	TRP	A	317	35.945	43.391	59.290	1.00	57.27	N
Atom	417	CA	TRP	A	317	36.685	44.637	59.129	1.00	58.89	C
Atom	418	CB	TRP	A	317	36.131	45.448	57.954	1.00	56.75	C
Atom	419	CG	TRP	A	317	36.126	44.706	56.656	1.00	60.19	C
Atom	420	CD1	TRP	A	317	35.038	44.214	55.999	1.00	61.58	C
Atom	421	NE1	TRP	A	317	35.429	43.592	54.838	1.00	60.20	N
Atom	422	CE2	TRP	A	317	36.793	43.675	54.726	1.00	61.65	C
Atom	423	CD2	TRP	A	317	37.265	44.372	55.855	1.00	63.55	C
Atom	424	CE3	TRP	A	317	38.642	44.592	55.983	1.00	58.40	C
Atom	425	CZ3	TRP	A	317	39.486	44.116	54.994	1.00	56.88	C
Atom	426	CH2	TRP	A	317	38.982	43.427	53.882	1.00	57.90	C
Atom	427	CZ2	TRP	A	317	37.642	43.197	53.731	1.00	59.98	C
Atom	428	C	TRP	A	317	36.618	45.478	60.399	1.00	60.65	C
Atom	429	O	TRP	A	317	35.565	45.584	61.032	1.00	67.13	O
Atom	430	N	LYS	A	318	37.739	46.083	60.770	1.00	57.63	N
Atom	431	CA	LYS	A	318	37.747	46.983	61.914	1.00	61.90	C
Atom	432	CB	LYS	A	318	38.063	46.222	63.199	1.00	59.32	C
Atom	433	CG	LYS	A	318	39.477	45.681	63.284	1.00	61.07	C
Atom	434	CD	LYS	A	318	39.858	45.452	64.742	1.00	70.94	C
Atom	435	CE	LYS	A	318	41.014	44.471	64.895	1.00	66.10	C
Atom	436	NZ	LYS	A	318	41.190	44.074	66.325	1.00	62.93	N
Atom	437	C	LYS	A	318	38.737	48.123	61.726	1.00	62.42	C
Atom	438	O	LYS	A	318	39.444	48.181	60.718	1.00	59.97	O
Atom	439	N	GLU	A	319	38.780	49.025	62.704	1.00	66.43	N
Atom	440	CA	GLU	A	319	39.706	50.155	62.680	1.00	64.32	C
Atom	441	CB	GLU	A	319	39.533	51.023	63.930	1.00	61.29	C
Atom	442	CG	GLU	A	319	40.312	52.329	63.892	1.00	64.44	C
Atom	443	CD	GLU	A	319	39.814	53.271	62.811	1.00	75.35	C
Atom	444	OE1	GLU	A	319	38.673	53.081	62.338	1.00	81.68	O
Atom	445	OE2	GLU	A	319	40.559	54.202	62.435	1.00	74.64	O
Atom	446	C	GLU	A	319	41.146	49.666	62.577	1.00	59.62	C
Atom	447	O	GLU	A	319	41.658	49.023	63.494	1.00	54.40	O
Atom	448	N	PRO	A	320	41.804	49.970	61.451	1.00	59.49	N
Atom	449	CA	PRO	A	320	43.168	49.512	61.174	1.00	56.85	C
Atom	450	CB	PRO	A	320	43.454	50.111	59.793	1.00	57.20	C
Atom	451	CG	PRO	A	320	42.523	51.284	59.709	1.00	64.06	C
Atom	452	CD	PRO	A	320	41.272	50.768	60.336	1.00	57.37	C
Atom	453	C	PRO	A	320	44.157	50.058	62.195	1.00	60.52	C
Atom	454	O	PRO	A	320	44.025	51.198	62.642	1.00	64.61	O
Atom	455	N	ASN	A	321	45.143	49.245	62.555	1.00	65.22	N
Atom	456	CA	ASN	A	321	46.138	49.641	63.539	1.00	66.59	C
Atom	457	CB	ASN	A	321	45.628	49.326	64.945	1.00	61.83	C
Atom	458	CG	ASN	A	321	46.745	49.001	65.909	1.00	69.43	C
Atom	459	OD1	ASN	A	321	46.883	47.860	66.344	1.00	64.68	O
Atom	460	ND2	ASN	A	321	47.560	49.999	66.239	1.00	76.89	N
Atom	461	C	ASN	A	321	47.488	48.968	63.287	1.00	69.38	C
Atom	462	O	ASN	A	321	47.551	47.790	62.933	1.00	63.73	O
Atom	463	N	ILE	A	322	48.567	49.722	63.470	1.00	68.61	N
Atom	464	CA	ILE	A	322	49.909	49.205	63.239	1.00	64.66	C
Atom	465	CB	ILE	A	322	50.945	50.340	63.182	1.00	64.63	C
Atom	466	CG1	ILE	A	322	50.575	51.347	62.094	1.00	60.55	C
Atom	467	CD1	ILE	A	322	51.485	52.546	62.046	1.00	60.98	C
Atom	468	CG2	ILE	A	322	52.345	49.778	62.953	1.00	66.33	C
Atom	469	C	ILE	A	322	50.316	48.229	64.336	1.00	69.19	C
Atom	470	O	ILE	A	322	50.138	48.508	65.522	1.00	66.41	O
Atom	471	N	VAL	A	323	50.863	47.086	63.928	1.00	66.73	N
Atom	472	CA	VAL	A	323	51.341	46.073	64.864	1.00	65.64	C
Atom	473	CB	VAL	A	323	50.523	44.771	64.765	1.00	64.69	C
Atom	474	CG1	VAL	A	323	49.143	44.966	65.372	1.00	66.00	C
Atom	475	CG2	VAL	A	323	50.422	44.314	63.318	1.00	62.04	C
Atom	476	C	VAL	A	323	52.820	45.763	64.646	1.00	65.79	C
Atom	477	O	VAL	A	323	53.519	45.342	65.568	1.00	69.39	O
Atom	478	N	LYS	A	324	53.292	45.969	63.421	1.00	65.09	N
Atom	479	CA	LYS	A	324	54.705	45.793	63.111	1.00	62.25	C
Atom	480	CB	LYS	A	324	54.937	44.447	62.421	1.00	61.18	C
Atom	481	CG	LYS	A	324	56.328	43.862	62.624	1.00	57.68	C
Atom	482	CD	LYS	A	324	57.405	44.718	61.985	1.00	63.13	C
Atom	483	CE	LYS	A	324	57.336	44.666	60.469	1.00	63.49	C
Atom	484	NZ	LYS	A	324	58.440	45.448	59.846	1.00	61.58	N
Atom	485	C	LYS	A	324	55.159	46.935	62.213	1.00	63.54	C
Atom	486	O	LYS	A	324	54.916	46.904	61.006	1.00	63.70	O
Atom	487	N	PRO	A	325	55.821	47.948	62.801	1.00	66.65	N
Atom	488	CA	PRO	A	325	56.225	49.162	62.084	1.00	66.53	C
Atom	489	CB	PRO	A	325	56.701	50.099	63.208	1.00	59.35	C
Atom	490	CG	PRO	A	325	56.278	49.443	64.499	1.00	62.90	C
Atom	491	CD	PRO	A	325	56.260	47.980	64.204	1.00	63.14	C
Atom	492	C	PRO	A	325	57.371	48.912	61.106	1.00	68.09	C
Atom	493	O	PRO	A	325	58.197	48.019	61.316	1.00	61.87	O
Atom	494	N	HIS	A	326	57.401	49.701	60.038	1.00	65.42	N
Atom	495	CA	HIS	A	326	58.505	49.687	59.091	1.00	67.92	C
Atom	496	CB	HIS	A	326	58.019	50.132	57.711	1.00	68.95	C
Atom	497	CG	HIS	A	326	59.071	50.102	56.656	1.00	71.14	C
Atom	498	ND1	HIS	A	326	60.182	49.278	56.727	1.00	71.06	N
Atom	499	CE1	HIS	A	326	60.929	49.456	55.661	1.00	70.78	C
Atom	500	NE2	HIS	A	326	60.348	50.358	54.884	1.00	71.72	N
Atom	501	CD2	HIS	A	326	59.185	50.769	55.483	1.00	72.16	C
Atom	502	C	HIS	A	326	59.594	50.614	59.619	1.00	75.36	C
Atom	503	O	HIS	A	326	59.442	51.837	59.594	1.00	78.21	O
Atom	504	N	GLU	A	327	60.686	50.027	60.102	1.00	78.90	N
Atom	505	CA	GLU	A	327	61.709	50.779	60.829	1.00	84.25	C
Atom	506	CB	GLU	A	327	62.819	49.856	61.339	1.00	88.12	C
Atom	507	CG	GLU	A	327	62.559	49.294	62.724	1.00	112.49	C
Atom	508	CD	GLU	A	327	63.806	49.270	63.594	1.00	127.96	C
Atom	509	OE1	GLU	A	327	63.757	49.835	64.710	1.00	136.76	O
Atom	510	OE2	GLU	A	327	64.834	48.708	63.158	1.00	120.52	O
Atom	511	C	GLU	A	327	62.320	51.961	60.085	1.00	86.38	C
Atom	512	O	GLU	A	327	63.005	52.782	60.689	1.00	93.45	O
Atom	513	N	LYS	A	328	62.072	52.055	58.784	1.00	83.36	N
Atom	514	CA	LYS	A	328	62.632	53.153	58.006	1.00	85.68	C
Atom	515	CB	LYS	A	328	63.549	52.622	56.901	1.00	87.27	C
Atom	516	CG	LYS	A	328	64.695	51.773	57.420	1.00	95.08	C
Atom	517	CD	LYS	A	328	65.922	51.868	56.528	1.00	101.62	C
Atom	518	CE	LYS	A	328	67.096	51.120	57.147	1.00	111.25	C
Atom	519	NZ	LYS	A	328	68.393	51.487	56.511	1.00	121.70	N
Atom	520	C	LYS	A	328	61.566	54.078	57.424	1.00	87.41	C
Atom	521	O	LYS	A	328	61.814	55.265	57.206	1.00	91.38	O
Atom	522	N	GLY	A	329	60.380	53.533	57.180	1.00	82.11	N
Atom	523	CA	GLY	A	329	59.308	54.300	56.574	1.00	77.04	C
Atom	524	C	GLY	A	329	58.532	55.159	57.554	1.00	75.14	C
Atom	525	O	GLY	A	329	58.692	55.040	58.770	1.00	75.56	O
Atom	526	N	ILE	A	330	57.695	56.040	57.016	1.00	73.05	N
Atom	527	CA	ILE	A	330	56.787	56.839	57.826	1.00	77.87	C
Atom	528	CB	ILE	A	330	56.462	58.178	57.143	1.00	81.89	C
Atom	529	CG1	ILE	A	330	57.750	58.956	56.867	1.00	75.94	C
Atom	530	CD1	ILE	A	330	57.530	60.269	56.143	1.00	81.39	C
Atom	531	CG2	ILE	A	330	55.506	58.999	57.998	1.00	81.79	C
Atom	532	C	ILE	A	330	55.502	56.047	58.037	1.00	76.29	C
Atom	533	O	ILE	A	330	54.621	56.035	57.179	1.00	75.07	O
Atom	534	N	ASN	A	331	55.409	55.382	59.182	1.00	75.58	N
Atom	535	CA	ASN	A	331	54.329	54.432	59.443	1.00	75.39	C
Atom	536	CB	ASN	A	331	54.559	53.713	60.774	1.00	71.81	C
Atom	537	CG	ASN	A	331	55.714	52.737	60.711	1.00	73.35	C
Atom	538	OD1	ASN	A	331	55.579	51.628	60.193	1.00	70.20	O
Atom	539	ND2	ASN	A	331	56.861	53.145	61.241	1.00	78.51	N
Atom	540	C	ASN	A	331	52.900	54.980	59.360	1.00	76.17	C
Atom	541	O	ASN	A	331	52.041	54.359	58.738	1.00	71.05	O
Atom	542	N	PRO	A	332	52.634	56.132	59.996	1.00	79.92	N
Atom	543	CA	PRO	A	332	51.276	56.678	59.907	1.00	72.21	C
Atom	544	CB	PRO	A	332	51.413	58.055	60.557	1.00	74.54	C
Atom	545	CG	PRO	A	332	52.550	57.901	61.512	1.00	71.06	C
Atom	546	CD	PRO	A	332	53.511	56.957	60.847	1.00	75.13	C
Atom	547	C	PRO	A	332	50.830	56.816	58.454	1.00	70.16	C
Atom	548	O	PRO	A	332	49.634	56.771	58.171	1.00	71.97	O
Atom	549	N	ASN	A	333	51.788	56.978	57.546	1.00	68.26	N
Atom	550	CA	ASN	A	333	51.479	57.101	56.126	1.00	70.33	C
Atom	551	CB	ASN	A	333	52.722	57.499	55.331	1.00	79.42	C
Atom	552	CG	ASN	A	333	52.942	58.998	55.305	1.00	86.19	C
Atom	553	OD1	ASN	A	333	54.072	59.467	55.161	1.00	82.66	O
Atom	554	ND2	ASN	A	333	51.860	59.760	55.443	1.00	77.93	N
Atom	555	C	ASN	A	333	50.899	55.817	55.563	1.00	70.97	C
Atom	556	O	ASN	A	333	50.016	55.846	54.705	1.00	73.13	O
Atom	557	N	TYR	A	334	51.406	54.688	56.045	1.00	67.42	N
Atom	558	CA	TYR	A	334	50.898	53.389	55.626	1.00	65.76	C
Atom	559	CB	TYR	A	334	51.781	52.269	56.173	1.00	65.46	C
Atom	560	CG	TYR	A	334	53.187	52.256	55.624	1.00	67.44	C
Atom	561	CD1	TYR	A	334	53.419	52.028	54.274	1.00	66.87	C
Atom	562	CE1	TYR	A	334	54.699	52.009	53.762	1.00	72.16	C
Atom	563	CZ	TYR	A	334	55.772	52.214	54.603	1.00	73.79	C
Atom	564	OH	TYR	A	334	57.046	52.192	54.082	1.00	71.32	O
Atom	565	CE2	TYR	A	334	55.571	52.441	55.953	1.00	68.67	C
Atom	566	CD2	TYR	A	334	54.282	52.459	56.455	1.00	67.30	C
Atom	567	C	TYR	A	334	49.461	53.200	56.102	1.00	69.92	C
Atom	568	O	TYR	A	334	48.589	52.786	55.338	1.00	66.35	O
Atom	569	N	LEU	A	335	49.226	53.506	57.375	1.00	71.93	N
Atom	570	CA	LEU	A	335	47.899	53.405	57.966	1.00	64.25	C
Atom	571	CB	LEU	A	335	47.940	53.836	59.432	1.00	62.42	C
Atom	572	CG	LEU	A	335	46.673	53.597	60.249	1.00	65.28	C
Atom	573	CD1	LEU	A	335	46.294	52.136	60.173	1.00	67.94	C
Atom	574	CD2	LEU	A	335	46.873	54.018	61.694	1.00	65.10	C
Atom	575	C	LEU	A	335	46.892	54.253	57.197	1.00	67.90	C
Atom	576	O	LEU	A	335	45.798	53.791	56.872	1.00	70.23	O
Atom	577	N	LEU	A	336	47.269	55.494	56.904	1.00	65.82	N
Atom	578	CA	LEU	A	336	46.394	56.402	56.167	1.00	71.41	C
Atom	579	CB	LEU	A	336	46.977	57.816	56.140	1.00	75.35	C
Atom	580	CG	LEU	A	336	46.912	58.609	57.447	1.00	73.26	C
Atom	581	CD1	LEU	A	336	47.571	59.966	57.277	1.00	67.92	C
Atom	582	CD2	LEU	A	336	45.473	58.761	57.916	1.00	62.81	C
Atom	583	C	LEU	A	336	46.147	55.915	54.743	1.00	67.68	C
Atom	584	O	LEU	A	336	45.049	56.070	54.208	1.00	68.49	O
Atom	585	N	ALA	A	337	47.172	55.329	54.134	1.00	70.76	N
Atom	586	CA	ALA	A	337	47.052	54.800	52.783	1.00	71.70	C
Atom	587	CB	ALA	A	337	48.375	54.201	52.333	1.00	66.78	C
Atom	588	C	ALA	A	337	45.935	53.764	52.711	1.00	70.85	C
Atom	589	O	ALA	A	337	45.128	53.762	51.781	1.00	65.11	O
Atom	590	N	TRP	A	338	45.892	52.886	53.706	1.00	67.05	N
Atom	591	CA	TRP	A	338	44.866	51.856	53.757	1.00	64.22	C
Atom	592	CB	TRP	A	338	45.174	50.835	54.852	1.00	63.47	C
Atom	593	CG	TRP	A	338	44.087	49.821	55.038	1.00	65.45	C
Atom	594	CD1	TRP	A	338	43.415	49.542	56.192	1.00	61.16	C
Atom	595	NE1	TRP	A	338	42.486	48.556	55.971	1.00	63.59	N
Atom	596	CE2	TRP	A	338	42.538	48.184	54.649	1.00	61.98	C
Atom	597	CD2	TRP	A	338	43.533	48.965	54.034	1.00	62.98	C
Atom	598	CE3	TRP	A	338	43.786	48.776	52.670	1.00	60.31	C
Atom	599	CZ3	TRP	A	338	43.049	47.832	51.981	1.00	59.56	C
Atom	600	CH2	TRP	A	338	42.065	47.072	52.626	1.00	61.47	C
Atom	601	CZ2	TRP	A	338	41.795	47.233	53.957	1.00	60.19	C
Atom	602	C	TRP	A	338	43.486	52.467	53.977	1.00	66.00	C
Atom	603	O	TRP	A	338	42.531	52.133	53.277	1.00	65.97	O
Atom	604	N	LYS	A	339	43.387	53.369	54.946	1.00	65.93	N
Atom	605	CA	LYS	A	339	42.119	54.035	55.219	1.00	68.94	C
Atom	606	CB	LYS	A	339	42.263	55.028	56.371	1.00	67.16	C
Atom	607	CG	LYS	A	339	42.345	54.378	57.741	1.00	67.13	C
Atom	608	CD	LYS	A	339	42.286	55.433	58.835	1.00	75.62	C
Atom	609	CE	LYS	A	339	42.698	54.858	60.181	1.00	78.54	C
Atom	610	NZ	LYS	A	339	42.982	55.925	61.184	1.00	84.99	N
Atom	611	C	LYS	A	339	41.589	54.735	53.973	1.00	67.94	C
Atom	612	O	LYS	A	339	40.396	54.675	53.677	1.00	71.15	O
Atom	613	N	GLN	A	340	42.483	55.394	53.244	1.00	65.33	N
Atom	614	CA	GLN	A	340	42.112	56.042	51.994	1.00	68.67	C
Atom	615	CB	GLN	A	340	43.311	56.773	51.392	1.00	71.11	C
Atom	616	CG	GLN	A	340	43.035	57.366	50.024	1.00	74.83	C
Atom	617	CD	GLN	A	340	44.159	58.252	49.532	1.00	76.69	C
Atom	618	OE1	GLN	A	340	45.071	58.598	50.285	1.00	76.71	O
Atom	619	NE2	GLN	A	340	44.097	58.630	48.262	1.00	80.28	N
Atom	620	C	GLN	A	340	41.568	55.020	51.002	1.00	71.36	C
Atom	621	O	GLN	A	340	40.645	55.310	50.243	1.00	71.81	O
Atom	622	N	VAL	A	341	42.143	53.822	51.017	1.00	72.45	N
Atom	623	CA	VAL	A	341	41.675	52.748	50.154	1.00	71.84	C
Atom	624	CB	VAL	A	341	42.567	51.495	50.267	1.00	72.69	C
Atom	625	CG1	VAL	A	341	41.917	50.314	49.563	1.00	67.21	C
Atom	626	CG2	VAL	A	341	43.949	51.773	49.693	1.00	66.64	C
Atom	627	C	VAL	A	341	40.236	52.383	50.493	1.00	71.68	C
Atom	628	O	VAL	A	341	39.385	52.298	49.608	1.00	76.28	O
Atom	629	N	LEU	A	342	39.969	52.172	51.779	1.00	71.75	N
Atom	630	CA	LEU	A	342	38.620	51.852	52.236	1.00	70.14	C
Atom	631	CB	LEU	A	342	38.591	51.642	53.751	1.00	62.97	C
Atom	632	CG	LEU	A	342	39.316	50.417	54.305	1.00	66.34	C
Atom	633	CD1	LEU	A	342	39.180	50.361	55.819	1.00	63.20	C
Atom	634	CD2	LEU	A	342	38.788	49.145	53.663	1.00	60.44	C
Atom	635	C	LEU	A	342	37.658	52.967	51.862	1.00	73.97	C
Atom	636	O	LEU	A	342	36.586	52.721	51.312	1.00	75.78	O
Atom	637	N	ALA	A	343	38.055	54.197	52.170	1.00	74.68	N
Atom	638	CA	ALA	A	343	37.231	55.365	51.898	1.00	73.37	C
Atom	639	CB	ALA	A	343	37.971	56.628	52.286	1.00	67.53	C
Atom	640	C	ALA	A	343	36.804	55.421	50.435	1.00	77.32	C
Atom	641	O	ALA	A	343	35.617	55.536	50.129	1.00	80.74	O
Atom	642	N	GLU	A	344	37.775	55.331	49.533	1.00	73.48	N
Atom	643	CA	GLU	A	344	37.492	55.419	48.106	1.00	81.86	C
Atom	644	CB	GLU	A	344	38.778	55.669	47.312	1.00	79.92	C
Atom	645	CG	GLU	A	344	39.444	56.998	47.658	1.00	86.11	C
Atom	646	CD	GLU	A	344	40.512	57.404	46.660	1.00	91.79	C
Atom	647	OE1	GLU	A	344	40.411	57.000	45.483	1.00	95.46	O
Atom	648	OE2	GLU	A	344	41.447	58.135	47.051	1.00	86.57	O
Atom	649	C	GLU	A	344	36.752	54.183	47.595	1.00	81.70	C
Atom	650	O	GLU	A	344	36.052	54.244	46.585	1.00	86.75	O
Atom	651	N	LEU	A	345	36.899	53.065	48.300	1.00	83.05	N
Atom	652	CA	LEU	A	345	36.147	51.859	47.971	1.00	79.69	C
Atom	653	CB	LEU	A	345	36.700	50.646	48.723	1.00	77.48	C
Atom	654	CG	LEU	A	345	37.889	49.925	48.081	1.00	79.66	C
Atom	655	CD1	LEU	A	345	38.555	48.992	49.079	1.00	78.96	C
Atom	656	CD2	LEU	A	345	37.460	49.160	46.832	1.00	73.98	C
Atom	657	C	LEU	A	345	34.664	52.055	48.277	1.00	82.17	C
Atom	658	O	LEU	A	345	33.800	51.538	47.570	1.00	81.88	O
Atom	659	N	GLN	A	346	34.377	52.811	49.332	1.00	81.52	N
Atom	660	CA	GLN	A	346	33.002	53.149	49.679	1.00	85.32	C
Atom	661	CB	GLN	A	346	32.945	53.844	51.039	1.00	86.41	C
Atom	662	CG	GLN	A	346	32.820	52.895	52.214	1.00	86.24	C
Atom	663	CD	GLN	A	346	33.223	53.541	53.523	1.00	92.31	C
Atom	664	OE1	GLN	A	346	34.222	54.258	53.593	1.00	95.22	O
Atom	665	NE2	GLN	A	346	32.451	53.286	54.572	1.00	93.03	N
Atom	666	C	GLN	A	346	32.372	54.035	48.611	1.00	90.94	C
Atom	667	O	GLN	A	346	31.194	53.891	48.292	1.00	95.87	O
Atom	668	N	ASP	A	347	33.162	54.952	48.063	1.00	88.88	N
Atom	669	CA	ASP	A	347	32.686	55.829	47.000	1.00	91.00	C
Atom	670	CB	ASP	A	347	33.823	56.709	46.479	1.00	95.55	C
Atom	671	CG	ASP	A	347	34.259	57.756	47.485	1.00	98.95	C
Atom	672	OD1	ASP	A	347	33.521	57.978	48.470	1.00	100.39	O
Atom	673	OD2	ASP	A	347	35.336	58.360	47.286	1.00	97.77	O
Atom	674	C	ASP	A	347	32.092	55.026	45.852	1.00	97.70	C
Atom	675	O	ASP	A	347	31.047	55.381	45.310	1.00	108.08	O
Atom	676	N	ILE	A	348	32.763	53.938	45.488	1.00	93.97	N
Atom	677	CA	ILE	A	348	32.333	53.119	44.362	1.00	101.99	C
Atom	678	CB	ILE	A	348	33.473	52.225	43.848	1.00	101.00	C
Atom	679	CG1	ILE	A	348	34.821	52.719	44.370	1.00	100.24	C
Atom	680	CD1	ILE	A	348	35.944	51.718	44.193	1.00	101.51	C
Atom	681	CG2	ILE	A	348	33.459	52.172	42.330	1.00	109.28	C
Atom	682	C	ILE	A	348	31.156	52.222	44.727	1.00	110.28	C
Atom	683	O	ILE	A	348	30.308	51.926	43.885	1.00	114.34	O
Atom	684	N	GLU	A	349	31.117	51.783	45.982	1.00	108.28	N
Atom	685	CA	GLU	A	349	30.064	50.887	46.446	1.00	108.25	C
Atom	686	CB	GLU	A	349	30.048	50.800	47.973	1.00	103.90	C
Atom	687	CG	GLU	A	349	29.086	49.755	48.505	1.00	101.97	C
Atom	688	CD	GLU	A	349	28.731	49.963	49.963	1.00	98.68	C
Atom	689	OE1	GLU	A	349	29.107	51.009	50.535	1.00	94.99	O
Atom	690	OE2	GLU	A	349	28.065	49.077	50.535	1.00	92.47	O
Atom	691	C	GLU	A	349	28.703	51.343	45.931	1.00	122.22	C
Atom	692	O	GLU	A	349	28.349	52.519	46.040	1.00	116.36	O
Atom	693	N	ASN	A	350	27.950	50.401	45.370	1.00	126.66	N
Atom	694	CA	ASN	A	350	26.687	50.703	44.703	1.00	123.73	C
Atom	695	CB	ASN	A	350	25.731	51.464	45.625	1.00	125.50	C
Atom	696	CG	ASN	A	350	24.744	50.548	46.327	1.00	129.38	C
Atom	697	OD1	ASN	A	350	24.808	49.325	46.192	1.00	119.48	O
Atom	698	ND2	ASN	A	350	23.820	51.140	47.078	1.00	123.78	N
Atom	699	C	ASN	A	350	26.878	51.449	43.386	1.00	126.05	C
Atom	700	O	ASN	A	350	27.284	50.855	42.388	1.00	127.58	O
Atom	701	N	GLU	A	351	26.593	52.749	43.385	1.00	128.53	N
Atom	702	CA	GLU	A	351	26.597	53.512	42.143	1.00	134.66	C
Atom	703	CB	GLU	A	351	28.029	53.738	41.652	1.00	129.91	C
Atom	704	CG	GLU	A	351	28.507	55.184	41.718	1.00	130.54	C
Atom	705	CD	GLU	A	351	28.584	55.737	43.132	1.00	126.54	C
Atom	706	OE1	GLU	A	351	28.078	55.083	44.070	1.00	126.25	O
Atom	707	OE2	GLU	A	351	29.154	56.837	43.300	1.00	119.67	O
Atom	708	C	GLU	A	351	25.795	52.753	41.093	1.00	140.20	C
Atom	709	O	GLU	A	351	24.664	52.334	41.344	1.00	144.17	O
Atom	710	N	GLU	A	352	26.387	52.575	39.919	1.00	135.51	N
Atom	711	CA	GLU	A	352	25.811	51.716	38.892	1.00	138.12	C
Atom	712	CB	GLU	A	352	24.927	52.509	37.928	1.00	145.30	C
Atom	713	CG	GLU	A	352	23.471	52.620	38.354	1.00	145.11	C
Atom	714	CD	GLU	A	352	23.161	53.921	39.068	1.00	150.85	C
Atom	715	OE1	GLU	A	352	24.099	54.559	39.593	1.00	148.34	O
Atom	716	OE2	GLU	A	352	21.973	54.306	39.095	1.00	151.17	O
Atom	717	C	GLU	A	352	26.925	51.018	38.125	1.00	134.80	C
Atom	718	O	GLU	A	352	27.083	49.799	38.208	1.00	134.03	O
Atom	719	N	LYS	A	353	27.701	51.800	37.383	1.00	134.65	N
Atom	720	CA	LYS	A	353	28.820	51.256	36.626	1.00	143.81	C
Atom	721	CB	LYS	A	353	28.873	51.859	35.218	1.00	148.43	C
Atom	722	CG	LYS	A	353	27.607	51.629	34.404	1.00	143.87	C
Atom	723	CD	LYS	A	353	27.905	51.475	32.918	1.00	149.09	C
Atom	724	CE	LYS	A	353	28.415	52.768	32.301	1.00	150.83	C
Atom	725	NZ	LYS	A	353	28.725	52.589	30.853	1.00	141.33	N
Atom	726	C	LYS	A	353	30.142	51.466	37.358	1.00	137.46	C
Atom	727	O	LYS	A	353	30.705	52.561	37.348	1.00	124.43	O
Atom	728	N	ILE	A	354	30.623	50.406	38.001	1.00	131.78	N
Atom	729	CA	ILE	A	354	31.920	50.434	38.665	1.00	123.01	C
Atom	730	CB	ILE	A	354	32.081	49.265	39.659	1.00	114.97	C
Atom	731	CG1	ILE	A	354	31.433	49.605	41.005	1.00	113.64	C
Atom	732	CD1	ILE	A	354	29.923	49.524	41.008	1.00	120.78	C
Atom	733	CG2	ILE	A	354	33.552	48.931	39.860	1.00	110.56	C
Atom	734	C	ILE	A	354	33.039	50.373	37.631	1.00	121.42	C
Atom	735	O	ILE	A	354	33.079	49.460	36.805	1.00	120.88	O
Atom	736	N	PRO	A	355	33.952	51.353	37.673	1.00	118.07	N
Atom	737	CA	PRO	A	355	35.060	51.469	36.719	1.00	115.23	C
Atom	738	CB	PRO	A	355	35.683	52.818	37.093	1.00	113.49	C
Atom	739	CG	PRO	A	355	35.338	52.978	38.541	1.00	110.06	C
Atom	740	CD	PRO	A	355	33.928	52.490	38.606	1.00	113.30	C
Atom	741	C	PRO	A	355	36.107	50.376	36.899	1.00	120.59	C
Atom	742	O	PRO	A	355	36.190	49.758	37.962	1.00	117.71	O
Atom	743	N	LYS	A	356	36.898	50.143	35.858	1.00	123.58	N
Atom	744	CA	LYS	A	356	38.095	49.329	35.990	1.00	121.36	C
Atom	745	CB	LYS	A	356	38.673	48.971	34.616	1.00	124.32	C
Atom	746	CG	LYS	A	356	38.057	47.746	33.949	1.00	122.58	C
Atom	747	CD	LYS	A	356	38.599	47.561	32.532	1.00	129.23	C
Atom	748	CE	LYS	A	356	40.066	47.141	32.525	1.00	129.83	C
Atom	749	NZ	LYS	A	356	40.233	45.660	32.620	1.00	122.70	N
Atom	750	C	LYS	A	356	39.125	50.115	36.796	1.00	123.03	C
Atom	751	O	LYS	A	356	39.215	51.338	36.678	1.00	115.29	O
Atom	752	N	THR	A	357	39.885	49.402	37.621	1.00	113.45	N
Atom	753	CA	THR	A	357	41.021	49.959	38.370	1.00	106.63	C
Atom	754	CB	THR	A	357	42.265	50.176	37.465	1.00	107.20	C
Atom	755	OG1	THR	A	357	43.401	50.486	38.280	1.00	106.43	O
Atom	756	CG2	THR	A	357	42.038	51.298	36.454	1.00	111.78	C
Atom	757	C	THR	A	357	40.753	51.196	39.262	1.00	105.55	C
Atom	758	O	THR	A	357	40.940	51.124	40.474	1.00	103.16	O
Atom	759	N	LYS	A	358	40.342	52.317	38.669	1.00	100.02	N
Atom	760	CA	LYS	A	358	40.040	53.548	39.416	1.00	96.81	C
Atom	761	CB	LYS	A	358	39.191	53.258	40.657	1.00	96.86	C
Atom	762	CG	LYS	A	358	38.923	54.484	41.526	1.00	96.47	C
Atom	763	CD	LYS	A	358	37.962	54.159	42.663	1.00	95.55	C
Atom	764	CE	LYS	A	358	37.304	55.415	43.219	1.00	91.78	C
Atom	765	NZ	LYS	A	358	38.283	56.324	43.861	1.00	89.06	N
Atom	766	C	LYS	A	358	41.272	54.356	39.822	1.00	95.71	C
Atom	767	O	LYS	A	358	42.285	53.801	40.246	1.00	96.71	O
Atom	768	N	ASN	A	359	41.163	55.677	39.702	1.00	99.64	N
Atom	769	CA	ASN	A	359	42.245	56.586	40.066	1.00	96.22	C
Atom	770	CB	ASN	A	359	42.328	57.750	39.075	1.00	102.21	C
Atom	771	CG	ASN	A	359	41.751	57.406	37.712	1.00	111.96	C
Atom	772	OD1	ASN	A	359	42.469	57.380	36.713	1.00	110.79	O
Atom	773	ND2	ASN	A	359	40.445	57.144	37.666	1.00	109.12	N
Atom	774	C	ASN	A	359	42.053	57.136	41.476	1.00	87.81	C
Atom	775	O	ASN	A	359	40.938	57.486	41.862	1.00	89.68	O
Atom	776	N	MET	A	360	43.139	57.227	42.236	1.00	86.57	N
Atom	777	CA	MET	A	360	43.053	57.654	43.627	1.00	85.93	C
Atom	778	CB	MET	A	360	43.860	56.721	44.533	1.00	88.04	C
Atom	779	CG	MET	A	360	43.341	55.295	44.577	1.00	83.50	C
Atom	780	SD	MET	A	360	44.052	54.351	45.938	1.00	88.13	S
Atom	781	CE	MET	A	360	43.281	55.145	47.344	1.00	76.71	C
Atom	782	C	MET	A	360	43.492	59.096	43.848	1.00	85.69	C
Atom	783	O	MET	A	360	44.227	59.672	43.045	1.00	84.91	O
Atom	784	N	ARG	A	361	43.033	59.662	44.958	1.00	87.50	N
Atom	785	CA	ARG	A	361	43.345	61.033	45.332	1.00	88.48	C
Atom	786	CB	ARG	A	361	42.456	61.448	46.506	1.00	92.56	C
Atom	787	CG	ARG	A	361	42.424	62.933	46.810	1.00	99.28	C
Atom	788	CD	ARG	A	361	41.231	63.264	47.695	1.00	108.29	C
Atom	789	NE	ARG	A	361	41.384	64.544	48.380	1.00	120.83	N
Atom	790	CZ	ARG	A	361	41.883	64.682	49.604	1.00	122.28	C
Atom	791	NH1	ARG	A	361	42.278	63.615	50.286	1.00	113.20	N
Atom	792	NH2	ARG	A	361	41.985	65.887	50.147	1.00	125.44	N
Atom	793	C	ARG	A	361	44.820	61.153	45.706	1.00	84.62	C
Atom	794	O	ARG	A	361	45.303	60.445	46.589	1.00	83.95	O
Atom	795	N	LYS	A	362	45.536	62.045	45.028	1.00	84.36	N
Atom	796	CA	LYS	A	362	46.966	62.212	45.267	1.00	87.05	C
Atom	797	CB	LYS	A	362	47.616	62.995	44.124	1.00	85.87	C
Atom	798	CG	LYS	A	362	47.288	62.448	42.744	1.00	85.22	C
Atom	799	CD	LYS	A	362	48.396	62.753	41.751	1.00	88.28	C
Atom	800	CE	LYS	A	362	48.048	62.238	40.363	1.00	99.03	C
Atom	801	NZ	LYS	A	362	46.950	63.035	39.740	1.00	109.31	N
Atom	802	C	LYS	A	362	47.239	62.885	46.611	1.00	84.90	C
Atom	803	O	LYS	A	362	47.656	64.040	46.670	1.00	84.95	O
Atom	804	N	THR	A	363	47.007	62.142	47.689	1.00	83.06	N
Atom	805	CA	THR	A	363	47.139	62.669	49.041	1.00	78.01	C
Atom	806	CB	THR	A	363	46.300	61.848	50.035	1.00	82.25	C
Atom	807	OG1	THR	A	363	46.872	60.543	50.180	1.00	82.74	O
Atom	808	CG2	THR	A	363	44.871	61.716	49.539	1.00	83.53	C
Atom	809	C	THR	A	363	48.584	62.681	49.525	1.00	79.18	C
Atom	810	O	THR	A	363	49.488	62.207	48.839	1.00	80.58	O
Atom	811	N	SER	A	364	48.787	63.223	50.719	1.00	80.66	N
Atom	812	CA	SER	A	364	50.108	63.280	51.325	1.00	76.51	C
Atom	813	CB	SER	A	364	50.020	63.936	52.703	1.00	74.83	C
Atom	814	OG	SER	A	364	51.171	63.655	53.479	1.00	93.98	O
Atom	815	C	SER	A	364	50.746	61.897	51.446	1.00	84.19	C
Atom	816	O	SER	A	364	51.908	61.703	51.083	1.00	82.15	O
Atom	817	N	GLN	A	365	49.979	60.939	51.957	1.00	82.05	N
Atom	818	CA	GLN	A	365	50.497	59.599	52.218	1.00	82.99	C
Atom	819	CB	GLN	A	365	49.455	58.754	52.953	1.00	79.55	C
Atom	820	CG	GLN	A	365	48.552	59.552	53.877	1.00	83.15	C
Atom	821	CD	GLN	A	365	47.308	60.066	53.178	1.00	80.19	C
Atom	822	OE1	GLN	A	365	46.565	59.299	52.566	1.00	76.09	O
Atom	823	NE2	GLN	A	365	47.069	61.369	53.274	1.00	84.96	N
Atom	824	C	GLN	A	365	50.911	58.897	50.929	1.00	80.16	C
Atom	825	O	GLN	A	365	51.980	58.290	50.859	1.00	71.14	O
Atom	826	N	LEU	A	366	50.058	58.979	49.912	1.00	79.32	N
Atom	827	CA	LEU	A	366	50.336	58.325	48.639	1.00	77.71	C
Atom	828	CB	LEU	A	366	49.095	58.309	47.746	1.00	80.89	C
Atom	829	CG	LEU	A	366	47.941	57.449	48.255	1.00	78.19	C
Atom	830	CD1	LEU	A	366	46.884	57.273	47.175	1.00	74.78	C
Atom	831	CD2	LEU	A	366	48.465	56.101	48.719	1.00	76.11	C
Atom	832	C	LEU	A	366	51.507	58.976	47.915	1.00	82.22	C
Atom	833	O	LEU	A	366	52.357	58.283	47.355	1.00	87.68	O
Atom	834	N	LYS	A	367	51.550	60.305	47.923	1.00	84.57	N
Atom	835	CA	LYS	A	367	52.679	61.026	47.347	1.00	83.70	C
Atom	836	CB	LYS	A	367	52.543	62.532	47.572	1.00	83.28	C
Atom	837	CG	LYS	A	367	51.544	63.222	46.661	1.00	90.40	C
Atom	838	CD	LYS	A	367	51.670	64.735	46.770	1.00	98.44	C
Atom	839	CE	LYS	A	367	50.597	65.442	45.955	1.00	109.33	C
Atom	840	NZ	LYS	A	367	50.752	66.923	46.022	1.00	121.11	N
Atom	841	C	LYS	A	367	53.982	60.529	47.961	1.00	80.64	C
Atom	842	O	LYS	A	367	54.938	60.230	47.251	1.00	86.53	O
Atom	843	N	TRP	A	368	54.008	60.434	49.286	1.00	74.56	N
Atom	844	CA	TRP	A	368	55.203	60.001	49.998	1.00	74.58	C
Atom	845	CB	TRP	A	368	55.005	60.118	51.510	1.00	71.73	C
Atom	846	CG	TRP	A	368	56.114	59.484	52.282	1.00	75.43	C
Atom	847	CD1	TRP	A	368	57.311	60.048	52.610	1.00	79.27	C
Atom	848	NE1	TRP	A	368	58.080	59.153	53.313	1.00	85.07	N
Atom	849	CE2	TRP	A	368	57.382	57.982	53.451	1.00	86.44	C
Atom	850	CD2	TRP	A	368	56.139	58.153	52.810	1.00	83.44	C
Atom	851	CE3	TRP	A	368	55.229	57.092	52.807	1.00	79.80	C
Atom	852	CZ3	TRP	A	368	55.586	55.912	53.432	1.00	79.09	C
Atom	853	CH2	TRP	A	368	56.830	55.771	54.061	1.00	75.04	C
Atom	854	CZ2	TRP	A	368	57.739	56.791	54.081	1.00	76.65	C
Atom	855	C	TRP	A	368	55.603	58.573	49.640	1.00	82.30	C
Atom	856	O	TRP	A	368	56.716	58.327	49.177	1.00	89.34	O
Atom	857	N	ALA	A	369	54.691	57.634	49.864	1.00	84.85	N
Atom	858	CA	ALA	A	369	54.969	56.220	49.633	1.00	81.63	C
Atom	859	CB	ALA	A	369	53.753	55.373	49.992	1.00	75.76	C
Atom	860	C	ALA	A	369	55.400	55.954	48.195	1.00	83.05	C
Atom	861	O	ALA	A	369	56.287	55.136	47.943	1.00	79.33	O
Atom	862	N	LEU	A	370	54.772	56.655	47.258	1.00	80.61	N
Atom	863	CA	LEU	A	370	55.065	56.476	45.842	1.00	84.86	C
Atom	864	CB	LEU	A	370	53.830	56.797	45.000	1.00	84.58	C
Atom	865	CG	LEU	A	370	52.632	55.883	45.270	1.00	87.55	C
Atom	866	CD1	LEU	A	370	51.361	56.437	44.644	1.00	80.91	C
Atom	867	CD2	LEU	A	370	52.909	54.471	44.773	1.00	80.59	C
Atom	868	C	LEU	A	370	56.263	57.315	45.394	1.00	94.08	C
Atom	869	O	LEU	A	370	56.464	57.534	44.199	1.00	95.78	O
Atom	870	N	GLY	A	371	57.057	57.770	46.362	1.00	91.39	N
Atom	871	CA	GLY	A	371	58.258	58.542	46.091	1.00	96.47	C
Atom	872	C	GLY	A	371	58.026	59.751	45.205	1.00	108.32	C
Atom	873	O	GLY	A	371	58.719	59.936	44.205	1.00	111.98	O
Atom	874	N	GLU	A	372	57.056	60.580	45.574	1.00	103.88	N
Atom	875	CA	GLU	A	372	56.700	61.738	44.762	1.00	108.20	C
Atom	876	CB	GLU	A	372	55.186	61.946	44.744	1.00	107.60	C
Atom	877	CG	GLU	A	372	54.685	62.523	43.436	1.00	116.88	C
Atom	878	CD	GLU	A	372	55.128	61.693	42.244	1.00	126.53	C
Atom	879	OE1	GLU	A	372	55.583	62.288	41.243	1.00	133.58	O
Atom	880	OE2	GLU	A	372	55.037	60.446	42.317	1.00	117.29	O
Atom	881	C	GLU	A	372	57.409	63.011	45.222	1.00	121.07	C
Atom	882	O	GLU	A	372	57.570	63.954	44.448	1.00	122.33	O
Atom	883	N	ASN	A	373	57.819	63.042	46.486	1.00	121.99	N
Atom	884	CA	ASN	A	373	58.655	64.133	46.973	1.00	123.48	C
Atom	885	CB	ASN	A	373	58.653	64.201	48.504	1.00	122.94	C
Atom	886	CG	ASN	A	373	58.270	62.879	49.150	1.00	120.74	C
Atom	887	OD1	ASN	A	373	57.432	62.842	50.053	1.00	110.60	O
Atom	888	ND2	ASN	A	373	58.872	61.788	48.684	1.00	112.32	N
Atom	889	C	ASN	A	373	60.071	64.007	46.422	1.00	123.04	C
Atom	890	O	ASN	A	373	60.843	64.966	46.427	1.00	129.13	O
Atom	891	N	MET	A	374	60.397	62.813	45.936	1.00	122.62	N
Atom	892	CA	MET	A	374	61.654	62.588	45.237	1.00	127.39	C
Atom	893	CB	MET	A	374	62.011	61.100	45.225	1.00	130.41	C
Atom	894	CG	MET	A	374	62.720	60.603	46.475	1.00	130.98	C
Atom	895	SD	MET	A	374	63.219	58.875	46.327	1.00	156.03	S
Atom	896	CE	MET	A	374	64.209	58.923	44.833	1.00	136.86	C
Atom	897	C	MET	A	374	61.560	63.105	43.807	1.00	132.76	C
Atom	898	O	MET	A	374	62.519	63.010	43.042	1.00	131.77	O
Atom	899	N	ALA	A	375	60.396	63.644	43.451	1.00	131.64	N
Atom	900	CA	ALA	A	375	60.186	64.197	42.117	1.00	133.74	C
Atom	901	CB	ALA	A	375	58.770	64.727	41.967	1.00	133.16	C
Atom	902	C	ALA	A	375	61.201	65.295	41.827	1.00	142.41	C
Atom	903	O	ALA	A	375	61.350	66.235	42.610	1.00	140.63	O
Atom	904	N	PRO	A	376	61.902	65.170	40.692	1.00	145.20	N
Atom	905	CA	PRO	A	376	63.001	66.033	40.241	1.00	136.34	C
Atom	906	CB	PRO	A	376	63.158	65.645	38.772	1.00	131.86	C
Atom	907	CG	PRO	A	376	62.707	64.229	38.724	1.00	130.32	C
Atom	908	CD	PRO	A	376	61.607	64.100	39.723	1.00	140.10	C
Atom	909	C	PRO	A	376	62.710	67.528	40.358	1.00	135.20	C
Atom	910	O	PRO	A	376	63.649	68.313	40.480	1.00	128.26	O
Atom	911	N	GLU	A	377	61.439	67.916	40.322	1.00	138.80	N
Atom	912	CA	GLU	A	377	61.091	69.332	40.381	1.00	138.15	C
Atom	913	CB	GLU	A	377	59.580	69.544	40.239	1.00	146.77	C
Atom	914	CG	GLU	A	377	58.985	69.095	38.914	1.00	149.87	C
Atom	915	CD	GLU	A	377	58.030	67.924	39.067	1.00	153.48	C
Atom	916	OE1	GLU	A	377	57.423	67.785	40.151	1.00	150.37	O
Atom	917	OE2	GLU	A	377	57.879	67.149	38.098	1.00	150.03	O
Atom	918	C	GLU	A	377	61.580	70.006	41.661	1.00	145.61	C
Atom	919	O	GLU	A	377	61.686	71.231	41.720	1.00	147.92	O
Atom	920	N	LYS	A	378	61.883	69.208	42.681	1.00	148.44	N
Atom	921	CA	LYS	A	378	62.187	69.753	44.003	1.00	154.06	C
Atom	922	CB	LYS	A	378	61.211	69.192	45.043	1.00	151.58	C
Atom	923	CG	LYS	A	378	59.760	69.582	44.797	1.00	151.87	C
Atom	924	CD	LYS	A	378	58.830	68.954	45.823	1.00	146.49	C
Atom	925	CE	LYS	A	378	58.789	67.443	45.674	1.00	138.21	C
Atom	926	NZ	LYS	A	378	58.275	67.034	44.337	1.00	136.10	N
Atom	927	C	LYS	A	378	63.631	69.547	44.473	1.00	151.27	C
Atom	928	O	LYS	A	378	64.112	68.416	44.541	1.00	142.61	O
Atom	929	N	VAL	A	379	64.293	70.663	44.787	1.00	154.34	N
Atom	930	CA	VAL	A	379	65.622	70.713	45.418	1.00	149.13	C
Atom	931	CB	VAL	A	379	66.338	69.344	45.468	1.00	148.75	C
Atom	932	CG1	VAL	A	379	67.118	69.098	44.190	1.00	150.57	C
Atom	933	CG2	VAL	A	379	67.254	69.268	46.686	1.00	153.14	C
Atom	934	C	VAL	A	379	66.512	71.766	44.748	1.00	151.00	C
Atom	935	O	VAL	A	379	66.095	72.417	43.790	1.00	151.82	O
Atom	936	N	ASP	A	380	67.731	71.935	45.256	1.00	152.20	N
Atom	937	CA	ASP	A	380	68.606	73.014	44.801	1.00	152.72	C
Atom	938	CB	ASP	A	380	68.731	74.079	45.893	1.00	151.20	C
Atom	939	CG	ASP	A	380	67.429	74.814	46.141	1.00	151.80	C
Atom	940	OD1	ASP	A	380	67.040	75.637	45.286	1.00	148.67	O
Atom	941	OD2	ASP	A	380	66.801	74.577	47.195	1.00	150.66	O
Atom	942	C	ASP	A	380	70.001	72.551	44.381	1.00	148.41	C
Atom	943	O	ASP	A	380	70.150	71.587	43.630	1.00	140.84	O
Atom	944	N	PHE	A	381	71.016	73.264	44.867	1.00	148.15	N
Atom	945	CA	PHE	A	381	72.416	72.945	44.594	1.00	145.69	C
Atom	946	CB	PHE	A	381	73.338	73.901	45.361	1.00	144.53	C
Atom	947	CG	PHE	A	381	74.659	74.156	44.682	1.00	150.10	C
Atom	948	CD1	PHE	A	381	74.938	75.394	44.122	1.00	148.21	C
Atom	949	CE1	PHE	A	381	76.149	75.632	43.498	1.00	146.05	C
Atom	950	CZ	PHE	A	381	77.095	74.632	43.429	1.00	150.54	C
Atom	951	CE2	PHE	A	381	76.831	73.396	43.982	1.00	145.87	C
Atom	952	CD2	PHE	A	381	75.620	73.163	44.605	1.00	147.23	C
Atom	953	C	PHE	A	381	72.701	71.506	45.003	1.00	147.26	C
Atom	954	O	PHE	A	381	73.702	70.914	44.597	1.00	148.23	O
Atom	955	N	GLU	A	382	71.807	70.954	45.815	1.00	150.93	N
Atom	956	CA	GLU	A	382	71.904	69.570	46.253	1.00	154.83	C
Atom	957	CB	GLU	A	382	70.884	69.305	47.365	1.00	156.09	C
Atom	958	CG	GLU	A	382	71.234	68.146	48.285	1.00	159.12	C
Atom	959	CD	GLU	A	382	70.460	66.883	47.964	1.00	155.82	C
Atom	960	OE1	GLU	A	382	71.095	65.869	47.607	1.00	155.10	O
Atom	961	OE2	GLU	A	382	69.215	66.906	48.069	1.00	154.20	O
Atom	962	C	GLU	A	382	71.670	68.644	45.062	1.00	152.82	C
Atom	963	O	GLU	A	382	71.726	67.421	45.184	1.00	151.25	O
Atom	964	N	ASP	A	383	71.415	69.247	43.905	1.00	149.55	N
Atom	965	CA	ASP	A	383	71.196	68.507	42.670	1.00	146.43	C
Atom	966	CB	ASP	A	383	70.415	69.373	41.681	1.00	135.21	C
Atom	967	CG	ASP	A	383	69.695	68.558	40.629	1.00	133.11	C
Atom	968	OD1	ASP	A	383	70.121	67.417	40.356	1.00	137.12	O
Atom	969	OD2	ASP	A	383	68.702	69.066	40.070	1.00	126.06	O
Atom	970	C	ASP	A	383	72.534	68.093	42.063	1.00	145.80	C
Atom	971	O	ASP	A	383	72.696	68.076	40.842	1.00	135.99	O
Atom	972	N	CYS	A	384	73.490	67.769	42.930	1.00	149.74	N
Atom	973	CA	CYS	A	384	74.832	67.388	42.502	1.00	146.31	C
Atom	974	CB	CYS	A	384	75.744	68.616	42.455	1.00	139.53	C
Atom	975	SG	CYS	A	384	75.045	70.036	41.584	1.00	134.66	S
Atom	976	C	CYS	A	384	75.433	66.339	43.436	1.00	143.87	C
Atom	977	O	CYS	A	384	76.566	66.483	43.898	1.00	138.09	O
Atom	978	N	LYS	A	385	74.668	65.286	43.711	1.00	149.14	N
Atom	979	CA	LYS	A	385	75.116	64.215	44.599	1.00	154.49	C
Atom	980	CB	LYS	A	385	73.984	63.777	45.540	1.00	150.61	C
Atom	981	CG	LYS	A	385	72.787	63.133	44.847	1.00	144.06	C
Atom	982	CD	LYS	A	385	72.027	64.131	43.991	1.00	142.52	C
Atom	983	CE	LYS	A	385	71.380	63.446	42.798	1.00	143.69	C
Atom	984	NZ	LYS	A	385	70.566	62.264	43.198	1.00	143.49	N
Atom	985	C	LYS	A	385	75.657	63.025	43.805	1.00	153.61	C
Atom	986	O	LYS	A	385	74.897	62.201	43.297	1.00	151.42	O
Atom	987	N	ASP	A	386	76.980	62.941	43.702	1.00	151.38	N
Atom	988	CA	ASP	A	386	77.613	61.916	42.881	1.00	147.90	C
Atom	989	CB	ASP	A	386	78.142	62.534	41.585	1.00	141.29	C
Atom	990	CG	ASP	A	386	77.524	63.889	41.288	1.00	136.26	C
Atom	991	OD1	ASP	A	386	76.749	63.994	40.314	1.00	126.10	O
Atom	992	OD2	ASP	A	386	77.812	64.850	42.032	1.00	137.26	O
Atom	993	C	ASP	A	386	78.755	61.234	43.627	1.00	152.94	C
Atom	994	O	ASP	A	386	79.869	61.754	43.677	1.00	158.53	O
Atom	995	N	VAL	A	387	78.477	60.067	44.201	1.00	154.31	N
Atom	996	CA	VAL	A	387	79.482	59.341	44.970	1.00	161.69	C
Atom	997	CB	VAL	A	387	78.848	58.223	45.831	1.00	162.05	C
Atom	998	CG1	VAL	A	387	79.884	57.625	46.775	1.00	150.79	C
Atom	999	CG2	VAL	A	387	77.662	58.762	46.618	1.00	159.92	C
Atom	1000	C	VAL	A	387	80.562	58.746	44.066	1.00	164.18	C
Atom	1001	O	VAL	A	387	81.465	59.453	43.614	1.00	153.43	O
Atom	1002	N	SER	A	388	80.459	57.447	43.804	1.00	166.98	N
Atom	1003	CA	SER	A	388	81.447	56.744	42.993	1.00	163.92	C
Atom	1004	CB	SER	A	388	81.432	55.246	43.311	1.00	162.13	C
Atom	1005	OG	SER	A	388	80.164	54.676	43.034	1.00	161.75	O
Atom	1006	C	SER	A	388	81.199	56.970	41.505	1.00	158.97	C
Atom	1007	O	SER	A	388	82.128	56.923	40.698	1.00	152.99	O
Atom	1008	N	GLU	A	397	80.349	46.159	49.850	1.00	138.48	N
Atom	1009	CA	GLU	A	397	79.540	46.200	51.063	1.00	134.17	C
Atom	1010	CB	GLU	A	397	80.082	47.254	52.032	1.00	135.08	C
Atom	1011	CG	GLU	A	397	80.528	48.545	51.364	1.00	145.09	C
Atom	1012	CD	GLU	A	397	81.178	49.510	52.339	1.00	148.85	C
Atom	1013	OE1	GLU	A	397	80.993	49.330	53.562	1.00	147.75	O
Atom	1014	OE2	GLU	A	397	81.872	50.445	51.883	1.00	144.18	O
Atom	1015	C	GLU	A	397	78.067	46.469	50.759	1.00	129.90	C
Atom	1016	O	GLU	A	397	77.600	47.601	50.895	1.00	123.43	O
Atom	1017	N	PRO	A	398	77.337	45.426	50.330	1.00	127.48	N
Atom	1018	CA	PRO	A	398	75.887	45.458	50.145	1.00	113.62	C
Atom	1019	CB	PRO	A	398	75.712	44.623	48.886	1.00	103.52	C
Atom	1020	CG	PRO	A	398	76.732	43.526	49.073	1.00	115.07	C
Atom	1021	CD	PRO	A	398	77.889	44.135	49.878	1.00	119.12	C
Atom	1022	C	PRO	A	398	75.190	44.775	51.314	1.00	103.10	C
Atom	1023	O	PRO	A	398	74.106	44.220	51.140	1.00	106.49	O
Atom	1024	N	LYS	A	399	75.827	44.817	52.482	1.00	105.66	N
Atom	1025	CA	LYS	A	399	75.306	44.235	53.724	1.00	96.49	C
Atom	1026	CB	LYS	A	399	74.203	45.108	54.343	1.00	94.11	C
Atom	1027	CG	LYS	A	399	72.955	45.276	53.493	1.00	106.89	C
Atom	1028	CD	LYS	A	399	71.866	46.031	54.236	1.00	114.53	C
Atom	1029	CE	LYS	A	399	70.551	45.967	53.479	1.00	116.89	C
Atom	1030	NZ	LYS	A	399	70.198	44.560	53.126	1.00	97.55	N
Atom	1031	C	LYS	A	399	74.866	42.771	53.624	1.00	92.60	C
Atom	1032	O	LYS	A	399	73.925	42.437	52.906	1.00	93.10	O
Atom	1033	N	PRO	A	400	75.553	41.894	54.369	1.00	87.25	N
Atom	1034	CA	PRO	A	400	75.313	40.449	54.349	1.00	83.83	C
Atom	1035	CB	PRO	A	400	76.628	39.876	54.875	1.00	78.85	C
Atom	1036	CG	PRO	A	400	77.176	40.945	55.764	1.00	81.58	C
Atom	1037	CD	PRO	A	400	76.638	42.268	55.293	1.00	79.87	C
Atom	1038	C	PRO	A	400	74.167	40.027	55.263	1.00	81.54	C
Atom	1039	O	PRO	A	400	73.942	40.642	56.307	1.00	81.24	O
Atom	1040	N	ARG	A	401	73.456	38.979	54.861	1.00	79.78	N
Atom	1041	CA	ARG	A	401	72.385	38.405	55.666	1.00	72.29	C
Atom	1042	CB	ARG	A	401	71.024	38.751	55.065	1.00	70.66	C
Atom	1043	CG	ARG	A	401	70.678	40.228	55.128	1.00	72.33	C
Atom	1044	CD	ARG	A	401	70.423	40.672	56.558	1.00	69.81	C
Atom	1045	NE	ARG	A	401	70.140	42.101	56.629	1.00	81.24	N
Atom	1046	CZ	ARG	A	401	68.954	42.642	56.370	1.00	92.20	C
Atom	1047	NH1	ARG	A	401	67.933	41.870	56.018	1.00	74.99	N
Atom	1048	NH2	ARG	A	401	68.790	43.955	56.461	1.00	93.37	N
Atom	1049	C	ARG	A	401	72.548	36.892	55.740	1.00	72.21	C
Atom	1050	O	ARG	A	401	73.023	36.265	54.794	1.00	76.72	O
Atom	1051	N	SER	A	402	72.155	36.303	56.863	1.00	68.12	N
Atom	1052	CA	SER	A	402	72.271	34.859	57.033	1.00	70.31	C
Atom	1053	CB	SER	A	402	72.651	34.520	58.473	1.00	71.40	C
Atom	1054	OG	SER	A	402	71.736	35.107	59.380	1.00	79.39	O
Atom	1055	C	SER	A	402	70.981	34.139	56.645	1.00	69.11	C
Atom	1056	O	SER	A	402	69.905	34.736	56.632	1.00	73.27	O
Atom	1057	N	LEU	A	403	71.100	32.856	56.318	1.00	70.48	N
Atom	1058	CA	LEU	A	403	69.946	32.056	55.922	1.00	67.84	C
Atom	1059	CB	LEU	A	403	70.384	30.660	55.474	1.00	65.53	C
Atom	1060	CG	LEU	A	403	69.258	29.708	55.064	1.00	62.36	C
Atom	1061	CD1	LEU	A	403	68.499	30.265	53.867	1.00	62.62	C
Atom	1062	CD2	LEU	A	403	69.799	28.321	54.762	1.00	56.24	C
Atom	1063	C	LEU	A	403	68.968	31.932	57.080	1.00	66.40	C
Atom	1064	O	LEU	A	403	69.378	31.808	58.235	1.00	70.82	O
Atom	1065	N	ALA	A	404	67.678	31.976	56.766	1.00	69.28	N
Atom	1066	CA	ALA	A	404	66.632	31.776	57.760	1.00	65.28	C
Atom	1067	CB	ALA	A	404	65.833	33.050	57.954	1.00	63.64	C
Atom	1068	C	ALA	A	404	65.725	30.638	57.312	1.00	66.90	C
Atom	1069	O	ALA	A	404	65.592	30.371	56.117	1.00	70.46	O
Atom	1070	N	SER	A	405	65.090	29.978	58.274	1.00	65.64	N
Atom	1071	CA	SER	A	405	64.262	28.813	57.983	1.00	61.41	C
Atom	1072	CB	SER	A	405	63.838	28.125	59.284	1.00	61.33	C
Atom	1073	OG	SER	A	405	63.409	29.071	60.248	1.00	61.56	O
Atom	1074	C	SER	A	405	63.034	29.139	57.132	1.00	60.17	C
Atom	1075	O	SER	A	405	62.480	28.259	56.471	1.00	57.99	O
Atom	1076	N	TRP	A	406	62.615	30.400	57.136	1.00	60.23	N
Atom	1077	CA	TRP	A	406	61.376	30.767	56.457	1.00	60.39	C
Atom	1078	CB	TRP	A	406	60.965	32.221	56.750	1.00	60.11	C
Atom	1079	CG	TRP	A	406	61.788	33.280	56.074	1.00	60.50	C
Atom	1080	CD1	TRP	A	406	62.778	34.034	56.638	1.00	62.85	C
Atom	1081	NE1	TRP	A	406	63.293	34.907	55.713	1.00	59.69	N
Atom	1082	CE2	TRP	A	406	62.635	34.737	54.527	1.00	59.85	C
Atom	1083	CD2	TRP	A	406	61.674	33.722	54.713	1.00	59.79	C
Atom	1084	CE3	TRP	A	406	60.861	33.353	53.638	1.00	58.10	C
Atom	1085	CZ3	TRP	A	406	61.030	34.001	52.426	1.00	59.83	C
Atom	1086	CH2	TRP	A	406	61.994	35.005	52.268	1.00	61.83	C
Atom	1087	CZ2	TRP	A	406	62.805	35.385	53.302	1.00	58.84	C
Atom	1088	C	TRP	A	406	61.384	30.474	54.955	1.00	58.72	C
Atom	1089	O	TRP	A	406	60.367	30.062	54.399	1.00	62.12	O
Atom	1090	N	ILE	A	407	62.526	30.668	54.303	1.00	59.80	N
Atom	1091	CA	ILE	A	407	62.614	30.443	52.861	1.00	57.57	C
Atom	1092	CB	ILE	A	407	63.940	30.976	52.270	1.00	58.50	C
Atom	1093	CG1	ILE	A	407	63.959	30.786	50.752	1.00	54.84	C
Atom	1094	CD1	ILE	A	407	62.814	31.464	50.041	1.00	53.56	C
Atom	1095	CG2	ILE	A	407	65.137	30.298	52.916	1.00	62.99	C
Atom	1096	C	ILE	A	407	62.417	28.971	52.481	1.00	55.86	C
Atom	1097	O	ILE	A	407	61.844	28.664	51.434	1.00	55.21	O
Atom	1098	N	GLN	A	408	62.887	28.062	53.332	1.00	56.99	N
Atom	1099	CA	GLN	A	408	62.680	26.634	53.094	1.00	59.81	C
Atom	1100	CB	GLN	A	408	63.556	25.779	54.014	1.00	54.96	C
Atom	1101	CG	GLN	A	408	63.236	24.282	53.971	1.00	57.53	C
Atom	1102	CD	GLN	A	408	63.763	23.589	52.722	1.00	64.31	C
Atom	1103	OE1	GLN	A	408	64.968	23.574	52.467	1.00	63.01	O
Atom	1104	NE2	GLN	A	408	62.860	22.998	51.944	1.00	58.84	N
Atom	1105	C	GLN	A	408	61.208	26.258	53.266	1.00	59.50	C
Atom	1106	O	GLN	A	408	60.668	25.463	52.495	1.00	56.46	O
Atom	1107	N	SER	A	409	60.568	26.831	54.282	1.00	59.11	N
Atom	1108	CA	SER	A	409	59.135	26.657	54.474	1.00	60.23	C
Atom	1109	CB	SER	A	409	58.657	27.441	55.693	1.00	59.96	C
Atom	1110	OG	SER	A	409	59.283	26.973	56.869	1.00	73.64	O
Atom	1111	C	SER	A	409	58.391	27.129	53.235	1.00	60.83	C
Atom	1112	O	SER	A	409	57.507	26.437	52.725	1.00	56.40	O
Atom	1113	N	GLU	A	410	58.757	28.316	52.762	1.00	55.80	N
Atom	1114	CA	GLU	A	410	58.173	28.868	51.550	1.00	60.04	C
Atom	1115	CB	GLU	A	410	58.916	30.136	51.128	1.00	56.93	C
Atom	1116	CG	GLU	A	410	58.578	31.360	51.958	1.00	54.07	C
Atom	1117	CD	GLU	A	410	57.204	31.923	51.648	1.00	57.31	C
Atom	1118	OE1	GLU	A	410	56.386	31.219	51.017	1.00	62.02	O
Atom	1119	OE2	GLU	A	410	56.939	33.079	52.038	1.00	63.53	O
Atom	1120	C	GLU	A	410	58.194	27.851	50.419	1.00	62.55	C
Atom	1121	O	GLU	A	410	57.175	27.610	49.776	1.00	67.91	O
Atom	1122	N	PHE	A	411	59.358	27.255	50.184	1.00	57.41	N
Atom	1123	CA	PHE	A	411	59.514	26.297	49.096	1.00	58.35	C
Atom	1124	CB	PHE	A	411	60.990	25.979	48.850	1.00	60.55	C
Atom	1125	CG	PHE	A	411	61.237	25.215	47.580	1.00	60.15	C
Atom	1126	CD1	PHE	A	411	61.109	25.838	46.349	1.00	58.70	C
Atom	1127	CE1	PHE	A	411	61.333	25.143	45.181	1.00	58.31	C
Atom	1128	CZ	PHE	A	411	61.689	23.811	45.229	1.00	59.78	C
Atom	1129	CE2	PHE	A	411	61.821	23.178	46.448	1.00	58.74	C
Atom	1130	CD2	PHE	A	411	61.596	23.879	47.615	1.00	57.79	C
Atom	1131	C	PHE	A	411	58.729	25.011	49.345	1.00	60.33	C
Atom	1132	O	PHE	A	411	58.133	24.450	48.425	1.00	58.90	O
Atom	1133	N	ASN	A	412	58.741	24.544	50.589	1.00	61.13	N
Atom	1134	CA	ASN	A	412	57.949	23.382	50.975	1.00	56.59	C
Atom	1135	CB	ASN	A	412	58.046	23.139	52.481	1.00	52.28	C
Atom	1136	CG	ASN	A	412	59.403	22.615	52.899	1.00	59.84	C
Atom	1137	OD1	ASN	A	412	60.112	21.995	52.107	1.00	64.47	O
Atom	1138	ND2	ASN	A	412	59.770	22.856	54.152	1.00	59.12	N
Atom	1139	C	ASN	A	412	56.490	23.559	50.574	1.00	61.50	C
Atom	1140	O	ASN	A	412	55.913	22.708	49.894	1.00	58.46	O
Atom	1141	N	LYS	A	413	55.901	24.672	50.999	1.00	62.06	N
Atom	1142	CA	LYS	A	413	54.509	24.971	50.693	1.00	63.34	C
Atom	1143	CB	LYS	A	413	54.086	26.274	51.371	1.00	66.11	C
Atom	1144	CG	LYS	A	413	54.419	26.355	52.853	1.00	66.44	C
Atom	1145	CD	LYS	A	413	53.215	26.072	53.735	1.00	75.20	C
Atom	1146	CE	LYS	A	413	52.851	24.602	53.760	1.00	78.20	C
Atom	1147	NZ	LYS	A	413	51.618	24.370	54.572	1.00	87.98	N
Atom	1148	C	LYS	A	413	54.300	25.096	49.190	1.00	66.20	C
Atom	1149	O	LYS	A	413	53.209	24.835	48.683	1.00	68.19	O
Atom	1150	N	ALA	A	414	55.348	25.506	48.482	1.00	63.27	N
Atom	1151	CA	ALA	A	414	55.272	25.699	47.037	1.00	62.45	C
Atom	1152	CB	ALA	A	414	56.492	26.452	46.538	1.00	57.36	C
Atom	1153	C	ALA	A	414	55.126	24.372	46.295	1.00	61.74	C
Atom	1154	O	ALA	A	414	54.575	24.325	45.195	1.00	58.30	O
Atom	1155	N	CYS	A	415	55.623	23.298	46.901	1.00	62.99	N
Atom	1156	CA	CYS	A	415	55.564	21.973	46.293	1.00	66.59	C
Atom	1157	CB	CYS	A	415	56.748	21.124	46.754	1.00	61.51	C
Atom	1158	SG	CYS	A	415	58.358	21.758	46.264	1.00	67.86	S
Atom	1159	C	CYS	A	415	54.267	21.255	46.636	1.00	69.78	C
Atom	1160	O	CYS	A	415	54.000	20.167	46.129	1.00	69.29	O
Atom	1161	N	GLU	A	416	53.466	21.869	47.500	1.00	70.43	N
Atom	1162	CA	GLU	A	416	52.236	21.251	47.981	1.00	62.53	C
Atom	1163	CB	GLU	A	416	51.761	21.935	49.262	1.00	64.49	C
Atom	1164	CG	GLU	A	416	52.572	21.587	50.493	1.00	69.11	C
Atom	1165	CD	GLU	A	416	51.945	22.117	51.771	1.00	82.89	C
Atom	1166	OE1	GLU	A	416	50.984	22.915	51.679	1.00	78.69	O
Atom	1167	OE2	GLU	A	416	52.411	21.732	52.867	1.00	85.51	O
Atom	1168	C	GLU	A	416	51.115	21.274	46.952	1.00	68.50	C
Atom	1169	O	GLU	A	416	51.096	22.110	46.049	1.00	67.59	O
Atom	1170	N	LEU	A	417	50.181	20.339	47.100	1.00	74.95	N
Atom	1171	CA	LEU	A	417	48.982	20.305	46.276	1.00	71.69	C
Atom	1172	CB	LEU	A	417	48.482	18.869	46.107	1.00	72.24	C
Atom	1173	CG	LEU	A	417	49.194	18.039	45.038	1.00	78.14	C
Atom	1174	CD1	LEU	A	417	48.882	16.555	45.185	1.00	69.20	C
Atom	1175	CD2	LEU	A	417	48.829	18.540	43.646	1.00	75.78	C
Atom	1176	C	LEU	A	417	47.900	21.168	46.906	1.00	74.07	C
Atom	1177	O	LEU	A	417	47.807	21.269	48.129	1.00	73.16	O
Atom	1178	N	THR	A	418	47.086	21.788	46.060	1.00	74.30	N
Atom	1179	CA	THR	A	418	46.013	22.665	46.508	1.00	73.87	C
Atom	1180	CB	THR	A	418	46.109	24.049	45.818	1.00	72.38	C
Atom	1181	OG1	THR	A	418	47.171	24.804	46.413	1.00	74.49	O
Atom	1182	CG2	THR	A	418	44.810	24.833	45.955	1.00	81.97	C
Atom	1183	C	THR	A	418	44.656	22.025	46.228	1.00	80.68	C
Atom	1184	O	THR	A	418	44.544	21.136	45.386	1.00	82.74	O
Atom	1185	N	ASP	A	419	43.632	22.462	46.953	1.00	81.64	N
Atom	1186	CA	ASP	A	419	42.274	22.005	46.700	1.00	84.73	C
Atom	1187	CB	ASP	A	419	41.427	22.121	47.970	1.00	91.30	C
Atom	1188	CG	ASP	A	419	41.759	21.049	48.995	1.00	99.95	C
Atom	1189	OD1	ASP	A	419	42.252	19.972	48.592	1.00	94.63	O
Atom	1190	OD2	ASP	A	419	41.521	21.281	50.200	1.00	99.60	O
Atom	1191	C	ASP	A	419	41.635	22.797	45.563	1.00	83.71	C
Atom	1192	O	ASP	A	419	40.425	23.023	45.561	1.00	92.50	O
Atom	1193	N	SER	A	420	42.452	23.219	44.601	1.00	80.83	N
Atom	1194	CA	SER	A	420	41.963	23.990	43.460	1.00	83.70	C
Atom	1195	CB	SER	A	420	41.838	25.474	43.815	1.00	77.99	C
Atom	1196	OG	SER	A	420	40.682	25.724	44.595	1.00	79.92	O
Atom	1197	C	SER	A	420	42.855	23.832	42.235	1.00	79.20	C
Atom	1198	O	SER	A	420	44.061	23.633	42.355	1.00	83.32	O
Atom	1199	N	SER	A	421	42.245	23.922	41.059	1.00	82.45	N
Atom	1200	CA	SER	A	421	42.973	23.869	39.799	1.00	83.16	C
Atom	1201	CB	SER	A	421	42.170	23.105	38.745	1.00	87.39	C
Atom	1202	OG	SER	A	421	42.775	23.201	37.467	1.00	92.51	O
Atom	1203	C	SER	A	421	43.251	25.286	39.320	1.00	79.62	C
Atom	1204	O	SER	A	421	42.390	26.162	39.416	1.00	75.20	O
Atom	1205	N	TRP	A	422	44.454	25.507	38.802	1.00	81.97	N
Atom	1206	CA	TRP	A	422	44.883	26.853	38.439	1.00	77.24	C
Atom	1207	CB	TRP	A	422	46.131	27.247	39.233	1.00	70.52	C
Atom	1208	CG	TRP	A	422	45.873	27.276	40.705	1.00	65.86	C
Atom	1209	CD1	TRP	A	422	46.088	26.264	41.593	1.00	64.70	C
Atom	1210	NE1	TRP	A	422	45.718	26.659	42.855	1.00	65.01	N
Atom	1211	CE2	TRP	A	422	45.245	27.944	42.800	1.00	60.70	C
Atom	1212	CD2	TRP	A	422	45.325	28.364	41.459	1.00	62.81	C
Atom	1213	CE3	TRP	A	422	44.900	29.657	41.132	1.00	63.01	C
Atom	1214	CZ3	TRP	A	422	44.418	30.474	42.142	1.00	63.07	C
Atom	1215	CH2	TRP	A	422	44.349	30.023	43.466	1.00	61.23	C
Atom	1216	CZ2	TRP	A	422	44.758	28.765	43.814	1.00	61.38	C
Atom	1217	C	TRP	A	422	45.119	27.014	36.943	1.00	80.71	C
Atom	1218	O	TRP	A	422	45.360	28.122	36.464	1.00	81.01	O
Atom	1219	N	ILE	A	423	45.032	25.911	36.207	1.00	89.85	N
Atom	1220	CA	ILE	A	423	45.250	25.937	34.765	1.00	95.06	C
Atom	1221	CB	ILE	A	423	46.722	25.638	34.421	1.00	91.38	C
Atom	1222	CG1	ILE	A	423	47.183	24.364	35.135	1.00	84.51	C
Atom	1223	CD1	ILE	A	423	48.600	23.951	34.794	1.00	84.35	C
Atom	1224	CG2	ILE	A	423	47.611	26.812	34.800	1.00	84.21	C
Atom	1225	C	ILE	A	423	44.378	24.921	34.036	1.00	106.56	C
Atom	1226	O	ILE	A	423	44.100	23.842	34.558	1.00	105.08	O
Atom	1227	N	GLU	A	424	43.949	25.273	32.827	1.00	118.30	N
Atom	1228	CA	GLU	A	424	43.246	24.336	31.959	1.00	126.00	C
Atom	1229	CB	GLU	A	424	42.750	25.047	30.698	1.00	133.89	C
Atom	1230	CG	GLU	A	424	41.639	24.321	29.951	1.00	147.95	C
Atom	1231	CD	GLU	A	424	40.256	24.677	30.468	1.00	159.12	C
Atom	1232	OE1	GLU	A	424	39.274	24.029	30.043	1.00	156.29	O
Atom	1233	OE2	GLU	A	424	40.151	25.607	31.296	1.00	154.83	O
Atom	1234	C	GLU	A	424	44.224	23.225	31.587	1.00	128.54	C
Atom	1235	O	GLU	A	424	45.435	23.393	31.735	1.00	121.99	O
Atom	1236	N	LEU	A	425	43.712	22.096	31.105	1.00	132.83	N
Atom	1237	CA	LEU	A	425	44.570	20.949	30.797	1.00	133.23	C
Atom	1238	CB	LEU	A	425	43.744	19.708	30.454	1.00	137.36	C
Atom	1239	CG	LEU	A	425	43.198	18.939	31.657	1.00	146.11	C
Atom	1240	CD1	LEU	A	425	41.792	19.410	32.006	1.00	142.64	C
Atom	1241	CD2	LEU	A	425	43.214	17.443	31.384	1.00	132.46	C
Atom	1242	C	LEU	A	425	45.598	21.223	29.700	1.00	134.04	C
Atom	1243	O	LEU	A	425	46.577	20.487	29.559	1.00	123.82	O
Atom	1244	N	ASP	A	426	45.370	22.274	28.920	1.00	144.28	N
Atom	1245	CA	ASP	A	426	46.356	22.721	27.941	1.00	146.33	C
Atom	1246	CB	ASP	A	426	45.783	22.680	26.521	1.00	149.70	C
Atom	1247	CG	ASP	A	426	44.292	22.953	26.486	1.00	153.00	C
Atom	1248	OD1	ASP	A	426	43.868	24.020	26.979	1.00	154.59	O
Atom	1249	OD2	ASP	A	426	43.546	22.098	25.960	1.00	154.15	O
Atom	1250	C	ASP	A	426	46.871	24.116	28.296	1.00	148.80	C
Atom	1251	O	ASP	A	426	46.996	24.450	29.474	1.00	147.26	O
Atom	1252	N	GLU	A	427	47.175	24.927	27.288	1.00	152.67	N
Atom	1253	CA	GLU	A	427	47.669	26.279	27.543	1.00	157.07	C
Atom	1254	CB	GLU	A	427	49.007	26.528	26.838	1.00	155.31	C
Atom	1255	CG	GLU	A	427	50.177	25.757	27.431	1.00	154.80	C
Atom	1256	CD	GLU	A	427	50.582	24.564	26.588	1.00	153.62	C
Atom	1257	OE1	GLU	A	427	51.164	24.776	25.502	1.00	146.73	O
Atom	1258	OE2	GLU	A	427	50.328	23.418	27.015	1.00	147.06	O
Atom	1259	C	GLU	A	427	46.659	27.361	27.168	1.00	159.19	C
Atom	1260	O	GLU	A	427	47.002	28.339	26.504	1.00	156.38	O
Atom	1261	N	ILE	A	428	45.414	27.178	27.598	1.00	156.03	N
Atom	1262	CA	ILE	A	428	44.377	28.185	27.397	1.00	158.60	C
Atom	1263	CB	ILE	A	428	42.970	27.558	27.343	1.00	158.12	C
Atom	1264	CG1	ILE	A	428	42.544	27.332	25.890	1.00	157.10	C
Atom	1265	CD1	ILE	A	428	41.089	26.938	25.729	1.00	153.34	C
Atom	1266	CG2	ILE	A	428	41.960	28.453	28.042	1.00	155.63	C
Atom	1267	C	ILE	A	428	44.417	29.240	28.499	1.00	159.79	C
Atom	1268	O	ILE	A	428	45.462	29.835	28.765	1.00	153.55	O
Atom	1269	N	ILE	A	438	51.730	12.107	20.694	1.00	134.66	N
Atom	1270	CA	ILE	A	438	52.908	11.268	20.887	1.00	144.95	C
Atom	1271	CB	ILE	A	438	53.976	11.533	19.804	1.00	146.99	C
Atom	1272	CG1	ILE	A	438	54.136	13.037	19.566	1.00	138.72	C
Atom	1273	CD1	ILE	A	438	55.315	13.397	18.688	1.00	133.80	C
Atom	1274	CG2	ILE	A	438	53.602	10.832	18.504	1.00	136.55	C
Atom	1275	C	ILE	A	438	53.505	11.477	22.277	1.00	143.35	C
Atom	1276	O	ILE	A	438	53.114	10.809	23.237	1.00	138.80	O
Atom	1277	N	ALA	A	439	54.459	12.398	22.377	1.00	145.09	N
Atom	1278	CA	ALA	A	439	54.986	12.822	23.666	1.00	138.34	C
Atom	1279	CB	ALA	A	439	56.380	13.412	23.509	1.00	138.91	C
Atom	1280	C	ALA	A	439	54.031	13.845	24.265	1.00	131.03	C
Atom	1281	O	ALA	A	439	54.184	14.264	25.413	1.00	129.61	O
Atom	1282	N	SER	A	440	53.044	14.245	23.467	1.00	131.32	N
Atom	1283	CA	SER	A	440	51.957	15.097	23.934	1.00	130.85	C
Atom	1284	CB	SER	A	440	50.929	15.302	22.821	1.00	136.55	C
Atom	1285	OG	SER	A	440	49.646	15.578	23.356	1.00	136.71	O
Atom	1286	C	SER	A	440	51.290	14.451	25.138	1.00	123.39	C
Atom	1287	O	SER	A	440	50.687	15.124	25.973	1.00	124.44	O
Atom	1288	N	MET	A	441	51.404	13.131	25.212	1.00	119.60	N
Atom	1289	CA	MET	A	441	50.879	12.365	26.332	1.00	123.66	C
Atom	1290	CB	MET	A	441	50.997	10.869	26.037	1.00	125.49	C
Atom	1291	CG	MET	A	441	51.494	10.016	27.187	1.00	121.45	C
Atom	1292	SD	MET	A	441	51.048	8.289	26.929	1.00	146.20	S
Atom	1293	CE	MET	A	441	52.565	7.458	27.393	1.00	136.66	C
Atom	1294	C	MET	A	441	51.583	12.726	27.638	1.00	121.69	C
Atom	1295	O	MET	A	441	50.960	12.752	28.700	1.00	120.56	O
Atom	1296	N	ARG	A	442	52.879	13.012	27.551	1.00	123.33	N
Atom	1297	CA	ARG	A	442	53.656	13.433	28.713	1.00	120.11	C
Atom	1298	CB	ARG	A	442	55.136	13.543	28.350	1.00	120.64	C
Atom	1299	CG	ARG	A	442	55.803	12.212	28.065	1.00	120.48	C
Atom	1300	CD	ARG	A	442	56.829	12.346	26.955	1.00	127.60	C
Atom	1301	NE	ARG	A	442	57.584	11.113	26.761	1.00	132.60	N
Atom	1302	CZ	ARG	A	442	58.887	10.995	26.984	1.00	126.21	C
Atom	1303	NH1	ARG	A	442	59.587	12.043	27.396	1.00	123.25	N
Atom	1304	NH2	ARG	A	442	59.493	9.832	26.784	1.00	129.47	N
Atom	1305	C	ARG	A	442	53.148	14.767	29.246	1.00	114.23	C
Atom	1306	O	ARG	A	442	52.962	14.934	30.451	1.00	111.51	O
Atom	1307	N	ARG	A	443	52.933	15.715	28.339	1.00	111.92	N
Atom	1308	CA	ARG	A	443	52.349	16.999	28.697	1.00	107.28	C
Atom	1309	CB	ARG	A	443	51.928	17.759	27.440	1.00	115.03	C
Atom	1310	CG	ARG	A	443	51.155	19.037	27.721	1.00	123.70	C
Atom	1311	CD	ARG	A	443	50.074	19.266	26.675	1.00	134.81	C
Atom	1312	NE	ARG	A	443	50.623	19.428	25.332	1.00	146.53	N
Atom	1313	CZ	ARG	A	443	49.917	19.273	24.216	1.00	142.46	C
Atom	1314	NH1	ARG	A	443	48.634	18.939	24.281	1.00	138.28	N
Atom	1315	NH2	ARG	A	443	50.494	19.442	23.034	1.00	137.12	N
Atom	1316	C	ARG	A	443	51.133	16.783	29.590	1.00	106.19	C
Atom	1317	O	ARG	A	443	50.989	17.423	30.631	1.00	104.04	O
Atom	1318	N	ASN	A	444	50.263	15.869	29.171	1.00	108.06	N
Atom	1319	CA	ASN	A	444	49.052	15.555	29.918	1.00	110.85	C
Atom	1320	CB	ASN	A	444	48.209	14.524	29.163	1.00	118.29	C
Atom	1321	CG	ASN	A	444	47.572	15.097	27.912	1.00	122.57	C
Atom	1322	OD1	ASN	A	444	47.527	16.313	27.726	1.00	122.36	O
Atom	1323	ND2	ASN	A	444	47.072	14.221	27.047	1.00	126.42	N
Atom	1324	C	ASN	A	444	49.338	15.070	31.336	1.00	105.36	C
Atom	1325	O	ASN	A	444	48.826	15.631	32.304	1.00	101.91	O
Atom	1326	N	TYR	A	445	50.153	14.025	31.454	1.00	105.18	N
Atom	1327	CA	TYR	A	445	50.521	13.488	32.762	1.00	105.34	C
Atom	1328	CB	TYR	A	445	51.570	12.381	32.624	1.00	110.91	C
Atom	1329	CG	TYR	A	445	50.995	11.004	32.390	1.00	116.63	C
Atom	1330	CD1	TYR	A	445	51.288	10.293	31.232	1.00	124.04	C
Atom	1331	CE1	TYR	A	445	50.764	9.031	31.017	1.00	129.17	C
Atom	1332	CZ	TYR	A	445	49.935	8.467	31.965	1.00	131.25	C
Atom	1333	OH	TYR	A	445	49.409	7.212	31.756	1.00	134.17	O
Atom	1334	CE2	TYR	A	445	49.631	9.155	33.123	1.00	124.23	C
Atom	1335	CD2	TYR	A	445	50.160	10.414	33.328	1.00	115.10	C
Atom	1336	C	TYR	A	445	51.056	14.586	33.674	1.00	103.86	C
Atom	1337	O	TYR	A	445	50.580	14.767	34.797	1.00	101.42	O
Atom	1338	N	PHE	A	446	52.055	15.309	33.179	1.00	101.45	N
Atom	1339	CA	PHE	A	446	52.673	16.401	33.920	1.00	94.81	C
Atom	1340	CB	PHE	A	446	53.722	17.096	33.045	1.00	95.04	C
Atom	1341	CG	PHE	A	446	54.341	18.310	33.678	1.00	91.77	C
Atom	1342	CD1	PHE	A	446	55.384	18.183	34.579	1.00	88.17	C
Atom	1343	CE1	PHE	A	446	55.958	19.298	35.156	1.00	88.62	C
Atom	1344	CZ	PHE	A	446	55.494	20.556	34.834	1.00	84.70	C
Atom	1345	CE2	PHE	A	446	54.458	20.697	33.935	1.00	80.69	C
Atom	1346	CD2	PHE	A	446	53.888	19.580	33.360	1.00	86.09	C
Atom	1347	C	PHE	A	446	51.630	17.404	34.411	1.00	94.62	C
Atom	1348	O	PHE	A	446	51.603	17.759	35.589	1.00	90.04	O
Atom	1349	N	THR	A	447	50.766	17.848	33.504	1.00	91.21	N
Atom	1350	CA	THR	A	447	49.738	18.829	33.834	1.00	87.48	C
Atom	1351	CB	THR	A	447	48.925	19.233	32.594	1.00	88.79	C
Atom	1352	OG1	THR	A	447	49.811	19.701	31.571	1.00	92.55	O
Atom	1353	CG2	THR	A	447	47.937	20.334	32.945	1.00	91.21	C
Atom	1354	C	THR	A	447	48.780	18.311	34.903	1.00	85.00	C
Atom	1355	O	THR	A	447	48.367	19.053	35.792	1.00	86.50	O
Atom	1356	N	ALA	A	448	48.425	17.035	34.811	1.00	90.88	N
Atom	1357	CA	ALA	A	448	47.529	16.427	35.785	1.00	95.60	C
Atom	1358	CB	ALA	A	448	47.139	15.025	35.339	1.00	95.49	C
Atom	1359	C	ALA	A	448	48.185	16.387	37.158	1.00	91.24	C
Atom	1360	O	ALA	A	448	47.514	16.242	38.179	1.00	89.22	O
Atom	1361	N	GLU	A	449	49.506	16.527	37.171	1.00	87.90	N
Atom	1362	CA	GLU	A	449	50.283	16.369	38.390	1.00	83.30	C
Atom	1363	CB	GLU	A	449	51.523	15.528	38.098	1.00	84.15	C
Atom	1364	CG	GLU	A	449	52.092	14.833	39.308	1.00	89.88	C
Atom	1365	CD	GLU	A	449	51.353	13.555	39.639	1.00	88.78	C
Atom	1366	OE1	GLU	A	449	50.898	12.870	38.698	1.00	95.32	O
Atom	1367	OE2	GLU	A	449	51.232	13.233	40.839	1.00	86.76	O
Atom	1368	C	GLU	A	449	50.702	17.713	38.981	1.00	80.75	C
Atom	1369	O	GLU	A	449	51.264	17.772	40.076	1.00	76.83	O
Atom	1370	N	VAL	A	450	50.415	18.790	38.258	1.00	83.63	N
Atom	1371	CA	VAL	A	450	50.924	20.111	38.618	1.00	79.89	C
Atom	1372	CB	VAL	A	450	52.087	20.513	37.678	1.00	73.63	C
Atom	1373	CG1	VAL	A	450	51.984	21.970	37.258	1.00	73.96	C
Atom	1374	CG2	VAL	A	450	53.430	20.208	38.333	1.00	70.48	C
Atom	1375	C	VAL	A	450	49.854	21.210	38.646	1.00	80.79	C
Atom	1376	O	VAL	A	450	50.043	22.258	39.267	1.00	73.34	O
Atom	1377	N	SER	A	451	48.726	20.958	37.989	1.00	81.01	N
Atom	1378	CA	SER	A	451	47.672	21.962	37.858	1.00	81.98	C
Atom	1379	CB	SER	A	451	46.523	21.420	37.005	1.00	85.16	C
Atom	1380	OG	SER	A	451	45.904	20.310	37.628	1.00	86.17	O
Atom	1381	C	SER	A	451	47.139	22.448	39.207	1.00	81.74	C
Atom	1382	O	SER	A	451	46.638	23.568	39.320	1.00	77.15	O
Atom	1383	N	HIS	A	452	47.248	21.603	40.228	1.00	78.81	N
Atom	1384	CA	HIS	A	452	46.751	21.942	41.558	1.00	76.60	C
Atom	1385	CB	HIS	A	452	46.003	20.752	42.168	1.00	80.91	C
Atom	1386	CG	HIS	A	452	44.657	20.499	41.552	1.00	89.72	C
Atom	1387	ND1	HIS	A	452	44.503	20.059	40.261	1.00	92.47	N
Atom	1388	CE1	HIS	A	452	43.210	19.922	39.997	1.00	86.51	C
Atom	1389	NE2	HIS	A	452	42.532	20.252	41.075	1.00	85.36	N
Atom	1390	CD2	HIS	A	452	43.411	20.617	42.070	1.00	85.53	C
Atom	1391	C	HIS	A	452	47.885	22.369	42.486	1.00	78.41	C
Atom	1392	O	HIS	A	452	47.675	22.586	43.675	1.00	78.50	O
Atom	1393	N	CYS	A	453	49.088	22.488	41.936	1.00	71.44	N
Atom	1394	CA	CYS	A	453	50.255	22.839	42.732	1.00	68.19	C
Atom	1395	CB	CYS	A	453	51.533	22.510	41.959	1.00	70.20	C
Atom	1396	SG	CYS	A	453	53.026	22.501	42.964	1.00	68.87	S
Atom	1397	C	CYS	A	453	50.236	24.314	43.127	1.00	67.29	C
Atom	1398	O	CYS	A	453	49.845	25.170	42.335	1.00	66.59	O
Atom	1399	N	ARG	A	454	50.660	24.606	44.353	1.00	65.22	N
Atom	1400	CA	ARG	A	454	50.696	25.984	44.836	1.00	64.95	C
Atom	1401	CB	ARG	A	454	51.082	26.030	46.315	1.00	64.60	C
Atom	1402	CG	ARG	A	454	51.242	27.432	46.869	1.00	60.61	C
Atom	1403	CD	ARG	A	454	51.122	27.450	48.380	1.00	67.79	C
Atom	1404	NE	ARG	A	454	49.793	27.043	48.831	1.00	75.17	N
Atom	1405	CZ	ARG	A	454	49.529	25.889	49.438	1.00	73.62	C
Atom	1406	NH1	ARG	A	454	50.505	25.025	49.677	1.00	65.29	N
Atom	1407	NH2	ARG	A	454	48.289	25.604	49.812	1.00	75.83	N
Atom	1408	C	ARG	A	454	51.657	26.830	44.005	1.00	63.07	C
Atom	1409	O	ARG	A	454	51.458	28.034	43.838	1.00	60.75	O
Atom	1410	N	ALA	A	455	52.700	26.193	43.483	1.00	61.62	N
Atom	1411	CA	ALA	A	455	53.624	26.871	42.586	1.00	58.00	C
Atom	1412	CB	ALA	A	455	54.724	25.927	42.141	1.00	58.04	C
Atom	1413	C	ALA	A	455	52.863	27.417	41.383	1.00	62.13	C
Atom	1414	O	ALA	A	455	53.118	28.526	40.919	1.00	61.14	O
Atom	1415	N	THR	A	456	51.913	26.629	40.890	1.00	67.41	N
Atom	1416	CA	THR	A	456	51.112	27.027	39.739	1.00	64.51	C
Atom	1417	CB	THR	A	456	50.230	25.877	39.230	1.00	65.80	C
Atom	1418	OG1	THR	A	456	51.045	24.723	38.996	1.00	72.08	O
Atom	1419	CG2	THR	A	456	49.538	26.273	37.935	1.00	64.08	C
Atom	1420	C	THR	A	456	50.235	28.232	40.061	1.00	63.57	C
Atom	1421	O	THR	A	456	50.042	29.107	39.214	1.00	68.58	O
Atom	1422	N	GLU	A	457	49.702	28.278	41.279	1.00	60.16	N
Atom	1423	CA	GLU	A	457	48.950	29.451	41.713	1.00	60.54	C
Atom	1424	CB	GLU	A	457	48.420	29.284	43.136	1.00	56.14	C
Atom	1425	CG	GLU	A	457	47.762	30.550	43.667	1.00	54.33	C
Atom	1426	CD	GLU	A	457	47.362	30.445	45.121	1.00	57.35	C
Atom	1427	OE1	GLU	A	457	47.634	29.395	45.743	1.00	59.90	O
Atom	1428	OE2	GLU	A	457	46.773	31.416	45.644	1.00	54.85	O
Atom	1429	C	GLU	A	457	49.833	30.688	41.639	1.00	62.33	C
Atom	1430	O	GLU	A	457	49.414	31.732	41.145	1.00	59.18	O
Atom	1431	N	TYR	A	458	51.059	30.559	42.141	1.00	60.76	N
Atom	1432	CA	TYR	A	458	52.015	31.660	42.114	1.00	63.39	C
Atom	1433	CB	TYR	A	458	53.349	31.258	42.756	1.00	59.65	C
Atom	1434	CG	TYR	A	458	53.245	30.950	44.233	1.00	58.63	C
Atom	1435	CD1	TYR	A	458	52.232	31.506	45.003	1.00	55.98	C
Atom	1436	CE1	TYR	A	458	52.129	31.234	46.353	1.00	52.56	C
Atom	1437	CZ	TYR	A	458	53.053	30.407	46.956	1.00	56.38	C
Atom	1438	OH	TYR	A	458	52.948	30.137	48.302	1.00	53.19	O
Atom	1439	CE2	TYR	A	458	54.076	29.848	46.216	1.00	57.03	C
Atom	1440	CD2	TYR	A	458	54.170	30.123	44.863	1.00	54.96	C
Atom	1441	C	TYR	A	458	52.239	32.157	40.690	1.00	65.69	C
Atom	1442	O	TYR	A	458	52.317	33.363	40.451	1.00	62.51	O
Atom	1443	N	ILE	A	459	52.337	31.222	39.747	1.00	64.41	N
Atom	1444	CA	ILE	A	459	52.492	31.568	38.337	1.00	66.13	C
Atom	1445	CB	ILE	A	459	52.569	30.315	37.447	1.00	65.62	C
Atom	1446	CG1	ILE	A	459	53.922	29.623	37.620	1.00	69.39	C
Atom	1447	CD1	ILE	A	459	54.067	28.350	36.813	1.00	65.19	C
Atom	1448	CG2	ILE	A	459	52.344	30.685	35.988	1.00	69.09	C
Atom	1449	C	ILE	A	459	51.339	32.440	37.855	1.00	70.68	C
Atom	1450	O	ILE	A	459	51.549	33.532	37.322	1.00	67.76	O
Atom	1451	N	MET	A	460	50.119	31.952	38.051	1.00	68.68	N
Atom	1452	CA	MET	A	460	48.927	32.660	37.597	1.00	69.35	C
Atom	1453	CB	MET	A	460	47.695	31.770	37.738	1.00	71.59	C
Atom	1454	CG	MET	A	460	47.772	30.492	36.914	1.00	74.07	C
Atom	1455	SD	MET	A	460	48.214	30.800	35.193	1.00	76.73	S
Atom	1456	CE	MET	A	460	46.958	31.987	34.717	1.00	78.74	C
Atom	1457	C	MET	A	460	48.723	33.967	38.356	1.00	68.48	C
Atom	1458	O	MET	A	460	48.324	34.978	37.774	1.00	69.99	O
Atom	1459	N	LYS	A	461	48.990	33.939	39.657	1.00	68.31	N
Atom	1460	CA	LYS	A	461	48.933	35.142	40.475	1.00	69.71	C
Atom	1461	CB	LYS	A	461	49.337	34.816	41.913	1.00	68.71	C
Atom	1462	CG	LYS	A	461	49.182	35.967	42.892	1.00	61.84	C
Atom	1463	CD	LYS	A	461	49.494	35.513	44.309	1.00	58.11	C
Atom	1464	CE	LYS	A	461	49.349	36.653	45.299	1.00	54.99	C
Atom	1465	NZ	LYS	A	461	49.740	36.238	46.672	1.00	56.77	N
Atom	1466	C	LYS	A	461	49.854	36.208	39.891	1.00	69.55	C
Atom	1467	O	LYS	A	461	49.487	37.376	39.800	1.00	67.54	O
Atom	1468	N	GLY	A	462	51.049	35.786	39.488	1.00	70.83	N
Atom	1469	CA	GLY	A	462	52.027	36.681	38.898	1.00	67.24	C
Atom	1470	C	GLY	A	462	51.630	37.190	37.525	1.00	71.56	C
Atom	1471	O	GLY	A	462	51.877	38.348	37.190	1.00	75.96	O
Atom	1472	N	VAL	A	463	51.017	36.323	36.726	1.00	72.44	N
Atom	1473	CA	VAL	A	463	50.559	36.704	35.394	1.00	73.59	C
Atom	1474	CB	VAL	A	463	50.015	35.493	34.615	1.00	68.22	C
Atom	1475	CG1	VAL	A	463	49.380	35.942	33.309	1.00	68.97	C
Atom	1476	CG2	VAL	A	463	51.124	34.494	34.354	1.00	71.53	C
Atom	1477	C	VAL	A	463	49.482	37.785	35.467	1.00	75.68	C
Atom	1478	O	VAL	A	463	49.570	38.813	34.796	1.00	73.47	O
Atom	1479	N	TYR	A	464	48.471	37.546	36.296	1.00	74.32	N
Atom	1480	CA	TYR	A	464	47.349	38.469	36.436	1.00	76.03	C
Atom	1481	CB	TYR	A	464	46.319	37.911	37.420	1.00	74.37	C
Atom	1482	CG	TYR	A	464	45.254	37.049	36.781	1.00	85.48	C
Atom	1483	CD1	TYR	A	464	45.581	35.843	36.169	1.00	86.40	C
Atom	1484	CE1	TYR	A	464	44.607	35.050	35.584	1.00	87.20	C
Atom	1485	CZ	TYR	A	464	43.288	35.458	35.612	1.00	95.56	C
Atom	1486	OH	TYR	A	464	42.312	34.676	35.035	1.00	97.90	O
Atom	1487	CE2	TYR	A	464	42.938	36.648	36.218	1.00	91.12	C
Atom	1488	CD2	TYR	A	464	43.918	37.436	36.798	1.00	88.77	C
Atom	1489	C	TYR	A	464	47.764	39.872	36.869	1.00	76.02	C
Atom	1490	O	TYR	A	464	47.512	40.845	36.161	1.00	76.26	O
Atom	1491	N	ILE	A	465	48.396	39.975	38.034	1.00	78.43	N
Atom	1492	CA	ILE	A	465	48.665	41.280	38.627	1.00	80.29	C
Atom	1493	CB	ILE	A	465	48.992	41.182	40.144	1.00	81.97	C
Atom	1494	CG1	ILE	A	465	50.484	41.372	40.401	1.00	83.13	C
Atom	1495	CD1	ILE	A	465	50.842	42.799	40.715	1.00	92.35	C
Atom	1496	CG2	ILE	A	465	48.471	39.878	40.741	1.00	78.41	C
Atom	1497	C	ILE	A	465	49.768	42.022	37.874	1.00	76.59	C
Atom	1498	O	ILE	A	465	49.823	43.252	37.901	1.00	77.44	O
Atom	1499	N	ASN	A	466	50.638	41.278	37.196	1.00	78.36	N
Atom	1500	CA	ASN	A	466	51.640	41.897	36.333	1.00	76.20	C
Atom	1501	CB	ASN	A	466	52.763	40.919	35.988	1.00	74.81	C
Atom	1502	CG	ASN	A	466	53.939	41.022	36.940	1.00	76.72	C
Atom	1503	OD1	ASN	A	466	54.469	42.108	37.177	1.00	77.55	O
Atom	1504	ND2	ASN	A	466	54.361	39.887	37.483	1.00	73.99	N
Atom	1505	C	ASN	A	466	51.012	42.457	35.063	1.00	75.91	C
Atom	1506	O	ASN	A	466	51.301	43.584	34.665	1.00	81.44	O
Atom	1507	N	THR	A	467	50.154	41.665	34.428	1.00	75.28	N
Atom	1508	CA	THR	A	467	49.377	42.155	33.299	1.00	76.96	C
Atom	1509	CB	THR	A	467	48.381	41.096	32.801	1.00	76.48	C
Atom	1510	OG1	THR	A	467	49.096	39.980	32.254	1.00	74.81	O
Atom	1511	CG2	THR	A	467	47.470	41.683	31.734	1.00	73.45	C
Atom	1512	C	THR	A	467	48.605	43.399	33.718	1.00	76.56	C
Atom	1513	O	THR	A	467	48.672	44.437	33.063	1.00	79.67	O
Atom	1514	N	ALA	A	468	47.878	43.281	34.824	1.00	74.96	N
Atom	1515	CA	ALA	A	468	47.094	44.385	35.361	1.00	76.83	C
Atom	1516	CB	ALA	A	468	46.416	43.969	36.658	1.00	68.74	C
Atom	1517	C	ALA	A	468	47.951	45.627	35.584	1.00	80.75	C
Atom	1518	O	ALA	A	468	47.589	46.726	35.164	1.00	80.95	O
Atom	1519	N	LEU	A	469	49.089	45.448	36.245	1.00	81.54	N
Atom	1520	CA	LEU	A	469	49.973	46.565	36.556	1.00	82.38	C
Atom	1521	CB	LEU	A	469	51.137	46.103	37.435	1.00	81.87	C
Atom	1522	CG	LEU	A	469	52.023	47.205	38.019	1.00	81.01	C
Atom	1523	CD1	LEU	A	469	51.183	48.198	38.794	1.00	80.93	C
Atom	1524	CD2	LEU	A	469	53.106	46.612	38.906	1.00	86.50	C
Atom	1525	C	LEU	A	469	50.498	47.231	35.287	1.00	85.00	C
Atom	1526	O	LEU	A	469	50.642	48.452	35.231	1.00	86.43	O
Atom	1527	N	LEU	A	470	50.779	46.424	34.268	1.00	85.45	N
Atom	1528	CA	LEU	A	470	51.264	46.946	32.995	1.00	85.47	C
Atom	1529	CB	LEU	A	470	51.644	45.803	32.053	1.00	89.13	C
Atom	1530	CG	LEU	A	470	52.336	46.212	30.750	1.00	88.68	C
Atom	1531	CD1	LEU	A	470	53.587	47.020	31.043	1.00	84.79	C
Atom	1532	CD2	LEU	A	470	52.668	44.990	29.906	1.00	85.35	C
Atom	1533	C	LEU	A	470	50.215	47.839	32.340	1.00	88.25	C
Atom	1534	O	LEU	A	470	50.495	48.987	31.995	1.00	88.93	O
Atom	1535	N	ASN	A	471	49.008	47.305	32.175	1.00	86.65	N
Atom	1536	CA	ASN	A	471	47.903	48.066	31.604	1.00	83.96	C
Atom	1537	CB	ASN	A	471	46.601	47.269	31.688	1.00	83.95	C
Atom	1538	CG	ASN	A	471	46.620	46.030	30.818	1.00	96.73	C
Atom	1539	OD1	ASN	A	471	47.061	46.071	29.669	1.00	96.91	O
Atom	1540	ND2	ASN	A	471	46.132	44.918	31.359	1.00	96.89	N
Atom	1541	C	ASN	A	471	47.733	49.410	32.297	1.00	86.92	C
Atom	1542	O	ASN	A	471	47.733	50.456	31.651	1.00	93.36	O
Atom	1543	N	ALA	A	472	47.592	49.373	33.618	1.00	83.65	N
Atom	1544	CA	ALA	A	472	47.419	50.590	34.401	1.00	87.96	C
Atom	1545	CB	ALA	A	472	47.261	50.251	35.876	1.00	86.96	C
Atom	1546	C	ALA	A	472	48.581	51.557	34.196	1.00	91.60	C
Atom	1547	O	ALA	A	472	48.390	52.771	34.163	1.00	87.38	O
Atom	1548	N	SER	A	473	49.784	51.009	34.056	1.00	93.59	N
Atom	1549	CA	SER	A	473	50.981	51.821	33.863	1.00	92.42	C
Atom	1550	CB	SER	A	473	52.237	50.951	33.926	1.00	90.26	C
Atom	1551	OG	SER	A	473	52.523	50.578	35.261	1.00	92.92	O
Atom	1552	C	SER	A	473	50.948	52.592	32.549	1.00	98.96	C
Atom	1553	O	SER	A	473	51.544	53.665	32.434	1.00	96.03	O
Atom	1554	N	CYS	A	474	50.250	52.042	31.561	1.00	99.37	N
Atom	1555	CA	CYS	A	474	50.136	52.685	30.259	1.00	101.03	C
Atom	1556	CB	CYS	A	474	50.178	51.641	29.141	1.00	101.43	C
Atom	1557	SG	CYS	A	474	51.761	50.785	28.980	1.00	105.38	S
Atom	1558	C	CYS	A	474	48.871	53.529	30.145	1.00	103.44	C
Atom	1559	O	CYS	A	474	48.914	54.663	29.674	1.00	110.09	O
Atom	1560	N	ALA	A	475	47.746	52.974	30.585	1.00	92.77	N
Atom	1561	CA	ALA	A	475	46.458	53.652	30.462	1.00	90.44	C
Atom	1562	CB	ALA	A	475	45.315	52.681	30.730	1.00	86.92	C
Atom	1563	C	ALA	A	475	46.337	54.875	31.372	1.00	98.34	C
Atom	1564	O	ALA	A	475	45.409	55.672	31.227	1.00	109.54	O
Atom	1565	N	ALA	A	476	47.271	55.024	32.304	1.00	91.84	N
Atom	1566	CA	ALA	A	476	47.233	56.144	33.239	1.00	97.06	C
Atom	1567	CB	ALA	A	476	47.128	55.634	34.672	1.00	95.53	C
Atom	1568	C	ALA	A	476	48.442	57.059	33.082	1.00	106.08	C
Atom	1569	O	ALA	A	476	48.347	58.131	32.489	1.00	114.77	O
Atom	1570	N	MET	A	477	49.574	56.623	33.626	1.00	104.39	N
Atom	1571	CA	MET	A	477	50.829	57.368	33.551	1.00	103.80	C
Atom	1572	CB	MET	A	477	51.127	57.816	32.116	1.00	102.32	C
Atom	1573	CG	MET	A	477	51.516	56.690	31.174	1.00	111.25	C
Atom	1574	SD	MET	A	477	52.488	57.285	29.774	1.00	124.71	S
Atom	1575	CE	MET	A	477	52.579	55.804	28.771	1.00	109.86	C
Atom	1576	C	MET	A	477	50.889	58.565	34.498	1.00	97.55	C
Atom	1577	O	MET	A	477	51.957	58.908	35.001	1.00	101.19	O
Atom	1578	N	ASP	A	478	49.749	59.200	34.739	1.00	95.02	N
Atom	1579	CA	ASP	A	478	49.716	60.389	35.586	1.00	102.85	C
Atom	1580	CB	ASP	A	478	49.282	61.614	34.775	1.00	107.29	C
Atom	1581	CG	ASP	A	478	49.603	62.924	35.477	1.00	110.52	C
Atom	1582	OD1	ASP	A	478	50.752	63.082	35.946	1.00	99.78	O
Atom	1583	OD2	ASP	A	478	48.707	63.793	35.557	1.00	107.84	O
Atom	1584	C	ASP	A	478	48.800	60.210	36.795	1.00	103.37	C
Atom	1585	O	ASP	A	478	48.592	61.143	37.571	1.00	101.37	O
Atom	1586	N	ASP	A	479	48.259	59.007	36.955	1.00	106.13	N
Atom	1587	CA	ASP	A	479	47.304	58.738	38.025	1.00	101.76	C
Atom	1588	CB	ASP	A	479	45.983	58.247	37.432	1.00	105.34	C
Atom	1589	CG	ASP	A	479	45.260	59.326	36.648	1.00	113.34	C
Atom	1590	OD1	ASP	A	479	44.688	60.241	37.283	1.00	112.05	O
Atom	1591	OD2	ASP	A	479	45.257	59.255	35.400	1.00	110.08	O
Atom	1592	C	ASP	A	479	47.817	57.722	39.042	1.00	95.32	C
Atom	1593	O	ASP	A	479	48.618	56.845	38.712	1.00	90.46	O
Atom	1594	N	PHE	A	480	47.354	57.852	40.282	1.00	97.20	N
Atom	1595	CA	PHE	A	480	47.581	56.828	41.292	1.00	89.73	C
Atom	1596	CB	PHE	A	480	47.624	57.429	42.698	1.00	84.55	C
Atom	1597	CG	PHE	A	480	48.804	58.316	42.948	1.00	77.93	C
Atom	1598	CD1	PHE	A	480	49.834	58.401	42.029	1.00	83.67	C
Atom	1599	CE1	PHE	A	480	50.927	59.216	42.267	1.00	86.33	C
Atom	1600	CZ	PHE	A	480	51.002	59.944	43.440	1.00	80.66	C
Atom	1601	CE2	PHE	A	480	49.986	59.858	44.367	1.00	81.92	C
Atom	1602	CD2	PHE	A	480	48.897	59.044	44.123	1.00	77.53	C
Atom	1603	C	PHE	A	480	46.442	55.824	41.211	1.00	88.58	C
Atom	1604	O	PHE	A	480	45.383	56.032	41.797	1.00	90.46	O
Atom	1605	N	GLN	A	481	46.661	54.738	40.481	1.00	86.33	N
Atom	1606	CA	GLN	A	481	45.602	53.774	40.223	1.00	90.84	C
Atom	1607	CB	GLN	A	481	45.807	53.125	38.854	1.00	94.71	C
Atom	1608	CG	GLN	A	481	44.547	53.032	38.015	1.00	94.16	C
Atom	1609	CD	GLN	A	481	44.098	54.383	37.489	1.00	104.11	C
Atom	1610	OE1	GLN	A	481	44.823	55.374	37.586	1.00	102.26	O
Atom	1611	NE2	GLN	A	481	42.896	54.428	36.924	1.00	108.23	N
Atom	1612	C	GLN	A	481	45.526	52.706	41.312	1.00	89.03	C
Atom	1613	O	GLN	A	481	46.547	52.271	41.845	1.00	81.80	O
Atom	1614	N	LEU	A	482	44.305	52.293	41.641	1.00	86.45	N
Atom	1615	CA	LEU	A	482	44.082	51.235	42.622	1.00	78.21	C
Atom	1616	CB	LEU	A	482	42.894	51.582	43.520	1.00	72.62	C
Atom	1617	CG	LEU	A	482	42.538	50.577	44.617	1.00	75.35	C
Atom	1618	CD1	LEU	A	482	43.610	50.533	45.700	1.00	70.68	C
Atom	1619	CD2	LEU	A	482	41.180	50.907	45.217	1.00	69.67	C
Atom	1620	C	LEU	A	482	43.827	49.908	41.915	1.00	78.34	C
Atom	1621	O	LEU	A	482	42.756	49.694	41.354	1.00	78.12	O
Atom	1622	N	ILE	A	483	44.813	49.018	41.943	1.00	72.84	N
Atom	1623	CA	ILE	A	483	44.700	47.743	41.244	1.00	71.52	C
Atom	1624	CB	ILE	A	483	45.961	47.429	40.414	1.00	72.13	C
Atom	1625	CG1	ILE	A	483	46.178	48.486	39.330	1.00	72.91	C
Atom	1626	CD1	ILE	A	483	46.868	49.735	39.824	1.00	78.59	C
Atom	1627	CG2	ILE	A	483	45.855	46.046	39.789	1.00	73.99	C
Atom	1628	C	ILE	A	483	44.460	46.583	42.202	1.00	72.14	C
Atom	1629	O	ILE	A	483	45.309	46.276	43.037	1.00	73.78	O
Atom	1630	N	PRO	A	484	43.294	45.933	42.085	1.00	70.37	N
Atom	1631	CA	PRO	A	484	43.029	44.726	42.870	1.00	71.49	C
Atom	1632	CB	PRO	A	484	41.589	44.364	42.483	1.00	69.80	C
Atom	1633	CG	PRO	A	484	40.994	45.632	41.976	1.00	71.41	C
Atom	1634	CD	PRO	A	484	42.119	46.358	41.306	1.00	74.99	C
Atom	1635	C	PRO	A	484	43.972	43.600	42.465	1.00	70.09	C
Atom	1636	O	PRO	A	484	44.237	43.422	41.276	1.00	67.19	O
Atom	1637	N	MET	A	485	44.482	42.864	43.447	1.00	67.59	N
Atom	1638	CA	MET	A	485	45.267	41.667	43.185	1.00	63.90	C
Atom	1639	CB	MET	A	485	46.285	41.435	44.301	1.00	66.48	C
Atom	1640	CG	MET	A	485	47.606	42.153	44.090	1.00	70.16	C
Atom	1641	SD	MET	A	485	48.714	41.947	45.490	1.00	77.95	S
Atom	1642	CE	MET	A	485	47.953	43.072	46.646	1.00	63.97	C
Atom	1643	C	MET	A	485	44.330	40.473	43.064	1.00	65.36	C
Atom	1644	O	MET	A	485	43.767	40.013	44.056	1.00	66.63	O
Atom	1645	N	ILE	A	486	44.163	39.974	41.845	1.00	64.87	N
Atom	1646	CA	ILE	A	486	43.154	38.957	41.577	1.00	66.04	C
Atom	1647	CB	ILE	A	486	42.018	39.538	40.709	1.00	63.95	C
Atom	1648	CG1	ILE	A	486	41.306	40.657	41.464	1.00	64.74	C
Atom	1649	CD1	ILE	A	486	40.262	41.358	40.648	1.00	77.14	C
Atom	1650	CG2	ILE	A	486	41.023	38.459	40.312	1.00	69.76	C
Atom	1651	C	ILE	A	486	43.722	37.716	40.899	1.00	68.18	C
Atom	1652	O	ILE	A	486	44.679	37.797	40.132	1.00	71.59	O
Atom	1653	N	SER	A	487	43.126	36.566	41.202	1.00	69.23	N
Atom	1654	CA	SER	A	487	43.437	35.320	40.513	1.00	73.86	C
Atom	1655	CB	SER	A	487	44.514	34.531	41.260	1.00	67.82	C
Atom	1656	OG	SER	A	487	44.014	33.992	42.471	1.00	63.93	O
Atom	1657	C	SER	A	487	42.165	34.490	40.382	1.00	73.36	C
Atom	1658	O	SER	A	487	41.229	34.647	41.167	1.00	70.76	O
Atom	1659	N	LYS	A	488	42.130	33.623	39.376	1.00	76.52	N
Atom	1660	CA	LYS	A	488	40.981	32.754	39.141	1.00	72.72	C
Atom	1661	CB	LYS	A	488	40.462	32.928	37.712	1.00	72.90	C
Atom	1662	CG	LYS	A	488	40.041	34.346	37.352	1.00	81.08	C
Atom	1663	CD	LYS	A	488	38.629	34.652	37.819	1.00	81.17	C
Atom	1664	CE	LYS	A	488	38.212	36.055	37.402	1.00	89.05	C
Atom	1665	NZ	LYS	A	488	38.297	36.248	35.927	1.00	92.54	N
Atom	1666	C	LYS	A	488	41.384	31.303	39.358	1.00	71.50	C
Atom	1667	O	LYS	A	488	42.547	30.943	39.174	1.00	78.04	O
Atom	1668	N	CYS	A	489	40.429	30.468	39.746	1.00	74.31	N
Atom	1669	CA	CYS	A	489	40.707	29.045	39.886	1.00	76.60	C
Atom	1670	CB	CYS	A	489	41.487	28.761	41.173	1.00	67.44	C
Atom	1671	SG	CYS	A	489	40.526	28.910	42.690	1.00	68.45	S
Atom	1672	C	CYS	A	489	39.442	28.197	39.826	1.00	85.80	C
Atom	1673	O	CYS	A	489	38.326	28.714	39.888	1.00	87.09	O
Atom	1674	N	ARG	A	490	39.639	26.889	39.704	1.00	83.19	N
Atom	1675	CA	ARG	A	490	38.548	25.934	39.591	1.00	85.93	C
Atom	1676	CB	ARG	A	490	38.702	25.142	38.293	1.00	101.10	C
Atom	1677	CG	ARG	A	490	37.414	24.612	37.689	1.00	104.63	C
Atom	1678	CD	ARG	A	490	37.686	23.982	36.324	1.00	122.93	C
Atom	1679	NE	ARG	A	490	38.036	24.980	35.313	1.00	136.22	N
Atom	1680	CZ	ARG	A	490	39.277	25.351	35.012	1.00	137.63	C
Atom	1681	NH1	ARG	A	490	40.308	24.806	35.643	1.00	120.49	N
Atom	1682	NH2	ARG	A	490	39.484	26.269	34.077	1.00	132.28	N
Atom	1683	C	ARG	A	490	38.607	24.991	40.789	1.00	88.07	C
Atom	1684	O	ARG	A	490	39.622	24.332	41.016	1.00	87.75	O
Atom	1685	N	THR	A	491	37.529	24.935	41.564	1.00	86.96	N
Atom	1686	CA	THR	A	491	37.508	24.116	42.774	1.00	93.68	C
Atom	1687	CB	THR	A	491	36.331	24.493	43.693	1.00	95.63	C
Atom	1688	OG1	THR	A	491	35.102	24.033	43.118	1.00	98.58	O
Atom	1689	CG2	THR	A	491	36.267	25.998	43.882	1.00	89.81	C
Atom	1690	C	THR	A	491	37.435	22.624	42.457	1.00	96.81	C
Atom	1691	O	THR	A	491	37.220	22.235	41.309	1.00	97.90	O
Atom	1692	N	LYS	A	492	37.624	21.797	43.482	1.00	100.37	N
Atom	1693	CA	LYS	A	492	37.486	20.355	43.339	1.00	102.80	C
Atom	1694	CB	LYS	A	492	37.636	19.668	44.697	1.00	103.43	C
Atom	1695	CG	LYS	A	492	38.610	20.337	45.648	1.00	109.13	C
Atom	1696	CD	LYS	A	492	38.242	20.041	47.096	1.00	109.80	C
Atom	1697	CE	LYS	A	492	38.191	18.544	47.366	1.00	109.10	C
Atom	1698	NZ	LYS	A	492	39.545	17.926	47.286	1.00	109.13	N
Atom	1699	C	LYS	A	492	36.102	20.056	42.794	1.00	108.46	C
Atom	1700	O	LYS	A	492	35.941	19.297	41.839	1.00	105.73	O
Atom	1701	N	GLU	A	493	35.102	20.667	43.421	1.00	108.53	N
Atom	1702	CA	GLU	A	493	33.705	20.450	43.064	1.00	106.03	C
Atom	1703	CB	GLU	A	493	32.782	21.128	44.081	1.00	110.39	C
Atom	1704	CG	GLU	A	493	31.318	20.731	43.966	1.00	131.11	C
Atom	1705	CD	GLU	A	493	31.067	19.276	44.329	1.00	139.93	C
Atom	1706	OE1	GLU	A	493	32.034	18.568	44.692	1.00	133.64	O
Atom	1707	OE2	GLU	A	493	29.896	18.843	44.249	1.00	137.52	O
Atom	1708	C	GLU	A	493	33.394	20.948	41.654	1.00	106.78	C
Atom	1709	O	GLU	A	493	32.409	20.528	41.045	1.00	117.05	O
Atom	1710	N	GLY	A	494	34.229	21.850	41.144	1.00	100.48	N
Atom	1711	CA	GLY	A	494	34.103	22.315	39.773	1.00	96.07	C
Atom	1712	C	GLY	A	494	33.758	23.786	39.613	1.00	100.38	C
Atom	1713	O	GLY	A	494	33.853	24.331	38.513	1.00	94.40	O
Atom	1714	N	ARG	A	495	33.359	24.428	40.707	1.00	98.93	N
Atom	1715	CA	ARG	A	495	32.953	25.832	40.674	1.00	100.52	C
Atom	1716	CB	ARG	A	495	32.420	26.265	42.042	1.00	106.85	C
Atom	1717	CG	ARG	A	495	31.308	25.388	42.610	1.00	118.96	C
Atom	1718	CD	ARG	A	495	29.937	25.789	42.080	1.00	127.94	C
Atom	1719	NE	ARG	A	495	29.678	25.265	40.741	1.00	135.43	N
Atom	1720	CZ	ARG	A	495	29.048	24.120	40.493	1.00	134.93	C
Atom	1721	NH1	ARG	A	495	28.609	23.371	41.495	1.00	137.12	N
Atom	1722	NH2	ARG	A	495	28.857	23.725	39.242	1.00	128.91	N
Atom	1723	C	ARG	A	495	34.114	26.741	40.280	1.00	95.96	C
Atom	1724	O	ARG	A	495	35.260	26.497	40.664	1.00	93.44	O
Atom	1725	N	ARG	A	496	33.817	27.787	39.514	1.00	87.69	N
Atom	1726	CA	ARG	A	496	34.816	28.800	39.188	1.00	88.28	C
Atom	1727	CB	ARG	A	496	34.518	29.455	37.837	1.00	98.02	C
Atom	1728	CG	ARG	A	496	35.052	28.661	36.658	1.00	113.02	C
Atom	1729	CD	ARG	A	496	34.888	29.395	35.336	1.00	123.36	C
Atom	1730	NE	ARG	A	496	35.868	28.936	34.354	1.00	137.22	N
Atom	1731	CZ	ARG	A	496	35.862	27.730	33.795	1.00	136.46	C
Atom	1732	NH1	ARG	A	496	34.925	26.850	34.119	1.00	131.65	N
Atom	1733	NH2	ARG	A	496	36.798	27.402	32.912	1.00	138.54	N
Atom	1734	C	ARG	A	496	34.903	29.851	40.290	1.00	89.44	C
Atom	1735	O	ARG	A	496	33.884	30.358	40.757	1.00	87.52	O
Atom	1736	N	LYS	A	497	36.124	30.175	40.702	1.00	86.66	N
Atom	1737	CA	LYS	A	497	36.332	31.093	41.814	1.00	81.09	C
Atom	1738	CB	LYS	A	497	36.961	30.356	42.993	1.00	82.71	C
Atom	1739	CG	LYS	A	497	35.969	29.830	44.009	1.00	88.26	C
Atom	1740	CD	LYS	A	497	36.698	29.202	45.191	1.00	94.51	C
Atom	1741	CE	LYS	A	497	37.929	30.020	45.582	1.00	89.73	C
Atom	1742	NZ	LYS	A	497	38.654	29.442	46.749	1.00	81.73	N
Atom	1743	C	LYS	A	497	37.202	32.287	41.451	1.00	81.56	C
Atom	1744	O	LYS	A	497	38.178	32.155	40.716	1.00	84.13	O
Atom	1745	N	THR	A	498	36.842	33.449	41.985	1.00	75.23	N
Atom	1746	CA	THR	A	498	37.639	34.656	41.829	1.00	71.23	C
Atom	1747	CB	THR	A	498	36.807	35.810	41.253	1.00	72.82	C
Atom	1748	OG1	THR	A	498	36.430	35.502	39.906	1.00	77.86	O
Atom	1749	CG2	THR	A	498	37.606	37.105	41.272	1.00	71.33	C
Atom	1750	C	THR	A	498	38.205	35.068	43.182	1.00	74.26	C
Atom	1751	O	THR	A	498	37.460	35.288	44.136	1.00	75.34	O
Atom	1752	N	ASN	A	499	39.527	35.172	43.257	1.00	70.67	N
Atom	1753	CA	ASN	A	499	40.206	35.447	44.514	1.00	63.91	C
Atom	1754	CB	ASN	A	499	41.331	34.435	44.716	1.00	65.39	C
Atom	1755	CG	ASN	A	499	40.891	33.014	44.423	1.00	68.37	C
Atom	1756	OD1	ASN	A	499	40.049	32.456	45.126	1.00	71.85	O
Atom	1757	ND2	ASN	A	499	41.464	32.420	43.381	1.00	65.34	N
Atom	1758	C	ASN	A	499	40.772	36.859	44.584	1.00	65.38	C
Atom	1759	O	ASN	A	499	41.314	37.365	43.603	1.00	69.00	O
Atom	1760	N	LEU	A	500	40.640	37.491	45.747	1.00	63.20	N
Atom	1761	CA	LEU	A	500	41.254	38.794	45.994	1.00	60.37	C
Atom	1762	CB	LEU	A	500	40.208	39.825	46.427	1.00	60.77	C
Atom	1763	CG	LEU	A	500	40.737	41.241	46.697	1.00	63.98	C
Atom	1764	CD1	LEU	A	500	41.074	41.959	45.394	1.00	61.84	C
Atom	1765	CD2	LEU	A	500	39.742	42.055	47.512	1.00	58.86	C
Atom	1766	C	LEU	A	500	42.327	38.671	47.070	1.00	59.67	C
Atom	1767	O	LEU	A	500	42.035	38.283	48.201	1.00	58.67	O
Atom	1768	N	TYR	A	501	43.564	39.007	46.718	1.00	61.16	N
Atom	1769	CA	TYR	A	501	44.682	38.914	47.650	1.00	55.17	C
Atom	1770	CB	TYR	A	501	45.960	38.572	46.896	1.00	56.38	C
Atom	1771	CG	TYR	A	501	45.953	37.225	46.223	1.00	58.00	C
Atom	1772	CD1	TYR	A	501	46.320	36.082	46.913	1.00	50.62	C
Atom	1773	CE1	TYR	A	501	46.327	34.851	46.297	1.00	53.18	C
Atom	1774	CZ	TYR	A	501	45.959	34.749	44.972	1.00	57.04	C
Atom	1775	OH	TYR	A	501	45.961	33.524	44.353	1.00	64.49	O
Atom	1776	CE2	TYR	A	501	45.591	35.868	44.264	1.00	58.92	C
Atom	1777	CD2	TYR	A	501	45.590	37.098	44.891	1.00	61.07	C
Atom	1778	C	TYR	A	501	44.904	40.210	48.414	1.00	58.54	C
Atom	1779	O	TYR	A	501	45.502	40.214	49.489	1.00	55.59	O
Atom	1780	N	GLY	A	502	44.424	41.306	47.840	1.00	58.69	N
Atom	1781	CA	GLY	A	502	44.635	42.627	48.392	1.00	56.68	C
Atom	1782	C	GLY	A	502	44.694	43.620	47.253	1.00	60.79	C
Atom	1783	O	GLY	A	502	44.205	43.339	46.162	1.00	65.65	O
Atom	1784	N	PHE	A	503	45.305	44.774	47.499	1.00	66.18	N
Atom	1785	CA	PHE	A	503	45.384	45.822	46.490	1.00	66.77	C
Atom	1786	CB	PHE	A	503	44.504	47.011	46.880	1.00	62.72	C
Atom	1787	CG	PHE	A	503	43.038	46.691	46.911	1.00	73.86	C
Atom	1788	CD1	PHE	A	503	42.443	46.213	48.067	1.00	70.23	C
Atom	1789	CE1	PHE	A	503	41.098	45.917	48.096	1.00	65.87	C
Atom	1790	CZ	PHE	A	503	40.329	46.093	46.964	1.00	69.17	C
Atom	1791	CE2	PHE	A	503	40.910	46.565	45.806	1.00	69.73	C
Atom	1792	CD2	PHE	A	503	42.256	46.861	45.782	1.00	67.96	C
Atom	1793	C	PHE	A	503	46.806	46.301	46.236	1.00	67.47	C
Atom	1794	O	PHE	A	503	47.692	46.166	47.081	1.00	64.76	O
Atom	1795	N	ILE	A	504	47.008	46.856	45.050	1.00	69.14	N
Atom	1796	CA	ILE	A	504	48.251	47.527	44.716	1.00	71.12	C
Atom	1797	CB	ILE	A	504	49.055	46.761	43.654	1.00	66.33	C
Atom	1798	CG1	ILE	A	504	49.603	45.458	44.241	1.00	74.06	C
Atom	1799	CD1	ILE	A	504	50.740	44.852	43.444	1.00	70.02	C
Atom	1800	CG2	ILE	A	504	50.194	47.615	43.140	1.00	69.94	C
Atom	1801	C	ILE	A	504	47.929	48.921	44.206	1.00	74.99	C
Atom	1802	O	ILE	A	504	47.016	49.103	43.404	1.00	70.71	O
Atom	1803	N	ILE	A	505	48.675	49.905	44.692	1.00	75.11	N
Atom	1804	CA	ILE	A	505	48.500	51.281	44.256	1.00	74.63	C
Atom	1805	CB	ILE	A	505	48.408	52.245	45.451	1.00	74.23	C
Atom	1806	CG1	ILE	A	505	47.268	51.819	46.382	1.00	74.58	C
Atom	1807	CD1	ILE	A	505	47.135	52.673	47.628	1.00	73.13	C
Atom	1808	CG2	ILE	A	505	48.208	53.672	44.966	1.00	68.69	C
Atom	1809	C	ILE	A	505	49.648	51.692	43.343	1.00	76.98	C
Atom	1810	O	ILE	A	505	50.806	51.723	43.759	1.00	74.69	O
Atom	1811	N	LYS	A	506	49.317	51.993	42.092	1.00	80.75	N
Atom	1812	CA	LYS	A	506	50.317	52.360	41.101	1.00	79.40	C
Atom	1813	CB	LYS	A	506	49.777	52.133	39.688	1.00	80.06	C
Atom	1814	CG	LYS	A	506	50.772	52.455	38.584	1.00	84.34	C
Atom	1815	CD	LYS	A	506	50.097	52.471	37.222	1.00	90.24	C
Atom	1816	CE	LYS	A	506	49.160	53.663	37.082	1.00	91.70	C
Atom	1817	NZ	LYS	A	506	49.897	54.961	37.048	1.00	87.41	N
Atom	1818	C	LYS	A	506	50.744	53.812	41.263	1.00	85.31	C
Atom	1819	O	LYS	A	506	49.913	54.690	41.497	1.00	85.19	O
Atom	1820	N	GLY	A	507	52.045	54.054	41.140	1.00	84.45	N
Atom	1821	CA	GLY	A	507	52.582	55.400	41.198	1.00	88.58	C
Atom	1822	C	GLY	A	507	52.453	56.090	39.855	1.00	99.97	C
Atom	1823	O	GLY	A	507	51.719	55.624	38.982	1.00	96.65	O
Atom	1824	N	ARG	A	508	53.169	57.199	39.686	1.00	98.69	N
Atom	1825	CA	ARG	A	508	53.101	57.974	38.449	1.00	99.18	C
Atom	1826	CB	ARG	A	508	54.206	59.032	38.406	1.00	111.68	C
Atom	1827	CG	ARG	A	508	53.791	60.349	39.027	1.00	116.27	C
Atom	1828	CD	ARG	A	508	52.581	60.909	38.304	1.00	106.41	C
Atom	1829	NE	ARG	A	508	51.813	61.828	39.137	1.00	111.22	N
Atom	1830	CZ	ARG	A	508	52.042	63.133	39.218	1.00	119.60	C
Atom	1831	NH1	ARG	A	508	53.025	63.677	38.515	1.00	117.51	N
Atom	1832	NH2	ARG	A	508	51.289	63.891	40.004	1.00	112.39	N
Atom	1833	C	ARG	A	508	53.140	57.103	37.195	1.00	101.22	C
Atom	1834	O	ARG	A	508	52.133	56.956	36.507	1.00	108.96	O
Atom	1835	N	SER	A	509	54.304	56.530	36.908	1.00	94.36	N
Atom	1836	CA	SER	A	509	54.479	55.634	35.762	1.00	99.65	C
Atom	1837	CB	SER	A	509	53.408	54.533	35.740	1.00	97.35	C
Atom	1838	OG	SER	A	509	52.232	54.945	35.066	1.00	88.11	O
Atom	1839	C	SER	A	509	54.536	56.358	34.411	1.00	111.15	C
Atom	1840	O	SER	A	509	53.931	55.915	33.433	1.00	108.69	O
Atom	1841	N	HIS	A	510	55.264	57.470	34.365	1.00	113.42	N
Atom	1842	CA	HIS	A	510	55.594	58.121	33.103	1.00	109.30	C
Atom	1843	CB	HIS	A	510	55.638	59.642	33.269	1.00	110.50	C
Atom	1844	CG	HIS	A	510	54.296	60.302	33.208	1.00	109.11	C
Atom	1845	ND1	HIS	A	510	53.786	61.052	34.246	1.00	103.79	N
Atom	1846	CE1	HIS	A	510	52.596	61.513	33.910	1.00	103.24	C
Atom	1847	NE2	HIS	A	510	52.313	61.090	32.690	1.00	103.00	N
Atom	1848	CD2	HIS	A	510	53.363	60.333	32.228	1.00	107.00	C
Atom	1849	C	HIS	A	510	56.968	57.628	32.670	1.00	119.53	C
Atom	1850	O	HIS	A	510	57.862	57.509	33.505	1.00	130.77	O
Atom	1851	N	LEU	A	511	57.117	57.328	31.380	1.00	124.12	N
Atom	1852	CA	LEU	A	511	58.422	57.056	30.747	1.00	137.93	C
Atom	1853	CB	LEU	A	511	59.593	57.155	31.735	1.00	137.46	C
Atom	1854	CG	LEU	A	511	60.123	58.589	31.901	1.00	138.60	C
Atom	1855	CD1	LEU	A	511	60.683	58.842	33.298	1.00	135.92	C
Atom	1856	CD2	LEU	A	511	61.142	58.953	30.815	1.00	125.68	C
Atom	1857	C	LEU	A	511	58.481	55.757	29.945	1.00	131.30	C
Atom	1858	O	LEU	A	511	58.098	54.695	30.432	1.00	126.45	O
Atom	1859	N	ARG	A	512	58.973	55.873	28.712	1.00	137.39	N
Atom	1860	CA	ARG	A	512	59.056	54.764	27.763	1.00	140.96	C
Atom	1861	CB	ARG	A	512	58.626	55.241	26.371	1.00	140.33	C
Atom	1862	CG	ARG	A	512	58.493	54.140	25.325	1.00	139.62	C
Atom	1863	CD	ARG	A	512	57.131	53.468	25.393	1.00	143.22	C
Atom	1864	NE	ARG	A	512	56.045	54.408	25.132	1.00	141.86	N
Atom	1865	CZ	ARG	A	512	55.310	54.985	26.076	1.00	134.24	C
Atom	1866	NH1	ARG	A	512	55.535	54.716	27.355	1.00	134.73	N
Atom	1867	NH2	ARG	A	512	54.345	55.830	25.742	1.00	134.39	N
Atom	1868	C	ARG	A	512	60.484	54.232	27.694	1.00	139.50	C
Atom	1869	O	ARG	A	512	61.070	54.132	26.615	1.00	142.92	O
Atom	1870	N	ASN	A	513	61.043	53.893	28.850	1.00	135.46	N
Atom	1871	CA	ASN	A	513	62.446	53.512	28.928	1.00	125.44	C
Atom	1872	CB	ASN	A	513	63.130	54.245	30.085	1.00	132.43	C
Atom	1873	CG	ASN	A	513	62.700	55.705	30.197	1.00	137.15	C
Atom	1874	OD1	ASN	A	513	62.826	56.316	31.259	1.00	136.52	O
Atom	1875	ND2	ASN	A	513	62.185	56.265	29.104	1.00	130.22	N
Atom	1876	C	ASN	A	513	62.643	52.007	29.071	1.00	123.04	C
Atom	1877	O	ASN	A	513	63.766	51.513	28.977	1.00	128.96	O
Atom	1878	N	ASP	A	514	61.544	51.291	29.301	1.00	117.56	N
Atom	1879	CA	ASP	A	514	61.555	49.829	29.426	1.00	112.59	C
Atom	1880	CB	ASP	A	514	62.049	49.166	28.137	1.00	111.51	C
Atom	1881	CG	ASP	A	514	60.911	48.714	27.241	1.00	118.40	C
Atom	1882	OD1	ASP	A	514	59.802	49.283	27.347	1.00	117.30	O
Atom	1883	OD2	ASP	A	514	61.127	47.786	26.433	1.00	119.26	O
Atom	1884	C	ASP	A	514	62.333	49.289	30.626	1.00	104.14	C
Atom	1885	O	ASP	A	514	62.024	48.212	31.138	1.00	98.36	O
Atom	1886	N	THR	A	515	63.348	50.026	31.062	1.00	106.19	N
Atom	1887	CA	THR	A	515	64.100	49.646	32.248	1.00	99.00	C
Atom	1888	CB	THR	A	515	65.618	49.618	31.981	1.00	106.99	C
Atom	1889	OG1	THR	A	515	66.245	48.687	32.872	1.00	105.95	O
Atom	1890	CG2	THR	A	515	66.228	51.001	32.177	1.00	114.33	C
Atom	1891	C	THR	A	515	63.794	50.621	33.378	1.00	103.41	C
Atom	1892	O	THR	A	515	64.252	50.451	34.509	1.00	98.92	O
Atom	1893	N	ASP	A	516	63.010	51.646	33.057	1.00	107.85	N
Atom	1894	CA	ASP	A	516	62.617	52.655	34.032	1.00	106.88	C
Atom	1895	CB	ASP	A	516	62.084	53.900	33.330	1.00	110.27	C
Atom	1896	CG	ASP	A	516	62.067	55.113	34.232	1.00	115.15	C
Atom	1897	OD1	ASP	A	516	61.576	56.170	33.792	1.00	123.43	O
Atom	1898	OD2	ASP	A	516	62.544	55.009	35.381	1.00	107.06	O
Atom	1899	C	ASP	A	516	61.550	52.087	34.951	1.00	96.40	C
Atom	1900	O	ASP	A	516	60.759	51.234	34.541	1.00	93.26	O
Atom	1901	N	VAL	A	517	61.523	52.570	36.189	1.00	91.04	N
Atom	1902	CA	VAL	A	517	60.691	51.968	37.221	1.00	87.05	C
Atom	1903	CB	VAL	A	517	61.497	51.719	38.516	1.00	87.89	C
Atom	1904	CG1	VAL	A	517	62.961	51.442	38.191	1.00	82.80	C
Atom	1905	CG2	VAL	A	517	61.376	52.903	39.459	1.00	85.95	C
Atom	1906	C	VAL	A	517	59.451	52.786	37.570	1.00	84.67	C
Atom	1907	O	VAL	A	517	59.472	54.018	37.559	1.00	89.22	O
Atom	1908	N	VAL	A	518	58.369	52.078	37.875	1.00	89.01	N
Atom	1909	CA	VAL	A	518	57.164	52.696	38.411	1.00	80.65	C
Atom	1910	CB	VAL	A	518	55.914	52.291	37.614	1.00	76.06	C
Atom	1911	CG1	VAL	A	518	55.999	50.829	37.209	1.00	79.16	C
Atom	1912	CG2	VAL	A	518	54.657	52.555	38.430	1.00	82.91	C
Atom	1913	C	VAL	A	518	56.988	52.272	39.865	1.00	77.38	C
Atom	1914	O	VAL	A	518	56.908	51.080	40.167	1.00	79.78	O
Atom	1915	N	ASN	A	519	56.943	53.247	40.765	1.00	81.60	N
Atom	1916	CA	ASN	A	519	56.774	52.954	42.179	1.00	78.44	C
Atom	1917	CB	ASN	A	519	57.139	54.171	43.028	1.00	82.35	C
Atom	1918	CG	ASN	A	519	58.632	54.408	43.088	1.00	86.30	C
Atom	1919	OD1	ASN	A	519	59.090	55.549	43.154	1.00	100.25	O
Atom	1920	ND2	ASN	A	519	59.403	53.327	43.054	1.00	80.52	N
Atom	1921	C	ASN	A	519	55.352	52.517	42.486	1.00	79.40	C
Atom	1922	O	ASN	A	519	54.398	53.053	41.929	1.00	82.03	O
Atom	1923	N	PHE	A	520	55.216	51.534	43.367	1.00	73.93	N
Atom	1924	CA	PHE	A	520	53.902	51.095	43.814	1.00	72.38	C
Atom	1925	CB	PHE	A	520	53.352	49.984	42.912	1.00	70.76	C
Atom	1926	CG	PHE	A	520	54.041	48.655	43.087	1.00	74.02	C
Atom	1927	CD1	PHE	A	520	53.609	47.755	44.049	1.00	69.33	C
Atom	1928	CE1	PHE	A	520	54.240	46.533	44.213	1.00	71.47	C
Atom	1929	CZ	PHE	A	520	55.310	46.196	43.407	1.00	72.46	C
Atom	1930	CE2	PHE	A	520	55.747	47.083	42.442	1.00	76.97	C
Atom	1931	CD2	PHE	A	520	55.114	48.304	42.286	1.00	75.06	C
Atom	1932	C	PHE	A	520	53.963	50.624	45.260	1.00	70.47	C
Atom	1933	O	PHE	A	520	55.023	50.247	45.760	1.00	68.64	O
Atom	1934	N	VAL	A	521	52.818	50.666	45.929	1.00	70.67	N
Atom	1935	CA	VAL	A	521	52.693	50.127	47.274	1.00	68.61	C
Atom	1936	CB	VAL	A	521	52.253	51.209	48.286	1.00	64.45	C
Atom	1937	CG1	VAL	A	521	51.574	52.359	47.573	1.00	71.14	C
Atom	1938	CG2	VAL	A	521	51.355	50.616	49.364	1.00	59.16	C
Atom	1939	C	VAL	A	521	51.708	48.970	47.249	1.00	62.15	C
Atom	1940	O	VAL	A	521	50.626	49.074	46.671	1.00	60.72	O
Atom	1941	N	SER	A	522	52.101	47.855	47.851	1.00	57.19	N
Atom	1942	CA	SER	A	522	51.248	46.680	47.879	1.00	61.72	C
Atom	1943	CB	SER	A	522	52.058	45.420	47.576	1.00	57.86	C
Atom	1944	OG	SER	A	522	53.020	45.179	48.588	1.00	59.87	O
Atom	1945	C	SER	A	522	50.559	46.547	49.231	1.00	59.21	C
Atom	1946	O	SER	A	522	51.125	46.897	50.265	1.00	56.48	O
Atom	1947	N	MET	A	523	49.330	46.042	49.208	1.00	54.51	N
Atom	1948	CA	MET	A	523	48.546	45.832	50.419	1.00	56.87	C
Atom	1949	CB	MET	A	523	47.485	46.924	50.554	1.00	58.52	C
Atom	1950	CG	MET	A	523	48.057	48.323	50.725	1.00	58.94	C
Atom	1951	SD	MET	A	523	46.849	49.621	50.394	1.00	69.59	S
Atom	1952	CE	MET	A	523	47.596	50.997	51.260	1.00	76.50	C
Atom	1953	C	MET	A	523	47.887	44.462	50.362	1.00	60.05	C
Atom	1954	O	MET	A	523	46.898	44.273	49.658	1.00	62.36	O
Atom	1955	N	GLU	A	524	48.436	43.506	51.105	1.00	55.73	N
Atom	1956	CA	GLU	A	524	48.002	42.119	50.978	1.00	58.16	C
Atom	1957	CB	GLU	A	524	49.154	41.268	50.447	1.00	53.42	C
Atom	1958	CG	GLU	A	524	49.892	41.922	49.293	1.00	54.85	C
Atom	1959	CD	GLU	A	524	51.053	41.092	48.794	1.00	56.83	C
Atom	1960	OE1	GLU	A	524	50.836	39.911	48.456	1.00	62.24	O
Atom	1961	OE2	GLU	A	524	52.180	41.622	48.728	1.00	62.43	O
Atom	1962	C	GLU	A	524	47.452	41.529	52.277	1.00	58.45	C
Atom	1963	O	GLU	A	524	48.033	41.706	53.345	1.00	54.88	O
Atom	1964	N	PHE	A	525	46.327	40.826	52.173	1.00	60.13	N
Atom	1965	CA	PHE	A	525	45.701	40.205	53.332	1.00	56.06	C
Atom	1966	CB	PHE	A	525	44.286	39.725	52.996	1.00	55.75	C
Atom	1967	CG	PHE	A	525	43.467	40.720	52.227	1.00	56.94	C
Atom	1968	CD1	PHE	A	525	43.335	42.022	52.674	1.00	57.98	C
Atom	1969	CE1	PHE	A	525	42.574	42.936	51.974	1.00	56.08	C
Atom	1970	CZ	PHE	A	525	41.925	42.550	50.817	1.00	55.46	C
Atom	1971	CE2	PHE	A	525	42.041	41.249	50.364	1.00	54.62	C
Atom	1972	CD2	PHE	A	525	42.804	40.341	51.070	1.00	54.55	C
Atom	1973	C	PHE	A	525	46.524	39.013	53.786	1.00	55.29	C
Atom	1974	O	PHE	A	525	47.128	38.323	52.970	1.00	57.41	O
Atom	1975	N	SER	A	526	46.534	38.766	55.090	1.00	54.58	N
Atom	1976	CA	SER	A	526	47.236	37.617	55.650	1.00	55.31	C
Atom	1977	CB	SER	A	526	48.750	37.869	55.679	1.00	54.88	C
Atom	1978	OG	SER	A	526	49.450	36.813	56.324	1.00	51.24	O
Atom	1979	C	SER	A	526	46.723	37.285	57.048	1.00	55.06	C
Atom	1980	O	SER	A	526	46.322	38.169	57.801	1.00	56.18	O
Atom	1981	N	LEU	A	527	46.727	35.999	57.376	1.00	51.02	N
Atom	1982	CA	LEU	A	527	46.428	35.542	58.724	1.00	51.31	C
Atom	1983	CB	LEU	A	527	45.720	34.189	58.681	1.00	53.47	C
Atom	1984	CG	LEU	A	527	44.203	34.193	58.886	1.00	59.57	C
Atom	1985	CD1	LEU	A	527	43.532	35.413	58.262	1.00	51.38	C
Atom	1986	CD2	LEU	A	527	43.599	32.900	58.363	1.00	53.04	C
Atom	1987	C	LEU	A	527	47.708	35.433	59.535	1.00	53.93	C
Atom	1988	O	LEU	A	527	47.666	35.179	60.736	1.00	57.61	O
Atom	1989	N	THR	A	528	48.843	35.634	58.872	1.00	54.42	N
Atom	1990	CA	THR	A	528	50.144	35.460	59.508	1.00	57.39	C
Atom	1991	CB	THR	A	528	51.268	35.263	58.470	1.00	55.86	C
Atom	1992	OG1	THR	A	528	51.009	34.087	57.694	1.00	62.06	O
Atom	1993	CG2	THR	A	528	52.611	35.116	59.164	1.00	49.02	C
Atom	1994	C	THR	A	528	50.513	36.625	60.418	1.00	59.31	C
Atom	1995	O	THR	A	528	50.564	37.774	59.983	1.00	59.82	O
Atom	1996	N	ASP	A	529	50.766	36.320	61.685	1.00	57.53	N
Atom	1997	CA	ASP	A	529	51.229	37.322	62.634	1.00	60.22	C
Atom	1998	CB	ASP	A	529	51.086	36.797	64.064	1.00	62.79	C
Atom	1999	CG	ASP	A	529	51.133	37.900	65.101	1.00	66.95	C
Atom	2000	OD1	ASP	A	529	51.669	38.989	64.804	1.00	63.33	O
Atom	2001	OD2	ASP	A	529	50.632	37.674	66.221	1.00	74.38	O
Atom	2002	C	ASP	A	529	52.686	37.668	62.335	1.00	61.47	C
Atom	2003	O	ASP	A	529	53.564	36.806	62.415	1.00	63.46	O
Atom	2004	N	PRO	A	530	52.948	38.936	61.985	1.00	60.30	N
Atom	2005	CA	PRO	A	530	54.291	39.372	61.579	1.00	58.30	C
Atom	2006	CB	PRO	A	530	54.078	40.824	61.146	1.00	57.76	C
Atom	2007	CG	PRO	A	530	52.821	41.256	61.818	1.00	59.76	C
Atom	2008	CD	PRO	A	530	51.970	40.039	61.986	1.00	59.18	C
Atom	2009	C	PRO	A	530	55.292	39.314	62.725	1.00	61.40	C
Atom	2010	O	PRO	A	530	56.491	39.469	62.499	1.00	65.44	O
Atom	2011	N	ARG	A	531	54.806	39.086	63.939	1.00	62.85	N
Atom	2012	CA	ARG	A	531	55.671	39.104	65.113	1.00	60.29	C
Atom	2013	CB	ARG	A	531	54.900	39.591	66.341	1.00	61.50	C
Atom	2014	CG	ARG	A	531	54.659	41.089	66.338	1.00	61.64	C
Atom	2015	CD	ARG	A	531	53.483	41.467	67.222	1.00	67.68	C
Atom	2016	NE	ARG	A	531	52.265	40.783	66.800	1.00	73.85	N
Atom	2017	CZ	ARG	A	531	51.053	41.034	67.283	1.00	67.01	C
Atom	2018	NH1	ARG	A	531	50.879	41.966	68.213	1.00	65.87	N
Atom	2019	NH2	ARG	A	531	50.010	40.352	66.831	1.00	64.69	N
Atom	2020	C	ARG	A	531	56.344	37.765	65.396	1.00	64.45	C
Atom	2021	O	ARG	A	531	57.273	37.695	66.201	1.00	69.93	O
Atom	2022	N	LEU	A	532	55.876	36.708	64.737	1.00	65.93	N
Atom	2023	CA	LEU	A	532	56.517	35.401	64.849	1.00	66.91	C
Atom	2024	CB	LEU	A	532	55.698	34.325	64.135	1.00	68.50	C
Atom	2025	CG	LEU	A	532	54.347	33.925	64.729	1.00	70.91	C
Atom	2026	CD1	LEU	A	532	53.694	32.854	63.871	1.00	68.78	C
Atom	2027	CD2	LEU	A	532	54.498	33.446	66.165	1.00	75.24	C
Atom	2028	C	LEU	A	532	57.918	35.449	64.249	1.00	67.94	C
Atom	2029	O	LEU	A	532	58.871	34.929	64.828	1.00	72.79	O
Atom	2030	N	GLU	A	533	58.031	36.070	63.079	1.00	65.14	N
Atom	2031	CA	GLU	A	533	59.310	36.206	62.391	1.00	60.89	C
Atom	2032	CB	GLU	A	533	59.410	35.203	61.240	1.00	53.93	C
Atom	2033	CG	GLU	A	533	59.428	33.749	61.677	1.00	53.23	C
Atom	2034	CD	GLU	A	533	59.314	32.790	60.508	1.00	61.24	C
Atom	2035	OE1	GLU	A	533	58.592	33.115	59.542	1.00	68.42	O
Atom	2036	OE2	GLU	A	533	59.937	31.706	60.555	1.00	59.73	O
Atom	2037	C	GLU	A	533	59.476	37.626	61.859	1.00	63.85	C
Atom	2038	O	GLU	A	533	59.411	37.853	60.650	1.00	63.55	O
Atom	2039	N	PRO	A	534	59.692	38.589	62.765	1.00	66.99	N
Atom	2040	CA	PRO	A	534	59.811	39.996	62.372	1.00	59.40	C
Atom	2041	CB	PRO	A	534	60.214	40.692	63.674	1.00	57.85	C
Atom	2042	CG	PRO	A	534	59.765	39.778	64.756	1.00	60.32	C
Atom	2043	CD	PRO	A	534	59.899	38.394	64.210	1.00	63.39	C
Atom	2044	C	PRO	A	534	60.900	40.184	61.325	1.00	60.03	C
Atom	2045	O	PRO	A	534	60.783	41.049	60.458	1.00	62.63	O
Atom	2046	N	HIS	A	535	61.946	39.369	61.407	1.00	56.34	N
Atom	2047	CA	HIS	A	535	63.078	39.491	60.498	1.00	57.85	C
Atom	2048	CB	HIS	A	535	64.171	38.477	60.851	1.00	64.18	C
Atom	2049	CG	HIS	A	535	63.703	37.056	60.865	1.00	62.94	C
Atom	2050	ND1	HIS	A	535	63.201	36.447	61.996	1.00	62.63	N
Atom	2051	CE1	HIS	A	535	62.878	35.197	61.714	1.00	61.37	C
Atom	2052	NE2	HIS	A	535	63.155	34.971	60.443	1.00	58.98	N
Atom	2053	CD2	HIS	A	535	63.676	36.117	59.889	1.00	61.58	C
Atom	2054	C	HIS	A	535	62.655	39.331	59.042	1.00	60.72	C
Atom	2055	O	HIS	A	535	63.177	40.010	58.156	1.00	62.17	O
Atom	2056	N	LYS	A	536	61.705	38.433	58.807	1.00	62.78	N
Atom	2057	CA	LYS	A	536	61.193	38.170	57.469	1.00	58.87	C
Atom	2058	CB	LYS	A	536	60.228	36.981	57.507	1.00	60.83	C
Atom	2059	CG	LYS	A	536	59.564	36.664	56.177	1.00	59.41	C
Atom	2060	CD	LYS	A	536	58.722	35.403	56.270	1.00	55.04	C
Atom	2061	CE	LYS	A	536	58.083	35.064	54.936	1.00	54.85	C
Atom	2062	NZ	LYS	A	536	57.444	33.723	54.972	1.00	57.21	N
Atom	2063	C	LYS	A	536	60.497	39.395	56.877	1.00	58.87	C
Atom	2064	O	LYS	A	536	60.429	39.551	55.658	1.00	57.72	O
Atom	2065	N	TRP	A	537	59.993	40.268	57.742	1.00	58.71	N
Atom	2066	CA	TRP	A	537	59.160	41.383	57.296	1.00	62.05	C
Atom	2067	CB	TRP	A	537	57.811	41.345	58.020	1.00	60.19	C
Atom	2068	CG	TRP	A	537	57.185	39.987	58.001	1.00	59.14	C
Atom	2069	CD1	TRP	A	537	57.031	39.141	59.058	1.00	57.70	C
Atom	2070	NE1	TRP	A	537	56.423	37.979	58.651	1.00	56.73	N
Atom	2071	CE2	TRP	A	537	56.179	38.056	57.299	1.00	56.68	C
Atom	2072	CD2	TRP	A	537	56.651	39.309	56.864	1.00	55.69	C
Atom	2073	CE3	TRP	A	537	56.520	39.638	55.509	1.00	55.53	C
Atom	2074	CZ3	TRP	A	537	55.934	38.723	54.656	1.00	56.97	C
Atom	2075	CH2	TRP	A	537	55.475	37.488	55.124	1.00	55.53	C
Atom	2076	CZ2	TRP	A	537	55.589	37.134	56.442	1.00	58.32	C
Atom	2077	C	TRP	A	537	59.809	42.755	57.472	1.00	63.96	C
Atom	2078	O	TRP	A	537	59.117	43.743	57.716	1.00	63.29	O
Atom	2079	N	GLU	A	538	61.130	42.817	57.334	1.00	65.96	N
Atom	2080	CA	GLU	A	538	61.860	44.063	57.545	1.00	65.11	C
Atom	2081	CB	GLU	A	538	63.367	43.843	57.392	1.00	63.72	C
Atom	2082	CG	GLU	A	538	63.848	43.763	55.954	1.00	74.08	C
Atom	2083	CD	GLU	A	538	65.357	43.655	55.848	1.00	83.85	C
Atom	2084	OE1	GLU	A	538	65.867	43.522	54.714	1.00	79.38	O
Atom	2085	OE2	GLU	A	538	66.032	43.703	56.897	1.00	90.45	O
Atom	2086	C	GLU	A	538	61.400	45.169	56.597	1.00	63.75	C
Atom	2087	O	GLU	A	538	61.392	46.347	56.964	1.00	68.13	O
Atom	2088	N	LYS	A	539	61.009	44.788	55.383	1.00	61.11	N
Atom	2089	CA	LYS	A	539	60.620	45.757	54.363	1.00	63.24	C
Atom	2090	CB	LYS	A	539	60.858	45.183	52.963	1.00	62.50	C
Atom	2091	CG	LYS	A	539	62.242	44.600	52.743	1.00	65.10	C
Atom	2092	CD	LYS	A	539	62.432	44.191	51.287	1.00	67.07	C
Atom	2093	CE	LYS	A	539	63.851	43.708	51.026	1.00	64.39	C
Atom	2094	NZ	LYS	A	539	64.164	42.471	51.788	1.00	69.03	N
Atom	2095	C	LYS	A	539	59.159	46.173	54.494	1.00	61.12	C
Atom	2096	O	LYS	A	539	58.668	46.982	53.708	1.00	60.34	O
Atom	2097	N	TYR	A	540	58.472	45.622	55.488	1.00	62.51	N
Atom	2098	CA	TYR	A	540	57.027	45.787	55.597	1.00	61.10	C
Atom	2099	CB	TYR	A	540	56.348	44.417	55.682	1.00	56.00	C
Atom	2100	CG	TYR	A	540	56.346	43.623	54.399	1.00	57.52	C
Atom	2101	CD1	TYR	A	540	57.370	42.730	54.111	1.00	57.44	C
Atom	2102	CE1	TYR	A	540	57.370	41.994	52.939	1.00	53.53	C
Atom	2103	CZ	TYR	A	540	56.333	42.146	52.042	1.00	58.19	C
Atom	2104	OH	TYR	A	540	56.316	41.422	50.870	1.00	62.99	O
Atom	2105	CE2	TYR	A	540	55.304	43.023	52.310	1.00	58.41	C
Atom	2106	CD2	TYR	A	540	55.314	43.754	53.481	1.00	55.21	C
Atom	2107	C	TYR	A	540	56.577	46.615	56.793	1.00	58.70	C
Atom	2108	O	TYR	A	540	57.186	46.577	57.859	1.00	58.88	O
Atom	2109	N	CYS	A	541	55.501	47.365	56.593	1.00	57.41	N
Atom	2110	CA	CYS	A	541	54.694	47.855	57.699	1.00	59.92	C
Atom	2111	CB	CYS	A	541	54.281	49.307	57.486	1.00	64.38	C
Atom	2112	SG	CYS	A	541	53.137	49.915	58.744	1.00	60.15	S
Atom	2113	C	CYS	A	541	53.454	46.979	57.735	1.00	57.68	C
Atom	2114	O	CYS	A	541	52.736	46.882	56.743	1.00	58.34	O
Atom	2115	N	VAL	A	542	53.206	46.322	58.862	1.00	57.96	N
Atom	2116	CA	VAL	A	542	52.066	45.418	58.959	1.00	62.20	C
Atom	2117	CB	VAL	A	542	52.490	44.014	59.434	1.00	59.73	C
Atom	2118	CG1	VAL	A	542	51.345	43.030	59.266	1.00	53.93	C
Atom	2119	CG2	VAL	A	542	53.707	43.543	58.662	1.00	55.81	C
Atom	2120	C	VAL	A	542	50.969	45.962	59.867	1.00	59.15	C
Atom	2121	O	VAL	A	542	51.198	46.233	61.045	1.00	59.44	O
Atom	2122	N	LEU	A	543	49.778	46.118	59.300	1.00	58.76	N
Atom	2123	CA	LEU	A	543	48.616	46.569	60.051	1.00	60.18	C
Atom	2124	CB	LEU	A	543	47.793	47.547	59.214	1.00	58.00	C
Atom	2125	CG	LEU	A	543	48.550	48.643	58.462	1.00	63.20	C
Atom	2126	CD1	LEU	A	543	47.574	49.527	57.697	1.00	58.91	C
Atom	2127	CD2	LEU	A	543	49.400	49.472	59.413	1.00	66.94	C
Atom	2128	C	LEU	A	543	47.726	45.399	60.457	1.00	57.06	C
Atom	2129	O	LEU	A	543	47.749	44.336	59.837	1.00	57.51	O
Atom	2130	N	GLU	A	544	46.945	45.600	61.510	1.00	63.24	N
Atom	2131	CA	GLU	A	544	45.856	44.691	61.820	1.00	60.38	C
Atom	2132	CB	GLU	A	544	45.794	44.390	63.316	1.00	57.13	C
Atom	2133	CG	GLU	A	544	44.755	43.344	63.684	1.00	65.52	C
Atom	2134	CD	GLU	A	544	44.811	42.943	65.146	1.00	71.03	C
Atom	2135	OE1	GLU	A	544	45.922	42.675	65.650	1.00	67.70	O
Atom	2136	OE2	GLU	A	544	43.742	42.884	65.788	1.00	81.49	O
Atom	2137	C	GLU	A	544	44.582	45.368	61.339	1.00	58.93	C
Atom	2138	O	GLU	A	544	44.228	46.447	61.811	1.00	59.98	O
Atom	2139	N	ILE	A	545	43.905	44.744	60.382	1.00	57.29	N
Atom	2140	CA	ILE	A	545	42.787	45.389	59.706	1.00	59.18	C
Atom	2141	CB	ILE	A	545	43.020	45.443	58.188	1.00	56.46	C
Atom	2142	CG1	ILE	A	545	43.180	44.027	57.631	1.00	52.09	C
Atom	2143	CD1	ILE	A	545	43.142	43.959	56.123	1.00	54.56	C
Atom	2144	CG2	ILE	A	545	44.236	46.298	57.871	1.00	58.41	C
Atom	2145	C	ILE	A	545	41.437	44.721	59.963	1.00	58.70	C
Atom	2146	O	ILE	A	545	40.422	45.122	59.391	1.00	58.95	O
Atom	2147	N	GLY	A	546	41.420	43.704	60.816	1.00	55.55	N
Atom	2148	CA	GLY	A	546	40.178	43.026	61.136	1.00	56.61	C
Atom	2149	C	GLY	A	546	40.374	41.729	61.891	1.00	57.50	C
Atom	2150	O	GLY	A	546	41.498	41.351	62.223	1.00	60.19	O
Atom	2151	N	ASP	A	547	39.266	41.052	62.170	1.00	60.09	N
Atom	2152	CA	ASP	A	547	39.298	39.753	62.827	1.00	61.20	C
Atom	2153	CB	ASP	A	547	38.881	39.883	64.289	1.00	56.47	C
Atom	2154	CG	ASP	A	547	40.059	40.158	65.200	1.00	64.54	C
Atom	2155	OD1	ASP	A	547	40.721	39.180	65.608	1.00	67.71	O
Atom	2156	OD2	ASP	A	547	40.323	41.340	65.512	1.00	57.58	O
Atom	2157	C	ASP	A	547	38.412	38.765	62.086	1.00	57.02	C
Atom	2158	O	ASP	A	547	37.321	39.114	61.644	1.00	58.76	O
Atom	2159	N	MET	A	548	38.897	37.537	61.938	1.00	54.03	N
Atom	2160	CA	MET	A	548	38.184	36.516	61.176	1.00	57.78	C
Atom	2161	CB	MET	A	548	39.052	36.008	60.018	1.00	56.59	C
Atom	2162	CG	MET	A	548	38.401	34.912	59.178	1.00	61.39	C
Atom	2163	SD	MET	A	548	39.357	34.479	57.707	1.00	63.03	S
Atom	2164	CE	MET	A	548	39.156	35.958	56.713	1.00	58.92	C
Atom	2165	C	MET	A	548	37.718	35.343	62.040	1.00	61.19	C
Atom	2166	O	MET	A	548	38.454	34.849	62.895	1.00	56.79	O
Atom	2167	N	LEU	A	549	36.487	34.904	61.799	1.00	61.09	N
Atom	2168	CA	LEU	A	549	35.908	33.761	62.496	1.00	62.00	C
Atom	2169	CB	LEU	A	549	34.453	34.052	62.875	1.00	59.57	C
Atom	2170	CG	LEU	A	549	34.202	34.705	64.238	1.00	52.87	C
Atom	2171	CD1	LEU	A	549	35.492	35.141	64.903	1.00	64.08	C
Atom	2172	CD2	LEU	A	549	33.248	35.872	64.103	1.00	54.21	C
Atom	2173	C	LEU	A	549	36.000	32.511	61.626	1.00	62.40	C
Atom	2174	O	LEU	A	549	35.408	32.449	60.551	1.00	66.69	O
Atom	2175	N	LEU	A	550	36.744	31.515	62.094	1.00	62.44	N
Atom	2176	CA	LEU	A	550	37.021	30.331	61.287	1.00	58.54	C
Atom	2177	CB	LEU	A	550	38.531	30.134	61.139	1.00	67.54	C
Atom	2178	CG	LEU	A	550	39.323	31.240	60.443	1.00	65.23	C
Atom	2179	CD1	LEU	A	550	40.813	31.046	60.670	1.00	68.77	C
Atom	2180	CD2	LEU	A	550	38.998	31.271	58.960	1.00	66.66	C
Atom	2181	C	LEU	A	550	36.420	29.070	61.884	1.00	64.67	C
Atom	2182	O	LEU	A	550	36.445	28.873	63.098	1.00	64.10	O
Atom	2183	N	ARG	A	551	35.881	28.217	61.018	1.00	74.38	N
Atom	2184	CA	ARG	A	551	35.447	26.883	61.415	1.00	74.55	C
Atom	2185	CB	ARG	A	551	34.609	26.249	60.306	1.00	85.07	C
Atom	2186	CG	ARG	A	551	33.260	26.919	60.082	1.00	92.20	C
Atom	2187	CD	ARG	A	551	32.172	26.322	60.974	1.00	111.63	C
Atom	2188	NE	ARG	A	551	32.378	26.612	62.393	1.00	110.91	N
Atom	2189	CZ	ARG	A	551	31.674	26.068	63.381	1.00	106.62	C
Atom	2190	NH1	ARG	A	551	30.712	25.195	63.113	1.00	116.57	N
Atom	2191	NH2	ARG	A	551	31.935	26.394	64.640	1.00	96.37	N
Atom	2192	C	ARG	A	551	36.677	26.030	61.703	1.00	75.39	C
Atom	2193	O	ARG	A	551	37.673	26.106	60.984	1.00	74.27	O
Atom	2194	N	THR	A	552	36.610	25.215	62.749	1.00	78.31	N
Atom	2195	CA	THR	A	552	37.791	24.507	63.229	1.00	65.43	C
Atom	2196	CB	THR	A	552	38.587	25.397	64.211	1.00	65.71	C
Atom	2197	OG1	THR	A	552	39.433	26.287	63.471	1.00	73.96	O
Atom	2198	CG2	THR	A	552	39.441	24.562	65.148	1.00	71.93	C
Atom	2199	C	THR	A	552	37.435	23.181	63.891	1.00	68.81	C
Atom	2200	O	THR	A	552	36.303	22.983	64.337	1.00	72.99	O
Atom	2201	N	ALA	A	553	38.402	22.270	63.936	1.00	70.81	N
Atom	2202	CA	ALA	A	553	38.220	20.982	64.591	1.00	69.85	C
Atom	2203	CB	ALA	A	553	39.550	20.245	64.678	1.00	73.57	C
Atom	2204	C	ALA	A	553	37.600	21.129	65.975	1.00	72.49	C
Atom	2205	O	ALA	A	553	36.897	20.235	66.445	1.00	76.32	O
Atom	2206	N	ILE	A	554	37.863	22.257	66.627	1.00	66.54	N
Atom	2207	CA	ILE	A	554	37.331	22.500	67.967	1.00	69.18	C
Atom	2208	CB	ILE	A	554	38.426	22.962	68.944	1.00	71.86	C
Atom	2209	CG1	ILE	A	554	38.879	24.384	68.600	1.00	74.24	C
Atom	2210	CD1	ILE	A	554	39.735	25.028	69.669	1.00	67.63	C
Atom	2211	CG2	ILE	A	554	39.594	21.985	68.927	1.00	67.10	C
Atom	2212	C	ILE	A	554	36.194	23.524	67.984	1.00	65.55	C
Atom	2213	O	ILE	A	554	35.652	23.838	69.043	1.00	65.49	O
Atom	2214	N	GLY	A	555	35.834	24.039	66.813	1.00	66.23	N
Atom	2215	CA	GLY	A	555	34.749	25.000	66.707	1.00	67.71	C
Atom	2216	C	GLY	A	555	35.170	26.329	66.102	1.00	67.68	C
Atom	2217	O	GLY	A	555	36.166	26.410	65.387	1.00	68.02	O
Atom	2218	N	GLN	A	556	34.409	27.379	66.389	1.00	66.99	N
Atom	2219	CA	GLN	A	556	34.718	28.703	65.856	1.00	67.72	C
Atom	2220	CB	GLN	A	556	33.479	29.604	65.865	1.00	59.52	C
Atom	2221	CG	GLN	A	556	33.669	30.910	65.109	1.00	68.01	C
Atom	2222	CD	GLN	A	556	32.375	31.698	64.938	1.00	76.12	C
Atom	2223	OE1	GLN	A	556	31.768	32.146	65.914	1.00	68.44	O
Atom	2224	NE2	GLN	A	556	31.959	31.886	63.689	1.00	64.44	N
Atom	2225	C	GLN	A	556	35.873	29.357	66.614	1.00	65.53	C
Atom	2226	O	GLN	A	556	35.861	29.442	67.843	1.00	61.10	O
Atom	2227	N	VAL	A	557	36.876	29.809	65.870	1.00	59.82	N
Atom	2228	CA	VAL	A	557	38.034	30.458	66.469	1.00	60.39	C
Atom	2229	CB	VAL	A	557	39.302	29.601	66.301	1.00	60.85	C
Atom	2230	CG1	VAL	A	557	39.715	29.536	64.843	1.00	68.63	C
Atom	2231	CG2	VAL	A	557	40.427	30.148	67.158	1.00	61.54	C
Atom	2232	C	VAL	A	557	38.250	31.839	65.845	1.00	61.67	C
Atom	2233	O	VAL	A	557	38.012	32.033	64.653	1.00	63.73	O
Atom	2234	N	SER	A	558	38.681	32.800	66.656	1.00	57.17	N
Atom	2235	CA	SER	A	558	38.893	34.162	66.180	1.00	58.11	C
Atom	2236	CB	SER	A	558	38.361	35.171	67.205	1.00	63.20	C
Atom	2237	OG	SER	A	558	38.298	36.485	66.662	1.00	60.40	O
Atom	2238	C	SER	A	558	40.373	34.415	65.904	1.00	61.95	C
Atom	2239	O	SER	A	558	41.208	34.294	66.799	1.00	64.06	O
Atom	2240	N	ARG	A	559	40.691	34.758	64.659	1.00	57.79	N
Atom	2241	CA	ARG	A	559	42.067	35.051	64.267	1.00	57.32	C
Atom	2242	CB	ARG	A	559	42.590	34.016	63.267	1.00	61.25	C
Atom	2243	CG	ARG	A	559	42.869	32.651	63.859	1.00	66.58	C
Atom	2244	CD	ARG	A	559	43.692	31.793	62.910	1.00	76.71	C
Atom	2245	NE	ARG	A	559	44.955	32.436	62.554	1.00	80.53	N
Atom	2246	CZ	ARG	A	559	45.967	31.826	61.944	1.00	79.06	C
Atom	2247	NH1	ARG	A	559	45.878	30.543	61.618	1.00	75.87	N
Atom	2248	NH2	ARG	A	559	47.073	32.500	61.663	1.00	71.23	N
Atom	2249	C	ARG	A	559	42.175	36.433	63.652	1.00	60.18	C
Atom	2250	O	ARG	A	559	41.375	36.793	62.791	1.00	61.02	O
Atom	2251	N	PRO	A	560	43.175	37.210	64.089	1.00	57.81	N
Atom	2252	CA	PRO	A	560	43.402	38.540	63.523	1.00	56.89	C
Atom	2253	CB	PRO	A	560	44.659	39.016	64.253	1.00	55.57	C
Atom	2254	CG	PRO	A	560	44.678	38.234	65.523	1.00	53.08	C
Atom	2255	CD	PRO	A	560	44.120	36.898	65.174	1.00	54.59	C
Atom	2256	C	PRO	A	560	43.681	38.452	62.030	1.00	55.23	C
Atom	2257	O	PRO	A	560	44.338	37.514	61.584	1.00	52.89	O
Atom	2258	N	MET	A	561	43.168	39.409	61.267	1.00	56.89	N
Atom	2259	CA	MET	A	561	43.555	39.544	59.871	1.00	53.86	C
Atom	2260	CB	MET	A	561	42.340	39.725	58.958	1.00	50.96	C
Atom	2261	CG	MET	A	561	42.734	40.088	57.532	1.00	52.87	C
Atom	2262	SD	MET	A	561	41.553	39.589	56.269	1.00	65.15	S
Atom	2263	CE	MET	A	561	40.467	41.012	56.246	1.00	60.75	C
Atom	2264	C	MET	A	561	44.513	40.719	59.713	1.00	57.06	C
Atom	2265	O	MET	A	561	44.234	41.832	60.167	1.00	52.26	O
Atom	2266	N	PHE	A	562	45.644	40.464	59.067	1.00	59.13	N
Atom	2267	CA	PHE	A	562	46.660	41.491	58.897	1.00	57.32	C
Atom	2268	CB	PHE	A	562	48.029	40.967	59.334	1.00	54.50	C
Atom	2269	CG	PHE	A	562	48.043	40.403	60.720	1.00	53.66	C
Atom	2270	CD1	PHE	A	562	48.125	41.241	61.818	1.00	51.40	C
Atom	2271	CE1	PHE	A	562	48.134	40.728	63.098	1.00	53.69	C
Atom	2272	CZ	PHE	A	562	48.060	39.360	63.291	1.00	55.77	C
Atom	2273	CE2	PHE	A	562	47.976	38.516	62.204	1.00	55.07	C
Atom	2274	CD2	PHE	A	562	47.966	39.036	60.928	1.00	53.44	C
Atom	2275	C	PHE	A	562	46.726	41.968	57.460	1.00	54.19	C
Atom	2276	O	PHE	A	562	46.364	41.246	56.531	1.00	53.63	O
Atom	2277	N	LEU	A	563	47.180	43.203	57.294	1.00	53.04	N
Atom	2278	CA	LEU	A	563	47.472	43.750	55.982	1.00	53.62	C
Atom	2279	CB	LEU	A	563	46.682	45.035	55.741	1.00	51.30	C
Atom	2280	CG	LEU	A	563	46.744	45.572	54.308	1.00	56.06	C
Atom	2281	CD1	LEU	A	563	45.949	44.681	53.358	1.00	56.80	C
Atom	2282	CD2	LEU	A	563	46.252	47.006	54.244	1.00	56.09	C
Atom	2283	C	LEU	A	563	48.963	44.045	55.898	1.00	55.06	C
Atom	2284	O	LEU	A	563	49.467	44.937	56.579	1.00	58.37	O
Atom	2285	N	TYR	A	564	49.670	43.284	55.072	1.00	53.83	N
Atom	2286	CA	TYR	A	564	51.088	43.526	54.854	1.00	53.77	C
Atom	2287	CB	TYR	A	564	51.792	42.242	54.424	1.00	50.50	C
Atom	2288	CG	TYR	A	564	52.042	41.287	55.569	1.00	53.43	C
Atom	2289	CD1	TYR	A	564	51.013	40.517	56.096	1.00	52.87	C
Atom	2290	CE1	TYR	A	564	51.242	39.646	57.146	1.00	53.89	C
Atom	2291	CZ	TYR	A	564	52.508	39.540	57.681	1.00	54.15	C
Atom	2292	OH	TYR	A	564	52.738	38.673	58.723	1.00	54.94	O
Atom	2293	CE2	TYR	A	564	53.542	40.298	57.178	1.00	51.54	C
Atom	2294	CD2	TYR	A	564	53.306	41.164	56.131	1.00	50.49	C
Atom	2295	C	TYR	A	564	51.292	44.628	53.825	1.00	54.76	C
Atom	2296	O	TYR	A	564	50.831	44.526	52.693	1.00	56.37	O
Atom	2297	N	VAL	A	565	51.977	45.689	54.232	1.00	53.43	N
Atom	2298	CA	VAL	A	565	52.178	46.844	53.367	1.00	55.63	C
Atom	2299	CB	VAL	A	565	51.541	48.109	53.970	1.00	57.71	C
Atom	2300	CG1	VAL	A	565	51.442	49.198	52.922	1.00	57.66	C
Atom	2301	CG2	VAL	A	565	50.166	47.792	54.547	1.00	56.42	C
Atom	2302	C	VAL	A	565	53.659	47.113	53.135	1.00	60.14	C
Atom	2303	O	VAL	A	565	54.476	46.966	54.041	1.00	65.88	O
Atom	2304	N	ARG	A	566	54.004	47.509	51.916	1.00	60.62	N
Atom	2305	CA	ARG	A	566	55.377	47.877	51.601	1.00	60.55	C
Atom	2306	CB	ARG	A	566	56.268	46.637	51.524	1.00	58.95	C
Atom	2307	CG	ARG	A	566	55.956	45.724	50.348	1.00	55.73	C
Atom	2308	CD	ARG	A	566	57.163	44.887	49.964	1.00	54.02	C
Atom	2309	NE	ARG	A	566	58.109	45.662	49.170	1.00	69.19	N
Atom	2310	CZ	ARG	A	566	59.348	45.267	48.891	1.00	62.92	C
Atom	2311	NH1	ARG	A	566	59.801	44.103	49.345	1.00	68.11	N
Atom	2312	NH2	ARG	A	566	60.142	46.034	48.158	1.00	59.65	N
Atom	2313	C	ARG	A	566	55.445	48.638	50.287	1.00	64.51	C
Atom	2314	O	ARG	A	566	54.603	48.453	49.408	1.00	63.97	O
Atom	2315	N	THR	A	567	56.452	49.496	50.160	1.00	70.40	N
Atom	2316	CA	THR	A	567	56.695	50.196	48.906	1.00	69.23	C
Atom	2317	CB	THR	A	567	57.416	51.542	49.125	1.00	69.59	C
Atom	2318	OG1	THR	A	567	58.707	51.305	49.698	1.00	73.75	O
Atom	2319	CG2	THR	A	567	56.608	52.440	50.053	1.00	64.50	C
Atom	2320	C	THR	A	567	57.541	49.296	48.017	1.00	68.45	C
Atom	2321	O	THR	A	567	58.208	48.384	48.505	1.00	58.68	O
Atom	2322	N	ASN	A	568	57.507	49.549	46.713	1.00	72.84	N
Atom	2323	CA	ASN	A	568	58.198	48.695	45.758	1.00	68.68	C
Atom	2324	CB	ASN	A	568	57.522	47.327	45.709	1.00	64.61	C
Atom	2325	CG	ASN	A	568	58.500	46.204	45.473	1.00	66.48	C
Atom	2326	OD1	ASN	A	568	58.270	45.071	45.895	1.00	72.14	O
Atom	2327	ND2	ASN	A	568	59.604	46.509	44.805	1.00	67.22	N
Atom	2328	C	ASN	A	568	58.202	49.330	44.374	1.00	68.09	C
Atom	2329	O	ASN	A	568	57.796	50.480	44.214	1.00	69.75	O
Atom	2330	N	GLY	A	569	58.657	48.581	43.374	1.00	67.65	N
Atom	2331	CA	GLY	A	569	58.696	49.083	42.014	1.00	72.00	C
Atom	2332	C	GLY	A	569	59.086	48.031	40.995	1.00	70.54	C
Atom	2333	O	GLY	A	569	59.764	47.059	41.318	1.00	71.47	O
Atom	2334	N	THR	A	570	58.643	48.226	39.758	1.00	74.61	N
Atom	2335	CA	THR	A	570	59.023	47.353	38.654	1.00	81.59	C
Atom	2336	CB	THR	A	570	57.959	46.272	38.372	1.00	79.46	C
Atom	2337	OG1	THR	A	570	56.659	46.783	38.689	1.00	80.41	O
Atom	2338	CG2	THR	A	570	58.226	45.027	39.202	1.00	91.22	C
Atom	2339	C	THR	A	570	59.240	48.161	37.385	1.00	85.13	C
Atom	2340	O	THR	A	570	59.124	49.384	37.389	1.00	82.78	O
Atom	2341	N	SER	A	571	59.561	47.462	36.304	1.00	90.28	N
Atom	2342	CA	SER	A	571	59.759	48.082	35.004	1.00	88.63	C
Atom	2343	CB	SER	A	571	61.243	48.083	34.632	1.00	94.51	C
Atom	2344	OG	SER	A	571	61.750	46.761	34.557	1.00	85.31	O
Atom	2345	C	SER	A	571	58.967	47.302	33.968	1.00	94.66	C
Atom	2346	O	SER	A	571	58.517	46.186	34.235	1.00	93.43	O
Atom	2347	N	LYS	A	572	58.797	47.891	32.790	1.00	103.65	N
Atom	2348	CA	LYS	A	572	58.123	47.216	31.692	1.00	96.24	C
Atom	2349	CB	LYS	A	572	58.278	48.024	30.406	1.00	103.60	C
Atom	2350	CG	LYS	A	572	57.890	49.486	30.546	1.00	110.08	C
Atom	2351	CD	LYS	A	572	56.434	49.713	30.177	1.00	114.59	C
Atom	2352	CE	LYS	A	572	56.280	49.927	28.678	1.00	122.51	C
Atom	2353	NZ	LYS	A	572	56.973	51.167	28.217	1.00	129.13	N
Atom	2354	C	LYS	A	572	58.725	45.831	31.508	1.00	89.59	C
Atom	2355	O	LYS	A	572	58.012	44.861	31.256	1.00	89.83	O
Atom	2356	N	ILE	A	573	60.046	45.749	31.642	1.00	90.26	N
Atom	2357	CA	ILE	A	573	60.764	44.489	31.467	1.00	94.27	C
Atom	2358	CB	ILE	A	573	62.294	44.705	31.366	1.00	92.18	C
Atom	2359	CG1	ILE	A	573	62.696	44.875	29.902	1.00	90.68	C
Atom	2360	CD1	ILE	A	573	62.358	43.671	29.040	1.00	99.11	C
Atom	2361	CG2	ILE	A	573	63.054	43.528	31.969	1.00	90.52	C
Atom	2362	C	ILE	A	573	60.447	43.471	32.558	1.00	89.39	C
Atom	2363	O	ILE	A	573	60.192	42.301	32.265	1.00	86.24	O
Atom	2364	N	LYS	A	574	60.464	43.914	33.811	1.00	87.88	N
Atom	2365	CA	LYS	A	574	60.170	43.022	34.927	1.00	90.51	C
Atom	2366	CB	LYS	A	574	60.469	43.701	36.266	1.00	89.12	C
Atom	2367	CG	LYS	A	574	61.948	43.967	36.507	1.00	86.87	C
Atom	2368	CD	LYS	A	574	62.225	44.339	37.957	1.00	91.09	C
Atom	2369	CE	LYS	A	574	62.070	43.140	38.884	1.00	110.36	C
Atom	2370	NZ	LYS	A	574	62.506	43.451	40.277	1.00	105.47	N
Atom	2371	C	LYS	A	574	58.719	42.554	34.871	1.00	88.76	C
Atom	2372	O	LYS	A	574	58.417	41.396	35.167	1.00	87.21	O
Atom	2373	N	MET	A	575	57.826	43.459	34.483	1.00	81.99	N
Atom	2374	CA	MET	A	575	56.423	43.112	34.299	1.00	82.20	C
Atom	2375	CB	MET	A	575	55.582	44.363	34.037	1.00	78.68	C
Atom	2376	CG	MET	A	575	55.222	45.135	35.295	1.00	79.94	C
Atom	2377	SD	MET	A	575	54.296	46.642	34.949	1.00	91.59	S
Atom	2378	CE	MET	A	575	55.607	47.735	34.405	1.00	92.30	C
Atom	2379	C	MET	A	575	56.247	42.113	33.163	1.00	82.95	C
Atom	2380	O	MET	A	575	55.407	41.220	33.235	1.00	84.88	O
Atom	2381	N	LYS	A	576	57.044	42.273	32.113	1.00	83.05	N
Atom	2382	CA	LYS	A	576	56.997	41.366	30.972	1.00	89.65	C
Atom	2383	CB	LYS	A	576	57.909	41.871	29.850	1.00	94.69	C
Atom	2384	CG	LYS	A	576	57.998	40.946	28.642	1.00	97.97	C
Atom	2385	CD	LYS	A	576	56.953	41.276	27.576	1.00	109.02	C
Atom	2386	CE	LYS	A	576	55.558	40.790	27.956	1.00	110.12	C
Atom	2387	NZ	LYS	A	576	54.572	41.029	26.860	1.00	109.27	N
Atom	2388	C	LYS	A	576	57.406	39.955	31.384	1.00	86.53	C
Atom	2389	O	LYS	A	576	56.720	38.981	31.071	1.00	78.88	O
Atom	2390	N	TRP	A	577	58.529	39.851	32.086	1.00	85.93	N
Atom	2391	CA	TRP	A	577	59.009	38.558	32.552	1.00	90.21	C
Atom	2392	CB	TRP	A	577	60.342	38.706	33.289	1.00	91.13	C
Atom	2393	CG	TRP	A	577	61.491	39.154	32.425	1.00	106.51	C
Atom	2394	CD1	TRP	A	577	62.481	40.029	32.772	1.00	110.83	C
Atom	2395	NE1	TRP	A	577	63.360	40.188	31.729	1.00	114.42	N
Atom	2396	CE2	TRP	A	577	62.949	39.414	30.678	1.00	122.04	C
Atom	2397	CD2	TRP	A	577	61.773	38.746	31.077	1.00	116.88	C
Atom	2398	CE3	TRP	A	577	61.147	37.881	30.172	1.00	120.02	C
Atom	2399	CZ3	TRP	A	577	61.706	37.717	28.916	1.00	126.40	C
Atom	2400	CH2	TRP	A	577	62.877	38.396	28.548	1.00	127.91	C
Atom	2401	CZ2	TRP	A	577	63.511	39.246	29.412	1.00	129.15	C
Atom	2402	C	TRP	A	577	57.977	37.897	33.462	1.00	87.70	C
Atom	2403	O	TRP	A	577	57.800	36.676	33.439	1.00	82.92	O
Atom	2404	N	GLY	A	578	57.297	38.716	34.258	1.00	86.34	N
Atom	2405	CA	GLY	A	578	56.281	38.232	35.175	1.00	80.98	C
Atom	2406	C	GLY	A	578	55.047	37.739	34.450	1.00	80.29	C
Atom	2407	O	GLY	A	578	54.420	36.765	34.864	1.00	76.48	O
Atom	2408	N	MET	A	579	54.698	38.416	33.361	1.00	78.84	N
Atom	2409	CA	MET	A	579	53.549	38.030	32.552	1.00	79.56	C
Atom	2410	CB	MET	A	579	53.208	39.132	31.547	1.00	78.76	C
Atom	2411	CG	MET	A	579	52.655	40.402	32.168	1.00	83.74	C
Atom	2412	SD	MET	A	579	52.295	41.660	30.927	1.00	82.84	S
Atom	2413	CE	MET	A	579	51.105	40.791	29.906	1.00	80.08	C
Atom	2414	C	MET	A	579	53.800	36.718	31.812	1.00	80.84	C
Atom	2415	O	MET	A	579	52.891	36.158	31.197	1.00	81.46	O
Atom	2416	N	GLU	A	580	55.034	36.230	31.878	1.00	79.43	N
Atom	2417	CA	GLU	A	580	55.422	35.038	31.136	1.00	81.85	C
Atom	2418	CB	GLU	A	580	56.549	35.372	30.159	1.00	87.44	C
Atom	2419	CG	GLU	A	580	56.161	36.356	29.070	1.00	91.90	C
Atom	2420	CD	GLU	A	580	57.357	36.829	28.268	1.00	108.07	C
Atom	2421	OE1	GLU	A	580	58.497	36.659	28.753	1.00	105.20	O
Atom	2422	OE2	GLU	A	580	57.157	37.369	27.158	1.00	113.44	O
Atom	2423	C	GLU	A	580	55.850	33.899	32.052	1.00	83.65	C
Atom	2424	O	GLU	A	580	56.486	32.946	31.610	1.00	82.11	O
Atom	2425	N	MET	A	581	55.489	33.989	33.327	1.00	84.29	N
Atom	2426	CA	MET	A	581	55.878	32.961	34.288	1.00	76.89	C
Atom	2427	CB	MET	A	581	55.399	33.318	35.694	1.00	75.91	C
Atom	2428	CG	MET	A	581	56.130	34.495	36.310	1.00	76.20	C
Atom	2429	SD	MET	A	581	55.676	34.747	38.033	1.00	77.39	S
Atom	2430	CE	MET	A	581	56.086	33.147	38.725	1.00	64.00	C
Atom	2431	C	MET	A	581	55.383	31.571	33.895	1.00	76.68	C
Atom	2432	O	MET	A	581	55.820	30.568	34.461	1.00	74.32	O
Atom	2433	N	ARG	A	582	54.473	31.516	32.927	1.00	80.33	N
Atom	2434	CA	ARG	A	582	54.011	30.243	32.385	1.00	78.04	C
Atom	2435	CB	ARG	A	582	53.011	30.467	31.250	1.00	87.55	C
Atom	2436	CG	ARG	A	582	51.629	30.911	31.697	1.00	92.16	C
Atom	2437	CD	ARG	A	582	50.661	30.902	30.525	1.00	95.36	C
Atom	2438	NE	ARG	A	582	49.304	31.286	30.907	1.00	94.28	N
Atom	2439	CZ	ARG	A	582	48.815	32.517	30.795	1.00	97.90	C
Atom	2440	NH1	ARG	A	582	49.575	33.493	30.315	1.00	83.31	N
Atom	2441	NH2	ARG	A	582	47.567	32.771	31.164	1.00	110.81	N
Atom	2442	C	ARG	A	582	55.190	29.425	31.871	1.00	80.28	C
Atom	2443	O	ARG	A	582	55.143	28.194	31.849	1.00	79.98	O
Atom	2444	N	ARG	A	583	56.243	30.120	31.452	1.00	79.90	N
Atom	2445	CA	ARG	A	583	57.446	29.467	30.954	1.00	77.94	C
Atom	2446	CB	ARG	A	583	58.555	30.491	30.710	1.00	83.44	C
Atom	2447	CG	ARG	A	583	58.185	31.626	29.771	1.00	91.82	C
Atom	2448	CD	ARG	A	583	58.270	31.212	28.314	1.00	101.01	C
Atom	2449	NE	ARG	A	583	58.299	32.378	27.434	1.00	113.97	N
Atom	2450	CZ	ARG	A	583	59.399	33.066	27.142	1.00	121.99	C
Atom	2451	NH1	ARG	A	583	60.565	32.703	27.658	1.00	118.47	N
Atom	2452	NH2	ARG	A	583	59.332	34.116	26.334	1.00	115.39	N
Atom	2453	C	ARG	A	583	57.930	28.426	31.952	1.00	77.46	C
Atom	2454	O	ARG	A	583	58.478	27.394	31.570	1.00	83.61	O
Atom	2455	N	CYS	A	584	57.724	28.705	33.235	1.00	73.39	N
Atom	2456	CA	CYS	A	584	58.135	27.792	34.297	1.00	73.01	C
Atom	2457	CB	CYS	A	584	57.755	28.354	35.667	1.00	68.49	C
Atom	2458	SG	CYS	A	584	58.475	29.973	36.023	1.00	70.75	S
Atom	2459	C	CYS	A	584	57.525	26.407	34.105	1.00	75.13	C
Atom	2460	O	CYS	A	584	58.168	25.394	34.375	1.00	73.34	O
Atom	2461	N	LEU	A	585	56.281	26.373	33.637	1.00	79.70	N
Atom	2462	CA	LEU	A	585	55.607	25.116	33.342	1.00	78.19	C
Atom	2463	CB	LEU	A	585	54.169	25.378	32.896	1.00	72.50	C
Atom	2464	CG	LEU	A	585	53.207	25.894	33.969	1.00	73.82	C
Atom	2465	CD1	LEU	A	585	51.983	26.530	33.330	1.00	68.84	C
Atom	2466	CD2	LEU	A	585	52.802	24.779	34.929	1.00	67.02	C
Atom	2467	C	LEU	A	585	56.364	24.354	32.261	1.00	80.59	C
Atom	2468	O	LEU	A	585	56.652	23.166	32.408	1.00	77.85	O
Atom	2469	N	LEU	A	586	56.687	25.050	31.176	1.00	80.81	N
Atom	2470	CA	LEU	A	586	57.440	24.461	30.076	1.00	81.21	C
Atom	2471	CB	LEU	A	586	57.602	25.473	28.941	1.00	87.19	C
Atom	2472	CG	LEU	A	586	56.468	25.513	27.914	1.00	98.03	C
Atom	2473	CD1	LEU	A	586	56.254	26.924	27.384	1.00	84.88	C
Atom	2474	CD2	LEU	A	586	56.743	24.533	26.780	1.00	92.36	C
Atom	2475	C	LEU	A	586	58.802	23.964	30.539	1.00	85.77	C
Atom	2476	O	LEU	A	586	59.089	22.770	30.473	1.00	88.44	O
Atom	2477	N	GLN	A	587	59.638	24.885	31.009	1.00	84.94	N
Atom	2478	CA	GLN	A	587	60.967	24.536	31.494	1.00	85.74	C
Atom	2479	CB	GLN	A	587	61.630	25.739	32.167	1.00	85.36	C
Atom	2480	CG	GLN	A	587	62.995	25.430	32.763	1.00	93.76	C
Atom	2481	CD	GLN	A	587	63.654	26.644	33.390	1.00	100.97	C
Atom	2482	OE1	GLN	A	587	62.999	27.453	34.050	1.00	104.32	O
Atom	2483	NE2	GLN	A	587	64.960	26.776	33.187	1.00	107.44	N
Atom	2484	C	GLN	A	587	60.905	23.364	32.467	1.00	85.97	C
Atom	2485	O	GLN	A	587	61.665	22.402	32.349	1.00	90.29	O
Atom	2486	N	SER	A	588	59.994	23.452	33.428	1.00	84.24	N
Atom	2487	CA	SER	A	588	59.819	22.394	34.415	1.00	81.50	C
Atom	2488	CB	SER	A	588	58.726	22.775	35.414	1.00	77.11	C
Atom	2489	OG	SER	A	588	58.613	21.811	36.441	1.00	87.51	O
Atom	2490	C	SER	A	588	59.474	21.075	33.730	1.00	89.39	C
Atom	2491	O	SER	A	588	60.046	20.030	34.044	1.00	88.83	O
Atom	2492	N	LEU	A	589	58.539	21.138	32.787	1.00	88.86	N
Atom	2493	CA	LEU	A	589	58.118	19.965	32.030	1.00	90.66	C
Atom	2494	CB	LEU	A	589	57.025	20.346	31.028	1.00	90.84	C
Atom	2495	CG	LEU	A	589	56.750	19.354	29.894	1.00	89.79	C
Atom	2496	CD1	LEU	A	589	56.311	18.007	30.444	1.00	88.21	C
Atom	2497	CD2	LEU	A	589	55.708	19.910	28.933	1.00	80.65	C
Atom	2498	C	LEU	A	589	59.286	19.311	31.298	1.00	88.50	C
Atom	2499	O	LEU	A	589	59.521	18.112	31.439	1.00	91.08	O
Atom	2500	N	GLN	A	590	60.010	20.105	30.515	1.00	86.90	N
Atom	2501	CA	GLN	A	590	61.128	19.598	29.725	1.00	94.65	C
Atom	2502	CB	GLN	A	590	61.840	20.748	29.011	1.00	89.39	C
Atom	2503	CG	GLN	A	590	61.010	21.386	27.910	1.00	95.11	C
Atom	2504	CD	GLN	A	590	61.704	22.565	27.262	1.00	104.97	C
Atom	2505	OE1	GLN	A	590	62.819	22.928	27.638	1.00	110.06	O
Atom	2506	NE2	GLN	A	590	61.045	23.174	26.282	1.00	105.62	N
Atom	2507	C	GLN	A	590	62.117	18.786	30.562	1.00	95.48	C
Atom	2508	O	GLN	A	590	62.571	17.723	30.139	1.00	97.49	O
Atom	2509	N	GLN	A	591	62.444	19.289	31.748	1.00	91.96	N
Atom	2510	CA	GLN	A	591	63.331	18.570	32.655	1.00	89.24	C
Atom	2511	CB	GLN	A	591	63.584	19.384	33.926	1.00	88.53	C
Atom	2512	CG	GLN	A	591	64.574	20.523	33.745	1.00	91.99	C
Atom	2513	CD	GLN	A	591	64.444	21.591	34.817	1.00	92.85	C
Atom	2514	OE1	GLN	A	591	64.951	22.703	34.666	1.00	101.97	O
Atom	2515	NE2	GLN	A	591	63.754	21.260	35.903	1.00	88.24	N
Atom	2516	C	GLN	A	591	62.751	17.206	33.003	1.00	96.77	C
Atom	2517	O	GLN	A	591	63.447	16.193	32.948	1.00	99.31	O
Atom	2518	N	ILE	A	592	61.470	17.184	33.353	1.00	96.10	N
Atom	2519	CA	ILE	A	592	60.799	15.937	33.687	1.00	98.52	C
Atom	2520	CB	ILE	A	592	59.357	16.187	34.170	1.00	92.47	C
Atom	2521	CG1	ILE	A	592	59.126	15.534	35.531	1.00	87.96	C
Atom	2522	CD1	ILE	A	592	59.842	16.233	36.652	1.00	84.37	C
Atom	2523	CG2	ILE	A	592	58.348	15.700	33.143	1.00	91.65	C
Atom	2524	C	ILE	A	592	60.768	15.041	32.453	1.00	105.06	C
Atom	2525	O	ILE	A	592	60.803	13.814	32.555	1.00	108.33	O
Atom	2526	N	GLU	A	593	60.713	15.673	31.285	1.00	103.14	N
Atom	2527	CA	GLU	A	593	60.631	14.959	30.019	1.00	104.18	C
Atom	2528	CB	GLU	A	593	60.296	15.933	28.888	1.00	101.17	C
Atom	2529	CG	GLU	A	593	59.492	15.325	27.755	1.00	108.35	C
Atom	2530	CD	GLU	A	593	58.666	16.359	27.009	1.00	118.82	C
Atom	2531	OE1	GLU	A	593	57.527	16.034	26.607	1.00	122.29	O
Atom	2532	OE2	GLU	A	593	59.149	17.499	26.834	1.00	107.72	O
Atom	2533	C	GLU	A	593	61.941	14.234	29.731	1.00	108.72	C
Atom	2534	O	GLU	A	593	61.971	13.009	29.618	1.00	116.41	O
Atom	2535	N	SER	A	594	63.025	14.996	29.628	1.00	101.91	N
Atom	2536	CA	SER	A	594	64.339	14.420	29.377	1.00	106.59	C
Atom	2537	CB	SER	A	594	65.404	15.516	29.318	1.00	110.69	C
Atom	2538	OG	SER	A	594	65.785	15.928	30.619	1.00	106.08	O
Atom	2539	C	SER	A	594	64.700	13.411	30.461	1.00	110.87	C
Atom	2540	O	SER	A	594	65.326	12.387	30.188	1.00	112.95	O
Atom	2541	N	MET	A	595	64.297	13.710	31.691	1.00	109.65	N
Atom	2542	CA	MET	A	595	64.594	12.849	32.828	1.00	108.13	C
Atom	2543	CB	MET	A	595	63.981	13.427	34.104	1.00	105.82	C
Atom	2544	CG	MET	A	595	64.812	13.197	35.354	1.00	98.80	C
Atom	2545	SD	MET	A	595	64.051	13.912	36.824	1.00	95.38	S
Atom	2546	CE	MET	A	595	62.951	12.588	37.314	1.00	98.54	C
Atom	2547	C	MET	A	595	64.059	11.444	32.578	1.00	108.36	C
Atom	2548	O	MET	A	595	64.528	10.472	33.170	1.00	108.23	O
Atom	2549	N	ILE	A	596	63.070	11.349	31.695	1.00	113.18	N
Atom	2550	CA	ILE	A	596	62.483	10.067	31.326	1.00	117.43	C
Atom	2551	CB	ILE	A	596	61.047	10.232	30.791	1.00	122.06	C
Atom	2552	CG1	ILE	A	596	60.079	10.490	31.949	1.00	121.40	C
Atom	2553	CD1	ILE	A	596	58.663	10.789	31.513	1.00	116.32	C
Atom	2554	CG2	ILE	A	596	60.619	8.998	30.015	1.00	125.91	C
Atom	2555	C	ILE	A	596	63.348	9.344	30.297	1.00	124.38	C
Atom	2556	O	ILE	A	596	63.467	8.121	30.328	1.00	129.89	O
Atom	2557	N	GLU	A	597	63.954	10.107	29.390	1.00	125.14	N
Atom	2558	CA	GLU	A	597	64.857	9.537	28.395	1.00	123.86	C
Atom	2559	CB	GLU	A	597	65.345	10.613	27.421	1.00	117.57	C
Atom	2560	CG	GLU	A	597	64.232	11.461	26.840	1.00	117.68	C
Atom	2561	CD	GLU	A	597	63.012	10.637	26.498	1.00	121.96	C
Atom	2562	OE1	GLU	A	597	61.939	10.906	27.076	1.00	123.05	O
Atom	2563	OE2	GLU	A	597	63.131	9.710	25.670	1.00	123.26	O
Atom	2564	C	GLU	A	597	66.044	8.876	29.083	1.00	125.65	C
Atom	2565	O	GLU	A	597	66.532	7.836	28.642	1.00	130.69	O
Atom	2566	N	ALA	A	598	66.498	9.486	30.174	1.00	125.03	N
Atom	2567	CA	ALA	A	598	67.601	8.939	30.956	1.00	129.41	C
Atom	2568	CB	ALA	A	598	68.103	9.967	31.960	1.00	124.65	C
Atom	2569	C	ALA	A	598	67.174	7.660	31.667	1.00	127.26	C
Atom	2570	O	ALA	A	598	67.869	7.168	32.556	1.00	135.33	O
Atom	2571	N	GLU	A	599	66.021	7.130	31.269	1.00	121.61	N
Atom	2572	CA	GLU	A	599	65.491	5.898	31.840	1.00	126.72	C
Atom	2573	CB	GLU	A	599	64.496	6.212	32.961	1.00	123.72	C
Atom	2574	CG	GLU	A	599	65.119	6.792	34.223	1.00	124.71	C
Atom	2575	CD	GLU	A	599	65.700	5.729	35.138	1.00	118.48	C
Atom	2576	OE1	GLU	A	599	65.984	6.051	36.312	1.00	112.27	O
Atom	2577	OE2	GLU	A	599	65.866	4.575	34.689	1.00	117.88	O
Atom	2578	C	GLU	A	599	64.817	5.045	30.767	1.00	131.61	C
Atom	2579	O	GLU	A	599	64.898	3.818	30.797	1.00	136.49	O
Atom	2580	N	SER	A	600	64.151	5.704	29.823	1.00	129.93	N
Atom	2581	CA	SER	A	600	63.448	5.013	28.744	1.00	130.99	C
Atom	2582	CB	SER	A	600	62.472	5.959	28.039	1.00	129.03	C
Atom	2583	OG	SER	A	600	61.269	6.093	28.774	1.00	128.30	O
Atom	2584	C	SER	A	600	64.408	4.409	27.727	1.00	137.49	C
Atom	2585	O	SER	A	600	64.177	3.311	27.219	1.00	138.88	O
Atom	2586	N	SER	A	601	65.480	5.132	27.424	1.00	136.51	N
Atom	2587	CA	SER	A	601	66.476	4.643	26.481	1.00	133.98	C
Atom	2588	CB	SER	A	601	67.457	5.756	26.112	1.00	127.75	C
Atom	2589	OG	SER	A	601	68.122	5.465	24.895	1.00	134.97	O
Atom	2590	C	SER	A	601	67.219	3.448	27.072	1.00	135.39	C
Atom	2591	O	SER	A	601	67.679	2.568	26.345	1.00	132.66	O
Atom	2592	N	VAL	A	602	67.324	3.423	28.398	1.00	134.47	N
Atom	2593	CA	VAL	A	602	67.991	2.333	29.104	1.00	139.35	C
Atom	2594	CB	VAL	A	602	68.510	2.789	30.486	1.00	139.31	C
Atom	2595	CG1	VAL	A	602	68.512	1.630	31.477	1.00	130.99	C
Atom	2596	CG2	VAL	A	602	69.898	3.391	30.353	1.00	133.83	C
Atom	2597	C	VAL	A	602	67.087	1.114	29.275	1.00	137.84	C
Atom	2598	O	VAL	A	602	67.519	−0.021	29.072	1.00	137.87	O
Atom	2599	N	LYS	A	603	65.834	1.354	29.646	1.00	139.99	N
Atom	2600	CA	LYS	A	603	64.883	0.270	29.873	1.00	141.53	C
Atom	2601	CB	LYS	A	603	63.797	0.702	30.862	1.00	140.37	C
Atom	2602	CG	LYS	A	603	64.265	0.761	32.310	1.00	139.98	C
Atom	2603	CD	LYS	A	603	64.751	−0.603	32.783	1.00	142.83	C
Atom	2604	CE	LYS	A	603	65.271	−0.545	34.212	1.00	137.68	C
Atom	2605	NZ	LYS	A	603	65.851	−1.847	34.650	1.00	126.51	N
Atom	2606	C	LYS	A	603	64.252	−0.225	28.572	1.00	139.44	C
Atom	2607	O	LYS	A	603	63.428	−1.141	28.584	1.00	132.71	O
Atom	2608	N	GLU	A	604	64.644	0.390	27.460	1.00	139.80	N
Atom	2609	CA	GLU	A	604	64.184	−0.011	26.130	1.00	138.14	C
Atom	2610	CB	GLU	A	604	64.392	−1.514	25.908	1.00	140.13	C
Atom	2611	CG	GLU	A	604	65.857	−1.928	25.871	1.00	135.79	C
Atom	2612	CD	GLU	A	604	66.047	−3.426	25.721	1.00	131.91	C
Atom	2613	OE1	GLU	A	604	67.090	−3.939	26.179	1.00	118.77	O
Atom	2614	OE2	GLU	A	604	65.155	−4.090	25.149	1.00	130.37	O
Atom	2615	C	GLU	A	604	62.736	0.388	25.841	1.00	138.57	C
Atom	2616	O	GLU	A	604	62.427	0.879	24.755	1.00	136.63	O
Atom	2617	N	LYS	A	605	61.854	0.179	26.813	1.00	141.21	N
Atom	2618	CA	LYS	A	605	60.452	0.562	26.668	1.00	138.83	C
Atom	2619	CB	LYS	A	605	59.545	−0.424	27.413	1.00	132.36	C
Atom	2620	CG	LYS	A	605	58.110	0.056	27.581	1.00	134.62	C
Atom	2621	CD	LYS	A	605	57.303	−0.869	28.477	1.00	139.57	C
Atom	2622	CE	LYS	A	605	56.035	−0.184	28.974	1.00	144.63	C
Atom	2623	NZ	LYS	A	605	55.175	0.314	27.861	1.00	135.22	N
Atom	2624	C	LYS	A	605	60.210	1.981	27.180	1.00	137.38	C
Atom	2625	O	LYS	A	605	60.948	2.478	28.031	1.00	135.56	O
Atom	2626	N	ASP	A	606	59.179	2.633	26.649	1.00	140.81	N
Atom	2627	CA	ASP	A	606	58.753	3.933	27.152	1.00	136.10	C
Atom	2628	CB	ASP	A	606	57.610	4.489	26.303	1.00	130.54	C
Atom	2629	CG	ASP	A	606	57.152	5.854	26.770	1.00	132.41	C
Atom	2630	OD1	ASP	A	606	57.989	6.780	26.818	1.00	135.66	O
Atom	2631	OD2	ASP	A	606	55.952	6.002	27.083	1.00	130.33	O
Atom	2632	C	ASP	A	606	58.309	3.794	28.605	1.00	133.11	C
Atom	2633	O	ASP	A	606	57.559	2.879	28.946	1.00	135.49	O
Atom	2634	N	MET	A	607	58.765	4.707	29.456	1.00	128.88	N
Atom	2635	CA	MET	A	607	58.566	4.563	30.896	1.00	126.19	C
Atom	2636	CB	MET	A	607	59.910	4.661	31.622	1.00	123.39	C
Atom	2637	CG	MET	A	607	60.857	3.514	31.318	1.00	127.66	C
Atom	2638	SD	MET	A	607	60.198	1.926	31.861	1.00	132.30	S
Atom	2639	CE	MET	A	607	60.048	2.211	33.624	1.00	119.39	C
Atom	2640	C	MET	A	607	57.574	5.554	31.504	1.00	122.00	C
Atom	2641	O	MET	A	607	57.277	5.482	32.697	1.00	120.28	O
Atom	2642	N	THR	A	608	57.059	6.471	30.691	1.00	119.80	N
Atom	2643	CA	THR	A	608	56.158	7.504	31.196	1.00	121.31	C
Atom	2644	CB	THR	A	608	55.608	8.389	30.061	1.00	121.90	C
Atom	2645	OG1	THR	A	608	54.583	7.684	29.354	1.00	131.28	O
Atom	2646	CG2	THR	A	608	56.719	8.767	29.095	1.00	128.64	C
Atom	2647	C	THR	A	608	54.990	6.906	31.979	1.00	119.72	C
Atom	2648	O	THR	A	608	54.694	7.338	33.093	1.00	115.46	O
Atom	2649	N	LYS	A	609	54.336	5.907	31.393	1.00	123.71	N
Atom	2650	CA	LYS	A	609	53.199	5.260	32.039	1.00	123.09	C
Atom	2651	CB	LYS	A	609	52.527	4.268	31.089	1.00	128.84	C
Atom	2652	CG	LYS	A	609	51.856	4.918	29.888	1.00	138.20	C
Atom	2653	CD	LYS	A	609	51.085	3.894	29.064	1.00	156.83	C
Atom	2654	CE	LYS	A	609	52.004	2.810	28.518	1.00	155.77	C
Atom	2655	NZ	LYS	A	609	51.270	1.851	27.647	1.00	159.00	N
Atom	2656	C	LYS	A	609	53.621	4.560	33.325	1.00	109.50	C
Atom	2657	O	LYS	A	609	53.021	4.765	34.378	1.00	107.67	O
Atom	2658	N	GLU	A	610	54.655	3.731	33.231	1.00	112.30	N
Atom	2659	CA	GLU	A	610	55.204	3.060	34.404	1.00	123.40	C
Atom	2660	CB	GLU	A	610	56.548	2.413	34.065	1.00	128.02	C
Atom	2661	CG	GLU	A	610	56.468	0.917	33.827	1.00	129.17	C
Atom	2662	CD	GLU	A	610	56.428	0.132	35.124	1.00	132.80	C
Atom	2663	OE1	GLU	A	610	57.462	0.091	35.825	1.00	131.46	O
Atom	2664	OE2	GLU	A	610	55.366	−0.443	35.442	1.00	129.57	O
Atom	2665	C	GLU	A	610	55.367	4.026	35.570	1.00	117.22	C
Atom	2666	O	GLU	A	610	54.842	3.799	36.659	1.00	111.69	O
Atom	2667	N	PHE	A	611	56.096	5.109	35.330	1.00	117.38	N
Atom	2668	CA	PHE	A	611	56.354	6.103	36.363	1.00	114.82	C
Atom	2669	CB	PHE	A	611	57.274	7.203	35.827	1.00	112.44	C
Atom	2670	CG	PHE	A	611	58.697	6.763	35.622	1.00	115.09	C
Atom	2671	CD1	PHE	A	611	59.260	5.788	36.428	1.00	115.37	C
Atom	2672	CE1	PHE	A	611	60.571	5.390	36.244	1.00	114.85	C
Atom	2673	CZ	PHE	A	611	61.337	5.976	35.260	1.00	112.48	C
Atom	2674	CE2	PHE	A	611	60.792	6.956	34.456	1.00	114.22	C
Atom	2675	CD2	PHE	A	611	59.481	7.347	34.641	1.00	113.55	C
Atom	2676	C	PHE	A	611	55.069	6.717	36.923	1.00	106.27	C
Atom	2677	O	PHE	A	611	54.755	6.560	38.105	1.00	102.31	O
Atom	2678	N	PHE	A	612	54.330	7.414	36.069	1.00	98.04	N
Atom	2679	CA	PHE	A	612	53.147	8.155	36.498	1.00	100.09	C
Atom	2680	CB	PHE	A	612	52.600	8.982	35.334	1.00	107.30	C
Atom	2681	CG	PHE	A	612	53.350	10.258	35.091	1.00	107.38	C
Atom	2682	CD1	PHE	A	612	53.138	11.363	35.900	1.00	104.26	C
Atom	2683	CE1	PHE	A	612	53.821	12.539	35.681	1.00	106.71	C
Atom	2684	CZ	PHE	A	612	54.723	12.626	34.643	1.00	104.50	C
Atom	2685	CE2	PHE	A	612	54.942	11.538	33.826	1.00	108.95	C
Atom	2686	CD2	PHE	A	612	54.257	10.360	34.049	1.00	112.42	C
Atom	2687	C	PHE	A	612	52.028	7.294	37.084	1.00	106.64	C
Atom	2688	O	PHE	A	612	51.167	7.800	37.802	1.00	103.36	O
Atom	2689	N	GLU	A	613	52.034	6.002	36.773	1.00	116.44	N
Atom	2690	CA	GLU	A	613	50.959	5.118	37.215	1.00	108.38	C
Atom	2691	CB	GLU	A	613	50.610	4.094	36.133	1.00	106.92	C
Atom	2692	CG	GLU	A	613	50.059	4.723	34.865	1.00	105.69	C
Atom	2693	CD	GLU	A	613	48.704	5.388	35.062	1.00	109.17	C
Atom	2694	OE1	GLU	A	613	48.019	5.085	36.060	1.00	99.41	O
Atom	2695	OE2	GLU	A	613	48.317	6.213	34.207	1.00	105.52	O
Atom	2696	C	GLU	A	613	51.236	4.433	38.548	1.00	111.46	C
Atom	2697	O	GLU	A	613	50.303	4.021	39.237	1.00	107.68	O
Atom	2698	N	ASN	A	614	52.511	4.313	38.909	1.00	117.58	N
Atom	2699	CA	ASN	A	614	52.867	3.792	40.227	1.00	121.99	C
Atom	2700	CB	ASN	A	614	52.564	2.292	40.350	1.00	122.69	C
Atom	2701	CG	ASN	A	614	53.117	1.483	39.197	1.00	132.57	C
Atom	2702	OD1	ASN	A	614	53.839	2.004	38.347	1.00	132.76	O
Atom	2703	ND2	ASN	A	614	52.784	0.197	39.165	1.00	128.04	N
Atom	2704	C	ASN	A	614	54.281	4.109	40.714	1.00	128.90	C
Atom	2705	O	ASN	A	614	54.587	5.256	41.038	1.00	113.22	O
Atom	2706	N	LYS	A	615	55.134	3.092	40.771	1.00	138.63	N
Atom	2707	CA	LYS	A	615	56.365	3.186	41.546	1.00	132.81	C
Atom	2708	CB	LYS	A	615	56.595	1.894	42.336	1.00	139.62	C
Atom	2709	CG	LYS	A	615	57.377	2.082	43.626	1.00	137.39	C
Atom	2710	CD	LYS	A	615	56.686	1.368	44.780	1.00	141.88	C
Atom	2711	CE	LYS	A	615	55.293	1.935	45.015	1.00	142.20	C
Atom	2712	NZ	LYS	A	615	54.496	1.073	45.926	1.00	129.30	N
Atom	2713	C	LYS	A	615	57.611	3.555	40.752	1.00	125.11	C
Atom	2714	O	LYS	A	615	57.645	3.466	39.523	1.00	119.68	O
Atom	2715	N	SER	A	616	58.631	3.937	41.513	1.00	125.44	N
Atom	2716	CA	SER	A	616	59.881	4.525	41.049	1.00	120.83	C
Atom	2717	CB	SER	A	616	59.853	4.895	39.569	1.00	114.99	C
Atom	2718	OG	SER	A	616	61.170	5.112	39.096	1.00	112.57	O
Atom	2719	C	SER	A	616	60.085	5.763	41.907	1.00	113.01	C
Atom	2720	O	SER	A	616	60.681	6.752	41.477	1.00	101.80	O
Atom	2721	N	GLU	A	617	59.537	5.697	43.120	1.00	116.89	N
Atom	2722	CA	GLU	A	617	59.764	6.693	44.154	1.00	95.78	C
Atom	2723	CB	GLU	A	617	58.915	6.368	45.385	1.00	104.09	C
Atom	2724	CG	GLU	A	617	58.741	7.517	46.363	1.00	114.93	C
Atom	2725	CD	GLU	A	617	57.550	7.326	47.286	1.00	119.59	C
Atom	2726	OE1	GLU	A	617	57.024	8.341	47.796	1.00	100.90	O
Atom	2727	OE2	GLU	A	617	57.135	6.164	47.491	1.00	121.26	O
Atom	2728	C	GLU	A	617	61.234	6.604	44.505	1.00	98.91	C
Atom	2729	O	GLU	A	617	61.608	6.561	45.677	1.00	100.44	O
Atom	2730	N	THR	A	618	62.062	6.555	43.466	1.00	104.95	N
Atom	2731	CA	THR	A	618	63.486	6.310	43.608	1.00	109.60	C
Atom	2732	CB	THR	A	618	63.941	5.058	42.806	1.00	120.50	C
Atom	2733	OG1	THR	A	618	63.039	3.968	43.043	1.00	113.43	O
Atom	2734	CG2	THR	A	618	65.351	4.635	43.208	1.00	101.19	C
Atom	2735	C	THR	A	618	64.267	7.530	43.140	1.00	105.00	C
Atom	2736	O	THR	A	618	65.369	7.405	42.608	1.00	112.03	O
Atom	2737	N	TRP	A	619	63.681	8.711	43.324	1.00	104.26	N
Atom	2738	CA	TRP	A	619	64.406	9.961	43.118	1.00	92.89	C
Atom	2739	CB	TRP	A	619	63.706	10.856	42.095	1.00	87.49	C
Atom	2740	CG	TRP	A	619	62.956	10.134	41.028	1.00	98.62	C
Atom	2741	CD1	TRP	A	619	61.670	9.675	41.094	1.00	101.12	C
Atom	2742	NE1	TRP	A	619	61.321	9.078	39.910	1.00	100.83	N
Atom	2743	CE2	TRP	A	619	62.384	9.146	39.047	1.00	105.52	C
Atom	2744	CD2	TRP	A	619	63.431	9.811	39.718	1.00	99.40	C
Atom	2745	CE3	TRP	A	619	64.641	10.013	39.047	1.00	94.75	C
Atom	2746	CZ3	TRP	A	619	64.764	9.551	37.750	1.00	107.20	C
Atom	2747	CH2	TRP	A	619	63.703	8.895	37.110	1.00	115.63	C
Atom	2748	CZ2	TRP	A	619	62.508	8.683	37.741	1.00	104.22	C
Atom	2749	C	TRP	A	619	64.497	10.706	44.443	1.00	83.55	C
Atom	2750	O	TRP	A	619	63.474	11.054	45.030	1.00	85.63	O
Atom	2751	N	PRO	A	620	65.722	10.937	44.930	1.00	82.79	N
Atom	2752	CA	PRO	A	620	65.900	11.722	46.156	1.00	86.41	C
Atom	2753	CB	PRO	A	620	67.412	11.658	46.396	1.00	84.36	C
Atom	2754	CG	PRO	A	620	67.859	10.429	45.682	1.00	79.67	C
Atom	2755	CD	PRO	A	620	66.984	10.335	44.469	1.00	82.65	C
Atom	2756	C	PRO	A	620	65.449	13.174	45.981	1.00	78.86	C
Atom	2757	O	PRO	A	620	65.775	13.815	44.981	1.00	75.82	O
Atom	2758	N	ILE	A	621	64.692	13.669	46.955	1.00	78.76	N
Atom	2759	CA	ILE	A	621	64.235	15.051	46.993	1.00	75.50	C
Atom	2760	CB	ILE	A	621	62.834	15.197	46.377	1.00	78.06	C
Atom	2761	CG1	ILE	A	621	61.871	14.207	47.040	1.00	77.14	C
Atom	2762	CD1	ILE	A	621	60.412	14.528	46.829	1.00	88.15	C
Atom	2763	CG2	ILE	A	621	62.876	14.986	44.871	1.00	77.05	C
Atom	2764	C	ILE	A	621	64.108	15.420	48.457	1.00	71.18	C
Atom	2765	O	ILE	A	621	63.615	16.492	48.802	1.00	64.53	O
Atom	2766	N	GLY	A	622	64.580	14.518	49.311	1.00	76.34	N
Atom	2767	CA	GLY	A	622	64.140	14.464	50.691	1.00	81.76	C
Atom	2768	C	GLY	A	622	64.830	15.299	51.744	1.00	70.85	C
Atom	2769	O	GLY	A	622	64.752	16.522	51.722	1.00	78.29	O
Atom	2770	N	GLU	A	623	65.478	14.616	52.683	1.00	74.86	N
Atom	2771	CA	GLU	A	623	65.960	15.226	53.919	1.00	83.47	C
Atom	2772	CB	GLU	A	623	66.675	16.554	53.656	1.00	95.20	C
Atom	2773	CG	GLU	A	623	68.091	16.411	53.113	1.00	102.18	C
Atom	2774	CD	GLU	A	623	69.069	15.870	54.144	1.00	97.18	C
Atom	2775	OE1	GLU	A	623	70.071	16.557	54.434	1.00	98.17	O
Atom	2776	OE2	GLU	A	623	68.831	14.764	54.673	1.00	96.44	O
Atom	2777	C	GLU	A	623	64.821	15.414	54.919	1.00	91.51	C
Atom	2778	O	GLU	A	623	63.989	16.310	54.772	1.00	81.01	O
Atom	2779	N	SER	A	624	64.793	14.548	55.928	1.00	101.81	N
Atom	2780	CA	SER	A	624	63.831	14.642	57.020	1.00	98.36	C
Atom	2781	CB	SER	A	624	62.614	13.751	56.751	1.00	92.54	C
Atom	2782	OG	SER	A	624	62.880	12.401	57.092	1.00	93.41	O
Atom	2783	C	SER	A	624	64.539	14.208	58.301	1.00	94.52	C
Atom	2784	O	SER	A	624	65.722	13.875	58.266	1.00	91.79	O
Atom	2785	N	PRO	A	625	63.832	14.225	59.442	1.00	98.70	N
Atom	2786	CA	PRO	A	625	64.479	13.732	60.663	1.00	103.15	C
Atom	2787	CB	PRO	A	625	63.337	13.727	61.680	1.00	101.56	C
Atom	2788	CG	PRO	A	625	62.438	14.819	61.220	1.00	93.59	C
Atom	2789	CD	PRO	A	625	62.497	14.788	59.715	1.00	94.42	C
Atom	2790	C	PRO	A	625	65.035	12.322	60.476	1.00	103.52	C
Atom	2791	O	PRO	A	625	66.068	11.984	61.056	1.00	93.92	O
Atom	2792	N	LYS	A	626	64.354	11.516	59.667	1.00	103.32	N
Atom	2793	CA	LYS	A	626	64.799	10.159	59.369	1.00	100.47	C
Atom	2794	CB	LYS	A	626	63.637	9.335	58.815	1.00	105.44	C
Atom	2795	CG	LYS	A	626	62.413	9.333	59.712	1.00	112.03	C
Atom	2796	CD	LYS	A	626	61.143	9.113	58.911	1.00	111.35	C
Atom	2797	CE	LYS	A	626	59.911	9.484	59.723	1.00	124.64	C
Atom	2798	NZ	LYS	A	626	58.705	9.645	58.860	1.00	129.01	N
Atom	2799	C	LYS	A	626	65.959	10.166	58.377	1.00	94.40	C
Atom	2800	O	LYS	A	626	66.637	9.155	58.195	1.00	99.11	O
Atom	2801	N	GLY	A	627	66.179	11.310	57.735	1.00	94.71	N
Atom	2802	CA	GLY	A	627	67.278	11.459	56.800	1.00	91.56	C
Atom	2803	C	GLY	A	627	66.827	11.484	55.352	1.00	87.59	C
Atom	2804	O	GLY	A	627	65.761	12.011	55.032	1.00	85.58	O
Atom	2805	N	MET	A	628	67.650	10.911	54.479	1.00	93.82	N
Atom	2806	CA	MET	A	628	67.359	10.851	53.052	1.00	90.56	C
Atom	2807	CB	MET	A	628	68.311	9.874	52.359	1.00	102.34	C
Atom	2808	CG	MET	A	628	67.977	9.594	50.901	1.00	100.31	C
Atom	2809	SD	MET	A	628	68.039	11.082	49.888	1.00	101.81	S
Atom	2810	CE	MET	A	628	69.647	11.720	50.352	1.00	84.99	C
Atom	2811	C	MET	A	628	65.915	10.442	52.796	1.00	91.86	C
Atom	2812	O	MET	A	628	65.396	9.528	53.437	1.00	90.16	O
Atom	2813	N	GLU	A	629	65.272	11.127	51.856	1.00	91.03	N
Atom	2814	CA	GLU	A	629	63.884	10.842	51.515	1.00	86.38	C
Atom	2815	CB	GLU	A	629	62.953	11.838	52.209	1.00	80.15	C
Atom	2816	CG	GLU	A	629	61.562	11.299	52.464	1.00	100.60	C
Atom	2817	CD	GLU	A	629	61.562	10.166	53.473	1.00	100.76	C
Atom	2818	OE1	GLU	A	629	62.112	10.356	54.580	1.00	94.06	O
Atom	2819	OE2	GLU	A	629	61.012	9.089	53.158	1.00	101.39	O
Atom	2820	C	GLU	A	629	63.680	10.879	50.000	1.00	86.26	C
Atom	2821	O	GLU	A	629	64.340	11.641	49.294	1.00	89.17	O
Atom	2822	N	GLU	A	630	62.768	10.051	49.501	1.00	86.58	N
Atom	2823	CA	GLU	A	630	62.543	9.958	48.061	1.00	87.17	C
Atom	2824	CB	GLU	A	630	63.101	8.643	47.514	1.00	90.56	C
Atom	2825	CG	GLU	A	630	64.572	8.421	47.830	1.00	92.59	C
Atom	2826	CD	GLU	A	630	65.177	7.294	47.018	1.00	94.36	C
Atom	2827	OE1	GLU	A	630	64.468	6.742	46.153	1.00	93.27	O
Atom	2828	OE2	GLU	A	630	66.361	6.963	47.241	1.00	96.04	O
Atom	2829	C	GLU	A	630	61.070	10.108	47.693	1.00	87.88	C
Atom	2830	O	GLU	A	630	60.187	9.907	48.526	1.00	88.40	O
Atom	2831	N	GLY	A	631	60.814	10.469	46.439	1.00	84.64	N
Atom	2832	CA	GLY	A	631	59.461	10.710	45.972	1.00	85.80	C
Atom	2833	C	GLY	A	631	59.288	10.358	44.509	1.00	82.95	C
Atom	2834	O	GLY	A	631	60.259	10.326	43.752	1.00	84.40	O
Atom	2835	N	SER	A	632	58.047	10.096	44.109	1.00	83.13	N
Atom	2836	CA	SER	A	632	57.753	9.710	42.733	1.00	90.06	C
Atom	2837	CB	SER	A	632	56.410	8.974	42.647	1.00	88.29	C
Atom	2838	OG	SER	A	632	55.332	9.802	43.055	1.00	86.18	O
Atom	2839	C	SER	A	632	57.765	10.904	41.782	1.00	82.07	C
Atom	2840	O	SER	A	632	57.793	12.056	42.211	1.00	83.75	O
Atom	2841	N	ILE	A	633	57.744	10.606	40.487	1.00	83.46	N
Atom	2842	CA	ILE	A	633	57.751	11.613	39.431	1.00	86.57	C
Atom	2843	CB	ILE	A	633	57.431	10.977	38.065	1.00	86.62	C
Atom	2844	CG1	ILE	A	633	57.688	9.469	38.106	1.00	103.94	C
Atom	2845	CD1	ILE	A	633	56.628	8.679	38.859	1.00	103.79	C
Atom	2846	CG2	ILE	A	633	58.226	11.657	36.954	1.00	82.97	C
Atom	2847	C	ILE	A	633	56.732	12.714	39.689	1.00	85.17	C
Atom	2848	O	ILE	A	633	56.929	13.862	39.291	1.00	79.59	O
Atom	2849	N	GLY	A	634	55.634	12.352	40.345	1.00	82.80	N
Atom	2850	CA	GLY	A	634	54.610	13.315	40.695	1.00	78.65	C
Atom	2851	C	GLY	A	634	55.187	14.444	41.525	1.00	83.48	C
Atom	2852	O	GLY	A	634	55.094	15.615	41.153	1.00	76.88	O
Atom	2853	N	LYS	A	635	55.792	14.085	42.653	1.00	79.86	N
Atom	2854	CA	LYS	A	635	56.434	15.058	43.528	1.00	80.73	C
Atom	2855	CB	LYS	A	635	56.955	14.375	44.795	1.00	79.34	C
Atom	2856	CG	LYS	A	635	55.858	13.717	45.617	1.00	95.76	C
Atom	2857	CD	LYS	A	635	56.398	13.019	46.851	1.00	104.62	C
Atom	2858	CE	LYS	A	635	55.266	12.405	47.659	1.00	97.56	C
Atom	2859	NZ	LYS	A	635	55.777	11.672	48.846	1.00	102.49	N
Atom	2860	C	LYS	A	635	57.566	15.762	42.793	1.00	77.12	C
Atom	2861	O	LYS	A	635	57.777	16.962	42.962	1.00	80.79	O
Atom	2862	N	VAL	A	636	58.285	15.010	41.967	1.00	76.00	N
Atom	2863	CA	VAL	A	636	59.370	15.574	41.174	1.00	79.36	C
Atom	2864	CB	VAL	A	636	60.089	14.494	40.343	1.00	80.70	C
Atom	2865	CG1	VAL	A	636	61.185	15.113	39.492	1.00	79.41	C
Atom	2866	CG2	VAL	A	636	60.669	13.427	41.253	1.00	82.27	C
Atom	2867	C	VAL	A	636	58.852	16.671	40.247	1.00	77.23	C
Atom	2868	O	VAL	A	636	59.450	17.742	40.145	1.00	77.82	O
Atom	2869	N	CYS	A	637	57.738	16.398	39.576	1.00	72.19	N
Atom	2870	CA	CYS	A	637	57.118	17.380	38.696	1.00	72.42	C
Atom	2871	CB	CYS	A	637	55.795	16.848	38.142	1.00	81.75	C
Atom	2872	SG	CYS	A	637	55.962	15.549	36.901	1.00	81.50	S
Atom	2873	C	CYS	A	637	56.867	18.684	39.441	1.00	74.97	C
Atom	2874	O	CYS	A	637	57.181	19.766	38.945	1.00	74.57	O
Atom	2875	N	ARG	A	638	56.300	18.572	40.638	1.00	75.11	N
Atom	2876	CA	ARG	A	638	55.965	19.743	41.440	1.00	71.66	C
Atom	2877	CB	ARG	A	638	55.025	19.361	42.586	1.00	71.75	C
Atom	2878	CG	ARG	A	638	53.595	19.091	42.148	1.00	72.75	C
Atom	2879	CD	ARG	A	638	52.700	18.758	43.333	1.00	72.70	C
Atom	2880	NE	ARG	A	638	53.052	17.481	43.948	1.00	78.15	N
Atom	2881	CZ	ARG	A	638	52.618	16.301	43.517	1.00	82.05	C
Atom	2882	NH1	ARG	A	638	51.816	16.235	42.463	1.00	73.50	N
Atom	2883	NH2	ARG	A	638	52.988	15.188	44.137	1.00	76.52	N
Atom	2884	C	ARG	A	638	57.212	20.434	41.982	1.00	71.12	C
Atom	2885	O	ARG	A	638	57.308	21.660	41.959	1.00	71.75	O
Atom	2886	N	THR	A	639	58.163	19.645	42.468	1.00	69.12	N
Atom	2887	CA	THR	A	639	59.407	20.193	42.996	1.00	69.30	C
Atom	2888	CB	THR	A	639	60.331	19.090	43.531	1.00	68.02	C
Atom	2889	OG1	THR	A	639	59.717	18.465	44.665	1.00	71.55	O
Atom	2890	CG2	THR	A	639	61.667	19.677	43.950	1.00	65.50	C
Atom	2891	C	THR	A	639	60.149	21.012	41.945	1.00	70.35	C
Atom	2892	O	THR	A	639	60.624	22.111	42.227	1.00	70.09	O
Atom	2893	N	LEU	A	640	60.243	20.477	40.733	1.00	69.36	N
Atom	2894	CA	LEU	A	640	60.910	21.186	39.647	1.00	66.39	C
Atom	2895	CB	LEU	A	640	61.148	20.259	38.453	1.00	71.48	C
Atom	2896	CG	LEU	A	640	62.232	19.200	38.670	1.00	71.92	C
Atom	2897	CD1	LEU	A	640	62.571	18.496	37.367	1.00	72.87	C
Atom	2898	CD2	LEU	A	640	63.469	19.838	39.269	1.00	64.54	C
Atom	2899	C	LEU	A	640	60.116	22.415	39.221	1.00	68.97	C
Atom	2900	O	LEU	A	640	60.690	23.421	38.806	1.00	73.04	O
Atom	2901	N	LEU	A	641	58.794	22.336	39.328	1.00	68.65	N
Atom	2902	CA	LEU	A	641	57.950	23.479	39.013	1.00	66.96	C
Atom	2903	CB	LEU	A	641	56.472	23.091	39.064	1.00	66.75	C
Atom	2904	CG	LEU	A	641	55.513	23.832	38.129	1.00	66.15	C
Atom	2905	CD1	LEU	A	641	54.169	24.030	38.813	1.00	67.27	C
Atom	2906	CD2	LEU	A	641	56.082	25.170	37.699	1.00	66.47	C
Atom	2907	C	LEU	A	641	58.236	24.583	40.022	1.00	66.42	C
Atom	2908	O	LEU	A	641	58.482	25.731	39.654	1.00	66.34	O
Atom	2909	N	ALA	A	642	58.213	24.217	41.300	1.00	65.72	N
Atom	2910	CA	ALA	A	642	58.482	25.158	42.378	1.00	62.38	C
Atom	2911	CB	ALA	A	642	58.409	24.457	43.726	1.00	59.78	C
Atom	2912	C	ALA	A	642	59.843	25.820	42.190	1.00	63.52	C
Atom	2913	O	ALA	A	642	59.970	27.039	42.303	1.00	63.41	O
Atom	2914	N	LYS	A	643	60.858	25.015	41.892	1.00	60.01	N
Atom	2915	CA	LYS	A	643	62.199	25.542	41.676	1.00	63.46	C
Atom	2916	CB	LYS	A	643	63.192	24.414	41.388	1.00	64.77	C
Atom	2917	CG	LYS	A	643	64.624	24.891	41.206	1.00	64.07	C
Atom	2918	CD	LYS	A	643	65.579	23.734	40.994	1.00	72.85	C
Atom	2919	CE	LYS	A	643	67.018	24.223	40.908	1.00	88.23	C
Atom	2920	NZ	LYS	A	643	67.987	23.089	40.808	1.00	95.20	N
Atom	2921	C	LYS	A	643	62.217	26.563	40.542	1.00	63.06	C
Atom	2922	O	LYS	A	643	62.759	27.658	40.688	1.00	59.19	O
Atom	2923	N	SER	A	644	61.624	26.198	39.412	1.00	61.31	N
Atom	2924	CA	SER	A	644	61.550	27.103	38.274	1.00	60.12	C
Atom	2925	CB	SER	A	644	60.851	26.423	37.100	1.00	63.23	C
Atom	2926	OG	SER	A	644	60.749	27.303	35.996	1.00	64.44	O
Atom	2927	C	SER	A	644	60.813	28.388	38.639	1.00	61.74	C
Atom	2928	O	SER	A	644	61.195	29.479	38.210	1.00	63.14	O
Atom	2929	N	VAL	A	645	59.759	28.252	39.438	1.00	63.43	N
Atom	2930	CA	VAL	A	645	58.943	29.396	39.833	1.00	63.72	C
Atom	2931	CB	VAL	A	645	57.592	28.955	40.434	1.00	59.72	C
Atom	2932	CG1	VAL	A	645	56.908	30.119	41.132	1.00	58.83	C
Atom	2933	CG2	VAL	A	645	56.696	28.394	39.350	1.00	59.71	C
Atom	2934	C	VAL	A	645	59.675	30.320	40.804	1.00	62.52	C
Atom	2935	O	VAL	A	645	59.617	31.542	40.669	1.00	60.59	O
Atom	2936	N	PHE	A	646	60.364	29.737	41.779	1.00	58.88	N
Atom	2937	CA	PHE	A	646	61.130	30.527	42.737	1.00	61.38	C
Atom	2938	CB	PHE	A	646	61.567	29.671	43.928	1.00	61.48	C
Atom	2939	CG	PHE	A	646	60.567	29.646	45.050	1.00	62.87	C
Atom	2940	CD1	PHE	A	646	59.227	29.399	44.796	1.00	59.06	C
Atom	2941	CE1	PHE	A	646	58.304	29.377	45.825	1.00	55.39	C
Atom	2942	CZ	PHE	A	646	58.714	29.600	47.124	1.00	56.74	C
Atom	2943	CE2	PHE	A	646	60.047	29.846	47.391	1.00	61.33	C
Atom	2944	CD2	PHE	A	646	60.966	29.869	46.357	1.00	62.52	C
Atom	2945	C	PHE	A	646	62.327	31.215	42.084	1.00	61.29	C
Atom	2946	O	PHE	A	646	62.699	32.322	42.473	1.00	57.57	O
Atom	2947	N	ASN	A	647	62.926	30.558	41.094	1.00	60.55	N
Atom	2948	CA	ASN	A	647	63.975	31.179	40.293	1.00	58.77	C
Atom	2949	CB	ASN	A	647	64.430	30.242	39.172	1.00	59.08	C
Atom	2950	CG	ASN	A	647	65.358	29.145	39.663	1.00	64.13	C
Atom	2951	OD1	ASN	A	647	66.006	29.279	40.701	1.00	62.43	O
Atom	2952	ND2	ASN	A	647	65.429	28.052	38.912	1.00	60.93	N
Atom	2953	C	ASN	A	647	63.463	32.478	39.690	1.00	65.02	C
Atom	2954	O	ASN	A	647	64.186	33.471	39.608	1.00	64.78	O
Atom	2955	N	SER	A	648	62.202	32.460	39.273	1.00	65.94	N
Atom	2956	CA	SER	A	648	61.583	33.612	38.636	1.00	60.36	C
Atom	2957	CB	SER	A	648	60.416	33.154	37.760	1.00	61.55	C
Atom	2958	OG	SER	A	648	59.943	34.204	36.934	1.00	75.70	O
Atom	2959	C	SER	A	648	61.111	34.628	39.674	1.00	63.54	C
Atom	2960	O	SER	A	648	61.266	35.837	39.492	1.00	65.43	O
Atom	2961	N	LEU	A	649	60.531	34.125	40.761	1.00	64.30	N
Atom	2962	CA	LEU	A	649	60.052	34.968	41.853	1.00	61.15	C
Atom	2963	CB	LEU	A	649	59.292	34.124	42.878	1.00	62.86	C
Atom	2964	CG	LEU	A	649	57.764	34.237	42.928	1.00	62.79	C
Atom	2965	CD1	LEU	A	649	57.173	34.671	41.592	1.00	57.76	C
Atom	2966	CD2	LEU	A	649	57.154	32.928	43.409	1.00	55.59	C
Atom	2967	C	LEU	A	649	61.192	35.699	42.545	1.00	60.41	C
Atom	2968	O	LEU	A	649	61.031	36.827	43.006	1.00	62.41	O
Atom	2969	N	TYR	A	650	62.345	35.047	42.621	1.00	63.70	N
Atom	2970	CA	TYR	A	650	63.491	35.610	43.319	1.00	61.27	C
Atom	2971	CB	TYR	A	650	63.933	34.678	44.447	1.00	57.52	C
Atom	2972	CG	TYR	A	650	62.976	34.623	45.615	1.00	58.29	C
Atom	2973	CD1	TYR	A	650	62.933	35.647	46.549	1.00	57.96	C
Atom	2974	CE1	TYR	A	650	62.064	35.598	47.620	1.00	61.03	C
Atom	2975	CZ	TYR	A	650	61.222	34.514	47.768	1.00	57.15	C
Atom	2976	OH	TYR	A	650	60.355	34.463	48.835	1.00	54.15	O
Atom	2977	CE2	TYR	A	650	61.245	33.484	46.853	1.00	54.41	C
Atom	2978	CD2	TYR	A	650	62.118	33.545	45.785	1.00	58.37	C
Atom	2979	C	TYR	A	650	64.659	35.876	42.376	1.00	63.59	C
Atom	2980	O	TYR	A	650	65.820	35.789	42.774	1.00	57.87	O
Atom	2981	N	ALA	A	651	64.341	36.202	41.127	1.00	64.11	N
Atom	2982	CA	ALA	A	651	65.359	36.524	40.136	1.00	60.08	C
Atom	2983	CB	ALA	A	651	64.715	36.957	38.833	1.00	56.28	C
Atom	2984	C	ALA	A	651	66.284	37.612	40.661	1.00	59.28	C
Atom	2985	O	ALA	A	651	65.827	38.629	41.184	1.00	60.12	O
Atom	2986	N	SER	A	652	67.587	37.388	40.522	1.00	59.07	N
Atom	2987	CA	SER	A	652	68.587	38.343	40.991	1.00	58.06	C
Atom	2988	CB	SER	A	652	68.642	38.346	42.521	1.00	59.23	C
Atom	2989	OG	SER	A	652	69.205	37.143	43.015	1.00	58.66	O
Atom	2990	C	SER	A	652	69.965	38.026	40.425	1.00	62.03	C
Atom	2991	O	SER	A	652	70.233	36.887	40.042	1.00	60.36	O
Atom	2992	N	PRO	A	653	70.841	39.041	40.359	1.00	66.59	N
Atom	2993	CA	PRO	A	653	72.217	38.822	39.910	1.00	58.66	C
Atom	2994	CB	PRO	A	653	72.881	40.173	40.161	1.00	53.15	C
Atom	2995	CG	PRO	A	653	71.776	41.155	40.078	1.00	54.73	C
Atom	2996	CD	PRO	A	653	70.574	40.460	40.654	1.00	55.28	C
Atom	2997	C	PRO	A	653	72.890	37.745	40.752	1.00	59.06	C
Atom	2998	O	PRO	A	653	73.609	36.908	40.205	1.00	64.74	O
Atom	2999	N	GLN	A	654	72.664	37.773	42.063	1.00	58.52	N
Atom	3000	CA	GLN	A	654	73.182	36.735	42.942	1.00	61.85	C
Atom	3001	CB	GLN	A	654	72.654	36.915	44.369	1.00	63.51	C
Atom	3002	CG	GLN	A	654	73.029	38.236	45.025	1.00	73.74	C
Atom	3003	CD	GLN	A	654	72.883	38.212	46.539	1.00	73.50	C
Atom	3004	OE1	GLN	A	654	73.093	37.182	47.179	1.00	71.84	O
Atom	3005	NE2	GLN	A	654	72.515	39.352	47.117	1.00	63.19	N
Atom	3006	C	GLN	A	654	72.826	35.349	42.418	1.00	64.18	C
Atom	3007	O	GLN	A	654	73.642	34.432	42.463	1.00	62.30	O
Atom	3008	N	LEU	A	655	71.609	35.210	41.903	1.00	62.33	N
Atom	3009	CA	LEU	A	655	71.124	33.923	41.415	1.00	59.28	C
Atom	3010	CB	LEU	A	655	69.599	33.928	41.298	1.00	55.72	C
Atom	3011	CG	LEU	A	655	68.994	32.586	40.874	1.00	56.39	C
Atom	3012	CD1	LEU	A	655	69.362	31.502	41.876	1.00	47.93	C
Atom	3013	CD2	LEU	A	655	67.483	32.693	40.710	1.00	59.18	C
Atom	3014	C	LEU	A	655	71.750	33.522	40.080	1.00	61.75	C
Atom	3015	O	LEU	A	655	72.129	32.367	39.886	1.00	60.05	O
Atom	3016	N	GLU	A	656	71.848	34.475	39.158	1.00	61.63	N
Atom	3017	CA	GLU	A	656	72.492	34.226	37.872	1.00	64.30	C
Atom	3018	CB	GLU	A	656	72.567	35.509	37.041	1.00	62.62	C
Atom	3019	CG	GLU	A	656	71.227	36.017	36.540	1.00	79.67	C
Atom	3020	CD	GLU	A	656	70.583	35.081	35.528	1.00	102.95	C
Atom	3021	OE1	GLU	A	656	70.608	35.412	34.323	1.00	116.88	O
Atom	3022	OE2	GLU	A	656	70.056	34.018	35.932	1.00	91.78	O
Atom	3023	C	GLU	A	656	73.894	33.671	38.093	1.00	65.94	C
Atom	3024	O	GLU	A	656	74.286	32.670	37.487	1.00	60.53	O
Atom	3025	N	GLY	A	657	74.640	34.332	38.972	1.00	57.60	N
Atom	3026	CA	GLY	A	657	75.987	33.914	39.301	1.00	54.55	C
Atom	3027	C	GLY	A	657	76.023	32.526	39.902	1.00	61.31	C
Atom	3028	O	GLY	A	657	76.693	31.636	39.380	1.00	68.52	O
Atom	3029	N	PHE	A	658	75.296	32.336	40.997	1.00	62.01	N
Atom	3030	CA	PHE	A	658	75.282	31.050	41.682	1.00	58.64	C
Atom	3031	CB	PHE	A	658	74.253	31.039	42.811	1.00	55.83	C
Atom	3032	CG	PHE	A	658	74.223	29.752	43.588	1.00	57.46	C
Atom	3033	CD1	PHE	A	658	75.154	29.510	44.584	1.00	54.25	C
Atom	3034	CE1	PHE	A	658	75.132	28.327	45.301	1.00	55.72	C
Atom	3035	CZ	PHE	A	658	74.173	27.371	45.023	1.00	54.07	C
Atom	3036	CE2	PHE	A	658	73.241	27.601	44.030	1.00	53.64	C
Atom	3037	CD2	PHE	A	658	73.269	28.783	43.318	1.00	56.83	C
Atom	3038	C	PHE	A	658	74.999	29.902	40.721	1.00	62.90	C
Atom	3039	O	PHE	A	658	75.731	28.922	40.689	1.00	61.96	O
Atom	3040	N	SER	A	659	73.931	30.025	39.943	1.00	64.10	N
Atom	3041	CA	SER	A	659	73.559	28.976	39.002	1.00	61.50	C
Atom	3042	CB	SER	A	659	72.361	29.415	38.166	1.00	61.78	C
Atom	3043	OG	SER	A	659	71.251	29.680	38.998	1.00	72.63	O
Atom	3044	C	SER	A	659	74.715	28.598	38.086	1.00	63.74	C
Atom	3045	O	SER	A	659	75.131	27.441	38.039	1.00	65.61	O
Atom	3046	N	ALA	A	660	75.227	29.582	37.356	1.00	64.22	N
Atom	3047	CA	ALA	A	660	76.322	29.356	36.422	1.00	59.50	C
Atom	3048	CB	ALA	A	660	76.765	30.670	35.802	1.00	51.21	C
Atom	3049	C	ALA	A	660	77.503	28.659	37.094	1.00	67.57	C
Atom	3050	O	ALA	A	660	78.070	27.710	36.550	1.00	65.55	O
Atom	3051	N	GLU	A	661	77.860	29.127	38.285	1.00	62.70	N
Atom	3052	CA	GLU	A	661	79.049	28.634	38.970	1.00	64.02	C
Atom	3053	CB	GLU	A	661	79.598	29.701	39.920	1.00	66.60	C
Atom	3054	CG	GLU	A	661	79.868	31.044	39.255	1.00	65.59	C
Atom	3055	CD	GLU	A	661	80.949	30.975	38.187	1.00	70.61	C
Atom	3056	OE1	GLU	A	661	81.463	29.869	37.913	1.00	66.72	O
Atom	3057	OE2	GLU	A	661	81.287	32.035	37.620	1.00	73.32	O
Atom	3058	C	GLU	A	661	78.815	27.329	39.727	1.00	60.69	C
Atom	3059	O	GLU	A	661	79.688	26.462	39.758	1.00	67.75	O
Atom	3060	N	SER	A	662	77.644	27.192	40.339	1.00	61.85	N
Atom	3061	CA	SER	A	662	77.330	25.997	41.116	1.00	61.18	C
Atom	3062	CB	SER	A	662	76.087	26.223	41.979	1.00	56.20	C
Atom	3063	OG	SER	A	662	74.962	26.536	41.177	1.00	56.79	O
Atom	3064	C	SER	A	662	77.132	24.783	40.214	1.00	62.28	C
Atom	3065	O	SER	A	662	77.280	23.643	40.654	1.00	64.49	O
Atom	3066	N	ARG	A	663	76.794	25.032	38.953	1.00	62.49	N
Atom	3067	CA	ARG	A	663	76.634	23.958	37.983	1.00	63.87	C
Atom	3068	CB	ARG	A	663	76.152	24.514	36.643	1.00	68.01	C
Atom	3069	CG	ARG	A	663	74.996	23.735	36.038	1.00	84.65	C
Atom	3070	CD	ARG	A	663	74.780	24.088	34.575	1.00	95.92	C
Atom	3071	NE	ARG	A	663	75.415	23.118	33.689	1.00	113.53	N
Atom	3072	CZ	ARG	A	663	74.857	21.971	33.316	1.00	122.79	C
Atom	3073	NH1	ARG	A	663	73.646	21.650	33.752	1.00	120.58	N
Atom	3074	NH2	ARG	A	663	75.510	21.146	32.508	1.00	118.60	N
Atom	3075	C	ARG	A	663	77.973	23.255	37.799	1.00	69.19	C
Atom	3076	O	ARG	A	663	78.042	22.026	37.745	1.00	71.18	O
Atom	3077	N	LYS	A	664	79.037	24.047	37.711	1.00	61.51	N
Atom	3078	CA	LYS	A	664	80.382	23.516	37.545	1.00	65.02	C
Atom	3079	CB	LYS	A	664	81.381	24.659	37.375	1.00	63.63	C
Atom	3080	CG	LYS	A	664	81.069	25.574	36.202	1.00	61.36	C
Atom	3081	CD	LYS	A	664	81.915	26.834	36.254	1.00	63.21	C
Atom	3082	CE	LYS	A	664	81.517	27.809	35.158	1.00	65.95	C
Atom	3083	NZ	LYS	A	664	82.294	29.079	35.231	1.00	67.00	N
Atom	3084	C	LYS	A	664	80.780	22.636	38.727	1.00	68.51	C
Atom	3085	O	LYS	A	664	81.252	21.516	38.545	1.00	68.67	O
Atom	3086	N	LEU	A	665	80.589	23.149	39.938	1.00	62.00	N
Atom	3087	CA	LEU	A	665	80.899	22.386	41.140	1.00	64.90	C
Atom	3088	CB	LEU	A	665	80.653	23.225	42.398	1.00	64.14	C
Atom	3089	CG	LEU	A	665	81.069	22.569	43.719	1.00	64.67	C
Atom	3090	CD1	LEU	A	665	82.511	22.087	43.642	1.00	63.54	C
Atom	3091	CD2	LEU	A	665	80.876	23.518	44.895	1.00	59.06	C
Atom	3092	C	LEU	A	665	80.068	21.110	41.178	1.00	69.51	C
Atom	3093	O	LEU	A	665	80.530	20.068	41.642	1.00	70.20	O
Atom	3094	N	LEU	A	666	78.838	21.203	40.684	1.00	68.16	N
Atom	3095	CA	LEU	A	666	77.956	20.049	40.606	1.00	68.69	C
Atom	3096	CB	LEU	A	666	76.579	20.475	40.094	1.00	70.39	C
Atom	3097	CG	LEU	A	666	75.534	19.371	39.923	1.00	73.79	C
Atom	3098	CD1	LEU	A	666	75.140	18.798	41.277	1.00	72.63	C
Atom	3099	CD2	LEU	A	666	74.315	19.893	39.180	1.00	70.22	C
Atom	3100	C	LEU	A	666	78.559	18.979	39.696	1.00	74.76	C
Atom	3101	O	LEU	A	666	78.663	17.811	40.073	1.00	73.02	O
Atom	3102	N	LEU	A	667	78.959	19.390	38.498	1.00	72.17	N
Atom	3103	CA	LEU	A	667	79.630	18.494	37.562	1.00	70.83	C
Atom	3104	CB	LEU	A	667	80.089	19.262	36.321	1.00	66.80	C
Atom	3105	CG	LEU	A	667	79.001	19.667	35.325	1.00	69.37	C
Atom	3106	CD1	LEU	A	667	79.606	20.450	34.171	1.00	69.60	C
Atom	3107	CD2	LEU	A	667	78.261	18.443	34.814	1.00	70.30	C
Atom	3108	C	LEU	A	667	80.829	17.829	38.226	1.00	69.76	C
Atom	3109	O	LEU	A	667	80.961	16.604	38.211	1.00	72.39	O
Atom	3110	N	ILE	A	668	81.694	18.650	38.813	1.00	68.83	N
Atom	3111	CA	ILE	A	668	82.904	18.165	39.469	1.00	68.97	C
Atom	3112	CB	ILE	A	668	83.730	19.327	40.047	1.00	68.90	C
Atom	3113	CG1	ILE	A	668	84.376	20.133	38.916	1.00	68.74	C
Atom	3114	CD1	ILE	A	668	84.894	21.484	39.345	1.00	66.70	C
Atom	3115	CG2	ILE	A	668	84.787	18.803	40.999	1.00	66.79	C
Atom	3116	C	ILE	A	668	82.587	17.167	40.578	1.00	74.15	C
Atom	3117	O	ILE	A	668	83.238	16.129	40.693	1.00	78.81	O
Atom	3118	N	VAL	A	669	81.584	17.482	41.392	1.00	72.53	N
Atom	3119	CA	VAL	A	669	81.198	16.607	42.494	1.00	73.04	C
Atom	3120	CB	VAL	A	669	80.123	17.249	43.395	1.00	68.56	C
Atom	3121	CG1	VAL	A	669	79.559	16.224	44.364	1.00	74.51	C
Atom	3122	CG2	VAL	A	669	80.711	18.415	44.156	1.00	72.01	C
Atom	3123	C	VAL	A	669	80.708	15.252	41.992	1.00	75.66	C
Atom	3124	O	VAL	A	669	81.023	14.217	42.576	1.00	78.09	O
Atom	3125	N	GLN	A	670	79.941	15.262	40.906	1.00	74.75	N
Atom	3126	CA	GLN	A	670	79.438	14.023	40.324	1.00	76.59	C
Atom	3127	CB	GLN	A	670	78.433	14.313	39.204	1.00	75.76	C
Atom	3128	CG	GLN	A	670	77.049	14.698	39.706	1.00	77.85	C
Atom	3129	CD	GLN	A	670	75.990	14.617	38.623	1.00	79.73	C
Atom	3130	OE1	GLN	A	670	76.295	14.689	37.433	1.00	80.66	O
Atom	3131	NE2	GLN	A	670	74.735	14.465	39.032	1.00	79.12	N
Atom	3132	C	GLN	A	670	80.579	13.146	39.815	1.00	81.31	C
Atom	3133	O	GLN	A	670	80.582	11.932	40.028	1.00	83.93	O
Atom	3134	N	ALA	A	671	81.549	13.765	39.148	1.00	83.81	N
Atom	3135	CA	ALA	A	671	82.709	13.043	38.637	1.00	79.81	C
Atom	3136	CB	ALA	A	671	83.633	13.984	37.877	1.00	72.69	C
Atom	3137	C	ALA	A	671	83.460	12.348	39.769	1.00	81.01	C
Atom	3138	O	ALA	A	671	83.608	11.125	39.768	1.00	81.26	O
Atom	3139	N	LEU	A	672	83.927	13.136	40.734	1.00	80.61	N
Atom	3140	CA	LEU	A	672	84.636	12.596	41.890	1.00	85.30	C
Atom	3141	CB	LEU	A	672	84.931	13.704	42.905	1.00	80.80	C
Atom	3142	CG	LEU	A	672	85.965	14.757	42.501	1.00	84.86	C
Atom	3143	CD1	LEU	A	672	86.123	15.802	43.596	1.00	81.94	C
Atom	3144	CD2	LEU	A	672	87.302	14.105	42.187	1.00	84.51	C
Atom	3145	C	LEU	A	672	83.843	11.475	42.556	1.00	87.91	C
Atom	3146	O	LEU	A	672	84.409	10.472	42.990	1.00	86.74	O
Atom	3147	N	ARG	A	673	82.528	11.655	42.630	1.00	84.29	N
Atom	3148	CA	ARG	A	673	81.640	10.670	43.236	1.00	87.98	C
Atom	3149	CB	ARG	A	673	80.205	11.209	43.265	1.00	84.37	C
Atom	3150	CG	ARG	A	673	79.140	10.215	43.706	1.00	78.01	C
Atom	3151	CD	ARG	A	673	77.849	10.946	44.049	1.00	82.47	C
Atom	3152	NE	ARG	A	673	76.653	10.203	43.658	1.00	86.49	N
Atom	3153	CZ	ARG	A	673	75.917	9.469	44.488	1.00	85.29	C
Atom	3154	NH1	ARG	A	673	76.252	9.368	45.768	1.00	78.29	N
Atom	3155	NH2	ARG	A	673	74.843	8.834	44.036	1.00	78.65	N
Atom	3156	C	ARG	A	673	81.707	9.327	42.506	1.00	90.89	C
Atom	3157	O	ARG	A	673	81.533	8.269	43.114	1.00	84.19	O
Atom	3158	N	ASP	A	674	81.968	9.374	41.203	1.00	85.70	N
Atom	3159	CA	ASP	A	674	82.071	8.159	40.400	1.00	88.22	C
Atom	3160	CB	ASP	A	674	81.453	8.371	39.016	1.00	88.66	C
Atom	3161	CG	ASP	A	674	79.944	8.513	39.064	1.00	102.99	C
Atom	3162	OD1	ASP	A	674	79.245	7.583	38.606	1.00	110.95	O
Atom	3163	OD2	ASP	A	674	79.456	9.549	39.565	1.00	98.78	O
Atom	3164	C	ASP	A	674	83.517	7.704	40.245	1.00	93.78	C
Atom	3165	O	ASP	A	674	83.829	6.880	39.383	1.00	93.53	O
Atom	3166	N	ASN	A	675	84.397	8.242	41.082	1.00	91.45	N
Atom	3167	CA	ASN	A	675	85.820	7.947	40.975	1.00	95.06	C
Atom	3168	CB	ASN	A	675	86.077	6.456	41.193	1.00	96.01	C
Atom	3169	CG	ASN	A	675	85.748	6.013	42.601	1.00	107.05	C
Atom	3170	OD1	ASN	A	675	86.321	6.513	43.568	1.00	107.61	O
Atom	3171	ND2	ASN	A	675	84.826	5.062	42.725	1.00	107.91	N
Atom	3172	C	ASN	A	675	86.396	8.391	39.633	1.00	93.25	C
Atom	3173	O	ASN	A	675	87.052	7.614	38.938	1.00	91.97	O
Atom	3174	N	LEU	A	676	86.140	9.646	39.275	1.00	87.12	N
Atom	3175	CA	LEU	A	676	86.687	10.228	38.054	1.00	90.86	C
Atom	3176	CB	LEU	A	676	85.578	10.517	37.040	1.00	86.32	C
Atom	3177	CG	LEU	A	676	85.337	9.456	35.964	1.00	86.09	C
Atom	3178	CD1	LEU	A	676	84.806	8.172	36.575	1.00	86.75	C
Atom	3179	CD2	LEU	A	676	84.382	9.988	34.908	1.00	88.17	C
Atom	3180	C	LEU	A	676	87.467	11.504	38.341	1.00	88.47	C
Atom	3181	O	LEU	A	676	87.023	12.355	39.111	1.00	90.16	O
Atom	3182	N	GLU	A	677	88.634	11.629	37.719	1.00	89.29	N
Atom	3183	CA	GLU	A	677	89.447	12.828	37.857	1.00	84.99	C
Atom	3184	CB	GLU	A	677	90.922	12.506	37.596	1.00	81.49	C
Atom	3185	CG	GLU	A	677	91.820	13.727	37.483	1.00	77.52	C
Atom	3186	CD	GLU	A	677	91.859	14.540	38.762	1.00	82.35	C
Atom	3187	OE1	GLU	A	677	91.722	15.780	38.681	1.00	71.67	O
Atom	3188	OE2	GLU	A	677	92.016	13.936	39.846	1.00	84.39	O
Atom	3189	C	GLU	A	677	88.961	13.898	36.887	1.00	81.18	C
Atom	3190	O	GLU	A	677	89.053	13.722	35.668	1.00	80.32	O
Atom	3191	N	PRO	A	678	88.433	15.007	37.427	1.00	71.70	N
Atom	3192	CA	PRO	A	678	87.978	16.143	36.620	1.00	73.21	C
Atom	3193	CB	PRO	A	678	87.430	17.122	37.665	1.00	71.47	C
Atom	3194	CG	PRO	A	678	87.160	16.293	38.876	1.00	77.35	C
Atom	3195	CD	PRO	A	678	88.228	15.242	38.865	1.00	76.99	C
Atom	3196	C	PRO	A	678	89.141	16.784	35.876	1.00	74.10	C
Atom	3197	O	PRO	A	678	88.941	17.357	34.807	1.00	74.63	O
Atom	3198	N	GLY	A	679	90.341	16.686	36.437	1.00	68.68	N
Atom	3199	CA	GLY	A	679	91.513	17.279	35.824	1.00	67.50	C
Atom	3200	C	GLY	A	679	92.055	18.424	36.654	1.00	67.31	C
Atom	3201	O	GLY	A	679	91.453	18.825	37.649	1.00	61.89	O
Atom	3202	N	THR	A	680	93.204	18.951	36.250	1.00	62.89	N
Atom	3203	CA	THR	A	680	93.778	20.104	36.929	1.00	64.47	C
Atom	3204	CB	THR	A	680	95.218	20.368	36.476	1.00	62.30	C
Atom	3205	OG1	THR	A	680	96.027	19.233	36.811	1.00	58.02	O
Atom	3206	CG2	THR	A	680	95.768	21.601	37.176	1.00	54.44	C
Atom	3207	C	THR	A	680	92.914	21.352	36.741	1.00	62.14	C
Atom	3208	O	THR	A	680	92.886	21.963	35.670	1.00	57.00	O
Atom	3209	N	PHE	A	681	92.210	21.719	37.805	1.00	65.30	N
Atom	3210	CA	PHE	A	681	91.247	22.807	37.761	1.00	62.48	C
Atom	3211	CB	PHE	A	681	89.836	22.229	37.602	1.00	62.48	C
Atom	3212	CG	PHE	A	681	88.739	23.241	37.745	1.00	66.71	C
Atom	3213	CD1	PHE	A	681	88.417	24.083	36.696	1.00	67.70	C
Atom	3214	CE1	PHE	A	681	87.403	25.011	36.823	1.00	64.74	C
Atom	3215	CZ	PHE	A	681	86.697	25.099	38.004	1.00	62.21	C
Atom	3216	CE2	PHE	A	681	87.007	24.260	39.056	1.00	63.72	C
Atom	3217	CD2	PHE	A	681	88.017	23.338	38.923	1.00	65.13	C
Atom	3218	C	PHE	A	681	91.359	23.621	39.044	1.00	58.11	C
Atom	3219	O	PHE	A	681	91.503	23.059	40.129	1.00	59.48	O
Atom	3220	N	ASP	A	682	91.313	24.944	38.919	1.00	56.69	N
Atom	3221	CA	ASP	A	682	91.410	25.816	40.084	1.00	58.15	C
Atom	3222	CB	ASP	A	682	91.721	27.251	39.661	1.00	58.40	C
Atom	3223	CG	ASP	A	682	91.996	28.155	40.843	1.00	64.16	C
Atom	3224	OD1	ASP	A	682	92.233	27.624	41.950	1.00	62.24	O
Atom	3225	OD2	ASP	A	682	91.976	29.393	40.669	1.00	67.23	O
Atom	3226	C	ASP	A	682	90.121	25.769	40.905	1.00	60.14	C
Atom	3227	O	ASP	A	682	89.313	26.699	40.869	1.00	60.25	O
Atom	3228	N	LEU	A	683	89.940	24.680	41.645	1.00	62.74	N
Atom	3229	CA	LEU	A	683	88.726	24.465	42.422	1.00	62.74	C
Atom	3230	CB	LEU	A	683	88.810	23.136	43.173	1.00	61.54	C
Atom	3231	CG	LEU	A	683	87.524	22.332	43.336	1.00	65.82	C
Atom	3232	CD1	LEU	A	683	87.651	21.379	44.511	1.00	69.08	C
Atom	3233	CD2	LEU	A	683	86.334	23.253	43.522	1.00	65.31	C
Atom	3234	C	LEU	A	683	88.503	25.610	43.404	1.00	61.70	C
Atom	3235	O	LEU	A	683	87.411	26.171	43.482	1.00	66.14	O
Atom	3236	N	GLY	A	684	89.542	25.947	44.160	1.00	61.01	N
Atom	3237	CA	GLY	A	684	89.457	27.025	45.125	1.00	53.85	C
Atom	3238	C	GLY	A	684	88.970	28.298	44.470	1.00	58.46	C
Atom	3239	O	GLY	A	684	88.204	29.062	45.058	1.00	61.28	O
Atom	3240	N	GLY	A	685	89.417	28.523	43.240	1.00	58.53	N
Atom	3241	CA	GLY	A	685	88.989	29.676	42.472	1.00	57.88	C
Atom	3242	C	GLY	A	685	87.497	29.627	42.225	1.00	58.33	C
Atom	3243	O	GLY	A	685	86.808	30.639	42.334	1.00	61.10	O
Atom	3244	N	LEU	A	686	87.001	28.438	41.894	1.00	59.54	N
Atom	3245	CA	LEU	A	686	85.570	28.218	41.698	1.00	58.70	C
Atom	3246	CB	LEU	A	686	85.299	26.770	41.291	1.00	58.31	C
Atom	3247	CG	LEU	A	686	83.840	26.383	41.044	1.00	59.77	C
Atom	3248	CD1	LEU	A	686	83.258	27.159	39.872	1.00	59.53	C
Atom	3249	CD2	LEU	A	686	83.730	24.889	40.801	1.00	60.93	C
Atom	3250	C	LEU	A	686	84.780	28.554	42.958	1.00	61.53	C
Atom	3251	O	LEU	A	686	83.743	29.211	42.890	1.00	60.35	O
Atom	3252	N	TYR	A	687	85.269	28.093	44.105	1.00	59.65	N
Atom	3253	CA	TYR	A	687	84.626	28.394	45.381	1.00	63.73	C
Atom	3254	CB	TYR	A	687	85.355	27.712	46.539	1.00	56.94	C
Atom	3255	CG	TYR	A	687	84.824	26.333	46.851	1.00	61.29	C
Atom	3256	CD1	TYR	A	687	84.098	26.091	48.010	1.00	64.52	C
Atom	3257	CE1	TYR	A	687	83.608	24.829	48.296	1.00	66.97	C
Atom	3258	CZ	TYR	A	687	83.840	23.793	47.414	1.00	67.79	C
Atom	3259	OH	TYR	A	687	83.360	22.534	47.685	1.00	66.16	O
Atom	3260	CE2	TYR	A	687	84.555	24.010	46.257	1.00	68.05	C
Atom	3261	CD2	TYR	A	687	85.040	25.273	45.980	1.00	68.02	C
Atom	3262	C	TYR	A	687	84.514	29.898	45.627	1.00	63.14	C
Atom	3263	O	TYR	A	687	83.505	30.372	46.155	1.00	66.02	O
Atom	3264	N	GLU	A	688	85.544	30.648	45.249	1.00	60.64	N
Atom	3265	CA	GLU	A	688	85.494	32.101	45.373	1.00	68.44	C
Atom	3266	CB	GLU	A	688	86.774	32.744	44.839	1.00	72.34	C
Atom	3267	CG	GLU	A	688	87.902	32.846	45.840	1.00	74.42	C
Atom	3268	CD	GLU	A	688	88.874	33.955	45.490	1.00	95.92	C
Atom	3269	OE1	GLU	A	688	90.097	33.696	45.460	1.00	114.90	O
Atom	3270	OE2	GLU	A	688	88.410	35.088	45.238	1.00	92.00	O
Atom	3271	C	GLU	A	688	84.302	32.640	44.601	1.00	67.38	C
Atom	3272	O	GLU	A	688	83.483	33.385	45.134	1.00	67.24	O
Atom	3273	N	ALA	A	689	84.215	32.249	43.335	1.00	63.37	N
Atom	3274	CA	ALA	A	689	83.140	32.703	42.466	1.00	65.20	C
Atom	3275	CB	ALA	A	689	83.246	32.030	41.107	1.00	58.93	C
Atom	3276	C	ALA	A	689	81.769	32.445	43.087	1.00	67.79	C
Atom	3277	O	ALA	A	689	80.914	33.328	43.121	1.00	70.41	O
Atom	3278	N	ILE	A	690	81.570	31.227	43.578	1.00	62.78	N
Atom	3279	CA	ILE	A	690	80.295	30.832	44.159	1.00	60.72	C
Atom	3280	CB	ILE	A	690	80.263	29.319	44.460	1.00	60.50	C
Atom	3281	CG1	ILE	A	690	80.284	28.513	43.161	1.00	63.23	C
Atom	3282	CD1	ILE	A	690	80.313	27.019	43.378	1.00	58.23	C
Atom	3283	CG2	ILE	A	690	79.039	28.968	45.283	1.00	64.01	C
Atom	3284	C	ILE	A	690	79.969	31.611	45.435	1.00	66.36	C
Atom	3285	O	ILE	A	690	78.882	32.179	45.568	1.00	64.52	O
Atom	3286	N	GLU	A	691	80.920	31.650	46.363	1.00	64.85	N
Atom	3287	CA	GLU	A	691	80.680	32.239	47.676	1.00	62.59	C
Atom	3288	CB	GLU	A	691	81.755	31.782	48.664	1.00	59.82	C
Atom	3289	CG	GLU	A	691	81.718	30.280	48.924	1.00	66.77	C
Atom	3290	CD	GLU	A	691	82.889	29.780	49.748	1.00	72.58	C
Atom	3291	OE1	GLU	A	691	83.938	30.458	49.766	1.00	72.93	O
Atom	3292	OE2	GLU	A	691	82.760	28.703	50.372	1.00	68.50	O
Atom	3293	C	GLU	A	691	80.566	33.762	47.651	1.00	64.79	C
Atom	3294	O	GLU	A	691	80.195	34.382	48.649	1.00	59.86	O
Atom	3295	N	GLU	A	692	80.874	34.363	46.508	1.00	64.37	N
Atom	3296	CA	GLU	A	692	80.743	35.806	46.362	1.00	65.92	C
Atom	3297	CB	GLU	A	692	81.793	36.351	45.395	1.00	66.86	C
Atom	3298	CG	GLU	A	692	81.476	36.110	43.934	1.00	78.93	C
Atom	3299	CD	GLU	A	692	82.657	36.402	43.027	1.00	97.65	C
Atom	3300	OE1	GLU	A	692	82.590	36.037	41.833	1.00	101.43	O
Atom	3301	OE2	GLU	A	692	83.654	36.987	43.509	1.00	91.71	O
Atom	3302	C	GLU	A	692	79.341	36.157	45.880	1.00	66.71	C
Atom	3303	O	GLU	A	692	78.954	37.327	45.851	1.00	69.99	O
Atom	3304	N	CYS	A	693	78.584	35.133	45.501	1.00	62.00	N
Atom	3305	CA	CYS	A	693	77.187	35.312	45.128	1.00	62.95	C
Atom	3306	CB	CYS	A	693	76.782	34.316	44.045	1.00	66.93	C
Atom	3307	SG	CYS	A	693	77.694	34.462	42.507	1.00	65.01	S
Atom	3308	C	CYS	A	693	76.306	35.109	46.349	1.00	63.50	C
Atom	3309	O	CYS	A	693	75.108	35.392	46.319	1.00	65.65	O
Atom	3310	N	LEU	A	694	76.913	34.607	47.420	1.00	58.29	N
Atom	3311	CA	LEU	A	694	76.204	34.350	48.665	1.00	61.63	C
Atom	3312	CB	LEU	A	694	76.744	33.087	49.332	1.00	59.55	C
Atom	3313	CG	LEU	A	694	76.909	31.877	48.415	1.00	59.76	C
Atom	3314	CD1	LEU	A	694	77.622	30.739	49.133	1.00	61.76	C
Atom	3315	CD2	LEU	A	694	75.559	31.425	47.891	1.00	60.62	C
Atom	3316	C	LEU	A	694	76.349	35.536	49.605	1.00	65.19	C
Atom	3317	O	LEU	A	694	77.255	35.576	50.436	1.00	70.59	O
Atom	3318	N	ILE	A	695	75.443	36.497	49.471	1.00	73.26	N
Atom	3319	CA	ILE	A	695	75.521	37.729	50.241	1.00	71.50	C
Atom	3320	CB	ILE	A	695	75.610	38.952	49.317	1.00	71.86	C
Atom	3321	CG1	ILE	A	695	76.686	38.734	48.249	1.00	62.87	C
Atom	3322	CD1	ILE	A	695	76.610	39.703	47.090	1.00	61.87	C
Atom	3323	CG2	ILE	A	695	75.886	40.204	50.129	1.00	73.24	C
Atom	3324	C	ILE	A	695	74.336	37.897	51.190	1.00	72.44	C
Atom	3325	O	ILE	A	695	74.515	37.917	52.408	1.00	73.41	O
Atom	3326	N	ASN	A	696	73.132	38.018	50.636	1.00	69.68	N
Atom	3327	CA	ASN	A	696	71.948	38.260	51.457	1.00	69.08	C
Atom	3328	CB	ASN	A	696	71.843	39.748	51.809	1.00	71.94	C
Atom	3329	CG	ASN	A	696	71.705	40.629	50.585	1.00	72.17	C
Atom	3330	OD1	ASN	A	696	71.214	40.195	49.544	1.00	70.89	O
Atom	3331	ND2	ASN	A	696	72.133	41.881	50.708	1.00	73.83	N
Atom	3332	C	ASN	A	696	70.621	37.765	50.872	1.00	66.51	C
Atom	3333	O	ASN	A	696	69.592	37.814	51.545	1.00	73.05	O
Atom	3334	N	ASP	A	697	70.635	37.293	49.629	1.00	63.12	N
Atom	3335	CA	ASP	A	697	69.407	36.804	49.006	1.00	60.56	C
Atom	3336	CB	ASP	A	697	69.573	36.670	47.490	1.00	60.40	C
Atom	3337	CG	ASP	A	697	68.281	36.269	46.796	1.00	64.21	C
Atom	3338	OD1	ASP	A	697	67.888	35.087	46.894	1.00	59.57	O
Atom	3339	OD2	ASP	A	697	67.657	37.137	46.149	1.00	67.35	O
Atom	3340	C	ASP	A	697	68.969	35.477	49.621	1.00	68.18	C
Atom	3341	O	ASP	A	697	69.735	34.514	49.645	1.00	65.45	O
Atom	3342	N	PRO	A	698	67.722	35.423	50.112	1.00	63.60	N
Atom	3343	CA	PRO	A	698	67.208	34.254	50.834	1.00	57.14	C
Atom	3344	CB	PRO	A	698	65.805	34.694	51.261	1.00	63.47	C
Atom	3345	CG	PRO	A	698	65.426	35.765	50.313	1.00	59.83	C
Atom	3346	CD	PRO	A	698	66.688	36.447	49.888	1.00	60.66	C
Atom	3347	C	PRO	A	698	67.124	33.026	49.937	1.00	55.66	C
Atom	3348	O	PRO	A	698	67.408	31.916	50.386	1.00	60.67	O
Atom	3349	N	TRP	A	699	66.731	33.229	48.684	1.00	56.03	N
Atom	3350	CA	TRP	A	699	66.596	32.133	47.730	1.00	58.65	C
Atom	3351	CB	TRP	A	699	65.861	32.620	46.479	1.00	54.60	C
Atom	3352	CG	TRP	A	699	65.741	31.608	45.376	1.00	55.91	C
Atom	3353	CD1	TRP	A	699	66.099	31.778	44.069	1.00	56.28	C
Atom	3354	NE1	TRP	A	699	65.829	30.638	43.356	1.00	58.01	N
Atom	3355	CE2	TRP	A	699	65.291	29.705	44.193	1.00	60.41	C
Atom	3356	CD2	TRP	A	699	65.216	30.276	45.480	1.00	58.98	C
Atom	3357	CE3	TRP	A	699	64.696	29.517	46.531	1.00	58.96	C
Atom	3358	CZ3	TRP	A	699	64.272	28.226	46.270	1.00	57.92	C
Atom	3359	CH2	TRP	A	699	64.358	27.681	44.981	1.00	58.42	C
Atom	3360	CZ2	TRP	A	699	64.862	28.402	43.935	1.00	58.41	C
Atom	3361	C	TRP	A	699	67.954	31.533	47.375	1.00	61.69	C
Atom	3362	O	TRP	A	699	68.118	30.314	47.350	1.00	60.04	O
Atom	3363	N	VAL	A	700	68.929	32.398	47.118	1.00	59.89	N
Atom	3364	CA	VAL	A	700	70.280	31.952	46.798	1.00	57.40	C
Atom	3365	CB	VAL	A	700	71.183	33.125	46.381	1.00	57.40	C
Atom	3366	CG1	VAL	A	700	72.644	32.717	46.429	1.00	58.80	C
Atom	3367	CG2	VAL	A	700	70.803	33.599	44.994	1.00	58.90	C
Atom	3368	C	VAL	A	700	70.911	31.217	47.973	1.00	58.18	C
Atom	3369	O	VAL	A	700	71.527	30.165	47.797	1.00	60.76	O
Atom	3370	N	LEU	A	701	70.749	31.768	49.171	1.00	57.55	N
Atom	3371	CA	LEU	A	701	71.298	31.145	50.369	1.00	58.45	C
Atom	3372	CB	LEU	A	701	71.029	32.006	51.605	1.00	61.34	C
Atom	3373	CG	LEU	A	701	71.683	33.391	51.638	1.00	61.58	C
Atom	3374	CD1	LEU	A	701	71.370	34.110	52.943	1.00	64.29	C
Atom	3375	CD2	LEU	A	701	73.177	33.270	51.441	1.00	60.34	C
Atom	3376	C	LEU	A	701	70.722	29.747	50.566	1.00	60.08	C
Atom	3377	O	LEU	A	701	71.424	28.835	51.000	1.00	60.76	O
Atom	3378	N	LEU	A	702	69.444	29.578	50.240	1.00	59.28	N
Atom	3379	CA	LEU	A	702	68.809	28.274	50.363	1.00	60.73	C
Atom	3380	CB	LEU	A	702	67.317	28.357	50.039	1.00	59.33	C
Atom	3381	CG	LEU	A	702	66.408	27.404	50.822	1.00	57.87	C
Atom	3382	CD1	LEU	A	702	65.124	27.137	50.052	1.00	59.56	C
Atom	3383	CD2	LEU	A	702	67.113	26.101	51.140	1.00	56.02	C
Atom	3384	C	LEU	A	702	69.495	27.283	49.430	1.00	62.03	C
Atom	3385	O	LEU	A	702	69.933	26.215	49.860	1.00	61.49	O
Atom	3386	N	ASN	A	703	69.587	27.644	48.152	1.00	60.25	N
Atom	3387	CA	ASN	A	703	70.250	26.794	47.170	1.00	61.68	C
Atom	3388	CB	ASN	A	703	70.246	27.454	45.790	1.00	58.28	C
Atom	3389	CG	ASN	A	703	68.878	27.428	45.139	1.00	62.35	C
Atom	3390	OD1	ASN	A	703	67.935	28.042	45.634	1.00	63.21	O
Atom	3391	ND2	ASN	A	703	68.764	26.720	44.020	1.00	65.89	N
Atom	3392	C	ASN	A	703	71.671	26.436	47.592	1.00	61.09	C
Atom	3393	O	ASN	A	703	72.138	25.320	47.361	1.00	59.56	O
Atom	3394	N	ALA	A	704	72.354	27.388	48.219	1.00	57.01	N
Atom	3395	CA	ALA	A	704	73.685	27.134	48.748	1.00	57.97	C
Atom	3396	CB	ALA	A	704	74.288	28.409	49.302	1.00	57.75	C
Atom	3397	C	ALA	A	704	73.610	26.060	49.827	1.00	62.69	C
Atom	3398	O	ALA	A	704	74.324	25.060	49.779	1.00	63.44	O
Atom	3399	N	SER	A	705	72.732	26.271	50.800	1.00	60.44	N
Atom	3400	CA	SER	A	705	72.515	25.291	51.853	1.00	60.45	C
Atom	3401	CB	SER	A	705	71.424	25.770	52.810	1.00	61.00	C
Atom	3402	OG	SER	A	705	71.231	24.848	53.866	1.00	55.16	O
Atom	3403	C	SER	A	705	72.128	23.945	51.255	1.00	62.72	C
Atom	3404	O	SER	A	705	72.596	22.899	51.705	1.00	64.15	O
Atom	3405	N	TRP	A	706	71.267	23.977	50.242	1.00	60.80	N
Atom	3406	CA	TRP	A	706	70.858	22.761	49.552	1.00	64.21	C
Atom	3407	CB	TRP	A	706	69.900	23.077	48.402	1.00	62.40	C
Atom	3408	CG	TRP	A	706	68.478	23.240	48.820	1.00	61.10	C
Atom	3409	CD1	TRP	A	706	67.924	22.859	50.006	1.00	58.93	C
Atom	3410	NE1	TRP	A	706	66.585	23.161	50.020	1.00	58.63	N
Atom	3411	CE2	TRP	A	706	66.245	23.730	48.822	1.00	59.93	C
Atom	3412	CD2	TRP	A	706	67.413	23.792	48.037	1.00	62.64	C
Atom	3413	CE3	TRP	A	706	67.337	24.340	46.752	1.00	62.31	C
Atom	3414	CZ3	TRP	A	706	66.114	24.800	46.301	1.00	64.31	C
Atom	3415	CH2	TRP	A	706	64.969	24.723	47.106	1.00	60.82	C
Atom	3416	CZ2	TRP	A	706	65.015	24.193	48.365	1.00	59.31	C
Atom	3417	C	TRP	A	706	72.073	22.024	49.013	1.00	64.99	C
Atom	3418	O	TRP	A	706	72.214	20.815	49.198	1.00	65.26	O
Atom	3419	N	PHE	A	707	72.953	22.761	48.344	1.00	66.07	N
Atom	3420	CA	PHE	A	707	74.142	22.163	47.753	1.00	64.70	C
Atom	3421	CB	PHE	A	707	74.972	23.205	47.005	1.00	64.65	C
Atom	3422	CG	PHE	A	707	75.986	22.610	46.075	1.00	70.54	C
Atom	3423	CD1	PHE	A	707	75.689	22.425	44.736	1.00	73.11	C
Atom	3424	CE1	PHE	A	707	76.619	21.876	43.876	1.00	75.15	C
Atom	3425	CZ	PHE	A	707	77.860	21.503	44.352	1.00	75.00	C
Atom	3426	CE2	PHE	A	707	78.167	21.680	45.687	1.00	74.91	C
Atom	3427	CD2	PHE	A	707	77.234	22.231	46.540	1.00	70.28	C
Atom	3428	C	PHE	A	707	74.988	21.486	48.823	1.00	62.37	C
Atom	3429	O	PHE	A	707	75.434	20.355	48.643	1.00	66.37	O
Atom	3430	N	ASN	A	708	75.200	22.178	49.938	1.00	59.11	N
Atom	3431	CA	ASN	A	708	75.928	21.601	51.061	1.00	60.54	C
Atom	3432	CB	ASN	A	708	75.906	22.546	52.261	1.00	61.84	C
Atom	3433	CG	ASN	A	708	76.827	23.731	52.084	1.00	66.96	C
Atom	3434	OD1	ASN	A	708	77.665	23.751	51.182	1.00	68.18	O
Atom	3435	ND2	ASN	A	708	76.679	24.729	52.947	1.00	67.56	N
Atom	3436	C	ASN	A	708	75.367	20.244	51.469	1.00	66.65	C
Atom	3437	O	ASN	A	708	76.116	19.309	51.742	1.00	68.63	O
Atom	3438	N	SER	A	709	74.044	20.145	51.519	1.00	70.30	N
Atom	3439	CA	SER	A	709	73.389	18.892	51.862	1.00	68.96	C
Atom	3440	CB	SER	A	709	71.890	19.110	52.034	1.00	70.81	C
Atom	3441	OG	SER	A	709	71.647	20.016	53.093	1.00	79.36	O
Atom	3442	C	SER	A	709	73.647	17.844	50.792	1.00	74.03	C
Atom	3443	O	SER	A	709	73.984	16.700	51.097	1.00	79.79	O
Atom	3444	N	PHE	A	710	73.483	18.238	49.535	1.00	68.35	N
Atom	3445	CA	PHE	A	710	73.797	17.351	48.427	1.00	69.99	C
Atom	3446	CB	PHE	A	710	73.579	18.050	47.087	1.00	68.85	C
Atom	3447	CG	PHE	A	710	74.328	17.417	45.948	1.00	73.78	C
Atom	3448	CD1	PHE	A	710	73.918	16.206	45.420	1.00	70.84	C
Atom	3449	CE1	PHE	A	710	74.602	15.624	44.372	1.00	70.98	C
Atom	3450	CZ	PHE	A	710	75.708	16.249	43.838	1.00	71.43	C
Atom	3451	CE2	PHE	A	710	76.129	17.458	44.354	1.00	75.76	C
Atom	3452	CD2	PHE	A	710	75.441	18.036	45.403	1.00	73.62	C
Atom	3453	C	PHE	A	710	75.242	16.899	48.534	1.00	75.14	C
Atom	3454	O	PHE	A	710	75.551	15.723	48.362	1.00	77.90	O
Atom	3455	N	LEU	A	711	76.121	17.850	48.830	1.00	74.79	N
Atom	3456	CA	LEU	A	711	77.552	17.597	48.936	1.00	74.05	C
Atom	3457	CB	LEU	A	711	78.281	18.903	49.256	1.00	72.39	C
Atom	3458	CG	LEU	A	711	79.798	18.942	49.084	1.00	80.54	C
Atom	3459	CD1	LEU	A	711	80.514	18.480	50.346	1.00	81.37	C
Atom	3460	CD2	LEU	A	711	80.217	18.120	47.874	1.00	83.76	C
Atom	3461	C	LEU	A	711	77.864	16.539	49.990	1.00	79.37	C
Atom	3462	O	LEU	A	711	78.759	15.712	49.808	1.00	78.54	O
Atom	3463	N	THR	A	712	77.120	16.568	51.090	1.00	78.56	N
Atom	3464	CA	THR	A	712	77.324	15.619	52.179	1.00	82.46	C
Atom	3465	CB	THR	A	712	76.541	16.028	53.441	1.00	78.38	C
Atom	3466	OG1	THR	A	712	76.939	17.343	53.848	1.00	85.11	O
Atom	3467	CG2	THR	A	712	76.808	15.050	54.577	1.00	82.04	C
Atom	3468	C	THR	A	712	76.929	14.196	51.788	1.00	86.69	C
Atom	3469	O	THR	A	712	77.633	13.238	52.109	1.00	90.13	O
Atom	3470	N	HIS	A	713	75.800	14.063	51.099	1.00	79.95	N
Atom	3471	CA	HIS	A	713	75.318	12.755	50.665	1.00	82.60	C
Atom	3472	CB	HIS	A	713	73.828	12.811	50.306	1.00	79.75	C
Atom	3473	CG	HIS	A	713	72.929	13.039	51.484	1.00	83.19	C
Atom	3474	ND1	HIS	A	713	72.553	12.028	52.337	1.00	84.33	N
Atom	3475	CE1	HIS	A	713	71.763	12.521	53.279	1.00	86.30	C
Atom	3476	NE2	HIS	A	713	71.618	13.813	53.063	1.00	86.12	N
Atom	3477	CD2	HIS	A	713	72.336	14.167	51.945	1.00	82.55	C
Atom	3478	C	HIS	A	713	76.121	12.228	49.479	1.00	82.76	C
Atom	3479	O	HIS	A	713	76.391	11.031	49.382	1.00	85.23	O
Atom	3480	N	ALA	A	714	76.503	13.131	48.583	1.00	82.45	N
Atom	3481	CA	ALA	A	714	77.200	12.756	47.358	1.00	82.03	C
Atom	3482	CB	ALA	A	714	77.296	13.950	46.414	1.00	78.13	C
Atom	3483	C	ALA	A	714	78.586	12.183	47.635	1.00	80.85	C
Atom	3484	O	ALA	A	714	79.032	11.258	46.956	1.00	76.31	O
Atom	3485	N	LEU	A	715	79.264	12.737	48.634	1.00	83.07	N
Atom	3486	CA	LEU	A	715	80.619	12.312	48.963	1.00	79.99	C
Atom	3487	CB	LEU	A	715	81.603	13.463	48.750	1.00	79.40	C
Atom	3488	CG	LEU	A	715	81.595	14.019	47.325	1.00	75.95	C
Atom	3489	CD1	LEU	A	715	82.396	15.306	47.240	1.00	77.40	C
Atom	3490	CD2	LEU	A	715	82.115	12.985	46.337	1.00	77.43	C
Atom	3491	C	LEU	A	715	80.705	11.770	50.387	1.00	89.14	C
Atom	3492	O	LEU	A	715	81.691	11.989	51.094	1.00	91.74	O
Atom	3493	N	LYS	A	716	79.656	11.061	50.794	1.00	97.46	N
Atom	3494	CA	LYS	A	716	79.626	10.389	52.085	1.00	101.58	C
Atom	3495	CB	LYS	A	716	78.294	9.659	52.271	1.00	100.90	C
Atom	3496	CG	LYS	A	716	77.900	9.402	53.719	1.00	110.27	C
Atom	3497	CD	LYS	A	716	77.045	10.536	54.264	1.00	112.85	C
Atom	3498	CE	LYS	A	716	76.372	10.140	55.571	1.00	115.02	C
Atom	3499	NZ	LYS	A	716	75.375	11.153	56.025	1.00	106.15	N
Atom	3500	C	LYS	A	716	80.764	9.382	52.141	1.00	111.23	C
Atom	3501	O	LYS	A	716	80.807	8.442	51.345	1.00	108.00	O
Atom	3502	OXT	LYS	A	716	81.660	9.485	52.978	1.00	117.50	O
TER	3502		LYS	A	716
Atom	3503	N	GLU	B	1	59.386	16.266	59.073	1.00	105.40	N
Atom	3504	CA	GLU	B	1	58.684	16.408	57.803	1.00	108.01	C
Atom	3505	CB	GLU	B	1	57.561	17.439	57.924	1.00	106.22	C
Atom	3506	CG	GLU	B	1	56.829	17.717	56.619	1.00	108.44	C
Atom	3507	CD	GLU	B	1	56.054	16.513	56.102	1.00	116.84	C
Atom	3508	OE1	GLU	B	1	56.633	15.407	56.023	1.00	108.99	O
Atom	3509	OE2	GLU	B	1	54.861	16.679	55.768	1.00	126.59	O
Atom	3510	C	GLU	B	1	59.638	16.791	56.673	1.00	101.83	C
Atom	3511	O	GLU	B	1	60.427	17.730	56.804	1.00	96.26	O
Atom	3512	N	THR	B	2	59.549	16.059	55.565	1.00	93.31	N
Atom	3513	CA	THR	B	2	60.446	16.233	54.422	1.00	87.24	C
Atom	3514	CB	THR	B	2	59.977	15.395	53.200	1.00	84.73	C
Atom	3515	OG1	THR	B	2	60.680	15.804	52.019	1.00	73.01	O
Atom	3516	CG2	THR	B	2	58.490	15.569	52.972	1.00	102.09	C
Atom	3517	C	THR	B	2	60.623	17.691	54.001	1.00	88.55	C
Atom	3518	O	THR	B	2	59.710	18.304	53.447	1.00	85.14	O
Atom	3519	N	ASP	B	3	61.802	18.242	54.281	1.00	84.43	N
Atom	3520	CA	ASP	B	3	62.196	19.531	53.727	1.00	69.27	C
Atom	3521	CB	ASP	B	3	63.288	20.178	54.582	1.00	64.77	C
Atom	3522	CG	ASP	B	3	62.732	20.908	55.790	1.00	77.08	C
Atom	3523	OD1	ASP	B	3	61.500	21.108	55.849	1.00	83.83	O
Atom	3524	OD2	ASP	B	3	63.525	21.286	56.678	1.00	71.04	O
Atom	3525	C	ASP	B	3	62.705	19.320	52.304	1.00	69.46	C
Atom	3526	O	ASP	B	3	63.811	18.826	52.106	1.00	72.37	O
Atom	3527	N	VAL	B	4	61.895	19.693	51.318	1.00	72.01	N
Atom	3528	CA	VAL	B	4	62.232	19.462	49.915	1.00	67.73	C
Atom	3529	CB	VAL	B	4	61.132	20.002	48.986	1.00	67.67	C
Atom	3530	CG1	VAL	B	4	61.331	19.497	47.561	1.00	63.35	C
Atom	3531	CG2	VAL	B	4	59.764	19.606	49.512	1.00	57.85	C
Atom	3532	C	VAL	B	4	63.571	20.083	49.523	1.00	66.16	C
Atom	3533	O	VAL	B	4	63.878	21.213	49.907	1.00	66.02	O
Atom	3534	N	ASN	B	5	64.358	19.334	48.755	1.00	65.98	N
Atom	3535	CA	ASN	B	5	65.660	19.791	48.283	1.00	58.21	C
Atom	3536	CB	ASN	B	5	66.757	19.340	49.252	1.00	61.91	C
Atom	3537	CG	ASN	B	5	68.153	19.744	48.798	1.00	65.96	C
Atom	3538	OD1	ASN	B	5	68.357	20.164	47.660	1.00	65.79	O
Atom	3539	ND2	ASN	B	5	69.122	19.612	49.696	1.00	63.88	N
Atom	3540	C	ASN	B	5	65.938	19.246	46.884	1.00	60.38	C
Atom	3541	O	ASN	B	5	66.437	18.130	46.742	1.00	68.53	O
Atom	3542	N	PRO	B	6	65.625	20.039	45.846	1.00	59.71	N
Atom	3543	CA	PRO	B	6	65.745	19.637	44.437	1.00	62.86	C
Atom	3544	CB	PRO	B	6	65.365	20.914	43.674	1.00	61.61	C
Atom	3545	CG	PRO	B	6	64.590	21.732	44.641	1.00	62.59	C
Atom	3546	CD	PRO	B	6	65.193	21.440	45.979	1.00	61.75	C
Atom	3547	C	PRO	B	6	67.159	19.201	44.036	1.00	66.27	C
Atom	3548	O	PRO	B	6	67.311	18.394	43.119	1.00	71.17	O
Atom	3549	N	THR	B	7	68.178	19.733	44.700	1.00	63.94	N
Atom	3550	CA	THR	B	7	69.554	19.412	44.340	1.00	67.51	C
Atom	3551	CB	THR	B	7	70.559	20.309	45.085	1.00	65.64	C
Atom	3552	OG1	THR	B	7	70.077	21.658	45.094	1.00	60.72	O
Atom	3553	CG2	THR	B	7	71.920	20.266	44.399	1.00	63.60	C
Atom	3554	C	THR	B	7	69.865	17.943	44.613	1.00	70.20	C
Atom	3555	O	THR	B	7	70.740	17.356	43.978	1.00	72.49	O
Atom	3556	N	LEU	B	8	69.132	17.352	45.551	1.00	70.58	N
Atom	3557	CA	LEU	B	8	69.311	15.944	45.885	1.00	71.88	C
Atom	3558	CB	LEU	B	8	68.424	15.548	47.066	1.00	71.26	C
Atom	3559	CG	LEU	B	8	68.798	16.163	48.414	1.00	73.26	C
Atom	3560	CD1	LEU	B	8	67.979	15.535	49.529	1.00	73.88	C
Atom	3561	CD2	LEU	B	8	70.288	15.998	48.682	1.00	72.04	C
Atom	3562	C	LEU	B	8	69.024	15.039	44.690	1.00	72.29	C
Atom	3563	O	LEU	B	8	69.517	13.914	44.623	1.00	74.23	O
Atom	3564	N	LEU	B	9	68.223	15.532	43.752	1.00	70.54	N
Atom	3565	CA	LEU	B	9	67.935	14.792	42.530	1.00	71.50	C
Atom	3566	CB	LEU	B	9	67.087	15.637	41.577	1.00	68.34	C
Atom	3567	CG	LEU	B	9	65.587	15.719	41.859	1.00	73.85	C
Atom	3568	CD1	LEU	B	9	64.943	16.824	41.035	1.00	66.07	C
Atom	3569	CD2	LEU	B	9	64.926	14.379	41.580	1.00	77.82	C
Atom	3570	C	LEU	B	9	69.226	14.388	41.835	1.00	75.42	C
Atom	3571	O	LEU	B	9	69.289	13.352	41.177	1.00	76.80	O
Atom	3572	N	PHE	B	10	70.255	15.216	41.986	1.00	75.59	N
Atom	3573	CA	PHE	B	10	71.525	14.986	41.309	1.00	76.72	C
Atom	3574	CB	PHE	B	10	72.332	16.281	41.207	1.00	71.34	C
Atom	3575	CG	PHE	B	10	71.725	17.292	40.282	1.00	72.28	C
Atom	3576	CD1	PHE	B	10	71.321	18.529	40.751	1.00	67.94	C
Atom	3577	CE1	PHE	B	10	70.757	19.456	39.900	1.00	70.77	C
Atom	3578	CZ	PHE	B	10	70.583	19.148	38.565	1.00	70.71	C
Atom	3579	CE2	PHE	B	10	70.977	17.915	38.087	1.00	77.67	C
Atom	3580	CD2	PHE	B	10	71.541	16.995	38.943	1.00	72.56	C
Atom	3581	C	PHE	B	10	72.349	13.880	41.962	1.00	77.38	C
Atom	3582	O	PHE	B	10	73.487	13.628	41.564	1.00	78.94	O
Atom	3583	N	LEU	B	11	71.771	13.228	42.965	1.00	76.01	N
Atom	3584	CA	LEU	B	11	72.348	12.010	43.514	1.00	73.01	C
Atom	3585	CB	LEU	B	11	71.741	11.689	44.877	1.00	68.05	C
Atom	3586	CG	LEU	B	11	72.230	12.509	46.069	1.00	70.96	C
Atom	3587	CD1	LEU	B	11	71.301	12.318	47.257	1.00	70.50	C
Atom	3588	CD2	LEU	B	11	73.667	12.149	46.435	1.00	74.24	C
Atom	3589	C	LEU	B	11	72.064	10.869	42.550	1.00	78.78	C
Atom	3590	O	LEU	B	11	72.720	9.828	42.587	1.00	84.89	O
Atom	3591	N	LYS	B	12	71.079	11.082	41.683	1.00	75.69	N
Atom	3592	CA	LYS	B	12	70.657	10.069	40.727	1.00	76.24	C
Atom	3593	CB	LYS	B	12	69.248	9.580	41.069	1.00	83.41	C
Atom	3594	CG	LYS	B	12	68.763	8.402	40.242	1.00	89.64	C
Atom	3595	CD	LYS	B	12	67.821	7.535	41.059	1.00	96.46	C
Atom	3596	CE	LYS	B	12	67.164	6.454	40.213	1.00	107.15	C
Atom	3597	NZ	LYS	B	12	66.047	6.980	39.375	1.00	100.69	N
Atom	3598	C	LYS	B	12	70.708	10.611	39.301	1.00	78.83	C
Atom	3599	O	LYS	B	12	71.258	9.973	38.406	1.00	81.06	O
Atom	3600	N	VAL	B	13	70.132	11.791	39.096	1.00	81.70	N
Atom	3601	CA	VAL	B	13	70.152	12.432	37.787	1.00	80.92	C
Atom	3602	CB	VAL	B	13	69.025	13.468	37.648	1.00	79.43	C
Atom	3603	CG1	VAL	B	13	68.935	13.968	36.211	1.00	80.40	C
Atom	3604	CG2	VAL	B	13	67.701	12.876	38.096	1.00	78.96	C
Atom	3605	C	VAL	B	13	71.487	13.130	37.574	1.00	86.69	C
Atom	3606	O	VAL	B	13	71.894	13.953	38.391	1.00	92.58	O
Atom	3607	N	PRO	B	14	72.178	12.797	36.475	1.00	91.24	N
Atom	3608	CA	PRO	B	14	73.467	13.418	36.153	1.00	88.51	C
Atom	3609	CB	PRO	B	14	73.984	12.570	34.983	1.00	94.58	C
Atom	3610	CG	PRO	B	14	73.156	11.319	34.996	1.00	91.99	C
Atom	3611	CD	PRO	B	14	71.821	11.745	35.511	1.00	94.74	C
Atom	3612	C	PRO	B	14	73.277	14.859	35.702	1.00	87.89	C
Atom	3613	O	PRO	B	14	72.354	15.139	34.936	1.00	92.73	O
Atom	3614	N	ALA	B	15	74.134	15.758	36.174	1.00	86.70	N
Atom	3615	CA	ALA	B	15	74.046	17.164	35.790	1.00	94.92	C
Atom	3616	CB	ALA	B	15	75.253	17.930	36.291	1.00	89.40	C
Atom	3617	C	ALA	B	15	73.911	17.287	34.274	1.00	102.36	C
Atom	3618	O	ALA	B	15	74.413	16.441	33.537	1.00	101.81	O
Atom	3619	N	GLN	B	16	73.235	18.345	33.830	1.00	103.36	N
Atom	3620	CA	GLN	B	16	72.829	18.532	32.434	1.00	110.11	C
Atom	3621	CB	GLN	B	16	73.691	17.716	31.464	1.00	111.20	C
Atom	3622	CG	GLN	B	16	75.082	18.275	31.226	1.00	118.75	C
Atom	3623	CD	GLN	B	16	76.072	17.214	30.779	1.00	121.89	C
Atom	3624	OE1	GLN	B	16	75.959	16.045	31.153	1.00	111.77	O
Atom	3625	NE2	GLN	B	16	77.055	17.620	29.981	1.00	120.87	N
Atom	3626	C	GLN	B	16	71.361	18.158	32.265	1.00	114.01	C
Atom	3627	O	GLN	B	16	70.734	17.637	33.188	1.00	110.87	O
Atom	3628	OXT	GLN	B	16	70.769	18.364	31.205	1.00	110.25	O
TER	3628		GLN	B	16
Atom	3629	O	HOH	X	1	33.971	37.191	59.197	1.00	42.96	O
Atom	3630	O	HOH	X	2	60.890	41.881	54.164	1.00	52.73	O
Atom	3631	O	HOH	X	3	42.943	31.901	51.275	1.00	57.80	O
Atom	3632	O	HOH	X	4	80.217	34.028	52.049	1.00	69.04	O
Atom	3633	O	HOH	X	5	71.529	22.085	54.618	1.00	69.34	O
Atom	3634	O	HOH	X	6	55.374	44.300	47.226	1.00	58.32	O
Atom	3635	O	HOH	X	7	89.186	24.862	48.284	1.00	54.83	O
Atom	3636	O	HOH	X	8	67.542	39.373	52.710	1.00	54.90	O
Atom	3637	O	HOH	X	9	71.696	23.946	45.242	1.00	62.51	O
Atom	3638	O	HOH	X	10	65.491	31.002	61.081	1.00	61.14	O
Atom	3639	O	HOH	X	11	33.792	43.942	62.464	1.00	59.22	O
Atom	3640	O	HOH	X	12	63.784	48.427	54.556	1.00	70.99	O
Atom	3641	O	HOH	X	13	31.711	43.270	60.900	1.00	61.88	O
Atom	3642	O	HOH	X	14	67.983	34.807	44.140	1.00	53.64	O
Atom	3643	O	HOH	X	15	47.385	38.276	50.237	1.00	60.26	O
Atom	3644	O	HOH	X	16	70.805	23.777	39.744	1.00	76.06	O
Atom	3645	O	HOH	X	17	49.291	52.769	66.147	1.00	71.24	O
Atom	3646	O	HOH	X	18	57.344	23.870	56.441	1.00	59.28	O
Atom	3647	O	HOH	X	19	44.196	23.786	49.444	1.00	77.54	O
Atom	3648	O	HOH	X	20	31.998	40.376	36.462	1.00	80.67	O
Atom	3649	O	HOH	X	21	61.261	45.024	42.557	1.00	79.17	O
Atom	3650	O	HOH	X	22	34.781	34.919	59.258	1.00	60.80	O
Atom	3651	O	HOH	X	23	74.429	25.531	55.372	1.00	66.35	O
Atom	3652	O	HOH	X	24	56.574	56.076	61.857	1.00	69.28	O
Atom	3653	O	HOH	X	25	28.615	46.523	45.185	1.00	72.19	O
Atom	3654	O	HOH	X	26	44.747	19.002	48.920	1.00	82.19	O
Atom	3655	O	HOH	X	27	60.616	51.821	45.702	1.00	79.45	O
Atom	3656	O	HOH	X	28	59.699	34.062	33.466	1.00	77.19	O
Atom	3657	O	HOH	X	29	45.829	27.468	49.150	1.00	70.04	O
Atom	3658	O	HOH	X	30	36.247	28.654	58.224	1.00	76.34	O
Atom	3659	O	HOH	X	31	68.008	35.619	37.743	1.00	64.75	O
Atom	3660	O	HOH	X	32	52.447	44.997	68.769	1.00	72.18	O
Atom	3661	O	HOH	X	33	36.213	54.780	55.326	1.00	85.33	O
Atom	3662	O	HOH	X	34	47.914	22.619	51.309	1.00	84.11	O
Atom	3663	O	HOH	X	35	54.918	32.204	57.781	1.00	64.17	O
Atom	3664	O	HOH	X	36	61.845	33.920	64.510	1.00	67.39	O
Atom	3665	O	HOH	X	37	67.162	41.308	50.608	1.00	71.57	O
Atom	3666	O	HOH	X	38	50.751	50.751	67.297	0.50	62.87	O
Atom	3667	O	HOH	X	39	85.278	17.345	52.387	1.00	84.03	O
Atom	3668	O	HOH	X	40	34.501	30.005	70.141	1.00	59.50	O
Atom	3669	O	HOH	X	41	43.141	44.745	34.218	1.00	85.92	O
Atom	3670	O	HOH	X	42	33.993	32.602	58.111	1.00	64.89	O
Atom	3671	O	HOH	X	43	65.773	33.965	37.223	1.00	67.60	O
Atom	3672	O	HOH	X	44	60.285	51.332	64.243	1.00	87.73	O
Atom	3673	O	HOH	X	45	62.634	30.619	35.680	1.00	79.46	O
Atom	3674	O	HOH	X	46	34.258	32.163	49.588	1.00	77.27	O
Atom	3675	O	HOH	X	47	46.058	35.320	62.696	1.00	55.79	O
Atom	3676	O	HOH	X	48	60.642	49.738	50.534	1.00	75.21	O
Atom	3677	O	HOH	X	49	88.202	22.541	48.912	1.00	61.86	O
Atom	3678	O	HOH	X	50	43.811	28.972	59.258	1.00	77.13	O
Atom	3679	O	HOH	X	51	62.053	48.564	52.574	1.00	64.85	O
Atom	3680	O	HOH	X	52	67.277	−6.429	25.096	1.00	94.62	O
Atom	3681	O	HOH	X	53	47.473	9.209	37.903	1.00	80.97	O
Atom	3682	O	HOH	X	54	63.473	47.031	39.930	1.00	84.21	O
End

Polymerase subunit PA protein derived from avian H5N1 influenza virus strains A/goose/Guangdong/1/96 is compared with PA protein sequences of type A influenza virus strains A/BrevigMission/1/1918 that outbreaks on a large scale in Europe, 1998, and two types of type B influenza virus strains B/Ann Arbor/1/1966 and type C influenza virus strains C/JJ/1950, the results of which are as shown in FIG. 1.

PA is divided by the inventor into two parts, and multiple fragments of varying lengths of two parts of a PA gene are cloned and expressed in Escherichia coli, wherein residues 1-256 (see FIG. 1 and FIG. 2) and residues 257-716 (see FIG. 4A) of the N-terminal of PA are well expressed and purified by being fused with GST (Glutathione S-Transferase) and a well-diffracted parental crystal of purified PA amino-terminal (PA_N) is obtained (see FIG. 3).

A preliminary crystallization experiment shows that the C-terminal of PA fails to obtain a crystal despite a lot of efforts has been made. Therefore, the inventor also uses a GST fusion method to express PB1 N-terminal peptides of 25 amino acids and 48 amino acids (see FIG. 4A, which is an electrophoretogram before and after the C-terminal of PA is fused with the GST or the N-terminal of PB1 is fused with the GST, wherein strand 1 PA_C CT is a control sample for the C-terminal of PA, strand 2 GST-PB1+PA_C is a sample in which the complex of the C-terminal of PA and the N-terminal of PB1 is fused with GST, strand 3 GST-PB1 is a sample in which the PB1_N terminal is fused with GST, strand 4 GST+PA_C is a sample in which the C-terminal of PA is fused with GST, and strand 5 GST CT is a GST control sample; wherein PA_C denotes an electrophoretic band of PA_C, GST-PB1 is an electrophoretic band in which the PB1_N terminal is fused with GST, and GST is a control electrophoretic band for GST). The results show that: GST-PB1 can bind to purified PA_C protein.

The in vitro binding experiment shows that the expressing bacterium of the corresponding polypeptides of PA and PB1 are mixed in proportion, and then these two proteins are co-purified through the Glutathione affinity columnand gel exclusion chromatograph, and so on. It is determined therefrom that the co-purification of the two can be realized, indicating the purified 460 amino acids of the C-terminal of PA may form a stable complex with the GST-PB1 polypeptide.

Further, the PA_C/PB1_N polypeptide complex is separated and purified after using protease to cleave the GST fusion peptide and then used in a crystallization experiment to obtain a crystal under multiple conditions, wherein a well-diffracted crystal is obtained under one condition. However, the separately purified PA C-terminal protein fails to obtain a crystal, implying that the addition of PB1 polypeptide helps to stabilize the PA protein.

Three-Dimensional Structure of PA_C/PB1_N Polypeptide Complex

A method of MAD is used to analyze a crystal structure of a complex of PA C-terminal 460 amino acids and PB1 N-terminal 25 amino acids, wherein the resolution is 2.9 Angstrom, the finally corrected R factor is 23%, and the R_free factor is 26%. In general, if the structure is indicated by lines, the PA part is, vividly speaking, like a wolf's head viewed from the side, which has an extruding mouth, a skull thereafter and a ringed neck (FIG. 4B). PB1 is like a bone bite by the mouth of PA. The PA part mainly consists of 13 α helixes, one small 3₁₀ helix, 7 β sheets and loops connected the preceding structures (FIGS. 1, 4B, and FIG. 5). In terms of structure, the PA protein part can be deemed to have two domains. One domain is an area binding to the PB1 polypeptide (domain I, viz. the first part of the PA C-terminal structure) and is composed of helixes and loops, wherein helixes 4, 5, 8, 9, 10, 11, 12, and 13 constitute the mouth and cheek parts of the wolf's head. Such a domain is relative narrow viewed from the top part of the wolf's head. The other domain (domain II, viz. the second part of the PA C-terminal structure) is a latter half part of the wolf's head composed of the remaining helixes and β sheets, which is relatively large viewed from the top, with a large loop connected below, and resembles the neck part of the wolf' head. The N-terminal of the PB1 polypeptide is located on the side surface of the wolf's head, and the C-terminal is located at the other side surface, which are equivalent to two check sides of the wolf's head. PA of the crystal in the present invention is a polypeptide with the PA N-terminal 256 residues removed. It is reported that the N-terminal is a main active area of PA protease, while the other relative far active site Ser624 is located on the other check side. It is thought that Ser624 is an amino acid of the PA protease active centre which constitutes a protease active area together with the removed part of PA. Therefore, the PA N-terminal removed part is located on the other side surface of the cheek. The second domain of the latter half part of the wolf's head is composed of the remaining helixes and β sheets. Seven differently oriented β sheets of varying lengths constitute a slight twisted plane and located in the center position of the domain, while α helixes are distributed at the periphery of the helix and constitute a Rossmann fold structure. There is a large groove at the junction of two domains to form a large loop about 25 Angstrom in diameter with the lower cervical ring (FIG. 5).

Interaction Between PA and PB1 Polypeptide

Helixes binding to the PB1 polypeptide in domain I are helix 4 (406-415), 8 (582-604aa), (633-650aa), 11 (653-674aa), and 13 (698-714aa), wherein three helixes (8, 11, 13) extend outwards nearly in parallel to form a nearly right-angled triangle viewed from α helix axis direction, the fourth helix (10) extends obliquely, the PB1 polypeptide is interposed therebetween (FIG. 5 and FIG. 6), and helix 4 interacts with the PB1_N peptide residue on the side surface. Four helixes forms a hydrophobic core in a region binding to the PB1 polypeptide, and the side chains thereof and the hydrophobic amino acid residues of PB1 are combined together by means of hydrophobic interaction and hydrogen bonds. The second-position aspartic acid to the fifteenth-position glutamine of the PB1 polypeptide can be observed in an electron density map. Such a result coincides with the previous 12 amino acids of the PB1_N terminal are key amino acids for PA binding to PB1 reported by Perez, etc. (Perez and Donis 2001). Further, the inventors analyze interaction between these amino acid residues and PA. The conserved LLFL peptide fragment of PB1 reported by the articles of Perez, etc. (Perez and Donis 2001) is present in a short helix and suspended in the middle of the hydrophobic core formed by PA. The amino acid residues of PA involved in forming the hydrophobic core are Leu666 of helix 11, Phe710 of helix 13, and Ile 633, Val636, and Leu640 of helix 10, etc. The amino acids of PA involved in binding to the PB1 polypeptide include Trp706 of helix 13, Gln670 of helix 11, etc., wherein Trp706 interacts with amino acids of Val3, N4, etc. of the PB1 short peptide by means of hydrophobic bonds, van der Waals forces, etc. Gln670 interacts with F9, V12, P13 and A14 of PB1 by means of hydrogen bonds, hydrophobic bonds, van der Waals forces, etc. T639 of helix 10 is involved in the interaction with Val3 (van der Waals forces). Q408 and N412 of helix 4 are involved in the reaction with Val3 and D2 of PB1. In addition, a loose loop interposed between helix 9 and helix 10 is also involved in the interaction with PB1, wherein 1621, G622, and E623 interact with D2 and N5, respectively, and T618 and P620 interact with L8 and K11, respectively. Helix 8 is distant from the PB1 polypeptide, mainly due to van der Waals forces. Such a result is substantially consistent with the function of the residues of the PB1 polypeptide being involved in binding reported by the documents. These amino acids involved in binding to PA are conserved across type A, B and C influenza viruses, and the PA residues involved in binding to the PB1 polypeptide are mostly conserved (FIG. 1). The analysis of a fine three-dimensional structure of a mode of binding PA to PB1 provides a powerful three-dimensional information platform for designing corresponding medicaments to inhibit the function of the influenza virus polymerase.

It is found from the results of analyzing the PA structure that a large groove (domain III) is provided at the conjunction of two domains below domain I (FIG. 8A). The surface of the large groove is enriched with basic amino acids, wherein some amino acids, such as K536, K328, R566, and so on, are highly conserved in the three types of influenza viruses. In addition, the 399th-position Lys and 401st-position Arg are also conserved (FIG. 1). Mutants at the sites of K536 and so on prove the importance of these sites, indicating that the large groove part is associated with the binding of nucleotide or RNA. In addition, a large annular chain part is provided below the groove. This fragment of polypeptide is formed by being pulled apart via interaction between the annular polypeptide fragment with another neighboring molecular surface in crystal packing. The electron density of part of amino acids can not be observed clearly. The large groove and the neck ring constitute a large loop about 25 Angstrom in diameter, and such a space is enough to accommodate a double RNA helix. As described above, on the surface of the groove inside the ring, there are mainly distributed conserved basic amino acids. Although the amino acids of the chain fragment are not highly conserved, the three types of influenza viruses are mainly composed of acidic amino acids. The conservativeness and structure specificity of the groove and the annular structure in the PA molecule imply their critical roles in the polymerase to make them become second drug targets besides the area in which PA binds to PB1.

RNA promoter binding capacity. In terms of the structure analyzed by the inventors, the inventors find that the large groove is a binding site for nucleotide or RNA, wherein the sites of K539, E538, and K328 are highly conserved across the three types of influenza viruses. The inventors deem that these amino acids are involved in binding to RNA nucleotide, especially in binding to RNA, indicating that the PA subunit plays an important role in binding to a promoter, RNA, and a process of RNA synthesis.

Between domain I and domain II, the helixes of domain I and the β sheets of domain II form a channel with a diameter of about 8 Angstrom to 15 Angstrom (FIGS. 8B and 8C). In such a structure analyzed by the inventors, one loose fragment of the N-terminal of PA resembles a rope lying in the channel. Since the N-terminal fragment is relatively far from the two ends of the channel, the inventors think that the N-terminal fragment is absent from the channel when the polymerase complex interacts with other host proteins to exhibit the polymerase's function. Thus, a channel is present in the middle of the domain, extending through the channel from the PA groove to the other side of the cheek of the wolf's head. On the surface of the channel, there exist some amino acids which are highly conserved in the three types of influenza viruses, e.g. R566, K539, and K574 located on the surface of the large groove, conserved E410, K460, E524, and K536 in the middle of the channel, and the like. It is found that some residues thereof have an influence on the polymerase activity. The researches of Fodor, etc. indicate that mutation of E524A abolishes the virus's capacity of RNA synthesis to inhibit virus production. Mutation of E410 decreases the polymerase activity (Fodor, Crow et al. 2002). Mutation of K539A is found not to influence mRNA synthesis but significantly influence gene replication of cRNA and vRNA, indicating that such an area is critical for replication of viral genome. It is known that the nucleotide has a size close to that of the channel (e.g. ATP has a length of about 14 Angstrom and a width of about 8 Angstrom, and other three nucleotides UCG have a size similar thereto). The inventors, thus, deem that such a channel allows the passage of nucleotide or other small molecules or interaction with other proteins in some cases. Therefore, the mutation of the surface residues will cause significant change of the polymerase activity. The unique structure and the functional importance of the channel make it become a third drug designing site for binding target.

In a specific embodiment, there is provided in the present invention a polypeptide, a protein, an inorganic compound, or an organic compound competing with the influenza virus polymerase PB1 to bind to PA_C, wherein the amino acid sequences of the polypeptide or protein contain a short LLFL motif of the short helix region formed by the PB1_N residues 5 to 11 of wild type influenza virus polymerase PB1.

Herein, part of atoms between Met595 and Val12, between Leu666 and Phe9, between Leu640 and Leu8, between Leu636 and Leu8, between Met628 and Leu7, between Phe710 and Thr6, between Trp706 and Thr6, between Trp706 and Pro5, between Phe411 and Pro5, and between Trp706 and Asn4 are involved in interaction within the scope of 4 Angstrom. Therefore, it can be seen that they bind to one another by means of hydrophobic interaction. Thus, polypeptides or compounds involved in hydrophobic interaction with the corresponding amino acids of the C-terminal of PA can be used as medicaments for inhibiting influenza virus.

There are many successful examples for designing a medicament based on a structure of target protein (Schneider, G. and Fechner, U., Nature Reviews Drug Discovery 2005, 4, 649). The LigBuilder program developed by the research group set up by Professor Lu Hua from Peking University has more than 700 worldwide registration users (Wang, R. X.; Gao, Y.; Lai, L. H., LigBuilder: A multi-purpose program for structure-based drug design. J. Mol. Mod. 2000, 6, 498). Many examples has been reported of designing a highly active inhibitor successfully using the LigBuilder program, for example, the Boehringer Ingelheim pharmaceutical company uses LigBuilder 1.2 to access and implement aided design for optimizing a highly active kinase inhibitor (Goldberg D R, Hao, M-H., et al., J. Med. Chem. 2007, 50, 4016).

Novel medicament design and calculation is conducted using the LigBuilder 2.0 program according to the crystal structure of the PAC-PB1N complex of the H5N1 virus RNA polymerase. First, directed at the PAC protein, an analysis of binding sites is made, wherein two binding sites wining highest scores are located in the “mouth” region and the “channel” region of the structure. Novel medicament design and calculation for these two sites are conducted using the LigBuilder 2.0 program to obtain some easily-synthesized compounds with high prediction activity.

Molecules binding to the “channel” region of the PA molecules are exemplified as follows:

R₁=—CH₃, —CH₂CH₃

R₂=—CH₃, —CH₂NH₂, —CH(OH)CH₃, —CH(CH₃)₂

Predicted Kd: 8.64 to 9.60

R₁=—NH₂

R₂=—COCH₃, —CH₂COCH₃, —CO, —OCH₂CH₃

R₃=—CH₂NH₂, —CH₂(NH₂)CH₂CH₃, —CH₂(NH₂)CH₂CH₂CH₃

Predicted Kd: 8.51 to 9.65

Molecules binding to the “mouth” region of the PA molecule are exemplified as follows:

R₁=—OH

R₂=—OH, —CO, —CONH₂, —CONHCH₃, COOH

R₃=—COOH, —NH₂, —C(NH₂)²⁺

R₄=—CH(OH)CH₃, CONH₂, CH(NH₂)CH₂OH

Predicted Kd: 8.52 to 8.96

R₁=—OH, —NHCO

R₂=—CH₂(OH)CH₃, —NHCH₃, —CH₂OH, —CH₂NH₂, —NH₂, —C(NH₂)²⁺

R₃=—NH₂, —C(NH₂)²⁺, —CH₂OH, —CO, —CH₂CO, —NHCO

R₄=—OH, —OCH₃

REFERENCE

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Claims

1. Crystal of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N, wherein the C-terminal of the influenza virus polymerase subunit PA-PAc is amino acid fragment from amino acid positions about 201˜ about 301 to about 650˜ terminal, the N-terminal of influenza virus polymerase subunit PB1-PB1N is short peptide within the 48 amino acids of the N-terminal of influenza virus polymerase subunit PB1-PB1N, wherein atoms of the Crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N has at least 40% atomic coordinates listed in table 1, or atomic coordinates of main chain carbon backbone of at least 40% amino acids in the crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N has average root mean square deviation smaller than or equal to 1.7 Angstrom with respect to the atomic coordinates listed in table 1.

2. The crystal of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N of claim 1, wherein the influenza virus selects from influenza virus A, B and C type, wherein the influenza virus preferably selects from influenza virus A type: A/goose/Guangdong/1/96, A/Brevig Mission/1/1918; influenza virus B type: B/Ann Arbor/1/1966 or influenza virus C type: C/JJ/1950.

3. The crystal of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N of claim 1, wherein the crystal of the complex has spacegroup of P4(1)2(1)2, parameter of the crystal is about: a=b=122 Angstrom, c=133 Angstrom, α=β=γ=90°.

4. The crystal of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N of claim 2, wherein the C-terminal of influenza virus A polymerase subunit PA-PAc consists of the first portion and the second portion, wherein the first portion consists of α helix 4, i.e. amino acids fragment of 406-414 positions, α helix 5, i.e. amino acids fragment of 440-450 positions, α helix 8, i.e. amino acids fragment of 583-603 positions, α helix 9, i.e, amino acids fragment of 608-613 positions, α helix 10, i.e. amino acids fragment of 633-649 positions, α helix 11, i.e. amino acids fragment of 653-673 positions, α helix 12, i.e. amino acids fragment of 683-691 positions, α helix 13, i.e. amino acids fragment of 698-714 positions, β sheet 8, i.e. amino acids fragment of 619-623 positions and β sheet 9, i.e. amino acids fragment of 628-631 positions; wherein the second portion mainly consists of p sheet 1, i.e. amino acids fragment of 290-292 positions, β sheet 2, i.e. amino acids fragment of 317-324 positions, β sheet 3, i.e. amino acids fragment of 480-491 positions, β sheet 4, i.e. amino acids fragment of 496-506 positions, β sheet 5, i.e. amino acids fragment of 517-526 positions, β sheet 6, i.e. amino acids fragment of 541-550 positions and β sheet 7, i.e. amino acids fragment of 557-571 positions; wherein the β sheets of the second portion of the C-terminal of PA-PAc is surrounded by α helix 1, i.e. amino acids fragment of 303-311 positions, α helix 2, i.e. amino acids fragment of 331-349 positions, α helix 3, i.e. amino acids fragment of 364-369 positions, α helix 6, i.e. amino acids fragment of 454-475 positions and α helix 7, i.e. amino acids fragment of 572-578 positions, wherein amino acids positions of corresponding fragments of influenza virus B and C type are shown in FIGS. 1A, 1B, 1C and FIGS. 10A, FIGS. 10B respectively.

5. The crystal of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N of claim 2, wherein the C-terminal of influenza virus A polymerase subunit PA-PAc interacts with N-terminal of PB1-PB1N mainly through α helix 8, α helix 10, α helix 11 and α helix 13, preferably through at least one amino acid selected from group consisting of Leu666 of α helix 11, Phe710 of α helix 13, Val636 of α helix 10, Leu640 of α helix 10, Trp706 of α helix 13 and Gln670 of α helix 11, wherein amino acids positions of corresponding fragments of influenza virus B and C type are shown in FIGS. 1A, 1B, 1C and FIG. 10A and FIGS. 10B respectively.

6. The crystal of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N of claim 2, wherein at least one amino acid selected from the group consisting of Ile621, Gly622, Glu623, Thr618 and Pro620 interacts with the influenza virus polymerase subunit PB1, the Ile621, Gly622, Glu623, Thr618 and Pro620 is in the ring peptide between α helix 9 and α helix 10 of C-terminal of influenza virus A polymerase subunit PA-PAc, wherein amino acids positions of corresponding fragments of influenza virus B and C type are shown in FIGS. 1A, 1B, 1C and FIG. 10A and FIGS. 10B respectively.

7. The crystal of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N of claim 2, wherein at least one amino acid selected from the group consisting of Asn647, Gln408, Cys584, Gln587, Gln591, Lys643, Asn647, Ser659, Lys663, Trp699 and Asn703 of the C-terminal of influenza virus A polymerase subunit PA-PAc constitutes “pocket” structure which interacts with the influenza virus polymerase subunit PB1N, wherein amino acids positions of corresponding fragments of influenza virus B and C type are shown in FIGS. 1A, 1B, 1C and FIG. 10A and FIGS. 10B respectively.

8. The crystal of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N of claim 2, wherein at least one amino acid selected from the group consisting of Trp406, Glu410, Lys461, Glu524, Phe525, Ser526, Lys536, Lys539, Tyr540, Leu563, Tyr564, Arg566 and Lys574 of the C-terminal of influenza virus A polymerase subunit PA-PAc constitutes “big groove” and “channel” structures which bind to nucleotide, RNA or other small molecular or proteins, wherein amino acids positions of corresponding fragments of influenza virus B and C type are shown in FIGS. 1A, 1B, 1C and FIG. 10A and FIGS. 10B respectively.

9. The crystal of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N of claim 2, wherein amino acids of 370˜405 positions of the C-terminal of influenza virus A polymerase subunit PA-PAc constitutes a big ring, wherein amino acids positions of corresponding fragments of influenza virus B and C type are shown in FIGS. 1A, 1B, 1C and FIG. 10A and FIGS. 10B respectively.

10. The crystal of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N of claim 4, wherein α helix 12 and α helix 13 of C-terminal of influenza virus polymerase subunit PA-PAc interact with other proteins, preferably at least one amino acid selected from the group consisting of Ile690, Glu691, Glu692, Cys693 and Asn696 of the α helix 12 and α helix 13 interacts with other proteins, wherein amino acids positions of corresponding fragments of influenza virus B and C type are shown in FIGS. 1A, 1B, 1C and FIG. 10A and FIG. 10B respectively.

11. The crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N of claim 4, wherein at least one amino acid selected from the group consisting of Lys506, Gly507, Arg508, Ser509, His510, Leu511, Arg512, Asn513 and Asp514 of the C-terminal of influenza virus A polymerase subunit PA-PAc interacts with other proteins, wherein His510 constitutes portion of the polymerase complex RNase, wherein amino acids positions of corresponding fragments of influenza virus B and C type are shown in FIGS. 1A, 1B, 1C and FIG. 10A and FIGS. 10B respectively.

12. Polypeptide, protein, inorganic compound or organic compound binding to at least one member selected from the group consisting of α helix 8, α helix 10, α helix 11 and α helix 13, wherein the influenza virus preferably select from influenza virus A type: A/goose/Guangdong/1/96, A/Brevig Mission/1/1918; influenza virus B type: B/Ann Arbor/1/1966 or influenza virus C type: C/JJ/1950, wherein the polypeptide, protein, inorganic compound or organic compound preferably bind to the member selected from the group consisting of Leu666 in α helix 11, Phe710 in α helix 13, Val636 and Leu640 in α helix 10, Trp706 in α helix 13, Gln670 in α helix 11, wherein amino acids positions of corresponding fragments of influenza virus B and C type are shown in FIGS. 1A, 1B, 1C and FIG. 10A and FIG. 10B respectively.

13-14. (canceled)

15. Polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates binding to at least one amino acid selected from the group consisting of Trp406, Glu410, Lys461, Glu524, Phe525, Ser526, Lys536, Lys539, Tyr540, Leu563, Tyr564, Arg566 and Lys574 of the C-terminal of influenza virus A polymerase subunit PA-PAc, wherein amino acids positions of corresponding fragments of influenza virus B and C type are shown in FIGS. 1A, 1B, 1C and FIG. 10A and FIGS. 10B respectively.

16-19. (canceled)

20. Polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates binding to PAc competed with influenza virus polymerase subunit PB1, wherein the polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates mainly interact with PAc through the hydrophobic core constituted by the α helix 8, α helix 11, α helix 13 and α helix 10, preferably interact with PAc through Met595 in α helix 8, Leu666 in α helix 11, Trp706 and Phe710 in α helix 13, Val636 and Val640 in α helix 10, wherein amino acids positions of corresponding fragments of influenza virus B and C type are shown in FIGS. 1A, 1B, 1C and FIG. 10A and FIGS. 10B respectively.

21. Polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates binding to PAc competed with influenza virus polymerase subunit PB1 of claim 20, wherein the amino acid sequence of the polypeptide or protein comprises at least three amino acids which is the same in corresponding position of short PTLLFL motif of the short helix domain constituted by the 5th˜10th residues Pro5, Thr6, Leu7, Leu8, Phe9 and Leu10 of N-terminal of wild influenza virus polymerase subunit PB1-PB1N, when the polypeptide or protein is aligned with the PTLLFL motif.

22-23. (canceled)

24. A method of expression and purifying of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N, include: (a) Construct carrier of gene sequence encoding amino acid positions about 201˜ about 301 to about 650˜ terminal of the C-terminal of influenza virus polymerase subunit PA-PAc, a tag protein fuse or not fuse to the carrier, prokaryotic cells or eukaryotic cells are transformed with said carrier in order to express the PAc with the tag protein;(b) A method similar with that of expressing PAc was used to express the PB1N with or without tag protein;(c) Proportional mix the influenza virus polymerase subunit PAc-expressing cell obtained from step (a) and the 48 amino acids within the N-terminal of influenza virus polymerase subunit PB1-expressing cell obtained from step (b), the resulted protein is separated through the specifically binding with the specific tag, the tag protein is removed from the protein through enzymolysis, the complex of PAc and PB1N is separated, the concentration of the complex is determined;Wherein the atoms of the Crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N has at least 40% atomic coordinates listed in table 1, or atomic coordinates of main chain carbon backbone of at least 40% amino acids in the crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N has average root mean square deviation smaller than or equal to 1.7 Angstrom with respect to the atomic coordinates listed in table 1.

25. The method of expression and purifying of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N of claim 24, wherein the tag protein selects from GST, Flag-tag, Myc-tag, MBP-tag, specific antibody; the carrier includes selective tag gene, the Proportional mixing in step (c) is mean that molar ratio of tag protein-PAc and tag protein-PB1N is 0.1:1˜1:0.1, preferably the molar ratio of tag protein-PAc and tag protein-PB1N is 0.5:1˜1:0.5, more preferably the molar ratio of tag protein-PAc and tag protein-PB1N is nearly 1:1, more preferably the tag protein is GST, the method recognizing the specific tag is performed through affinity column, the method of removing tag is preformed by proteinases, the method of separating the complex of PAc and PB1N is preformed through gel filtration or ion-exchange chromatography, the determining of concentration of protein is preformed through gel electrophoresis.

26. The method of expression and purifying complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N of claim 25, wherein the prokaryotic cell is Escherichia coli.

27. Method of cocrystallize the complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N, include: the protein concentration of the purified complex of PAc and PB1N is condensed to 5-30 mg/ml;the crystal growth condition is screened by gas sitting drop and hanging drop;crystal of the complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N is obtained.

28-34. (canceled)

35. Use of the crystal three-dimensional structure of complex of C-terminal of influenza virus polymerase subunit PA-PAc and N-terminal of influenza virus polymerase subunit PB1-PB1N in designing and screening polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates used in the treatment of diseases caused by the influenza virus infection, include: design polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates binding to specific portion through computer stimulation technology according to coordinates of three-dimensional structure of protein;search for polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates binding to specific portion through computer stimulation technology according to coordinates of three-dimensional structure of the protein;the designed or searched polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates according to coordinates of three-dimensional structure of the protein bind to any type of influenza virus polymerase protein which have at least 50% sequence identity with the PAc and the PB sequence, binding information is then analysed;the designed or searched polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates according to coordinates of three-dimensional structure of the protein bind to any type of influenza virus polymerase protein which have at least 50% sequence identity with the PAc and the PB1N sequence, and then crystallization is preformed, the binding information of polypeptide or compound molecular to protein is analysed through crystal diffraction method;wherein the polypeptide, protein, inorganic compound or organic compound, antibody or immune conjugates that bind to any type of influenza virus polymerase protein which had at least 50% sequence identity with the PAc and the PB sequence are candidate compound.

36-43. (canceled)