Crystal structure of interleukin-22 and uses thereof

FIELD OF THE INVENTION

[0002] The present invention relates to the fields of molecular biology, protein purification, protein crystallization, X-ray diffraction analysis, three-dimensional-structure determination, rational drug design and molecular modeling of related proteins and mutants. The present invention provides crystallization methods and crystallized human interleukin-22 (IL-22). The crystallized IL-22 is physically analyzed by X-ray diffraction techniques. The resulting X-ray diffraction patterns are of sufficiently high resolution to be useful for determining the three-dimensional structure of IL-22, molecular modeling of related proteins and mutants, as well as for determining molecules which bind thereto, or otherwise interact with the molecule.

BACKGROUND AND PRIOR ART

[0003] 1. Interleukins.

[0004] The last decade has seen knowledge of the immune system and its regulation expand tremendously. One area of particular research interest has focused on the regulatory proteins and glycoproteins of the immune system. One of the best known families of these regulatory molecules is the cytokines. These are molecules which are involved in the “communication” of cells with each other. The individual members of the cytokine family have been found to be involved in a wide variety of pathological conditions, such as cancer and allergies. Whereas sometimes the cytokines are involved in the pathology of the condition, they are also known as being therapeutically useful.

[0005] Interleukins are one type of cytokines. The literature on interleukins is vast. An exemplary, but by no means exhaustive listing of the patents in this area includes U.S. Pat. No. 4,778,879 to Mertelsmann et al.; U.S. Pat. No. 4,490,289 to Stem; U.S. Pat. No. 4,518,584 to Mark et al.; and U.S. Pat. No. 4,851,512 to Miyaji et al., all of which involve interleukin-2 or “IL-2.” Additional patents have issued which relate to interleukin-1 (“IL-1”), such as U.S. Pat. No. 4,808,611 to Cosman. The disclosure of all of these patents are incorporated by reference herein. More recent patents on different interleukins include U.S. Pat. Nos. 5,694,234 (IL-13); 5,650,492 (IL-12); 5,700,664, 5,371,193 and 5,215,895 (IL-11); 5,728,377, 5,710,251, 5,328,989 (IL-10); 5,580,753, 5,587,302, 5,157,112, 5,208,218 (IL-9); 5,194,375, 4,965,195 (IL-7); 5,723,120, 5,178,856 (IL-6), and 5,017,691 (IL-4). Even a cursory review of this patent literature shows the diversity of the properties of the members of the interleukin family. One can assume that the larger cytokines family shows even more diversity. See, e.g., Aggarwal et al., ed., Human Cytokines: Handbook For Basic And Clinical Research (Blackwell Scientific Publications, 1992); Paul, ed., Fundamental Immunology (Raven Press, 1993), pp. 763-836. All cited references are incorporated by reference herein.

[0006] 2. Interleukin-9.

[0007] The lymphokine IL-9, previously referred to as “P40,” is a T-cell derived molecule which was originally identified as a factor that sustained permanent antigen independent growth of T4 cell lines. See, e.g., Uyttenhove et al. (1988) Proc. Natl. Acad. Sci. USA 85: 6934; Van Snick et al. (1989) J. Exp. Med. 169: 363; Simpson et al. (1989) Eur. J. Biochem. 183: 715; all of which are incorporated herein by reference.

[0008] IL-9 activity was at first observed on T4-restricted cell lines. IL-9 does not, however, show activity on CTLs or freshly isolated T cells. See, e.g., Uyttenhove et al., supra, Schmitt et al. (1989) Eur. J. Immunol. 19: 2167. Subsequent experiments demonstrated that T-cell-growth factor III (TCGF III) is identical to mast cell growth enhancing activity (MEA), a factor that potentiates the proliferative response of bone-marrow-derived mast cells to IL-3. Studies on IL-9 have shown that it also supports erythroid colony formation (Donahue et al. (1990) Blood 75(12): 2271-2275); promotes the proliferation of myeloid erythroid burst formation (Williams et al. (1990) Blood 76: 306-311); supports clonal maturation of burst-forming-unit-erythrocytes (BFU-E) of adult and fetal origin (Holbrook et al. (1991) Blood 77(10): 2129-2134); and stimulates proliferation of megakaryoblastic leukemia cells (Yang et al. (1989) Blood 74: 1880). IL-9 expression has also been implicated in Hodgkin's disease and large cell anaplastic lymphoma (Merz et al. (1990) Blood 78(8): 1311-1317). Genetic analyses of mice susceptible or resistant to the development of bronchial hyperresponsiveness have linked the IL-9 gene and its expression to bronchial hyperresponsiveness susceptibility. See, e.g., Nicolaides et al. (1997) Proc. Natl. Acad. Sci. USA 94: 13175-13180. Studies with IL-9-transgenic mice demonstrate that increased IL-9 expression produces lung mastocytosis, hypereosinophilia, bronchial hyperresponsiveness and high levels of IgE. See, e.g., Temann et al., J. Exp. Med. 188: 1307-1320, 1998; Godfraind et al. (1998) J. Immunol. 160: 3989-3996; McLane et al. (1999) Am. J. Resp. Cell. Mol. 19: 713-720. Genetic studies in humans have also linked IL-9 and IL-9R genes to asthma. See, e.g., Doull et al. (1996) Am. J. Respir. Crit. Care Med. 153: 1280-1284; Holroyd et al. (1998) Genomics 52: 233-235, 1998. In combination, these observations strongly suggest that IL-9 plays a major role in bronchial hyperresponsiveness, asthma and allergies. See, e.g., PCT Application US96/12757 (Levitt, et al.), and PCT Application US97/21992 (Levitt, et al.), both of which are incorporated herein by reference.

[0009] IL-9 is known to affect the levels of other molecules in subjects. See e.g., Louahed et al. 1995) J. Immunol. 154: 5061-5070; Demoulin et al. (1996) Mol. Cell. Biol. 16: 4710-4716; both of which are incorporated herein by reference. It will be recognized that the molecules affected have their own functions in biological systems. For example, many of the known activities of IL-9 are mediated by activation of STAT transcription factors. See e.g., Louahed et al. (1995) J. Immunol. 154: 5061-5070; Demoulin et al. (1996) Mol. Cell. Biol. 16: 4710-4716; both of which are incorporated herein by reference. As such, there is continued interest in trying to identify molecules whose presence and/or level is affected by other molecules, such as cytokines.

[0010] 3. Interleukin-22

[0011] Interleukin-22 (IL-22) is a cytokine that is induced by IL-9 in T cells and mast cells. See, e.g., Dumoutier et al. (2000) J. Immunol. 164: 1814-1819; WO 00/24758 and U.S. application Ser. No. 09/419,568, which are all incorporated herein by reference. The induction of IL-22 expression by IL-9 is rapid—within 1 hour. IL-22 is a 20 kDa protein that has an N-terminal hydrophobic signal peptide and shares amino-acid-sequence homology to interleukin-10 (IL-10). In addition, IL-22 binds two receptors that are members of the class-II-cytokine-receptor family. See, e.g., Xie et al. (2000) J. Biol. Chem. 275: 31335-31339; Kotenko et al. (2001) J. Biol. Chem. 276: 2725-2732. Recent results demonstrate that the functional IL-22 receptor complex consists of two receptor chains, the CRF2-9 (IL22R) chain and the CRF2-4 (IL-10R2 or IL-10Rβ) chain. See, e.g., Xie et al. (2000) J. Biol. Chem. 275: 31335-31339; Kotenko et al. (2001) J. Biol. Chem. 276: 2725-2732. Interestingly, CRF2-4, which binds an IL-10 homodimer, is a functional component of the IL-10 signaling complex. See, e.g., Temann, et al. (1998) J. Exp. Med. 188: 1307-1320. Although this is the first example of the involvement of a class-II-cytokine-receptor in multiple distinct cytokine signaling complexes, sharing of the gamma-common chain is observed in IL-2, IL-4, IL-7, IL-9 and IL-15 receptor complexes. Other members of the class-II-receptor family include the two interferon-γ (IFN-γ) receptor chains (Rα and Rβ), the two chains of the IFN-α/β receptor, and tissue factor. In contrast, the growth hormone (GH) and prolactin receptors, for example, are members of the class-I-cytokine-receptor family.

[0012] Human and mouse IL-22 (IL-22 and mIL-22, respectively) comprise 179 amino-acid residues, including four cysteine residues, and share about 79% sequence identity. In contrast, IL-22 shares only 25% sequence identity with human IL-10 (hIL-10), and mIL-22 shares only 22% sequence identity with hIL-10. The regions of highest sequence identity are located in the C-terminal half of IL-22 and hIL-10. The fact that this region is critical for IL-10 activity, suggests that IL-22 and IL-10 share common or related biological activities.

[0013] Although IL-22 appears to play a critical role in immune function, in vivo studies in mice have demonstrated that lipopolysaccharide (LPS) induces the expression of IL-22 in numerous organs. See, e.g., Dumoutier et al. (2000) Proc. Natl. Acad. Sci. U.S.A. 97: 10144-10149. IL-22 also activates signal transducer and activator of transcription factors (STAT), specifically STAT-1 and STAT-3, in several hepatoma cell lines. The stimulation of HepG2-human-hepatoma cells up-regulates the production of acute-phase reactants such as serum amyloid A, α-1-antichymotrypsin and haptoglobin. See, e.g., Dumoutier et al. (2000) Proc. Natl. Acad. Sci. U.S.A. 97: 10144-10149. A similar induction of acute-phase reactants was observed upon injection of IL-22 into mouse liver. These findings suggest that IL-22 plays a role in the inflammatory response. Importantly, the IL-22 gene is located on human chromosome 12q near a cluster of genetic loci linked to asthma. See, e.g., Xie et al. (2000) J. Biol. Chem. 275: 31335-31339; Kotenko, et al. (2001) J. Biol. Chem. 276: 2725-2732. Thus, these findings, the induction of IL-22 by IL-9, and the association of IL-9 with inflammation and airway hyperreactivity disorders, in combination, implicate IL-22 in the etiology of asthma and allergy.

[0014] The present invention discloses a refined three-dimensional structure of IL-22 of sufficient resolution to identify the IL-22 dimerization interface and the specific amino acid residues that are involved in stabilizing the IL-22 dimer. Although both IL-10 and IL-22 form dimers, and IL-10 binds its receptor as a dimer, the present invention demonstrates that IL-22 binds the IL-22 receptor as a monomer. The present invention provides mutant IL-22 wherein the mutation or mutations destabilize the dimer. These IL-22 mutants provide IL-22 in its biologically active form and are useful as therapeutic agents. The three-dimensional structure of IL-22 of the present invention is also of sufficient resolution to allow the identification of the specific amino acids involved in binding the IL-22 receptor. In addition the present invention provides mutant IL-22 wherein the mutation(s) modify the ability of the mutant IL-22 to bind its receptor. Human IL-22 mutants with increased affinity for the IL-22 receptor are therapeutically useful agonists and antagonists. Furthermore, the present invention provides a crystal structure of sufficient quality for use in methods of rational drug design to produce therapeutically relevant molecules.

SUMMARY OF THE INVENTION

[0015] The present invention provides methods for identifying a mammalian IL-22 mutant with modified ability to dimerize, said method comprising the steps of: (a) constructing a three-dimensional structure of IL-22 defined by the atomic coordinates shown in Table 4; (b) employing the three-dimensional structure and modeling methods to identify an amino acid involved in stabilizing a dimer of IL-22; (c) producing a mammalian IL-22 having a mutation at an amino acid identified in (b); and (d) assaying said mutant IL-22 to determine the ability of said mutant to dimerize as compared to an IL-22 control, wherein a difference in dimerization between said mutant and said control is indicative of a modified ability to dimerize. As used herein, “IL-22”, “T-cell-inducible factor (TIF)” and “IL-TIF/IL-22” each refer to a cytokine of about 20 kDa that has an N-terminal hydrophobic signal peptide amino acid sequence homology to interleukin 10 (IL-10), and is upregulated by interleukin-9 (IL-9) in T cells and mast cells. See, e.g., Dumoutier et al. (2000) J. Immunol. 164: 1814-1819. As used herein, “mammalian IL-22” or “IL-22” refers to a mammalian cytokine of about 20 kDa as determined by SDS-PAGE, which has an N-terminal hydrophobic signal peptide, amino acid sequence homology to interleukin 10 (IL-10), and is upregulated by interleukin-9 (IL-9) in T cells and mast cells. Preferably, mammalian IL-22 is from, for example, human, horses, cows, sheep, goats, cats, dogs, pigs, rats and mice. More preferably, mammalian IL-22 is human IL-22 (IL-22). In a preferred embodiment, “human IL-22” consists of the amino acid sequence of SEQ ID NO: 2.

[0016] As used herein, “ability to dimerize” refers to the ability of two IL-22 monomers to form an IL-22 dimer. Mutations that either strengthen inter-monomer contacts or weaken the inter-monomer interactions modify the ability of IL-22 to dimerize. As used herein, “stabilizing the dimer” refers to the effect of an energetically favorable mutation that strengthens inter-monomer contacts. As used herein, an amino acid is “involved” in stabilizing the dimer when the amino acid directly or indirectly contributes to the stability of the dimer—either sterically or through non-covalent bonding (i.e. van der Waals interactions, hydrogen bonding, hydrophobic interactions, etc.), and the like. As used herein, “mutation site” refers to a single amino acid of an IL-22. The IL-22 mutant, however, includes IL-22 molecules that contain mutations at one or more mutation sites. As used herein, “mutation” or “mutations” refers to a substitution of one or more amino acids; a deletion of one or more amino acids; or the addition of one or more amino acids. Preferably, a mutation of the present invention is the substitution, deletion or addition of a single amino acid at one or more mutation sites.

[0017] In a preferred embodiment, the “mutation site”, that is identified by the three-dimensional structure of IL-22 and modeling methods of the present invention, is an amino acid at a position that is at or near the dimerization interface. More preferably, the “mutation site” is one or more amino acids that are located at the dimerization interface. As used herein, “dimerization interface” refers to the contact area between the two monomers of a dimer. In a preferred embodiment, the contact area between the two monomers of a dimer include amino acid positions 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, at least two of these amino acid positions or all of these amino acid positions of SEQ ID NO: 2. More preferably, the dimerization interface comprises amino acids at positions corresponding to positions 44, 48, 49, 57, 61, 64, 73, 75, 83, 166, 168, 175, 176, or 179 of SEQ ID NO: 2, at least two of these amino acid positions, or all of these amino acid positions.

[0018] The present invention also provides an isolated peptide selected from the group consisting of:

[0019] (a) an amino acid sequence consisting essentially of amino acids 61-71 of SEQ ID NO: 2;

[0020] (b) an amino acid sequence consisting essentially of amino acids 61-162 of SEQ ID NO: 2;

[0021] (c) an amino acid sequence consisting essentially of amino acids 61-169 of SEQ ID NO: 2;

[0022] (d) an amino acid sequence consisting essentially of amino acids 162-169 of SEQ ID NO: 2;

[0023] (e) an amino acid sequence consisting essentially of amino acids 98-104 of SEQ ID NO: 2; and

[0024] (f) an amino acid sequence consisting essentially of amino acids 98-157 of SEQ ID NO: 2.

[0025] In a preferred embodiment the amino acid sequence of the isolated peptide contains a mutation at one or more positions corresponding to position 61, 70, 71, 98-104, 154-157, 162, 166, and 169 of SEQ ID NO: 2.

[0026] Another embodiment of the present invention provides mimetics of peptides corresponding to Region 1 or Region 2, mimetics of fragments of peptides corresponding to Region 1 or Region 2 that bind an IL-22 receptor or an IL-22 receptor chain CRF2-4 and/or CRF2-9 or mutants of peptides corresponding to Region 1 or Region 2 and/or mutants thereof.

[0027] The mimetics of the present invention includes peptide-containing molecules that mimic elements of protein secondary structure. See e.g., Johnson et al, In: Biotechnology And Pharmacy (Pezzuto et al., eds.; Chapman and Hall, New York, (1993); Coligan et al. (1991) Current Protocols in Immunology 1(2): Chapter 5; both incorporated by reference herein. The underlying rationale behind the use of peptide mimetics is that the peptide backbone of proteins exists chiefly to orient amino acid side chains in such a way as to facilitate molecular interactions, such as those of antibody and antigen or receptor and ligand. A peptide mimetic permits molecular interactions similar to the natural molecule. These principles may be used, in conjunction with the principles outline above, to engineer second generation molecules having IL-22-receptor-binding properties that are improved as compared to unmodified IL-22.

[0028] As used herein, the terms “peptidomimetic” and “mimetic” is intended to include peptide analogues which serve as appropriate substitutes for peptides in interactions with, for example, receptors. The peptidomimetic must possess not only affinity, but also efficacy and substrate function. That is, a peptidomimetic exhibits functions of a peptide, without restriction of structure to amino acid constituents. Peptidomimetics, methods for their preparation and use are described in Morgan et al. (1989). See e.g., Morgan et al. In: Ann. Rep. Med. Chem. (Virick F. J., et al., eds.; Academic Press, San Diego, Calif., 1989) pp. 243-253; incorporated by reference herein. Peptidomimetics and the mutant polypeptides of the present invention may also include targeting moieties or molecules that direct the mimetics and polypeptides to specific tissues and cells. Many targeting moieties are known, and include, for example, asialoglycoproteins (See e.g., U.S. Pat. No. 5,166,320 to Wu) and other ligands which are transported into cells via receptor-mediated endocytosis.

[0029] Peptide combinatorial libraries are particularly useful for identifying the mimetics of the present invention (Simon et al. (1992) Proc. Natl. Acad. Sci. USA 89: 9367; incorporated herein by reference) and can be used to generate chemically diverse libraries of novel molecules. Once the peptide libraries are generated, they can be screened, for example, by using antibodies—polyclonal or monoclonal antibodies—that are specific to the mutant peptides corresponding to Region 1 and Region 2 of an IL-22, or mutant peptides of the present invention. These antibodies may be added to mimetics derived from the peptide libraries. After a period of incubation and a wash to remove unbound antibody, the presence of bound antibody is determined by standard ELISA assays. See, e.g., Harlow & Lane Antibodies: A Laboratory Manual (Cold Spring Harbor Laboratory; Cold Spring Harbor, N.Y., 1988) pg. 553. Wells that do not contain bound antibody indicate the presence of peptide mimetics that bind to the antibody. Methods for identifying active compounds in pools of small molecules include fractionating the pool by reverse phase HPLC or affinity selection/mass spectroscopy. See, e.g., Nedved et al. (1996) Anal. Chem. 68: 4228; Zuckermann et al. (1994) J. Med. Chem. 37: 2678; both incorporated herein by reference.

[0030] As used herein, the term “mimetic”, is not limited to peptide-based mimetics or peptidomimetics. As used herein, the term “mimetics”, refers to any molecule capable of mimicking IL-22 and the biological properties of IL-22 (i.e., binding activity and/or and inducing a receptor-mediated downstream biological effect characteristic of IL-22). The mimetics of the present invention may be a protein, peptide, or non-peptidyl based organic molecule. Accordingly, the term “mimetic” embraces any substance having IL-22-like activity, regardless of the chemical or biochemical nature thereof. The mimetics of the present invention may be a simple or complex substance produced by a living system or through chemical or biochemical synthetic techniques. A mimetic of the present invention can be a large molecule, e.g., a mutant IL-22 dimer or monomer, as described herein, or a small molecule, e.g., an organic molecule prepared de novo according to the principles of rational drug design. The mimetics of the present invention that are based on mutants of IL-22 also include any substance that structurally resembles a solvent-exposed surface epitope of IL-22 and binds an IL-22 receptor or IL-22 receptor chains. Methods of modeling, identifying and producing the mimetics of the present invention are disclosed in U.S. Pat. Nos. 5,835,382; 6,090,609; 6,242,201; 6,251,620; 6,273,598; and 6,303,287; all incorporated herein by reference.

[0031] The present invention also provides methods for identifying and producing mimetics of an IL-22 receptor or IL-22 receptor chain comprising the steps of: a) constructing a three-dimensional structure of hIL-22 defined by the atomic coordinates shown in Table 4; b) employing the three-dimensional structure and modeling methods to identify one or more surface accessible amino acids or one or more amino acids involved in receptor binding; c) producing a mimetic that binds or interacts with the IL-22 at one or more amino acids identified in (b); and c) assaying said mimetic to determine the ability of said mimetic to prevent or reduce the binding of IL-22 to an IL-22 receptor or receptor chain as compared o an IL-22 control, wherein a difference in IL-22 binding between said mimetic and said control is indicative of an IL-22 receptor or IL-22 receptor chain mimetic. In a preferred embodiment, the surface accessible amino acids comprise one or more amino acids selected from the group consisting the amino acids listed in Table 5. In another embodiment, the one or more amino acids involved in IL-22 receptor or IL-22 receptor chain binding are preferably the amino acids comprising Region 1 and/or Region 2. More preferably, the one or more amino acids involved in IL-22 receptor or IL-22 receptor chain binding are selected from the group consisting of the amino acid at a position corresponding to position 61, 70, 71, 162, 166, 169, 98, 99, 100, 101, 102, 103, 104, 154, 155, 156 and 157 of SEQ ID NO: 2.

[0032] The present invention also provides a mimetic of an IL-22 receptor or IL-22 receptor chain that is produced by a method comprising the steps of: a) constructing a three-dimensional structure of hIL-22 defined by the atomic coordinates shown in Table 4; b) employing the three-dimensional structure and modeling methods to identify one or more surface accessible amino acids or one or more amino acids involved in receptor binding; c) producing a mimetic that binds or interacts with the IL-22 at one or more amino acids identified in (b); and c) assaying said mimetic to determine the ability of said mimetic to prevent or reduce the binding of IL-22 to an IL-22 receptor or receptor chain as compared o an IL-22 control, wherein a difference in IL-22 binding between said mimetic and said control is indicative of an IL-22 receptor or IL-22 receptor chain mimetic. In a preferred embodiment, the surface accessible amino acids comprise one or more amino acids selected from the group consisting the amino acids listed in Table 5. In another embodiment, the one or more amino acids involved in IL-22 receptor or IL-22 receptor chain binding are preferably the amino acids comprising Region 1 and/or Region 2. More preferably, the one or more amino acids involved in IL-22 receptor or IL-22 receptor chain binding are selected from the group consisting of the amino acid at a position corresponding to position 61, 70, 71, 162, 166, 169, 98, 99, 100, 101, 102, 103, 104, 154, 155, 156 and 157 of SEQ ID NO: 2.

[0033] The present invention also provides antibodies or fragments thereof that specifically bind to one or more epitopes in a region comprising an IL-22 dimerization interface and/or a region involved in IL-22 receptor or IL-22 receptor chain binding. In a preferred embodiment, the antibodies of the present invention are polyclonal antibodies. In a more preferred embodiment, the antibodies of the present invention are monoclonal antibodies. The antibodies of the present invention bind one or more epitopes in a region comprising an IL-22 dimerization interface and/or a region involved in IL-22 receptor or IL-22 receptor chain binding and preferably prevent or interfere with the formation of IL-22 dimers and/or prevent or interfere with the binding of IL-22 to an IL-22 receptor or IL-22 receptor chain, respectively. In a preferred embodiment, the one or more epitopes are located in a region comprising the IL-22 dimerization interface. In a more preferred embodiment, the one or more epitopes comprise one or more of the amino acids selected from the group consisting of amino acids corresponding to positions 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, or 179 of SEQ ID NO: 2. In a most preferred embodiment, the one or more epitopes comprise one or more of the amino acids selected from the group consisting of amino acids corresponding to positions 44, 48, 49, 57, 61, 64, 73, 75, 83, 166, 168, 175, 176, or 179 of SEQ ID NO: 2. In a preferred embodiment, the one or more epitopes are located in a region comprising the IL-22 receptor- or IL-22-receptor-chain-binding domains. In a more preferred embodiment, the one or more epitopes are located in Region 1 and/or Region 2. In a most preferred embodiment, the epitopes in Region 1 comprise one or more of the amino acids at positions corresponding to positions 61, 70, 71, 162, 166, and 169 of SEQ ID NO: 2. In a most preferred embodiment, the epitopes in Region 2 comprise one or more of the amino acids at positions corresponding to positions 98, 99, 100, 101, 102, 103, 104 154, 155, 156, or 157 of SEQ ID NO: 2.

[0034] The present invention also provides methods for identifying a mutant of a mammalian IL-22 with modified ability to bind an IL-22 receptor, said method comprising the steps of: (a) constructing a three-dimensional structure of IL-22 defined by the atomic coordinates shown in Table 4; (b) employing the three-dimensional structure and modeling methods to identify an amino acid involved in receptor binding; (c) producing any IL-22 having a mutation at an amino acid identified in (b); and (d) assaying said mutant IL-22 to determine the ability of said mutant to bind to the IL-22 receptor as compared to an IL-22 control, wherein a difference in binding between said mutant and said IL-22 control is indicative of a modified ability to bind the IL-22 receptor. As used herein, “IL-22 control” refers to an unmodified mammalian IL-22 that is identical to the mutant IL-22 prior to incorporation of the mutation.

[0035] In a preferred embodiment, the mutation site is located in an IL-22-receptor-binding site. More preferably, the IL-22-receptor-binding site is Region 1 or Region 2. As used herein, “Region 1” refers to the region of IL-22 that is formed by helix A, loop AB and helix F and binds to the IL-22-receptor chain, CRF2-4 and/or CRF2-9. As used herein, “Region 2” refers to the region of IL-22 that is formed by helix C and helix E and binds to the IL-22-receptor chain, CRF2-4. In a more preferred embodiment, the mutation site in Region 1 is selected from one or more of the amino acids at positions corresponding to positions 61, 70, 71, 162, 166, and 169 of SEQ ID NO: 2. In another embodiment, the mutation in site in Region 2 is selected from at least one of the amino acids at positions corresponding to positions 98, 99, 100, 101, 102, 103, 104 154, 155, 156, or 157 of SEQ ID NO: 2.

[0036] The present invention also provides a mutant IL-22 comprising at least one amino acid substitution in Region 1 or Region 2 or a combination thereof. More preferably, the mutant IL-22 comprises a mutation in Region 1 at one or more positions corresponding to position 44, 48, 49, 57, 61, 64, 73, 75, 83, 166, 168, 175, 176, and 179 of SEQ ID NO: 2, and/or a mutation in Region 2 at one or more positions corresponding to positions 98, 99, 100, 101, 102, 103, 104, 154, 155, 156, or 157 of SEQ ID NO: 2. The present invention also contemplates mutant IL-22 molecules that comprise Region 1, wherein the mutant IL-22 comprises a mutation at one or more positions corresponding to position 44, 48, 49, 57, 61, 64, 73, 75, 83, 166, 168, 175, 176, or 179 of SEQ ID NO: 2, and/or a mutant IL-22 molecule that comprises Region 2, wherein the mutant IL-22 comprises a mutation at one or more positions corresponding to position 98, 99, 100, 101, 102, 103, 104, 154, 155, 156, or 157 of SEQ ID NO: 2.

[0037] The present invention also provides a mutant IL-22 comprising at least one amino acid substitution at an IL-22 dimerization interface. Preferably, the dimerization interface comprises amino acids at positions corresponding to positions 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 5, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, or 179 of SEQ ID NO: 2. More preferably, the dimerization interface comprises amino acids at positions corresponding to positions 44, 48, 49, 57, 61, 64, 73, 75, 83, 166, 168, 175, 176, or 179 of SEQ ID NO: 2.

[0038] In another embodiment, the present invention provides a mutant IL-22 comprising at, least one amino acid substitution at a IL-22 dimerization interface, wherein the mutation(s) are at a position or positions that stabilize an IL-22 dimer. Preferably, the mutation or mutations are selected from one or more of the group consisting of:

[0039] (a) an amino acid at a position corresponding to position 166 or 175 of SEQ ID NO: 2;

[0040] (b) an amino acid at a position corresponding to position 57 or 176 of SEQ ID NO: 2;

[0041] (c) an amino acid at a position corresponding to position 73 or 83 of SEQ ID NO: 2;

[0042] (d) an amino acid at a position corresponding to position 44 or 64 of SEQ ID NO: 2;

[0043] (e) an amino acid at a position corresponding to position 168 or 175 of SEQ ID NO: 2;

[0044] (f) an amino acid at a position corresponding to position 75 or 176 of SEQ ID NO: 2;

[0045] (g) an amino acid at a position corresponding to position 48 or 61 of SEQ ID NO: 2;

[0046] (h) an amino acid at a position corresponding to position 44 or 166 of SEQ ID NO: 2;

[0047] (i) an amino acid at a position corresponding to position 61 or 179 of SEQ ID NO: 2; and

[0048] (j) an amino acid at a position corresponding to position 49 or 61 of SEQ ID NO: 2.

[0049] More preferably, the mutation is at one or more amino acid positions corresponding to position 175 of SEQ ID NO: 2, wherein the substitution is any amino acid except arginine and lysine; position 166 of SEQ ID NO: 2, wherein the substitution is any amino acid except glutamate, asp artate, glutamine, asp aragine, serine, threonine and cysteine; position 176 of SEQ ID NO: 2, wherein the substitution is any amino acid except arginine, lysine, asparagine and glutamine; position 73 of SEQ ID NO: 2, wherein the substitution is any amino acid except arginine and lysine; position 44 of SEQ ID NO: 2, wherein the substitution is any amino acid except arginine and lysine; position 64 of SEQ ID NO: 2, wherein the substitution is any amino acid except glutamate, aspartate, glutamine, asparagine, serine, threonine and cysteine; position 168 of SEQ ID NO: 2; wherein the substitution is any amino acid except glutamate, aspartate, glutamine, asparagine, serine, threonine and cysteine; position 61 of SEQ ID NO: 2, wherein the substitution is any amino acid except arginine and lysine; position 166 of SEQ ID NO: 2, wherein the substitution is any amino acid except glutamate, aspartate, glutamate, glutamine, asparagine, serine, threonine and cysteine; and position 49 of SEQ ID NO: 2, wherein the substitution is any amino acid except glutamine, asparagine, glutamate and aspartate.

[0050] The present invention also provides isolated polynucleotides that encode a mutant IL-22 comprising at least one amino acid substitution in Region 1 or Region 2. More preferably, the polynucleotides encode the mutant IL-22 that comprises a mutation in Region 1 at one or more positions corresponding to position 44, 48, 49, 57, 61, 64, 73, 75, 83, 166, 168, 175, 176, and 179 of SEQ ID NO: 2, and/or a mutation in Region 2 at one or more positions corresponding to positions 98, 99, 100, 101, 102, 103, 104, 154, 155, 156, or 157 of SEQ ID NO: 2. The present invention also contemplates polynucleotides that encode mutant IL-22 molecules that comprise Region 1, wherein the mutant IL-22 comprises at least one mutation at a position corresponding to position 44, 48, 49, 57, 61, 64, 73, 75, 83, 166, 168, 175, 176, or 179 of SEQ ID NO: 2, and/or a mutant IL-22 molecule that comprises Region 2, wherein the mutant IL-22 comprises at least one mutation at a position corresponding to position 98, 99, 100, 101, 102, 103, 104, 154, 155, 156, or 157 of SEQ ID NO: 2.

[0051] In another embodiment, the isolated polynucleotides encode mutant IL-22 comprising at least one amino acid substitution at a IL-22 dimerization interface. Preferably, the dimerization interface comprises amino acids at positions corresponding to positions 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, or 179 of SEQ ID NO: 2. More preferably, the dimerization interface comprises amino acids at positions corresponding to positions 44, 48, 49, 57, 61, 64, 73, 75, 83, 166, 168, 175, 176, or 179 of SEQ ID NO: 2.

[0052] In another embodiment, the present invention provides isolated polynucleotides that encode a mutant IL-22 comprising at least one amino acid substitution at an IL-22 dimerization interface, wherein the mutation or mutations are at a position or positions that stabilize an IL-22 dimer. Preferably, the mutation or mutations are selected from one of more of the group consisting of:

[0053] (a) an amino acid at a position corresponding to position 166 or 175 of SEQ ID NO: 2;

[0054] (b) an amino acid at a position corresponding to position 57 or 176 of SEQ ID NO: 2;

[0055] (c) an amino acid at a position corresponding to position 73 or 83 of SEQ ID NO: 2;

[0056] (d) an amino acid at a position corresponding to position 44 or 64 of SEQ ID NO: 2;

[0057] (e) an amino acid at a position corresponding to position 168 or 175 of SEQ ID NO: 2;

[0058] (f) an amino acid at a position corresponding to position 75 or 176 of SEQ ID NO: 2;

[0059] (g) an amino acid at a position corresponding to position 48 or 61 of SEQ ID NO: 2;

[0060] (h) an amino acid at a position corresponding to position 44 or 166 of SEQ ID NO: 2;

[0061] (i) an amino acid at a position corresponding to position 61 or 179 of SEQ ID NO: 2; and

[0062] (j) an amino acid at a position corresponding to position 49 or 61 of SEQ ID NO: 2.

[0063] More preferably, the isolated polynucleotides encode an IL-22 mutant, wherein the mutation is at one or more amino acid positions corresponding to position 175 of SEQ ID NO: 2, wherein the substitution is any amino acid except arginine and lysine; position 166 of SEQ ID NO: 2, wherein the substitution is any amino acid except glutamate, aspartate, glutamine, asparagine, serine, threonine and cysteine; position 176 of SEQ ID NO: 2, wherein the substitution is any amino acid except arginine, lysine, asparagine and glutamine; position 73 of SEQ ID NO: 2, wherein the substitution is any amino acid except arginine and lysine; position 44 of SEQ ID NO: 2, wherein the substitution is any amino acid except arginine and lysine; position 64 of SEQ ID NO: 2, wherein the substitution is any amino acid except glutamate, aspartate, glutamine, asparagine, serine, threonine and cysteine; position 168 of SEQ ID NO: 2; wherein the substitution is any amino acid except glutamate, aspartate, glutamine, asparagine, serine, threonine and cysteine; position 61 of SEQ ID NO: 2, wherein the substitution is any amino acid except arginine and lysine; position 166 of SEQ ID NO: 2, wherein the substitution is any amino acid except glutamate, aspartate, glutamate, glutamine, asparagine, serine, threonine and cysteine; and position 49 of SEQ ID NO: 2, wherein the substitution is any amino acid except glutamine, asparagine, glutamate and aspartate.

[0064] The present invention also provides a mutant IL-22 comprising at least one amino acid substitution at one or more glycosylation sites, wherein the substitution prevents or reduces the glycosylation of IL-22. In a preferred embodiment, the at least one amino acid substitution is at a position selected from the group consisting of amino acid positions corresponding to position 54, 55, 56, 97, 98 or 99 of SEQ ID NO: 2. In a more preferred embodiment, the at least one amino acid substitution corresponds to position 54, 56, 97, or 99 of SEQ ID NO: 2, or a combination thereof.

[0065] In another embodiment, the mutant IL-22 comprises one or more amino acid substitutions, wherein the substitution or substitutions produce a glycosylation site at the dimerization interface. In a preferred embodiment, the glycosylation site consists of the amino acid sequence Asn-Xaa-Thr/Ser. In one embodiment, insertion of a glycosylation site increases the glycosylation of IL-22. In another embodiment, insertion of a glycosylation site increases the glycosylation of IL-22 and prevents or reduces the dimerization of IL-22 as compared to an unsubstituted IL-22.

[0066] In another embodiment, a mutant IL-22 of the present invention comprising a mutation in Region 1, Region 2, or at the dimerization interface, further comprises one or more amino acid substitutions, wherein the substitution or substitutions produce a glycosylation site at the dimerization interface. In a preferred embodiment, the glycosylation site consists of the amino acid sequence Asn-Xaa-Thr/Ser. In one embodiment, insertion of a glycosylation site increases the glycosylation of IL-22. In another embodiment, insertion of a glycosylation site increases the glycosylation of IL-22 and prevents or reduces the dimerization of IL-22 as compared to an unsubstituted IL-22.

[0067] The present invention also provides a computer system comprising: a) a memory comprising atomic coordinates shown in Table 4; and b) a processor in electrical communication with the memory; wherein the processor generates a molecular model having a three dimensional shape representative of at least a portion of a mammalian IL-22. In a preferred embodiment, the atomic coordinates shown in Table 4 are stored on a computer readable diskette.

[0068] The present invention also provides cloning and expression vectors that comprise the polynucleotides of the present invention. In another embodiment, host cells are transformed with the vectors of the present invention and are used in methods of producing the encoded mutant IL-22 that comprise culturing the host cells and isolating the mutant IL-22.

[0069] The present invention also provides pharmaceutical compositions comprising the mutant IL-22, peptides or mimetics of the present invention and a pharmaceutically acceptable carrier. As used herein, “pharmaceutically acceptable carrier” refers to any carrier, solvent, diluent, vehicle, excipient, adjuvant, additive, preservative, and the like, including any combination thereof, that is routinely used in the art.

[0070] Physiological saline solution, for example, is a preferred carrier, but other pharmaceutically acceptable carriers are also contemplated by the present invention. The primary solvent in such a carrier may be either aqueous or non-aqueous. The carrier may contain other pharmaceutically acceptable excipients for modifying or maintaining pH, osmolarity, viscosity, clarity, color, sterility, stability, rate of dissolution, and/or odor. Similarly, the carrier may contain still other pharmaceutically acceptable excipients for modifying or maintaining the stability, rate of dissolution, release, or absorption or penetration across the blood-brain barrier.

[0071] The pharmaceutical compositions of the present invention may be administered orally, topically, parenterally, rectally or by inhalation spray in dosage unit formulations that contain conventional non-toxic pharmaceutically acceptable carriers, adjuvants and vehicles. As used herein, “parenterally” refers to subcutaneous, intravenous, intramuscular, intrasternal, intrathecal, and intracerebral injection, including infusion techniques.

[0072] The pharmaceutical compositions may be administered parenterally in a sterile medium. The compositions, depending on the vehicle and concentration used, may be suspended or dissolved in the vehicle. Advantageously, adjuvants such as local anesthetics, preservatives and buffering agents can be dissolved in the vehicle. The most preferred route of parenteral administration of the pharmaceutical compositions of the present invention is subcutaneous, intramuscular, intrathecal or intracerebral. Other embodiments of the present invention encompass administration of the composition in combination with one or more agents that promote penetration of active ingredients across the blood-brain barrier, and/or slow-release of the active ingredient(s). Such excipients include those substances usually and customarily used to formulate dosages for parenteral administration in either unit dose or multi-dose form or for direct infusion into the CSF by continuous or periodic infusion from an implanted pump.

[0073] The desired or optimal dose of the compositions of the present invention may be obtained by parenteral administration that is repeated daily, more frequently, or less frequently. The compositions may also be infused continuously or periodically from an implanted pump. The frequency of dosing will depend on the pharmacokinetic parameters of the specific mutant IL-22, peptide or mimetic in the formulation and the route of administration.

[0074] In more preferred embodiments, the pharmaceutical compositions are administered as orally active formulations, inhalant spray or suppositories. The pharmaceutical compositions of the present invention may be in a form suitable for oral use, for example, as tablets, troches, lozenges, aqueous or oily suspensions, dispersible powders or granules, emulsions, hard or soft capsules, syrups or elixirs.

[0075] Active ingredient may be combined with the carrier materials in an amount to produce a single dosage form. The amount of the active ingredient will vary, depending upon the identity of the mutant, peptide, or mimetic, the host treated, and the particular mode of administration.

[0076] Regardless of the manner of administration, however, the specific dose is calculated according to approximate body weight or body surface area of the patient. Further refinement of the dosing calculations necessary to optimize dosing for each of the contemplated formulations is routinely conducted by those of ordinary skill in the art without undue experimentation, especially in view of the dosage information and assays disclosed herein.

[0077] The present invention also provides a method of treating a subject in need of IL-22, comprising the step of administering one of the pharmaceutical composition of the present invention, wherein the pharmaceutical composition is an IL-22-receptor agonist.

[0078] The present invention also provides a method of inhibiting IL-22 in a subject in need thereof, comprising the step of administering one of the pharmaceutical composition of the present invention, wherein the pharmaceutical composition inhibits the activation of an IL-22 receptor by IL-22.

[0079] The present invention also provides for methods for determining if a substance of interest associates with IL-22, or an IL-22 mutein, as described, supra, or any of the regions defined by the structure coordinates defined herein. One such way to determine associates is to carry out computational means to perform fitting operations between the IL-22 moiety and the substance of interest, followed by analysis of the results. Such methods are taught, e.g., by U.S. Pat. No. 6,303,287, which is incorporated by reference in its entirety, as well as by EP 935 609B1, its European counterpart, which is also incorporated by reference. With respect to the '287 patent, attention is drawn to the claims thereof, which provide guidelines for the methodologies of the invention described herein.

[0080] Also a part of the invention are methods utilizing the crystalline structures described herein, in order to carry out studies for drug modeling and drug development, as the type of structural analysis described supra is key to such work. By determining interaction, and studying points of high and low interaction, one can determine optimal structures of useful antagonists and/or agonists of IL-22 and the homologues described herein. Once molecules are found that interact with the crystalline structures of the invention, one can isolate the resulting complexes of crystal and ligand such as what was done in the '287 and '609 patents, cited supra.

[0081] Yet a further aspect of this invention are data storage media, such as CD-ROMs, which are machine readable and include at least a portion of one or more of the IL-22 and IL-22 related structures described herein.

BRIEF DESCRIPTION OF THE DRAWINGS

[0082]
FIG. 1. (A) Stereoview of the Cα trace of the dimeric structure of IL-22. (B) Schematic representation of the secondary structure of IL-22 monomer A, according to PROCHECK (Laskowski et al. (1993) J. Appl. Crystallogr. 26: 283-291; Polikarpov et al. (1997) Nucl. Instrum. Methods 405: 159-164), showing the location of the two disulfide bonds (Cys40-Cys132 and Cys89-Cys178). The figures were prepared using Molscript (Dauter, et al. (2000) Acta Cryst. D56: 232-237), Bobscript (Nagem et al. (2001) Acta Cryst. D57: 996-1002) and Raster3D (Perrakis et al. (1999) Nature Struct. Biol. 6: 458-463).

[0083]
FIG. 2. Least-square fit of monomer A to monomer B. The root-mean-square deviation (rmsd) is shown as a function of residue numbers. Only main chain atoms were used in calculation.

[0084]
FIG. 3. Contact surface of the IL-22 dimer, shaded according to residue hydrophobicity (A,B) and electrostatic potential (C,D). (A,C) show the interface of monomer A, whereas (B,D) show the interface of monomer B. In parts (A) and (B) the darker the stippled shading the greater the hydrophobicity. In parts (C) and (D) areas of negative, positive and neutral electrostatic potential are in medium stippling, dark stippling and light or no stippling, respectively. The figures were prepared with GRASP. See, e.g., Brünger, et al. (1998) Acta Cryst. D54: 905-921.

[0085]
FIG. 4. Secondary structure diagram showing the superposition of an IL-22 monomer (in medium stippling) onto (A) a hIL-10 dimer (from helices A to D in dark stippling and from helices E′ to F′ in light stippling; helices A′ to D′, E and F were omitted) and (B) a hIFN-γ dimer (from helices A to D in light stippling and from helix E′ to F′ in black; helices A′ to D′, E and F were omitted). Superposition of an IL-22 dimer (in dark stippling and no stippling) onto (C) a hIL-10 dimer (in black and light stippling) and (D) a hIFN-γ dimer (in medium stippling and light stippling).

[0086]
FIG. 5. Primary structure alignment of murine, and human IL-22 (SEQ ID NO: 3 and 2 respectively) and human IL-10 (SEQ ID NO: 1). Whenever possible, the three dimensional information was used to improve alignment. Disulfide bonds in IL-22 are marked with filled-in circles. The amino acid similarity between IL-22 and hIL-10, as calculated by the program ALSCRIPT (Nicholls et al. (1991) Struct. Funct. Genet. 11: 281-296), are boxed. Residues conserved in mIL-22 and IL-22 are boxed in the sequence of mIL-22. The loops and helices of human IL-22's secondary structure are depicted. The figure was drawn using the program ALSCRIPT (Nicholls et al. (1991) Struct. Funct. Genet. 11: 281-296).

[0087]
FIG. 6. (A) Superposition of the hIFN-γ/hIFN-γRα complex (hIFN-γ light stippling and medium stippling; hIFN-γRα normal) onto IL-22 monomer (dark stippling). Superposition of (B) hIFN-γ (light stippling and darkest stippling) and (C) hIL-10 (darkest stippling and light stippling) onto IL-22 in a coil representation of the potential receptor binding site of IL-22 (medium stippling). Residues involved in direct interaction with a receptor chain are also shown.

DETAILED DESCRIPTION OF THE INVENTION

[0088] The present invention provides methods for crystallizing human interleukin-22. The resultant crystals diffract X-rays with sufficiently high resolution to allow determination of the atomic coordinates and solve the three-dimensional structure of IL-22. The three-dimensional structure, as provided on computer-readable media described herein, is useful for rational drug design of IL-22-related mimetics, IL-22 mutants and ligands of the IL-22 receptor. Such mimetics, mutants and ligands are useful for treating and inhibiting IL-22-mediated processes or IL-22-related disorders and diseases such as asthma, inflammation and cancer.

[0089] 1. IL-22 Crystallization.

[0090] The isolation and purification of human IL-22, including polynucleotides, vectors and transformed or transfected host cells encoding IL-22, and recombinant methods of IL-22 production, are described in WO 00/24758 and U.S. application Ser. No. 09/419,568, which are both incorporated herein in their entirety. The amino acid sequences of mouse IL-22, human IL-22 and human IL-10 are presented in FIG. 5 as SEQ ID NO: 3, 2, and 1, respectively.

[0091] Recombinant IL-22 of the present invention may be produced by the following process or other recombinant protein expression methods:

[0092] a. constructing, by conventional molecular-biology methods, an expression vector comprising an operon that encodes IL-22, thereby producing a vector for the expression of IL-22;

[0093] b. transferring the expression vectors to a host cell by conventional molecular biology methods to produce a transfected or transformed host cell for the expression of IL-22; and

[0094] c. culturing the transfected or transformed cell by conventional molecular-biology methods so as to produce IL-22.

[0095] The IL-22 of the present invention may be produced using conventional molecular-biology methods. The term “conventional molecular biology methods” refers to techniques for manipulating polynucleotides that are well known to the person of ordinary skill in the art of molecular biology. Examples of such well known techniques can be found in Sambrook et al. Molecular Cloning: A Laboratory Manual, 3rd Edition (Cold Spring Harbor, N.Y.; 2001). Examples of conventional molecular biology techniques include, but are not limited to, in vitro ligation, restriction-endonuclease digestion, PCR, cellular transformation and transfection, hybridization, electrophoresis, DNA sequencing, and the like.

[0096] Specifically, the general methods for construction of the vector of the invention, transfection of cells to produce the host cell of the invention, and culturing of cells to produce the IL-22 of the present invention are all conventional molecular biology methods. Likewise, once produced, the IL-22 of the present invention may be purified by standard procedures of the art, including ammonium-sulfate precipitation, affinity-column chromatography, gel electrophoresis and the like.

[0097] The present invention also provides polynucleotide vectors for the replication, manipulation and expression of the isolated polynucleotides of the present invention. Preferably, the vectors allow expression of the isolated polynucleotides of the present invention in either prokaryotic or eukaryotic cells. Prokaryotic cells are selected from bacterial cells, e.g. Escherichia coli, and eukaryotic cells are selected from insect, fungal, e.g. Saccharomyces, Pichia pastoris, and mammalian cells, e.g. Chinese hamster ovary (CHO) and human. The vectors of the present invention may contain regulatory elements that allow inducible or constitutive expression of the operably-linked polynucleotide, confer antibiotic resistance, improve secretion, purification and detection, e.g. His and antigen tags, and the like.

[0098] The host cells may be either a bacterial cell such as Escherichia coli, or a eukaryotic cell. Mammalian cells such as Chinese hamster ovary cells, may also be used. Notably, the choice of expression vector is dependent upon the choice of host cell, and may be selected so as to have the desired expression and regulatory characteristics in the selected host cell.

[0099] The first prerequisite for solving the three-dimensional structure of a protein by X-ray crystallography is a well-ordered crystal that will strongly diffract X-rays. X-rays are directed onto a regular, repeating array of identical molecules so that the X-rays are diffracted from it in a pattern from which the structure of an individual molecule can be retrieved. Different crystal forms can be more or less well-ordered and hence give diffraction patterns of different quality. As a general rule, the more closely the protein molecules pack, and consequently the less water the crystals contain, the better is the diffraction pattern because the molecules are better ordered in the crystal. Well-ordered crystals of globular protein molecules are large, spherical, or ellipsoidal objects with irregular surfaces, and crystals thereof contain large holes or channels that are formed between the individual molecules. These channels, which usually occupy more than half the volume of the crystal, are filled with disordered solvent molecules. The protein molecules are in contact with each other at only a few small regions. This is one reason why structures of proteins determined by X-ray crystallography are generally the same as those for the proteins in solution.

[0100] The formation of crystals is dependent on a number of different parameters, including pH, temperature, protein, concentration, the nature of the solvent and precipitant, as well as the presence of added ions or ligands. Crystallization experiments may be needed to screen all these parameters for the few combinations that might give crystals suitable for X-ray diffraction analysis. Crystallization robots can automate and speed up the work of reproducibly setting up large number of crystallization experiments.

[0101] A pure and homogeneous protein sample is important for successful crystallization. Proteins obtained from cloned genes in efficient expression vectors can quickly be purified to homogeneity in large quantities in a few purification steps. A protein to be crystallized is preferably at least 93-99% pure, according to standard criteria of homogeneity. Crystals form when molecules are precipitated very slowly from supersaturated solutions. The most frequently used procedure for making protein crystals is the hanging-drop method, in which a drop of protein solution is brought very gradually to supersaturation by loss of water from the droplet to the larger reservoir that contains salt or polyethylene glycol solution.

[0102] In general, IL-22 is purified as described in WO 00/24758 and U.S. application Ser. No. 09/419,568, which are both incorporated herein by reference. The resulting IL-22 is in sufficiently pure and concentrated for crystallization. The purified IL-22 preferably runs as a single band under reducing or nonreducing polyacrylamide gel electrophoresis (PAGE) (nonreducing conditions are used to evaluate the presence of disulfide bonds). Purified IL-22 is preferably crystallized using the hanging drop method under varying conditions of at least one of the following: pH, buffer type, buffer concentration, salt type, polymer type, polymer concentration, other precipitating agents and concentration of purified and cleaved IL-22. See, e.g., the methods provided in a commercial kit, such as CRYSTAL SCREEN (Hampton Research, Riverside, Calif.); Taylor et al. (1992) J. Mol. Biol. 226:1287-1290; Takimoto et al. (1992), infra.

[0103] Crystallization conditions suitable to produce diffraction-quality crystals may be selected from a buffer containing, for example: between 1 and 100 mg/ml IL-22 in 10-200 mM buffer (pH 4-9) (e.g., phosphate, cacodylate, acetates, imidazole, Tris HCl, sodium HEPES); and optionally a salt (e.g., calcium chloride, sodium citrate, magnesium chloride, ammonium acetate, ammonium sulfate, potassium phosphate, magnesium acetate, zinc acetate; calcium acetate); and optionally 0-50% of a polymer (e.g., polyethylene glycol (PEG); average molecular weight 200-10,000); and optionally other precipitating agents (salts: potassium or sodium tartrate, ammonium sulfate, sodium acetate, lithium sulfate, sodium formate, sodium citrate, magnesium formate, sodium phosphate, potassium sulfate, ammonium phosphate); and optionally organics e.g., 2-propanol; non-volatile: 2-methyl-2,4-pentanediol).

[0104] The above mixtures are used and screened by varying at least one of pH, buffer type; buffer concentration, precipitating salt type or concentration, PEG type, PEG concentration, and protein concentration. Crystals ranging in size from 0.2-0.7 mm are formed in 1-7 days. From one to ten crystals are observed in one drop and crystal forms, such as, but not limited to, bipyramidal, rhomboid, and cubic, are suitable. Initial X-ray analyses indicate that such crystals diffract at moderately high to high resolution. When fewer crystals are produced in a drop, they can be much larger size, e.g., 0.4-0.9 mm. These crystals diffract X-rays to at least 3.5 Å resolution, such as 1.5-3.5 Å, or any range of value therein, such as 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3.0, with 3.0 Å or less being preferred.

[0105] 2. X-Ray Diffraction and Structure Determination.

[0106] The X-ray diffraction patterns of the invention are of sufficiently high resolution for three-dimensional modeling of IL-22 and IL-22-related molecules, such as IL-22-receptor ligands and IL-22-receptor-chain mimics. Preferably the resolution is in the range of 1.5 to 3.5 Å, more preferably 1.5-3.0 Å and most preferably about 1.9 Å.

[0107] X-rays may be produced by high-voltage tubes in which an anode emits X-rays of a specific wavelength upon bombardment by accelerating electrons. More powerful X-ray beams can be produced in synchrotron storage rings where electrons (or positrons) travel near the speed of light. These particles emit very strong radiation at all wavelengths—from short gamma rays to visible light. When used as an X-ray source, however, only X-ray radiation is channeled from the storage ring. Polychromatic X-ray beams are produced by having a broad window that allows through X-ray radiation with wavelengths of 0.2-3.5 Å.

[0108] In diffraction experiments, a narrow and parallel beam of X-rays is taken out from the X-ray source and directed onto the crystal to produce diffracted beams. The incident primary beam causes damage to both protein and solvent molecules. The crystal is, therefore, usually cooled to prolong its lifetime (e.g., −220 to −50 C). The primary beam must strike the crystal from many different directions to produce all possible diffraction spots, and so the crystal is rotated in the beam during the experiment.

[0109] The diffracted spots are recorded either on a film, the classical method, or by an electronic detector. The exposed film is measured and digitized by a scanning device, whereas electronic detectors feed the signals they detect directly in a digitized form into a computer. Electronic area detectors significantly reduce the time required for data collection.

[0110] When the primary beam from an X-ray source strikes the crystal, some of the X-rays interact with the electrons on each atom and cause them to oscillate. The oscillating electrons serve as a new source of X-rays, which are emitted in almost all directions, referred to as scattering. When atoms and their electrons are arranged in a regular three-dimensional array, the X-rays emitted from the oscillating electrons interfere with one another. In most cases, these X-rays, colliding from different directions, cancel each other out; those from certain directions, however, will add together to produce diffracted beams of radiation that can be recorded as a pattern on a photographic plate or detector.

[0111] The diffraction pattern obtained in an X-ray experiment is related to the crystal that caused the diffraction. X-rays that are reflected from adjacent planes travel different distances, and diffraction only occurs when the difference in distance is equal to the wavelength of the X-ray beam. This distance is dependent on the reflection angle, which is equal to the angle between the primary beam and the planes.

[0112] The relationship between the reflection angle (θ), the distance between the planes (d), and the wavelength (λ) is given by Bragg's law: 2dsinθ.λ. This relationship can be used to determine the size of the unit cell in the crystal. Briefly, the position on the film of the diffraction data relates each spot to a specific set of planes through the crystal. By using Bragg's law, these positions can be used to determine the size of the unit cell.

[0113] Each atom in a crystal scatters X-rays in all directions, and only those that positively interfere with one another, according to Bragg's law, give rise to diffracted beams that can be recorded as a distinct diffraction spot above background. Each diffraction spot is the result of interference of all X-rays with the same diffraction angle emerging from all atoms. For the protein crystal of myoglobin, for example, each of the about 20,000 diffracted beams that have been measured contain scattered X-rays from each of the around 1500 atoms in the molecule. To extract information about individual atoms from such a system requires considerable computation. The mathematical tool that is used to handle such problems is called the Fourier transform.

[0114] Each diffracted beam, which is recorded as a spot on the film, is defined by three properties: the amplitude, which we can measure from the intensity of the spot; the wavelength, which is set by the X-ray source; and the phase, which is lost in X-ray experiments. All three properties are needed for all of the diffracted beams, in order to determine the position of the atoms giving rise to the diffracted beams.

[0115] For larger molecules, protein crystallographers have determined the phases in many cases using a method called multiple isomorphous replacement (MIR) (including heavy metal scattering), which requires the introduction of new X-ray scatterers into the unit cell of the crystal. These additions are usually heavy atoms that contribute significantly to the diffraction pattern. Since such heavy metals contain many more electrons than the carbon, hydrogen, oxygen, nitrogen and sulfur atoms of the protein, they scatter X-rays more strongly. All diffracted beams would therefore increase in intensity after heavy-metal substitution if all interference were positive. In fact, however, some interference is negative; consequently, following heavy-metal substitution, some spots measurably increase in intensity, others decrease, and many show no detectable difference. Isomorphous replacement is usually done by diffusing different heavy-metal complexes into the channels of the preformed protein crystals. The protein molecules expose side chains (such as SH groups) into these solvent channels that are able to bind heavy metals. It is also possible to replace endogenous light metals in metalloproteins with heavier ones, e.g., zinc by mercury, or calcium by samarium.

[0116] Phase differences between diffracted spots can be determined from intensity changes following heavy-metal substitution. First, the intensity differences are used to deduce the positions of the heavy atoms in the crystal unit cell. Fourier summations of these intensity differences give maps of the vectors between the heavy atoms—the so-called Patterson maps. From these vector maps the atomic arrangement of the heavy atoms is deduced. From the positions of the heavy metals in the unit cell, one can calculate the amplitudes and phases of their contribution to the diffracted beams of protein crystals containing heavy metals.

[0117] This knowledge is then used to find the phase of the contribution from the protein in the absence of the heavy-metal atoms. As both the phase and amplitude of the heavy metals, the amplitude of the protein alone, and the amplitude of the protein plus heavy metals is known, one phase and three amplitudes are known. From this, the interference of the X-rays scattered by the heavy metals and protein can be calculated to see if it is constructive or destructive. The extent of positive or negative interference, with knowledge of the phase of the heavy metal, gives an estimate of the phase of the protein. Because two different phase angles are determined and are equally good solutions, a second heavy-metal complex can be used which also gives two possible phase angles. Only one of these will have the same value as one of the two previous phase angles; it therefore represents the correct phase angle. In practice, more than two different heavy-metal complexes are usually made in order to give a reasonably good phase determination for all reflections. Notably, each individual phase estimate contains experimental errors arising from errors in the measured amplitudes, and for many reflections, the intensity differences are too small to measure after one particular isomorphous replacement.

[0118] The amplitudes and the phases of the diffraction data from the protein crystals are used to calculate an electron-density map of the repeating unit of the crystal. This map then has to be interpreted as a polypeptide chain with a particular amino acid sequence. The interpretation of the electron-density map is complicated by several limitations of the data. First of all, the map itself contains errors, mainly due to errors in the phase angles. In addition, the quality of the map depends on the resolution of the diffraction data, which depends on crystal quality and degree of order. This directly influences the image that can be produced. The resolution is measured in Ångstrom units—as this number decreases, the resolution increases and consequently, the amount of molecular detail observed also increases.

[0119] Building the initial model begins by determining how the polypeptide chain weaves its way through the electron-density map. The resulting chain trace constitutes a hypothesis, by which one tries to match the density of the side chains to the known sequence of the polypeptide. When a reasonable chain trace has finally been obtained, an initial model is built to give the best fit of the atoms to the electron density. Computer graphics are used both for chain tracing and for model building to present the data and manipulate the models.

[0120] The initial model will contain some errors. Provided the protein crystals diffract to a sufficiently high resolution—better than 3.5 Å—most or substantially all of the errors can be removed by crystallographic refinement of the model using computer algorithms. In this process, the model is modified to minimize the difference between the experimentally observed diffraction amplitudes and those calculated for a hypothetical crystal containing the model, instead of the real molecule. This difference is expressed as an R factor (residual disagreement), which is 0.0 for exact agreement and about 0.59 for total disagreement.

[0121] In general, the R factor is preferably between 0.15 and 0.35, and more preferably between about 0.24-0.28 for a well-determined protein structure. The residual difference is a consequence of errors and imperfections in the data. These derive from various sources, including slight variations in the conformation of the protein molecules, as well as inaccurate corrections both for the presence of solvent and for differences in the orientation of the microcrystals from which the crystal is built. This means that the final model represents an average of molecules that are slightly different both in conformation and orientation. In refined structures at high resolution, there are usually no major errors in the orientation of individual residues, and the estimated errors in atomic positions are usually around 0.1-0.2 Å, provided the amino acid sequence is known. Hydrogen bonds, both within the protein and to bound ligands, can be identified with a high degree of confidence.

[0122] Most X-ray structures are determined to a resolution between 1.7 Å and 3.5 Å. Electron-density maps with this resolution range are preferably interpreted by fitting the known amino acid sequences into regions of electron density in which individual atoms are not resolved.

[0123] The IL-22 crystals are analyzed using a suitable X-ray source and diffraction patterns are obtained. Crystals are preferably stable for at least 10 hrs in the X-ray beam. Frozen crystals (e.g., −220 to −50 C) could also be used for longer X-ray exposures (e.g., 24-72 hrs), the crystals being relatively more stable to the X-rays in the frozen state. To collect the maximum number of useful reflections, multiple frames are optionally collected as the crystal is rotated in the X-ray beam, e.g., for 24-72 hrs. Larger crystals (>0.2 mm) are preferred, to increase the resolution of the X-ray diffraction. Alternatively, crystals may be analyzed using a synchrotron high-energy X-ray source. Using frozen crystals, X-ray diffraction data is collected on crystals that diffract to a relatively high resolution of 3.5 Å or less, sufficient to solve the three-dimensional structure of IL-22 in considerable detail, as presented herein. Specifically, crystals were soaked in different cryosoaking solutions, mounted in a rayon loop and finally flash-cooled to 80 K in a cold nitrogen stream. Data collection was performed at the Protein Crystallography beamline (LNLS, Campinas, Brazil; Polikarpov et al. (1997) J. Synchrotron Rad. 5: 72-76; Polikarpov et al. (1997) Nucl. Instrum. Methods A 405: 159-164) and at the X4A beamline (NSLS, Upton, USA), using a MAR345 image plate and a Quantum-4 CCD detector.

[0124] The heavy metal derivatives are used to determine the phase, e.g., by the isomorphous replacement method. Heavy atom isomorphous derivatives of IL-22 are used for X-ray crystallography, where the structure is solved using one or several derivatives, which, (when combined) improves the overall figure of merit. Derivatives are identified through Patterson maps and/or cross-phase difference Fourier maps, e.g., using commercially-available software, including the CCP4 package (SERC Collaborative Computing Project No. 4, Daresbury Laboratory, UK, 1979); SIRAS; SHARP [35]; DREAR [31] and SnB 2.1 [32]; and SOLOMON [36]. The program MLPHARE (Wolf et al., eds., Isomorphous Replacement and Anomalous Scattering: Proceedings of CCP4 Study Weekend, pp. 80-86, SERC Daresbury Lab., UK (1991)) is optionally used for refinement of the heavy atom parameters and the phases derived from them by comparing at least one of completeness (%), resolution (in Å), Rr (%), heavy atom concentration (mM), soaking time, heavy atom sites, phasing power (acentric, centric). Addition of heavy atom derivatives produce an MIR map with recognizable features.

[0125] Once the initial phases are calculated to 3.2 Å, they may be improved and extended to a higher resolution of 2.8 Å, using solvent flattening, histogram matching and/or Sayre's equation in the program DM. See e.g., Cowtan et al. (1993) Acta Crystallogr. 49: 148-157. The skeletonization of the DM procedure is optionally used to improve connectivity in the bulk of the protein envelope. Both the MIR and density modified maps are optionally used in subsequent stages, to provide sufficient resolution and/or modeling of surface structures.

[0126] Skeletonized representations of electron density maps are then computed. These maps are automatically or manually edited using suitable software, e.g., the graphics package FRODO (Jones et al. (1991), infra) to give a continuous Cα trace. The IL-22 sequence is then aligned to the trace. Initially pieces of idealized polypeptide backbone were placed into regions of the electron density map with obvious secondary structures (e.g., α-helix, β-sheet). After a polyalanine model was constructed for the protein, amino acid side-chains were added where density was present in the maps. The amino acid sequence of IL-22 was then examined for regions with distinct side-chain patterns (e.g., three consecutive aromatic rings). When a pattern in the sequence was found to match an area of the map, the correct side-chains were built onto the existing model. Eventually fragments containing recognizable sequence motifs were connected into a single chain, completing the tracing of the amino acid sequence into the maps. Cycles of simulated annealing against these data, may be refined using the program X-PLOR for molecular dynamics for R-factor refinement. See e.g., Brünger et al. (1987) J. Mol. Biol. 203: 803-816. This refinement was followed by manual rebuilding with FRODO using experimental and 2Fo-Fc maps. The model may be further refined using a least-squares refinement program, such as TNT. See e.g., Tronrud et al. (1987) Acta Crystallogr. A 43: 489-501. One or more of the above modeling steps may performed to provide a molecular 3-D model of IL-22. It is preferred that the IL-22 models has no residues in disallowed regions of the Ramachandran plot, and gives a positive 3D-1D profile (Luthy et al. (1992) Nature 356: 83-85; Kraulis (1991), infra), suggesting that all the residues are in acceptable environments.

[0127] Alternatively, a program such as ARP (Lamzin et al. (1993) Acta Cryst. D49: 129-147) may be used to add crystallographic waters and as a tool to check for bad areas in the model. The programs PROCHECK (Lackowski et al. (1993) J. Appl. Cryst. 26: 283-291), WHATIF (Vriend (1990) J. Mol. Graph. 8: 52-56), PROFILE 3D (Luthy et al. (1992) Nature 356: 83-85), and ERRAT (Colovos et al. (1993) Protein Science 2: 1511-1519), as well as the geometrical analysis generated by X-PLOR were used to check the structure for errors. Anisotropic scaling between Fobs and Fcalc may be applied after careful assessment of the quality and completeness of the data. The program DSSP may be used to assign the secondary structure elements (Kabsch et al. (1983) Biopolymers 22: 2577-2637). A program such as SUPPOS (from the BIOMOL crystallographic computing package) can be used for some or all of the least-squares superpositions of various models and parts of models. The program ALIGN (Cohen (1986) J. Mol. Biol. 190: 593-604) may be used to superimpose N- and C-terminal domains of IL-22. Solvent accessible surfaces and electrostatic potentials can be calculated using such programs as GRASP (Nicholls et al. (1991), infra).

[0128] 3. Rational Drug Design and Molecular Modeling of IL-22 and IL-22-Related Proteins.

[0129] Three-dimensional modeling is performed using the diffraction coordinates from the X-ray diffraction patterns and atomic coordinates of the present invention. The coordinates are entered into one or more computer programs for molecular modeling, as known in the art. Such molecular modeling can utilize known X-ray diffraction molecular modeling algorithms or molecular modeling software to generate atomic coordinates corresponding to the three-dimensional structure of at least one IL-22 or a fragment thereof.

[0130] The entry of the coordinates of the X-ray diffraction patterns and the amino acid sequence into such programs results in the calculation of the most probable secondary, tertiary and quaternary structures of the protein, including overall atomic coordinates of a IL-22 or a fragment thereof. These structures are combined and refined by additional calculations using such programs to determine the probable or actual three-dimensional structure of the IL-22, including potential or actual active or binding sites of the protein.

[0131] Such molecular modeling and related programs useful for rational drug design of ligands or mimetics, are contemplated by the present invention. The drug design uses computer modeling programs which calculate how different molecules interact with the various sites of the IL-22, how IL-22 monomers interact with other IL-22 monomers, how IL-22 interacts with IL-22-receptor mimetics and IL-22 receptors. This procedure determines potential ligands or mimetics of a IL-22. The actual IL-22-ligand complexes or mimetics are crystallized and analyzed using X-ray diffraction. The diffraction pattern coordinates are similarly used to calculate the three-dimensional interaction of a ligand and the IL-22.

[0132] An amino acid sequence of a IL-22 protein and/or X-ray diffraction data, useful for computer molecular modeling of IL-22, can be “provided” in a variety of mediums to facilitate use thereof. As used herein, provided refers to a manufacture, which contains, for example, a IL-22 amino acid sequence and/or atomic coordinate/X-ray diffraction data of the present invention, e.g., an amino acid sequence of SEQ ID NO: 2, a representative fragment thereof, or an amino acid sequence having at least 80-100% overall identity to an amino acid sequence of SEQ ID NO: 2. Such a method provides the amino acid sequence and/or X-ray diffraction data in a form which allows a skilled artisan to analyze and molecular model the three-dimensional structure of a IL-22-related protein, including one or more subdomains thereof.

[0133] In one application of this embodiment, IL-22, or at least one subdomain thereof, amino acid sequence and/or X-ray diffraction data of the present invention is recorded on computer readable medium. As used herein, “computer readable medium” refers to any medium which can be read and accessed directly by a computer. Such media include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage medium, and magnetic tape; optical storage media such as optical discs or CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media. A skilled artisan can readily appreciate how any of the presently known computer readable mediums can be used to create a manufacture comprising computer readable medium having recorded thereon an amino acid sequence and/or X-ray diffraction data of the present invention.

[0134] As used herein, “recorded” refers to a process for storing information on computer readable medium. A skilled artisan can readily adopt any known method for recording information on computer readable medium to generate manufactures comprising an amino acid sequence and/or atomic coordinate/X-ray diffraction data information of the present invention. A variety of data storage structures are available to a skilled artisan for creating a computer readable medium having recorded thereon an amino acid sequence and/or atomic coordinate/X-ray diffraction data of the present invention. The choice of the data storage structure will generally be based on the means chosen to access the stored information. In addition, a variety of data processor programs and formats can be used to store the sequence and X-ray data information of the present invention on computer readable medium. The sequence information can be represented in a word processing text file, formatted in commercially-available software such as WordPerfect and MICROSOFT Word, or represented in the form of an ASCII file, stored in a database application, such as DB2, Sybase, Oracle, or the like. A skilled artisan can readily adapt any number of dataprocessor structuring formats (e.g. text file or database) in order to obtain computer readable medium having recorded thereon the information of the present invention.

[0135] By providing computer readable medium having stored thereon an IL-22 or related sequence protein and/or atomic coordinates based on X-ray diffraction data, a skilled artisan can routinely access the sequence and atomic coordinate or X-ray diffraction data to model a IL-22 or related protein, a subdomain thereof, mimetic, or a ligand thereof. Computer algorithms are publicly and commercially available which allow a skilled artisan to access this data provided in a computer readable medium and analyze it for molecular modeling and/or RDD. See, e.g., Biotechnology Software Directory, MaryAnn Liebert Publ., New York (1995). A variety of comparing means can be used to compare a target sequence or target motif with the data storage means to identify structural motifs or electron density maps derived in part from the atomic coordinate/X-ray diffraction data. A skilled artisan can readily recognize that any one of the publicly available computer modeling programs can be used as the search means for the computer-based systems of the present invention.

[0136] Several approaches can be taken for the use of the crystal structure of a IL-22 in the rational design of a relevant activity similar to that of the unmutated IL-22. A computer-assisted, manual examination of an IL-22-receptor-binding site structure is optionally done. Software such as GRID (Goodford (1985) J. Med. Chem. 28: 849-857), a program that determines probable interaction sites between probes with various functional group characteristics and the protein surface, is used to analyze the surface sites to determine structures of similar inhibiting proteins or compounds. The GRID calculations, with suitable inhibiting groups on molecules (e.g., protonated primary amines) as the probe, are used to identify potential hotspots around accessible positions at suitable energy contour levels.

[0137] A therapeutic IL-22 or related protein of the present invention can be, but is not limited to, IL-22-receptor ligands that bind to IL-22 receptors as either agonists or antagonists; IL-22-receptor-chain mimetics or antibodies that bind to endogenous IL-22 and impairs the binding of IL-22 to endogenous receptors. The program DOCK (Kuntz et al. (1982) J. Mol. Biol.161: 269-288) may be used to analyze receptor binding sites, dimerization interfaces and/or ligand binding site and suggest ligands or amino acid residues with complementary steric properties. Several methodologies for searching three-dimensional databases to test pharmacophore hypotheses and select compounds for screening are available. These include the program CAVEAT (Bacon et al. (1992) J. Mol. Biol. 225: 849-858), which uses databases of cyclic compounds which can act as “spacers” to connect any number of chemical fragments already positioned in the active site. This allows one skilled in the art to quickly generate hundreds of possible ways to connect the fragments already known or suspected to be necessary for tight binding. The program LUDI (Bohm et al. (1992) J. Comput.-Aid. Mol. Des. 6: 61-78) can determine a list of interactions sites into which to place both hydrogen bonding and hydrophobic fragments. LUDI then uses a library of approximately 600 linkers to connect up to four different interaction sites into fragments. Then smaller “bridging” groups such as —CH2— and —COO— are used to connect these fragments. For example, for the enzyme DHFR, the placements of key functional groups in the well-known inhibitor methotrexate were reproduced by LUDI. See also, Rothstein et al. (1992) J. Med. Chem. 36: 1700-1710.

[0138] Once IL-22-receptor ligands or mimetics are identified, crystallographic studies of, the IL-22 ligand and its receptor complex and the IL-22-receptor mimetic and its IL-22 complex may be performed to confirm and refine the ligand or mimetic properties. Direct measurements of receptor binding or complex formation provide further confirmation that the modeled mimetic and ligands are high affinity IL-22 agonists, antagonists or inhibitors. Any suitable assay for receptor binding or complex formation may be used. The atomic coordinates of IL-22 are useful in the generation of molecular models of related proteins and of IL-22-receptor mimetics and ligands. Utilizing CLUSTAL (a multiple sequence alignment program in PC-Gene) and the Homology module (a structure-based homology modeling program in InsightII on a Silicon Graphics Incorporated workstation), molecular models (and the corresponding three-dimensional coordinates files) of numerous mimetics and ligands are generated. With these files, mutants and mimetics of the present invention are mapped and new ones designed. The results described herein demonstrate that tight-binding mimetics and ligands of an IL-22 receptor, or related protein, based on the crystal structure of IL-22, are provided by the present invention.

[0139] The term “antibody” as used herein, unless indicated otherwise, is used broadly to refer to both antibody molecules and a variety of antibody-derived molecules. Such antibody-derived molecules comprise at least one variable region (either a heavy chain of light chain variable region) and include molecules such as Fab fragments, F(ab)2 fragments, single chain (sc) antibodies, diabodies, triabodies, tetrabodies, individual antibody light chains, individual antibody heavy chains, chimeric fusions between antibody chains and other molecules, and the like. As used herein “antigen-binding fragment” or “antigen-binding domain” or “Fab fragment” refer to the about 45 kDa fragment obtained by papain digestion of an immunoglobulin molecule and consist of one intact light chain linked by disulfide bond to the n-terminal portion of the contiguous heavy chain. As used herein, “F(ab)2 fragment refers to the about 90 kDa protein produced by pepsin hydrolysis of an immunoglobulin molecule. It consists of the N-terminal pepsin cleavage product and contains both antigen binding fragments of a divalent immunoglobulin, such as IgD, IgE, and IgG. Neither the “antigen-binding fragment” nor “F(ab)2 fragment” contain the about 50 kDa Fc fragment produced by papain digestion of an immunoglobulin molecule that contains the c-terminal halves of the immunoglobulin heavy chains, which are linked by two disulfide bonds, and contain sites necessary for compliment fixation.

[0140] As used herein, the term “humanized” antibody refers to a molecule that has its CDRs—complementarily determining regions—derived from a non-human-species immunoglobulin and the remainder of the antibody molecule derived mainly from a human immunoglobulin. As used herein “immunoglobulin” refers to any member of a group of glycoproteins occurring in higher mammals that are major components of the immune system. As used herein, “immunoglobulins” comprise four polypeptide chains-2 identical light chains and two identical heavy chains that are linked together by disulfide bonds. An immunoglobulin consists of the antigen binding domains, which are each comprised of the light chains and the end-terminal portion of the heavy chain, and the Fc region, which is necessary for a variety of functions, such as compliment fixation. There are five classes of immunoglobulins wherein the primary structure of the heavy chain, in the Fc region, determines the immunoglobulin class. Specifically, the alpha, delta, epsilon, gamma, and mu chains correspond to IgA, IgD, IgE, IgG and IgM, respectively. As used herein “immunoglobulin” includes all subclasses of alpha, delta, epsilon, gamma, and mu and also refers to any natural (e.g., IgA and IgM) or synthetic multimers of the four-chain immunoglobulin structure.

[0141] As used herein, “Fv or Fv fragment” refers to the N-terminal part of the Fab fragment of an immunoglobulin molecule, consisting of the variable region of the heavy chain and the variable region of the light chain. As used herein, “scFv” refers to a polypeptide comprising the heavy chain variable region and light chain variable region of a parent immunoglobulin, wherein the heavy chain variable region and the light chain variable region are linked by a peptide linker. As used herein, “diabody” refers to an scFv dimer. As used herein, “triabody” refers to an scFv trimer, and “tetrabody” refers to an scFV tetramer. As used herein, “heavy chain” refers to the heavier of the two types of polypeptide chain in immunoglobulin molecules that contain the antigenic determinants that differentiate the various Ig classes, e.g., IgA, IgD, IgE, IgG, IgM, and the domains necessary for compliment fixation placental transfer, mucosal secretion, and interaction with FC receptor. As used herein, “heavy chain variable region” refers to the amino-terminal domain of heavy chain that is involved in antigen binding and combines with the light chain variable region to form the antigen binding domain of the immunoglobulin. As used herein, “light chain” refers to the shorter of the two types of polypeptide chain in an Ig molecule of any class. Light chains comprise variable and constant regions. As used herein, “light chain variable region” refers to the amino-terminal domain of the light chain and is involved in antigen binding and combines with the heavy chain to form the antigen binding region.

[0142] The term “variable region” as used herein in reference to immunoglobulin molecules has the ordinary meaning given to the term by the person of ordinary skill in the art of immunology. Both antibody heavy chains and antibody light chains may be divided into a “variable region” and a “constant region.” The point of division between a variable region and a constant region may readily be determined by the person of ordinary skill in the art by reference to standard texts describing antibody structure, e.g. Kabat et al. (1991) Sequences of Proteins of Immunological Interest. 5th Edition. U.S. Department of Health and Human Services, U.S. Government Printing Office.

[0143] The recombinant production of immunoglobulin molecules, including humanized antibodies are described in U.S. Pat. No. 4,816,397 (Boss et al.), U.S. Pat. No. 4,816,567 (Cabilly et al.) U.K. patent GB 2,188,638 (Winter et al.), and U.K. patent GB 2,209,757; all of which are incorporated herein by reference. Techniques for the recombinant expression of immunoglobulins, including humanized immunoglobulins, can also be found, among other places in Goeddel et al. (1991) Gene Expression Technology, Methods in Enzymology Vol. 185, and Borreback (1992) Antibody Engineering, W. H. Freeman, all of which are incorporated herein by reference. Additional information concerning the generation, design and expression of recombinant antibodies can be found in Mayforth (1993) Designing Antibodies, Academic Press, San Diego and Harlow (1988) Antibodies—A laboratory manual. First Edition. Cold Spring Harbor Laboratory, all of which are incorporated herein by reference.

[0144] Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the compounds of the present invention and practice the claimed methods. The following working examples therefore, specifically point out preferred embodiments of the present invention, and are not to be construed as limiting in any way the remainder of the disclosure.

EXAMPLES

Example 1

Protein Expression and Purification

[0145] A cDNA encoding IL-22 sequence lacking the signal peptide was subcloned into the E. coli expression vector pET2a, generating pEThTIF. The recombinant protein expressed from this vector contains a methionine at the N-terminus, followed by the amino acid sequence starting at Gln29 to the C-terminus. Vector pEThTIF was transformed into E. coli strain BL21 (DE3)-codon plus-RII. The resulting strain was maintained in LB medium containing Ampicillin (100 μg/ml) and Chloramphenicol (34 μg/ml). Induction of IL-22 express was performed at 37° C. for 4 hours with 1 mM IPTG, which was added when the cultures reached an OD660 of approximately 1.0-1.3. Under these conditions, up to 50 mg/l of IL-22 were obtained. Cells were lysed by using a high pressure cell (French Press) and the inclusion bodies were washed once in buffer containing 50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 1 mM EDTA, 1 mM DTT and 0.5% sodium deoxycholate and once in the same buffer lacking sodium deoxycholate. The inclusion bodies were solubilized in 25 mM MES pH 5.5, 8 M urea, 10 mM EDTA, and 0.1 mM DTT. Protein concentration was adjusted to 100 μg/ml and refolded by dialysis in buffer containing Tris-HCl pH 8.0, 0.5 M arginine, 1 mM reduced glutathione, 0.1 mM oxidized glutathione, 2 mM EDTA and 0.1 mM PMSF. Refolding was performed for 20 h at 4° C. Refolded samples were concentrated 100 fold with a YM3 AMICON membrane and loaded onto a Superdex 75 10/30 HP column (Amersham-Pharmacia), which was eluted with buffer containing 25 mM MES pH 5.4 and 150 mM NaCl. Human IL-22 peak fractions were concentrated to 5 mg/ml with a YM3 AMICON membrane and desalted using a Hiprep 26/10 column (Amersham-Pharmacia) with elution buffer containing 10 mM MES pH 5.4. Human IL-22 was concentrated again to 5 mg/ml and lyophilized in 1 mg fractions.

Example 2

Protein Crystallization

[0146] Preliminary screening of the crystallization conditions was performed using a sparse-matrix screen at 291 K (Crystal Screen I and II, Hampton Research Corp.). Small crystals were found in the condition number 18, 26 and 29 of the Crystal Screen I kit. Several attempts to enhance crystal quality were performed, including pH and precipitant concentration refinement, detergent addition, and macroseeding. Well diffracting crystals were obtained in hanging drops equilibrated against a reservoir solution consisting of 0.9 M sodium tartrate, TRITON X-100 detergent and 0.1 M HEPES at pH 7.5. The crystallization drops contained equal volumes (1 μl) of reservoir and purified IL-22 (10 mg/ml in 20 mM MES buffer at pH 5.4) solutions. The protein crystallized in the space group P212121, with unit-cell dimensions a=55.43, b=61.61, c=73.43 Å.

Example 3

Data Collection

[0147] Crystals were soaked in different cryosoaking solutions, mounted in a rayon loop and finally flash-cooled to 80° K in a cold-nitrogen stream. Data collection was performed at the Protein Crystallography beamline (LNLS, Campinas, Brazil; Dumoutier et al. (2000) Genes and Immunity 1: 488-494; Cookson, (2000) Nature 402s: B5-B 11) and at the X4A beamline (NSLS, Upton, USA), using a MAR345 image plate and a Quantum-4 CCD detector, respectively. Three diffraction datasets were collected to a resolution beyond 1.95 Å. Diffraction images were processed and scaled with the programs DENZO and SCALEPACK. See e.g., Walter et al. (1995) Biochemistry 34: 12118-12125.

Example 4

Heavy-Atom Derivatives and Phasing

[0148] The structure was solved by SIRAS. An iodine derivative was obtained by soaking the crystal for 180 seconds in 2 μl of cryoprotectant solution containing 0.125 M sodium iodide following the novel “quick cryo soaking” derivatization procedure. See e.g., Kotenko et al. (1997) EMBO J. 16: 5894-5903; Zdanov et al. (1995) Structure 3: 591-601. The data sets of an iodine derivative (1-IL-22) and a native crystal (Nat-IL-22) were collected at the Protein Crystallography beamline (Dumoutier et al. (2000) Genes and Immunity 1: 488-494; Cookson (2000) Nature 402s: B5-B11) at LNLS (Campinas, São Paulo, Brazil). The heavy-atom positions of the iodine derivative were determined by direct methods with the programs DREAR (Ealick et al. (1991) Science 252: 698-702) and SnB 2.1 (Josephson et al. (2000) J. Biol. Chem. 275: 13552-13557). The bimodal distribution of the Rmin histogram was used to identify the correct solution (Trèze (1999) The cytokine network and immune functions. Oxford University Press, Oxford; Barton, (1993) Protein Eng. 6: 37-40). The heavy-atom substructure obtained directly from SnB was initially refined with the CNS package using anomalous and isomorphous difference Fourier maps. Refined coordinates were then input into SHARP (Otwinowski et al. (1997) Methods Enzymol. 276: 307-326) for phase calculation, resulting in an overall figure of merit of 0.45 for all reflections in the range of 21.7-2.40 Å. Density modification with solvent flattening was performed using the program SOLOMON. See e.g., Blessing, et al. (1999) J. Appl. Cryst. 32: 664-670. Due to the high resolution and completeness of the I-IL-22 data set, and also the quality of solvent-flattened electron-density map, an automatic construction of an IL-22-hybrid model could be performed by the ARP/wARP program. See e.g., Thiel, et al. (2000) Structure 8: 927-936. The nucleotide-based IL-22 primary structure was used in the final-model-side-chain assignment. See e.g., Dumoutier et al. (2000) Proc. Natl. Acad. Sci. U.S.A. 97: 10144-10149.

[0149] One mercury derivative was also obtained using traditional methods of derivatization. The Hg derivative (Hg-IL-22) data set was collected at the X4A beamline at NSLS (Upton, N.Y., USA) and was used at latter stages of refinement and construction of disordered loops. This latter derivative was prepared using traditional methods for derivatization of protein crystals. Details of native and derivative crystal preparation, as well as data statistics, are summarized in Table 1.

Example 5

Model Building

[0150] 1. Refinement.

[0151] A. The initial model was obtained without manual intervention after 6 ARP/wARP jobs and more than 4000 REFMAC cycles. See e.g., Weeks, et al. (1999) J. Appl. Cryst. 32: 120-124. In the last cycle, after almost 72 hours of uninterrupted CPU time in a Pentium III 500 MHz, 81.6% of the total amino acid residues were corrected traced.

[0152] B. The initial structure of IL-22 was improved by a number of cycles of refinement and rebuilding using CNS package. See e.g., Polikarpov, et al. (1997) J. Synchrotron Rad. 5: 72-76. Interlaced refinement of model against Nat-IL-22, Hg-IL-22 and I-IL-22 data sets were used to allow a complete trace of main chain atoms through disordered regions. The initial model contained 231 amino acid residues (in nine distinct chains) and 809 water molecules. The isolated cDNA of IL-22 encodes a protein of 179 amino acids, of which the first 22 amino acids are predicted to function as a signal sequence. (Xie et al. (2000) J. Biol. Chem. 275: 31335-31339). The N-terminal amino acid analysis of IL-22 confirms that the mature protein begins at amino acid residue 34. Construction of disordered loops and filling of main chain gaps were performed manually using the program O. See e.g., Debaerdemacker, et al. (1983) Acta Cryst. A39: 193-196. Finally, the model was refined against a Nat-IL-22 data set, starting with a simulated annealing protocol in the program CNS. After several iterations of energy minimization, B-factor refinement, and bulk-solvent and anisotropic corrections, the final Rfactor and Rfree were 0.191 and 0.225, respectively, for the Nat-IL-22 data in the resolution range of 21.7-1.92 Å. The final model includes 283 residues (two chains) and 189 water molecules. The refined model of IL-22,a dimer in the asymmetric unit (FIG. 1a), includes monomer A with 142 amino acid residues (Ser38-Ile179), monomer B with 141 amino acid residues (His39-Ile179) and 189 water molecules. About 93.8% and 6.2% of the amino acid residues adopt a conformation that corresponds to the most favored and additionally allowed regions of the Ramachandran plot, respectively. See e.g., Table 2 for further information about refinement and geometry statistics. No residues have been encountered in the disallowed regions of the Ramachandran plot.

[0153] As shown in FIG. 1b, each monomer of IL-22 model is characterized by six α-helices (A-F) that fold in a compact bundle. Helix A (amino acid residues Lys44-Ser64) is linked to a short helix B (Glu77-Pe80) by a large loop AB (Leu65-Gly76). Helix A has a kink at Gln48-Gln49, presumably due to a hydrogen bond between Nε-Gln49 and O-Ser45 (2.79 Å and 2.55 Å in monomers A and B, respectively). This divides helix A into unequal parts: A1 and A2. The loop BC (His81-Glu87) connects helix B to helix C (Arg88-Glu102). The helix C is joined to helix F by a disulfide bond between Cys89 and Cys178. Another loop (CD; Val103-Try114) links helix C to helix D (Met15-Leu129). According to PROCHECK (Laskowski et al. (1993) J. Appl. Crystallogr. 26: 283-291), a small difference in secondary structure between monomers is observed at the loop CD region. A small α-helix is observed between amino acid residues Phe105 and Gln107 of the monomer B. Helix D is connected to helix E by a disordered loop (DE; Ser130-Asp138). This loop is stabilized, at least in the vicinity of Cys132, by another disulfide bond between Cys132 and Cys40, the latter in the N-terminal coil. Finally, a simple junction EF (Gly156) joins the last two helices E (Leu139-Leu155) and F (Glu157-Cys178). Probably, as a consequence of a disulfide bond between Cys89 and Cys178, the latter belonging to the C-terminal of helix F, a kink at Glu166 divides helix F into two parts: F1 and F2.

[0154] 2. Dimer Formation.

[0155] An expressive part (61%) of the volume of the asymmetric unit (6.27×104 Å3) is occupied by a dimer of IL-22. A small fraction of this volume (8%) is filled with ordered water molecules. The monomers are essentially equal, however, a number of significant differences in the main chain conformation are observed in the vicinity of amino acid residues Gln48, Asn69, Gln136 and Lys154 (FIG. 2). These differences are mostly explained by crystallographic and non-crystallographic contacts. The reason for a significant positional difference between monomers around Gln48 is the fact that this region in monomer A is involved in interface interactions, whereas the same region in monomer B is exposed to the solvent. In addition, the presence of two intramolecular interactions—Oδ1-Asp43/Oγ-Ser45 with 2.64 Å in monomer A and O-Asn46/Nε2-Gln49 with 2.55 Å in monomer B—contribute to a relative change in main-chain atoms positions between residues Leu42 and Pro50. A second conformational difference around Asn69 is a consequence of a crystallographic contact between side chain atoms of Asn69 and Thr70 of monomers A and B, respectively. Gly136 is localized in the disordered loop DE. This fact explains the root-mean-square-deviation (rmsd) around 2.0 Å in the vicinity of this amino acid residue. Finally, the last major difference between monomers is found close to Lys154. In this region, three distinct interactions of Lys153 and Lys154 from monomer B—Oε1-Glu102/Nζ-Lys153 with 2.68 Å, Oδ1-Asn46/Nζ-Lys153 with 2.78 Å and Oε1-Glu160/Nζ-Lys154 with 2.80 Å, which are absent in monomer A—are responsible for a high rmsd of main-chain atoms.

[0156] Unlike the hIL-10, the IL-22 dimeric structure formation does not require the intertwining of the main chain of each monomer (FIG. 1). An interface area of approximately 2250 Å2, which corresponds to 30% of the total surface area of a monomer, is involved in the dimer formation. The buried surface for the chosen dimer conformation is at least two times larger than any other buried surface area (˜960 Å2 or less). Also, the dimer interface, which is formed mostly by residuesArg41 to Phe80 and Asp168 to Ile179 in monomer A and Thr53 to Arg88 and Glu166 to Ile179 in monomer B, has a significant number of hydrophobic residues. Intermolecular interface contacts closer than 3.2 Å are listed in Table 3. The electrostatic and hydrophobic distribution of the IL-22 surface together with the position of the principal amino acid residues involved in the formation of the dimer are given in FIG. 3.

[0157] According to the predicted primary structure, human IL-22 has three potential glycosylation sties (Asn-Xaa-Thr/Ser) localized in helix A (Asn54-Arg55-Thr56) (site #1), loop AB (Asn68-Asn69-Thr70) (site #2) and helix C (Asn97-Phe98-Thr99) (site #3). Since the recombinant IL-22 used in crystallization is not glycosylated, we attempted the analysis of the possible interactions between oligosaccharides and IL-22 by calculating the accessible area of each residue in all three putative glycosylation sites. The results demonstrate that site #2, localized at the loop AB, is the one with the larger accessible area. A solvent-accessible area of approximately 37 Å2 was found for Nδ2-Asn68 and for Oγ1-Thr70 atoms, indicating that there is no steric hindrance to their participation in N-glycosyl and O-glycosyl links, respectively. On the other hand, sites #1 and #3 seem to participate only in N-glycosyl linkages. The accessible area of Oγ1-Thr56 and Oγ1-Thr99 is 0 and 6 Å2, whereas Nδ2-Asn54 and Nδ2-Asn97 atoms possess, respectively, the surface-accessible area of 24 and 18 Å2. This structural analysis is in agreement with biochemical studies suggesting that these three sites are of N-glycosyl type. (Kotenko et al. (2001) J. Biol. Chem. 276: 2725-2732). Consistent with biophysical observations, the present structure shows that putative glycosylation sites #1 and #2 reside near the dimer interface, and that glycosylation at these positions would disrupt dimer formation.

[0158] 3. Comparison of IL-22 to the Structures of IL-10 and IFN-γ.

[0159] As shown in FIG. 2, the crystallographic structure of hIL-22 is a compact dimer, with a buried surface area of approximately 2250 Å2. Several intermolecular interactions along the interface surface keep the monomers together. Each monomer is formed by six α-helices (A-F) from the same polypeptide chain. Quite in contrast, the crystallographic structures of hIL-10 (Levitt et al. (1999) J. Allergy Clin. Immunol. 103: S485-S491; Laskowski et al. (1993) J. Appl. Crystallogr. 26: 283-291; Kraulis et al. (1991) J. appl. Cryst. 24: 946-950) and hIFN-γ (Esnouf (1997) J. Mol. Graph. 15: 133-138; McLane et al. (1998) Am. J. respir. Cell Mol. Biol. 19: 713-720) revealed the presence of a homodimer composed of two α-helical domains formed by intertwining of α-helices donated by the first and the second monomer composing a dimer. The first four helices of one chain (A-D), together with the helices E′ and F′ from the second chain, compose the first domain. Helices A′ to D′, E and F form the second domain.

[0160] There are significant structural similarities between IL-22, IL-10 and IFN-γ (FIG. 4). In all these proteins, helices A to D of each monomer form a rigid frame with a highly hydrophobic depression in its middle. This depression is covered in IL-22 by helices E and F from the same monomer, whereas in hIL-10 and hIFN-γ this is accomplished by helices E′ and F′ (from the second monomer). The basic reason for these differences is in the loop DE. There are two cysteine residues Cys126 and Cys132 at the hIL-10 DE loop that make two distinct disulfide bonds with residues Cys30 and Cys80, respectively. (Here we adopted the residue numbering according to the hIL-10 cDNA sequence). These two S—S bridges restrict the flexibility of the amino acid chain and the length of the loop DE in such a manner that helices E and F can not fold onto their respective monomer to occupy position of their counterparts E′ and F′. This leads to the intertwined dimer formation. See e.g., Levitt et al. (1999) J. Allergy Clin. Immunol. 103: S485-S491; Laskowski et al. (1993) J. Appl. Crystallogr. 26: 283-291; Kraulis et al. (1991) J. appl. Cryst. 24: 946-950. A monomeric form of hIL-10 could only possibly be created when the Cys80-Cys132 disulfide bond were to be reduced, or if a small amino acid chain were inserted after Cys132. See e.g., Levitt et al. (1999) J. Allergy Clin. Immunol. 103: S485-S491. The latter approach has been applied with success to hIL-10, where insertion of a small polypeptide linker in the loop that connects the swapped secondary structure elements led to the formation of a monomeric protein. See e.g., Merritt, et al. (1997) Methods Enzymol. 277: 505-524. Similarly, the hIFN-γ intertwined dimer is formed because the loop DE is not long enough to allow the fold of helix E and F into the same domain.

[0161] In IL-22, just one disulfide bond (Cys40-Cys132) exists at the loop DE, which allows sufficient flexibility and extension of the loop to bring helices E and F into close contact with helices A to D and to complete the folding of the monomer. A second disulfide bond, in the C-terminal of helix F (Cys89-Cys178), adds to a rigidity of a final IL-22 structure.

[0162] The best superposition of IL-22 onto hIL-10 and hIFN-γ was obtained using a single domain of the hIL-10 and hIFN-γ onto IL-22 yielding an rmsd of 1.9 Å and 2.3 Å for 432 and 300 pairs of main chain atoms, respectively. Helices A to D of the IL-22 monomer superimpose with helices A to D of one of the monomers of hIL-10 and hIFN-γ. Helices E and F fit nicely into the spatial position occupied by helices E′ and F′ of the second monomer. The three-dimensional superposition of the structures allowed us to perform a structure-based sequence alignment for IL-22 and IL-10 that is shown in FIG. 5. Inspection of the superposition of IL-22 and hIL-10 revealed strong similarities in the conformation of the main-chain trace of helices E (E′) and F (F′), and to a lesser extent, the conformation of several parts of loop AB, helix C and helix D. Each of these regions represent high sequence similarity. Some significant differences in the regions of the N-terminal coil, helix A, helix B, loop BC, loop CD and loop DE were also observed.

[0163] Reasonable superposition of hIL-10 or hIFN-γ dimers onto IL-22 dimer was proven to be impossible. In each case, dimer formation is so much different that only one domain of IL-22 could be superimposed with an hIL-10 (or hIFN-γ) domain. A second domain of each structure occupies completely different spatial positions (FIGS. 4c and 4d). Whereas the intertwining of α-helices is essential for the formation and integrity of molecules adapting a form of the V-shaped dimers (i.e., hIL-10 and hIFN-γ), in IL-22 dimer formation is not required for folding. It must be stressed that the buried surface on the ML-2 interface coincides with the outer part of the hIL-10 and hIFN-γ V-shaped-dimer surfaces (FIGS. 4c and 4d).

[0164] 4. Receptor Binding Sites.

[0165] Two receptor chains—CRF2-4 and CRF2-9—have been identified for IL-22. The CRD2-4 receptor chain is common between IL-22 and IL-10 and is necessary for signaling, whereas CRD2-9 is specific for IL-22. See e.g., Xie et al. (2000) J. Biol. Chem. 275: 31335-31339; Kotenko et al. (2001) J. Biol. Chem. 276: 2725-2732; both incorporated herein by reference. CRF2-9 bears primary sequence homology to the another receptor chain of IL-10—IL-10R1. The binding affinity of IL-22 and IL-10 to CRF2-4 is different. CRF2-4 alone is sufficient to bind IL-22, while the presence of a second receptor chain is required for efficient IL-10 binding. Moreover, both CRF2-9 and CRF2-4 share significant sequence homology to the IFN-γ receptor, IFN-γRα. The three-dimensional structure of hIFN-γRα was recently solved as a complex with its ligand (McLane et al. (1998) Am. J. Respir. Cell Mol. Biol. 19: 713-720; incorporated herein by reference), and the structure of IL-22 was superimposed onto the structure of the hIFN-γ/hIFNRα complex to identify the residues involved in IL-22/receptor interactions. A similar structural comparison with the hGH/hGHBP complex has been used in receptor-binding-site analysis of IL-10. See e.g., Levitt, et al. (1999) J. Allergy Clin. Immunol. 103: S485-S491; incorporated herein by reference.

[0166] The superposition of IL-22 onto the hIFN-γ/IFNRα complex indicates that one possible receptor binding site is localized in the region formed by helix A, loop AB and helix F of IL-22 (Region 1, R1; see FIGS. 4d and 6a). Among the 17 residues involved in hIFN-γ/hIFNRα interactions (closer than 3.4 Å), only two residues do not have their IL-22 structural counterparts localized in R1. Nine of the seventeen residues localized in R1 are not sufficiently close to their hIFN-γ counterparts, which may explain the inability of IL-22 to bind to hIFN-γRα. The major differences between hIFN-γ and IL-22 within R1 are observed in the loop AB and distances of more than 7 Å are found between their main chains. As shown in FIG. 6b, six relatively conserved residues (Lys61, Thr70, Asp71, Lys162, Glu166 and Leu169), however, occupy almost the same spatial position as six hIFN-γ residues—Lys35, Asp47, Asn48, Lys131, Glu135, Gln138.

[0167] A comparison with the hIL-10 putative receptor binding site (Levitt, et al. (1999) J. Allergy Clin. Immunol. 103: S485-S491; incorporated herein by reference) shows that Region 1—helix A, loop AB and helix F′ in the case of hIL-10—is involved in receptor interactions. Amino acid residues Gln60, Asp62, Asn63, Lys156, Glu160, Asp162, Asp166 and Glu169 of the hIL-10 binding site having their IL-22 counterparts in residues Asn68, Thr70, Asp71, Lys162, Glu166, Asp168, Met172 and Arg175. Among these eight residues, Thr70, Asp71, Lys162 and Glu166 were also found in the IL-22:IFN-γ/INF-γRα comparison. The superposition of the hIL-10 putative binding Region 1 onto IL-22 is shown in FIG. 6c. The three-dimensional structure comparison of IL-22 with either IFN-γ/INF-γRα or hGH/hGHBP complexes demonstrates that Region 1 is the receptor binding site.

[0168] The three-dimensional similarities observed between IL-22 and hIL-10 in Region 1, especially between helices F and F′, also indicate that this region is the CRF2-4 binding site. In addition, the gylcosylation site in the IL-22 AB loop may interfere with receptor binding. The homology of INF-γRα CRF2-9 also suggests that R1 is the recognition/binding site for CRF2-9. Notably, in the present crystallographic model, the region 1 of each monomer is hidden at the dimer interface. Moreover, a few potential receptor-binding residues are directly involved in dimer formation (see Table 3). Therefore, a IL-22-receptor chain can only bind a monomer of IL-22, and thus, requires the dissociation of the dimer observed in the present crystallographic structure. In contrast, the hIL-10 dimer does not require disruption prior to interaction with the receptor, since the hIL-10-receptor-binding site is localized at the outer part of the B-shaped-dimer surface (FIGS. 4c and 4d).

[0169] Although the RZ binding site in IL-22 cannot be easily inferred from inspection of the interactions between hINF-γ and hINF-γRα, region Z, which comprises the terminal portions of helices C and E of each IL-22 monomer, is a binding site for CRF2-4. A sequence comparison between IL-22 and several IL-10 identifies several amino acids that are conserved within the Region 2 (R2) region—FTLEEVL (SEQ ID NO: 4) and KLGE (SEQ ID NO: 5) in IL-22 helices C and E, respectively. Region 2 is localized at the surface of IL-22, which is opposite to R1. Localization of each binding region (R1 and R2) on the opposite sides of the IL-22 molecule allows IL-22 to interact with two receptor chains simultaneously. In hIL-10, the amino acids corresponding to the region R2 are localized at the inner part of the V-shaped dimer surface. The angle between each hIL-10 domain in the V-shaped dimer is large enough to allow interaction of two CRF2-4 receptor chains with the two binding sites in RZ 2 (FIG. 4c).

1TABLE 1Details of the preparation and data-collection statisticsof IL-22 crystals. Statistical values for the highestresolution shells are shown in parentheses.Nat-IL-22I-IL-22Hg-IL-22Space groupP212121P212121P212121Unit cella = 55.43;a = 56.05;a = 56.04;parametersb = 61.61;b = 61.78;b = 61.71;(Å)c = 73.47c = 73.63c = 74.61Resolution21.7 - 1.9221.8 - 1.9222.4 - 1.90(Å)(1.96 - 1.92)(1.96 - 1.92)(1.97 - 1.90)No. of6767718287655855reflectionsNo. of unique181393777729854reflections1<I/σ(I)>14.4(2.5)13.4(3.1)8.2(2.1)Multiplicity3.7(3.1)4.8(4.3)1.9(1.7)Completeness91.2(75.1)99.9(99.7)75.9(77.9)Rmerge28.6(50.8)11.7(43.9)10.0(49.9)Data collected103.2248.670.0(degrees)CryoprotectantMother liquorMother liquorMother liquorsolution15% ethyl. glycol15% ethyl. glycol15% ethyl. glycol0.125 M NaI5 mM HgCl2Soaking time30seconds180seconds10hours1Multiplicity of derivative (native) data sets calculated with Friedel-related reflections treated separately (as equivalent). 2Rmerge = Σhkl |Ihkl − <Ihkl>| / Σhkl Ihkl

[0170]

2

TABLE 2

Refinement statistics and quality of the IL-22 model.1

GENERAL INFORMATION

Disulfide bonds
Cys40-Cys132 and Cys89-Cys178

Cis-peptides
Pro113

Alternative conformations
Met172 in monomer A

Asp43, Ser45, Arg55, Ile75, His81,

Arg124, Ile161 and Leu174 in monomer B

REFINEMENT STATISTICS (21.7 - 1.92 Å)

Total number of reflections
17238

Working set number of reflections
16372

R-factor (%)
19.1

Test set number of reflections
866

R-free (%)
22.5

Total number of protein atoms
2330

Total number of water molecules
189

GEOMETRY STATISTICS

Rmsd bond distances (Å)
0.006

Rmsd bond angles (°)
1.1

Average B factors

residue atoms (Å2) (A, B)
24.3 (22.3, 26.2)

mainchain atoms (Å2) (A, B)
22.1 (20.2, 24.1)

sidechain atoms (Å2) (A, B)
26.3 (24.4, 28.1)

water molecules (Å2)
37.3

Average rmsd B factor

residue atoms (Å2) (A, B)
2.5 (2.6, 2.5)

mainchain atoms (Å2) (A, B)
1.0 (1.0, 1.0)

sidechain atoms (Å2) (A, B)
1.9 (2.0, 1.8)

water molecules (Å2)
11.4

Ramachandran plot2

residues in most favored region (%)
93.8

residues in additionally allowed regions (%)
6.2

residues in generously allowed regions (%)
0.0

residues in disallowed regions (%)
0.0

NON-CRYSTALLOGRAPHIC SYMMETRY3

Rmsd coordinates

Cα atoms (Å)
0.911

mainchain atoms (Å)
0.884

all bonded atoms (Å)
1.670

Rmsd B factors

Cα atoms (Å2)
10.04

mainchain atoms (Å2)
10.05

all bonded atoms (Å)
10.77

1
Amino acid residues correspond to residues in human IL-22, SEQ ID NO: 2.

2
Residue regions as defined by PROCHECK (Laskowski et al. (1993) J. Appl. Crystallogr. 26: 283-291).

3
Non-crystallographic symmetry of subunits A and B.

[0171]

3

TABLE 3

Intermolecular contacts (monomers A* and B**).

The distance cut-off of 3.2 Å was used.1

Residue*
Atom*
Residue**
Atom**
Distance (Å)

Arg175
Nη2
Glu166
Oε1
2.57

Phe57
O
Asn176
Nδ2
2.64

Arg73
Nη2
Val83
O
2.71

Lys44
Nζ
Ser64
Oγ
2.85

Arg175
Nη1
Asp168
Oδ2
2.86

Asn176
Nδ2
Ile75
O
2.91

Gln48
O
Lys61
Cε
2.96

Lys44
Nζ
Glu166
Oε1
2.98

Lys61
Nζ
Ile179
OT1
3.12

Gln49
Oε1
Lys61
Nζ
3.15

1
Amino acid residues correspond to residues in human IL-22, SEQ ID NO: 2.

[0172]

4

TABLE 4

Atomic Coordinates of human IL-22 determined as described herein.1

CRYST1 55.430 61.610 73.470 90.00 90.00 90.00 P 21 21 21

SCALE1 0.01804 0.00000 0.00000 0.00000

SCALE2 0.00000 0.01623 0.00000 0.00000

SCALE3 0.00000 0.00000 0.01361 0.00000

ATOM
1
CB
SER A
38
8.633
14.375
24.449
1.00
47.79
A

C

ATOM
2
OG
SER A
38
8.362
14.381
23.062
1.00
49.55
A

O

ATOM
3
C
SER A
38
8.165
16.820
24.641
1.00
44.87
A

C

ATOM
4
O
SER A
38
7.431
17.426
23.855
1.00
44.76
A

O

ATOM
5
N
SER A
38
6.339
15.165
24.930
1.00
47.40
A

N

ATOM
6
CA
SER A
38
7.787
15.434
25.155
1.00
46.37
A

C

ATOM
7
N
HIS A
39
9.311
17.315
25.099
1.00
42.59
A

N

ATOM
8
CA
HIS A
39
9.807
18.631
24.708
1.00
40.15
A

C

ATOM
9
CB
HIS A
39
10.759
19.164
25.780
1.00
43.57
A

C

ATOM
10
CG
HIS A
39
11.980
18.320
25.978
1.00
46.37
A

C

ATOM
11
CD2
HIS A
39
13.290
18.653
26.075
1.00
48.11
A

C

ATOM
12
ND1
HIS A
39
11.923
16.950
26.124
1.00
48.60
A

N

ATOM
13
CE1
HIS A
39
13.143
16.476
26.302
1.00
49.04
A

C

ATOM
14
NE2
HIS A
39
13.992
17.489
26.276
1.00
48.92
A

N

ATOM
15
C
HIS A
39
10.535
18.557
23.371
1.00
36.84
A

C

ATOM
16
O
HIS A
39
11.370
17.680
23.157
1.00
36.46
A

O

ATOM
17
N
CYS A
40
10.221
19.475
22.465
1.00
32.36
A

N

ATOM
18
CA
CYS A
40
10.875
19.461
21.169
1.00
29.17
A

C

ATOM
19
C
CYS A
40
12.286
20.011
21.292
1.00
26.49
A

C

ATOM
20
O
CYS A
40
12.490
21.114
21.793
1.00
24.81
A

O

ATOM
21
CB
CYS A
40
10.095
20.298
20.162
1.00
29.95
A

C

ATOM
22
SG
CYS A
40
8.366
19.818
19.887
1.00
28.05
A

S

ATOM
23
N
ARG A
41
13.259
19.238
20.828
1.00
24.42
A

N

ATOM
24
CA
ARG A
41
14.648
19.657
20.890
1.00
24.30
A

C

ATOM
25
CB
ARG A
41
15.144
19.580
22.339
1.00
28.36
A

C

ATOM
26
CG
ARG A
41
16.568
20.046
22.548
1.00
35.78
A

C

ATOM
27
CD
ARG A
41
16.733
20.673
23.927
1.00
40.37
A

C

ATOM
28
NE
ARG A
41
15.954
21.902
24.052
1.00
43.92
A

N

ATOM
29
CZ
ARG A
41
15.888
22.643
25.155
1.00
47.14
A

C

ATOM
30
NH1
ARG A
41
16.558
22.282
26.244
1.00
46.80
A

N

ATOM
31
NH2
ARG A
41
15.147
23.745
25.169
1.00
49.17
A

N

ATOM
32
C
ARG A
41
15.489
18.762
19.990
1.00
22.91
A

C

ATOM
33
O
ARG A
41
15.087
17.650
19.668
1.00
22.24
A

O

ATOM
34
N
LEU A
42
16.650
19.265
19.578
1.00
20.60
A

N

ATOM
35
CA
LEU A
42
17.568
18.528
18.715
1.00
17.57
A

C

ATOM
36
CB
LEU A
42
17.411
18.989
17.264
1.00
17.84
A

C

ATOM
37
CG
LEU A
42
16.086
18.717
16.557
1.00
18.08
A

C

ATOM
38
CD1
LEU A
42
16.074
19.406
15.195
1.00
17.09
A

C

ATOM
39
CD2
LEU A
42
15.902
17.218
16.405
1.00
18.48
A

C

ATOM
40
C
LEU A
42
18.992
18.814
19.184
1.00
16.85
A

C

ATOM
41
O
LEU A
42
19.391
19.973
19.306
1.00
18.05
A

O

ATOM
42
N
ASP A
43
19.760
17.766
19.455
1.00
15.30
A

N

ATOM
43
CA
ASP A
43
21.130
17.962
19.902
1.00
13.64
A

C

ATOM
44
CB
ASP A
43
21.815
16.607
20.093
1.00
13.53
A

C

ATOM
45
CG
ASP A
43
23.177
16.732
20.753
1.00
18.06
A

C

ATOM
46
OD1
ASP A
43
24.185
16.931
20.042
1.00
15.90
A

O

ATOM
47
OD2
ASP A
43
23.235
16.645
21.993
1.00
20.18
A

O

ATOM
48
C
ASP A
43
21.869
18.802
18.855
1.00
12.61
A

C

ATOM
49
O
ASP A
43
21.634
18.661
17.655
1.00
12.49
A

O

ATOM
50
N
LYS A
44
22.755
19.682
19.303
1.00
11.01
A

N

ATOM
51
CA
LYS A
44
23.497
20.525
18.373
1.00
11.24
A

C

ATOM
52
CB
LYS A
44
24.368
21.536
19.129
1.00
11.63
A

C

ATOM
53
CG
LYS A
44
24.903
22.642
18.219
1.00
14.43
A

C

ATOM
54
CD
LYS A
44
25.657
23.738
18.977
1.00
16.69
A

C

ATOM
55
CE
LYS A
44
26.076
24.856
18.021
1.00
16.93
A

C

ATOM
56
NZ
LYS A
44
26.812
25.974
18.696
1.00
17.12
A

N

ATOM
57
C
LYS A
44
24.375
19.734
17.392
1.00
10.50
A

C

ATOM
58
O
LYS A
44
24.702
20.240
16.321
1.00
10.60
A

O

ATOM
59
N
SER A
45
24.753
18.507
17.745
1.00
8.11
A

N

ATOM
60
CA
SER A
45
25.585
17.699
16.844
1.00
10.59
A

C

ATOM
61
CB
SER A
45
25.941
16.352
17.479
1.00
10.95
A

C

ATOM
62
OG
SER A
45
24.779
15.624
17.827
1.00
12.31
A

O

ATOM
63
C
SER A
45
24.907
17.460
15.499
1.00
11.14
A

C

ATOM
64
O
SER A
45
25.571
17.208
14.496
1.00
10.24
A

O

ATOM
65
N
ASN A
46
23.582
17.533
15.477
1.00
10.77
A

N

ATOM
66
CA
ASN A
46
22.841
17.352
14.232
1.00
10.71
A

C

ATOM
67
CB
ASN A
46
21.335
17.486
14.476
1.00
10.57
A

C

ATOM
68
CG
ASN A
46
20.737
16.244
15.094
1.00
11.94
A

C

ATOM
69
OD1
ASN A
46
20.651
15.204
14.443
1.00
12.54
A

O

ATOM
70
ND2
ASN A
46
20.333
16.339
16.361
1.00
8.37
A

N

ATOM
71
C
ASN A
46
23.231
18.402
13.207
1.00
11.00
A

C

ATOM
72
O
ASN A
46
23.116
18.172
12.011
1.00
11.41
A

O

ATOM
73
N
PHE A
47
23.691
19.551
13.688
1.00
11.89
A

N

ATOM
74
CA
PHE A
47
24.028
20.671
12.812
1.00
13.43
A

C

ATOM
75
CB
PHE A
47
23.217
21.890
13.254
1.00
13.84
A

C

ATOM
76
CG
PHE A
47
21.760
21.593
13.463
1.00
13.84
A

C

ATOM
77
CD1
PHE A
47
20.886
21.510
12.377
1.00
15.85
A

C

ATOM
78
CD2
PHE A
47
21.273
21.347
14.739
1.00
12.02
A

C

ATOM
79
CE1
PHE A
47
19.543
21.182
12.567
1.00
15.39
A

C

ATOM
80
CE2
PHE A
47
19.937
21.019
14.940
1.00
14.91
A

C

ATOM
81
CZ
PHE A
47
19.068
20.935
13.855
1.00
12.76
A

C

ATOM
82
C
PHE A
47
25.498
21.047
12.773
1.00
12.62
A

C

ATOM
83
O
PHE A
47
25.846
22.136
12.312
1.00
13.52
A

O

ATOM
84
N
GLN A
48
26.361
20.152
13.243
1.00
13.34
A

N

ATOM
85
CA
GLN A
48
27.789
20.436
13.281
1.00
12.80
A

C

ATOM
86
CB
GLN A
48
28.300
20.324
14.719
1.00
12.87
A

C

ATOM
87
CG
GLN A
48
27.678
21.326
15.686
1.00
14.56
A

C

ATOM
88
CD
GLN A
48
28.082
21.066
17.116
1.00
16.25
A

C

ATOM
89
OE1
GLN A
48
27.892
19.965
17.634
1.00
18.12
A

O

ATOM
90
NE2
GLN A
48
28.644
22.075
17.766
1.00
15.04
A

N

ATOM
91
C
GLN A
48
28.636
19.542
12.388
1.00
14.54
A

C

ATOM
92
O
GLN A
48
29.860
19.568
12.486
1.00
13.57
A

O

ATOM
93
N
GLN A
49
27.998
18.749
11.528
1.00
12.16
A

N

ATOM
94
CA
GLN A
49
28.742
17.858
10.640
1.00
12.52
A

C

ATOM
95
CB
GLN A
49
27.990
16.530
10.503
1.00
12.58
A

C

ATOM
96
CG
GLN A
49
27.439
16.022
11.847
1.00
12.67
A

C

ATOM
97
CD
GLN A
49
28.483
16.019
12.961
1.00
15.57
A

C

ATOM
98
OE1
GLN A
49
29.730
15.772
12.598
1.00
12.50
A

O

ATOM
99
NE2
GLN A
49
28.165
16.234
14.136
1.00
14.24
A

N

ATOM
100
C
GLN A
49
28.941
18.568
9.295
1.00
12.85
A

C

ATOM
101
O
GLN A
49
27.985
18.899
8.589
1.00
11.22
A

O

ATOM
102
N
PRO A
50
30.204
18.823
8.927
1.00
13.42
A

N

ATOM
103
CD
PRO A
50
31.449
18.453
9.628
1.00
12.27
A

C

ATOM
104
CA
PRO A
50
30.492
19.514
7.666
1.00
12.60
A

C

ATOM
105
CB
PRO A
50
32.022
19.622
7.663
1.00
11.32
A

C

ATOM
106
CG
PRO A
50
32.460
18.448
8.495
1.00
14.19
A

C

ATOM
107
C
PRO A
50
29.948
18.944
6.370
1.00
11.49
A

C

ATOM
108
O
PRO A
50
29.464
19.697
5.520
1.00
10.14
A

O

ATOM
109
N
TYR A
51
30.001
17.629
6.205
1.00
11.00
A

N

ATOM
110
CA
TYR A
51
29.530
17.056
4.955
1.00
12.96
A

C

ATOM
111
CB
TYR A
51
29.750
15.535
4.932
1.00
14.28
A

C

ATOM
112
CG
TYR A
51
29.310
14.977
3.603
1.00
16.43
A

C

ATOM
113
CD1
TYR A
51
30.152
15.062
2.498
1.00
16.36
A

C

ATOM
114
CE1
TYR A
51
29.742
14.584
1.244
1.00
18.58
A

C

ATOM
115
CD2
TYR A
51
28.041
14.386
3.425
1.00
17.28
A

C

ATOM
116
CE2
TYR A
51
27.619
13.935
2.175
1.00
17.57
A

C

ATOM
117
CZ
TYR A
51
28.476
14.041
1.089
1.00
19.05
A

C

ATOM
118
OH
TYR A
51
28.068
13.623
−0.157
1.00
20.18
A

O

ATOM
119
C
TYR A
51
28.068
17.375
4.634
1.00
11.00
A

C

ATOM
120
O
TYR A
51
27.773
17.999
3.612
1.00
12.39
A

O

ATOM
121
N
ILE A
52
27.159
16.938
5.494
1.00
10.51
A

N

ATOM
122
CA
ILE A
52
25.746
17.175
5.222
1.00
10.19
A

C

ATOM
123
CB
ILE A
52
24.838
16.307
6.125
1.00
7.95
A

C

ATOM
124
CG2
ILE A
52
24.850
16.814
7.558
1.00
7.43
A

C

ATOM
125
CG1
ILE A
52
23.427
16.282
5.537
1.00
9.73
A

C

ATOM
126
CD
ILE A
52
23.341
15.576
4.193
1.00
9.58
A

C

ATOM
127
C
ILE A
52
25.351
18.640
5.335
1.00
9.53
A

C

ATOM
128
O
ILE A
52
24.416
19.073
4.671
1.00
10.79
A

O

ATOM
129
N
THR A
53
26.053
19.407
6.167
1.00
10.80
A

N

ATOM
130
CA
THR A
53
25.739
20.828
6.293
1.00
9.84
A

C

ATOM
131
CB
THR A
53
26.507
21.481
7.459
1.00
11.16
A

C

ATOM
132
OG1
THR A
53
26.155
20.833
8.690
1.00
12.87
A

O

ATOM
133
CG2
THR A
53
26.163
22.967
7.554
1.00
9.20
A

C

ATOM
134
C
THR A
53
26.126
21.519
4.977
1.00
11.45
A

C

ATOM
135
O
THR A
53
25.410
22.387
4.479
1.00
11.63
A

O

ATOM
136
N
ASN A
54
27.257
21.114
4.407
1.00
13.24
A

N

ATOM
137
CA
ASN A
54
27.708
21.691
3.141
1.00
13.84
A

C

ATOM
138
CB
ASN A
54
29.105
21.170
2.785
1.00
14.48
A

C

ATOM
139
CG
ASN A
54
29.639
21.771
1.500
1.00
14.91
A

C

ATOM
140
OD1
ASN A
54
29.687
22.986
1.348
1.00
18.44
A

O

ATOM
141
ND2
ASN A
54
30.045
20.920
0.571
1.00
19.20
A

N

ATOM
142
C
ASN A
54
26.719
21.350
2.025
1.00
12.10
A

C

ATOM
143
O
ASN A
54
26.380
22.200
1.205
1.00
13.81
A

O

ATOM
144
N
ARG A
55
26.260
20.102
1.997
1.00
14.14
A

N

ATOM
145
CA
ARG A
55
25.290
19.664
0.994
1.00
13.41
A

C

ATOM
146
CB
ARG A
55
24.950
18.180
1.176
1.00
15.87
A

C

ATOM
147
CG
ARG A
55
26.059
17.196
0.801
1.00
19.73
A

C

ATOM
148
CD
ARG A
55
26.505
17.386
−0.642
1.00
23.68
A

C

ATOM
149
NE
ARG A
55
27.405
16.325
−1.085
1.00
25.59
A

N

ATOM
150
CZ
ARG A
55
28.442
16.519
−1.891
1.00
27.42
A

C

ATOM
151
NH1
ARG A
55
28.710
17.733
−2.343
1.00
28.76
A

N

ATOM
152
NH2
ARG A
55
29.216
15.503
−2.241
1.00
27.48
A

N

ATOM
153
C
ARG A
55
24.007
20.480
1.129
1.00
11.99
A

C

ATOM
154
O
ARG A
55
23.412
20.893
0.134
1.00
11.77
A

O

ATOM
155
N
THR A
56
23.575
20.701
2.367
1.00
12.12
A

N

ATOM
156
CA
THR A
56
22.357
21.464
2.605
1.00
10.35
A

C

ATOM
157
CB
THR A
56
22.017
21.513
4.104
1.00
12.01
A

C

ATOM
158
OG1
THR A
56
21.792
20.180
4.591
1.00
7.11
A

O

ATOM
159
CG2
THR A
56
20.766
22.340
4.337
1.00
8.42
A

C

ATOM
160
C
THR A
56
22.483
22.889
2.062
1.00
12.24
A

C

ATOM
161
O
THR A
56
21.604
23.370
1.345
1.00
8.45
A

O

ATOM
162
N
PHE A
57
23.571
23.573
2.399
1.00
11.55
A

N

ATOM
163
CA
PHE A
57
23.753
24.937
1.914
1.00
12.54
A

C

ATOM
164
CB
PHE A
57
24.929
25.609
2.624
1.00
12.16
A

C

ATOM
165
CG
PHE A
57
24.568
26.181
3.960
1.00
13.36
A

C

ATOM
166
CD1
PHE A
57
24.313
25.354
5.046
1.00
13.15
A

C

ATOM
167
CD2
PHE A
57
24.464
27.553
4.130
1.00
14.39
A

C

ATOM
168
CE1
PHE A
57
23.961
25.887
6.282
1.00
14.05
A

C

ATOM
169
CE2
PHE A
57
24.113
28.092
5.359
1.00
12.06
A

C

ATOM
170
CZ
PHE A
57
23.862
27.259
6.438
1.00
13.80
A

C

ATOM
171
C
PHE A
57
23.936
25.003
0.398
1.00
13.58
A

C

ATOM
172
O
PHE A
57
23.483
25.952
−0.244
1.00
13.09
A

O

ATOM
173
N
MET A
58
24.579
23.992
−0.177
1.00
13.90
A

N

ATOM
174
CA
MET A
58
24.782
23.969
−1.622
1.00
15.62
A

C

ATOM
175
CB
MET A
58
25.750
22.859
−2.019
1.00
16.17
A

C

ATOM
176
CG
MET A
58
27.164
23.047
−1.506
1.00
21.09
A

C

ATOM
177
SD
MET A
58
28.342
21.989
−2.379
1.00
27.56
A

S

ATOM
178
CE
MET A
58
27.683
20.368
−2.012
1.00
26.89
A

C

ATOM
179
C
MET A
58
23.454
23.759
−2.337
1.00
13.03
A

C

ATOM
180
O
MET A
58
23.215
24.322
−3.405
1.00
11.50
A

O

ATOM
181
N
LEU A
59
22.589
22.940
−1.749
1.00
12.01
A

N

ATOM
182
CA
LEU A
59
21.286
22.696
−2.347
1.00
12.06
A

C

ATOM
183
CB
LEU A
59
20.548
21.587
−1.597
1.00
12.51
A

C

ATOM
184
CG
LEU A
59
19.085
21.390
−2.012
1.00
13.80
A

C

ATOM
185
CD1
LEU A
59
18.991
21.124
−3.512
1.00
14.82
A

C

ATOM
186
CD2
LEU A
59
18.486
20.243
−1.225
1.00
10.84
A

C

ATOM
187
C
LEU A
59
20.474
23.990
−2.307
1.00
14.49
A

C

ATOM
188
O
LEU A
59
19.769
24.325
−3.262
1.00
13.13
A

O

ATOM
189
N
ALA A
60
20.578
24.718
−1.195
1.00
14.81
A

N

ATOM
190
CA
ALA A
60
19.857
25.974
−1.046
1.00
14.10
A

C

ATOM
191
CB
ALA A
60
20.077
26.545
0.344
1.00
14.30
A

C

ATOM
192
C
ALA A
60
20.339
26.963
−2.100
1.00
15.08
A

C

ATOM
193
O
ALA A
60
19.537
27.621
−2.761
1.00
12.89
A

O

ATOM
194
N
LYS A
61
21.654
27.065
−2.263
1.00
14.92
A

N

ATOM
195
CA
LYS A
61
22.209
27.985
−3.246
1.00
14.74
A

C

ATOM
196
CB
LYS A
61
23.740
27.926
−3.227
1.00
16.05
A

C

ATOM
197
CG
LYS A
61
24.421
28.890
−4.194
1.00
17.02
A

C

ATOM
198
CD
LYS A
61
24.047
30.325
−3.891
1.00
19.86
A

C

ATOM
199
CE
LYS A
61
24.717
31.288
−4.854
1.00
24.25
A

C

ATOM
200
NZ
LYS A
61
24.367
32.697
−4.518
1.00
25.65
A

N

ATOM
201
C
LYS A
61
21.687
27.665
−4.642
1.00
15.27
A

C

ATOM
202
O
LYS A
61
21.161
28.537
−5.328
1.00
14.82
A

O

ATOM
203
N
GLU A
62
21.819
26.411
−5.057
1.00
15.81
A

N

ATOM
204
CA
GLU A
62
21.353
26.001
−6.373
1.00
18.42
A

C

ATOM
205
CB
GLU A
62
21.572
24.498
−6.555
1.00
20.56
A

C

ATOM
206
CG
GLU A
62
21.338
24.016
−7.969
1.00
27.23
A

C

ATOM
207
CD
GLU A
62
21.791
22.573
−8.214
1.00
31.47
A

C

ATOM
208
OE1
GLU A
62
22.875
22.136
−7.748
1.00
32.95
A

O

ATOM
209
OE2
GLU A
62
21.044
21.870
−8.914
1.00
33.23
A

O

ATOM
210
C
GLU A
62
19.879
26.348
−6.592
1.00
17.89
A

C

ATOM
211
O
GLU A
62
19.514
26.908
−7.625
1.00
16.93
A

O

ATOM
212
N
ALA A
63
19.029
26.021
−5.623
1.00
17.26
A

N

ATOM
213
CA
ALA A
63
17.605
26.316
−5.752
1.00
16.93
A

C

ATOM
214
CB
ALA A
63
16.832
25.692
−4.598
1.00
16.38
A

C

ATOM
215
C
ALA A
63
17.341
27.818
−5.801
1.00
17.17
A

C

ATOM
216
O
ALA A
63
16.477
28.280
−6.552
1.00
16.33
A

O

ATOM
217
N
SER A
64
18.079
28.586
−5.006
1.00
15.83
A

N

ATOM
218
CA
SER A
64
17.876
30.026
−4.992
1.00
18.51
A

C

ATOM
219
CB
SER A
64
18.748
30.686
−3.918
1.00
19.42
A

C

ATOM
220
OG
SER A
64
20.118
30.643
−4.267
1.00
21.79
A

O

ATOM
221
C
SER A
64
18.187
30.625
−6.364
1.00
19.15
A

C

ATOM
222
O
SER A
64
17.632
31.659
−6.739
1.00
18.21
A

O

ATOM
223
N
LEU A
65
19.067
29.966
−7.116
1.00
20.27
A

N

ATOM
224
CA
LEU A
65
19.433
30.454
−8.442
1.00
19.37
A

C

ATOM
225
CB
LEU A
65
20.727
29.797
−8.924
1.00
19.96
A

C

ATOM
226
CG
LEU A
65
22.002
30.321
−8.250
1.00
20.32
A

C

ATOM
227
CD1
LEU A
65
23.174
29.425
−8.604
1.00
21.39
A

C

ATOM
228
CD2
LEU A
65
22.268
31.752
−8.694
1.00
19.85
A

C

ATOM
229
C
LEU A
65
18.317
30.182
−9.429
1.00
20.47
A

C

ATOM
230
O
LEU A
65
18.318
30.707
−10.545
1.00
19.18
A

O

ATOM
231
N
ALA A
66
17.363
29.358
−9.010
1.00
18.96
A

N

ATOM
232
CA
ALA A
66
16.231
29.022
−9.859
1.00
20.12
A

C

ATOM
233
CB
ALA A
66
15.983
27.521
−9.822
1.00
19.46
A

C

ATOM
234
C
ALA A
66
14.989
29.775
−9.390
1.00
21.39
A

C

ATOM
235
O
ALA A
66
13.926
29.661
−9.985
1.00
20.75
A

O

ATOM
236
N
ASP A
67
15.141
30.560
−8.331
1.00
22.23
A

N

ATOM
237
CA
ASP A
67
14.036
31.320
−7.761
1.00
24.31
A

C

ATOM
238
CB
ASP A
67
14.022
31.084
−6.246
1.00
25.00
A

C

ATOM
239
CG
ASP A
67
13.134
32.055
−5.497
1.00
24.66
A

C

ATOM
240
OD1
ASP A
67
12.112
32.513
−6.056
1.00
24.92
A

O

ATOM
241
OD2
ASP A
67
13.465
32.341
−4.328
1.00
21.55
A

O

ATOM
242
C
ASP A
67
14.116
32.813
−8.083
1.00
25.59
A

C

ATOM
243
O
ASP A
67
15.012
33.511
−7.609
1.00
25.98
A

O

ATOM
244
N
ASN A
68
13.172
33.297
−8.889
1.00
27.63
A

N

ATOM
245
CA
ASN A
68
13.138
34.708
−9.271
1.00
30.16
A

C

ATOM
246
CB
ASN A
68
12.696
34.857
−10.731
1.00
32.04
A

C

ATOM
247
CG
ASN A
68
13.815
34.567
−11.710
1.00
35.26
A

C

ATOM
248
OD1
ASN A
68
14.891
35.160
−11.627
1.00
37.18
A

O

ATOM
249
ND2
ASN A
68
13.567
33.661
−12.651
1.00
36.56
A

N

ATOM
250
C
ASN A
68
12.245
35.585
−8.401
1.00
31.73
A

C

ATOM
251
O
ASN A
68
12.134
36.785
−8.649
1.00
31.89
A

O

ATOM
252
N
ASN A
69
11.586
34.992
−7.408
1.00
32.78
A

N

ATOM
253
CA
ASN A
69
10.698
35.744
−6.519
1.00
35.19
A

C

ATOM
254
CB
ASN A
69
9.746
34.801
−5.772
1.00
36.74
A

C

ATOM
255
CG
ASN A
69
9.056
33.805
−6.688
1.00
40.93
A

C

ATOM
256
OD1
ASN A
69
8.300
34.186
−7.586
1.00
41.57
A

O

ATOM
257
ND2
ASN A
69
9.311
32.515
−6.461
1.00
40.68
A

N

ATOM
258
C
ASN A
69
11.542
36.510
−5.501
1.00
35.09
A

C

ATOM
259
O
ASN A
69
11.646
36.109
−4.339
1.00
32.29
A

O

ATOM
260
N
THR A
70
12.134
37.615
−5.942
1.00
35.82
A

N

ATOM
261
CA
THR A
70
12.979
38.430
−5.078
1.00
37.87
A

C

ATOM
262
CB
THR A
70
13.852
39.386
−5.906
1.00
38.42
A

C

ATOM
263
OG1
THR A
70
13.014
40.346
−6.555
1.00
38.69
A

O

ATOM
264
CG2
THR A
70
14.631
38.623
−6.960
1.00
38.88
A

C

ATOM
265
C
THR A
70
12.192
39.275
−4.072
1.00
38.60
A

C

ATOM
266
O
THR A
70
12.781
39.904
−3.190
1.00
40.16
A

O

ATOM
267
N
ASP A
71
10.868
39.282
−4.196
1.00
39.04
A

N

ATOM
268
CA
ASP A
71
10.017
40.069
−3.305
1.00
39.32
A

C

ATOM
269
CB
ASP A
71
8.838
40.662
−4.078
1.00
42.61
A

C

ATOM
270
CG
ASP A
71
9.276
41.445
−5.281
1.00
47.01
A

C

ATOM
271
OD1
ASP A
71
9.915
40.831
−6.152
1.00
49.64
A

O

ATOM
272
OD2
ASP A
71
8.991
42.661
−5.362
1.00
50.35
A

O

ATOM
273
C
ASP A
71
9.451
39.301
−2.119
1.00
37.56
A

C

ATOM
274
O
ASP A
71
8.886
39.906
−1.206
1.00
37.36
A

O

ATOM
275
N
VAL A
72
9.590
37.979
−2.128
1.00
33.02
A

N

ATOM
276
CA
VAL A
72
9.040
37.171
−1.048
1.00
29.68
A

C

ATOM
277
CB
VAL A
72
8.003
36.165
−1.590
1.00
31.44
A

C

ATOM
278
CG1
VAL A
72
7.361
35.408
−0.437
1.00
31.76
A

C

ATOM
279
CG2
VAL A
72
6.951
36.899
−2.416
1.00
34.37
A

C

ATOM
280
C
VAL A
72
10.074
36.392
−0.252
1.00
26.18
A

C

ATOM
281
O
VAL A
72
11.011
35.825
−0.814
1.00
24.53
A

O

ATOM
282
N
ARG A
73
9.879
36.372
1.061
1.00
24.81
A

N

ATOM
283
CA
ARG A
73
10.744
35.656
1.996
1.00
25.04
A

C

ATOM
284
CB
ARG A
73
11.426
36.640
2.951
1.00
27.84
A

C

ATOM
285
CG
ARG A
73
12.237
35.992
4.066
1.00
31.02
A

C

ATOM
286
CD
ARG A
73
13.488
35.315
3.527
1.00
33.29
A

C

ATOM
287
NE
ARG A
73
14.469
36.271
3.019
1.00
37.87
A

N

ATOM
288
CZ
ARG A
73
15.093
37.178
3.765
1.00
39.29
A

C

ATOM
289
NH1
ARG A
73
14.847
37.266
5.066
1.00
39.10
A

N

ATOM
290
NH2
ARG A
73
15.967
38.002
3.207
1.00
42.25
A

N

ATOM
291
C
ARG A
73
9.819
34.739
2.783
1.00
23.44
A

C

ATOM
292
O
ARG A
73
8.797
35.189
3.303
1.00
23.25
A

O

ATOM
293
N
LEU A
74
10.158
33.458
2.871
1.00
20.73
A

N

ATOM
294
CA
LEU A
74
9.311
32.522
3.602
1.00
18.25
A

C

ATOM
295
CB
LEU A
74
9.412
31.120
2.994
1.00
19.13
A

C

ATOM
296
CG
LEU A
74
8.937
30.973
1.546
1.00
19.57
A

C

ATOM
297
CD1
LEU A
74
9.020
29.523
1.122
1.00
19.10
A

C

ATOM
298
CD2
LEU A
74
7.504
31.462
1.420
1.00
19.94
A

C

ATOM
299
C
LEU A
74
9.655
32.466
5.081
1.00
18.81
A

C

ATOM
300
O
LEU A
74
8.772
32.562
5.930
1.00
17.72
A

O

ATOM
301
N
ILE A
75
10.940
32.307
5.391
1.00
17.09
A

N

ATOM
302
CA
ILE A
75
11.375
32.239
6.781
1.00
16.71
A

C

ATOM
303
CB
ILE A
75
12.503
31.195
6.948
1.00
17.07
A

C

ATOM
304
CG2
ILE A
75
13.077
31.258
8.361
1.00
17.86
A

C

ATOM
305
CG1
ILE A
75
11.950
29.798
6.642
1.00
18.78
A

C

ATOM
306
CD
ILE A
75
12.978
28.681
6.749
1.00
18.86
A

C

ATOM
307
C
ILE A
75
11.848
33.612
7.263
1.00
17.51
A

C

ATOM
308
O
ILE A
75
12.939
34.062
6.931
1.00
15.26
A

O

ATOM
309
N
GLY A
76
11.017
34.281
8.052
1.00
18.34
A

N

ATOM
310
CA
GLY A
76
11.389
35.600
8.530
1.00
21.35
A

C

ATOM
311
C
GLY A
76
10.608
36.007
9.761
1.00
23.15
A

C

ATOM
312
O
GLY A
76
9.916
35.187
10.357
1.00
21.36
A

O

ATOM
313
N
GLU A
77
10.706
37.282
10.125
1.00
26.14
A

N

ATOM
314
CA
GLU A
77
10.043
37.817
11.313
1.00
27.91
A

C

ATOM
315
CB
GLU A
77
10.118
39.349
11.300
1.00
31.26
A

C

ATOM
316
CG
GLU A
77
9.551
40.011
12.548
1.00
36.17
A

C

ATOM
317
CD
GLU A
77
9.807
41.508
12.584
1.00
39.76
A

C

ATOM
318
OE1
GLU A
77
9.440
42.203
11.609
1.00
39.06
A

O

ATOM
319
OE2
GLU A
77
10.375
41.986
13.591
1.00
41.22
A

O

ATOM
320
C
GLU A
77
8.595
37.370
11.517
1.00
27.70
A

C

ATOM
321
O
GLU A
77
8.235
36.899
12.595
1.00
28.81
A

O

ATOM
322
N
LYS A
78
7.767
37.514
10.491
1.00
27.14
A

N

ATOM
323
CA
LYS A
78
6.364
37.125
10.594
1.00
26.90
A

C

ATOM
324
CB
LYS A
78
5.652
37.351
9.254
1.00
29.37
A

C

ATOM
325
CG
LYS A
78
6.481
36.998
8.023
1.00
34.70
A

C

ATOM
326
CD
LYS A
78
7.597
38.018
7.773
1.00
35.71
A

C

ATOM
327
CE
LYS A
78
8.457
37.619
6.584
1.00
37.67
A

C

ATOM
328
NZ
LYS A
78
9.458
38.670
6.251
1.00
39.35
A

N

ATOM
329
C
LYS A
78
6.147
35.688
11.061
1.00
24.99
A

C

ATOM
330
O
LYS A
78
5.244
35.419
11.850
1.00
24.73
A

O

ATOM
331
N
LEU A
79
6.974
34.765
10.580
1.00
23.10
A

N

ATOM
332
CA
LEU A
79
6.851
33.360
10.954
1.00
21.97
A

C

ATOM
333
CB
LEU A
79
7.903
32.533
10.206
1.00
21.38
A

C

ATOM
334
CG
LEU A
79
7.963
31.034
10.510
1.00
19.79
A

C

ATOM
335
CD1
LEU A
79
6.618
30.386
10.186
1.00
18.36
A

C

ATOM
336
CD2
LEU A
79
9.076
30.395
9.688
1.00
18.38
A

C

ATOM
337
C
LEU A
79
7.005
33.126
12.457
1.00
22.48
A

C

ATOM
338
O
LEU A
79
6.378
32.232
13.026
1.00
21.54
A

O

ATOM
339
N
PHE A
80
7.839
33.936
13.898
1.00
24.35
A

N

ATOM
340
CA
PHE A
80
8.102
33.799
14.525
1.00
25.81
A

C

ATOM
341
CB
PHE A
80
9.599
33.972
14.768
1.00
24.41
A

C

ATOM
342
CG
PHE A
80
10.447
33.009
13.990
1.00
24.03
A

C

ATOM
343
CD1
PHE A
80
10.510
31.667
14.351
1.00
23.62
A

C

ATOM
344
CD2
PHE A
80
11.158
33.437
12.875
1.00
23.15
A

C

ATOM
345
CE1
PHE A
80
11.270
30.759
13.606
1.00
23.39
A

C

ATOM
346
CE2
PHE A
80
11.917
32.543
12.125
1.00
23.09
A

C

ATOM
347
CZ
PHE A
80
11.974
31.200
12.491
1.00
23.28
A

C

ATOM
348
C
PHE A
80
7.324
34.775
15.410
1.00
28.55
A

C

ATOM
349
O
PHE A
80
7.362
34.676
16.637
1.00
28.74
A

O

ATOM
350
N
HIS A
81
6.618
35.711
14.787
1.00
30.56
A

N

ATOM
351
CA
HIS A
81
5.849
36.711
15.519
1.00
32.02
A

C

ATOM
352
CB
HIS A
81
5.051
37.579
14.540
1.00
34.06
A

C

ATOM
353
CG
HIS A
81
4.321
38.711
15.193
1.00
36.89
A

C

ATOM
354
CD2
HIS A
81
2.996
38.959
15.325
1.00
37.63
A

C

ATOM
355
ND1
HIS A
81
4.971
39.748
15.829
1.00
38.12
A

N

ATOM
356
CE1
HIS A
81
4.078
40.585
16.325
1.00
38.01
A

C

ATOM
357
NE2
HIS A
81
2.873
40.129
16.033
1.00
38.42
A

N

ATOM
358
C
HIS A
81
4.902
36.097
16.547
1.00
30.87
A

C

ATOM
359
O
HIS A
81
4.060
35.268
16.211
1.00
32.80
A

O

ATOM
360
N
GLY A
82
5.046
36.511
17.802
1.00
30.56
A

N

ATOM
361
CA
GLY A
82
4.192
35.997
18.859
1.00
29.32
A

C

ATOM
362
C
GLY A
82
4.593
34.640
19.420
1.00
28.91
A

C

ATOM
363
O
GLY A
82
3.989
34.165
20.380
1.00
29.61
A

O

ATOM
364
N
VAL A
83
5.609
34.011
18.835
1.00
26.58
A

N

ATOM
365
CA
VAL A
83
6.064
32.697
19.295
1.00
24.46
A

C

ATOM
366
CB
VAL A
83
6.569
31.855
18.096
1.00
24.84
A

C

ATOM
367
CG1
VAL A
83
6.971
30.470
18.531
1.00
24.49
A

C

ATOM
368
CG2
VAL A
83
5.480
31.749
17.066
1.00
24.95
A

C

ATOM
369
C
VAL A
83
7.180
32.847
20.328
1.00
23.20
A

C

ATOM
370
O
VAL A
83
8.218
33.429
20.043
1.00
20.58
A

O

ATOM
371
N
SER A
84
6.956
32.336
21.535
1.00
22.74
A

N

ATOM
372
CA
SER A
84
7.961
32.427
22.586
1.00
22.59
A

C

ATOM
373
CB
SER A
84
7.325
32.136
23.942
1.00
24.87
A

C

ATOM
374
OG
SER A
84
6.740
30.847
23.960
1.00
28.28
A

O

ATOM
375
C
SER A
84
9.091
31.438
22.319
1.00
22.22
A

C

ATOM
376
O
SER A
84
8.891
30.428
21.649
1.00
19.25
A

O

ATOM
377
N
MET A
85
10.271
31.723
22.860
1.00
22.89
A

N

ATOM
378
CA
MET A
85
11.438
30.864
22.661
1.00
23.51
A

C

ATOM
379
CB
MET A
85
12.626
31.391
23.470
1.00
26.40
A

C

ATOM
380
CG
MET A
85
12.965
32.850
23.205
1.00
32.22
A

C

ATOM
381
SD
MET A
85
13.130
33.234
21.443
1.00
38.24
A

S

ATOM
382
CE
MET A
85
11.634
34.156
21.178
1.00
39.11
A

C

ATOM
383
C
MET A
85
11.213
29.391
23.010
1.00
21.82
A

C

ATOM
384
O
MET A
85
11.799
28.506
22.387
1.00
21.96
A

O

ATOM
385
N
SER A
86
10.377
29.121
24.006
1.00
20.05
A

N

ATOM
386
CA
SER A
86
10.123
27.743
24.405
1.00
20.16
A

C

ATOM
387
CB
SER A
86
9.504
27.701
25.801
1.00
20.31
A

C

ATOM
388
OG
SER A
86
8.281
28.406
25.816
1.00
19.38
A

O

ATOM
389
C
SER A
86
9.215
26.993
23.436
1.00
20.16
A

C

ATOM
390
O
SER A
86
9.039
25.780
23.563
1.00
21.23
A

O

ATOM
391
N
GLU A
87
8.633
27.702
22.475
1.00
18.55
A

N

ATOM
392
CA
GLU A
87
7.757
27.044
21.505
1.00
19.19
A

C

ATOM
393
CB
GLU A
87
6.381
27.717
21.480
1.00
21.48
A

C

ATOM
394
CG
GLU A
87
5.848
28.071
22.849
1.00
27.63
A

C

ATOM
395
CD
GLU A
87
4.583
28.925
22.796
1.00
30.13
A

C

ATOM
396
OE1
GLU A
87
4.609
30.033
22.220
1.00
30.21
A

O

ATOM
397
OE2
GLU A
87
3.553
28.497
23.344
1.00
33.94
A

O

ATOM
398
C
GLU A
87
8.337
27.066
20.095
1.00
17.25
A

C

ATOM
399
O
GLU A
87
7.786
26.443
19.189
1.00
15.95
A

O

ATOM
400
N
ARG A
88
9.447
27.778
19.910
1.00
16.02
A

N

ATOM
401
CA
ARG A
88
10.081
27.887
18.599
1.00
15.63
A

C

ATOM
402
CB
ARG A
88
11.356
28.729
18.693
1.00
18.69
A

C

ATOM
403
CG
ARG A
88
11.146
30.190
19.067
1.00
23.67
A

C

ATOM
404
CD
ARG A
88
10.457
30.944
17.961
1.00
26.36
A

C

ATOM
405
NE
ARG A
88
10.175
32.337
18.311
1.00
30.28
A

N

ATOM
406
CZ
ARG A
88
11.044
33.337
18.206
1.00
31.77
A

C

ATOM
407
NH1
ARG A
88
12.270
33.111
17.762
1.00
34.62
A

N

ATOM
408
NH2
ARG A
88
10.678
34.574
18.518
1.00
30.69
A

N

ATOM
409
C
ARG A
88
10.423
26.541
17.951
1.00
15.43
A

C

ATOM
410
O
ARG A
88
10.153
26.333
16.767
1.00
15.17
A

O

ATOM
411
N
CYS A
89
11.025
25.628
18.708
1.00
12.14
A

N

ATOM
412
CA
CYS A
89
11.381
24.342
18.120
1.00
13.07
A

C

ATOM
413
C
CYS A
89
10.133
23.605
17.611
1.00
14.78
A

C

ATOM
414
O
CYS A
89
10.158
23.020
16.528
1.00
13.46
A

O

ATOM
415
CB
CYS A
89
12.169
23.472
19.107
1.00
12.57
A

C

ATOM
416
SG
CYS A
89
12.780
21.964
18.306
1.00
15.35
A

S

ATOM
417
N
TYR A
90
9.044
23.653
18.378
1.00
13.52
A

N

ATOM
418
CA
TYR A
90
7.789
23.017
17.970
1.00
14.36
A

C

ATOM
419
CB
TYR A
90
6.729
23.149
19.063
1.00
16.25
A

C

ATOM
420
CG
TYR A
90
5.386
22.598
18.640
1.00
20.73
A

C

ATOM
421
CD1
TYR A
90
5.172
21.220
18.551
1.00
22.84
A

C

ATOM
422
CE1
TYR A
90
3.936
20.704
18.142
1.00
25.51
A

C

ATOM
423
CD2
TYR A
90
4.334
23.453
18.308
1.00
21.97
A

C

ATOM
424
CE2
TYR A
90
3.095
22.947
17.894
1.00
25.27
A

C

ATOM
425
CZ
TYR A
90
2.908
21.575
17.813
1.00
26.64
A

C

ATOM
426
OH
TYR A
90
1.698
21.073
17.393
1.00
31.95
A

O

ATOM
427
C
TYR A
90
7.283
23.691
16.699
1.00
12.19
A

C

ATOM
428
O
TYR A
90
6.762
23.032
15.797
1.00
13.82
A

O

ATOM
429
N
LEU A
91
7.430
25.011
16.630
1.00
13.87
A

N

ATOM
430
CA
LEU A
91
7.020
25.763
15.445
1.00
14.25
A

C

ATOM
431
CB
LEU A
91
7.279
27.259
15.657
1.00
16.00
A

C

ATOM
432
CG
LEU A
91
7.389
28.125
14.403
1.00
20.38
A

C

ATOM
433
CD1
LEU A
91
6.049
28.180
13.691
1.00
20.90
A

C

ATOM
434
CD2
LEU A
91
7.848
29.522
14.795
1.00
23.19
A

C

ATOM
435
C
LEU A
91
7.841
25.271
14.250
1.00
14.26
A

C

ATOM
436
O
LEU A
91
7.298
25.011
13.166
1.00
13.95
A

O

ATOM
437
N
MET A
92
9.156
25.144
14.454
1.00
13.32
A

N

ATOM
438
CA
MET A
92
10.054
24.693
13.386
1.00
12.34
A

C

ATOM
439
CB
MET A
92
11.520
24.855
13.791
1.00
13.46
A

C

ATOM
440
CG
MET A
92
11.943
26.329
13.855
1.00
13.93
A

C

ATOM
441
SD
MET A
92
11.513
27.272
12.365
1.00
19.44
A

S

ATOM
442
CE
MET A
92
12.398
26.314
11.091
1.00
16.94
A

C

ATOM
443
C
MET A
92
9.763
23.272
12.941
1.00
13.49
A

C

ATOM
444
O
MET A
92
9.975
22.924
11.777
1.00
14.17
A

O

ATOM
445
N
LYS A
93
9.255
22.465
13.864
1.00
12.98
A

N

ATOM
446
CA
LYS A
93
8.889
21.097
13.557
1.00
13.82
A

C

ATOM
447
CB
LYS A
93
8.385
20.395
14.810
1.00
13.12
A

C

ATOM
448
CG
LYS A
93
7.672
19.082
14.522
1.00
18.61
A

C

ATOM
449
CD
LYS A
93
6.889
18.604
15.736
1.00
18.28
A

C

ATOM
450
CE
LYS A
93
6.085
17.352
15.441
1.00
20.53
A

C

ATOM
451
NZ
LYS A
93
5.352
16.889
16.657
1.00
19.33
A

N

ATOM
452
C
LYS A
93
7.770
21.124
12.526
1.00
13.87
A

C

ATOM
453
O
LYS A
93
7.760
20.328
11.593
1.00
15.68
A

O

ATOM
454
N
GLN A
94
6.823
22.043
12.700
1.00
15.16
A

N

ATOM
455
CA
GLN A
94
5.692
22.144
11.778
1.00
15.15
A

C

ATOM
456
CB
GLN A
94
4.630
23.089
12.344
1.00
17.59
A

C

ATOM
457
CG
GLN A
94
4.254
22.779
13.786
1.00
23.02
A

C

ATOM
458
CD
GLN A
94
3.713
21.376
13.964
1.00
25.41
A

C

ATOM
459
OE1
GLN A
94
3.829
20.788
15.038
1.00
31.14
A

O

ATOM
460
NE2
GLN A
94
3.110
20.836
12.917
1.00
25.01
A

N

ATOM
461
C
GLN A
94
6.157
22.644
10.419
1.00
13.97
A

C

ATOM
462
O
GLN A
94
5.687
22.179
9.378
1.00
13.38
A

O

ATOM
463
N
VAL A
95
7.082
23.599
10.429
1.00
12.42
A

N

ATOM
464
CA
VAL A
95
7.598
24.140
9.183
1.00
11.71
A

C

ATOM
465
CB
VAL A
95
8.539
25.324
9.420
1.00
12.14
A

C

ATOM
466
CG1
VAL A
95
9.180
25.740
8.107
1.00
13.43
A

C

ATOM
467
CG2
VAL A
95
7.767
26.483
9.997
1.00
12.64
A

C

ATOM
468
C
VAL A
95
8.373
23.060
8.452
1.00
12.55
A

C

ATOM
469
O
VAL A
95
8.269
22.930
7.232
1.00
10.70
A

O

ATOM
470
N
LEU A
96
9.150
22.287
9.210
1.00
11.35
A

N

ATOM
471
CA
LEU A
96
9.953
21.212
8.639
1.00
9.86
A

C

ATOM
472
CB
LEU A
96
10.822
20.559
9.712
1.00
10.52
A

C

ATOM
473
CG
LEU A
96
11.572
19.302
9.248
1.00
12.76
A

C

ATOM
474
CD1
LEU A
96
12.575
19.657
8.158
1.00
11.47
A

C

ATOM
475
CD2
LEU A
96
12.282
18.662
10.445
1.00
11.92
A

C

ATOM
476
C
LEU A
96
9.088
20.145
7.994
1.00
10.33
A

C

ATOM
477
O
LEU A
96
9.327
19.751
6.855
1.00
10.88
A

O

ATOM
478
N
ASN A
97
8.086
19.669
8.725
1.00
11.10
A

N

ATOM
479
CA
ASN A
97
7.215
18.630
8.192
1.00
12.58
A

C

ATOM
480
CB
ASN A
97
6.270
18.130
9.290
1.00
15.76
A

C

ATOM
481
CG
ASN A
97
7.013
17.361
10.377
1.00
16.70
A

C

ATOM
482
OD1
ASN A
97
8.146
16.920
10.168
1.00
19.35
A

O

ATOM
483
ND2
ASN A
97
6.380
17.182
11.525
1.00
17.01
A

N

ATOM
484
C
ASN A
97
6.462
19.114
6.964
1.00
11.81
A

C

ATOM
485
O
ASN A
97
6.281
18.361
6.006
1.00
12.10
A

O

ATOM
486
N
PHE A
98
6.037
20.374
6.971
1.00
12.85
A

N

ATOM
487
CA
PHE A
98
5.347
20.917
5.806
1.00
13.45
A

C

ATOM
488
CB
PHE A
98
4.907
22.357
6.052
1.00
14.09
A

C

ATOM
489
CG
PHE A
98
4.623
23.121
4.788
1.00
17.24
A

C

ATOM
490
CD1
PHE A
98
3.535
22.793
3.986
1.00
18.81
A

C

ATOM
491
CD2
PHE A
98
5.472
24.141
4.378
1.00
18.95
A

C

ATOM
492
CE1
PHE A
98
3.301
23.469
2.790
1.00
19.48
A

C

ATOM
493
CE2
PHE A
98
5.247
24.820
3.188
1.00
18.82
A

C

ATOM
494
CZ
PHE A
98
4.163
24.484
2.392
1.00
18.93
A

C

ATOM
495
C
PHE A
98
6.316
20.906
4.629
1.00
13.98
A

C

ATOM
496
O
PHE A
98
5.991
20.458
3.519
1.00
12.54
A

O

ATOM
497
N
THR A
99
7.519
21.405
4.878
1.00
12.46
A

N

ATOM
498
CA
THR A
99
8.509
21.473
3.818
1.00
12.12
A

C

ATOM
499
CB
THR A
99
9.789
22.174
4.297
1.00
13.25
A

C

ATOM
500
OG1
THR A
99
9.459
23.469
4.825
1.00
11.71
A

O

ATOM
501
CG2
THR A
99
10.745
22.345
3.137
1.00
12.11
A

C

ATOM
502
C
THR A
99
8.852
20.099
3.260
1.00
11.68
A

C

ATOM
503
O
THR A
99
9.081
19.950
2.061
1.00
12.57
A

O

ATOM
504
N
LEU A
100
8.892
19.092
4.124
1.00
12.47
A

N

ATOM
505
CA
LEU A
100
9.189
17.741
3.668
1.00
13.58
A

C

ATOM
506
CB
LEU A
100
9.405
16.817
4.870
1.00
13.64
A

C

ATOM
507
CG
LEU A
100
10.794
16.844
5.519
1.00
14.13
A

C

ATOM
508
CD1
LEU A
100
10.766
16.117
6.859
1.00
15.07
A

C

ATOM
509
CD2
LEU A
100
11.788
16.191
4.583
1.00
11.06
A

C

ATOM
510
C
LEU A
100
8.056
17.179
2.802
1.00
15.63
A

C

ATOM
511
O
LEU A
100
8.285
16.726
1.684
1.00
14.71
A

O

ATOM
512
N
GLU A
101
6.838
17.223
3.332
1.00
15.43
A

N

ATOM
513
CA
GLU A
101
5.660
16.687
2.656
1.00
17.18
A

C

ATOM
514
CB
GLU A
101
4.467
16.670
3.618
1.00
18.69
A

C

ATOM
515
CG
GLU A
101
4.530
15.627
4.730
1.00
22.02
A

C

ATOM
516
CD
GLU A
101
4.465
14.207
4.212
1.00
26.32
A

C

ATOM
517
OE1
GLU A
101
3.657
13.940
3.299
1.00
27.27
A

O

ATOM
518
OE2
GLU A
101
5.212
13.344
4.724
1.00
29.94
A

O

ATOM
519
C
GLU A
101
5.220
17.375
1.370
1.00
17.32
A

C

ATOM
520
O
GLU A
101
4.913
16.706
0.378
1.00
17.41
A

O

ATOM
521
N
GLU A
102
5.194
18.702
1.378
1.00
16.65
A

N

ATOM
522
CA
GLU A
102
4.725
19.442
0.212
1.00
16.41
A

C

ATOM
523
CB
GLU A
102
3.629
20.402
0.657
1.00
19.20
A

C

ATOM
524
CG
GLU A
102
2.440
19.644
1.233
1.00
23.30
A

C

ATOM
525
CD
GLU A
102
1.369
20.554
1.771
1.00
26.38
A

C

ATOM
526
OE1
GLU A
102
0.828
21.357
0.981
1.00
25.51
A

O

ATOM
527
OE2
GLU A
102
1.073
20.465
2.984
1.00
27.95
A

O

ATOM
528
C
GLU A
102
5.745
20.170
−0.650
1.00
16.28
A

C

ATOM
529
O
GLU A
102
5.385
20.783
−1.653
1.00
14.86
A

O

ATOM
530
N
VAL A
103
7.015
20.109
−0.271
1.00
12.43
A

N

ATOM
531
CA
VAL A
103
8.045
20.755
−1.077
1.00
13.07
A

C

ATOM
532
CB
VAL A
103
8.742
21.907
−0.320
1.00
12.76
A

C

ATOM
533
CG1
VAL A
103
9.889
22.458
−1.162
1.00
12.19
A

C

ATOM
534
CG2
VAL A
103
7.753
23.024
−0.027
1.00
13.33
A

C

ATOM
535
C
VAL A
103
9.122
19.763
−1.509
1.00
13.14
A

C

ATOM
536
O
VAL A
103
9.271
19.462
−2.690
1.00
13.73
A

O

ATOM
537
N
LEU A
104
9.863
19.248
−0.538
1.00
12.65
A

N

ATOM
538
CA
LEU A
104
10.952
18.330
−0.824
1.00
14.40
A

C

ATOM
539
CB
LEU A
104
11.785
18.113
0.441
1.00
14.50
A

C

ATOM
540
CG
LEU A
104
12.438
19.396
0.972
1.00
14.36
A

C

ATOM
541
CD1
LEU A
104
13.126
19.115
2.295
1.00
15.72
A

C

ATOM
542
CD2
LEU A
104
13.441
19.928
−0.050
1.00
14.39
A

C

ATOM
543
C
LEU A
104
10.544
16.989
−1.415
1.00
15.37
A

C

ATOM
544
O
LEU A
104
11.215
16.480
−2.313
1.00
12.81
A

O

ATOM
545
N
PHE A
105
9.467
16.399
−0.916
1.00
15.46
A

N

ATOM
546
CA
PHE A
105
9.054
15.115
−1.466
1.00
17.77
A

C

ATOM
547
CB
PHE A
105
7.926
14.508
−0.621
1.00
18.57
A

C

ATOM
548
CG
PHE A
105
8.400
13.952
0.706
1.00
20.35
A

C

ATOM
549
CD1
PHE A
105
9.750
14.016
1.066
1.00
22.06
A

C

ATOM
550
CD2
PHE A
105
7.505
13.366
1.590
1.00
21.24
A

C

ATOM
551
CE1
PHE A
105
10.193
13.501
2.288
1.00
22.72
A

C

ATOM
552
CE2
PHE A
105
7.935
12.847
2.817
1.00
21.30
A

C

ATOM
553
CZ
PHE A
105
9.280
12.914
3.168
1.00
24.04
A

C

ATOM
554
C
PHE A
105
8.658
15.282
−2.935
1.00
17.82
A

C

ATOM
555
O
PHE A
105
9.150
14.549
−3.798
1.00
17.32
A

O

ATOM
556
N
PRO A
106
7.788
16.263
−3.244
1.00
19.25
A

N

ATOM
557
CD
PRO A
106
6.995
17.100
−2.323
1.00
18.44
A

C

ATOM
558
CA
PRO A
106
7.372
16.487
−4.634
1.00
19.95
A

C

ATOM
559
CB
PRO A
106
6.417
17.672
−4.521
1.00
20.31
A

C

ATOM
560
CG
PRO A
106
5.806
17.480
−3.174
1.00
19.88
A

C

ATOM
561
C
PRO A
106
8.563
16.800
−5.541
1.00
20.82
A

C

ATOM
562
O
PRO A
106
8.553
16.483
−6.734
1.00
19.57
A

O

ATOM
563
N
GLN A
107
9.593
17.417
−4.964
1.00
21.36
A

N

ATOM
564
CA
GLN A
107
10.791
17.800
−5.714
1.00
21.96
A

C

ATOM
565
CB
GLN A
107
11.198
19.233
−5.335
1.00
22.81
A

C

ATOM
566
CG
GLN A
107
10.156
20.298
−5.638
1.00
24.02
A

C

ATOM
567
CD
GLN A
107
10.184
20.735
−7.086
1.00
27.15
A

C

ATOM
568
OE1
GLN A
107
9.302
21.459
−7.547
1.00
28.19
A

O

ATOM
569
NE2
GLN A
107
11.211
20.306
−7.811
1.00
27.09
A

N

ATOM
570
C
GLN A
107
11.968
16.872
−5.438
1.00
22.05
A

C

ATOM
571
O
GLN A
107
13.090
17.145
−5.871
1.00
21.11
A

O

ATOM
572
N
SER A
108
11.709
15.773
−4.734
1.00
22.40
A

N

ATOM
573
CA
SER A
108
12.756
14.829
−4.342
1.00
24.12
A

C

ATOM
574
CB
SER A
108
12.142
13.665
−3.559
1.00
21.76
A

C

ATOM
575
OG
SER A
108
11.263
12.909
−4.370
1.00
25.11
A

O

ATOM
576
C
SER A
108
13.667
14.276
−5.434
1.00
25.68
A

C

ATOM
577
O
SER A
108
14.823
13.942
−5.168
1.00
25.48
A

O

ATOM
578
N
ASP A
109
13.165
14.179
−6.658
1.00
28.58
A

N

ATOM
579
CA
ASP A
109
13.976
13.654
−7.750
1.00
29.53
A

C

ATOM
580
CB
ASP A
109
13.131
12.719
−8.623
1.00
31.30
A

C

ATOM
581
CG
ASP A
109
11.897
13.398
−9.189
1.00
33.47
A

C

ATOM
582
OD1
ASP A
109
11.371
14.328
−8.542
1.00
33.88
A

O

ATOM
583
OD2
ASP A
109
11.443
12.987
−10.278
1.00
33.45
A

O

ATOM
584
C
ASP A
109
14.587
14.765
−8.593
1.00
30.64
A

C

ATOM
585
O
ASP A
109
15.058
14.527
−9.706
1.00
32.81
A

O

ATOM
586
N
ARG A
110
14.592
15.979
−8.050
1.00
29.79
A

N

ATOM
587
CA
ARG A
110
15.145
17.134
−8.748
1.00
28.46
A

C

ATOM
588
CB
ARG A
110
14.107
18.251
−8.819
1.00
31.87
A

C

ATOM
589
CG
ARG A
110
14.497
19.382
−9.753
1.00
37.18
A

C

ATOM
590
CD
ARG A
110
13.655
19.374
−11.020
1.00
41.24
A

C

ATOM
591
NE
ARG A
110
12.340
19.974
−10.803
1.00
43.98
A

N

ATOM
592
CZ
ARG A
110
12.146
21.255
−10.497
1.00
44.48
A

C

ATOM
593
NH1
ARG A
110
13.180
22.074
−10.373
1.00
44.65
A

N

ATOM
594
NH2
ARG A
110
10.916
21.718
−10.315
1.00
45.63
A

N

ATOM
595
C
ARG A
110
16.384
17.629
−8.008
1.00
25.45
A

C

ATOM
596
O
ARG A
110
16.715
17.118
−6.942
1.00
25.04
A

O

ATOM
597
N
PHE A
111
17.070
18.616
−8.576
1.00
22.98
A

N

ATOM
598
CA
PHE A
111
18.278
19.163
−7.965
1.00
22.26
A

C

ATOM
599
CB
PHE A
111
17.900
20.022
−6.749
1.00
21.90
A

C

ATOM
600
CG
PHE A
111
17.148
21.274
−7.111
1.00
18.30
A

C

ATOM
601
CD1
PHE A
111
17.795
22.325
−7.747
1.00
20.61
A

C

ATOM
602
CD2
PHE A
111
15.793
21.381
−6.866
1.00
19.71
A

C

ATOM
603
CE1
PHE A
111
17.101
23.461
−8.135
1.00
20.07
A

C

ATOM
604
CE2
PHE A
111
15.085
22.520
−7.254
1.00
20.77
A

C

ATOM
605
CZ
PHE A
111
15.742
23.557
−7.890
1.00
22.06
A

C

ATOM
606
C
PHE A
111
19.281
18.070
−7.561
1.00
23.53
A

C

ATOM
607
O
PHE A
111
19.819
18.082
−6.453
1.00
21.50
A

O

ATOM
608
N
GLN A
112
19.528
17.125
−8.468
1.00
24.20
A

N

ATOM
609
CA
GLN A
112
20.486
16.042
−8.215
1.00
24.96
A

C

ATOM
610
CB
GLN A
112
20.397
14.962
−9.304
1.00
27.91
A

C

ATOM
611
CG
GLN A
112
19.033
14.309
−9.375
1.00
32.20
A

C

ATOM
612
CD
GLN A
112
18.866
13.316
−10.503
1.00
36.00
A

C

ATOM
613
OE1
GLN A
112
17.772
12.806
−10.719
1.00
37.02
A

O

ATOM
614
NE2
GLN A
112
19.946
13.033
−11.225
1.00
37.13
A

N

ATOM
615
C
GLN A
112
21.897
16.630
−8.196
1.00
26.21
A

C

ATOM
616
O
GLN A
112
22.184
17.597
−8.908
1.00
27.42
A

O

ATOM
617
N
PRO A
113
22.806
16.047
−7.392
1.00
25.53
A

N

ATOM
618
CD
PRO A
113
24.251
16.272
−7.577
1.00
25.70
A

C

ATOM
619
CA
PRO A
113
22.577
14.900
−6.506
1.00
25.89
A

C

ATOM
620
CB
PRO A
113
23.853
14.098
−6.695
1.00
26.16
A

C

ATOM
621
CG
PRO A
113
24.876
15.203
−6.687
1.00
25.44
A

C

ATOM
622
C
PRO A
113
22.385
15.287
−5.032
1.00
25.87
A

C

ATOM
623
O
PRO A
113
22.095
14.434
−4.195
1.00
25.05
A

O

ATOM
624
N
TYR A
114
22.541
16.571
−4.717
1.00
26.68
A

N

ATOM
625
CA
TYR A
114
22.430
17.029
−3.331
1.00
27.34
A

C

ATOM
626
CB
TYR A
114
22.838
18.510
−3.228
1.00
30.74
A

C

ATOM
627
CG
TYR A
114
24.167
18.813
−3.898
1.00
33.96
A

C

ATOM
628
CD1
TYR A
114
25.228
17.916
−3.804
1.00
36.01
A

C

ATOM
629
CE1
TYR A
114
26.435
18.161
−4.438
1.00
38.72
A

C

ATOM
630
CD2
TYR A
114
24.354
19.979
−4.648
1.00
35.86
A

C

ATOM
631
CE2
TYR A
114
25.568
20.238
−5.290
1.00
37.49
A

C

ATOM
632
CZ
TYR A
114
26.601
19.321
−5.178
1.00
39.49
A

C

ATOM
633
OH
TYR A
114
27.809
19.560
−5.789
1.00
40.81
A

O

ATOM
634
C
TYR A
114
21.069
16.810
−2.677
1.00
26.15
A

C

ATOM
635
O
TYR A
114
20.987
16.549
−1.476
1.00
24.90
A

O

ATOM
636
N
MET A
115
20.006
16.906
−3.467
1.00
25.38
A

N

ATOM
637
CA
MET A
115
18.662
16.721
−2.948
1.00
24.05
A

C

ATOM
638
CB
MET A
115
17.646
16.865
−4.084
1.00
24.96
A

C

ATOM
639
CG
MET A
115
16.206
16.603
−3.708
1.00
24.12
A

C

ATOM
640
SD
MET A
115
15.563
17.820
−2.574
1.00
23.41
A

S

ATOM
641
CE
MET A
115
15.122
19.162
−3.708
1.00
23.60
A

C

ATOM
642
C
MET A
115
18.535
15.348
−2.300
1.00
24.70
A

C

ATOM
643
O
MET A
115
17.980
15.225
−1.218
1.00
22.93
A

O

ATOM
644
N
GLN A
116
19.085
14.327
−2.951
1.00
23.45
A

N

ATOM
645
CA
GLN A
116
19.005
12.962
−2.453
1.00
23.38
A

C

ATOM
646
CB
GLN A
116
19.439
12.001
−3.561
1.00
25.27
A

C

ATOM
647
CG
GLN A
116
18.491
12.034
−4.765
1.00
28.21
A

C

ATOM
648
CD
GLN A
116
18.550
13.344
−5.550
1.00
29.58
A

C

ATOM
649
OE1
GLN A
116
17.549
13.786
−6.116
1.00
32.33
A

O

ATOM
650
NE2
GLN A
116
19.727
13.956
−5.600
1.00
27.60
A

N

ATOM
651
C
GLN A
116
19.766
12.683
−1.160
1.00
21.18
A

C

ATOM
652
O
GLN A
116
19.570
11.650
−0.527
1.00
21.75
A

O

ATOM
653
N
GLU A
117
20.632
13.603
−0.761
1.00
19.23
A

N

ATOM
654
CA
GLU A
117
21.383
13.426
0.472
1.00
18.78
A

C

ATOM
655
CB
GLU A
117
22.834
13.851
0.272
1.00
22.01
A

C

ATOM
656
CG
GLU A
117
23.574
13.015
−0.751
1.00
26.21
A

C

ATOM
657
CD
GLU A
117
25.011
13.446
−0.915
1.00
28.09
A

C

ATOM
658
OE1
GLU A
117
25.245
14.584
−1.373
1.00
31.04
A

O

ATOM
659
OE2
GLU A
117
25.907
12.643
−0.583
1.00
29.29
A

O

ATOM
660
C
GLU A
117
20.765
14.252
1.592
1.00
15.64
A

C

ATOM
661
O
GLU A
117
20.748
13.834
2.742
1.00
12.05
A

O

ATOM
662
N
VAL A
118
20.247
15.423
1.233
1.00
12.54
A

N

ATOM
663
CA
VAL A
118
19.643
16.340
2.190
1.00
10.94
A

C

ATOM
664
CB
VAL A
118
19.521
17.752
1.571
1.00
13.38
A

C

ATOM
665
CG1
VAL A
118
18.818
18.689
2.529
1.00
11.25
A

C

ATOM
666
CG2
VAL A
118
20.913
18.285
1.227
1.00
11.27
A

C

ATOM
667
C
VAL A
118
18.266
15.887
2.686
1.00
12.41
A

C

ATOM
668
O
VAL A
118
17.971
15.999
3.872
1.00
12.25
A

O

ATOM
669
N
VAL A
119
17.427
15.372
1.793
1.00
11.42
A

N

ATOM
670
CA
VAL A
119
16.097
14.942
2.208
1.00
13.06
A

C

ATOM
671
CB
VAL A
119
15.275
14.419
1.007
1.00
14.89
A

C

ATOM
672
CG1
VAL A
119
14.001
13.738
1.495
1.00
13.96
A

C

ATOM
673
CG2
VAL A
119
14.937
15.586
0.072
1.00
12.52
A

C

ATOM
674
C
VAL A
119
16.123
13.902
3.337
1.00
12.86
A

C

ATOM
675
O
VAL A
119
15.425
14.069
4.335
1.00
13.99
A

O

ATOM
676
N
PRO A
120
16.933
12.832
3.208
1.00
13.22
A

N

ATOM
677
CD
PRO A
120
17.731
12.385
2.052
1.00
13.49
A

C

ATOM
678
CA
PRO A
120
16.979
11.825
4.274
1.00
13.95
A

C

ATOM
679
CB
PRO A
120
17.979
10.798
3.743
1.00
13.50
A

C

ATOM
680
CG
PRO A
120
17.776
10.882
2.264
1.00
16.77
A

C

ATOM
681
C
PRO A
120
17.427
12.439
5.590
1.00
13.93
A

C

ATOM
682
O
PRO A
120
16.951
12.058
6.652
1.00
13.50
A

O

ATOM
683
N
PHE A
121
18.357
13.385
5.508
1.00
11.40
A

N

ATOM
684
CA
PHE A
121
18.860
14.078
6.692
1.00
11.01
A

C

ATOM
685
CB
PHE A
121
19.978
15.048
6.270
1.00
10.39
A

C

ATOM
686
CG
PHE A
121
20.327
16.085
7.309
1.00
12.29
A

C

ATOM
687
CD1
PHE A
121
20.796
15.713
8.561
1.00
10.86
A

C

ATOM
688
CD2
PHE A
121
20.220
17.440
7.011
1.00
12.84
A

C

ATOM
689
CE1
PHE A
121
21.153
16.678
9.506
1.00
11.52
A

C

ATOM
690
CE2
PHE A
121
20.573
18.416
7.951
1.00
13.64
A

C

ATOM
691
CZ
PHE A
121
21.042
18.034
9.195
1.00
11.27
A

C

ATOM
692
C
PHE A
121
17.715
14.837
7.383
1.00
9.92
A

C

ATOM
693
O
PHE A
121
17.474
14.658
8.575
1.00
10.41
A

O

ATOM
694
N
LEU A
122
17.003
15.673
6.631
1.00
8.04
A

N

ATOM
695
CA
LEU A
122
15.895
16.445
7.202
1.00
9.54
A

C

ATOM
696
CB
LEU A
122
15.364
17.439
6.167
1.00
9.32
A

C

ATOM
697
CG
LEU A
122
16.417
18.482
5.780
1.00
10.24
A

C

ATOM
698
CD1
LEU A
122
15.888
19.366
4.658
1.00
12.89
A

C

ATOM
699
CD2
LEU A
122
16.779
19.325
6.997
1.00
10.42
A

C

ATOM
700
C
LEU A
122
14.765
15.551
7.714
1.00
9.19
A

C

ATOM
701
O
LEU A
122
14.133
15.853
8.729
1.00
11.17
A

O

ATOM
702
N
ALA A
123
14.508
14.454
7.012
1.00
10.07
A

N

ATOM
703
CA
ALA A
123
13.473
13.518
7.432
1.00
11.76
A

C

ATOM
704
CB
ALA A
123
13.307
12.415
6.385
1.00
11.58
A

C

ATOM
705
C
ALA A
123
13.844
12.901
8.785
1.00
12.42
A

C

ATOM
706
O
ALA A
123
12.972
12.651
9.629
1.00
10.87
A

O

ATOM
707
N
ARG A
124
15.129
12.637
8.996
1.00
13.52
A

N

ATOM
708
CA
ARG A
124
15.537
12.057
10.268
1.00
15.12
A

C

ATOM
709
CB
ARG A
124
16.998
11.599
10.230
1.00
16.39
A

C

ATOM
710
CG
ARG A
124
17.222
10.361
9.361
1.00
18.81
A

C

ATOM
711
CD
ARG A
124
18.514
9.644
9.730
1.00
19.88
A

C

ATOM
712
NE
ARG A
124
19.684
10.503
9.592
1.00
21.22
A

N

ATOM
713
CZ
ARG A
124
20.241
10.818
8.429
1.00
21.14
A

C

ATOM
714
NH1
ARG A
124
19.739
10.339
7.300
1.00
21.19
A

N

ATOM
715
NH2
ARG A
124
21.292
11.620
8.398
1.00
21.84
A

N

ATOM
716
C
ARG A
124
15.319
13.052
11.396
1.00
14.67
A

C

ATOM
717
O
ARG A
124
14.968
12.666
12.509
1.00
14.02
A

O

ATOM
718
N
LEU A
125
15.512
14.336
11.113
1.00
12.38
A

N

ATOM
719
CA
LEU A
125
15.305
15.348
12.142
1.00
12.66
A

C

ATOM
720
CB
LEU A
125
15.757
16.724
11.655
1.00
11.19
A

C

ATOM
721
CG
LEU A
125
17.257
16.863
11.400
1.00
12.07
A

C

ATOM
722
CD1
LEU A
125
17.571
18.262
10.880
1.00
11.21
A

C

ATOM
723
CD2
LEU A
125
18.015
16.567
12.691
1.00
10.90
A

C

ATOM
724
C
LEU A
125
13.824
15.384
12.457
1.00
12.64
A

C

ATOM
725
O
LEU A
125
13.424
15.502
13.615
1.00
13.64
A

O

ATOM
726
N
SER A
126
13.010
15.289
11.412
1.00
11.87
A

N

ATOM
727
CA
SER A
126
11.567
15.301
11.584
1.00
12.10
A

C

ATOM
728
CB
SER A
126
10.869
15.199
10.219
1.00
12.32
A

C

ATOM
729
OG
SER A
126
9.511
14.794
10.350
1.00
12.93
A

O

ATOM
730
C
SER A
126
11.174
14.124
12.466
1.00
14.19
A

C

ATOM
731
O
SER A
126
10.379
14.267
13.397
1.00
14.24
A

O

ATOM
732
N
ASN A
127
11.751
12.960
12.182
1.00
15.34
A

N

ATOM
733
CA
ASN A
127
11.441
11.761
12.953
1.00
19.77
A

C

ATOM
734
CB
ASN A
127
12.143
10.532
12.363
1.00
22.15
A

C

ATOM
735
CG
ASN A
127
11.687
9.236
13.020
1.00
27.13
A

C

ATOM
736
OD1
ASN A
127
10.492
8.925
13.039
1.00
29.33
A

O

ATOM
737
ND2
ASN A
127
12.634
8.479
13.564
1.00
27.25
A

N

ATOM
738
C
ASN A
127
11.839
11.922
14.416
1.00
19.60
A

C

ATOM
739
O
ASN A
127
11.162
11.412
15.305
1.00
19.90
A

O

ATOM
740
N
ARG A
128
12.934
12.629
14.672
1.00
19.27
A

N

ATOM
741
CA
ARG A
128
13.396
12.855
16.043
1.00
20.04
A

C

ATOM
742
CB
ARG A
128
14.783
13.534
15.992
1.00
20.58
A

C

ATOM
743
CG
ARG A
128
15.659
13.507
17.262
1.00
24.13
A

C

ATOM
744
CD
ARG A
128
15.120
14.392
18.371
1.00
27.44
A

C

ATOM
745
NE
ARG A
128
16.165
14.909
19.249
1.00
27.58
A

N

ATOM
746
CZ
ARG A
128
15.991
15.179
20.539
1.00
29.81
A

C

ATOM
747
NH1
ARG A
128
14.809
14.970
21.107
1.00
29.81
A

N

ATOM
748
NH2
ARG A
128
16.991
15.671
21.256
1.00
27.09
A

N

ATOM
749
C
ARG A
128
12.373
13.743
16.788
1.00
20.54
A

C

ATOM
750
O
ARG A
128
12.069
13.519
17.967
1.00
18.67
A

O

ATOM
751
N
LEU A
129
11.850
14.753
16.098
1.00
19.98
A

N

ATOM
752
CA
LEU A
129
10.876
15.669
16.695
1.00
21.90
A

C

ATOM
753
CB
LEU A
129
10.813
16.965
15.886
1.00
19.92
A

C

ATOM
754
CG
LEU A
129
12.044
17.872
15.908
1.00
19.27
A

C

ATOM
755
CD1
LEU A
129
11.925
18.930
14.824
1.00
19.33
A

C

ATOM
756
CD2
LEU A
129
12.188
18.504
17.287
1.00
16.10
A

C

ATOM
757
C
LEU A
129
9.474
15.075
16.750
1.00
25.34
A

C

ATOM
758
O
LEU A
129
8.592
15.579
17.452
1.00
25.92
A

O

ATOM
759
N
SER A
130
9.270
14.007
15.994
1.00
28.06
A

N

ATOM
760
CA
SER A
130
7.969
13.364
15.910
1.00
33.42
A

C

ATOM
761
CB
SER A
130
8.095
11.979
15.288
1.00
32.53
A

C

ATOM
762
OG
SER A
130
8.750
11.096
16.177
1.00
35.12
A

O

ATOM
763
C
SER A
130
7.200
13.233
17.210
1.00
36.11
A

C

ATOM
764
O
SER A
130
7.681
12.658
18.190
1.00
38.33
A

O

ATOM
765
N
THR A
131
5.993
13.785
17.200
1.00
39.23
A

N

ATOM
766
CA
THR A
131
5.098
13.700
18.340
1.00
42.38
A

C

ATOM
767
CB
THR A
131
4.968
12.214
18.733
1.00
44.32
A

C

ATOM
768
OG1
THR A
131
4.843
11.445
17.527
1.00
47.57
A

O

ATOM
769
CG2
THR A
131
3.725
11.944
19.561
1.00
45.19
A

C

ATOM
770
C
THR A
131
5.448
14.576
19.558
1.00
42.64
A

C

ATOM
771
O
THR A
131
4.710
14.560
20.551
1.00
43.84
A

O

ATOM
772
N
CYS A
132
6.559
15.325
19.496
1.00
41.52
A

N

ATOM
773
CA
CYS A
132
6.930
16.219
20.603
1.00
39.84
A

C

ATOM
774
C
CYS A
132
5.899
17.299
20.541
1.00
40.10
A

C

ATOM
775
O
CYS A
132
5.358
17.570
19.471
1.00
40.22
A

O

ATOM
776
CB
CYS A
132
8.309
16.869
20.413
1.00
36.93
A

C

ATOM
777
SG
CYS A
132
8.480
18.000
18.999
1.00
32.53
A

S

ATOM
778
N
HIS A
133
5.624
17.927
21.673
1.00
40.74
A

N

ATOM
779
CA
HIS A
133
4.629
18.979
21.689
1.00
41.87
A

C

ATOM
780
CB
HIS A
133
3.251
18.373
21.933
1.00
44.51
A

C

ATOM
781
CG
HIS A
133
3.122
17.694
23.260
1.00
47.49
A

C

ATOM
782
CD2
HIS A
133
2.913
16.396
23.583
1.00
48.42
A

C

ATOM
783
ND1
HIS A
133
3.241
18.371
24.455
1.00
48.25
A

N

ATOM
784
CE1
HIS A
133
3.114
17.518
25.457
1.00
48.41
A

C

ATOM
785
NE2
HIS A
133
2.915
16.313
24.955
1.00
48.80
A

N

ATOM
786
C
HIS A
133
4.916
20.023
22.750
1.00
41.49
A

C

ATOM
787
O
HIS A
133
5.897
19.924
23.488
1.00
40.33
A

O

ATOM
788
N
ILE A
134
4.050
21.030
22.811
1.00
41.32
A

N

ATOM
789
CA
ILE A
134
4.176
22.099
23.794
1.00
42.67
A

C

ATOM
790
CB
ILE A
134
4.176
23.493
23.120
1.00
42.74
A

C

ATOM
791
CG2
ILE A
134
5.446
23.663
22.301
1.00
42.04
A

C

ATOM
792
CG1
ILE A
134
2.918
23.649
22.255
1.00
41.70
A

C

ATOM
793
CD
ILE A
134
2.780
24.957
21.499
1.00
41.81
A

C

ATOM
794
C
ILE A
134
3.000
21.999
24.763
1.00
43.64
A

C

ATOM
795
O
ILE A
134
1.906
21.571
24.387
1.00
43.52
A

O

ATOM
796
N
GLU A
135
3.229
22.391
26.011
1.00
44.33
A

N

ATOM
797
CA
GLU A
135
2.189
22.319
27.031
1.00
45.59
A

C

ATOM
798
CB
GLU A
135
2.832
22.272
28.431
1.00
47.61
A

C

ATOM
799
CG
GLU A
135
3.765
23.448
28.742
1.00
50.52
A

C

ATOM
800
CD
GLU A
135
4.589
23.260
30.002
1.00
51.87
A

C

ATOM
801
OE1
GLU A
135
5.538
22.454
29.942
1.00
51.72
A

O

ATOM
802
OE2
GLU A
135
4.301
23.912
31.037
1.00
52.55
A

O

ATOM
803
C
GLU A
135
1.191
23.474
26.938
1.00
45.27
A

C

ATOM
804
O
GLU A
135
0.204
23.512
27.674
1.00
45.54
A

O

ATOM
805
N
GLY A
136
1.447
24.415
26.033
1.00
44.63
A

N

ATOM
806
CA
GLY A
136
0.557
25.553
25.878
1.00
43.02
A

C

ATOM
807
C
GLY A
136
−0.268
25.466
24.612
1.00
42.19
A

C

ATOM
808
O
GLY A
136
−0.205
24.469
23.894
1.00
42.03
A

O

ATOM
809
N
ASP A
137
−1.048
26.507
24.341
1.00
41.98
A

N

ATOM
810
CA
ASP A
137
−1.881
26.544
23.146
1.00
41.03
A

C

ATOM
811
CB
ASP A
137
−2.996
27.576
23.310
1.00
43.41
A

C

ATOM
812
CG
ASP A
137
−3.844
27.710
22.064
1.00
45.06
A

C

ATOM
813
OD1
ASP A
137
−4.458
26.704
21.647
1.00
47.37
A

O

ATOM
814
OD2
ASP A
137
−3.892
28.821
21.499
1.00
45.71
A

O

ATOM
815
C
ASP A
137
−1.016
26.908
21.944
1.00
39.51
A

C

ATOM
816
O
ASP A
137
−0.162
27.783
22.036
1.00
39.46
A

O

ATOM
817
N
ASP A
138
−1.241
26.244
20.814
1.00
38.39
A

N

ATOM
818
CA
ASP A
138
−0.439
26.511
19.621
1.00
37.99
A

C

ATOM
819
CB
ASP A
138
0.168
25.208
19.102
1.00
39.01
A

C

ATOM
820
CG
ASP A
138
−0.874
24.264
18.548
1.00
39.32
A

C

ATOM
821
OD1
ASP A
138
−2.070
24.475
18.826
1.00
39.65
A

O

ATOM
822
OD2
ASP A
138
−0.500
23.307
17.842
1.00
41.75
A

O

ATOM
823
C
ASP A
138
−1.219
27.186
18.501
1.00
36.81
A

C

ATOM
824
O
ASP A
138
−0.832
27.116
17.335
1.00
35.87
A

O

ATOM
825
N
LEU A
139
−2.315
27.849
18.857
1.00
34.57
A

N

ATOM
826
CA
LEU A
139
−3.139
28.532
17.870
1.00
33.64
A

C

ATOM
827
CB
LEU A
139
−4.321
29.219
18.563
1.00
34.78
A

C

ATOM
828
CG
LEU A
139
−5.618
29.352
17.757
1.00
36.95
A

C

ATOM
829
CD1
LEU A
139
−6.663
30.071
18.602
1.00
36.17
A

C

ATOM
830
CD2
LEU A
139
−5.364
30.112
16.464
1.00
36.43
A

C

ATOM
831
C
LEU A
139
−2.326
29.561
17.079
1.00
31.14
A

C

ATOM
832
O
LEU A
139
−2.461
29.666
15.862
1.00
30.79
A

O

ATOM
833
N
HIS A
140
−1.483
30.318
17.769
1.00
29.61
A

N

ATOM
834
CA
HIS A
140
−0.671
31.329
17.103
1.00
29.77
A

C

ATOM
835
CB
HIS A
140
0.039
32.210
18.138
1.00
32.63
A

C

ATOM
836
CG
HIS A
140
0.926
31.453
19.078
1.00
35.82
A

C

ATOM
837
CD2
HIS A
140
2.183
31.706
19.515
1.00
36.65
A

C

ATOM
838
ND1
HIS A
140
0.524
30.297
19.713
1.00
37.28
A

N

ATOM
839
CE1
HIS A
140
1.496
29.870
20.500
1.00
38.18
A

C

ATOM
840
NE2
HIS A
140
2.514
30.707
20.399
1.00
36.65
A

N

ATOM
841
C
HIS A
140
0.342
30.664
16.180
1.00
28.45
A

C

ATOM
842
O
HIS A
140
0.639
31.171
15.102
1.00
28.05
A

O

ATOM
843
N
ILE A
141
0.857
29.514
16.597
1.00
27.82
A

N

ATOM
844
CA
ILE A
141
1.825
28.784
15.790
1.00
26.79
A

C

ATOM
845
CB
ILE A
141
2.424
27.616
16.595
1.00
26.52
A

C

ATOM
846
CG2
ILE A
141
3.057
26.598
15.667
1.00
24.81
A

C

ATOM
847
CG1
ILE A
141
3.434
28.174
17.605
1.00
26.50
A

C

ATOM
848
CD
ILE A
141
3.981
27.146
18.563
1.00
28.45
A

C

ATOM
849
C
ILE A
141
1.168
28.269
14.516
1.00
27.29
A

C

ATOM
850
O
ILE A
141
1.749
28.344
13.434
1.00
26.99
A

O

ATOM
851
N
GLN A
142
−0.053
27.760
14.647
1.00
28.53
A

N

ATOM
852
CA
GLN A
142
−0.788
27.249
13.497
1.00
27.65
A

C

ATOM
853
CB
GLN A
142
−2.128
26.667
13.940
1.00
29.20
A

C

ATOM
854
CG
GLN A
142
−2.026
25.340
14.674
1.00
32.99
A

C

ATOM
855
CD
GLN A
142
−3.388
24.786
15.049
1.00
35.51
A

C

ATOM
856
OE1
GLN A
142
−4.111
25.378
15.850
1.00
40.18
A

O

ATOM
857
NE2
GLN A
142
−3.748
23.651
14.464
1.00
36.87
A

N

ATOM
858
C
GLN A
142
−1.025
28.354
12.473
1.00
26.74
A

C

ATOM
859
O
GLN A
142
−0.895
28.132
11.272
1.00
26.24
A

O

ATOM
860
N
ARG A
143
−1.376
29.542
12.953
1.00
27.29
A

N

ATOM
861
CA
ARG A
143
−1.622
30.679
12.071
1.00
27.82
A

C

ATOM
862
CB
ARG A
143
−2.106
31.886
12.878
1.00
29.63
A

C

ATOM
863
CG
ARG A
143
−3.526
31.758
13.405
1.00
34.47
A

C

ATOM
864
CD
ARG A
143
−3.788
32.781
14.507
1.00
39.86
A

C

ATOM
865
NE
ARG A
143
−5.170
32.741
14.977
1.00
44.13
A

N

ATOM
866
CZ
ARG A
143
−5.575
33.213
16.152
1.00
46.89
A

C

ATOM
867
NH1
ARG A
143
−4.701
33.762
16.987
1.00
47.65
A

N

ATOM
868
NH2
ARG A
143
−6.856
33.132
16.493
1.00
48.27
A

N

ATOM
869
C
ARG A
143
−0.363
31.064
11.301
1.00
26.24
A

C

ATOM
870
O
ARG A
143
−0.410
31.289
10.094
1.00
24.10
A

O

ATOM
871
N
ASN A
144
0.761
31.136
12.004
1.00
25.57
A

N

ATOM
872
CA
ASN A
144
2.024
31.511
11.377
1.00
25.34
A

C

ATOM
873
CB
ASN A
144
3.113
31.670
12.442
1.00
25.23
A

C

ATOM
874
CG
ASN A
144
2.901
32.901
13.310
1.00
27.47
A

C

ATOM
875
OD1
ASN A
144
1.855
33.552
13.238
1.00
25.19
A

O

ATOM
876
ND2
ASN A
144
3.894
33.225
14.137
1.00
26.15
A

N

ATOM
877
C
ASN A
144
2.460
30.508
10.319
1.00
24.78
A

C

ATOM
878
O
ASN A
144
2.963
30.896
9.259
1.00
24.90
A

O

ATOM
879
N
VAL A
145
2.262
29.222
10.599
1.00
23.95
A

N

ATOM
880
CA
VAL A
145
2.638
28.177
9.650
1.00
22.12
A

C

ATOM
881
CB
VAL A
145
2.578
26.771
10.298
1.00
22.24
A

C

ATOM
882
CG1
VAL A
145
2.893
25.703
9.265
1.00
22.51
A

C

ATOM
883
CG2
VAL A
145
3.571
26.688
11.442
1.00
19.36
A

C

ATOM
884
C
VAL A
145
1.705
28.219
8.445
1.00
23.02
A

C

ATOM
885
O
VAL A
145
2.143
28.075
7.304
1.00
20.64
A

O

ATOM
886
N
GLN A
146
0.417
28.430
8.703
1.00
24.15
A

N

ATOM
887
CA
GLN A
146
−0.566
28.491
7.630
1.00
23.03
A

C

ATOM
888
CB
GLN A
146
−1.962
28.746
8.197
1.00
25.85
A

C

ATOM
889
CG
GLN A
146
−3.056
28.631
7.153
1.00
27.55
A

C

ATOM
890
CD
GLN A
146
−3.028
27.291
6.443
1.00
27.72
A

C

ATOM
891
OE1
GLN A
146
−2.920
27.228
5.221
1.00
28.53
A

O

ATOM
892
NE2
GLN A
146
−3.125
26.210
7.210
1.00
29.98
A

N

ATOM
893
C
GLN A
146
−0.227
29.586
6.625
1.00
23.12
A

C

ATOM
894
O
GLN A
146
−0.409
29.411
5.422
1.00
22.07
A

O

ATOM
895
N
LYS A
147
0.253
30.720
7.120
1.00
21.60
A

N

ATOM
896
CA
LYS A
147
0.609
31.826
6.242
1.00
23.99
A

C

ATOM
897
CB
LYS A
147
0.982
33.069
7.054
1.00
27.26
A

C

ATOM
898
CG
LYS A
147
1.356
34.266
6.183
1.00
33.40
A

C

ATOM
899
CD
LYS A
147
0.223
34.614
5.211
1.00
37.04
A

C

ATOM
900
CE
LYS A
147
0.599
35.760
4.278
1.00
38.65
A

C

ATOM
901
NZ
LYS A
147
0.882
37.019
5.027
1.00
40.65
A

N

ATOM
902
C
LYS A
147
1.778
31.441
5.349
1.00
24.34
A

C

ATOM
903
O
LYS A
147
1.860
31.861
4.193
1.00
21.81
A

O

ATOM
904
N
LEU A
148
2.696
30.650
5.894
1.00
23.83
A

N

ATOM
905
CA
LEU A
148
3.844
30.216
5.120
1.00
23.73
A

C

ATOM
906
CB
LEU A
148
4.864
29.516
6.029
1.00
24.60
A

C

ATOM
907
CG
LEU A
148
6.213
29.108
5.425
1.00
25.23
A

C

ATOM
908
CD1
LEU A
148
7.213
28.802
6.539
1.00
27.40
A

C

ATOM
909
CD2
LEU A
148
6.023
27.897
4.535
1.00
25.60
A

C

ATOM
910
C
LEU A
148
3.315
29.272
4.043
1.00
21.03
A

C

ATOM
911
O
LEU A
148
3.706
29.364
2.885
1.00
22.18
A

O

ATOM
912
N
LYS A
149
2.411
28.376
4.422
1.00
21.82
A

N

ATOM
913
CA
LYS A
149
1.834
27.439
3.461
1.00
22.95
A

C

ATOM
914
CB
LYS A
149
0.852
26.495
4.148
1.00
24.40
A

C

ATOM
915
CG
LYS A
149
1.462
25.605
5.209
1.00
26.03
A

C

ATOM
916
CD
LYS A
149
0.433
24.591
5.683
1.00
29.36
A

C

ATOM
917
CE
LYS A
149
1.026
23.603
6.667
1.00
31.50
A

C

ATOM
918
NZ
LYS A
149
0.039
22.535
7.000
1.00
33.82
A

N

ATOM
919
C
LYS A
149
1.098
28.204
2.366
1.00
23.21
A

C

ATOM
920
O
LYS A
149
1.239
27.899
1.177
1.00
21.94
A

O

ATOM
921
N
ASP A
150
0.319
29.203
2.771
1.00
22.28
A

N

ATOM
922
CA
ASP A
150
−0.441
30.003
1.814
1.00
23.20
A

C

ATOM
923
CB
ASP A
150
−1.303
31.054
2.526
1.00
25.06
A

C

ATOM
924
CG
ASP A
150
−2.359
30.444
3.430
1.00
27.96
A

C

ATOM
925
OD1
ASP A
150
−2.832
29.327
3.140
1.00
29.25
A

O

ATOM
926
OD2
ASP A
150
−2.731
31.100
4.428
1.00
30.84
A

O

ATOM
927
C
ASP A
150
0.487
30.716
0.844
1.00
22.09
A

C

ATOM
928
O
ASP A
150
0.201
30.804
−0.349
1.00
22.07
A

O

ATOM
929
N
THR A
151
1.599
31.228
1.360
1.00
20.13
A

N

ATOM
930
CA
THR A
151
2.557
31.949
0.533
1.00
20.21
A

C

ATOM
931
CB
THR A
151
3.676
32.578
1.390
1.00
21.32
A

C

ATOM
932
OG1
THR A
151
3.097
33.422
2.392
1.00
22.82
A

O

ATOM
933
CG2
THR A
151
4.602
33.410
0.520
1.00
23.30
A

C

ATOM
934
C
THR A
151
3.184
31.045
−0.521
1.00
19.34
A

C

ATOM
935
O
THR A
151
3.403
31.466
−1.659
1.00
16.62
A

O

ATOM
936
N
VAL A
152
3.482
29.809
−0.134
1.00
17.83
A

N

ATOM
937
CA
VAL A
152
4.071
28.849
−1.056
1.00
20.82
A

C

ATOM
938
CB
VAL A
152
4.465
27.545
−0.322
1.00
19.02
A

C

ATOM
939
CG1
VAL A
152
4.739
26.433
−1.323
1.00
21.92
A

C

ATOM
940
CG2
VAL A
152
5.716
27.782
0.507
1.00
20.80
A

C

ATOM
941
C
VAL A
152
3.087
28.535
−2.183
1.00
22.16
A

C

ATOM
942
O
VAL A
152
3.479
28.449
−3.346
1.00
23.43
A

O

ATOM
943
N
LYS A
153
1.810
28.379
−1.843
1.00
24.38
A

N

ATOM
944
CA
LYS A
153
0.789
28.087
−2.849
1.00
27.82
A

C

ATOM
945
CB
LYS A
153
−0.534
27.732
−2.176
1.00
31.58
A

C

ATOM
946
CG
LYS A
153
−0.441
26.583
−1.209
1.00
35.04
A

C

ATOM
947
CD
LYS A
153
−1.778
26.401
−0.548
1.00
40.47
A

C

ATOM
948
CE
LYS A
153
−1.689
25.379
0.560
1.00
43.02
A

C

ATOM
949
NZ
LYS A
153
−2.952
25.190
1.344
1.00
44.36
A

N

ATOM
950
C
LYS A
153
0.585
29.279
−3.784
1.00
29.16
A

C

ATOM
951
O
LYS A
153
0.437
29.108
−4.996
1.00
28.68
A

O

ATOM
952
N
LYS A
154
0.580
30.484
−3.218
1.00
28.50
A

N

ATOM
953
CA
LYS A
154
0.402
31.699
−4.005
1.00
29.69
A

C

ATOM
954
CB
LYS A
154
0.479
32.942
−3.106
1.00
32.52
A

C

ATOM
955
CG
LYS A
154
−0.616
33.048
−2.053
1.00
37.41
A

C

ATOM
956
CD
LYS A
154
−0.339
34.206
−1.095
1.00
40.74
A

C

ATOM
957
CE
LYS A
154
−1.385
34.290
0.009
1.00
42.32
A

C

ATOM
958
NZ
LYS A
154
−1.038
35.319
1.032
1.00
42.89
A

N

ATOM
959
C
LYS A
154
1.496
31.788
−5.064
1.00
28.78
A

C

ATOM
960
O
LYS A
154
1.291
32.351
−6.144
1.00
28.74
A

O

ATOM
961
N
LEU A
155
2.661
31.232
−4.738
1.00
26.21
A

N

ATOM
962
CA
LEU A
155
3.805
31.253
−5.640
1.00
24.24
A

C

ATOM
963
CB
LEU A
155
5.118
31.313
−4.847
1.00
22.63
A

C

ATOM
964
CG
LEU A
155
5.392
32.561
−3.979
1.00
24.03
A

C

ATOM
965
CD1
LEU A
155
6.695
32.374
−3.263
1.00
25.32
A

C

ATOM
966
CD2
LEU A
155
5.518
33.828
−4.793
1.00
23.74
A

C

ATOM
967
C
LEU A
155
3.807
30.058
−6.576
1.00
22.47
A

C

ATOM
968
O
LEU A
155
4.504
30.059
−7.590
1.00
22.33
A

O

ATOM
969
N
GLY A
156
3.009
29.051
−6.240
1.00
23.16
A

N

ATOM
970
CA
GLY A
156
2.927
27.864
−7.068
1.00
22.02
A

C

ATOM
971
C
GLY A
156
4.208
27.063
−7.063
1.00
21.25
A

C

ATOM
972
O
GLY A
156
4.829
26.876
−6.020
1.00
21.24
A

O

ATOM
973
N
GLU A
157
4.604
26.585
−8.236
1.00
20.06
A

N

ATOM
974
CA
GLU A
157
5.816
25.788
−8.371
1.00
21.41
A

C

ATOM
975
CB
GLU A
157
6.055
25.449
−9.849
1.00
23.31
A

C

ATOM
976
CG
GLU A
157
7.319
24.650
−10.107
1.00
28.64
A

C

ATOM
977
CD
GLU A
157
7.147
23.189
−9.770
1.00
31.67
A

C

ATOM
978
OE1
GLU A
157
6.397
22.891
−8.824
1.00
34.33
A

O

ATOM
979
OE2
GLU A
157
7.765
22.334
−10.439
1.00
33.96
A

O

ATOM
980
C
GLU A
157
7.029
26.539
−7.817
1.00
19.72
A

C

ATOM
981
O
GLU A
157
7.860
25.971
−7.105
1.00
19.07
A

O

ATOM
982
N
SER A
158
7.129
27.821
−8.147
1.00
18.69
A

N

ATOM
983
CA
SER A
158
8.249
28.624
−7.680
1.00
19.07
A

C

ATOM
984
CB
SER A
158
8.218
30.006
−8.337
1.00
20.27
A

C

ATOM
985
OG
SER A
158
7.058
30.717
−7.957
1.00
24.37
A

O

ATOM
986
C
SER A
158
8.225
28.761
−6.158
1.00
17.90
A

C

ATOM
987
O
SER A
158
9.214
29.166
−5.549
1.00
16.77
A

O

ATOM
988
N
GLY A
159
7.088
28.433
−5.552
1.00
15.07
A

N

ATOM
989
CA
GLY A
159
6.975
28.500
−4.108
1.00
13.85
A

C

ATOM
990
C
GLY A
159
7.806
27.375
−3.524
1.00
12.96
A

C

ATOM
991
O
GLY A
159
8.496
27.545
−2.521
1.00
11.66
A

O

ATOM
992
N
GLU A
160
7.729
26.215
−4.163
1.00
13.13
A

N

ATOM
993
CA
GLU A
160
8.486
25.046
−3.741
1.00
14.60
A

C

ATOM
994
CB
GLU A
160
8.017
23.820
−4.522
1.00
16.03
A

C

ATOM
995
CG
GLU A
160
6.665
23.291
−4.073
1.00
17.68
A

C

ATOM
996
CD
GLU A
160
6.076
22.326
−5.082
1.00
19.55
A

C

ATOM
997
OE1
GLU A
160
6.849
21.556
−5.687
1.00
19.93
A

O

ATOM
998
OE2
GLU A
160
4.843
22.341
−5.266
1.00
24.36
A

O

ATOM
999
C
GLU A
160
9.972
25.293
−3.988
1.00
13.84
A

C

ATOM
1000
O
GLU A
160
10.819
24.908
−3.180
1.00
13.51
A

O

ATOM
1001
N
ILE A
161
10.278
25.941
−5.109
1.00
13.97
A

N

ATOM
1002
CA
ILE A
161
11.659
26.262
−5.457
1.00
15.01
A

C

ATOM
1003
CB
ILE A
161
11.752
26.949
−6.853
1.00
16.72
A

C

ATOM
1004
CG2
ILE A
161
13.191
27.359
−7.146
1.00
15.56
A

C

ATOM
1005
CG1
ILE A
161
11.225
26.012
−7.947
1.00
16.62
A

C

ATOM
1006
CD
ILE A
161
11.853
24.641
−7.954
1.00
19.54
A

C

ATOM
1007
C
ILE A
161
12.220
27.219
−4.399
1.00
14.73
A

C

ATOM
1008
O
ILE A
161
13.351
27.053
−3.927
1.00
15.29
A

O

ATOM
1009
N
LYS A
162
11.424
28.216
−4.024
1.00
11.62
A

N

ATOM
1010
CA
LYS A
162
11.852
29.185
−3.021
1.00
12.12
A

C

ATOM
1011
CB
LYS A
162
10.787
30.269
−2.829
1.00
12.70
A

C

ATOM
1012
CG
LYS A
162
11.098
31.245
−1.697
1.00
11.50
A

C

ATOM
1013
CD
LYS A
162
10.128
32.416
−1.676
1.00
15.16
A

C

ATOM
1014
CE
LYS A
162
10.361
33.352
−2.853
1.00
15.54
A

C

ATOM
1015
NZ
LYS A
162
11.753
33.881
−2.894
1.00
17.14
A

N

ATOM
1016
C
LYS A
162
12.146
28.503
−1.686
1.00
13.23
A

C

ATOM
1017
O
LYS A
162
13.160
28.792
−1.050
1.00
13.30
A

O

ATOM
1018
N
ALA A
163
11.260
27.603
−1.266
1.00
12.38
A

N

ATOM
1019
CA
ALA A
163
11.438
26.880
−0.009
1.00
12.47
A

C

ATOM
1020
CB
ALA A
163
10.286
25.913
0.211
1.00
12.98
A

C

ATOM
1021
C
ALA A
163
12.756
26.117
−0.011
1.00
13.14
A

C

ATOM
1022
O
ALA A
163
13.452
26.062
1.008
1.00
12.48
A

O

ATOM
1023
N
ILE A
164
13.095
25.516
−1.149
1.00
12.42
A

N

ATOM
1024
CA
ILE A
164
14.346
24.780
−1.260
1.00
11.86
A

C

ATOM
1025
CB
ILE A
164
14.435
23.993
−2.589
1.00
12.07
A

C

ATOM
1026
CG2
ILE A
164
15.731
23.202
−2.635
1.00
10.78
A

C

ATOM
1027
CG1
ILE A
164
13.262
23.017
−2.718
1.00
12.17
A

C

ATOM
1028
CD
ILE A
164
13.278
22.229
−4.022
1.00
12.86
A

C

ATOM
1029
C
ILE A
164
15.491
25.800
−1.204
1.00
12.22
A

C

ATOM
1030
O
ILE A
164
16.541
25.545
−0.610
1.00
11.10
A

O

ATOM
1031
N
GLY A
165
15.281
26.955
−1.826
1.00
10.67
A

N

ATOM
1032
CA
GLY A
165
16.303
27.989
−1.813
1.00
12.02
A

C

ATOM
1033
C
GLY A
165
16.550
28.534
−0.417
1.00
13.62
A

C

ATOM
1034
O
GLY A
165
17.609
29.107
−0.140
1.00
12.29
A

O

ATOM
1035
N
GLU A
166
15.571
28.365
0.468
1.00
12.40
A

N

ATOM
1036
CA
GLU A
166
15.698
28.837
1.846
1.00
13.51
A

C

ATOM
1037
CB
GLU A
166
14.395
29.508
2.309
1.00
13.61
A

C

ATOM
1038
CG
GLU A
166
14.217
30.919
1.757
1.00
16.87
A

C

ATOM
1039
CD
GLU A
166
13.013
31.651
2.334
1.00
18.65
A

C

ATOM
1040
OE1
GLU A
166
12.660
31.392
3.504
1.00
15.68
A

O

ATOM
1041
OE2
GLU A
166
12.435
32.507
1.618
1.00
18.26
A

O

ATOM
1042
C
GLU A
166
16.068
27.720
2.821
1.00
13.52
A

C

ATOM
1043
O
GLU A
166
15.908
27.877
4.028
1.00
12.78
A

O

ATOM
1044
N
LEU A
167
16.563
26.594
2.310
1.00
12.05
A

N

ATOM
1045
CA
LEU A
167
16.937
25.505
3.203
1.00
11.58
A

C

ATOM
1046
CB
LEU A
167
17.366
24.264
2.417
1.00
13.77
A

C

ATOM
1047
CG
LEU A
167
16.223
23.441
1.818
1.00
14.22
A

C

ATOM
1048
CD1
LEU A
167
16.778
22.130
1.246
1.00
16.24
A

C

ATOM
1049
CD2
LEU A
167
15.179
23.155
2.895
1.00
16.98
A

C

ATOM
1050
C
LEU A
167
18.048
25.922
4.158
1.00
12.19
A

C

ATOM
1051
O
LEU A
167
18.206
25.334
5.233
1.00
11.69
A

O

ATOM
1052
N
ASP A
168
18.816
26.937
3.770
1.00
12.76
A

N

ATOM
1053
CA
ASP A
168
19.887
27.419
4.625
1.00
13.15
A

C

ATOM
1054
CB
ASP A
168
20.843
28.342
3.848
1.00
16.25
A

C

ATOM
1055
CG
ASP A
168
20.139
29.497
3.160
1.00
19.91
A

C

ATOM
1056
OD1
ASP A
168
18.915
29.421
2.926
1.00
18.66
A

O

ATOM
1057
OD2
ASP A
168
20.827
30.487
2.832
1.00
20.94
A

O

ATOM
1058
C
ASP A
168
19.279
28.116
5.836
1.00
13.72
A

C

ATOM
1059
O
ASP A
168
19.777
27.975
6.953
1.00
15.78
A

O

ATOM
1060
N
LEU A
169
18.190
28.851
5.622
1.00
13.06
A

N

ATOM
1061
CA
LEU A
169
17.499
29.523
6.717
1.00
13.54
A

C

ATOM
1062
CB
LEU A
169
16.525
30.577
6.173
1.00
14.93
A

C

ATOM
1063
CG
LEU A
169
17.254
31.653
5.365
1.00
16.86
A

C

ATOM
1064
CD1
LEU A
169
16.306
32.688
4.873
1.00
17.37
A

C

ATOM
1065
CD2
LEU A
169
18.260
32.337
6.229
1.00
19.91
A

C

ATOM
1066
C
LEU A
169
16.738
28.499
7.556
1.00
12.68
A

C

ATOM
1067
O
LEU A
169
16.595
28.659
8.770
1.00
13.63
A

O

ATOM
1068
N
LEU A
170
16.251
27.446
6.905
1.00
12.87
A

N

ATOM
1069
CA
LEU A
170
15.526
26.397
7.604
1.00
12.73
A

C

ATOM
1070
CB
LEU A
170
14.937
25.387
6.612
1.00
13.33
A

C

ATOM
1071
CG
LEU A
170
14.185
24.231
7.280
1.00
14.18
A

C

ATOM
1072
CD1
LEU A
170
13.048
24.789
8.111
1.00
15.94
A

C

ATOM
1073
CD2
LEU A
170
13.649
23.275
6.225
1.00
15.77
A

C

ATOM
1074
C
LEU A
170
16.514
25.677
8.506
1.00
11.78
A

C

ATOM
1075
O
LEU A
170
16.230
25.398
9.671
1.00
10.15
A

O

ATOM
1076
N
PHE A
171
17.676
25.371
7.947
1.00
12.13
A

N

ATOM
1077
CA
PHE A
171
18.716
24.684
8.690
1.00
11.64
A

C

ATOM
1078
CB
PHE A
171
19.938
24.478
7.787
1.00
12.34
A

C

ATOM
1079
CG
PHE A
171
21.100
23.800
8.465
1.00
13.38
A

C

ATOM
1080
CD1
PHE A
171
21.980
24.529
9.262
1.00
12.95
A

C

ATOM
1081
CD2
PHE A
171
21.330
22.438
8.282
1.00
12.74
A

C

ATOM
1082
CE1
PHE A
171
23.077
23.911
9.862
1.00
12.19
A

C

ATOM
1083
CE2
PHE A
171
22.426
21.808
8.878
1.00
13.42
A

C

ATOM
1084
CZ
PHE A
171
23.303
22.549
9.670
1.00
9.66
A

C

ATOM
1085
C
PHE A
171
19.097
25.487
9.933
1.00
12.85
A

C

ATOM
1086
O
PHE A
171
19.112
24.956
11.047
1.00
13.16
A

O

ATOM
1087
N
MET A
172
19.367
26.773
9.739
1.00
12.41
A

N

ATOM
1088
CA
MET A
172
19.770
27.633
10.845
1.00
13.98
A

C

ATOM
1089
CB
AMET A
172
20.339
28.952
10.310
0.80
15.64
A

C

ATOM
1090
CB
BMET A
172
20.370
28.959
10.355
0.20
14.94
A

C

ATOM
1091
CG
AMET A
172
21.571
28.732
9.435
0.80
16.09
A

C

ATOM
1092
CG
BMET A
172
19.527
29.804
9.448
0.20
15.64
A

C

ATOM
1093
SD
AMET A
172
22.552
30.211
9.177
0.80
21.52
A

S

ATOM
1094
SD
BMET A
172
20.472
31.295
9.068
0.20
14.45
A

S

ATOM
1095
CE
AMET A
172
21.697
30.932
7.776
0.80
17.67
A

C

ATOM
1096
CE
BMET A
172
21.541
30.699
7.752
0.20
18.36
A

C

ATOM
1097
C
MET A
172
18.662
27.902
11.848
1.00
13.07
A

C

ATOM
1098
O
MET A
172
18.937
28.048
13.039
1.00
13.04
A

O

ATOM
1099
N
SER A
173
17.418
27.947
11.379
1.00
13.08
A

N

ATOM
1100
CA
SER A
173
16.284
28.199
12.261
1.00
11.55
A

C

ATOM
1101
CB
SER A
173
15.044
28.557
11.440
1.00
11.95
A

C

ATOM
1102
OG
SER A
173
15.174
29.828
10.818
1.00
14.62
A

O

ATOM
1103
C
SER A
173
16.019
26.963
13.127
1.00
11.91
A

C

ATOM
1104
O
SER A
173
15.713
27.082
14.315
1.00
14.96
A

O

ATOM
1105
N
LEU A
174
16.121
25.777
12.529
1.00
11.90
A

N

ATOM
1106
CA
LEU A
174
15.927
24.539
13.279
1.00
12.23
A

C

ATOM
1107
CB
LEU A
174
16.053
23.319
12.351
1.00
13.54
A

C

ATOM
1108
CG
LEU A
174
14.780
22.851
11.634
1.00
15.89
A

C

ATOM
1109
CD1
LEU A
174
15.132
21.898
10.491
1.00
14.93
A

C

ATOM
1110
CD2
LEU A
174
13.845
22.183
12.637
1.00
12.22
A

C

ATOM
1111
C
LEU A
174
16.999
24.465
14.371
1.00
12.75
A

C

ATOM
1112
O
LEU A
174
16.710
24.160
15.521
1.00
13.46
A

O

ATOM
1113
N
ARG A
175
18.243
24.746
13.993
1.00
11.68
A

N

ATOM
1114
CA
ARG A
175
19.360
24.709
14.930
1.00
14.76
A

C

ATOM
1115
CB
ARG A
175
20.673
24.990
14.177
1.00
12.95
A

C

ATOM
1116
CG
ARG A
175
21.888
25.301
15.040
1.00
15.09
A

C

ATOM
1117
CD
ARG A
175
23.156
25.325
14.175
1.00
13.01
A

C

ATOM
1118
NE
ARG A
175
24.292
25.954
14.847
1.00
16.67
A

N

ATOM
1119
CZ
ARG A
175
25.566
25.771
14.505
1.00
15.77
A

C

ATOM
1120
NH1
ARG A
175
25.888
24.962
13.502
1.00
11.71
A

N

ATOM
1121
NH2
ARG A
175
26.525
26.429
15.144
1.00
16.45
A

N

ATOM
1122
C
ARG A
175
19.146
25.733
16.051
1.00
14.85
A

C

ATOM
1123
O
ARG A
175
19.163
25.392
17.235
1.00
16.14
A

O

ATOM
1124
N
ASN A
176
18.898
26.978
15.678
1.00
12.31
A

N

ATOM
1125
CA
ASN A
176
18.708
28.021
16.678
1.00
13.85
A

C

ATOM
1126
CB
ASN A
176
18.582
29.387
16.000
1.00
11.88
A

C

ATOM
1127
CG
ASN A
176
19.870
29.825
15.332
1.00
15.20
A

C

ATOM
1128
OD1
ASN A
176
20.956
29.382
15.705
1.00
14.68
A

O

ATOM
1129
ND2
ASN A
176
19.759
30.709
14.350
1.00
13.94
A

N

ATOM
1130
C
ASN A
176
17.519
27.799
17.612
1.00
13.45
A

C

ATOM
1131
O
ASN A
176
17.609
28.060
18.812
1.00
13.27
A

O

ATOM
1132
N
ALA A
177
16.410
27.303
17.079
1.00
12.70
A

N

ATOM
1133
CA
ALA A
177
15.233
27.092
17.913
1.00
13.82
A

C

ATOM
1134
CB
ALA A
177
13.961
27.151
17.049
1.00
12.99
A

C

ATOM
1135
C
ALA A
177
15.240
25.793
18.701
1.00
13.69
A

C

ATOM
1136
O
ALA A
177
14.581
25.693
19.735
1.00
13.56
A

O

ATOM
1137
N
CYS A
178
16.013
24.808
18.255
1.00
12.34
A

N

ATOM
1138
CA
CYS A
178
15.954
23.505
18.917
1.00
12.68
A

C

ATOM
1139
C
CYS A
178
17.144
23.035
19.788
1.00
12.67
A

C

ATOM
1140
O
CYS A
178
16.965
22.126
20.591
1.00
12.42
A

O

ATOM
1141
CB
CYS A
178
15.703
22.419
17.872
1.00
12.70
A

C

ATOM
1142
SG
CYS A
178
14.143
22.611
16.953
1.00
13.36
A

S

ATOM
1143
N
ILE A
179
18.323
23.620
19.637
1.00
15.23
A

N

ATOM
1144
CA
ILE A
179
19.456
23.173
20.438
1.00
18.51
A

C

ATOM
1145
CB
ILE A
179
20.789
23.611
19.808
1.00
17.80
A

C

ATOM
1146
CG2
ILE A
179
20.887
23.039
18.390
1.00
15.56
A

C

ATOM
1147
CG1
ILE A
179
20.891
25.138
19.793
1.00
17.43
A

C

ATOM
1148
CD
ILE A
179
22.185
25.660
19.200
1.00
18.12
A

C

ATOM
1149
C
ILE A
179
19.384
23.657
21.886
1.00
22.43
A

C

ATOM
1150
OT1
ILE A
179
19.937
22.965
22.766
1.00
24.68
A

O

ATOM
1151
OT2
ILE A
179
18.783
24.728
22.123
1.00
25.46
A

O

ATOM
1152
CB
HIS B
39
27.892
44.470
−6.060
1.00
45.22
B

C

ATOM
1153
CG
HIS B
39
28.041
43.710
−7.341
1.00
48.50
B

C

ATOM
1154
CD2
HIS B
39
27.587
42.488
−7.704
1.00
50.10
B

C

ATOM
1155
ND1
HIS B
39
28.700
44.216
−8.442
1.00
50.41
B

N

ATOM
1156
CE1
HIS B
39
28.644
43.338
−9.428
1.00
50.37
B

C

ATOM
1157
NE2
HIS B
39
27.974
42.281
−9.007
1.00
50.98
B

N

ATOM
1158
C
HIS B
39
29.987
43.757
−4.873
1.00
43.85
B

C

ATOM
1159
O
HIS B
39
31.015
43.319
−5.402
1.00
43.28
B

O

ATOM
1160
N
HIS B
39
29.995
45.653
−6.496
1.00
43.51
B

N

ATOM
1161
CA
HIS B
39
29.215
44.936
−5.463
1.00
44.10
B

C

ATOM
1162
N
CYS B
40
29.484
43.231
−3.770
1.00
42.96
B

N

ATOM
1163
CA
CYS B
40
30.174
42.138
−3.125
1.00
42.42
B

C

ATOM
1164
C
CYS B
40
29.968
40.767
−3.775
1.00
42.46
B

C

ATOM
1165
O
CYS B
40
28.844
40.378
−4.077
1.00
42.43
B

O

ATOM
1166
CB
CYS B
40
29.771
42.107
−1.658
1.00
41.23
B

C

ATOM
1167
SG
CYS B
40
30.160
43.644
−0.756
1.00
38.48
B

S

ATOM
1168
N
ARG B
41
31.068
40.041
−3.980
1.00
42.65
B

N

ATOM
1169
CA
ARG B
41
31.038
38.705
−4.584
1.00
43.37
B

C

ATOM
1170
CB
ARG B
41
30.698
38.804
−6.076
1.00
44.07
B

C

ATOM
1171
CG
ARG B
41
30.800
37.482
−6.831
1.00
45.44
B

C

ATOM
1172
CD
ARG B
41
30.385
37.641
−8.290
1.00
46.08
B

C

ATOM
1173
NE
ARG B
41
30.473
36.388
−9.038
1.00
47.65
B

N

ATOM
1174
CZ
ARG B
41
31.612
35.781
−9.356
1.00
47.69
B

C

ATOM
1175
NH1
ARG B
41
32.774
36.307
−8.992
1.00
49.10
B

N

ATOM
1176
NH2
ARG B
41
31.590
34.646
−10.040
1.00
47.59
B

N

ATOM
1177
C
ARG B
41
32.390
38.014
−4.407
1.00
43.67
B

C

ATOM
1178
O
ARG B
41
33.417
38.683
−4.295
1.00
43.52
B

O

ATOM
1179
N
LEU B
42
32.381
36.682
−4.382
1.00
43.47
B

N

ATOM
1180
CA
LEU B
42
33.600
35.902
−4.210
1.00
44.42
B

C

ATOM
1181
CB
LEU B
42
33.695
35.356
−2.774
1.00
42.98
B

C

ATOM
1182
CG
LEU B
42
33.903
36.365
−1.643
1.00
41.64
B

C

ATOM
1183
CD1
LEU B
42
33.743
35.674
−0.299
1.00
41.04
B

C

ATOM
1184
CD2
LEU B
42
35.283
36.981
−1.768
1.00
40.35
B

C

ATOM
1185
C
LEU B
42
33.647
34.744
−5.195
1.00
45.72
B

C

ATOM
1186
O
LEU B
42
32.635
34.098
−5.470
1.00
45.97
B

O

ATOM
1187
N
ASP B
43
34.834
34.483
−5.735
1.00
46.61
B

N

ATOM
1188
CA
ASP B
43
34.998
33.394
−6.693
1.00
47.21
B

C

ATOM
1189
CB
AASP B
43
36.396
33.446
−7.314
0.50
48.39
B

C

ATOM
1190
CB
BASP B
43
36.405
33.416
−7.276
0.50
48.20
B

C

ATOM
1191
CG
AASP B
43
36.566
32.454
−8.457
0.50
49.57
B

C

ATOM
1192
CG
BASP B
43
36.845
34.805
−7.676
0.50
49.13
B

C

ATOM
1193
OD1
AASP B
43
35.827
32.564
−9.459
0.50
50.63
B

O

ATOM
1194
OD1
BASP B
43
37.622
35.414
−6.914
0.50
50.04
B

O

ATOM
1195
OD2
AASP B
43
37.432
31.557
−8.358
0.50
49.95
B

O

ATOM
1196
OD2
BASP B
43
36.422
35.282
−8.749
0.50
49.61
B

O

ATOM
1197
C
ASP B
43
34.785
32.037
−6.023
1.00
47.20
B

C

ATOM
1198
O
ASP B
43
35.203
31.836
−4.884
1.00
46.97
B

O

ATOM
1199
N
LYS B
44
34.151
31.108
−6.736
1.00
47.14
B

N

ATOM
1200
CA
LYS B
44
33.869
29.771
−6.212
1.00
46.50
B

C

ATOM
1201
CB
LYS B
44
33.244
28.904
−7.310
1.00
48.36
B

C

ATOM
1202
CG
LYS B
44
31.876
29.408
−7.787
1.00
50.69
B

C

ATOM
1203
CD
LYS B
44
31.231
28.403
−8.735
1.00
52.34
B

C

ATOM
1204
CE
LYS B
44
29.832
28.829
−9.150
1.00
53.13
B

C

ATOM
1205
NZ
LYS B
44
29.175
27.806
−10.015
1.00
54.70
B

N

ATOM
1206
C
LYS B
44
35.121
29.094
−5.665
1.00
45.46
B

C

ATOM
1207
O
LYS B
44
35.083
28.353
−4.677
1.00
45.04
B

O

ATOM
1208
N
SER B
45
36.246
29.362
−6.314
1.00
44.73
B

N

ATOM
1209
CA
SER B
45
37.514
28.777
−5.899
1.00
44.17
B

C

ATOM
1210
CB
ASER B
45
38.659
29.317
−6.765
0.50
44.61
B

C

ATOM
1211
CB
BSER B
45
38.645
29.351
−6.767
0.50
44.45
B

C

ATOM
1212
OG
ASER B
45
39.915
28.799
−6.349
0.50
45.01
B

O

ATOM
1213
OG
BSER B
45
38.341
29.256
−8.145
0.50
44.34
B

O

ATOM
1214
C
SER B
45
37.828
29.037
−4.430
1.00
43.68
B

C

ATOM
1215
O
SER B
45
38.358
28.164
−3.739
1.00
43.94
B

O

ATOM
1216
N
ASN B
46
37.504
30.237
−3.958
1.00
43.08
B

N

ATOM
1217
CA
ASN B
46
37.758
30.613
−2.573
1.00
41.72
B

C

ATOM
1218
CB
ASN B
46
37.229
32.023
−2.313
1.00
42.60
B

C

ATOM
1219
CG
ASN B
46
37.938
33.069
−3.134
1.00
42.66
B

C

ATOM
1220
OD1
ASN B
46
37.794
33.119
−4.353
1.00
43.85
B

O

ATOM
1221
ND2
ASN B
46
38.726
33.906
−2.471
1.00
43.52
B

N

ATOM
1222
C
ASN B
46
37.118
29.655
−1.569
1.00
40.56
B

C

ATOM
1223
O
ASN B
46
37.615
29.501
−0.457
1.00
40.87
B

O

ATOM
1224
N
PHE B
47
36.012
29.020
−1.949
1.00
39.67
B

N

ATOM
1225
CA
PHE B
47
35.319
28.103
−1.050
1.00
37.86
B

C

ATOM
1226
CB
PHE B
47
33.832
28.458
−1.007
1.00
37.18
B

C

ATOM
1227
CG
PHE B
47
33.549
29.753
−0.297
1.00
38.02
B

C

ATOM
1228
CD1
PHE B
47
33.520
29.807
1.093
1.00
37.75
B

C

ATOM
1229
CD2
PHE B
47
33.346
30.928
−1.017
1.00
37.55
B

C

ATOM
1230
CE1
PHE B
47
33.293
31.013
1.755
1.00
37.90
B

C

ATOM
1231
CE2
PHE B
47
33.120
32.137
−0.364
1.00
37.70
B

C

ATOM
1232
CZ
PHE B
47
33.094
32.179
1.024
1.00
37.15
B

C

ATOM
1233
C
PHE B
47
35.505
26.620
−1.365
1.00
38.38
B

C

ATOM
1234
O
PHE B
47
34.863
25.764
−0.758
1.00
39.24
B

O

ATOM
1235
N
GLN B
48
36.379
26.309
−2.313
1.00
37.58
B

N

ATOM
1236
CA
GLN B
48
36.642
24.915
−2.636
1.00
37.04
B

C

ATOM
1237
CB
GLN B
48
36.928
24.757
−4.129
1.00
38.28
B

C

ATOM
1238
CG
GLN B
48
35.687
24.947
−4.988
1.00
40.62
B

C

ATOM
1239
CD
GLN B
48
35.964
24.815
−6.471
1.00
41.52
B

C

ATOM
1240
OE1
GLN B
48
35.040
24.827
−7.284
1.00
42.61
B

O

ATOM
1241
NE2
GLN B
48
37.238
24.692
−6.832
1.00
42.47
B

N

ATOM
1242
C
GLN B
48
37.835
24.476
−1.793
1.00
35.19
B

C

ATOM
1243
O
GLN B
48
38.900
24.139
−2.307
1.00
35.18
B

O

ATOM
1244
N
GLN B
49
37.635
24.504
−0.480
1.00
33.48
B

N

ATOM
1245
CA
GLN B
49
38.661
24.131
0.484
1.00
32.10
B

C

ATOM
1246
CB
GLN B
49
39.186
25.377
1.211
1.00
34.97
B

C

ATOM
1247
CG
GLN B
49
40.433
26.012
0.597
1.00
39.74
B

C

ATOM
1248
CD
GLN B
49
40.157
26.729
−0.707
1.00
42.56
B

C

ATOM
1249
OE1
GLN B
49
40.844
26.316
−1.768
1.00
44.68
B

O

ATOM
1250
NE2
GLN B
49
39.341
27.649
−0.760
1.00
44.50
B

N

ATOM
1251
C
GLN B
49
38.077
23.157
1.503
1.00
29.66
B

C

ATOM
1252
O
GLN B
49
37.583
23.569
2.556
1.00
28.91
B

O

ATOM
1253
N
PRO B
50
38.114
21.850
1.199
1.00
26.63
B

N

ATOM
1254
CD
PRO B
50
38.639
21.200
−0.013
1.00
26.53
B

C

ATOM
1255
CA
PRO B
50
37.570
20.860
2.134
1.00
24.12
B

C

ATOM
1256
CB
PRO B
50
37.720
19.541
1.375
1.00
26.35
B

C

ATOM
1257
CG
PRO B
50
38.902
19.796
0.468
1.00
26.74
B

C

ATOM
1258
C
PRO B
50
38.287
20.846
3.476
1.00
20.94
B

C

ATOM
1259
O
PRO B
50
37.652
20.728
4.522
1.00
20.16
B

O

ATOM
1260
N
TYR B
51
39.608
20.978
3.451
1.00
18.35
B

N

ATOM
1261
CA
TYR B
51
40.384
20.964
4.688
1.00
17.88
B

C

ATOM
1262
CB
TYR B
51
41.877
21.137
4.394
1.00
19.37
B

C

ATOM
1263
CG
TYR B
51
42.737
21.177
5.638
1.00
18.71
B

C

ATOM
1264
CD1
TYR B
51
43.015
20.014
6.352
1.00
19.74
B

C

ATOM
1265
CE1
TYR B
51
43.777
20.043
7.512
1.00
20.59
B

C

ATOM
1266
CD2
TYR B
51
43.250
22.385
6.118
1.00
20.02
B

C

ATOM
1267
CE2
TYR B
51
44.018
22.428
7.282
1.00
21.12
B

C

ATOM
1268
CZ
TYR B
51
44.274
21.253
7.973
1.00
22.10
B

C

ATOM
1269
OH
TYR B
51
45.008
21.287
9.137
1.00
24.61
B

O

ATOM
1270
C
TYR B
51
39.933
22.065
5.637
1.00
17.24
B

C

ATOM
1271
O
TYR B
51
39.560
21.793
6.773
1.00
17.29
B

O

ATOM
1272
N
ILE B
52
39.969
23.304
5.160
1.00
17.58
B

N

ATOM
1273
CA
ILE B
52
39.571
24.448
5.973
1.00
21.11
B

C

ATOM
1274
CB
ILE B
52
39.827
25.760
5.210
1.00
24.48
B

C

ATOM
1275
CG2
ILE B
52
39.180
26.934
5.937
1.00
26.45
B

C

ATOM
1276
CG1
ILE B
52
41.342
25.956
5.062
1.00
26.38
B

C

ATOM
1277
CD
ILE B
52
41.748
27.215
4.340
1.00
31.77
B

C

ATOM
1278
C
ILE B
52
38.114
24.378
6.426
1.00
19.79
B

C

ATOM
1279
O
ILE B
52
37.782
24.812
7.530
1.00
20.54
B

O

ATOM
1280
N
THR B
53
37.246
23.834
5.579
1.00
18.58
B

C

ATOM
1281
CA
THR B
53
35.837
23.701
5.932
1.00
17.34
B

C

ATOM
1282
CB
THR B
53
35.032
23.103
4.765
1.00
19.54
B

C

ATOM
1283
OG1
THR B
53
35.186
23.939
3.610
1.00
21.25
B

O

ATOM
1284
CG2
THR B
53
33.558
23.017
5.121
1.00
18.98
B

C

ATOM
1285
C
THR B
53
35.732
22.782
7.146
1.00
16.46
B

C

ATOM
1286
O
THR B
53
35.092
23.116
8.139
1.00
17.44
B

O

ATOM
1287
N
ASN B
54
36.393
21.632
7.074
1.00
16.45
B

N

ATOM
1288
CA
ASN B
54
36.376
20.675
8.178
1.00
15.65
B

C

ATOM
1289
CB
ASN B
54
37.164
19.413
7.806
1.00
17.11
B

C

ATOM
1290
CG
ASN B
54
36.359
18.455
6.942
1.00
19.54
B

C

ATOM
1291
OD1
ASN B
54
35.337
18.827
6.372
1.00
19.10
B

O

ATOM
1292
ND2
ASN B
54
36.826
17.221
6.835
1.00
20.54
B

N

ATOM
1293
C
ASN B
54
36.969
21.288
9.441
1.00
16.14
B

C

ATOM
1294
O
ASN B
54
36.422
21.134
10.535
1.00
16.51
B

O

ATOM
1295
N
ARG B
55
38.087
21.990
9.284
1.00
16.11
B

N

ATOM
1296
CA
ARG B
55
38.748
22.618
10.425
1.00
16.50
B

C

ATOM
1297
CB
AARG B
55
40.100
23.214
10.006
0.50
18.63
B

C

ATOM
1298
CB
BARG B
55
40.069
23.223
10.002
0.50
18.75
B

C

ATOM
1299
CG
AARG B
55
41.043
22.199
9.379
0.50
22.49
B

C

ATOM
1300
CG
BARG B
55
41.066
22.263
9.348
0.50
22.67
B

C

ATOM
1301
CD
AARG B
55
41.300
21.017
10.307
0.50
25.57
B

C

ATOM
1302
CD
BARG B
55
41.866
21.447
10.363
0.50
26.03
B

C

ATOM
1303
NE
AARG B
55
42.403
21.236
11.238
0.50
28.75
B

N

ATOM
1304
NE
BARG B
55
41.176
20.260
10.872
0.50
28.52
B

N

ATOM
1305
CZ
AARG B
55
42.799
20.343
12.141
0.50
30.20
B

C

ATOM
1306
CZ
BARG B
55
41.716
19.416
11.751
0.50
30.40
B

C

ATOM
1307
NH1
AARG B
55
42.180
19.173
12.241
0.50
32.50
B

N

ATOM
1308
NH1
BARG B
55
42.935
19.643
12.215
0.50
31.14
B

N

ATOM
1309
NH2
AARG B
55
43.825
20.611
12.935
0.50
31.35
B

N

ATOM
1310
NH2
BARG B
55
41.066
18.325
12.142
0.50
30.17
B

N

ATOM
1311
C
ARG B
55
37.883
23.712
11.041
1.00
13.93
B

C

ATOM
1312
O
ARG B
55
37.924
23.939
12.252
1.00
13.25
B

O

ATOM
1313
N
THR B
56
37.100
24.392
10.208
1.00
14.26
B

N

ATOM
1314
CA
THR B
56
36.230
25.452
10.693
1.00
11.34
B

C

ATOM
1315
CB
THR B
56
35.585
26.237
9.525
1.00
14.38
B

C

ATOM
1316
OG1
THR B
56
36.614
26.908
8.779
1.00
14.44
B

O

ATOM
1317
CG2
THR B
56
34.587
27.266
10.052
1.00
11.15
B

C

ATOM
1318
C
THR B
56
35.149
24.817
11.556
1.00
13.75
B

C

ATOM
1319
O
THR B
56
34.817
25.319
12.631
1.00
14.25
B

O

ATOM
1320
N
PHE B
57
34.598
23.700
11.089
1.00
13.72
B

N

ATOM
1321
CA
PHE B
57
33.565
23.018
11.851
1.00
13.15
B

C

ATOM
1322
CB
PHE B
57
32.899
21.932
11.001
1.00
13.02
B

C

ATOM
1323
CG
PHE B
57
31.799
22.453
10.117
1.00
11.26
B

C

ATOM
1324
CD1
PHE B
57
32.085
23.289
9.044
1.00
12.61
B

C

ATOM
1325
CD2
PHE B
57
30.472
22.125
10.377
1.00
11.56
B

C

ATOM
1326
CE1
PHE B
57
31.069
23.792
8.241
1.00
14.35
B

C

ATOM
1327
CE2
PHE B
57
29.443
22.621
9.582
1.00
11.35
B

C

ATOM
1328
CZ
PHE B
57
29.741
23.458
8.509
1.00
11.81
B

C

ATOM
1329
C
PHE B
57
34.138
22.431
13.142
1.00
13.86
B

C

ATOM
1330
O
PHE B
57
33.444
22.354
14.153
1.00
14.13
B

O

ATOM
1331
N
MET B
58
35.405
22.029
13.124
1.00
15.45
B

N

ATOM
1332
CA
MET B
58
36.004
21.481
14.335
1.00
16.62
B

C

ATOM
1333
CB
MET B
58
37.325
20.792
14.017
1.00
21.38
B

C

ATOM
1334
CG
MET B
58
37.130
19.435
13.368
1.00
27.49
B

C

ATOM
1335
SD
MET B
58
36.220
18.220
14.333
1.00
33.41
B

S

ATOM
1336
CE
MET B
58
37.378
17.916
15.662
1.00
29.95
B

C

ATOM
1337
C
MET B
58
36.221
22.601
15.343
1.00
15.87
B

C

ATOM
1338
O
MET B
58
36.000
22.429
16.538
1.00
14.52
B

O

ATOM
1339
N
LEU B
59
36.652
23.755
14.852
1.00
14.79
B

N

ATOM
1340
CA
LEU B
59
36.871
24.898
15.719
1.00
13.60
B

C

ATOM
1341
CB
LEU B
59
37.416
26.076
14.910
1.00
12.59
B

C

ATOM
1342
CG
LEU B
59
37.506
27.417
15.643
1.00
12.48
B

C

ATOM
1343
CD1
LEU B
59
38.352
27.260
16.896
1.00
13.58
B

C

ATOM
1344
CD2
LEU B
59
38.105
28.476
14.710
1.00
11.97
B

C

ATOM
1345
C
LEU B
59
35.540
25.283
16.364
1.00
13.10
B

C

ATOM
1346
O
LEU B
59
35.480
25.538
17.566
1.00
14.28
B

O

ATOM
1347
N
ALA B
60
34.477
25.325
15.558
1.00
11.11
B

N

ATOM
1348
CA
ALA B
60
33.145
25.670
16.055
1.00
12.18
B

C

ATOM
1349
CB
ALA B
60
32.148
25.744
14.879
1.00
11.09
B

C

ATOM
1350
C
ALA B
60
32.665
24.659
17.103
1.00
12.00
B

C

ATOM
1351
O
ALA B
60
32.070
25.031
18.119
1.00
9.58
B

O

ATOM
1352
N
LYS B
61
32.915
23.376
16.863
1.00
12.27
B

N

ATOM
1353
CA
LYS B
61
32.515
22.351
17.818
1.00
13.95
B

C

ATOM
1354
CB
LYS B
61
32.842
20.952
17.294
1.00
14.14
B

C

ATOM
1355
CG
LYS B
61
31.862
20.412
16.282
1.00
19.93
B

C

ATOM
1356
CD
LYS B
61
32.281
19.014
15.841
1.00
19.80
B

C

ATOM
1357
CE
LYS B
61
31.339
18.454
14.799
1.00
23.77
B

C

ATOM
1358
NZ
LYS B
61
32.028
17.403
14.007
1.00
22.83
B

N

ATOM
1359
C
LYS B
61
33.228
22.534
19.143
1.00
13.07
B

C

ATOM
1360
O
LYS B
61
32.611
22.446
20.203
1.00
13.89
B

O

ATOM
1361
N
GLU B
62
34.532
22.782
19.079
1.00
12.95
B

N

ATOM
1362
CA
GLU B
62
35.335
22.955
20.289
1.00
13.90
B

C

ATOM
1363
CB
GLU B
62
36.804
23.164
19.906
1.00
15.80
B

C

ATOM
1364
CG
GLU B
62
37.756
23.426
21.071
1.00
19.60
B

C

ATOM
1365
CD
GLU B
62
37.749
22.321
22.122
1.00
23.26
B

C

ATOM
1366
OE1
GLU B
62
37.759
21.127
21.747
1.00
23.30
B

O

ATOM
1367
OE2
GLU B
62
37.746
22.654
23.332
1.00
25.11
B

O

ATOM
1368
C
GLU B
62
34.841
24.116
21.137
1.00
13.12
B

C

ATOM
1369
O
GLU B
62
34.654
23.974
22.346
1.00
15.86
B

O

ATOM
1370
N
ALA B
63
34.638
25.269
20.509
1.00
12.37
B

N

ATOM
1371
CA
ALA B
63
34.164
26.444
21.228
1.00
11.98
B

C

ATOM
1372
CB
ALA B
63
34.214
27.674
20.322
1.00
10.58
B

C

ATOM
1373
C
ALA B
63
32.743
26.220
21.732
1.00
12.40
B

C

ATOM
1374
O
ALA B
63
32.383
26.695
22.802
1.00
14.78
B

O

ATOM
1375
N
SER B
64
31.938
25.487
20.967
1.00
13.59
B

N

ATOM
1376
CA
SER B
64
30.557
25.225
21.361
1.00
14.14
B

C

ATOM
1377
CB
SER B
64
29.825
24.450
20.266
1.00
13.79
B

C

ATOM
1378
OG
SER B
64
29.537
25.295
19.166
1.00
15.71
B

O

ATOM
1379
C
SER B
64
30.464
24.468
22.680
1.00
16.02
B

C

ATOM
1380
O
SER B
64
29.456
24.576
23.389
1.00
14.81
B

O

ATOM
1381
N
LEU B
65
31.516
23.715
23.009
1.00
16.10
B

N

ATOM
1382
CA
LEU B
65
31.546
22.951
24.258
1.00
18.41
B

C

ATOM
1383
CB
LEU B
65
32.829
22.124
24.362
1.00
19.27
B

C

ATOM
1384
CG
LEU B
65
33.084
21.082
23.277
1.00
19.94
B

C

ATOM
1385
CD1
LEU B
65
34.420
20.401
23.556
1.00
21.12
B

C

ATOM
1386
CD2
LEU B
65
31.941
20.069
23.233
1.00
19.85
B

C

ATOM
1387
C
LEU B
65
31.461
23.873
25.472
1.00
21.28
B

C

ATOM
1388
O
LEU B
65
30.913
23.496
26.508
1.00
20.85
B

O

ATOM
1389
N
ALA B
66
31.993
25.084
25.337
1.00
22.77
B

N

ATOM
1390
CA
ALA B
66
31.991
26.041
26.440
1.00
23.05
B

C

ATOM
1391
CB
ALA B
66
33.340
26.759
26.505
1.00
23.03
B

C

ATOM
1392
C
ALA B
66
30.864
27.063
26.349
1.00
25.33
B

C

ATOM
1393
O
ALA B
66
30.794
27.989
27.160
1.00
24.62
B

O

ATOM
1394
N
ASP B
67
29.984
26.895
25.366
1.00
24.71
B

N

ATOM
1395
CA
ASP B
67
28.859
27.805
25.169
1.00
24.59
B

C

ATOM
1396
CB
ASP B
67
28.843
28.293
23.715
1.00
21.80
B

C

ATOM
1397
CG
ASP B
67
27.658
29.193
23.409
1.00
23.11
B

C

ATOM
1398
OD1
ASP B
67
27.492
30.220
24.101
1.00
21.79
B

O

ATOM
1399
OD2
ASP B
67
26.894
28.881
22.468
1.00
22.86
B

O

ATOM
1400
C
ASP B
67
27.539
27.105
25.484
1.00
24.11
B

C

ATOM
1401
O
ASP B
67
27.339
25.961
25.090
1.00
24.85
B

O

ATOM
1402
N
ASN B
68
26.643
27.781
26.199
1.00
23.66
B

N

ATOM
1403
CA
ASN B
68
25.341
27.190
26.505
1.00
26.10
B

C

ATOM
1404
CB
ASN B
68
24.606
27.991
27.584
1.00
26.12
B

C

ATOM
1405
CG
ASN B
68
23.178
27.507
27.791
1.00
28.10
B

C

ATOM
1406
OD1
ASN B
68
22.902
26.309
27.704
1.00
30.31
B

O

ATOM
1407
ND2
ASN B
68
22.267
28.432
28.075
1.00
29.58
B

N

ATOM
1408
C
ASN B
68
24.514
27.191
25.223
1.00
26.09
B

C

ATOM
1409
O
ASN B
68
24.122
28.252
24.733
1.00
25.01
B

O

ATOM
1410
N
ASN B
69
24.245
26.006
24.682
1.00
26.55
B

N

ATOM
1411
CA
ASN B
69
23.488
25.905
23.435
1.00
28.23
B

C

ATOM
1412
CB
ASN B
69
23.321
24.443
23.029
1.00
29.69
B

C

ATOM
1413
CG
ASN B
69
24.642
23.743
22.885
1.00
32.95
B

C

ATOM
1414
OD1
ASN B
69
25.616
24.339
22.428
1.00
33.35
B

O

ATOM
1415
ND2
ASN B
69
24.690
22.470
23.268
1.00
35.41
B

N

ATOM
1416
C
ASN B
69
22.129
26.575
23.462
1.00
27.38
B

C

ATOM
1417
O
ASN B
69
21.754
27.280
22.527
1.00
26.91
B

O

ATOM
1418
N
THR B
70
21.386
26.367
24.533
1.00
27.43
B

N

ATOM
1419
CA
THR B
70
20.063
26.963
24.620
1.00
31.14
B

C

ATOM
1420
CB
THR B
70
19.290
26.312
25.724
1.00
33.84
B

C

ATOM
1421
OG1
THR B
70
20.017
26.483
26.949
1.00
38.79
B

O

ATOM
1422
CG2
THR B
70
19.099
24.825
25.414
1.00
35.38
B

C

ATOM
1423
C
THR B
70
20.084
28.472
24.850
1.00
29.99
B

C

ATOM
1424
O
THR B
70
19.032
29.100
24.983
1.00
31.80
B

O

ATOM
1425
N
ASP B
71
21.280
29.048
24.900
1.00
28.37
B

N

ATOM
1426
CA
ASP B
71
21.420
30.481
25.102
1.00
25.20
B

C

ATOM
1427
CB
ASP B
71
22.838
30.798
25.589
1.00
24.99
B

C

ATOM
1428
CG
ASP B
71
22.995
32.241
26.019
1.00
25.37
B

C

ATOM
1429
OD1
ASP B
71
21.991
32.842
26.457
1.00
24.56
B

O

ATOM
1430
OD2
ASP B
71
24.120
32.775
25.929
1.00
24.43
B

O

ATOM
1431
C
ASP B
71
21.124
31.210
23.789
1.00
24.70
B

C

ATOM
1432
O
ASP B
71
20.958
30.579
22.741
1.00
25.80
B

O

ATOM
1433
N
VAL B
72
21.051
32.536
23.852
1.00
22.24
B

N

ATOM
1434
CA
VAL B
72
20.769
33.352
22.674
1.00
21.58
B

C

ATOM
1435
CB
VAL B
72
20.887
34.856
23.015
1.00
21.53
B

C

ATOM
1436
CG1
VAL B
72
22.310
35.177
23.443
1.00
21.59
B

C

ATOM
1437
CG2
VAL B
72
20.468
35.711
21.818
1.00
24.37
B

C

ATOM
1438
C
VAL B
72
21.729
33.005
21.534
1.00
21.11
B

C

ATOM
1439
O
VAL B
72
22.864
32.600
21.773
1.00
17.71
B

O

ATOM
1440
N
ARG B
73
21.259
33.162
20.300
1.00
19.03
B

N

ATOM
1441
CA
ARG B
73
22.062
32.861
19.120
1.00
21.00
B

C

ATOM
1442
CB
ARG B
73
21.242
32.005
18.145
1.00
20.05
B

C

ATOM
1443
CG
ARG B
73
20.914
30.607
18.658
1.00
22.93
B

C

ATOM
1444
CD
ARG B
73
22.184
29.788
18.848
1.00
23.32
B

C

ATOM
1445
NE
ARG B
73
22.541
29.607
20.253
1.00
26.02
B

N

ATOM
1446
CZ
ARG B
73
23.792
29.534
20.701
1.00
28.62
B

C

ATOM
1447
NH1
ARG B
73
24.810
29.643
19.850
1.00
27.83
B

N

ATOM
1448
NH2
ARG B
73
24.032
29.318
21.991
1.00
24.28
B

N

ATOM
1449
C
ARG B
73
22.562
34.130
18.422
1.00
19.92
B

C

ATOM
1450
O
ARG B
73
22.231
35.242
18.823
1.00
23.35
B

O

ATOM
1451
N
LEU B
74
23.361
33.956
17.375
1.00
18.84
B

N

ATOM
1452
CA
LEU B
74
23.928
35.091
16.644
1.00
18.10
B

C

ATOM
1453
CB
LEU B
74
25.452
35.071
16.764
1.00
17.88
B

C

ATOM
1454
CG
LEU B
74
26.021
35.213
18.178
1.00
17.88
B

C

ATOM
1455
CD1
LEU B
74
27.514
34.966
18.146
1.00
19.62
B

C

ATOM
1456
CD2
LEU B
74
25.711
36.602
18.727
1.00
16.68
B

C

ATOM
1457
C
LEU B
74
23.550
35.113
15.172
1.00
18.69
B

C

ATOM
1458
O
LEU B
74
22.990
36.094
14.678
1.00
17.25
B

O

ATOM
1459
N
ILE B
75
23.864
34.026
14.478
1.00
18.86
B

N

ATOM
1460
CA
ILE B
75
23.565
33.900
13.055
1.00
19.94
B

C

ATOM
1461
CB
AILE B
75
24.683
33.133
12.315
0.50
19.70
B

C

ATOM
1462
CB
BILE B
75
24.685
33.159
12.306
0.50
19.21
B

C

ATOM
1463
CG2
AILE B
75
24.354
33.044
10.830
0.50
20.21
B

C

ATOM
1464
CG2
BILE B
75
24.280
32.922
10.857
0.50
19.75
B

C

ATOM
1465
CG1
AILE B
75
26.032
33.829
12.533
0.50
21.96
B

C

ATOM
1466
CG1
BILE B
75
25.976
33.983
12.354
0.50
20.78
B

C

ATOM
1467
CD
AILE B
75
26.075
35.259
12.036
0.50
21.49
B

C

ATOM
1468
CD
BILE B
75
27.167
33.330
11.684
0.50
19.44
B

C

ATOM
1469
C
ILE B
75
22.250
33.159
12.850
1.00
19.75
B

C

ATOM
1470
O
ILE B
75
22.118
32.001
13.241
1.00
19.53
B

O

ATOM
1471
N
GLY B
76
21.279
33.834
12.244
1.00
20.72
B

N

ATOM
1472
CA
GLY B
76
19.991
33.215
12.002
1.00
21.85
B

C

ATOM
1473
C
GLY B
76
19.144
34.080
11.090
1.00
23.94
B

C

ATOM
1474
O
GLY B
76
19.583
35.137
10.625
1.00
21.15
B

O

ATOM
1475
N
GLU B
77
17.915
33.637
10.849
1.00
24.76
B

N

ATOM
1476
CA
GLU B
77
16.994
34.355
9.981
1.00
25.59
B

C

ATOM
1477
CB
GLU B
77
15.622
33.683
10.024
1.00
28.23
B

C

ATOM
1478
CG
GLU B
77
14.939
33.702
11.385
1.00
29.97
B

C

ATOM
1479
CD
GLU B
77
14.300
35.043
11.702
1.00
31.49
B

C

ATOM
1480
OE1
GLU B
77
13.646
35.618
10.805
1.00
31.82
B

O

ATOM
1481
OE2
GLU B
77
14.438
35.516
12.851
1.00
32.75
B

O

ATOM
1482
C
GLU B
77
16.863
35.826
10.340
1.00
26.42
B

C

ATOM
1483
O
GLU B
77
16.733
36.667
9.454
1.00
25.64
B

O

ATOM
1484
N
LYS B
78
16.903
36.141
11.632
1.00
26.48
B

N

ATOM
1485
CA
LYS B
78
16.769
37.529
12.071
1.00
26.66
B

C

ATOM
1486
CB
LYS B
78
16.769
37.614
13.607
1.00
29.51
B

C

ATOM
1487
CG
LYS B
78
17.949
36.911
14.306
1.00
34.38
B

C

ATOM
1488
CD
LYS B
78
17.866
35.363
14.172
1.00
34.31
B

C

ATOM
1489
CE
LYS B
78
19.033
34.584
14.838
1.00
35.41
B

C

ATOM
1490
NZ
LYS B
78
19.360
35.086
16.206
1.00
33.27
B

N

ATOM
1491
C
LYS B
78
17.845
38.439
11.488
1.00
25.68
B

C

ATOM
1492
O
LYS B
78
17.585
39.607
11.182
1.00
25.09
B

O

ATOM
1493
N
LEU B
79
19.049
37.903
11.322
1.00
22.46
B

N

ATOM
1494
CA
LEU B
79
20.158
38.663
10.759
1.00
22.51
B

C

ATOM
1495
CB
LEU B
79
21.421
37.790
10.744
1.00
21.91
B

C

ATOM
1496
CG
LEU B
79
22.765
38.360
10.272
1.00
21.91
B

C

ATOM
1497
CD1
LEU B
79
23.199
39.526
11.164
1.00
20.83
B

C

ATOM
1498
CD2
LEU B
79
23.819
37.255
10.317
1.00
18.82
B

C

ATOM
1499
C
LEU B
79
19.833
39.125
9.332
1.00
23.76
B

C

ATOM
1500
O
LEU B
79
20.355
40.139
8.858
1.00
21.25
B

O

ATOM
1501
N
PHE B
80
18.957
38.389
8.655
1.00
23.14
B

N

ATOM
1502
CA
PHE B
80
18.605
38.721
7.283
1.00
24.04
B

C

ATOM
1503
CB
PHE B
80
18.576
37.448
6.434
1.00
22.67
B

C

ATOM
1504
CG
PHE B
80
19.852
36.665
6.484
1.00
22.24
B

C

ATOM
1505
CD1
PHE B
80
20.086
35.754
7.508
1.00
22.35
B

C

ATOM
1506
CD2
PHE B
80
20.837
36.863
5.527
1.00
22.73
B

C

ATOM
1507
CE1
PHE B
80
21.286
35.051
7.578
1.00
23.09
B

C

ATOM
1508
CE2
PHE B
80
22.039
36.164
5.591
1.00
24.92
B

C

ATOM
1509
CZ
PHE B
80
22.262
35.255
6.622
1.00
23.28
B

C

ATOM
1510
C
PHE B
80
17.289
39.474
7.113
1.00
25.53
B

C

ATOM
1511
O
PHE B
80
16.817
39.650
5.989
1.00
25.25
B

O

ATOM
1512
N
HIS B
81
16.705
39.928
8.218
1.00
26.38
B

N

ATOM
1513
CA
HIS B
81
15.444
40.662
8.192
1.00
27.94
B

C

ATOM
1514
CB
AHIS B
81
15.100
41.146
9.593
0.50
31.29
B

C

ATOM
1515
CB
BHIS B
81
15.009
41.082
9.560
0.50
31.04
B

C

ATOM
1516
CG
AHIS B
81
13.748
41.770
9.701
0.50
34.69
B

C

ATOM
1517
CG
BHIS B
81
14.361
40.000
10.367
0.50
33.94
B

C

ATOM
1518
CD2
AHIS B
81
12.617
41.581
8.966
0.50
35.93
B

C

ATOM
1519
CD2
BHIS B
81
14.072
38.713
10.063
0.50
35.25
B

C

ATOM
1520
ND1
AHIS B
81
13.422
42.706
10.655
0.50
36.16
B

N

ATOM
1521
ND1
BHIS B
81
13.923
40.196
11.660
0.50
35.74
B

N

ATOM
1522
CE1
AHIS B
81
12.158
43.070
10.511
0.50
37.27
B

C

ATOM
1523
CE1
BHIS B
81
13.393
39.075
12.117
0.50
36.86
B

C

ATOM
1524
NE2
AHIS B
81
11.653
42.400
9.493
0.50
37.17
B

N

ATOM
1525
NE2
BHIS B
81
13.470
38.160
11.168
0.50
36.06
B

N

ATOM
1526
C
HIS B
81
15.507
41.870
7.260
1.00
27.52
B

C

ATOM
1527
O
HIS B
81
16.309
42.781
7.473
1.00
27.00
B

O

ATOM
1528
N
GLY B
82
14.685
41.857
6.213
1.00
26.26
B

N

ATOM
1529
CA
GLY B
82
14.667
42.960
5.270
1.00
24.51
B

C

ATOM
1530
C
GLY B
82
15.874
43.081
4.366
1.00
24.60
B

C

ATOM
1531
O
GLY B
82
16.060
44.108
3.722
1.00
25.03
B

O

ATOM
1532
N
VAL B
83
16.702
42.044
4.317
1.00
26.22
B

N

ATOM
1533
CA
VAL B
83
17.894
42.058
3.474
1.00
24.22
B

C

ATOM
1534
CB
VAL B
83
19.099
41.422
4.198
1.00
23.59
B

C

ATOM
1535
CG1
VAL B
83
20.338
41.501
3.315
1.00
21.40
B

C

ATOM
1536
CG2
VAL B
83
19.332
42.121
5.526
1.00
20.96
B

C

ATOM
1537
C
VAL B
83
17.635
41.282
2.188
1.00
26.23
B

C

ATOM
1538
O
VAL B
83
17.400
40.078
2.220
1.00
26.03
B

O

ATOM
1539
N
SER B
84
17.671
41.974
1.055
1.00
29.00
B

N

ATOM
1540
CA
SER B
84
17.438
41.317
−0.226
1.00
31.27
B

C

ATOM
1541
CB
SER B
84
17.307
42.360
−1.341
1.00
31.72
B

C

ATOM
1542
OG
SER B
84
18.503
43.103
−1.500
1.00
34.12
B

O

ATOM
1543
C
SER B
84
18.599
40.374
−0.522
1.00
32.20
B

C

ATOM
1544
O
SER B
84
19.659
40.476
0.099
1.00
31.68
B

O

ATOM
1545
N
MET B
85
18.396
39.454
−1.462
1.00
32.77
B

N

ATOM
1546
CA
MET B
85
19.434
38.492
−1.837
1.00
33.78
B

C

ATOM
1547
CB
MET B
85
18.916
37.542
−2.925
1.00
36.68
B

C

ATOM
1548
CG
MET B
85
17.883
36.545
−2.439
1.00
40.28
B

C

ATOM
1549
SD
MET B
85
18.469
35.551
−1.056
1.00
48.72
B

S

ATOM
1550
CE
MET B
85
19.962
34.852
−1.742
1.00
44.99
B

C

ATOM
1551
C
MET B
85
20.704
39.167
−2.342
1.00
32.27
B

C

ATOM
1552
O
MET B
85
21.814
38.650
−2.165
1.00
33.11
B

O

ATOM
1553
N
SER B
86
20.538
40.323
−2.971
1.00
30.58
B

N

ATOM
1554
CA
SER B
86
21.669
41.053
−3.521
1.00
31.46
B

C

ATOM
1555
CB
SER B
86
21.187
42.065
−4.573
1.00
32.63
B

C

ATOM
1556
OG
SER B
86
20.319
43.052
−4.031
1.00
39.50
B

O

ATOM
1557
C
SER B
86
22.492
41.774
−2.471
1.00
29.04
B

C

ATOM
1558
O
SER B
86
23.608
42.227
−2.746
1.00
28.91
B

O

ATOM
1559
N
GLU B
87
21.941
41.863
−1.265
1.00
26.59
B

N

ATOM
1560
CA
GLU B
87
22.608
42.539
−0.162
1.00
24.76
B

C

ATOM
1561
CB
GLU B
87
21.601
43.420
0.581
1.00
25.49
B

C

ATOM
1562
CG
GLU B
87
20.847
44.392
−0.313
1.00
29.17
B

C

ATOM
1563
CD
GLU B
87
19.853
45.248
0.449
1.00
30.87
B

C

ATOM
1564
OE1
GLU B
87
19.028
44.689
1.206
1.00
30.33
B

O

ATOM
1565
OE2
GLU B
87
19.891
46.484
0.283
1.00
35.00
B

O

ATOM
1566
C
GLU B
87
23.257
41.563
0.821
1.00
23.73
B

C

ATOM
1567
O
GLU B
87
24.029
41.972
1.685
1.00
21.32
B

O

ATOM
1568
N
ARG B
88
22.957
40.276
0.676
1.00
22.70
B

N

ATOM
1569
CA
ARG B
88
23.499
39.261
1.578
1.00
24.54
B

C

ATOM
1570
CB
ARG B
88
22.967
37.881
1.194
1.00
25.66
B

C

ATOM
1571
CG
ARG B
88
21.509
37.681
1.537
1.00
27.47
B

C

ATOM
1572
CD
ARG B
88
21.118
36.224
1.391
1.00
29.90
B

C

ATOM
1573
NE
ARG B
88
19.755
35.977
1.853
1.00
33.50
B

N

ATOM
1574
CZ
ARG B
88
19.197
34.772
1.926
1.00
34.03
B

C

ATOM
1575
NH1
ARG B
88
19.888
33.699
1.569
1.00
34.95
B

N

ATOM
1576
NH2
ARG B
88
17.947
34.642
2.350
1.00
35.52
B

N

ATOM
1577
C
ARG B
88
25.018
39.187
1.727
1.00
23.31
B

C

ATOM
1578
O
ARG B
88
25.522
39.058
2.841
1.00
23.06
B

O

ATOM
1579
N
CYS B
89
25.756
39.256
0.626
1.00
23.32
B

N

ATOM
1580
CA
CYS B
89
27.208
39.170
0.739
1.00
22.87
B

C

ATOM
1581
C
CYS B
89
27.778
40.378
1.486
1.00
22.34
B

C

ATOM
1582
O
CYS B
89
28.706
40.238
2.287
1.00
20.71
B

O

ATOM
1583
CB
CYS B
89
27.865
39.037
−0.639
1.00
22.30
B

C

ATOM
1584
SG
CYS B
89
29.668
38.836
−0.507
1.00
24.58
B

S

ATOM
1585
N
TYR B
90
27.207
41.555
1.232
1.00
22.12
B

N

ATOM
1586
CA
TYR B
90
27.636
42.786
1.891
1.00
21.33
B

C

ATOM
1587
CB
TYR B
90
26.896
43.990
1.307
1.00
24.19
B

C

ATOM
1588
CG
TYR B
90
27.227
45.299
1.989
1.00
25.69
B

C

ATOM
1589
CD1
TYR B
90
28.484
45.897
1.838
1.00
26.69
B

C

ATOM
1590
CE1
TYR B
90
28.795
47.101
2.483
1.00
26.25
B

C

ATOM
1591
CD2
TYR B
90
26.290
45.933
2.803
1.00
26.17
B

C

ATOM
1592
CE2
TYR B
90
26.591
47.130
3.452
1.00
27.02
B

C

ATOM
1593
CZ
TYR B
90
27.842
47.707
3.288
1.00
26.75
B

C

ATOM
1594
OH
TYR B
90
28.129
48.891
3.925
1.00
28.36
B

O

ATOM
1595
C
TYR B
90
27.310
42.652
3.375
1.00
20.94
B

C

ATOM
1596
O
TYR B
90
28.081
43.075
4.239
1.00
21.09
B

O

ATOM
1597
N
LEU B
91
26.156
42.065
3.658
1.00
17.63
B

N

ATOM
1598
CA
LEU B
91
25.724
41.828
5.031
1.00
18.40
B

C

ATOM
1599
CB
LEU B
91
24.349
41.158
5.025
1.00
19.21
B

C

ATOM
1600
CG
LEU B
91
23.874
40.595
6.361
1.00
22.33
B

C

ATOM
1601
CD1
LEU B
91
23.538
41.736
7.296
1.00
19.22
B

C

ATOM
1602
CD2
LEU B
91
22.657
39.700
6.137
1.00
23.86
B

C

ATOM
1603
C
LEU B
91
26.734
40.912
5.741
1.00
17.20
B

C

ATOM
1604
O
LEU B
91
27.210
41.211
6.841
1.00
17.10
B

O

ATOM
1605
N
MET B
92
27.056
39.791
5.107
1.00
16.43
B

N

ATOM
1606
CA
MET B
92
27.997
38.847
5.685
1.00
17.07
B

C

ATOM
1607
CB
MET B
92
28.002
37.552
4.871
1.00
16.48
B

C

ATOM
1608
CG
MET B
92
26.703
36.752
4.979
1.00
17.63
B

C

ATOM
1609
SD
MET B
92
26.128
36.605
6.690
1.00
17.99
B

S

ATOM
1610
CE
MET B
92
27.492
35.700
7.425
1.00
14.17
B

C

ATOM
1611
C
MET B
92
29.410
39.430
5.790
1.00
18.87
B

C

ATOM
1612
O
MET B
92
30.187
39.048
6.670
1.00
17.61
B

O

ATOM
1613
N
LYS B
93
29.747
40.350
4.891
1.00
20.69
B

N

ATOM
1614
CA
LYS B
93
31.060
40.988
4.936
1.00
20.45
B

C

ATOM
1615
CB
LYS B
93
31.219
41.984
3.791
1.00
21.79
B

C

ATOM
1616
CG
LYS B
93
32.527
42.755
3.838
1.00
22.89
B

C

ATOM
1617
CD
LYS B
93
32.490
43.949
2.892
1.00
27.03
B

C

ATOM
1618
CE
LYS B
93
33.765
44.778
2.995
1.00
28.50
B

C

ATOM
1619
NZ
LYS B
93
33.700
46.001
2.138
1.00
30.45
B

N

ATOM
1620
C
LYS B
93
31.181
41.732
6.267
1.00
19.66
B

C

ATOM
1621
O
LYS B
93
32.200
41.649
6.946
1.00
19.17
B

O

ATOM
1622
N
GLN B
94
30.131
42.456
6.637
1.00
19.14
B

N

ATOM
1623
CA
GLN B
94
30.136
43.201
7.890
1.00
19.70
B

C

ATOM
1624
CB
GLN B
94
28.814
43.956
8.061
1.00
21.16
B

C

ATOM
1625
CG
GLN B
94
28.392
44.765
6.844
1.00
22.73
B

C

ATOM
1626
CD
GLN B
94
29.451
45.752
6.397
1.00
22.05
B

C

ATOM
1627
OE1
GLN B
94
29.802
45.806
5.217
1.00
26.54
B

O

ATOM
1628
NE2
GLN B
94
29.963
46.541
7.333
1.00
18.51
B

N

ATOM
1629
C
GLN B
94
30.329
42.244
9.071
1.00
18.12
B

C

ATOM
1630
O
GLN B
94
31.121
42.510
9.980
1.00
17.93
B

O

ATOM
1631
N
VAL B
95
29.592
41.138
9.055
1.00
14.83
B

N

ATOM
1632
CA
VAL B
95
29.679
40.140
10.117
1.00
13.76
B

C

ATOM
1633
CB
VAL B
95
28.635
39.025
9.906
1.00
13.80
B

C

ATOM
1634
CG1
VAL B
95
28.812
37.932
10.944
1.00
12.84
B

C

ATOM
1635
CG2
VAL B
95
27.246
39.611
9.997
1.00
11.25
B

C

ATOM
1636
C
VAL B
95
31.079
39.529
10.149
1.00
13.82
B

C

ATOM
1637
O
VAL B
95
31.690
39.410
11.211
1.00
13.76
B

O

ATOM
1638
N
LEU B
96
31.583
39.149
8.980
1.00
14.12
B

N

ATOM
1639
CA
LEU B
96
32.918
38.570
8.870
1.00
15.35
B

C

ATOM
1640
CB
LEU B
96
33.251
38.298
7.403
1.00
15.65
B

C

ATOM
1641
CG
LEU B
96
34.721
37.969
7.126
1.00
16.49
B

C

ATOM
1642
CD1
LEU B
96
35.100
36.677
7.833
1.00
13.79
B

C

ATOM
1643
CD2
LEU B
96
34.947
37.856
5.628
1.00
15.98
B

C

ATOM
1644
C
LEU B
96
34.010
39.471
9.465
1.00
16.84
B

C

ATOM
1645
O
LEU B
96
34.856
39.007
10.238
1.00
16.28
B

O

ATOM
1646
N
ASN B
97
33.994
40.752
9.097
1.00
15.44
B

N

ATOM
1647
CA
ASN B
97
34.997
41.699
9.590
1.00
16.09
B

C

ATOM
1648
CB
ASN B
97
34.901
43.021
8.821
1.00
17.20
B

C

ATOM
1649
CG
ASN B
97
35.362
42.873
7.385
1.00
18.71
B

C

ATOM
1650
OD1
ASN B
97
36.125
41.961
7.081
1.00
18.61
B

O

ATOM
1651
ND2
ASN B
97
34.910
43.761
6.499
1.00
17.57
B

N

ATOM
1652
C
ASN B
97
34.896
41.940
11.085
1.00
15.40
B

C

ATOM
1653
O
ASN B
97
35.914
42.005
11.777
1.00
16.22
B

O

ATOM
1654
N
PHE B
98
33.673
42.066
11.588
1.00
14.94
B

N

ATOM
1655
CA
PHE B
98
33.476
42.266
13.017
1.00
14.55
B

C

ATOM
1656
CB
PHE B
98
31.986
42.369
13.356
1.00
13.40
B

C

ATOM
1657
CG
PHE B
98
31.700
42.315
14.834
1.00
15.06
B

C

ATOM
1658
CD1
PHE B
98
31.958
43.415
15.649
1.00
14.98
B

C

ATOM
1659
CD2
PHE B
98
31.200
41.150
15.418
1.00
14.58
B

C

ATOM
1660
CE1
PHE B
98
31.720
43.360
17.032
1.00
14.56
B

C

ATOM
1661
CE2
PHE B
98
30.957
41.077
16.799
1.00
13.20
B

C

ATOM
1662
CZ
PHE B
98
31.218
42.188
17.608
1.00
12.63
B

C

ATOM
1663
C
PHE B
98
34.055
41.074
13.764
1.00
14.69
B

C

ATOM
1664
O
PHE B
98
34.793
41.227
14.735
1.00
14.16
B

O

ATOM
1665
N
THR B
99
33.705
39.880
13.300
1.00
14.39
B

N

ATOM
1666
CA
THR B
99
34.154
38.651
13.932
1.00
13.57
B

C

ATOM
1667
CB
THR B
99
33.490
37.433
13.257
1.00
12.94
B

C

ATOM
1668
OG1
THR B
99
32.059
37.576
13.316
1.00
12.53
B

O

ATOM
1669
CG2
THR B
99
33.896
36.143
13.958
1.00
12.70
B

C

ATOM
1670
C
THR B
99
35.677
38.516
13.893
1.00
13.81
B

C

ATOM
1671
O
THR B
99
36.295
38.142
14.884
1.00
12.81
B

O

ATOM
1672
N
LEU B
100
36.285
38.830
12.754
1.00
14.39
B

N

ATOM
1673
CA
LEU B
100
37.735
38.732
12.645
1.00
15.17
B

C

ATOM
1674
CB
LEU B
100
38.181
39.035
11.213
1.00
17.01
B

C

ATOM
1675
CG
LEU B
100
38.047
37.902
10.187
1.00
19.42
B

C

ATOM
1676
CD1
LEU B
100
38.195
38.470
8.778
1.00
20.62
B

C

ATOM
1677
CD2
LEU B
100
39.105
36.830
10.460
1.00
19.19
B

C

ATOM
1678
C
LEU B
100
38.439
39.694
13.608
1.00
16.32
B

C

ATOM
1679
O
LEU B
100
39.276
39.289
14.412
1.00
15.91
B

O

ATOM
1680
N
GLU B
101
38.079
40.968
13.533
1.00
15.77
B

N

ATOM
1681
CA
GLU B
101
38.717
41.982
14.365
1.00
17.05
B

C

ATOM
1682
CB
GLU B
101
38.439
43.370
13.781
1.00
20.26
B

C

ATOM
1683
CG
GLU B
101
39.123
43.627
12.449
1.00
25.68
B

C

ATOM
1684
CD
GLU B
101
38.898
45.038
11.941
1.00
29.94
B

C

ATOM
1685
OE1
GLU B
101
39.087
45.992
12.730
1.00
31.04
B

O

ATOM
1686
OE2
GLU B
101
38.541
45.192
10.752
1.00
31.88
B

O

ATOM
1687
C
GLU B
101
38.366
41.992
15.846
1.00
15.48
B

C

ATOM
1688
O
GLU B
101
39.232
42.214
16.684
1.00
14.15
B

O

ATOM
1689
N
GLU B
102
37.103
41.749
16.169
1.00
14.59
B

N

ATOM
1690
CA
GLU B
102
36.664
41.792
17.558
1.00
16.25
B

C

ATOM
1691
CB
GLU B
102
35.292
42.462
17.624
1.00
15.08
B

C

ATOM
1692
CG
GLU B
102
35.257
43.884
17.055
1.00
16.02
B

C

ATOM
1693
CD
GLU B
102
35.992
44.893
17.928
1.00
15.88
B

C

ATOM
1694
OE1
GLU B
102
35.953
44.745
19.168
1.00
15.08
B

O

ATOM
1695
OE2
GLU B
102
36.595
45.846
17.383
1.00
15.59
B

O

ATOM
1696
C
GLU B
102
36.611
40.451
18.283
1.00
17.63
B

C

ATOM
1697
O
GLU B
102
36.475
40.408
19.510
1.00
16.52
B

O

ATOM
1698
N
VAL B
103
36.721
39.357
17.539
1.00
16.71
B

N

ATOM
1699
CA
VAL B
103
36.660
38.039
18.151
1.00
16.91
B

C

ATOM
1700
CB
VAL B
103
35.392
37.286
17.709
1.00
16.05
B

C

ATOM
1701
CG1
VAL B
103
35.394
35.881
18.310
1.00
19.19
B

C

ATOM
1702
CG2
VAL B
103
34.157
38.054
18.144
1.00
18.67
B

C

ATOM
1703
C
VAL B
103
37.845
37.128
17.862
1.00
17.70
B

C

ATOM
1704
O
VAL B
103
38.540
36.680
18.784
1.00
16.69
B

O

ATOM
1705
N
LEU B
104
38.067
36.855
16.581
1.00
16.37
B

N

ATOM
1706
CA
LEU B
104
39.137
35.960
16.168
1.00
18.90
B

C

ATOM
1707
CB
LEU B
104
38.984
35.614
14.687
1.00
15.60
B

C

ATOM
1708
CG
LEU B
104
37.636
34.955
14.362
1.00
16.30
B

C

ATOM
1709
CD1
LEU B
104
37.541
34.663
12.874
1.00
14.16
B

C

ATOM
1710
CD2
LEU B
104
37.485
33.671
15.162
1.00
16.44
B

C

ATOM
1711
C
LEU B
104
40.539
36.471
16.447
1.00
20.44
B

C

ATOM
1712
O
LEU B
104
41.326
35.780
17.086
1.00
20.16
B

O

ATOM
1713
N
PHE B
105
40.870
37.666
15.979
1.00
21.99
B

N

ATOM
1714
CA
PHE B
105
42.213
38.166
16.239
1.00
27.13
B

C

ATOM
1715
CB
PHE B
105
42.387
39.579
15.675
1.00
28.81
B

C

ATOM
1716
CG
PHE B
105
42.367
39.634
14.168
1.00
31.64
B

C

ATOM
1717
CD1
PHE B
105
42.837
38.563
13.411
1.00
33.85
B

C

ATOM
1718
CD2
PHE B
105
41.888
40.757
13.506
1.00
34.49
B

C

ATOM
1719
CE1
PHE B
105
42.831
38.611
12.015
1.00
34.86
B

C

ATOM
1720
CE2
PHE B
105
41.879
40.816
12.110
1.00
35.62
B

C

ATOM
1721
CZ
PHE B
105
42.351
39.739
11.365
1.00
35.69
B

C

ATOM
1722
C
PHE B
105
42.538
38.122
17.734
1.00
27.95
B

C

ATOM
1723
O
PHE B
105
43.607
37.656
18.121
1.00
28.77
B

O

ATOM
1724
N
PRO B
106
41.613
38.587
18.594
1.00
28.70
B

N

ATOM
1725
CD
PRO B
106
40.390
39.341
18.266
1.00
28.83
B

C

ATOM
1726
CA
PRO B
106
41.836
38.578
20.045
1.00
27.96
B

C

ATOM
1727
CB
PRO B
106
40.590
39.280
20.589
1.00
28.83
B

C

ATOM
1728
CG
PRO B
106
40.223
40.214
19.481
1.00
28.82
B

C

ATOM
1729
C
PRO B
106
41.991
37.166
20.622
1.00
27.58
B

C

ATOM
1730
O
PRO B
106
42.607
36.983
21.671
1.00
25.86
B

O

ATOM
1731
N
GLN B
107
41.419
36.174
19.945
1.00
26.57
B

N

ATOM
1732
CA
GLN B
107
41.499
34.784
20.394
1.00
27.34
B

C

ATOM
1733
CB
GLN B
107
40.119
34.123
20.321
1.00
25.90
B

C

ATOM
1734
CG
GLN B
107
39.027
34.737
21.181
1.00
27.05
B

C

ATOM
1735
CD
GLN B
107
39.054
34.228
22.601
1.00
27.78
B

C

ATOM
1736
OE1
GLN B
107
39.453
33.093
22.852
1.00
29.49
B

O

ATOM
1737
NE2
GLN B
107
38.613
35.056
23.539
1.00
24.76
B

N

ATOM
1738
C
GLN B
107
42.457
33.994
19.497
1.00
28.04
B

C

ATOM
1739
O
GLN B
107
42.514
32.769
19.572
1.00
28.67
B

O

ATOM
1740
N
SER B
108
43.206
34.697
18.654
1.00
29.80
B

N

ATOM
1741
CA
SER B
108
44.125
34.059
17.710
1.00
31.32
B

C

ATOM
1742
CB
SER B
108
44.873
35.129
16.917
1.00
31.54
B

C

ATOM
1743
OG
SER B
108
45.612
35.971
17.784
1.00
33.99
B

O

ATOM
1744
C
SER B
108
45.131
33.064
18.291
1.00
32.91
B

C

ATOM
1745
O
SER B
108
45.661
32.220
17.562
1.00
32.09
B

O

ATOM
1746
N
ASP B
109
45.399
33.156
19.589
1.00
33.94
B

N

ATOM
1747
CA
ASP B
109
46.346
32.243
20.221
1.00
36.43
B

C

ATOM
1748
CB
ASP B
109
47.268
33.002
21.178
1.00
38.99
B

C

ATOM
1749
CG
ASP B
109
48.429
33.660
20.464
1.00
41.54
B

C

ATOM
1750
OD1
ASP B
109
48.195
34.463
19.536
1.00
43.90
B

O

ATOM
1751
OD2
ASP B
109
49.585
33.370
20.834
1.00
45.38
B

O

ATOM
1752
C
ASP B
109
45.669
31.103
20.965
1.00
35.97
B

C

ATOM
1753
O
ASP B
109
46.340
30.261
21.558
1.00
37.38
B

O

ATOM
1754
N
ARG B
110
44.342
31.070
20.929
1.00
34.07
B

N

ATOM
1755
CA
ARG B
110
43.595
30.019
21.606
1.00
32.11
B

C

ATOM
1756
CB
ARG B
110
42.483
30.628
22.457
1.00
34.24
B

C

ATOM
1757
CG
ARG B
110
42.974
31.587
23.523
1.00
38.78
B

C

ATOM
1758
CD
ARG B
110
41.799
32.210
24.253
1.00
42.57
B

C

ATOM
1759
NE
ARG B
110
42.213
33.153
25.285
1.00
46.77
B

N

ATOM
1760
CZ
ARG B
110
42.872
32.815
26.389
1.00
48.68
B

C

ATOM
1761
NH1
ARG B
110
43.198
31.545
26.610
1.00
48.55
B

N

ATOM
1762
NH2
ARG B
110
43.197
33.750
27.274
1.00
49.15
B

N

ATOM
1763
C
ARG B
110
42.989
29.047
20.601
1.00
29.74
B

C

ATOM
1764
O
ARG B
110
43.132
29.216
19.391
1.00
28.95
B

O

ATOM
1765
N
PHE B
111
42.314
28.025
21.119
1.00
28.23
B

N

ATOM
1766
CA
PHE B
111
41.671
27.018
20.289
1.00
25.68
B

C

ATOM
1767
CB
PHE B
111
40.429
27.619
19.627
1.00
25.02
B

C

ATOM
1768
CG
PHE B
111
39.351
28.002
20.604
1.00
21.00
B

C

ATOM
1769
CD1
PHE B
111
38.563
27.029
21.206
1.00
22.14
B

C

ATOM
1770
CD2
PHE B
111
39.151
29.331
20.954
1.00
21.84
B

C

ATOM
1771
CE1
PHE B
111
37.586
27.374
22.146
1.00
21.32
B

C

ATOM
1772
CE2
PHE B
111
38.178
29.687
21.891
1.00
22.27
B

C

ATOM
1773
CZ
PHE B
111
37.397
28.704
22.487
1.00
20.90
B

C

ATOM
1774
C
PHE B
111
42.610
26.436
19.239
1.00
25.72
B

C

ATOM
1775
O
PHE B
111
42.240
26.272
18.080
1.00
23.01
B

O

ATOM
1776
N
GLN B
112
43.829
26.119
19.659
1.00
26.79
B

N

ATOM
1777
CA
GLN B
112
44.820
25.530
18.764
1.00
28.39
B

C

ATOM
1778
CB
GLN B
112
46.211
25.622
19.392
1.00
29.98
B

C

ATOM
1779
CG
GLN B
112
46.709
27.043
19.587
1.00
33.82
B

C

ATOM
1780
CD
GLN B
112
48.085
27.100
20.227
1.00
36.64
B

C

ATOM
1781
OE1
GLN B
112
49.036
26.482
19.742
1.00
39.25
B

O

ATOM
1782
NE2
GLN B
112
48.199
27.847
21.320
1.00
36.49
B

N

ATOM
1783
C
GLN B
112
44.470
24.063
18.501
1.00
28.37
B

C

ATOM
1784
O
GLN B
112
43.903
23.389
19.358
1.00
27.65
B

O

ATOM
1785
N
PRO B
113
44.820
23.545
17.313
1.00
28.65
B

N

ATOM
1786
CD
PRO B
113
44.778
22.094
17.054
1.00
28.84
B

C

ATOM
1787
CA
PRO B
113
45.511
24.236
16.220
1.00
28.88
B

C

ATOM
1788
CB
PRO B
113
46.398
23.144
15.658
1.00
29.67
B

C

ATOM
1789
CG
PRO B
113
45.455
21.976
15.683
1.00
28.06
B

C

ATOM
1790
C
PRO B
113
44.550
24.757
15.160
1.00
29.20
B

C

ATOM
1791
O
PRO B
113
44.981
25.265
14.127
1.00
31.40
B

O

ATOM
1792
N
TYR B
114
43.253
24.624
15.414
1.00
29.48
B

N

ATOM
1793
CA
TYR B
114
42.232
25.047
14.459
1.00
29.46
B

C

ATOM
1794
CB
TYR B
114
40.839
24.695
14.992
1.00
30.23
B

C

ATOM
1795
CG
TYR B
114
40.717
23.288
15.537
1.00
30.05
B

C

ATOM
1796
CD1
TYR B
114
40.943
22.177
14.724
1.00
32.21
B

C

ATOM
1797
CE1
TYR B
114
40.840
20.881
15.230
1.00
32.84
B

C

ATOM
1798
CD2
TYR B
114
40.383
23.069
16.871
1.00
31.34
B

C

ATOM
1799
CE2
TYR B
114
40.278
21.784
17.385
1.00
32.91
B

C

ATOM
1800
CZ
TYR B
114
40.508
20.695
16.562
1.00
33.51
B

C

ATOM
1801
OH
TYR B
114
40.413
19.424
17.081
1.00
35.76
B

O

ATOM
1802
C
TYR B
114
42.271
26.530
14.117
1.00
28.68
B

C

ATOM
1803
O
TYR B
114
42.347
26.909
12.948
1.00
29.12
B

O

ATOM
1804
N
MET B
115
42.213
27.366
15.146
1.00
28.56
B

N

ATOM
1805
CA
MET B
115
42.214
28.816
14.973
1.00
27.58
B

C

ATOM
1806
CB
MET B
115
42.343
29.488
16.344
1.00
27.94
B

C

ATOM
1807
CG
MET B
115
42.184
30.992
16.341
1.00
26.96
B

C

ATOM
1808
SD
MET B
115
40.483
31.474
16.055
1.00
27.58
B

S

ATOM
1809
CE
MET B
115
39.757
31.233
17.663
1.00
25.68
B

C

ATOM
1810
C
MET B
115
43.322
29.326
14.050
1.00
27.41
B

C

ATOM
1811
O
MET B
115
43.087
30.163
13.181
1.00
27.38
B

O

ATOM
1812
N
GLN B
116
44.530
28.814
14.240
1.00
28.20
B

N

ATOM
1813
CA
GLN B
116
45.679
29.243
13.458
1.00
29.73
B

C

ATOM
1814
CB
GLN B
116
46.935
28.565
13.997
1.00
31.41
B

C

ATOM
1815
CG
GLN B
116
47.200
28.852
15.474
1.00
34.08
B

C

ATOM
1816
CD
GLN B
116
46.074
28.388
16.390
1.00
35.14
B

C

ATOM
1817
OE1
GLN B
116
45.649
27.235
16.338
1.00
34.39
B

O

ATOM
1818
NE2
GLN B
116
45.590
29.292
17.239
1.00
37.03
B

N

ATOM
1819
C
GLN B
116
45.579
29.037
11.948
1.00
30.97
B

C

ATOM
1820
O
GLN B
116
46.279
29.697
11.184
1.00
31.99
B

O

ATOM
1821
N
GLU B
117
44.714
28.129
11.513
1.00
31.07
B

N

ATOM
1822
CA
GLU B
117
44.549
27.875
10.086
1.00
30.90
B

C

ATOM
1823
CB
GLU B
117
44.409
26.375
9.839
1.00
33.41
B

C

ATOM
1824
CG
GLU B
117
45.624
25.581
10.273
1.00
37.00
B

C

ATOM
1825
CD
GLU B
117
45.416
24.089
10.155
1.00
39.15
B

C

ATOM
1826
OE1
GLU B
117
44.547
23.549
10.877
1.00
41.69
B

O

ATOM
1827
OE2
GLU B
117
46.123
23.460
9.339
1.00
40.83
B

O

ATOM
1828
C
GLU B
117
43.328
28.601
9.532
1.00
28.96
B

C

ATOM
1829
O
GLU B
117
43.359
29.151
8.428
1.00
29.54
B

O

ATOM
1830
N
VAL B
118
42.256
28.613
10.314
1.00
25.88
B

N

ATOM
1831
CA
VAL B
118
41.021
29.256
9.898
1.00
23.47
B

C

ATOM
1832
CB
VAL B
118
39.869
28.897
10.868
1.00
23.29
B

C

ATOM
1833
CG1
VAL B
118
38.603
29.663
10.491
1.00
21.92
B

C

ATOM
1834
CG2
VAL B
118
39.618
27.391
10.829
1.00
22.44
B

C

ATOM
1835
C
VAL B
118
41.115
30.773
9.772
1.00
22.53
B

C

ATOM
1836
O
VAL B
118
40.622
31.347
8.804
1.00
21.65
B

O

ATOM
1837
N
VAL B
119
41.748
31.429
10.739
1.00
23.10
B

N

ATOM
1838
CA
VAL B
119
41.856
32.885
10.696
1.00
23.11
B

C

ATOM
1839
CB
VAL B
119
42.573
33.432
11.941
1.00
23.48
B

C

ATOM
1840
CG1
VAL B
119
42.727
34.937
11.830
1.00
24.03
B

C

ATOM
1841
CG2
VAL B
119
41.771
33.094
13.182
1.00
25.07
B

C

ATOM
1842
C
VAL B
119
42.537
33.427
9.438
1.00
22.58
B

C

ATOM
1843
O
VAL B
119
42.025
34.350
8.805
1.00
21.65
B

O

ATOM
1844
N
PRO B
120
43.705
32.874
9.063
1.00
23.16
B

N

ATOM
1845
CD
PRO B
120
44.529
31.844
9.721
1.00
23.03
B

C

ATOM
1846
CA
PRO B
120
44.371
33.378
7.856
1.00
22.66
B

C

ATOM
1847
CB
PRO B
120
45.574
32.452
7.715
1.00
23.90
B

C

ATOM
1848
CG
PRO B
120
45.899
32.114
9.133
1.00
23.90
B

C

ATOM
1849
C
PRO B
120
43.434
33.294
6.654
1.00
23.50
B

C

ATOM
1850
O
PRO B
120
43.346
34.226
5.846
1.00
21.52
B

O

ATOM
1851
N
PHE B
121
42.727
32.169
6.555
1.00
23.36
B

N

ATOM
1852
CA
PHE B
121
41.786
31.932
5.466
1.00
22.84
B

C

ATOM
1853
CB
PHE B
121
41.168
30.541
5.585
1.00
23.11
B

C

ATOM
1854
CG
PHE B
121
40.089
30.278
4.579
1.00
24.84
B

C

ATOM
1855
CD1
PHE B
121
40.400
30.074
3.241
1.00
25.82
B

C

ATOM
1856
CD2
PHE B
121
38.755
30.260
4.966
1.00
25.84
B

C

ATOM
1857
CE1
PHE B
121
39.396
29.856
2.302
1.00
25.59
B

C

ATOM
1858
CE2
PHE B
121
37.744
30.043
4.033
1.00
27.74
B

C

ATOM
1859
CZ
PHE B
121
38.067
29.841
2.699
1.00
26.97
B

C

ATOM
1860
C
PHE B
121
40.679
32.974
5.474
1.00
22.35
B

C

ATOM
1861
O
PHE B
121
40.382
33.572
4.443
1.00
22.39
B

O

ATOM
1862
N
LEU B
122
40.059
33.180
6.633
1.00
22.63
B

N

ATOM
1863
CA
LEU B
122
39.003
34.181
6.732
1.00
21.52
B

C

ATOM
1864
CB
LEU B
122
38.321
34.102
8.109
1.00
20.83
B

C

ATOM
1865
CG
LEU B
122
37.578
32.795
8.420
1.00
20.51
B

C

ATOM
1866
CD1
LEU B
122
36.959
32.858
9.813
1.00
19.20
B

C

ATOM
1867
CD2
LEU B
122
36.501
32.566
7.375
1.00
19.61
B

C

ATOM
1868
C
LEU B
122
39.527
35.600
6.460
1.00
21.22
B

C

ATOM
1869
O
LEU B
122
38.805
36.409
5.890
1.00
20.75
B

O

ATOM
1870
N
ALA B
123
40.771
35.878
6.853
1.00
22.05
B

N

ATOM
1871
CA
ALA B
123
41.379
37.190
6.637
1.00
24.52
B

C

ATOM
1872
CB
ALA B
123
42.804
37.224
7.280
1.00
24.63
B

C

ATOM
1873
C
ALA B
123
41.489
37.419
5.129
1.00
26.44
B

C

ATOM
1874
O
ALA B
123
41.225
38.505
4.618
1.00
25.74
B

O

ATOM
1875
N
ARG B
124
41.941
36.397
4.381
1.00
27.56
B

N

ATOM
1876
CA
ARG B
124
42.092
36.492
2.915
1.00
28.25
B

C

ATOM
1877
CB
AARG B
124
42.562
35.166
2.361
0.50
31.53
B

C

ATOM
1878
CB
BARG B
124
42.543
35.160
2.316
0.50
31.52
B

C

ATOM
1879
CG
AARG B
124
43.971
34.730
2.819
0.50
34.27
B

C

ATOM
1880
CG
BARG B
124
43.953
34.764
2.660
0.50
34.62
B

C

ATOM
1881
CD
AARG B
124
44.500
33.566
1.961
0.50
36.72
B

C

ATOM
1882
CD
BARG B
124
44.485
33.793
1.624
0.50
36.96
B

C

ATOM
1883
NE
AARG B
124
44.367
32.250
2.587
0.50
38.21
B

N

ATOM
1884
NE
BARG B
124
43.633
32.620
1.416
0.50
39.16
B

N

ATOM
1885
CZ
AARG B
124
45.302
31.685
3.346
0.50
39.41
B

C

ATOM
1886
CZ
BARG B
124
42.571
32.573
0.613
0.50
39.85
B

C

ATOM
1887
NH1A
ARG B
124
46.444
32.318
3.574
0.50
39.45
B

N

ATOM
1888
NH1B
ARG B
124
42.196
33.638
−0.084
0.50
39.88
B

N

ATOM
1889
NH2A
ARG B
124
45.097
30.487
3.874
0.50
40.70
B

N

ATOM
1890
NH2B
ARG B
124
41.878
31.449
0.504
0.50
40.63
B

N

ATOM
1891
C
ARG B
124
40.755
36.861
2.270
1.00
28.59
B

C

ATOM
1892
O
ARG B
124
40.699
37.698
1.347
1.00
28.10
B

O

ATOM
1893
N
LEU B
125
39.685
36.193
2.734
1.00
28.01
B

N

ATOM
1894
CA
LEU B
125
38.367
36.466
2.203
1.00
25.98
B

C

ATOM
1895
CB
LEU B
125
37.333
35.525
2.822
1.00
27.46
B

C

ATOM
1896
CG
LEU B
125
37.385
34.019
2.530
1.00
27.82
B

C

ATOM
1897
CD1
LEU B
125
36.107
33.354
3.052
1.00
26.92
B

C

ATOM
1898
CD2
LEU B
125
37.519
33.771
1.039
1.00
27.76
B

C

ATOM
1899
C
LEU B
125
37.940
37.905
2.469
1.00
25.43
B

C

ATOM
1900
O
LEU B
125
37.301
38.547
1.629
1.00
25.94
B

O

ATOM
1901
N
SER B
126
38.262
38.392
3.660
1.00
24.59
B

N

ATOM
1902
CA
SER B
126
37.937
39.757
4.040
1.00
25.45
B

C

ATOM
1903
CB
SER B
126
38.427
40.030
5.463
1.00
25.70
B

C

ATOM
1904
OG
SER B
126
38.216
41.382
5.819
1.00
24.65
B

O

ATOM
1905
C
SER B
126
38.671
40.668
3.067
1.00
26.58
B

C

ATOM
1906
O
SER B
126
38.126
41.664
2.584
1.00
25.56
B

O

ATOM
1907
N
ASN B
127
39.920
40.311
2.789
1.00
28.53
B

N

ATOM
1908
CA
ASN B
127
40.766
41.069
1.875
1.00
31.42
B

C

ATOM
1909
CB
ASN B
127
42.149
40.415
1.810
1.00
33.56
B

C

ATOM
1910
CG
ASN B
127
43.145
41.230
1.017
1.00
37.76
B

C

ATOM
1911
OD1
ASN B
127
43.392
42.396
1.326
1.00
41.52
B

O

ATOM
1912
ND2
ASN B
127
43.734
40.617
−0.008
1.00
37.74
B

N

ATOM
1913
C
ASN B
127
40.114
41.110
0.492
1.00
31.83
B

C

ATOM
1914
O
ASN B
127
40.081
42.154
−0.160
1.00
32.67
B

O

ATOM
1915
N
ARG B
128
39.584
39.971
0.057
1.00
33.16
B

N

ATOM
1916
CA
ARG B
128
38.919
39.872
−1.239
1.00
35.03
B

C

ATOM
1917
CB
ARG B
128
38.477
38.429
−1.499
1.00
37.42
B

C

ATOM
1918
CG
ARG B
128
39.572
37.384
−1.393
1.00
40.66
B

C

ATOM
1919
CD
ARG B
128
40.484
37.388
−2.602
1.00
44.62
B

C

ATOM
1920
NE
ARG B
128
41.399
36.248
−2.596
1.00
47.25
B

N

ATOM
1921
CZ
ARG B
128
42.370
36.069
−1.706
1.00
49.09
B

C

ATOM
1922
NH1
ARG B
128
42.562
36.957
−0.737
1.00
49.49
B

N

ATOM
1923
NH2
ARG B
128
43.155
35.002
−1.787
1.00
49.90
B

N

ATOM
1924
C
ARG B
128
37.686
40.780
−1.311
1.00
35.69
B

C

ATOM
1925
O
ARG B
128
37.401
41.370
−2.352
1.00
35.80
B

O

ATOM
1926
N
LEU B
129
36.955
40.886
−0.206
1.00
35.75
B

N

ATOM
1927
CA
LEU B
129
35.746
41.709
−0.161
1.00
36.71
B

C

ATOM
1928
CB
LEU B
129
34.816
41.213
0.952
1.00
35.61
B

C

ATOM
1929
CG
LEU B
129
34.227
39.810
0.784
1.00
36.13
B

C

ATOM
1930
CD1
LEU B
129
33.424
39.445
2.017
1.00
35.68
B

C

ATOM
1931
CD2
LEU B
129
33.344
39.761
−0.454
1.00
34.32
B

C

ATOM
1932
C
LEU B
129
36.018
43.200
0.043
1.00
37.24
B

C

ATOM
1933
O
LEU B
129
35.086
43.989
0.178
1.00
37.30
B

O

ATOM
1934
N
SER B
130
37.291
43.577
0.059
1.00
39.20
B

N

ATOM
1935
CA
SER B
130
37.693
44.969
0.268
1.00
41.51
B

C

ATOM
1936
CB
SER B
130
39.122
45.191
−0.238
1.00
41.64
B

C

ATOM
1937
OG
SER B
130
40.062
44.614
0.651
1.00
44.96
B

O

ATOM
1938
C
SER B
130
36.789
46.030
−0.345
1.00
41.71
B

C

ATOM
1939
O
SER B
130
36.579
46.056
−1.550
1.00
43.01
B

O

ATOM
1940
N
THR B
131
36.259
46.900
0.508
1.00
42.65
B

N

ATOM
1941
CA
THR B
131
35.399
48.012
0.103
1.00
43.65
B

C

ATOM
1942
CB
THR B
131
36.223
49.110
−0.617
1.00
44.32
B

C

ATOM
1943
OG1
THR B
131
36.682
48.620
−1.885
1.00
45.77
B

O

ATOM
1944
CG2
THR B
131
37.428
49.511
0.236
1.00
44.02
B

C

ATOM
1945
C
THR B
131
34.161
47.723
−0.747
1.00
43.82
B

C

ATOM
1946
O
THR B
131
33.401
48.649
−1.041
1.00
43.74
B

O

ATOM
1947
N
CYS B
132
33.945
46.470
−1.146
1.00
43.43
B

N

ATOM
1948
CA
CYS B
132
32.762
46.157
−1.949
1.00
42.56
B

C

ATOM
1949
C
CYS B
132
31.564
46.639
−1.146
1.00
42.53
B

C

ATOM
1950
O
CYS B
132
31.515
46.452
0.068
1.00
42.41
B

O

ATOM
1951
CB
CYS B
132
32.644
44.651
−2.205
1.00
41.08
B

C

ATOM
1952
SG
CYS B
132
32.191
43.674
−0.738
1.00
40.07
B

S

ATOM
1953
N
HIS B
133
30.608
47.277
−1.813
1.00
44.03
B

N

ATOM
1954
CA
HIS B
133
29.434
47.790
−1.120
1.00
45.92
B

C

ATOM
1955
CB
HIS B
133
29.661
49.247
−0.723
1.00
48.01
B

C

ATOM
1956
CG
HIS B
133
29.999
50.136
−1.877
1.00
50.95
B

C

ATOM
1957
CD2
HIS B
133
29.344
51.195
−2.408
1.00
51.52
B

C

ATOM
1958
ND1
HIS B
133
31.132
49.961
−2.642
1.00
52.14
B

N

ATOM
1959
CE1
HIS B
133
31.161
50.875
−3.596
1.00
52.81
B

C

ATOM
1960
NE2
HIS B
133
30.088
51.636
−3.477
1.00
52.91
B

N

ATOM
1961
C
HIS B
133
28.158
47.680
−1.940
1.00
45.88
B

C

ATOM
1962
O
HIS B
133
28.143
47.067
−3.005
1.00
45.95
B

O

ATOM
1963
N
ILE B
134
27.086
48.281
−1.433
1.00
46.79
B

N

ATOM
1964
CA
ILE B
134
25.798
48.245
−2.110
1.00
48.22
B

C

ATOM
1965
CB
ILE B
134
24.686
47.725
−1.172
1.00
47.47
B

C

ATOM
1966
CG2
ILE B
134
25.035
46.328
−0.684
1.00
47.42
B

C

ATOM
1967
CG1
ILE B
134
24.515
48.672
0.016
1.00
46.57
B

C

ATOM
1968
CD
ILE B
134
23.426
48.248
0.977
1.00
47.17
B

C

ATOM
1969
C
ILE B
134
25.385
49.614
−2.644
1.00
49.84
B

C

ATOM
1970
O
ILE B
134
26.079
50.611
−2.439
1.00
49.80
B

O

ATOM
1971
N
GLU B
135
24.243
49.642
−3.326
1.00
50.44
B

N

ATOM
1972
CA
GLU B
135
23.700
50.860
−3.921
1.00
51.87
B

C

ATOM
1973
CB
GLU B
135
22.405
50.531
−4.671
1.00
53.19
B

C

ATOM
1974
CG
GLU B
135
22.597
49.598
−5.859
1.00
55.61
B

C

ATOM
1975
CD
GLU B
135
23.283
48.298
−5.475
1.00
57.90
B

C

ATOM
1976
OE1
GLU B
135
22.787
47.613
−4.554
1.00
58.58
B

O

ATOM
1977
OE2
GLU B
135
24.317
47.963
−6.093
1.00
59.79
B

O

ATOM
1978
C
GLU B
135
23.445
51.989
−2.918
1.00
51.36
B

C

ATOM
1979
O
GLU B
135
24.324
52.820
−2.677
1.00
51.02
B

O

ATOM
1980
N
GLY B
136
22.245
52.022
−2.341
1.00
50.44
B

N

ATOM
1981
CA
GLY B
136
21.930
53.074
−1.393
1.00
49.30
B

C

ATOM
1982
C
GLY B
136
21.197
52.672
−0.128
1.00
47.53
B

C

ATOM
1983
O
GLY B
136
20.289
51.839
−0.147
1.00
46.93
B

O

ATOM
1984
N
ASP B
137
21.614
53.284
0.976
1.00
46.58
B

N

ATOM
1985
CA
ASP B
137
21.027
53.064
2.293
1.00
45.28
B

C

ATOM
1986
CB
ASP B
137
19.559
53.486
2.277
1.00
47.28
B

C

ATOM
1987
CG
ASP B
137
18.981
53.623
3.661
1.00
48.41
B

C

ATOM
1988
OD1
ASP B
137
19.131
52.681
4.465
1.00
48.28
B

O

ATOM
1989
OD2
ASP B
137
18.378
54.675
3.947
1.00
51.40
B

O

ATOM
1990
C
ASP B
137
21.133
51.650
2.844
1.00
43.55
B

C

ATOM
1991
O
ASP B
137
20.277
50.803
2.590
1.00
43.30
B

O

ATOM
1992
N
ASP B
138
22.184
51.416
3.620
1.00
40.92
B

N

ATOM
1993
CA
ASP B
138
22.419
50.118
4.237
1.00
38.17
B

C

ATOM
1994
CB
ASP B
138
23.899
49.774
4.155
1.00
37.09
B

C

ATOM
1995
CG
ASP B
138
24.751
50.703
4.992
1.00
38.19
B

C

ATOM
1996
OD1
ASP B
138
24.292
51.828
5.283
1.00
38.67
B

O

ATOM
1997
OD2
ASP B
138
25.882
50.319
5.354
1.00
39.46
B

O

ATOM
1998
C
ASP B
138
21.988
50.124
5.712
1.00
36.48
B

C

ATOM
1999
O
ASP B
138
22.428
49.286
6.501
1.00
36.23
B

O

ATOM
2000
N
LEU B
139
21.124
51.065
6.076
1.00
35.08
B

N

ATOM
2001
CA
LEU B
139
20.650
51.196
7.450
1.00
33.13
B

C

ATOM
2002
CB
LEU B
139
19.592
52.298
7.533
1.00
36.06
B

C

ATOM
2003
CG
LEU B
139
19.099
52.661
8.934
1.00
37.59
B

C

ATOM
2004
CD1
LEU B
139
20.224
53.321
9.706
1.00
39.27
B

C

ATOM
2005
CD2
LEU B
139
17.909
53.599
8.840
1.00
40.35
B

C

ATOM
2006
C
LEU B
139
20.087
49.903
8.030
1.00
31.75
B

C

ATOM
2007
O
LEU B
139
20.423
49.524
9.153
1.00
31.56
B

O

ATOM
2008
N
HIS B
140
19.227
49.226
7.275
1.00
29.29
B

N

ATOM
2009
CA
HIS B
140
18.634
47.975
7.748
1.00
27.87
B

C

ATOM
2010
CB
HIS B
140
17.598
47.465
6.738
1.00
29.34
B

C

ATOM
2011
CG
HIS B
140
18.158
47.209
5.374
1.00
30.92
B

C

ATOM
2012
CD2
HIS B
140
18.179
46.088
4.614
1.00
32.52
B

C

ATOM
2013
ND1
HIS B
140
18.796
48.183
4.636
1.00
33.09
B

N

ATOM
2014
CE1
HIS B
140
19.187
47.672
3.481
1.00
33.64
B

C

ATOM
2015
NE2
HIS B
140
18.826
46.403
3.442
1.00
33.59
B

N

ATOM
2016
C
HIS B
140
19.714
46.912
7.977
1.00
24.95
B

C

ATOM
2017
O
HIS B
140
19.614
46.083
8.878
1.00
24.47
B

O

ATOM
2018
N
ILE B
141
20.752
46.946
7.156
1.00
23.58
B

N

ATOM
2019
CA
ILE B
141
21.840
45.991
7.289
1.00
22.50
B

C

ATOM
2020
CB
ILE B
141
22.765
46.043
6.059
1.00
23.20
B

C

ATOM
2021
CG2
ILE B
141
23.982
45.171
6.283
1.00
22.62
B

C

ATOM
2022
CG1
ILE B
141
21.983
45.592
4.818
1.00
24.14
B

C

ATOM
2023
CD
ILE B
141
22.783
45.609
3.541
1.00
26.45
B

C

ATOM
2024
C
ILE B
141
22.641
46.287
8.556
1.00
22.44
B

C

ATOM
2025
O
ILE B
141
22.899
45.390
9.361
1.00
19.54
B

O

ATOM
2026
N
GLN B
142
23.020
47.548
8.738
1.00
21.44
B

N

ATOM
2027
CA
GLN B
142
23.792
47.932
9.913
1.00
20.93
B

C

ATOM
2028
CB
GLN B
142
24.152
49.418
9.858
1.00
23.51
B

C

ATOM
2029
CG
GLN B
142
25.108
49.807
8.734
1.00
27.67
B

C

ATOM
2030
CD
GLN B
142
26.345
48.920
8.666
1.00
31.25
B

C

ATOM
2031
OE1
GLN B
142
26.874
48.488
9.692
1.00
33.98
B

O

ATOM
2032
NE2
GLN B
142
26.819
48.659
7.451
1.00
31.45
B

N

ATOM
2033
C
GLN B
142
23.031
47.634
11.202
1.00
19.58
B

C

ATOM
2034
O
GLN B
142
23.621
47.216
12.195
1.00
19.52
B

O

ATOM
2035
N
ARG B
143
21.718
47.847
11.182
1.00
19.46
B

N

ATOM
2036
CA
ARG B
143
20.891
47.598
12.355
1.00
18.97
B

C

ATOM
2037
CB
ARG B
143
19.454
48.084
12.117
1.00
19.80
B

C

ATOM
2038
CG
ARG B
143
18.572
47.982
13.361
1.00
20.29
B

C

ATOM
2039
CD
ARG B
143
17.151
48.457
13.118
1.00
24.78
B

C

ATOM
2040
NE
ARG B
143
17.081
49.859
12.703
1.00
27.22
B

N

ATOM
2041
CZ
ARG B
143
16.831
50.261
11.459
1.00
29.43
B

C

ATOM
2042
NH1
ARG B
143
16.625
49.367
10.499
1.00
28.10
B

N

ATOM
2043
NH2
ARG B
143
16.785
51.557
11.172
1.00
29.11
B

N

ATOM
2044
C
ARG B
143
20.879
46.116
12.716
1.00
19.02
B

C

ATOM
2045
O
ARG B
143
20.936
45.751
13.896
1.00
18.36
B

O

ATOM
2046
N
ASN B
144
20.795
45.259
11.703
1.00
17.05
B

N

ATOM
2047
CA
ASN B
144
20.783
43.822
11.944
1.00
17.50
B

C

ATOM
2048
CB
ASN B
144
20.492
43.053
10.649
1.00
16.62
B

C

ATOM
2049
CG
ASN B
144
19.062
43.240
10.169
1.00
18.56
B

C

ATOM
2050
OD1
ASN B
144
18.280
43.963
10.781
1.00
15.87
B

O

ATOM
2051
ND2
ASN B
144
18.714
42.582
9.070
1.00
18.04
B

N

ATOM
2052
C
ASN B
144
22.125
43.381
12.503
1.00
16.92
B

C

ATOM
2053
O
ASN B
144
22.181
42.547
13.400
1.00
16.92
B

O

ATOM
2054
N
VAL B
145
23.205
43.943
11.967
1.00
15.33
B

N

ATOM
2055
CA
VAL B
145
24.544
43.598
12.423
1.00
15.98
B

C

ATOM
2056
CB
VAL B
145
25.615
44.191
11.469
1.00
17.14
B

C

ATOM
2057
CG1
VAL B
145
27.020
43.920
12.007
1.00
17.91
B

C

ATOM
2058
CG2
VAL B
145
25.456
43.584
10.080
1.00
18.98
B

C

ATOM
2059
C
VAL B
145
24.760
44.118
13.846
1.00
16.15
B

C

ATOM
2060
O
VAL B
145
25.396
43.454
14.672
1.00
13.69
B

O

ATOM
2061
N
GLN B
146
24.221
45.302
14.134
1.00
14.53
B

N

ATOM
2062
CA
GLN B
146
24.359
45.893
15.464
1.00
12.59
B

C

ATOM
2063
CB
GLN B
146
23.598
47.222
15.546
1.00
12.98
B

C

ATOM
2064
CG
GLN B
146
23.739
47.970
16.885
1.00
15.51
B

C

ATOM
2065
CD
GLN B
146
25.100
48.641
17.058
1.00
18.34
B

C

ATOM
2066
OE1
GLN B
146
25.593
49.306
16.148
1.00
17.29
B

O

ATOM
2067
NE2
GLN B
146
25.700
48.483
18.233
1.00
19.22
B

N

ATOM
2068
C
GLN B
146
23.814
44.926
16.516
1.00
13.75
B

C

ATOM
2069
O
GLN B
146
24.388
44.778
17.592
1.00
11.09
B

O

ATOM
2070
N
LYS B
147
22.703
44.267
16.205
1.00
14.74
B

N

ATOM
2071
CA
LYS B
147
22.112
43.326
17.147
1.00
15.33
B

C

ATOM
2072
CB
LYS B
147
20.820
42.737
16.575
1.00
19.41
B

C

ATOM
2073
CG
LYS B
147
19.632
43.681
16.657
1.00
24.48
B

C

ATOM
2074
CD
LYS B
147
18.351
43.003
16.173
1.00
27.59
B

C

ATOM
2075
CE
LYS B
147
17.113
43.791
16.583
1.00
30.10
B

C

ATOM
2076
NZ
LYS B
147
17.197
45.226
16.199
1.00
32.34
B

N

ATOM
2077
C
LYS B
147
23.075
42.202
17.488
1.00
14.99
B

C

ATOM
2078
O
LYS B
147
23.242
41.851
18.656
1.00
13.88
B

O

ATOM
2079
N
LEU B
148
23.698
41.630
16.463
1.00
13.47
B

N

ATOM
2080
CA
LEU B
148
24.646
40.546
16.664
1.00
11.96
B

C

ATOM
2081
CB
LEU B
148
25.128
40.020
15.309
1.00
11.28
B

C

ATOM
2082
CG
LEU B
148
26.174
38.901
15.273
1.00
13.54
B

C

ATOM
2083
CD1
LEU B
148
26.101
38.200
13.936
1.00
12.19
B

C

ATOM
2084
CD2
LEU B
148
27.561
39.466
15.516
1.00
12.71
B

C

ATOM
2085
C
LEU B
148
25.818
41.072
17.486
1.00
12.75
B

C

ATOM
2086
O
LEU B
148
26.256
40.428
18.434
1.00
13.22
B

O

ATOM
2087
N
LYS B
149
26.309
42.254
17.121
1.00
12.62
B

N

ATOM
2088
CA
LYS B
149
27.423
42.886
17.818
1.00
13.95
B

C

ATOM
2089
CB
LYS B
149
27.794
44.203
17.124
1.00
13.88
B

C

ATOM
2090
CG
LYS B
149
28.555
43.999
15.828
1.00
17.34
B

C

ATOM
2091
CD
LYS B
149
28.430
45.170
14.872
1.00
22.47
B

C

ATOM
2092
CE
LYS B
149
28.881
46.482
15.472
1.00
25.42
B

C

ATOM
2093
NZ
LYS B
149
29.064
47.513
14.402
1.00
24.53
B

N

ATOM
2094
C
LYS B
149
27.122
43.137
19.293
1.00
14.22
B

C

ATOM
2095
O
LYS B
149
27.956
42.850
20.151
1.00
15.40
B

O

ATOM
2096
N
ASP B
150
25.939
43.663
19.593
1.00
13.64
B

N

ATOM
2097
CA
ASP B
150
25.576
43.928
20.988
1.00
13.95
B

C

ATOM
2098
CB
ASP B
150
24.198
44.589
21.080
1.00
15.50
B

C

ATOM
2099
CG
ASP B
150
24.172
45.985
20.493
1.00
16.66
B

C

ATOM
2100
OD1
ASP B
150
25.253
46.586
20.324
1.00
16.66
B

O

ATOM
2101
OD2
ASP B
150
23.055
46.480
20.212
1.00
19.61
B

O

ATOM
2102
C
ASP B
150
25.554
42.661
21.843
1.00
13.62
B

C

ATOM
2103
O
ASP B
150
25.986
42.655
23.002
1.00
12.88
B

O

ATOM
2104
N
THR B
151
25.017
41.591
21.276
1.00
12.91
B

N

ATOM
2105
CA
THR B
151
24.926
40.326
21.988
1.00
14.27
B

C

ATOM
2106
CB
THR B
151
24.211
39.278
21.127
1.00
16.02
B

C

ATOM
2107
OG1
THR B
151
22.904
39.763
20.802
1.00
15.49
B

O

ATOM
2108
CG2
THR B
151
24.101
37.951
21.862
1.00
15.10
B

C

ATOM
2109
C
THR B
151
26.313
39.830
22.340
1.00
14.06
B

C

ATOM
2110
O
THR B
151
26.554
39.381
23.460
1.00
15.38
B

O

ATOM
2111
N
VAL B
152
27.231
39.915
21.383
1.00
12.61
B

N

ATOM
2112
CA
VAL B
152
28.594
39.469
21.621
1.00
13.27
B

C

ATOM
2113
CB
VAL B
152
29.429
39.499
20.321
1.00
13.23
B

C

ATOM
2114
CG1
VAL B
152
30.900
39.371
20.647
1.00
12.74
B

C

ATOM
2115
CG2
VAL B
152
29.001
38.354
19.409
1.00
13.59
B

C

ATOM
2116
C
VAL B
152
29.283
40.335
22.672
1.00
12.43
B

C

ATOM
2117
O
VAL B
152
29.916
39.817
23.587
1.00
13.68
B

O

ATOM
2118
N
LYS B
153
29.141
41.653
22.549
1.00
11.31
B

N

ATOM
2119
CA
LYS B
153
29.786
42.570
23.489
1.00
9.49
B

C

ATOM
2120
CB
LYS B
153
29.720
44.011
22.965
1.00
9.07
B

C

ATOM
2121
CG
LYS B
153
30.559
44.253
21.708
1.00
7.62
B

C

ATOM
2122
CD
LYS B
153
32.027
43.864
21.936
1.00
9.41
B

C

ATOM
2123
CE
LYS B
153
32.891
44.041
20.688
1.00
9.65
B

C

ATOM
2124
NZ
LYS B
153
34.308
43.621
20.957
1.00
8.41
B

N

ATOM
2125
C
LYS B
153
29.231
42.505
24.902
1.00
9.60
B

C

ATOM
2126
O
LYS B
153
29.990
42.550
25.872
1.00
10.58
B

O

ATOM
2127
N
LYS B
154
27.917
42.398
25.034
1.00
10.82
B

N

ATOM
2128
CA
LYS B
154
27.318
42.330
26.362
1.00
12.31
B

C

ATOM
2129
CB
LYS B
154
25.787
42.296
26.255
1.00
14.53
B

C

ATOM
2130
CG
LYS B
154
25.109
41.913
27.561
1.00
20.06
B

C

ATOM
2131
CD
LYS B
154
23.589
42.030
27.501
1.00
24.39
B

C

ATOM
2132
CE
LYS B
154
22.991
41.812
28.891
1.00
24.64
B

C

ATOM
2133
NZ
LYS B
154
21.499
41.697
28.874
1.00
27.27
B

N

ATOM
2134
C
LYS B
154
27.808
41.105
27.138
1.00
14.73
B

C

ATOM
2135
O
LYS B
154
27.940
41.141
28.366
1.00
13.45
B

O

ATOM
2136
N
LEU B
155
28.090
40.026
26.412
1.00
14.59
B

N

ATOM
2137
CA
LEU B
155
28.546
38.783
27.024
1.00
15.48
B

C

ATOM
2138
CB
LEU B
155
28.120
37.596
26.156
1.00
14.97
B

C

ATOM
2139
CG
LEU B
155
26.614
37.319
26.219
1.00
16.78
B

C

ATOM
2140
CD1
LEU B
155
26.251
36.184
25.283
1.00
17.88
B

C

ATOM
2141
CD2
LEU B
155
26.233
36.976
27.659
1.00
18.88
B

C

ATOM
2142
C
LEU B
155
30.043
38.710
27.305
1.00
16.52
B

C

ATOM
2143
O
LEU B
155
30.522
37.749
27.904
1.00
16.70
B

O

ATOM
2144
N
GLY B
156
30.788
39.723
26.878
1.00
16.38
B

N

ATOM
2145
CA
GLY B
156
32.213
39.716
27.146
1.00
17.98
B

C

ATOM
2146
C
GLY B
156
32.918
38.521
26.542
1.00
18.96
B

C

ATOM
2147
O
GLY B
156
32.658
38.159
25.398
1.00
19.62
B

O

ATOM
2148
N
GLU B
157
33.807
37.897
27.305
1.00
20.01
B

N

ATOM
2149
CA
GLU B
157
34.547
36.751
26.790
1.00
22.65
B

C

ATOM
2150
CB
GLU B
157
35.504
36.198
27.844
1.00
26.57
B

C

ATOM
2151
CG
GLU B
157
36.377
35.060
27.323
1.00
32.56
B

C

ATOM
2152
CD
GLU B
157
37.622
34.860
28.160
1.00
36.42
B

C

ATOM
2153
OE1
GLU B
157
37.487
34.500
29.348
1.00
39.12
B

O

ATOM
2154
OE2
GLU B
157
38.738
35.071
27.632
1.00
40.09
B

O

ATOM
2155
C
GLU B
157
33.642
35.628
26.304
1.00
21.05
B

C

ATOM
2156
O
GLU B
157
33.940
34.972
25.309
1.00
19.94
B

O

ATOM
2157
N
SER B
158
32.551
35.395
27.025
1.00
20.79
B

N

ATOM
2158
CA
SER B
158
31.602
34.357
26.650
1.00
20.47
B

C

ATOM
2159
CB
SER B
158
30.481
34.264
27.684
1.00
21.91
B

C

ATOM
2160
OG
SER B
158
31.000
33.902
28.948
1.00
26.50
B

O

ATOM
2161
C
SER B
158
31.006
34.696
25.291
1.00
19.88
B

C

ATOM
2162
O
SER B
158
30.649
33.803
24.519
1.00
20.24
B

O

ATOM
2163
N
GLY B
159
30.890
35.991
25.010
1.00
18.62
B

N

ATOM
2164
CA
GLY B
159
30.343
36.426
23.733
1.00
17.19
B

C

ATOM
2165
C
GLY B
159
31.272
36.008
22.611
1.00
15.21
B

C

ATOM
2166
O
GLY B
159
30.828
35.574
21.536
1.00
13.42
B

O

ATOM
2167
N
GLU B
160
32.569
36.138
22.862
1.00
12.99
B

N

ATOM
2168
CA
GLU B
160
33.571
35.759
21.880
1.00
15.94
B

C

ATOM
2169
CB
GLU B
160
34.963
36.197
22.349
1.00
18.02
B

C

ATOM
2170
CG
GLU B
160
35.143
37.708
22.329
1.00
21.23
B

C

ATOM
2171
CD
GLU B
160
36.471
38.151
22.913
1.00
25.05
B

C

ATOM
2172
OE1
GLU B
160
37.519
37.597
22.522
1.00
26.71
B

O

ATOM
2173
OE2
GLU B
160
36.467
39.065
23.758
1.00
26.22
B

O

ATOM
2174
C
GLU B
160
33.533
34.252
21.646
1.00
16.05
B

C

ATOM
2175
O
GLU B
160
33.584
33.791
20.503
1.00
16.68
B

O

ATOM
2176
N
ILE B
161
33.430
33.489
22.728
1.00
15.72
B

N

ATOM
2177
CA
ILE B
161
33.380
32.033
22.628
1.00
15.75
B

C

ATOM
2178
CB
AILE B
161
33.334
31.371
24.025
0.50
17.43
B

C

ATOM
2179
CB
BILE B
161
33.345
31.389
24.043
0.50
17.65
B

C

ATOM
2180
CG2
AILE B
161
33.225
29.860
23.887
0.50
18.33
B

C

ATOM
2181
CG2
BILE B
161
33.204
29.879
23.924
0.50
18.35
B

C

ATOM
2182
CG1
AILE B
161
34.588
31.753
24.820
0.50
18.68
B

C

ATOM
2183
CG1
BILE B
161
34.627
31.750
24.803
0.50
18.95
B

C

ATOM
2184
CD
AILE B
161
35.890
31.386
24.139
0.50
18.08
B

C

ATOM
2185
CD
BILE B
161
34.640
31.314
26.252
0.50
19.38
B

C

ATOM
2186
C
ILE B
161
32.151
31.616
21.828
1.00
15.04
B

C

ATOM
2187
O
ILE B
161
32.233
30.745
20.960
1.00
13.38
B

O

ATOM
2188
N
LYS B
162
31.017
32.251
22.110
1.00
14.57
B

N

ATOM
2189
CA
LYS B
162
29.782
31.938
21.401
1.00
14.05
B

C

ATOM
2190
CB
LYS B
162
28.621
32.771
21.954
1.00
14.23
B

C

ATOM
2191
CG
LYS B
162
27.299
32.559
21.206
1.00
15.87
B

C

ATOM
2192
CD
LYS B
162
26.211
33.520
21.678
1.00
16.15
B

C

ATOM
2193
CE
LYS B
162
25.913
33.359
23.163
1.00
18.43
B

C

ATOM
2194
NZ
LYS B
162
25.341
32.018
23.490
1.00
22.02
B

N

ATOM
2195
C
LYS B
162
29.933
32.208
19.910
1.00
12.51
B

C

ATOM
2196
O
LYS B
162
29.445
31.442
19.078
1.00
13.34
B

O

ATOM
2197
N
ALA B
163
30.611
33.297
19.574
1.00
12.30
B

N

ATOM
2198
CA
ALA B
163
30.822
33.656
18.177
1.00
12.59
B

C

ATOM
2199
CB
ALA B
163
31.474
35.036
18.089
1.00
12.94
B

C

ATOM
2200
C
ALA B
163
31.684
32.617
17.454
1.00
12.63
B

C

ATOM
2201
O
ALA B
163
31.435
32.281
16.293
1.00
13.56
B

O

ATOM
2202
N
ILE B
164
32.704
32.111
18.135
1.00
13.23
B

N

ATOM
2203
CA
ILE B
164
33.578
31.107
17.532
1.00
10.59
B

C

ATOM
2204
CB
ILE B
164
34.824
30.853
18.403
1.00
12.38
B

C

ATOM
2205
CG2
ILE B
164
35.701
29.767
17.768
1.00
8.98
B

C

ATOM
2206
CG1
ILE B
164
35.617
32.155
18.566
1.00
9.24
B

C

ATOM
2207
CD
ILE B
164
36.746
32.058
19.590
1.00
11.68
B

C

ATOM
2208
C
ILE B
164
32.793
29.804
17.379
1.00
12.14
B

C

ATOM
2209
O
ILE B
164
33.009
29.049
16.431
1.00
12.85
B

O

ATOM
2210
N
GLY B
165
31.868
29.558
18.305
1.00
10.88
B

N

ATOM
2211
CA
GLY B
165
31.063
28.345
18.252
1.00
13.41
B

C

ATOM
2212
C
GLY B
165
30.109
28.337
17.072
1.00
14.68
B

C

ATOM
2213
O
GLY B
165
29.583
27.290
16.686
1.00
14.73
B

O

ATOM
2214
N
GLU B
166
29.890
29.512
16.495
1.00
13.01
B

N

ATOM
2215
CA
GLU B
166
29.011
29.656
15.349
1.00
14.06
B

C

ATOM
2216
CB
GLU B
166
28.031
30.773
15.621
1.00
16.63
B

C

ATOM
2217
CG
GLU B
166
27.344
30.594
16.942
1.00
21.35
B

C

ATOM
2218
CD
GLU B
166
26.278
29.510
16.908
1.00
25.81
B

C

ATOM
2219
OE1
GLU B
166
26.648
28.326
16.873
1.00
31.72
B

O

ATOM
2220
OE2
GLU B
166
25.065
29.822
16.913
1.00
30.04
B

O

ATOM
2221
C
GLU B
166
29.767
29.952
14.062
1.00
11.84
B

C

ATOM
2222
O
GLU B
166
29.164
30.323
13.054
1.00
11.51
B

O

ATOM
2223
N
LEU B
167
31.084
29.781
14.090
1.00
10.92
B

N

ATOM
2224
CA
LEU B
167
31.895
30.033
12.903
1.00
12.37
B

C

ATOM
2225
CB
LEU B
167
33.391
29.836
13.195
1.00
15.29
B

C

ATOM
2226
CG
LEU B
167
34.115
31.001
13.872
1.00
20.06
B

C

ATOM
2227
CD1
LEU B
167
35.562
30.612
14.125
1.00
22.06
B

C

ATOM
2228
CD2
LEU B
167
34.033
32.247
12.996
1.00
20.29
B

C

ATOM
2229
C
LEU B
167
31.496
29.137
11.739
1.00
13.10
B

C

ATOM
2230
O
LEU B
167
31.733
29.481
10.585
1.00
12.57
B

O

ATOM
2231
N
ASP B
168
30.901
27.986
12.034
1.00
12.74
B

N

ATOM
2232
CA
ASP B
168
30.478
27.100
10.960
1.00
14.28
B

C

ATOM
2233
CB
ASP B
168
30.058
25.727
11.515
1.00
13.57
B

C

ATOM
2234
CG
ASP B
168
29.185
25.821
12.760
1.00
17.07
B

C

ATOM
2235
OD1
ASP B
168
28.964
26.930
13.295
1.00
14.89
B

O

ATOM
2236
OD2
ASP B
168
28.723
24.755
13.218
1.00
18.76
B

O

ATOM
2237
C
ASP B
168
29.335
27.767
10.186
1.00
12.65
B

C

ATOM
2238
O
ASP B
168
29.312
27.747
8.958
1.00
13.63
B

O

ATOM
2239
N
LEU B
169
28.403
28.379
10.903
1.00
11.65
B

N

ATOM
2240
CA
LEU B
169
27.293
29.068
10.255
1.00
14.38
B

C

ATOM
2241
CB
LEU B
169
26.245
29.481
11.283
1.00
15.94
B

C

ATOM
2242
CG
LEU B
169
25.462
28.363
11.971
1.00
18.22
B

C

ATOM
2243
CD1
LEU B
169
24.391
28.973
12.880
1.00
18.16
B

C

ATOM
2244
CD2
LEU B
169
24.822
27.472
10.913
1.00
20.52
B

C

ATOM
2245
C
LEU B
169
27.791
30.311
9.520
1.00
15.25
B

C

ATOM
2246
O
LEU B
169
27.249
30.701
8.483
1.00
14.55
B

O

ATOM
2247
N
LEU B
170
28.821
30.944
10.062
1.00
15.29
B

N

ATOM
2248
CA
LEU B
170
29.359
32.133
9.421
1.00
16.17
B

C

ATOM
2249
CB
LEU B
170
30.418
32.795
10.309
1.00
16.47
B

C

ATOM
2250
CG
LEU B
170
31.234
33.908
9.639
1.00
18.75
B

C

ATOM
2251
CD1
LEU B
170
30.309
34.997
9.152
1.00
20.23
B

C

ATOM
2252
CD2
LEU B
170
32.242
34.479
10.622
1.00
20.78
B

C

ATOM
2253
C
LEU B
170
29.976
31.742
8.088
1.00
16.04
B

C

ATOM
2254
O
LEU B
170
29.754
32.397
7.069
1.00
17.27
B

O

ATOM
2255
N
PHE B
171
30.748
30.663
8.104
1.00
15.59
B

N

ATOM
2256
CA
PHE B
171
31.418
30.173
6.905
1.00
17.71
B

C

ATOM
2257
CB
PHE B
171
32.313
28.978
7.271
1.00
18.23
B

C

ATOM
2258
CG
PHE B
171
33.023
28.355
6.093
1.00
23.19
B

C

ATOM
2259
CD1
PHE B
171
32.324
27.606
5.147
1.00
25.08
B

C

ATOM
2260
CD2
PHE B
171
34.395
28.521
5.930
1.00
25.84
B

C

ATOM
2261
CE1
PHE B
171
32.982
27.031
4.053
1.00
26.30
B

C

ATOM
2262
CE2
PHE B
171
35.064
27.949
4.840
1.00
26.12
B

C

ATOM
2263
CZ
PHE B
171
34.353
27.204
3.902
1.00
25.36
B

C

ATOM
2264
C
PHE B
171
30.413
29.773
5.824
1.00
15.84
B

C

ATOM
2265
O
PHE B
171
30.545
30.158
4.657
1.00
15.02
B

O

ATOM
2266
N
MET B
172
29.411
28.991
6.207
1.00
15.66
B

N

ATOM
2267
CA
MET B
172
28.407
28.548
5.241
1.00
14.21
B

C

ATOM
2268
CB
MET B
172
27.505
27.484
5.859
1.00
14.82
B

C

ATOM
2269
CG
MET B
172
28.167
26.139
6.076
1.00
17.32
B

C

ATOM
2270
SD
MET B
172
28.576
25.335
4.523
1.00
19.02
B

S

ATOM
2271
CE
MET B
172
30.140
24.649
4.909
1.00
18.35
B

C

ATOM
2272
C
MET B
172
27.552
29.701
4.723
1.00
15.52
B

C

ATOM
2273
O
MET B
172
27.216
29.750
3.543
1.00
16.04
B

O

ATOM
2274
N
SER B
173
27.191
30.623
5.610
1.00
17.55
B

N

ATOM
2275
CA
SER B
173
26.368
31.766
5.225
1.00
19.47
B

C

ATOM
2276
CB
SER B
173
25.962
32.554
6.462
1.00
18.60
B

C

ATOM
2277
OG
SER B
173
25.085
31.797
7.272
1.00
20.37
B

O

ATOM
2278
C
SER B
173
27.123
32.671
4.262
1.00
21.94
B

C

ATOM
2279
O
SER B
173
26.551
33.201
3.303
1.00
22.14
B

O

ATOM
2280
N
LEU B
174
28.412
32.853
4.523
1.00
22.66
B

N

ATOM
2281
CA
LEU B
174
29.252
33.688
3.676
1.00
23.53
B

C

ATOM
2282
CB
ALEU B
174
30.652
33.804
4.287
0.50
23.45
B

C

ATOM
2283
CB
BLEU B
174
30.671
33.756
4.215
0.50
23.44
B

C

ATOM
2284
CG
ALEU B
174
31.647
34.741
3.608
0.50
23.66
B

C

ATOM
2285
CG
BLEU B
174
31.036
34.904
5.148
0.50
23.44
B

C

ATOM
2286
CD1
ALEU B
174
31.128
36.165
3.669
0.50
23.07
B

C

ATOM
2287
CD1
BLEU B
174
32.414
34.656
5.737
0.50
22.70
B

C

ATOM
2288
CD2
ALEU B
174
32.995
34.633
4.308
0.50
22.85
B

C

ATOM
2289
CD2
BLEU B
174
31.012
36.205
4.367
0.50
23.54
B

C

ATOM
2290
C
LEU B
174
29.340
33.097
2.274
1.00
25.13
B

C

ATOM
2291
O
LEU B
174
29.225
33.814
1.282
1.00
25.73
B

O

ATOM
2292
N
ARG B
175
29.547
31.785
2.204
1.00
25.47
B

N

ATOM
2293
CA
ARG B
175
29.641
31.074
0.933
1.00
26.85
B

C

ATOM
2294
CB
ARG B
175
29.872
29.584
1.196
1.00
28.61
B

C

ATOM
2295
CG
ARG B
175
30.384
28.818
0.006
1.00
31.65
B

C

ATOM
2296
CD
ARG B
175
30.369
27.331
0.279
1.00
35.80
B

C

ATOM
2297
NE
ARG B
175
29.017
26.786
0.193
1.00
37.83
B

N

ATOM
2298
CZ
ARG B
175
28.317
26.731
−0.935
1.00
41.57
B

C

ATOM
2299
NH1
ARG B
175
28.849
27.183
−2.060
1.00
42.90
B

N

ATOM
2300
NH2
ARG B
175
27.084
26.238
−0.944
1.00
42.15
B

N

ATOM
2301
C
ARG B
175
28.365
31.264
0.101
1.00
26.48
B

C

ATOM
2302
O
ARG B
175
28.416
31.705
−1.049
1.00
27.29
B

O

ATOM
2303
N
ASN B
176
27.216
30.954
0.690
1.00
24.26
B

N

ATOM
2304
CA
ASN B
176
25.943
31.095
−0.010
1.00
25.29
B

C

ATOM
2305
CB
ASN B
176
24.831
30.435
0.798
1.00
22.74
B

C

ATOM
2306
CG
ASN B
176
24.682
28.972
0.469
1.00
24.13
B

C

ATOM
2307
OD1
ASN B
176
25.668
28.285
0.187
1.00
22.83
B

O

ATOM
2308
ND2
ASN B
176
23.447
28.479
0.503
1.00
20.65
B

N

ATOM
2309
C
ASN B
176
25.539
32.522
−0.348
1.00
26.76
B

C

ATOM
2310
O
ASN B
176
24.759
32.753
−1.276
1.00
26.72
B

O

ATOM
2311
N
ALA B
177
26.068
33.481
0.397
1.00
25.95
B

N

ATOM
2312
CA
ALA B
177
25.729
34.870
0.162
1.00
26.17
B

C

ATOM
2313
CB
ALA B
177
25.737
35.633
1.487
1.00
24.10
B

C

ATOM
2314
C
ALA B
177
26.663
35.550
−0.826
1.00
25.49
B

C

ATOM
2315
O
ALA B
177
26.275
36.511
−1.478
1.00
25.51
B

O

ATOM
2316
N
CYS B
178
27.879
35.033
−0.964
1.00
27.87
B

N

ATOM
2317
CA
CYS B
178
28.862
35.671
−1.820
1.00
27.66
B

C

ATOM
2318
C
CYS B
178
29.271
34.977
−3.128
1.00
29.33
B

C

ATOM
2319
O
CYS B
178
29.732
35.666
−4.035
1.00
31.34
B

O

ATOM
2320
CB
CYS B
178
30.123
35.902
−0.991
1.00
27.05
B

C

ATOM
2321
SG
CYS B
178
29.912
37.031
0.419
1.00
25.07
B

S

ATOM
2322
N
ILE B
179
29.109
33.664
−3.245
1.00
30.95
B

N

ATOM
2323
CA
ILE B
179
29.490
33.008
−4.491
1.00
31.56
B

C

ATOM
2324
CB
ILE B
179
29.681
31.496
−4.309
1.00
32.47
B

C

ATOM
2325
CG2
ILE B
179
30.764
31.239
−3.275
1.00
34.45
B

C

ATOM
2326
CG1
ILE B
179
28.356
30.851
−3.899
1.00
33.65
B

C

ATOM
2327
CD
ILE B
179
28.408
29.343
−3.849
1.00
35.23
B

C

ATOM
2328
C
ILE B
179
28.441
33.220
−5.576
1.00
31.05
B

C

ATOM
2329
OT1
ILE B
179
27.279
33.539
−5.240
1.00
29.84
B

O

ATOM
2330
OT2
ILE B
179
28.806
33.043
−6.756
1.00
32.57
B

O

HETATM
2331
O
HOH W
201
27.297
23.446
24.432
1.00
10.44
W

O

HETATM
2332
O
HOH W
202
29.001
24.489
16.199
1.00
15.87
W

O

HETATM
2333
O
HOH W
203
11.736
25.818
21.510
1.00
19.00
W

O

HETATM
2334
O
HOH W
204
24.143
15.462
11.058
1.00
16.00
W

O

HETATM
2335
O
HOH W
205
13.986
10.421
2.897
1.00
47.98
W

O

HETATM
2336
O
HOH W
206
9.264
23.783
21.316
1.00
19.55
W

O

HETATM
2337
O
HOH W
207
26.417
26.497
21.231
1.00
16.89
W

O

HETATM
2338
O
HOH W
208
25.199
18.812
10.440
1.00
16.53
W

O

HETATM
2339
O
HOH W
209
27.671
14.819
7.534
1.00
15.58
W

O

HETATM
2340
O
HOH W
210
17.220
31.319
12.529
1.00
18.46
W

O

HETATM
2341
O
HOH W
211
7.763
15.191
13.315
1.00
16.34
W

O

HETATM
2342
O
HOH W
212
25.429
52.025
16.393
1.00
21.97
W

O

HETATM
2343
O
HOH W
213
4.366
14.026
−0.146
1.00
16.43
W

O

HETATM
2344
O
HOH W
214
30.378
15.252
8.290
1.00
17.71
W

O

HETATM
2345
O
HOH W
215
29.716
36.103
14.680
1.00
26.32
W

O

HETATM
2346
O
HOH W
216
29.851
44.950
27.330
1.00
16.23
W

O

HETATM
2347
O
HOH W
217
25.965
42.188
−1.336
1.00
26.70
W

O

HETATM
2348
O
HOH W
218
32.742
40.348
23.501
1.00
19.93
W

O

HETATM
2349
O
HOH W
219
21.669
14.477
11.866
1.00
21.69
W

O

HETATM
2350
O
HOH W
220
34.189
40.928
21.191
1.00
21.11
W

O

HETATM
2351
O
HOH W
221
13.503
33.656
−0.622
1.00
21.91
W

O

HETATM
2352
O
HOH W
222
24.529
39.089
−2.108
1.00
22.69
W

O

HETATM
2353
O
HOH W
223
20.087
30.335
−0.404
1.00
26.82
W

O

HETATM
2354
O
HOH W
224
21.910
37.842
18.502
1.00
21.17
W

O

HETATM
2355
O
HOH W
225
19.543
26.452
−10.389
1.00
24.04
W

O

HETATM
2356
O
HOH W
226
15.561
31.685
14.681
1.00
45.81
W

O

HETATM
2357
O
HOH W
227
32.308
36.045
30.019
1.00
28.38
W

O

HETATM
2358
O
HOH W
228
17.729
31.816
1.688
1.00
18.99
W

O

HETATM
2359
O
HOH W
229
25.158
23.427
25.705
1.00
23.41
W

O

HETATM
2360
O
HOH W
230
27.991
29.102
19.752
1.00
20.66
W

O

HETATM
2361
O
HOH W
231
3.725
18.194
12.154
1.00
33.73
W

O

HETATM
2362
O
HOH W
232
37.621
42.067
21.510
1.00
27.85
W

O

HETATM
2363
O
HOH W
233
19.597
28.257
20.861
1.00
28.65
W

O

HETATM
2364
O
HOH W
234
20.056
40.743
13.648
1.00
32.86
W

O

HETATM
2365
O
HOH W
235
11.670
39.187
7.650
1.00
30.82
W

O

HETATM
2366
O
HOH W
236
18.418
33.049
20.243
1.00
26.85
W

O

HETATM
2367
O
HOH W
237
23.466
27.862
16.542
1.00
25.38
W

O

HETATM
2368
O
HOH W
238
36.544
43.733
3.953
1.00
24.65
W

O

HETATM
2369
O
HOH W
239
20.855
44.986
20.266
1.00
20.67
W

O

HETATM
2370
O
HOH W
240
6.104
33.041
6.261
1.00
34.43
W

O

HETATM
2371
O
HOH W
241
22.194
38.315
15.523
1.00
30.42
W

O

HETATM
2372
O
HOH W
242
26.322
47.696
12.361
1.00
28.82
W

O

HETATM
2373
O
HOH W
243
29.634
17.921
1.255
1.00
23.78
W

O

HETATM
2374
O
HOH W
244
12.805
39.529
5.415
1.00
48.81
W

O

HETATM
2375
O
HOH W
245
9.624
26.277
4.198
1.00
24.30
W

O

HETATM
2376
O
HOH W
246
7.395
13.510
7.017
1.00
35.04
W

O

HETATM
2377
O
HOH W
247
30.410
33.686
14.273
1.00
21.60
W

O

HETATM
2378
O
HOH W
248
36.748
43.355
23.420
1.00
28.82
W

O

HETATM
2379
O
HOH W
249
19.550
13.720
10.528
1.00
21.91
W

O

HETATM
2380
O
HOH W
250
17.891
27.372
−12.427
1.00
32.70
W

O

HETATM
2381
O
HOH W
251
31.614
45.127
10.612
1.00
28.57
W

O

HETATM
2382
O
HOH W
252
36.318
24.599
24.398
1.00
27.35
W

O

HETATM
2383
O
HOH W
253
27.851
21.966
22.159
1.00
35.57
W

O

HETATM
2384
O
HOH W
254
12.195
26.188
3.549
1.00
21.42
W

O

HETATM
2385
O
HOH W
255
14.952
35.943
7.315
1.00
31.47
W

O

HETATM
2386
O
HOH W
256
25.476
31.892
15.021
1.00
42.15
W

O

HETATM
2387
O
HOH W
257
33.419
16.973
5.504
1.00
24.87
W

O

HETATM
2388
O
HOH W
258
2.676
21.388
9.316
1.00
35.75
W

O

HETATM
2389
O
HOH W
259
25.575
34.428
−3.222
1.00
39.98
W

O

HETATM
2390
O
HOH W
260
14.941
30.863
−2.385
1.00
26.04
W

O

HETATM
2391
O
HOH W
261
41.672
27.415
23.709
1.00
35.93
W

O

HETATM
2392
O
HOH W
262
18.136
30.604
21.993
1.00
31.10
W

O

HETATM
2393
O
HOH W
263
32.907
42.731
25.674
1.00
26.77
W

O

HETATM
2394
O
HOH W
264
21.328
33.022
−5.079
1.00
32.93
W

O

HETATM
2395
O
HOH W
265
28.052
12.336
6.540
1.00
22.14
W

O

HETATM
2396
O
HOH W
266
2.099
19.008
5.021
1.00
32.55
W

O

HETATM
2397
O
HOH W
267
29.794
31.341
25.289
1.00
32.81
W

O

HETATM
2398
O
HOH W
268
20.757
45.357
22.862
1.00
36.33
W

O

HETATM
2399
O
HOH W
269
18.249
16.829
−10.961
1.00
31.63
W

O

HETATM
2400
O
HOH W
270
5.371
13.454
−3.003
1.00
38.53
W

O

HETATM
2401
O
HOH W
271
29.440
31.283
29.531
1.00
42.43
W

O

HETATM
2402
O
HOH W
272
28.073
49.822
16.597
1.00
34.43
W

O

HETATM
2403
O
HOH W
273
9.569
37.651
14.685
1.00
41.67
W

O

HETATM
2404
O
HOH W
274
3.582
23.223
−3.241
1.00
41.20
W

O

HETATM
2405
O
HOH W
275
39.303
37.931
25.088
1.00
35.26
W

O

HETATM
2406
O
HOH W
276
27.169
49.230
14.079
1.00
27.21
W

O

HETATM
2407
O
HOH W
277
17.385
35.595
−7.830
1.00
39.15
W

O

HETATM
2408
O
HOH W
278
36.093
19.433
19.171
1.00
57.03
W

O

HETATM
2409
O
HOH W
279
31.185
14.743
10.858
1.00
33.84
W

O

HETATM
2410
O
HOH W
280
16.886
31.999
−1.178
1.00
30.74
W

O

HETATM
2411
O
HOH W
281
23.320
12.684
6.853
1.00
38.74
W

O

HETATM
2412
O
HOH W
282
35.109
41.222
24.391
1.00
35.21
W

O

HETATM
2413
O
HOH W
283
43.171
19.919
0.844
1.00
31.45
W

O

HETATM
2414
O
HOH W
284
21.356
14.695
23.557
1.00
28.47
W

O

HETATM
2415
O
HOH W
285
24.661
10.570
6.602
1.00
45.63
W

O

HETATM
2416
O
HOH W
286
4.247
12.050
1.832
1.00
39.46
W

O

HETATM
2417
O
HOH W
287
40.280
39.948
24.240
1.00
33.27
W

O

HETATM
2418
O
HOH W
288
20.284
56.897
0.611
1.00
44.29
W

O

HETATM
2419
O
HOH W
289
23.310
31.108
15.564
1.00
38.31
W

O

HETATM
2420
O
HOH W
290
48.053
26.077
15.288
1.00
47.19
W

O

HETATM
2421
O
HOH W
291
12.020
16.304
20.731
1.00
28.99
W

O

HETATM
2422
O
HOH W
292
41.231
23.934
2.570
1.00
33.94
W

O

HETATM
2423
O
HOH W
293
18.669
11.706
−13.630
1.00
36.09
W

O

HETATM
2424
O
HOH W
294
8.109
34.730
7.563
1.00
39.26
W

O

HETATM
2425
O
HOH W
295
15.600
35.689
−4.228
1.00
41.15
W

O

HETATM
2426
O
HOH W
296
−4.142
24.573
20.605
1.00
42.87
W

O

HETATM
2427
O
HOH W
297
15.622
34.076
15.219
1.00
42.95
W

O

HETATM
2428
O
HOH W
298
38.169
40.792
23.402
1.00
45.01
W

O

HETATM
2429
O
HOH W
299
27.537
26.052
−3.736
1.00
52.95
W

O

HETATM
2430
O
HOH W
300
35.494
16.860
10.304
1.00
43.09
W

O

HETATM
2431
O
HOH W
301
41.551
21.663
1.380
1.00
36.94
W

O

HETATM
2432
O
HOH W
302
45.225
29.031
6.035
1.00
40.03
W

O

HETATM
2433
O
HOH W
303
31.772
47.636
4.279
1.00
35.07
W

O

HETATM
2434
O
HOH W
304
16.888
20.002
−11.152
1.00
39.19
W

O

HETATM
2435
O
HOH W
305
15.036
31.029
17.354
1.00
42.31
W

O

HETATM
2436
O
HOH W
306
8.035
38.484
2.278
1.00
36.39
W

O

HETATM
2437
O
HOH W
307
7.021
9.870
24.009
1.00
46.58
W

O

HETATM
2438
O
HOH W
308
−0.328
27.092
−6.529
1.00
39.32
W

O

HETATM
2439
O
HOH W
309
32.290
44.882
−6.224
1.00
41.91
W

O

HETATM
2440
O
HOH W
310
−2.886
27.829
1.400
1.00
46.46
W

O

HETATM
2441
O
HOH W
311
45.080
21.111
1.259
1.00
43.31
W

O

HETATM
2442
O
HOH W
312
34.187
18.021
11.951
1.00
33.37
W

O

HETATM
2443
O
HOH W
313
42.013
42.835
15.912
1.00
35.29
W

O

HETATM
2444
O
HOH W
314
21.506
9.309
4.752
1.00
35.56
W

O

HETATM
2445
O
HOH W
315
33.745
38.255
30.145
1.00
42.37
W

O

HETATM
2446
O
HOH W
316
26.849
28.079
−7.783
1.00
42.24
W

O

HETATM
2447
O
HOH W
317
22.190
18.955
−5.896
1.00
44.87
W

O

HETATM
2448
O
HOH W
318
5.056
11.251
−3.217
1.00
43.78
W

O

HETATM
2449
O
HOH W
319
30.465
47.010
−8.187
1.00
60.12
W

O

HETATM
2450
O
HOH W
320
25.131
34.069
−7.705
1.00
40.30
W

O

HETATM
2451
O
HOH W
321
−1.120
23.587
2.285
1.00
57.54
W

O

HETATM
2452
O
HOH W
322
27.796
32.147
25.994
1.00
52.28
W

O

HETATM
2453
O
HOH W
323
2.796
19.619
−4.238
1.00
43.84
W

O

HETATM
2454
O
HOH W
324
4.253
33.074
8.597
1.00
38.14
W

O

HETATM
2455
O
HOH W
325
28.162
22.354
26.470
1.00
46.35
W

O

HETATM
2456
O
HOH W
326
17.658
41.562
−4.831
1.00
45.26
W

O

HETATM
2457
O
HOH W
327
12.525
24.278
23.101
1.00
49.33
W

O

HETATM
2458
O
HOH W
328
1.417
20.936
21.185
1.00
51.98
W

O

HETATM
2459
O
HOH W
329
5.110
34.325
4.685
1.00
47.55
W

O

HETATM
2460
O
HOH W
330
23.854
24.173
−8.875
1.00
53.09
W

O

HETATM
2461
O
HOH W
331
26.863
30.894
27.666
1.00
47.65
W

O

HETATM
2462
O
HOH W
332
32.534
14.831
7.143
1.00
39.84
W

O

HETATM
2463
O
HOH W
333
15.358
12.945
−2.666
1.00
37.81
W

O

HETATM
2464
O
HOH W
334
44.680
33.725
22.138
1.00
49.77
W

O

HETATM
2465
O
HOH W
335
12.020
38.120
13.522
1.00
58.79
W

O

HETATM
2466
O
HOH W
336
42.127
30.661
−3.910
1.00
44.39
W

O

HETATM
2467
O
HOH W
337
1.727
20.705
6.878
1.00
45.75
W

O

HETATM
2468
O
HOH W
338
−0.384
35.128
−7.818
1.00
49.01
W

O

HETATM
2469
O
HOH W
339
21.057
43.781
28.030
1.00
40.90
W

O

HETATM
2470
O
HOH W
340
11.861
9.923
3.834
1.00
41.37
W

O

HETATM
2471
O
HOH W
341
37.937
37.279
28.479
1.00
59.04
W

O

HETATM
2472
O
HOH W
342
6.363
12.922
12.257
1.00
43.48
W

O

HETATM
2473
O
HOH W
343
2.799
32.430
24.168
1.00
60.02
W

O

HETATM
2474
O
HOH W
344
29.796
50.785
1.614
1.00
53.08
W

O

HETATM
2475
O
HOH W
345
−0.874
32.698
−7.319
1.00
39.33
W

O

HETATM
2476
O
HOH W
346
36.654
46.102
−3.751
1.00
49.64
W

O

HETATM
2477
O
HOH W
347
22.253
20.580
21.775
1.00
38.38
W

O

HETATM
2478
O
HOH W
348
23.536
39.353
28.221
1.00
50.03
W

O

HETATM
2479
O
HOH W
349
21.979
23.483
27.337
1.00
56.78
W

O

HETATM
2480
O
HOH W
350
15.688
9.390
6.304
1.00
39.68
W

O

HETATM
2481
O
HOH W
351
17.446
31.911
24.017
1.00
49.08
W

O

HETATM
2482
O
HOH W
352
20.424
32.203
−1.926
1.00
52.71
W

O

HETATM
2483
O
HOH W
353
7.374
38.066
19.040
1.00
52.43
W

O

HETATM
2484
O
HOH W
354
40.616
34.974
29.409
1.00
43.05
W

O

HETATM
2485
O
HOH W
355
13.964
28.600
20.763
1.00
45.36
W

O

HETATM
2486
O
HOH W
356
21.968
11.935
4.239
1.00
34.43
W

O

HETATM
2487
O
HOH W
357
40.741
40.054
−5.266
1.00
50.01
W

O

HETATM
2488
O
HOH W
358
1.011
22.226
10.873
1.00
47.98
W

O

HETATM
2489
O
HOH W
359
30.521
24.949
−3.484
1.00
51.24
W

O

HETATM
2490
O
HOH W
360
30.394
22.663
13.867
1.00
35.80
W

O

HETATM
2491
O
HOH W
361
1.298
28.757
23.599
1.00
45.73
W

O

HETATM
2492
O
HOH W
362
10.037
16.429
−9.605
1.00
43.70
W

O

HETATM
2493
O
HOH W
363
2.342
16.995
19.296
1.00
53.29
W

O

HETATM
2494
O
HOH W
364
18.754
21.800
−12.588
1.00
56.18
W

O

HETATM
2495
O
HOH W
365
18.388
23.021
28.255
1.00
48.80
W

O

HETATM
2496
O
HOH W
366
12.812
40.928
2.593
1.00
50.81
W

O

HETATM
2497
O
HOH W
367
20.573
19.834
−9.838
1.00
49.46
W

O

HETATM
2498
O
HOH W
368
3.924
11.192
4.654
1.00
47.96
W

O

HETATM
2499
O
HOH W
369
23.969
20.116
−9.041
1.00
44.24
W

O

HETATM
2500
O
HOH W
370
40.480
32.964
1.998
1.00
52.22
W

O

HETATM
2501
O
HOH W
371
20.730
46.882
18.743
1.00
38.87
W

O

HETATM
2502
O
HOH W
372
29.891
46.902
11.620
1.00
41.85
W

O

HETATM
2503
O
HOH W
373
27.107
45.779
−9.724
1.00
49.81
W

O

HETATM
2504
O
HOH W
374
45.521
35.688
5.405
1.00
50.64
W

O

HETATM
2505
O
HOH W
375
8.631
12.370
10.753
1.00
41.87
W

O

HETATM
2506
O
HOH W
376
−1.414
24.184
8.066
1.00
45.18
W

O

HETATM
2507
O
HOH W
377
25.847
26.771
−9.623
1.00
50.58
W

O

HETATM
2508
O
HOH W
378
17.044
35.686
20.995
1.00
46.08
W

O

HETATM
2509
O
HOH W
379
31.859
30.020
27.009
1.00
44.41
W

O

HETATM
2510
O
HOH W
380
15.331
35.172
17.686
1.00
42.80
W

O

HETATM
2511
O
HOH W
381
30.163
27.844
−12.299
1.00
48.94
W

O

HETATM
2512
O
HOH W
382
26.459
20.674
25.974
1.00
50.90
W

O

HETATM
2513
O
HOH W
383
11.215
40.705
−7.869
1.00
44.77
W

O

HETATM
2514
O
HOH W
384
39.653
28.993
25.532
1.00
42.77
W

O

HETATM
2515
O
HOH W
385
8.320
22.025
23.135
1.00
40.98
W

O

HETATM
2516
O
HOH W
386
19.109
57.899
2.281
1.00
52.58
W

O

HETATM
2517
O
HOH W
387
23.211
31.034
3.809
0.68
12.76
W

O

HETATM
2518
O
HOH W
388
23.669
33.864
2.886
0.68
17.24
W

O

HETATM
2519
O
HOH W
389
22.013
32.823
3.876
0.68
32.76
W

O

END

1
Amino acid residues correspond to residues in human IL-22, SEQ ID NO: 2.

[0173]

5

TABLE 5

Solvent exposed residues of hIL-22.1

Solvent Exposed

Solvent Exposed

Residue
Area (Å2)2
Residue
Area (Å2)

SER38
80.00
HIS39
131.00

ARG41
112.00
ASP43
91.00

LYS44
82.00
SER45
49.00

ASN46
46.00
GLN48
103.00

GLN49
91.00
PRO50
99.00

TYR51
124.00
ILE52
24.00

THR53
27.00
ASN54
81.00

ARG55
51.00
PHE57
69.00

MET58
51.00
LYS61
123.00

GLU62
70.00
SER64
42.00

LEU65
135.00
ALA66
53.00

ASP67
27.00
ASN68
141.00

ASN69
35.00
THR70
126.00

ASP71
142.00
VAL72
45.00

ARG73
141.00
LEU74
11.00

ILE75
18.00
GLY76
13.00

GLU77
159.00
LYS78
116.00

PHE80
39.00
HIS81
141.00

GLY82
60.00
SER84
49.00

MET85
131.00
SER86
103.00

GLU87
22.00
ARG88
53.00

TYR90
31.00
LYS93
20.00

GLN94
49.00
ASN97
40.00

PHE98
10.00
GLU101
113.00

GLU102
83.00
PHE105
86.00

PRO106
72.00
SER108
46.00

ASP109
113.00
ARG110
96.00

PHE111
23.00
GLN112
136.00

PRO113
78.00
TYR114
54.00

GLN116
79.00
GLU117
60.00

VAL119
16.00
PRO120
58.00

PHE121
13.00
ALA123
33.00

ARG124
157.00
LEU125
3.00

SER126
20.00
ASN127
114.00

ARG128
126.00
SER130
54.00

THR131
117.00
HIS133
105.00

ILE134
30.00
GLU135
195.00

GLY136
39.00
ASP137
102.00

ASP138
39.00
LEU139
73.00

HIS140
48.00
GLN142
115.00

ARG143
155.00
ASN144
27.00

GLN146
80.00
LYS147
109.00

LYS149
53.00
ASP150
53.00

THR151
21.00
LYS153
127.00

LYS154
147.00
LEU155
37.00

GLY156
29.00
GLU157
104.00

SER158
32.00
GLU160
35.00

ILE161
11.00
LYS162
6.00

ALA163
11.00
GLY165
11.00

GLU166
15.00
ASP168
40.00

LEU169
38.00
MET172
86.00

SER173
15.00
ARG175
70.00

ASN176
112.00
ALA177
21.00

ILE179
89.00

Total area of chain A: 7584.

1
Amino acid residues correspond to residues in human IL-22, SEQ ID NO: 2.

2
Solvent exposed areas c

[0174]

	Number	Date	Country
	60317937	Sep 2001	US
	60333150	Nov 2001	US

	Number	Date	Country
Parent	10050552	Jan 2002	US
Child	10238965	Sep 2002	US

Crystal structure of interleukin-22 and uses thereof

Information

Publication Number

Date Filed

Date Published

Inventors

CPC

US Classifications

International Classifications

Abstract

Description

Claims

RELATED APPLICATIONS

Provisional Applications (2)

Continuation in Parts (1)