WO2012054438A1 - Anti-pcsk9 - Google Patents

Anti-pcsk9 Download PDF

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Publication number
WO2012054438A1
WO2012054438A1 PCT/US2011/056649 US2011056649W WO2012054438A1 WO 2012054438 A1 WO2012054438 A1 WO 2012054438A1 US 2011056649 W US2011056649 W US 2011056649W WO 2012054438 A1 WO2012054438 A1 WO 2012054438A1
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Prior art keywords
atom
hydrochloride
antibody
arg
tyr
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French (fr)
Inventor
Joseph A. Hedrick
Leonard G. Presta
Diane Hollenbaugh
Nicholas Murgolo
Jun Lu
Gopalakrishnan Parthasarathy
Noel Byrne
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Merck Sharp and Dohme LLC
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Schering Corp
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Definitions

  • the present invention relates to anti-PCSK9 antibodies and methods of treatment using such antibodies.
  • PCSK9 Proprotein convertase subtilisin-kexin type 9
  • NARC-1 neural apoptosis- regulated convertase 1
  • PCSK9 is a proteinase K-like subtilase identified as the 9th member of the secretory subtilase family.
  • the gene for PCSK9 localizes to human chromosome Ip33-p34.3.
  • PCSK9 is expressed in cells capable of proliferation and differentiation including, for example, hepatocytes, kidney mesenchymal cells, intestinal ileum, and colon epithetia as well as embryonic brain telencephalon neurons.
  • human PCSK9 which is ⁇ 22-kb long with 12 exons encoding a 692 amino acid protein, can be found, for example, at Deposit No. NP_777596.2.
  • Human, mouse and rat PCSK9 nucleic acid sequences have been deposited; see, e.g., GenBank Accession Nos.: AX 127530 (also AX207686), AX207688, and AX207690, respectively.
  • PCSK9 is a natural inhibitor of the low density lipoprotein receptor (LDLr) (Costet et al. Trends Biochem Sci 33 (2008): 426-434) and the hepatic form plays a major role in controlling cholesterolemia (Lagace et al., J Clin Invest 16 (2006): 2995-3005; Rashid et al., Proc Natl Acad Sci USA 102 (2005): 5374-5379; Zaid ef a/., Hepato!ogy 48 (2008): 646- 654).
  • PCSK9 gain-of-f unction mutations are associated to hypercholesterolemia and premature atherosclerosis.
  • PCSK9 loss-of-f unction mutations result in lower plasma LDL-chofesterol concentrations and a reduced risk for coronary heart disease.
  • LDL particles can transport cholesterol into the artery wall, increased levels are associated with atherosclerosis. Over time vulnerable plaques rupture, activate blood clotting and produce heart attack, stroke, and peripheral vascular disease symptoms and major debilitating events.
  • One therapy to reduce LDL is administration of a therapeutic antibody that targets PCSK9. JB2010.7161
  • the present invention provides an isolated antibody or antigen-binding fragment thereof ⁇ e.g., a humanized antibody, a recombinant antibody a monoclonal antibody, a labeled antibody, a bivalent antibody, a polyclonal antibody, a bispecific antibody, a chimeric antibody, an anti-idiotypic antibody, a bispecific antibody a camelized single domain antibody, a diabody, an scfv, an scfv dimer, a dsfv, a (dsfv) 2 , a dsFv-dsfv', a bispecific ds diabody, an Fv, an Fab, an Fab', an F(ab')2, or a domain antibody) comprising one or more members selected from the group consisting of: a polypeptide comprising CDR-H1 , CDR-H2 and CDR-H3 of the variable region the LPD1462 heavy chain immunoglobulin which comprises the amino acid sequence of
  • the isolated antibody or antigen-binding fragment thereof of claim 1 comprising one or more members selected from the group consisting of: HCDR1 comprising the amino acid sequence GYTFTDYYMN (SEQ ID NO: 12), HCDR2 comprising the amino acid sequence DINPNNGG YNQKFKG (SEQ ID NO: 13) and HCDR3 comprising the amino acid sequence GIITEIAEDF (SEQ ID NO: 14); and LCDR1 comprises the amino acid sequence KASQNVGTNVV (amino acids 24-34 or SEQ ID NO: 7), LCDR2 comprises the amino acid sequence SASYRYS (amino acids 50-56 of SEQ ID NO: 7) and LCDR3 comprises the amino acid sequence QQYKTYPYT (amino acids 89-97 of SEQ ID NO: 7) (e.g., both).
  • the isolated antibody or antigen-binding fragment thereof of claim 1 comprising one or more members selected from the group consisting of:
  • the antibody or antigen- binding fragment thereof of claim 1 is linked to an immunoglobulin constant region such as a K light chain, ⁇ 1 heavy chain, ⁇ 2 heavy chain, y3 heavy chain or y4 heavy chain, in an embodiment of the invention, the antibody or antigen-binding fragment is in a pharmaceutical composition comprising the antibody or fragment in association with a pharmaceutically acceptable carrier.
  • the present invention also provides a composition comprising the antibody or antigen-binding fragment thereof of claim 1 in association with a further chemotherapeutic agent; e.g., wherein the further chemotherapeutic agent is a
  • cardiovascular agent an adrenergic blocker, an antihypertensive agent, an angiotensin JB2010.7161 system inhibitor, an angiotensin-converting enzyme inhibitor, a coronary vasodilator, a diuretic, an adrenergic stimulant or an HMG-CoA reductase inhibitor, or e.g., wherein the further chemotherapeutic agent is ezetimibe, lovastatin, atorvastatin, pravastatin,
  • rosuvastatin rosuvastatin, fluvastatin, rivastatin, simvastatin, an azetidinone, bunolol hydrochloride, acebutoiol, alprenolol hydrochloride, atenolol, carteolol hydrochloride, celiprolol
  • hydrochloride isosorbide dinitrate, sosorbide mononitrate, nitroglycerin, verapamil hydrochloride, chromonar, clonitate, droprenilamine, lidoflazine, prenylamtne, propatyl nitrate, mioflazine hydrochloride, mixidine, molsidomine, isosorbide mononitrate, erythrityl tetranitrate, clonitrate, dipyridamole; nicorandil, pyridinecarboxamide, nifedipine; perhexiline maleate; oxprenolo!, pentrinitrol, verapamil, althiazide, benzthiazide, buthiazide,
  • the present invention further includes an isolated polypeptide comprising an amino acid sequence that comprises CDR-L1 , CDR-L2 and CDR-L3 of the variable region the LPD1282 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO:7; as well a polypeptide comprising any 1 , 2 or 3 CDRs of any of the immunoglobulin chains disclosed herein. Also included is an isolated polynucleotide encoding any of the polypeptides set forth herein, e.g.
  • a composition comprising: an isolated
  • the scope of the present invention also includes an isolated vector comprising any of the foregoing polynucleotides (e.g., a plasmid vector); as well as an isolated host cell comprising any of the foregoing
  • polynucleotides e.g. , wherein the polynucletide is in a vector
  • a vector e.g.. a Chinese hamster ovary cell, a Pichia cell or a P.pastoris cell.
  • the present invention also provides a method for reducing total cholesterol level; low density lipoprotein cholesterol level; a po lipo rotein B level; total cholesterol/high density lipoprotein ratio; or low density lipoprotein/high density lipoprotein ratio; or for treating or preventing hypercholesterolemia (e.g., primary hypercholesterolemia, e.g..
  • hypercholesterolemia e.g., primary hypercholesterolemia, e.g..
  • the subject has elevated serum LDL, e , wherein the subject has previously taken one or more LDL lowering drugs and.for example, has not achieved normal levels of LDL), hyperlipidemia, hypertriglyceridaemia, sitosterolemia, atherosclerosis, arteriosclerosis, coronary heart disease, vascular inflammation or xanthoma, in a subject, comprising administering, to said subject, a therapeutically effective amount of the antibody or antigen-binding fragment thereof; optionally in association with a further chemotherapeutic agent.
  • the further chemotherapeutic agent is a cardiovascular agent, an adrenergic blocker, an antihypertensive agent, an angiotensin system inhibitor, an angiotensin-converting enzyme inhibitor, a coronary vasodilator, a diuretic, an adrenergic stimulant or an HMG-CoA reductase inhibitor; or the further chemotherapeutic agent is JB2010.7161 ezetimibe, lovastatin, atorvastatin, pravastatin, rosuvastatin, fluvastatin, rivastatin, simvastatin, an azetidinone, bunoloi hydrochloride, acebutoloi, alprenolol hydrochloride, atenolol, carteoiol hydrochioride, celiprolol hydrochloride; cetamolol hydrochloride, labetalol hydrochloride, e
  • hydrochloride isosorbide dinitrate, sosorbide mononitrate, nitroglycerin, verapamil hydrochloride, chromonar, clonitate, droprenilamine, iidoflazine, prenylamine, propatyl nitrate, mioflazine hydrochloride, mixidine, molsidomine, isosorbide mononitrate, erythrityl tetranitrate, clonitrate, dipyridamole; nicorandii, pyridinecarboxamide, nifedipine; perhexiiine maleate; oxprenolol, pentrinitrol, verapamil, althiazide, benzthiazide, buthiazide,
  • the present invention also provides a method for producing the antibody or antigen- binding fragment therof comprising introducing one or more polynucleotides into one or more JB2010.7161 host cells; which polynucleotides encodes and direct expression of said heavy and/or light chain immunoglobulins; and growing said host cells under conditions whereby said heavy and light chain immunoglobulins are expressed.
  • said polynucleotide encoding and directing expression of said light chain and said polynucleotide encoding and directing expression of said heavy chain are in separate host cells.
  • the present invention also encompasses a crystalline composition
  • a crystalline composition comprising PCS 9 complexed with a Fab with a three dimensional structure characterized by structural coordinates comprising a root mean square deviation of common residue backbone atoms or alpha carbon atoms of less than about 1.5 A when superimposed on backbone atoms or alpha carbon atoms described by structural coordinates of Table 5 (e.g., wherein the crystalline composition has a three dimensional structure characterized by the structural coordinates of Table 5).
  • Figure 1 (A & B). Relative LDL-c lowering in cynomolgous monkeys with
  • LPD1282/LPD1462-lgG2 (1 F11-lgG2) (A) or LPD1282/LPD1462-lgG4 (1 F11-lgG4) (B).
  • Figure 2 Three dimensional representation of a human PCSK9/Fab (SEQ ID NO: 18 and 19) complex.
  • Figure 3 Three dimensional representation of the binding region between PCS 9. and the Fab.
  • the region is characterized by a lasso and post arrangement and a
  • the antibodies of the present invention are particularly advantageous.
  • Mouse antibodies possessing superior PCSK9 inhibitory activity must be humanized before use in human subjects. Typically, however, the binding affinity associated with a mouse antibody is reduced when moved into a human framework. As a result, the frameworks typically must be modified so as to restore binding affinity to levels comparable to that of the parental mouse JB2010.7161 antibody. If the binding energy associated with binding between antibody CDRs and an antigen is derived mainiy from a few CDR residues, then the optimization process is usually straight-forward. If the interaction between the antigen and CDRs is extensive, e.g., involving multiple residues, then optimization can be a very difficult and complex process.
  • the antibodies of the present invention are also extraordinary in that they bind to PCSK9 in a rather unusual place-at the furin processing site of PCSK9; accordingly, the scope of the present invention also includes any antibody or antigen-binding fragment thereof that binds to PCSK9 at the linear epitope EDGTRFHRQASKC (amino acids 21 1 -223 of SEQ ID NO:8) or at the furin processing site; along with a composition thereof comprising such an antibody or fragment in association with a further therapeutic agent (e.g., any of those discussed herein) or a pharmaceutical composition comprising such an antibody or fragment combined with a pharmaceutically acceptable carrier (e.g., any of those discussed herein) as well as method for treating any of the medical conditions discussed herein.
  • the epitope set forth above appears in each of these species of PCSK9. This facilitates animal model experimentation with the antibody or an antigen-binding fragment thereof of the present invention in mice and chimpanzees.
  • the antibody or antigen-binding fragment thereof of the present invention cross-reacts with human, mouse and chimpanzee PCSK9.
  • the present invention also includes a polypeptide (e.g., an oligopeptide) consisting of or consisting essentially of the amino acid sequence EDGTRFHRQASKC (amino acids 211- 223 of SEQ ID NO:8) optionally fused to a heterologous protein or further comprising one or several additional PCSK9 residues (e.g. , 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10) that are naturally contiguous with the N- or C-terminal end of EDGTRFHRQASKC (amino acids 211-223 of JB2010.7161
  • LPD1282/LPD1462 which is also known as 1 F11 , or the like comprises the LPD1282 and LPD1462 variabie domain chain sequences.
  • LPD1282/LPD1462-lgG2 indicates that the LPD1282/LPD1462 antibody heavy chain is conjugated to an lgG2 constant domain, e.g., wherein the light chain is conjugated to a kappa light chain constant domain.
  • Other antibodies or antigen-binding fragments thereof with other chain combinations may also be named using this convention (e.g. , LPD1282/LPD1462-lgG4).
  • subject or “patient” or the like includes any mammal such as a human, chimpanzee, monkey (e.g., cynomolgous monkey), rat, mouse, dog, cat, horse, cow, goat or sheep.
  • HAART highly active antiretrovirai therapy
  • CCR5 receptor antagonist CCR5 receptor antagonist, entry inhibitor, nucleoside and nucleotide reverse transcriptase inhibitor ( RTI), Non-nucieoside reverse transcriptase inhibitors (NNRTI), protease inhibitor, integrase inhibitor, and/or maturation inhibitor); is intolerant of HMG Co-A reductase inhibitor therapy; suffers from acute coronary syndrome; is on immunosuppressive therapy (e.g., wherein the subject has received an organ transplant); is diabetic; and/or, will, in the future, receive percutaneous coronary intervention.
  • RTI nucleoside and nucleotide reverse transcriptase inhibitor
  • NRTI Non-nucieoside reverse transcriptase inhibitors
  • protease inhibitor integrase inhibitor
  • maturation inhibitor e.g., integrase inhibitor, and/or maturation inhibitor
  • Oligonucleotide Synthesis (M.J. Gait ed. 1984); Nucleic Acid Hybridization (B.D. Hames & S.J. Higgins eds. (1985)); Transcription And Translation (B.D. Hames & S.J. Higgins, eds. (1984)); Animal Ceil Culture (R.I. Freshney, ed. (1986)); Immobilized Cells And Enzymes (IRL Press, (1986)); B. Perbal, A Practical Guide To Molecular Cloning (1984); F.M. Ausubel, et al. (eds,), Current Protocols in Molecular Biology, John Wiley & Sons, Inc. (1994).
  • polynucleotides of the present invention may, in an embodiment of the invention, be flanked by natural regulatory (expression control) sequences, or may be associated with heterologous sequences, including promoters, internal ribosome entry sites (IRES) and other ribosome binding site sequences, enhancers, response elements, suppressors, signal sequences, polyadenylation sequences, introns, 5'- and 3'- non-coding regions, and the like.
  • promoters promoters
  • IRS internal ribosome entry sites
  • enhancers enhancers, response elements, suppressors, signal sequences, polyadenylation sequences, introns, 5'- and 3'- non-coding regions, and the like.
  • the polynucleotides of the present invention may be operably associated with a promoter.
  • a "promoter” or “promoter sequence” is, in an embodiment of the invention, a DNA regulatory region capable of binding an RNA polymerase in a cell (e.g., directly or through other promoter-bound proteins or substances) and initiating transcription of a coding sequence.
  • a promoter sequence is, in general, bounded at its 3' terminus by the
  • transcription initiation site and extends upstream (5' direction) to include the minimum number of bases or elements necessary to initiate transcription at any level.
  • a transcription initiation site (conveniently defined, for example, by mapping with nuclease S1 ), as well as protein binding domains (consensus sequences) responsible for the binding of RNA polymerase.
  • the promoter may be operably associated with other expression control sequences, including enhancer and repressor sequences or with a nucleic acid of the invention. Promoters which may be used to control gene expression include, but are not limited to, cytomegalovirus (CMV) promoter (U.S.
  • Patent Nos. 5,385,839 and 5,168,062) the SV40 early promoter region (Benoist, et at. , ( 981) Nature 290:304-310), the promoter contained in the 3' long terminal repeat of Rous sarcoma virus (Yamamoto, et al., (1980) Cell 22:787-797), the herpes thymidine kinase promoter (Wagner, et al., (1981) Proc. Natl. Acad. Sci. USA 78:1441 -1445), the regulatory sequences of the metallothionein gene (Brinster, et aL, (1982) Nature 296:39-42);
  • prokaryotic expression vectors such as the ⁇ -lactamase promoter (Villa- Komaroff, et al., (1978) Proc. Natl. Acad. Sci. USA 75:3727-3731 ), or the tac promoter (DeBoer, et ah, (1983) Proc. Natl. Acad. Sci. USA 80:21-25); see also “Useful proteins from recombinant bacteria" in Scientific American (1 80) 242:74-94; and promoter elements from yeast or other fungi such as the Gal 4 promoter, the ADC (alcohol dehydrogenase) promoter, PGK
  • vector examples include a vehicle (e.g., a ptasmid) by which a DNA or RNA sequence can be introduced into a host cell, so as to transform the host and, optionally, promote expression and/or replication of the introduced sequence.
  • vehicle e.g., a ptasmid
  • host cell includes any eel! of any organism that is selected, modified, transfected, transformed, grown, or used or manipulated in any way, for the production of a substance by the cell, for example the expression or replication, by the cell, of a gene, a DNA JB2010.7161 or RNA sequence, a protein or an enzyme.
  • a host eel! can be a eukaryotic cell or prokaryotic cell.
  • a eukaryotic cell can be, for example, a Chinese hamster ovary cell (e.g., CHO-K1 or DXB1 1), a HeLa cell, an NIH 3T3 cell, or a yeast or fungal cell, such as S.cerevisiae, any Pichia cell, Pichia pasforis, Pichia flnlandica, Pichia trehalophila, Pichia koc!amae, Pichia membranaefaciens, Pichia minuta ⁇ Ogataea minuta, Pichia lindneri), Pichia opuntiae, Pichia thermotolerans, Pichia salictaria, Pichia guercuum, Pichia pijperi, Pichia stiptis, Pichia methanolica, Pichia, Saccharomyces cerevisiae, Saccharomyces, ⁇ polymorpha, Kluyveromyces, Kluyveromy
  • a prokaryotic cell can be, for example, a bacterial cell such as E.coli (e.g., BL21 or BL21 DE3); see U.S. Patent Nos. 4,952,496, 5,693,489 and 5,869,320 and in Davan!oo, P., et a!., (1984) Proc. Natl. Acad. Sci. USA 81 , 2035-2039; Studier, F. W., er a/. , (1986) J. Moi. Bioi. 189: 113-130; Rosenberg, A. H., et ai , (1987) Gene 56: 125-135; and Dunn, J. J., ef a/., (1988) Gene 68: 259 which are herein incorporated by reference.
  • E.coli e.g., BL21 or BL21 DE3
  • the present invention contemplates any superficial or slight modification to the amino acid or nucleotide sequences which correspond to the immunoglobulin chains of the antibodies or antigen-binding fragments thereof of the invention. Antibodies and antigen- binding fragments thereof comprising one or more of such modified chains form part of the present invention.
  • the present invention contemplates sequence-conservative variants and function-conservative variants. "Sequence-conservative variants" of immunoglobulin chains are those in which a change of one or more nucleotides in a given codon results in no alteration in the amino acid encoded at that position. Function- conservative variants of the immunoglobulin chains of the invention are also contemplated by the present invention.
  • “Function-conservative variants” are those in which one or more amino acid residues in a protein have been changed without altering the overall conformation and function of the polypeptide, including, but, by no means, limited to, replacement of an amino acid with one having similar properties. Amino acids with similar properties are well known in the art.
  • polar/hydrophilic amino acids which may be interchangeable include asparagine, glutamine, serine, cysteine, threonine, lysine, arginine, histidine, aspartic acid and glutamic acid; nonpolar/hydrophobic amino acids which may be interchangeable include glycine, alanine, valine, leucine, isoleucine, proline, tyrosine, phenylalanine, tryptophan and methionine; acidic amino acids which may be interchangeable include aspartic acid and glutamic acid and basic amino acids which may be interchangeable include histidine, lysine and arginine.
  • Conservative substitutions of an amino acid sequence refer to those wherein an amino acid of one subtype (e.g., polar/hydrophilic) is replaced with another JB2010.7161 amino acid of the same subtype; and, in an embodiment of the invention, wherein the conservatively substituted polypeptide retains essentially the same level of biological activity (e.g., binding affinity of a substituted anti-PCSK9 antibody for PCSK9).
  • the present invention includes nucleic acids encoding immunoglobulin chains of the present invention as well as nucleic acids which hybridize thereto.
  • the nucleic acids hybridize under low stringency conditions, more preferably under moderate stringency conditions and most preferably under high stringency conditions and, in an embodiment of the invention, exhibit PCSK9 binding activity when part if an antibody or antigen-binding fragment thereof.
  • a nucleic acid molecule is "hybridizabie" to another nucleic acid moiecu!e, when a single stranded form of the nucleic acid molecule can anneal to the other nucleic acid molecule under the appropriate conditions of temperature and solution ionic strength (see Sambrook, et a/., supra).
  • a stringent wash condition under which a membrane comprising hybridized nucleic acids may be washed of excess, non-hybridizing nucleic acids is 2XSSC at 65°C; whereas a stringent wash would be 0.1 X SSC at 65°C.
  • a stringent wash can include a series of washes at 65°C in decreasing salt concentrations (e.g., 3XSSC/0.2% SDS, then 1 x
  • a hybridization condition may be 6XSSC; 0.2% SDS; IXDenhard s blocking solution, or 1 % w/v milk; 10-50 ng/ml probe (denatured first); 65°C incubation, with agitation, for 18-24 hours.
  • a recipe for 20X SSC per liter is NaC1 175.3 g (3 molar final in
  • nucleic acids comprising immunoglobulin chain nucleotide sequences and immunoglobulin chain polypeptides comprising amino acid sequences which are at least about 70% identical, preferably at least about 80% identical, more preferably at least about 90% identical and most preferably at least about 95% identical (e.g., 95%, 96%, 97%, 98%, 99%, 100%) to the reference immunoglobulin chain nucleotide and immunoglobulin chain amino acid sequences of the present invention (i.e., as discussed herein) when the comparison is performed by a BLAST algorithm wherein the parameters of the algorithm are selected to give the largest match between the respective sequences over the entire length of the respective reference sequences.
  • Immunoglobulin chain polypeptides comprising amino acid sequences which are at least about 70% similar, preferably at least about 80% similar, more preferably at least about 90% similar and most preferably at least about 95% similar (e.g. , 95%, 96%, 97%, 98%, 99%, 100%) to the reference immunoglobulin chain amino acid sequences of of the present invention when the comparison is performed with a BLAST algorithm wherein the parameters of the algorithm are selected to give the JB2010.7161 largest match between the respective sequences over the entire length of the respective reference sequences, are also included in the present invention.
  • Sequence identity refers to exact matches between the nucleotides or amino acids of two sequences which are being compared.
  • Sequence similarity refers to both exact matches between the amino acids of two polypeptides which are being compared in addition to matches between nonidentical, biochemically related amino acids. Biochemically related amino acids which share similar properties and may be interchangeable are discussed above.
  • oligopeptide refers to a peptide, generally of no more than about 100 amino acids (e.g., 10, 20, 30, 40, 50, 60, 70, 80, or 90).
  • BLAST ALGORITHMS Altschul, S.F., et ai, (1990) J. ol. Biol. 215:403-410; Gish, W., et ai., (1993) Nature Genet. 3:266-272; Madden, T.L., et ai, (1996) Meth. Enzymol. 266:131-141; Altschul, S.F., et ai, (1997) Nucleic Acids Res. 25:3389-3402; Zhang, J., et ai., (1997) Genome Res.
  • the present invention includes methods and compositions comprising anti-PCSK9 antibodies and antigen-binding fragments thereof (e.g., LPD1282/LPD1462; 1 F11).
  • anti-PCSK9 antibody or the like refers to a full antibody that binds specifically to PCSK9 (e.g., human PCSK9); for example, monoclonal antibodies, polyclonal antibodies, bispecific antibodies, chimeric antibodies, recombinant antibodies, anti-idiotypic antibodies, humanized antibodies and bispecific antibodies.
  • antigen-binding fragment of an antibody JB2010.7161 encompasses a fragment or a derivative of an antibody, typically including at least a portion of the antigen-binding or variable regions (e.g.
  • the invention includes any antibody or antigen-binding fragment thereof comprising one or more of the light chain and/or heavy chain immunoglobulin CDRs set forth herein.
  • the antibody or fragment comprises all 3 light chain and/or all 3 heavy chain CDRs.
  • any of the antibodies and antigen-binding fragments that are discussed anywhere herein are further characterized by possessing one or more functional characteristics such as inhibiting the ability of PCSK9 to associate with LDL (low density lipoprotein) receptor, i.e., by competing with LDL receptor for PCSK9 binding; or lowering LDL levels in rhesus monkeys (e.g., under the conditions described crizo in Example 2), e.g., to a similar degree; or binding to the
  • PCSK9 furin processing site e.g., at the specific PCSK9 peptide epitope discussed herein; or binding to PCSK9 with a K D of about 10 '8 or a higher affinity (e.g., 10 9 M or 10 10 M) (any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic).
  • the scope of the present invention also includes any antibody or antigen-binding fragment thereof that binds to PCSK9 at the linear epitope EDGTRFHRQASKC (amino acids 21 1-223 of SEQ ID NO:8) or at the PCSK9 furin processing site; along with a composition thereof comprising such an antibody or fragment in association with a further therapeutic agent (e.g., any of those discussed herein) or a pharmaceutical composition comprising such an antibody or fragment combined with a pharmaceutically acceptable carrier (e.g., any of those discussed herein) as well as method for treating any of the medical conditions discussed herein (any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic).
  • a further therapeutic agent e.g., any of those discussed herein
  • a pharmaceutical composition comprising such an antibody or fragment combined with a pharmaceutically acceptable carrier
  • the antibody or antigen-binding fragment thereof has a linear epitope in PCSK9 including residues EDGTRFHRQASKC (amino acids 211-223 of SEQ ID NO:8); optionally, excluding residue D212; optionally including residues S188, R251 and/or C255 (any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic). Accordingly, the present invention also encompasses any antibody or antigen-binding fragment thereof that contacts PCSK9 in a similar manner. In an JB2010.7161 embodiment of the invention, the antibody or antigen-binding fragment thereof of the present invention contacts the following specific atoms in the PCSK9 antigen:
  • the heavy chain tyrosine 32 contacts PCSK9, for example at the specific tyrosine 32 atom set forth in the table above (any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic).
  • tyrosine 32 interacts with PCSK9 in a lasso-post arrangement; wherein, the post, tyrosine 32, is situated inside of a flexible loop comprising PCSK9 residues 2 0-222 (any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic).
  • the foi!owing specific atoms in the light chain of the antibody or antigen-binding fragment thereof of the present invention contact PCSK9:
  • any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic).
  • five tyrosines, 36, 55, 91 , 94 and 96, of the light chain of an antibody or antigen-binding fragment thereof of the present invention make hydrophobic interactions with PCSK9; for example, between PCS 9 and the specific atoms of the five tyrosines (any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this
  • antibodies and immunoglobulin chains of the present invention include those wherein the light chain variable domain is LPD1640 comprising the following amino acid sequence wherein the five tyrosines are numbered:
  • antibodies of the present invention include those wherein the light chain variable domain is LPD1282 comprising the following amino acid sequence wherein the five tyrosines are numbered:
  • SEQ ID NO: 7 The scope of the present invention encompasses antibodies and antigen- binding fragments thereof comprising tyrosines at amino acid positions 36, 55, 91 , 94 and 96 wherein the light chain residue numbering is as set forth above for SEQ ID NO: 5 or 7, i.e., wherein residue 1 is the first residue of the mature light chain variable region (any antibody or JB2010.7161 antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic).
  • the root mean square deviation is about 1 .5 A or about 1.0 A or about 0.75 A or about 0.5 A or about 0.25 A or about 0.10 A; forms part of the present invention.
  • the coordinates are exactly as set forth in Table 5.
  • any antibody or antigen-binding fragment thereof that, when converted to a Fab antigen-binding fragment format, is, itself, characterized by a three dimensional structure, which structure is characterized by atoms positioned in space as described in the portion of the structural coordinates set forth in Table 5 (or a set of structural coordinates coordinates that has a RMSD of conserved residue backbone atoms (N, Ca, C, O) or of a!pha carbon atoms (Ca) only of less than about 1.5 A (e.g., 1.0 A, 0.75 A, 0.5 A, 0.25 A, 0.1 A) when superimposed-using backbone atoms or alpha carbon atoms -on the relevant structure coordinates of Table 5) that relates to the Fab moiety is part of the present invention (any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic).
  • the anti-PCSK9 antibodies and antigen-binding fragments thereof used in the present invention include antibodies and fragments which were raised against or bind to the whole PCSK9 protein as well as antibodies raised against or that bind to particular short epitopes within PCSK9.
  • the present invention includes isolated polypeptides (e.g. , antibodies and antigen- binding fragments thereof) comprising one or more (e.g., 3) CDRs taken from any light and/or heavy chain immunoglobulin set forth herein as defined by the convention set forth in Kabat, "Sequences of Proteins of Immunological Interest” (National Institutes of Health, Bethesda, Md., 1987 and 1991 ) or in Chothia et al. , J. Mol. Biol. 196:901 (1987); Nature 342:878 (1989); and J. Mol. Biol. 186:651 (1989) (Kabat or Chothia) or Al-Lazikani et al., J. Mol. Biol. 273: 927-948 (1997). JB2010.7161
  • the present invention includes anti-PCSK9 antibodies and antigen-binding fragments thereof which bind specifically to PCSK9, for example, human PCSK9.
  • an anti-human PCSK9 antibody binds to human PCSK9 without any detectable binding to any other species of PCSK9 (e.g., no detectable binding to a rat PCSK9).
  • specific anti-PCSK9 binding refers to binding of the antibody to PCSK9 or an antigenic fragment thereof with a K D of about 10 "8 M or greater affinity.
  • an anti-PCSK9 antibody or antigen-binding fragment of the present invention binds to human PCSK9 with a K D of about 6, 6.4, 7, 8, 9, 10 or 10.7 n .
  • an antibody or antigen-binding fragment thereof of the present invention inhibits human PCSK9-mediated functional effects in a HepG2 celi-based LDL-c uptake assay with an IC 50 for human PCSK9 of about 9.8 nM.
  • an anti-PCSK9 antibody or antigen-binding fragment thereof of the present invention binds to human, cynomoigous monkey, rat and mouse PCSK9.
  • an anti-PCSK9 antibody or antigen-binding fragment of the present invention does not bind signigicantiy to the Fc Gamma Receptor (e.g.
  • an anti-PCSK9 antibody or antigen-binding fragment thereof of the present invention has an in vivo half life of about 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 days.
  • Any suitable method for generating antibodies may be used.
  • a recipient may be immunized with PCSK9 or an immunogenic fragment thereof.
  • Any suitable method of immunization can be used. Such methods can include adjuvants
  • PCSK9 any suitable source of PCSK9 can be used as the immunogen for the generation of the antibodies and fragments of the compositions and methods disclosed herein.
  • Such forms include, but are not limited whole protein, peptide(s), and epitopes generated through recombinant, synthetic, chemical or enzymatic degradation means known in the art.
  • the present invention also includes an isolated polypeptide consisting of or consisting essentially of the amino acid sequence EDGTRFHRQASKC (amino acids 211 -223 of SEQ ID NO:8) optionally fused to a heterologous protein or molecule (e.g., keyhole limpet hemocyanin (KLH)) or further comprising one or several additional PCSK9 residues (e.g., 1 , 2, 3, 4, 5, 6, 7, 8, 9, 0) that are naturally contiguous with the N- or C-terminal end of EDGTRFHRQASKC (amino acids 211 -223 of SEQ ID NO:8).
  • a heterologous protein or molecule e.g., keyhole limpet hemocyanin (KLH)
  • additional PCSK9 residues e.g., 1 , 2, 3, 4, 5, 6, 7, 8, 9, 0
  • Multimers comprising more than one (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10) of such peptides forms part of the present invention.
  • a method for producing an anti-PCSK9 antibody or antigen-binding fragment thereof comprsing immunizing a host animal (goat, rat, rabbit) with such a peptide also form part of JB2010.7161 the present invention.
  • a composition comprising such a peptide, e.g. , a vaccine, including an adjuvant or carrier forms part of the present invention.
  • the eliciting antigen may be a single epitope, multiple epitopes, or the entire PCSK9 protein alone or in combination with one or more immunogenicity enhancing agents known in the art.
  • polypeptides and antibodies of the present invention may be used with or without modification, including chimeric or humanized antibodies. Frequently, the polypeptides and antibodies will be labeled by joining, either covalently or non-covalentiy, a substance that provides for a detectable signal, A wide variety of labels and conjugation techniques are known and are reported extensively in both the scientific and patent literature.
  • Suitable labels include radionuclides, enzymes, substrates, cofactors, inhibitors, fluorescent moieties, chemiluminescent moieties, magnetic particles, and the like. Patents teaching the use of such labels include U.S. Patent Nos. 3,817,837; 3,850,752; 3,939,350; 3,996,345; 4,277,437; 4,275,149; and 4,366,241.
  • Fab fragment are known in the art.
  • the fragments contain the region on an antibody that binds to antigens. It contains one constant and one variable domain of each of the heavy and the light chain.
  • Fab fragments can be generated in the laboratory.
  • the enzyme papain can be used to cleave an antibody into two Fab fragments and an Fc fragment.
  • the enzyme pepsin cleaves below hinge region, so a F(ab') 2 fragment and a pFc' fragment is formed.
  • the F(ab') 2 fragment can be split into two Fab' fragments by mild reduction.
  • Disulfide stabilized Fv fragments and “dsFv” include molecules having a variable heavy chain (VH) and a variable light chain (V L ) which are linked by a disulfide bridge.
  • VH variable heavy chain
  • V L variable light chain
  • the "Fv region” comprises the variable regions from both the heavy and light chains, but lacks the constant regions.
  • single-chain Fv or “scFv” antibody refers to antibody fragments comprising the VH and V L domains of an antibody, wherein these domains are present in a single polypeptide chain.
  • the Fv polypeptide further comprises a
  • polypeptide linker between the VH and V L domains which enables the V H and VL chains to pair and form a binding site (e.g., 5-12 residues long).
  • a domain antibody is either the variable domain of an antibody heavy chain (VH domain) or the variable domain of an antibody light chain (V L domain).
  • VH domain variable domain of an antibody heavy chain
  • V L domain variable domain of an antibody light chain
  • Each domain antibody contains three of the six naturally occurring complementarity determining regions (CDRs) from an antibody.
  • a “bivalent antibody” comprises two antigen-binding sites. In some instances, the two binding sites have the same antigen specificities. However, bivalent antibodies may be bispecific.
  • the present invention comprises scfv dimers and dsfv dimers, each of which scfv and dsfv moieties may have a common or different antigen binding specificity.
  • a (dsfv)2 comprises three peptide chains: two V H moieties linked by a peptide linker and bound by disulfide bridges to two linked V L moieties.
  • a bispecific ds diabody comprises a VH r Vl_2 (tethered by a peptide linker) linked, by a disulfide bridge between the VHi and VLi, to a VL1-VH2 moiety (also tethered by a peptide linker), in an embodiment of the invention, a bispecific dsfv-dsfv' also comprises three peptide chains: a VH-
  • an scfv dimer (a bivalent diabody) comprises a VH-VL moiety wherein the heavy and light chains are bound to by a peptide linker and dimerized with another such moiety such that V H s of one chain coordinate with the V L s of another chain and form two identical binding sites.
  • a bispecific diabody comprises VHrVL 2 moiety (linked by a peptide linker) associated with a VL1-VH2 (linked by a peptide linker), wherein the VH-i and VLi coordinate and the VH 2 and VL 2 coordinate and each coordinated set has diverse antigen specificities.
  • monoclonal antibody refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic epitope. In contrast, conventional (polyclonal) antibody preparations typically include a multitude of antibodies directed against (or specific for) different epitopes. Monoclonal antibodies to be used in accordance with the JB2010.7161 present invention may be made recombinantly or by the hybridoma method first described by Kohler et al.
  • Monoclonal antibodies may be prepared from various mammalian hosts, such as mice, rats, other rodents, humans, other primates, ere.
  • ANTIBODIES A LABORATORY MANUAL CSH Press; Goding (1986) MONOCLONAL ANTIBODIES: PRINCIPLES AND PRACTICE (2d ed.) Academic Press, New York, NY.
  • monoclonal antibodies may be obtained by a variety of techniques familiar to researchers skilled in the art. Typicaily, spleen cells from an animal immunized with a desired antigen are immortalized, commonly by fusion with a myeloma cell. See Kohler and Milstein (1976) Eur. J. Immunol. 6:51 -519. Alternative methods of immortalization include tra sformation with Epstein Barr Virus, oncogenes, or retroviruses, or other methods known in the art.
  • Colonies arising from single immortaiized cells are screened for production of antibodies of the desired specificity and affinity for the antigen, and yield of the monoclonal antibodies produced by such cells may be enhanced by various techniques, including injection into the peritoneal cavity of a vertebrate host.
  • Antibodies of the present invention include “chimeric” antibodies
  • immunoglobulins in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity JB2010.7161
  • variable domains are obtained from an antibody from an
  • the parental antibody such as a mouse
  • the constant domain sequences are obtained from human antibodies, so that the resulting chimeric antibody will be less likely to elicit an adverse immune response in a human subject than the parental mouse antibody.
  • a recombinant antibody or antigen-binding fragment thereof of the invention is, in an embodiment of the invention, an antibody which is produced recombinantly, e.g., expressed from a polynucleotide which has been introduced into an organism (e.g., a plasmid containing a polynucleotide encoding the antibody or fragment transformed into a bacterial cell (e.g., E.coli) or a mammalian cell (e.g., CHO cell)), followed by isolation of the antibody or fragment from the organism.
  • Recombinant immunoglobulins may be produced by the methods set forth in Cabilly U.S. Patent No. 4,816,567.
  • the present invention comprises methods for expressing any antibody or antigen- binding fragment thereof or polypeptide of the present invention,
  • an embodiment of the present invention comprises a process for producing an
  • a host cell e.g., a single host cell
  • a CHO cell e.g., CHO-K1 or DXB11 cell
  • the polynucleotides are operably linked to a promoter such as a CMV promoter.
  • the present invention also comprises a process for producing an immunoglobulin molecule or an immunologically functional immunoglobulin fragment comprising introducing transforming a first haploid yeast host cell (e.g., Pichia such as Pichia pastoris) with a first haploid yeast host cell (e.g., Pichia such as Pichia pastoris) with a first haploid yeast host cell (e.g., Pichia such as Pichia pastoris) with a first haploid yeast host cell (e.g., Pichia such as Pichia pastoris) with a first haploid yeast host cell (e.g., Pichia such as Pichia pastoris) with a first haploid yeast host cell (e.g., Pichia such as Pichia pastoris) with a first haploid yeast host cell (e.g., Pichia such as Pichia pastoris) with a first
  • polynucleotide encoding at least the variable domain of the immunoglobulin heavy chain or light chain and transforming a second haploid yeast host cell (e.g., Pichia such as Pichia pastoris) with a second polynucleotide encoding the other chain, allowing the haploid cells to form polyploids, such as diploids, (e.g., via mating), selecting the polyploids from the haploids, and growing the polyploids under conditions wherein the JB2010.7161 heavy and light chains are expressed in the polyploids and, optionally, secreted into the culture medium.
  • a second haploid yeast host cell e.g., Pichia such as Pichia pastoris
  • polynucleotides introduced into a host cell remain ectopic whereas in another embodiment of the invention, the polynucleotide is integrated into the chromosomal DNA of the host cell
  • a method for producing an antibody or fragment or polypeptide further comprises isolating the chains that are expressed from the host cell and/or culture medium.
  • diabodies refers to small antibody fragments with two antigen-binding sites, which fragments comprise a heavy chain variable domain (V H ) connected to a light chain variable domain (VL) in the same polypeptide chain (V H -VL or VL-VH).
  • V H heavy chain variable domain
  • VL light chain variable domain
  • the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites.
  • Diabodies are described more fully in, e.g., EP 404,097; WO 93/1 1161 ; and Holliger et al. (1993) Proc. Natl. Acad. Sci. USA 90: 6444-6448. For a review of engineered antibody variants generally see Holliger and Hudson (2005) Nat. Biotechnol. 23:1126-1 36.
  • a humanized antibody typically comprises a FR region having, substantially, the amino acid sequence of a human immunoglobulin and CDRs having, substantially, the amino acid sequence of a non-human immunoglobulin. These non-human amino acid residues are referred to as "import" residues, which are typically taken from an "import" antibody or antibody domain, e.g., a variable domain of an antibody.
  • An import antibody typically! has a desired affinity and/or specificity, or other desirable biological activity.
  • the humanized antibody typically also will comprise at least a portion of a human immunoglobulin constant domain.
  • an embodiment of the invention includes humanized anti-PCSK9 (e.g., anti-human PCSK9) antibodies comprising mouse immunoglobulin CDRs and human immunoglobulin framework regions fused to a human immunoglobulin constant domain.
  • humanized anti-PCSK9 e.g., anti-human PCSK9 antibodies comprising mouse immunoglobulin CDRs and human immunoglobulin framework regions fused to a human immunoglobulin constant domain.
  • the present invention also includes isolated polypeptides comprising the amino acid sequences of any of the immunoglobulin chains set forth herein as well as variants thereof, e.g., as discussed herein, along with isolated polynucleotides encoding said polypeptides and variants, vectors comprising the polynucleotides and isolated host cells comprising the polynucleotides and vectors (e.g., CHO cells, bacterial cells such as E. coli and fungal cells such as S.cerevisiae and Pichia such as Pichia pastoris).
  • vectors comprising the polynucleotides and isolated host cells comprising the polynucleotides and vectors (e.g., CHO cells, bacterial cells such as E. coli and fungal cells such as S.cerevisiae and Pichia such as Pichia pastoris).
  • polypeptides, variants and JB2010.7161 polynucleotides, etc. may be used, for example, as intermediates in the generation of an anti-PCSK9 antibody or antigen-binding fragment thereof.
  • Methods for making the polypeptides are also included: comprising introducing the polynucleotide or vector into a host cell and culturing the host cell under conditions whereby the polypeptide is expressed and, optionally, secreted and, optionally, isolating the polypeptide.
  • the heavy chain and/or light chain immunoglobulin sequences of the anti-PCSK9 antibodies of the present invention are set forth below. CDR sequences are underscored.
  • the present invention also includes antibodies and antigen- binding fragments thereof comprising the CDRs of the heavy and/or light chain
  • the present invention also includes antibodies and antigen-binding fragments thereof comprising any combination of the heavy and light chain immunoglobulins set forth herein.
  • antibodies and antigen-binding fragments thereof comprising the light chain LPD1282 (e.g., fused to a kappa light chain constant domain) and the heavy chain LPD1462 (e.g., fused to a gamma-2 or 4 heavy chain constant domain) are within the scope of the present invention.
  • An antibody comprising a light chain variable region of LPD1282 and a heavy chain variable region of LPD1462 is designated as LPD1282/LPD1462.
  • the present invention also encompasses an anti-PCSK9 Fab comprising the heavy chain amino acid sequence:
  • an isolated polypeptide or variant thereof comprising the amino acid sequence of SEQ ID NO: 18 or 19 is part of the present invention.
  • the scope of the present invention includes any antibody or antigen-binding fragment thereof or light chain immunoglobulin or isolated polypeptide comprising the consensus JB2010.7161 amino acid sequence set forth below (SEQ ID NO: 20). Positions in the consensus sequence wherein the three chains differ are indicated with an X. The chain may be, at these X positions, any of the corresponding residues of the three chains, e.g. , the residue possessed by two of the three chains at that position.
  • the present invention includes consensus sequences comprising any possible combination of the indicated residues at the X positions.
  • LPD1260 RFSGSGSGTDFTLTISSLQPEDFATYYCQQYKTYPYTFGQGTKVEIKR
  • the scope of the present invention inciudes any antibody or antigen-binding fragment thereof or heavy chain immunoglobulin or isolated polypeptide comprising the consensus amino acid sequence set forth below (SEQ ID NO: 21 ). Positions in the consensus sequence wherein the three chains differ are indicated with an X. The chain may be, at these X positions, any of the corresponding residues of the three chains, e.g. , the residue possessed by two of the three chains at that position.
  • the present invention includes consensus sequences comprising any possible combination of the indicated residues at the X positions.
  • the present invention includes compositions and methods comprising antibodies and antigen-binding fragments thereof (e.g., LPD1282/LPD1462) which bind specifically to PCSK9, for example, human PCSK9.
  • the present invention includes a complex between any isolated antibody or antigen-binding fragment thereof bound to PCSK9 (e.g. , human PCSK9) (e.g., PCSK9 such as human PCSK9 in a eel! in the body of a subject such as a human).
  • PCSK9 e.g., human PCSK9
  • specific PCSK9 polypeptide sequences or antigenic fragments thereof from various species set forth below may be used as an antigen: JB2010.7161
  • GTVSSRRSW PLPLLLLLLLLLGPAGARAQEDEDGDYSELVIALRSEEDGLAEAPEHGTTATFHRCA D PWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPHV DYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLVEVYLLDTSIQSDHREIEGRVMVTDFENVPE EDGTRFHRQASKCDSHGTHLAGVVSGRDAGVA GASMRSLRVLNCQG GTVSGTLIGLEFIRKSQLVQPV GPLVVLLPLAGGYSRVL AACQRLARAGVVLVT AGNF DDACLYSPAS PEVITVGATNAQDQPVTLG LGTNFGRCVDLFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSA KDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWS
  • the present invention provides methods for treating or preventing disorders of cholesterol or lipid homeostasis that are mediated, at least in part, by PCSK9, and disorders and complications associated therewith, e.g., hypercholesterolemia, hyperlipidemia, hypertriglyceridaemia, atherosclerosis, primary heterogeneous familial hypercholesterolemia, arteriosclerosis, coronary heart disease, vascular inflammation and elevated serum LDL by administering a therapeutically effective amount of an anti-PCSK9 antibody (e.g., as set forth herein, e.g.
  • the antibody or fragment is administered to reduce serum LDL levels by at least about 25% or 50% (e.g. , about 25-50%) (for at least about 20 to 30 days following a dose).
  • a subject with a disorder of cholesterol or lipid homeostasis that are mediated, at least in part, by PCSK9, or a disorder or complication associated therewith is administered a therapeutically effective amount of the anti-PCSK9 antibody or antigen-binding fragment thereof to lower the serum LDL wherein the subject is HIV-positive and receiving highly active antiretroviral therapy (HAART; e.g. , CCR5 receptor antagonist, entry inhibitor, nucleoside and nucleotide reverse transcriptase inhibitor (NRTI), JB2010.7161
  • HAART highly active antiretroviral therapy
  • Non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitor, integrase inhibitor, and/or maturation inhibitor); is intolerant of H G Co-A reductase inhibitor therapy; suffers from acute coronary syndrome; is on immunosuppressive therapy (e.g., wherein the subject has received an organ transplant); is diabetic; and/or, will, in the future, receive percutaneous coronary intervention.
  • NRTI Non-nucleoside reverse transcriptase inhibitors
  • hypercholesterolemia includes, e.g. , familial and non-familial
  • Familial hypercholesterolemia is an autosomal dominant disorder characterized by elevation of serum cholesterol bound to low density lipoprotein (LDL). Familial hypercholesterolemia includes both heterozygous FHC and homozygous FHC; methods for treating or preventing any of which by administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g., LPD1462/LPD1282) form part of the present invention.
  • a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention e.g., LPD1462/LPD1282
  • Hyperlipidemia is an elevation of lipids in the bloodstream. These lipids include cholesterol, cholesterol esters, phospholipids and triglycerides. Hyperlipidemia includes for example, type I, lla, lib, III, IV and V; methods for treating or preventing any of which by administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention ⁇ e.g. , LPD1462/LPD1282) form part of the present invention.
  • Sitosterolemia is a rare inherited plant sterol storage disease.
  • the metabolic defect in the affected patient causes hyperabsorption of sitosterol from the gastrointestinal tract, decreased hepatic secretion of sitosterol with subsequent decreased elimination, and altered cholesterol synthesis.
  • sitosterolemia by administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g. , LPD1462/LPD1282) form part of the present invention
  • Atherosclerosis includes hardening of arteries associated with deposition of fatty substances, cholesterol, cellular waste products, calcium and fibrin in the inner lining of an artery. The buildup that results is called plaque.
  • Methods for treating or preventing atherosclerosis by administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention form part of the present invention
  • Arteriosclerosis includes the diffuse build-up and deposition of calcium in artery walls which leads to hardening. Methods for treating or preventing arteriosclerosis by
  • anti-PCSK9 antibody or antigen binding fragment thereof of the present invention form part of the present invention JB2010.7161
  • the present invention also provides methods for improving blood cholesterol markers associated with increased risk of heart disease. These markers include, but are not limited to, high total cholesterol, high LDL, high total cholesterol to HDL ratio and high LDL to HDL ratio.
  • a total cholesterol of less than 200 mg/dL is considered desirable, 200-239 mg/dL is considered borderline high and 240 mg/dL and above is considered high.
  • the present invention comprises methods for reducing total cholesterol, e.g. , to less than or equal to about 200 mg/dL by administering a therapeutically effective amount of anti- PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g.,
  • a blood LDL level of less than 100 mg/dL is considered optimal; 100-129 mg/dL is considered near optimal/above optimal, 130-159 mg/dL is considered borderline high, 160- 89 mg/dL is considered high and 190 mg/dL and above is considered very high.
  • the present invention comprises methods for reducing LDL, e.g. , to less than about 100 mg/dL by administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g., LPD1462/LPD1282).
  • HDL levels considered normal are at least 35 - 40 mg/dL.
  • the present invention comprises methods for increasing HDL, e.g., to greater than or equal to about 35-40 mg/dL by administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g.,
  • Another indicator of heart disease risk is the ratio of total cholesterol to HDL.
  • a very low risk of heart disease correlates with a ratio of ⁇ 3.4 (men) or ⁇ 3.3
  • the present invention comprises methods for reducing the ratio of total cholesterol to HDL, e.g., to less than about 4.5 or 5.0 by administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g., LPD1462/LPD1282).
  • a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention e.g., LPD1462/LPD1282.
  • a further indicator of heart disease risk is the ratio of LDL to HDL.
  • a very low risk is associated with a ratio of 1 (men) or 1.5 (women)
  • an average risk is associated with a ratio of 3.6 (men) or 3.2 (women)
  • a moderate risk is associated with a ratio of 6.3 (men) or 5.0 (women)
  • a high risk is associated with a ratio of 8 (men) or 6.1 (women).
  • the present invention comprises methods for the ratio of LDL to HDL, e.g., to less than or equal to about 3.2 or 3.6 by administering a therapeutically effective amount of JB2010.7161 anti-PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g. , LPD1462/LPD1282).
  • anti-PCSK9 antibodies and antigen-binding fragments thereof of the invention are formulated into a pharmaceuticai formulation which comprises a pharmaceutically acceptable carrier.
  • a pharmaceutically acceptable carrier for general information concerning formulations, see, e.g., Gilman, et al., (eds.) (1990), The Pharmacological Bases of Therapeutics, 8th Ed., Pergamon Press; A. Gennaro (ed.),
  • an anti-PCSK9 antibody or antigen-binding fragment thereof of the invention (e.g. , LPD1462/LPD1282) is formulated with a
  • a pharmaceutically acceptable carrier that includes a buffer (e.g. , water and a buffer).
  • a buffer e.g. , water and a buffer.
  • an anti-PCSK9 antibody or fragment of the invention e.g., LPD1462/LPD1282
  • such a formulation or any other pharmaceuticai formulation including an anti-PCSK9 antibody or fragment of the invention and a
  • the formulation is lyophilized or aqueous.
  • the anti-PCSK9 antibodies and antigen-binding fragments thereof of the present invention can be formulated according to known methods to prepare pharmaceutically useful compositions, whereby the antibody or fragment is combined in admixture with a pharmaceutically acceptable carrier, e.g., following antibody immunoglobulin synthesis, for example, as discussed herein.
  • a pharmaceutically acceptable carrier e.g., following antibody immunoglobulin synthesis, for example, as discussed herein.
  • Carriers, excipients or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate and other organic acids; antioxidants including JB2010.7161 ascorbic acid; low molecular weight polypeptides; proteins, such as serum albumin, gelatin or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone, amino acids such as glycine, giutamine, asparagine, arginine or lysine; monosaccharides, disaccharides and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt-forming counterions such as sodium; and/or nonionic surfactants such as Tween, Pluronics or PEG.
  • buffers such as phosphate, citrate and other organic acids
  • antioxidants including JB2010.7161 ascorbic acid
  • compositions to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes, prior to or following lyophilization and reconstitution.
  • Therapeutic or pharmaceutical compositions or formulations herein generally are placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle.
  • the route of administration of the antibodies and antigen-binding fragments thereof of the invention are, in an embodiment of the invention, by a parenteral route (e.g. , intravenous, subcutaneous, intraarterial, intratumoral, intramuscular, intraperitoneal).
  • a parenteral route e.g. , intravenous, subcutaneous, intraarterial, intratumoral, intramuscular, intraperitoneal.
  • Dosages and desired anti-PCSK9 concentrations of pharmaceutical compositions of the present invention may vary depending on the particular use envisioned.
  • a disorder in a subject When used to treat a disorder in a subject (e.g., as discussed herein), a
  • a therapeutically effective dosage or amount of anti-PCSK9 antibody or antigen-binding fragment thereof is administered to the subject.
  • a therapeutically effective dosage is a dosage sufficient to decrease serum LDL to any detectable degree, e.g., by about 25% to about 50%.
  • a therapeutically effective dosage of anti-PCSK9 antibody or antigen-binding fragment thereof for treatment of hypercholesterolemia, heterogeneous familial hypercholesterolemia, hyperlipidemia, hypertriglyceridaemia, sitosteroiemia, atherosclerosis, arteriosclerosis, coronary heart disease, vascular inflammation or xanthoma or for treatment of any blood marker of heart disease risk (e.g., as discussed herein) is about 0.5, 0.75, 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19 or 20 mg/kg of body weight, e.g., in a volume of about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19 or 20 ml, e.g., at a rate of once every week, 2 JB2010.7161 weeks, 3 weeks, 4 weeks,
  • injection device such as a needle and syringe or an injection pump.
  • an agent e.g. , further therapeutic agents discussed herein
  • administration and dosage of an agent is done according to the schedule listed in the product information sheet of the agents, in the Physicians' Desk Reference 2003 (Physicians' Desk Reference, 57th Ed); Medical Economics Company; ISBN; 1563634457; 57th edition (November 2002), as well as therapeutic protocols well known in the art.
  • a physician or clinician may monitor the blood cholesterol HDL or LDL levels or other marker levels associated with a cholesterol or lipid homeostasis disorder or disorder or complication associated therewith, in a subject being treated or about to be treated with an anti-PCSK9 antibody or antigen-binding fragment thereof (e.g., LPD1462/LPD1282), and make adjustments to the subject's treatment regimen as needed to reach a positive medical outcome.
  • an anti-PCSK9 antibody or antigen-binding fragment thereof e.g., LPD1462/LPD1282
  • the present invention provides methods and compositions for treating disorders of lipid and cholesterol metabolism (e.g., any set forth herein) by administering an anti-PCSK9 antibody or antigen-binding fragment thereof.
  • Any antibody or antigen-binding fragment thereof of the present invention e.g. , LPD1462/LPD1282; 1 F11
  • Any additional or further chemotherapeutic agent e.g., any that is discussed herein.
  • the further chemotherapeutic agent is a cardiovascular agent, an adrenergic blocker, an antihypertensive agent, an angiotensin system inhibitor, an angiotensin- converting enzyme (ACE) inhibitor, a coronary vasodilator, a diuretic or an adrenergic stimulant.
  • the further therapeutic agent is a cholesterol lowering medication such as an HMG-CoA reductase inhibitor.
  • the scope of the present invention also encompasses methods for treating or preventing a disorder of cholesterol or lipid homeostasis or any disorder or complication associated therewith by administering a therapeutically effective amount of the anti-PCSK9 antibody or antigen-binding fragment thereof (e.g.
  • the subject also suffers from a further medical condition such as, for example, hypertension, angina, cardiac arrhythmia, renal disease, congestive heart disease, myocardial infarction, enlarged heart, alcoholic cardiomyopathy, congenital heart disease, ischemic cardiomyopathy, hypertensive cardiomyopathy, valvular cardiomyopathy, inflammatory cardiomyopathy, myocardiodystrophy, dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic JB2010.7161 right ventricular cardiomyopathy, restrictive cardiomyopathy, noncompaction
  • a further medical condition such as, for example, hypertension, angina, cardiac arrhythmia, renal disease, congestive heart disease, myocardial infarction, enlarged heart, alcoholic cardiomyopathy, congenital heart disease, ischemic cardiomyopathy, hypertensive cardiomyopathy, valvular cardiomyopathy, inflammatory cardiomyopathy, myocardiodystrophy, dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic JB2010
  • cardiomyopathy thrombosis or pericarditis; comprising further administering a further chemotherapeutic agent that treats or prevents such a further medical condition.
  • a further chemotherapeutic agent that treats or prevents such a further medical condition.
  • Cardiovascular agents which may used in connection with the present invention include those for treatment or prevention of lipid and/or cholesterol disorders or hypertension and other cardiovascular disorders and diseases. Disorders of lipid or cholesteroi metabolism may be caused or aggravated by hypertension. Hypertension is defined as persistently high blood pressure. Generally, adults are classified as being hypertensive when systolic blood pressure is persistently above 140 mmHg or when diastolic blood pressure is above 90 mmHg. Long-term risks for cardiovascular mortality increase in a direct relationship with persistent blood pressure. Examples of
  • antihypertensive agents which may be used in the present invention include e.g., calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-!! receptor antagonists, diuretics, adrenergic blockers including beta-adrenergic receptor blockers and alpha-adrenergic receptor blockers or diuretics.
  • ACE angiotensin-converting enzyme
  • adrenergic blockers including beta-adrenergic receptor blockers and alpha-adrenergic receptor blockers or diuretics.
  • cardiac drugs that may be provided in association with an anti-PCSK9 antibody or antigen-binding fragment thereof includes anti-anginal agents, such as adrenergic stimulants or coronary vasodilators and HMG-CoA reductase inhibitors.
  • anti-anginal agents such as adrenergic stimulants or coronary vasodilators and HMG-CoA reductase inhibitors.
  • HMG-CoA reductase inhibitors inhibit the HMG-CoA reductase enzyme and, thus, reduce production of cholesterol in the body of a subject.
  • HMG-CoA reductase inhibitors inhibit the HMG-CoA reductase enzyme and, thus, reduce production of cholesterol in the body of a subject.
  • JB2010.7161 include, e.g., iovastatin, atorvastatin, ravastatin, rosuvastatin, fluvastatin, rivastatin and
  • Adrenergic blockers include those compounds which are ⁇ -receptor inhibitors and/or a-receptor inhibitors.
  • Adrenergic blockers which are p-receptor inhibitors include a class of drugs that antagonize the cardiovascular effects of catecholamines in hypertension, angina pectoris, and cardiac arrhythmias
  • p-adrenergic receptor blockers include, but are not limited to, bunolol hydrochloride (1(2H)-Naphthalenone, 5-[3- ⁇ 1 ,1-dimethylethyl)amino]-2- hydroxypropoxy]-3,4-dihydro-, hydrochloride, CAS RN 31969-05-8 which can be obtained from Parke-Davis); acebutolol ( ⁇ N-[3-Acetyl-4-[2 ⁇ hydroxy-3-[(1
  • acebutolol hydrochloride such as N-[3-acetyl-4-[2-hydroxy-3-[1-methyl- ethyle)amino]propoxy]phenyl]-,monohydrocochloride, ( ⁇ -;-3'-Acetyl-4'-[2-hydroxy-3- (isopropylamino)propoxyjbutyranilide monohydrochloride, for example, SECTRAL Capsules available from Wyeth-Ayerst); alprenolol hydrochloride (2-Propanol, 1-[(1-methy!ethyi)amino]- 3 ⁇ [2-(2-propenyl)phenoxy]-,hydrochloride, CAS RN 13707-88-5 see Netherlands Patent Application No.
  • Atenolol such as benzeneacetamide 4-[2'-hydroxy-3'-[(1- methylethyl)ammo]propoxy3- , for example, TENORMIN I.V. Injection available from
  • carteolol hydrochloride such as 5-[3-[(1 ,1-dimethylethyl)amino]-2- hydroxypropoxy]-3,4-dihydro-2(1 H)-quinolinone monohydrochloride, for example, Cartrol Filmtab Tablets available from Abbott; Celipro!ol hydrochloride (3-[3-Acetyl-4-[3-(ferf- JB2010.7161 butylamino)-2-hydroxypropoxyl]phenyl]-1 ) 1-diethyiurea monohydrochloride, CAS RN 57470- 78-7, also see in US Patent No.
  • cetamolol hydrochloride (Acetamide, 2-[2-[3- [ ⁇ 1 ,1-dimethylethyl)amino]-2-hydroxypropoxy]-phenoxy]-N-methyi-,monohydrochioride, CAS RN 77590-95-5, see also US Patent No.
  • labetalol hydrochloride such as 5-[1- hydroxy-2-[(1-methyl-3-phenyIpropyl) amino] ethyljsalicyiamide monohydrochloride, for example, NORMODYNE Tablets available from Schering; esmolol hydrochloride ( ( ⁇ )-Methyl p-[2-hydroxy-3-(isopropylamino) propoxy] hydrocinnamate hydrochloride, for example, BREVIBLOC Injection available from Baxter); levobetaxolol hydrochloride (such as (S)-1-[p- [2-(cyclopropylmethoxy)ethyl]phenoxy]-3-(isopropylamino)-2-propanol hydrochloride, for example, BETAXON Ophthalmic Suspension available from Alcon); levobunolol
  • hydrochloride such as (-)-5-[3-(tert-Butylamino)-2-hydroxypropoxy]-3,4-dihydro-1 (2H)- naphthalenone hydrochloride, for example, BETAGAN Liquififm with C CAP Compliance Cap available from Allergan); nadolol (such as 1-(tert-butylamino)-3-[(5,6,7,8-tetrahydro-cis-6,7- dihydroxy-1-naphtbyl)oxy]-2-propanol, for example, Nadolol Tablets available from ylan); practolol (Acetamide, N-[4-[2-hydroxy-3-[1-methylethyl)amino]-propoxy]phenyl]-, CAS RN
  • cicloprolol hydrochloride such 2-Propanol, 1-[4-[2-(cyclopropylmethoxy)ethoxy]phenoxy3-3-[1- methylethyl)amino]-, hydrochloride, A.A.S.
  • hydrochloride (Benzamide, 2-hydroxy-5-[1-hydroxy-2-[1-methyl-3-phenylpropyl)amino]ethyl]- , monohydrochloride, CAS RN 75659-08-4); exaprolol hydrochloride (2-Propanol, 1-(2- cyclohexylphenoxy)-3-[(1-methyiethyl)amino3-,hydrochloride CAS RN 59333-90-3); flestolol JB2010.7161 sulfate (Benzoic acid, 2-fluro-,3-[[2-[aminocarbonyl)amino]-1-dimethylethyl]amino]-2- hydroxypropyl ester, ( ⁇ )- sulfate ⁇ 1 :1) (salt), CAS RN 88844-73-9; metaloi hydrochloride (Methanesulfonamide, N-E4-[1-hydroxy-2-
  • Adrenergic receptors which are a-receptor inhibitors act to block vasoconstriction induced by endogenous catecholamines. The resulting fail in peripheral resistance leads to a fall in mean blood pressure.
  • Suitable adrenergic receptors which are a-receptor inhibitors include, but are not limited to, fenspiride hydrochloride (which may be prepared as disclosed in US Patent No. 3,399,192 herein incorporated by reference); proroxan (CAS RN: 33743-96-3); alfuzosin hydrochloride (CAS RN: 81403-68-1); and labetalol hydrochloride as described above or combinations thereof.
  • Adrenergic blockers with a- and ⁇ -receptor inhibitor activity which may be used with the present invention include, but are not limited to, bretylium tosylate (CAS RN: 61-75-6); dihydroergtamine mesylate (such as ergotaman-3', 6', 18-trione,9,-10-dihydro-12'-hydroxy-2'- methyl-S'-fphenylmethylJ-.tS alpha))-, monomethanesulfonate, for example, DHE 45 Injection available from Novartis); carvediiol (such as ( ⁇ )-1-(Carbazol-4-yloxy)-3-[[2-(o- methoxyphenoxy)ethyl]amino]-2-propanol, for example, COREG Tablets available from SmithKline Beecham);.
  • bretylium tosylate CAS RN: 61-75-6
  • dihydroergtamine mesylate such
  • labetalol such as 5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl) amino] ethyljsalicylamide monohydrochloride, for example, NOR ODYNE Tablets available from Schering
  • bretylium tosylate Benzenemethanaminium, 2-bromo-N-ethyl-N,N-dimethyh salt with 4-methylbenzenesulfonic acid (1 :1) CAS RN 61-75-6
  • phento!amine mesylate Phenol, 3-Ef(4,5-dihydro-1H-imidazol-2-yl)methyl](4-methylphenyl)amino]-, monomethanesulfonate (salt) CAS RN 65-28-1
  • soiypertine tartrate 5H-1 ,3-Dioxolo[4,5-fJindoie, 7-[2-[4-(2- methoxyphenyl)-1-
  • An angiotensin system inhibitor is an agent that interferes with the function, synthesis or catabo!ism of angiotensin II.
  • agents which may be used in the present invention, include, but are not limited to, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II antagonists, angiotensin II receptor antagonists, agents that activate the catabolism of angiotensin II and agents that prevent the synthesis of angiotensin I from which angiotensin II is ultimately derived.
  • ACE angiotensin-converting enzyme
  • the renin-angiotensin system is involved in the regulation of hemodynamics and water and electrolyte balance.
  • Angiotensin I and angiotensin II are synthesized by the enzymatic renin-angiotensin pathway. The synthetic process is initiated when the enzyme renin acts on angiotensinogen, a pseudoglobuiin in blood plasma, to produce the cecapeptide angiotensin I.
  • Angiotensin I is converted by angiotensin- converting enzyme (ACE) to angiotensin li.
  • ACE angiotensin- converting enzyme
  • the latter is an active pressor substance which has been implicated as a causative agent in several forms of hypertension in various mammalian species.
  • Angiotensin II receptor antagonists are compounds which interfere with the activity of angiotensin II by binding to angiotensin II receptors and interfering with its activity.
  • Angiotensin II receptor antagonists which may be used in the present invention are well known and include peptide compounds and non-peptide compounds.
  • Non-limiting examples of angiotensin II receptor antagonists include: candesartan cilexetil (1 H-Benzimidazole-7- carboxylic acid, 2-ethoxy-1-[[2'-(1 H-tetrazo!-5-yl)[1 ,1 , -biphenyl]-4-yl3methyl]-, 1- [[(cyclohexyloxy)carbonyl]oxy]ethyl ester ) CAS RN 145040-37-5); telmisartan( [1 ,1 - Biphenyl]-2-carboxylic acid, 4'-[(1 ,4'-dimethyi-2'-propyl[2,6'-bi-1 H-benzimidazol]-1'-yl)methyl]- CAS RN 144701-48-4); candesartan (1 H-
  • Angiotensin-converting enzyme is an enzyme which catalyzes the conversion of angiotensin I to angiotensin II.
  • ACE inhibitors which may be used in the present invention include amino acids and derivatives thereof, peptides, including di- and tri- peptides and antibodies to ACE which intervene renin-angiotensin system by inhibiting the activity of ACE thereby reducing or eliminating the formation of pressor substance angiotensin II.
  • ACE inhibitors have been used medically to treat hypertension, congestive heart failure, JB2010.7161 myocardial infarction and renal disease.
  • Suitable ACE inhibitors include, but are not limited to, benazepril hydrochloride (such as 3-[[1-(ethoxycarbonyl)-3-phenyl-(1 S)-propyl]amino]- 2,3,4,5-tetrahydro-2-oxo-1 H -1-(3S)-benzazepine-1 -acetic acid monohydrochloride, for example, LOTREL ® Capsules available from Novartis); captopril (such as 1-[(2S)-3- mercapto-2-methylpropionyl)-L-proline, for example, CAPTOPRIL Tablets available from ylan); fosinopril (such as L-proline, 4-cyclohexyl-1-[[[2-methyl-1 ⁇ (1-oxopropoxy) propoxy] (4-phenylbutyl) phosphinyl] acetyl]-, sodium salt, trans - ,for example, MONOPR!L Tablets
  • perindopril erbumine such as 2S,3aS,7aS)-1-[(S)-N-[(S)-1- Carboxybutyl]alanyl]hexahydro-2-indolinecarboxylic acid, 1 -ethyl ester, compound with tert- butylamine (1 :1), for example, ACEON Tablets available from Soivay
  • quinapril such as [3S- [2[R*(R*)],3R*]3-2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1 ,2,3,4- tetrahydro-3-isoquinolinecarboxyIic acid, monohydrochloride, for example, ACCURETIC Tablets available from Parke-Davis); ramipril (such as 2-aza-bicycio [3.3.0]-octane-3- carb
  • maleate such as (S)-1-[N -[1-(ethoxycarbonyi)-3- phenylpropylj-L-alanyl]-L-proline, (Z)-2- butenedioate salt (1 :1)., for example, VASOTEC Tablets available from Merck); lisinopril (such as ( S )-1-[ N 2-(1-carboxy-3-phenylpropyl)-L-lysyl]-L-proline dihydrate, for example, PRINZIDE Tablets available from Merck); delapril (which may be prepared as disclosed in US Patent No. 4,385,051); and spirapril (which may be prepared as disclosed in US Patent No.
  • spiraprilat 1 (,4-Dithia-7-azasptro[4-4]nonane-8-carboxylic acid, 7-[(2S)-2-[[(1 S)-1-carboxy-3- phenyipropyl]amino]-1-oxopropyl]-, (8S)- CAS RN 83602-05-5); teprotide (Bradykinin potentiator BPP9a CAS RN 35115-60-7); lisinopril (L-Proiine, N2-[(1 S)-1 -carboxy-3 ⁇ phenylpropyl]-L-lysy!- CAS RN 76547-98-3); zofenopril (L-Proline, 1-[(2S)-3-(benzoyithio)-2- methyl-1 -oxopropyl]-4-(phenyithio)-, calcium salt (2:1 ), (4S)- CAS RN 8
  • Calcium channel blockers are a class of compounds having important therapeutic value in the control of a variety of diseases including several cardiovascular disorders such as hypertension, angina, and cardiac arrhythmias (Fleckenstein, Cir. Res. V. 52 (suppl. 1), p. 13-16 (1983); Fleckenstein, Experimental Facts and Therapeutic Prospects, John Wiley, New York (1983); McCail, D., Curr. Pract Cardiol., v. 10, p. 1-11 (1985)). Calcium channel blockers are a heterogeneous group of drugs that prevent or slow the entry of calcium into cells by regulating cellular calcium channels (Remington, The Science and Practice of Pharmacy, Nineteenth Edition, Mack Publishing Company, Eaton, PA, p. 963 (1995)).
  • Calcium channel blockers useful in the present invention include but are not limited to, the besylate salt of amlodipine (such as 3-ethyl-5-methyl-2-(2-aminoethoxymethyl)-4-(2- chlorophenyl)-1 ,4-dihydro-6-methyl-3,5-pyridinedicarboxylate benzenesulphonate, for example, NORVASC available from Pfizer); clentiazem maleate (1 ,5-Benzothiazepin-4(5H)- one, 3-(acetySoxy)-8-chloro-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-(2S- cis)-, (Z)-2-butenedioate (1 :1), see also U.S.
  • amlodipine such as 3-ethyl-5-methyl-2-(2-aminoethoxymethyl)-4-(2- chlorophenyl
  • Patent No. 4,567,195 isradipine (3,5- Pyridinedicarboxylic acid, 4-(4-benzofurazanyi)-1 ! 4-dihydro-2,6-dimethyl-,methyl 1- methylethyl ester, ( ⁇ )-4(4-benzofurazanyl)-1 ,4-dihydro-2,6-dimethyl-3,5- pyridinedicarboxylate, see also US Patent 4,466,972); nimodipine (such as is isopropyl (2 - methoxyethyl) 1 , 4- dihydro - 2, 6 - dimethyl - 4 - (3 - nitrophenyl) - 3, 5 - pyridine - dicarboxylate, for example, NIMOTOP available from Bayer); felodipine (such as ethyl methy!
  • Cardiovascular agents of the present invention which also act as "anti-anginal agents", are useful in the present invention.
  • Angina includes those symptoms that occur when myocardial oxygen availability is insufficient to meet myocardial oxygen demand.
  • Non- limiting examples of these agents include: ranolazine (hydrochloridel-Piperazineacetamide, N-(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-, dihydrochloride CAS RN 95635-56-6); betaxoiol hydrochloride (2-Propanol, 1-[4-[2
  • butoprozine hydrochloride Metal Organic Chemical Vaporous acetylation (Methanone, [4-[3(dibutylamino)propoxyJphenyfJ(2- ethyl-3-indolizinyl)-, monohydrochloride CAS RN 62134-34-3); cinepazet maleatel- Piperazineacetic acid, 4-t1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-, ethyl ester, (2Z)-2- butenedioate (1 :1) CAS RN 50679-07-7); tosifen (Benzenesulfonamide, 4-methyl-N-[[ (1S)- 1 -methy!-2-phenylethylJamino]carbonyi]- CAS RN 32295-18-4); verapamilhydrochloride (Benzeneacetonitrile, .alpha.-[3-[[2-(3,4-d
  • Coronary vasodilators may act to reduce angina systems by increasing the oxygen supply to the heart.
  • Coronary vasodilators useful in the present invention include, but are not limited to, diltiazem hydrochloride (such as 1 ,5-Benzothiazepin- 4(5H)-one,3-(acetyloxy)-5[2 ⁇ (dimethylamino)ethyl]-2,-3-dihydro-2(4-methoxyphenyl)-, monohydrochloride, (+)-cis, for example, TIAZAC Capsules available from Forest);
  • diltiazem hydrochloride such as 1 ,5-Benzothiazepin- 4(5H)-one,3-(acetyloxy)-5[2 ⁇ (dimethylamino)ethyl]-2,-3-dihydro-2(4-methoxyphenyl)-, monohydrochloride, (+)-cis, for example
  • isosorbide dinitrate such as 1 ,4:3,6-dianhydro-D-giucitol 2,5-dinrtrate, for example, ISORDIL TITRADOSE Tablets available from Wyeth-Ayerst
  • sosorbide mononitrate such as 1 ,4:3,6-dianhydro-D-glucitol,5-nitrate, an organic nitrate, for example, Ismo JB2010.7161
  • nitroglycerin such as 2,3 propanetriol trinitrate, for example, NITROSTAT Tablets available from Parke-Davis
  • verapamil hydrochloride such as benzeneacetonitrile, ( ⁇ ) ⁇ (aIpha)[3[[2-(3,4
  • pyridinecarboxamide N-[2-(nitrooxy)ethyl]-Nisoidipine3,5-Pyridinedicarboxylic acid, 1 ,4- dihydro-2,6-dimethyi-4-(2-nitrophenyl)-, methyl 2-methylpropyl ester CAS RN 63675-72- 9
  • nifedipines 5-Pyridinedicarboxylic acid, 1 ,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-, dimethyl ester CAS RN 21829-25-4
  • perhexiline maleate Piperidine, 2-(2,2- dicyclohexylethyl)-, (2Z)-2-butenedioate (1 :1) CAS RN 6724-53-4
  • diuretic includes compounds that increase the excretion of solutes (mainly NaCI) and water.
  • solutes mainly NaCI
  • water In general, the primary goal of diuretic therapy is to reduce extracellular fluid volume in order to lower blood pressure or rid the body of excess interstitial fluid JB2010.7161
  • Non-limiting examples of diuretics which may be used within the scope of this invention include althiazide (which may be prepared as disclosed in British Patent No.
  • chlorothiazide which may be prepared as disclosed in U.S. 2,809,194; spironolactone (CAS Number 52-01-7); and triamterene (CAS Number 396-01-0).
  • Adrenergic stimulants useful as cardiovascular agents in the present invention include, but are not limited to, guanfacine hydrochloride (such as N-amidino-2-(2,6- dichlorophenyl) acetamide hydrochloride, for example, TENEX Tablets available from
  • methyldopa-hydrochlorothiazide such as levo-3-(3,4-dihydroxyphenyl)-2- methylalanine
  • Hydrochlorothiazide such as 6-chloro-3,4-dihydro-2 H -1 ,2,4- benzothiadiazine-7- sulfonamide 1 ,1 -dioxide, for example, the combination as, for example, ALDORIL Tablets available from Merck
  • methyldopa-chlorothiazide such as 6-chloro-2 H -1 , 2, 4-benzothiadiazine-7-sulfonamide 1 , 1 -dioxide and methyldopa as described above, for example, ALDOCLORr Tablets available from Merck
  • clonidine hydrochloride such as 2- (2,6-dichlorophenylamino)-2-imidazoline hydrochloride and chlorthalidone (such as 2-chloro-
  • anti-PCSK9 antibodies and antigen-binding fragments thereof may also be administered in association with any substituted azetidinone which inhibits intestinal cholesterol absorption.
  • azetidinones include ezetimibe
  • Patent No. 5,846,966 or RE37721) optionally in combination with any HMG CoA reductase inhibitor such as simvastatin or atorvastatin.
  • JB2010.7161 HMG CoA reductase inhibitor
  • chemotherapeutic agents that may be administered in association with an anti-PCSK9 antibody or antigen-binding fragment thereof or EGF-A polypeptide include fish oil, eicosaepenanoic acid, docosahexanoic acid, linoleic acid, niacin, fibrates such as fenofibrate, gemfibrozil and bile acid sequestrants such as cholestyramine, colestipol and colesevelam.
  • chemotherapeutic agents include althiazide (2H-1 ,2,4-Benzothiadiazine-7- sulfonamide, 6-chloro-3 t 4-dihydro-3-[(2-propenylthio)methyl]-, 1 ,1 -dioxide CAS RN 5588- 16-9); benzthiazide (2H-1 ,2,4-Benzothiadiazine-7-sulfonamide, 6-chioro-3- [[(phenylmethyl)thio]methylj-, 1 ,1 -dioxide CAS RN 91-33-8); captopril (L-Proline, 1-[(2S)-3- mercapto-2-methyl-1 -oxopropyl]- CAS RN 62571-86-2); carvedilol (2-Propanol, 1-(9H- carbazol-4-yloxy)-3-[I2-(2-methoxyphenoxy)ethyl]amino]- CAS RN 72956-0
  • chlorothiazide sodium 2-Propanol, 1 -(9H-carbazol-4-yloxy)-3-[[2-(2- methoxyphenoxy)ethyl]amino]- CAS RN 72956-09-3
  • clonidine hydrochloride (1 H-lmidazoi- 2-amine, N-(2,6-dichlorophenyl)-4,5-dihydro-, monohydrochloride CAS RN 4205-91-8
  • delapnl hydrochloride (2H-1 , 2,4- Benzothiadiazine-7-sulfonamide, 3-bicyclo[2.2.1]hept-5-en-2-yl-6-
  • quinaprilat (3-lsoquinolinecarboxylic acid, 2-[(2S)-2-[[(1S)-1- carboxy-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-, (3SJ- CAS RN 82768-85- 2); quinapril hydrochloride (3-isoquinoltnecarboxylic acid, 2-[(2S)-2-[[(1S)-1-(ethoxycarbonyl)- JB2010.7161
  • Biphenyl]-2-carboxylic acid 4 ⁇ [(1 ,4'-dimethyl-2'-propyl[2,6'-bi-1 H-benzimidazolj-l '-yl)methyl]- CAS RN 144701-48-4); candesartan1 H-Benzimidazole-7-carboxy!ic acid, 2-ethoxy-1 -[[2'- (1 H-tetrazol-5-yl)[1 ,1 '-biphenyl3-4-yl]methyl]- CAS RN 139481-59-7); amlodipine
  • compositions of the invention e.g., anti-PCSK9 antibody or antigen-binding fragment thereof along with ezetimibe
  • each component can be administered to a subject at a different time than when the other component is administered; for example, each administration may be given non- simultaneously (e.g., separately or sequentially) at several intervals over a given period of time.
  • the separate components may be administered to a subject by the same or by a different route (e.g., wherein an anti-PCSK9 antibody is administered parenteraily and ezetimibe is administered orally).
  • the present invention includes crystals comprising any antibody or antigen-binding fragment thereof of the invention compiexed with PCSK9 or a peptide epitope thereof.
  • polypeptide In the microbatch method, polypeptide is mixed with precipitants to achieve supersaturation, the vessel is sealed and set aside until crystals appear.
  • polypeptide In the dialysis method, polypeptide is retained in a sealed dialysis membrane which is piaced into a solution containing precipitant. Equilibration across the membrane increases the precipitant concentration thereby causing the polypeptide to reach supersaturation levels.
  • X-ray diffraction data can be collected.
  • One method for determining structure with X-ray diffraction data includes use of synchrotron radiation, under standard cryogenic condition; however, alternative methods may also be used.
  • crystals can be characterized by using X-rays produced by a conventional source, such as a sealed tube or a rotating anode. Methods of characterization include, but are not limited to, precession photography, oscillation photography and diffractometer data collection.
  • crysta!lizable compositions provided by this invention are amenable to X-ray crystallography for providing the three-dimensional structure of the PCSK9/antibody or fragment complex.
  • the present invention includes crystals which effectively diffract X-rays for the determination of the atomic coordinates of the PCSK9/antibody or fragment complex to a resolution of greater than about 5.0 Angstroms (e.g.
  • an anti-PCSK9 antibody or antigen-binding fragment thereof of the present invention e.g. , a Fab comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 18 and the light chain amino acid sequence set forth in SEQ ID NO: 19
  • the present invention includes PCSK9/antibody or fragment complex crystals whose three-dimensional structure is described by the structure coordinates set forth in Table 5.
  • the scope of the present invention also includes crystals that possess structural coordinates which are similar to those set forth in Table 5. Structural similarity between crystals is discussed in detail below.
  • structure coordinates refers to Cartesian coordinates derived from mathematical equations related to the patterns obtained on diffraction of a beam of X-rays by the atoms (scattering centers) of a molecule.
  • the diffraction data are used to calculate electron density maps and to establish the positions of the individual atoms of the molecule.
  • a set of structure coordinates for an enzyme or an enzyme-complex or a portion thereof is a relative set of points that define a shape in three dimensions.
  • an entirely different set of coordinates could define a similar or identical shape.
  • slight variations in the individual coordinates will have little effect on overall shape.
  • the present invention includes crystals exhibiting structural coordinates which are similar to those set forth in Table 5 but for crystallographic permutations of the structure coordinates, fractionaltzation of the structure coordinates, additions, subtractions, rotations or translations to sets of the structure coordinates or any combinations of the above.
  • modifications in the crystal structure due to mutations, additions, substitutions, and/or deletions of amino acids, or other changes in any of the components that make up the crystal may also account for variations in structure coordinates. If such variations are within an acceptable standard error as compared to the coordinates of Table 5, the resulting three-dimensional shape is considered to be the same and, accordingly, the modified crystal is considered to be within the scope of the present invention.
  • the Molecular Similarity application permits comparisons between different structures, different conformations of the same structure, and different parts of the same structure.
  • the procedure used in Molecular Similarity to compare structures is divided into four steps: 1) input the structures to be compared; 2) define the atom equivalences in these structures; 3) perform a fitting operation; and 4) analyze the results.
  • Each structure is JB2010.7161 identified by a name.
  • One structure is identified as the target ⁇ i.e., the fixed structure); all remaining structures are working structures ⁇ i.e., moving structures). Since atom
  • equivalency within QUANTA is defined by user input, for the purpose of this invention we will define equivalent atoms as alpha carbon atoms (Ca) or all protein backbone atoms (N, Ca, C and O) for all conserved residues between the two structures being compared.
  • Ca alpha carbon atoms
  • N Ca, C and O
  • the fitting operation uses a least squares fitting algorithm that computes the optimum translation and rotation to be applied to the moving structure, such that the root mean square difference of the fit over the specified pairs of equivalent atom is an absolute minimum. This number, given in Angstroms, is reported by QUANTA.
  • RMSD root mean square deviation
  • the term "least squares” relates to a method based on the principle that the best estimate of a value is that in which the sum of the squares of the deviations of observed values is a minimum.
  • any crystalline molecule characterized by a set of structure coordinates that has a RMSD of conserved residue backbone atoms (N, Ca, C, 0) or of alpha carbon atoms (Ca) only of less than about 1.5 A when superimposed-using backbone atoms or alpha carbon atoms -on the relevant structure coordinates of Table 5 are considered identical and are within the scope of the present invention.
  • the root mean square deviation is about 1.5 A or about 1 .0 A or about 0.75 A or about 0,5 A or about 0.25 A or about 0.10 A .
  • the present invention also encompasses any non-crystalline antibody or antigen- binding fragment thereof that, when converted to a Fab antigen-binding fragment format, binds to human PCSK9 in a manner characterized by a three dimensional structure which is characterized by a set of structure coordinates that has a RMSD of conserved residue backbone atoms (N, Ca, C, O) or of alpha carbon atoms (Ca) only of less than about 1 ,5 A when superimposed-using backbone atoms or alpha carbon atoms -on the relevant structure coordinates of Table 5 are considered identical and are within the scope of the present invention.
  • the root mean square deviation is about 1 .5 A or about 1.0 A or about 0.75 A or about 0.5 A or about 0.25 A or about 0.10 A . JB2010.7161
  • the present invention is intended to exemplify the present invention and not to be a limitation thereof. Any method or composition (including any isolated immunoglobulin chain polypeptide or antibody or antigen-binding fragment thereof comprising such a chain, or the CDRs of the chain, or combination or composition or method of use or production thereof as discussed herein) embodied in the Examples section falls within the scope of the present invention.
  • Example 1 Humanization and optimization of anti-PCSK9 antibodies.
  • the anti-PCSK9 antibodies of the present invention are the product of extensive efforts involving frequent failures to identify a humanized version of a mouse antibody with acceptable characteristics.
  • the process involved first comparing the mouse anti-PCSK9 antibody sequence to a group of known human germline immunoglobulin sequences. This comparison included assigning the mouse variable region sequences residue numbers according to Kabat; then delineating the CDR and FR regions in the sequence, again, according to Kabat. After the CDRs and FRs were delineated, a predetermined numerical score was assigned to each specific residue position at which the mouse and human antibody germline sequences were identical. After the scores were assigned, a total of all of the residue scores was generated for each human germline sequence.
  • the human germline sequence with the highest total residue score was identified and selected as the human acceptor germline sequence to be used for further humanization.
  • the scores assigned to the matching heavy and light chains are shown below in tables 1 and 2, respectively.
  • a numerical score of 1 was assigned for each FR residue position for which the mouse and human antibody germline sequences were identical but not scored according to tables 1 and 2.
  • the initial humanized antibody 1259/1260, exhibited no detectable binding to human PCSK9.
  • Such an initially humanized antibody requires only a small number of mutations to the framework region to restore high affinity binding to the antigen.
  • the antibodies in the present invention were extremely sensitive to any mutations in the frameworks. The reason for this sensitivity was likely that the antibody CDRs (in the mouse parental antibody) made extensive contacts with the hPCSK9 antigen.
  • other antibodies derive most of their avidity for an antigen through the interation of a small number of CDR residues that, in general, are concentrated in heavy chain CDR3.
  • any given mutation in a variable domain herein is likely to severely perturb the CDR/antigen contact.
  • the 1 62/1640 antibody was the result of a surprising and unexpected discovery that mutation of threonine 93 in light chain CDR3 to g!utamine increased affinity for hPCSK9 by 774pM units.
  • mutation of T93 generated a non-naturally occurring set of CDRs with high affinity for human PCSK9.
  • CDRs being the epitope binding moiety of an antibody that is the product of complicated in vivo selection mechanisms can be very sensitive to any changes; particularly non-conservative changes such as threonine to glutamine.
  • Antibody 1462/1378 with light chain mutation VL N32A exhibited a K D of 5514 pM for hPCSK9 whereas 1462/1640, which had the VL N32A T93Q mutations exhibited a K D of 4740 pM for hPCSK9.
  • LPD1282/LPD1462-lgG2 (1F11-lgG2) treated Cynomo!gus monkeys was also used for the measurement of lipoprotein a (Lp(a)), a risk factor for coronary heart disease.
  • Lp(a) lipoprotein a
  • PCSK9:Fab complex was generated by incubating a 1.5 molar excess of Fab with PCSK9, followed by purification on a size-exclusion chromatography. 9.9mg/mi PCSK9:Fab complex crystallized in 0.1 M Tris pH 8.5, 2.5M ammonium acetate at 4°C. Crystals were transferred to cryoprotectants consisting of the well solution supplemented with glycerol and flash-frozen in liquid nitrogen. A 2.8 angstrom dataset was collected at the I CA beamline (Argonne National Labs, The Advanced Photon Source) by NAXTRX, INC. Diffraction images were integrated using XDS (Kabsch W: XDS.
  • the Fab heavy chain amino acid sequence was:
  • the Fab light chain amino acid sequence was:
  • the epitope of the Fab was identified by determining Solvent Accessible Surface Area for the complex and the Fab and PCSK9 components separately using the MSMS program.
  • the antibody had a linear epitope in PCSK9 including residues EDGTRFHRQASKC (amino acids 211-223 of SEQ ID NO:8) wherein residue D212 in this loop was not buried by the Fab. Moreover, atoms of S188, R251 and C255 were also buried by the Fab. Accordingly, the present invention also encompasses any antibody or antigen-binding fragment thereof that contacts PCSK9 in a similar manner.
  • the antibody binds right at the furin processing site in the PCSK9 catalytic domain (RFHR 215-218 and FH 216-217 is deepest in the binding site).
  • Tabie 4b Solvent Accessible Surface Area Analysis Fab Heavy Chain Residues Contacted by PCSK9.

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Abstract

The present invention provides, in part, an anti-PCSK9 antibody and methods for treating medical disorders, such as elevated LDL, using such an antibody.

Description

10.7161
Anti-PCSK9
This application claims the benefit of U.S. provisional patent application no.
61/405,938, filed October 22, 2010, which is herein incorporated by reference in its entirety.
Field of the Invention
The present invention relates to anti-PCSK9 antibodies and methods of treatment using such antibodies.
Background of the Invention
Proprotein convertase subtilisin-kexin type 9 (PCSK9), also known as neural apoptosis- regulated convertase 1 (NARC-1), is a proteinase K-like subtilase identified as the 9th member of the secretory subtilase family. The gene for PCSK9 localizes to human chromosome Ip33-p34.3. PCSK9 is expressed in cells capable of proliferation and differentiation including, for example, hepatocytes, kidney mesenchymal cells, intestinal ileum, and colon epithetia as well as embryonic brain telencephalon neurons.
The gene sequence for human PCSK9, which is ~22-kb long with 12 exons encoding a 692 amino acid protein, can be found, for example, at Deposit No. NP_777596.2. Human, mouse and rat PCSK9 nucleic acid sequences have been deposited; see, e.g., GenBank Accession Nos.: AX 127530 (also AX207686), AX207688, and AX207690, respectively.
PCSK9 is a natural inhibitor of the low density lipoprotein receptor (LDLr) (Costet et al. Trends Biochem Sci 33 (2008): 426-434) and the hepatic form plays a major role in controlling cholesterolemia (Lagace et al., J Clin Invest 16 (2006): 2995-3005; Rashid et al., Proc Natl Acad Sci USA 102 (2005): 5374-5379; Zaid ef a/., Hepato!ogy 48 (2008): 646- 654). PCSK9 gain-of-f unction mutations are associated to hypercholesterolemia and premature atherosclerosis. In contrast, PCSK9 loss-of-f unction mutations result in lower plasma LDL-chofesterol concentrations and a reduced risk for coronary heart disease.
Because LDL particles can transport cholesterol into the artery wall, increased levels are associated with atherosclerosis. Over time vulnerable plaques rupture, activate blood clotting and produce heart attack, stroke, and peripheral vascular disease symptoms and major debilitating events.
Thus, effective therapies to lower LDL levels in a patient are valuable. One therapy to reduce LDL is administration of a therapeutic antibody that targets PCSK9. JB2010.7161
Summary of the invention
The present invention provides an isolated antibody or antigen-binding fragment thereof {e.g., a humanized antibody, a recombinant antibody a monoclonal antibody, a labeled antibody, a bivalent antibody, a polyclonal antibody, a bispecific antibody, a chimeric antibody, an anti-idiotypic antibody, a bispecific antibody a camelized single domain antibody, a diabody, an scfv, an scfv dimer, a dsfv, a (dsfv)2, a dsFv-dsfv', a bispecific ds diabody, an Fv, an Fab, an Fab', an F(ab')2, or a domain antibody) comprising one or more members selected from the group consisting of: a polypeptide comprising CDR-H1 , CDR-H2 and CDR-H3 of the variable region the LPD1462 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO: 1 ; and a polypeptide comprising CDR- L1 , CDR-L2 and CDR-L3 of the variable region the LPD1640 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO: 4 (e.g., both). For example, in an embodiment of the invention, the isolated antibody or antigen-binding fragment thereof of claim 1 comprising one or more members selected from the group consisting of: HCDR1 comprising the amino acid sequence GYTFTDYYMN (SEQ ID NO: 12), HCDR2 comprising the amino acid sequence DINPNNGG YNQKFKG (SEQ ID NO: 13) and HCDR3 comprising the amino acid sequence GIITEIAEDF (SEQ ID NO: 14); and LCDR1 comprises the amino acid sequence KASQNVGTNVV (amino acids 24-34 or SEQ ID NO: 7), LCDR2 comprises the amino acid sequence SASYRYS (amino acids 50-56 of SEQ ID NO: 7) and LCDR3 comprises the amino acid sequence QQYKTYPYT (amino acids 89-97 of SEQ ID NO: 7) (e.g., both). In an embodiment of the invention, the isolated antibody or antigen-binding fragment thereof of claim 1 comprising one or more members selected from the group consisting of:
QVQLVQSGAEVK PGASVKVSCKVS GYTFTDYYMN VRQAPGQGLEWIG DINPNNGGAIYNQKFKG RATLTVDKSTSTAYMELRSLRSDDTAVYYCTS GIITEIAEDF GQGTLVTVSS (SEQ ID NO: 2) and DIQMTQSPSSLSASVGDRVTITC KASQNVGTNVV
WYQQKPGKAPKALIH SASYRYS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYKTYPYT FGQGTKVEIKR (SEQ ID NO: 7). In an embodiment of the invention, the antibody or antigen- binding fragment thereof of claim 1 is linked to an immunoglobulin constant region such as a K light chain, γ1 heavy chain, γ2 heavy chain, y3 heavy chain or y4 heavy chain, in an embodiment of the invention, the antibody or antigen-binding fragment is in a pharmaceutical composition comprising the antibody or fragment in association with a pharmaceutically acceptable carrier. The present invention also provides a composition comprising the antibody or antigen-binding fragment thereof of claim 1 in association with a further chemotherapeutic agent; e.g., wherein the further chemotherapeutic agent is a
cardiovascular agent, an adrenergic blocker, an antihypertensive agent, an angiotensin JB2010.7161 system inhibitor, an angiotensin-converting enzyme inhibitor, a coronary vasodilator, a diuretic, an adrenergic stimulant or an HMG-CoA reductase inhibitor, or e.g., wherein the further chemotherapeutic agent is ezetimibe, lovastatin, atorvastatin, pravastatin,
rosuvastatin, fluvastatin, rivastatin, simvastatin, an azetidinone, bunolol hydrochloride, acebutoiol, alprenolol hydrochloride, atenolol, carteolol hydrochloride, celiprolol
hydrochloride; cetamolol hydrochloride, labetalol hydrochloride, esmo!ol hydrochloride, levobetaxolol hydrochloride, levobunolol hydrochloride, nadolol, practolol, propranolol hydrochloride, sotalol hydrochloride, timolol, timolol maleate, bisoprolol; bisoprolol fumarate, nebivalol, cicloprolol hydrochloride, dexpropranolol hydrochloride, diacetolol hydrochloride, dilevalol hydrochloride, exaprolol hydrochloride, flestolol sulfate, metalol hydrochloride, metoprolol 2-Propanol, metoproloi tartrate, pamatolol sulfate, penbutolol sulfate, practolol, tiprenolol hydrochloride, tolamolol fenspiride hydrochloride, proroxan, alfuzosin
hydrochloride, labetalol hydrochloride, bretylium tosylate, dihydroergtamine mesylate, carvedilol, labetalol, bretylium tosylate, phentolamine mesylate, soiypertine tartrate, zolertine hydrochloride, candesartan cilexetil, telmisartan, candesartan; losartan potassium, benazepril hydrochloride, captopril, fosinopril, moexipril hydrochloride, perindopril erbumine, quinapril, ramipril, enalapril maleate, lisinopril, delapril, spirapril, delapril hydrochloride, libenzapril, pentopril, perindopril 1H-lndole-2-carboxylic acid, quinaprilat, spirapril
hydrochloride, spiraprilat, teprotide, zofenopril, amlodipine besylate, clentiazem maleate, isradipine, nimodipine, felodipine, nilvadipine; diltiazem hydrochloride, verapamil
hydrochloride, teludipine hydrochloride, belfosdil, fostedil, ranolazine, butoprozine
hydrochloride, tosifen, molsidomine, ranolazine hydrochloride, tosifen, diltiazem
hydrochloride, isosorbide dinitrate, sosorbide mononitrate, nitroglycerin, verapamil hydrochloride, chromonar, clonitate, droprenilamine, lidoflazine, prenylamtne, propatyl nitrate, mioflazine hydrochloride, mixidine, molsidomine, isosorbide mononitrate, erythrityl tetranitrate, clonitrate, dipyridamole; nicorandil, pyridinecarboxamide, nifedipine; perhexiline maleate; oxprenolo!, pentrinitrol, verapamil, althiazide, benzthiazide, buthiazide,
chlorothiazide, spironolactone, triamterene, guanfacine hydrochloride, methyldopa- hydrochlorothiazide combined with Hydrochlorothiazide, methyldopa-chlorothiazide, clonidine hydrochloride, chlorthalidone, clonidine hydrochloride, cionidine, althiazide, benzthiazide, captopril, carvedilol, chlorothiazide, clonidine hydrochloride, cyclothiazide, delapril hydrochloride, dilevalol hydrochloride, delapril hydrochloride, doxazosin mesylate, fosinopril sodium, moexipril hydrochloride, monatepil maleate, metoprolol succinate, guanfacine hydrochloride, methyldopa, quinaprilat, quinapril hydrochloride, primidolo!, prazosin hydrochloride, pelanserin hydrochloride, phenoxybenzamine hydrochloride, candesartan JB2010.7161 cilexetil, telmisartan, candesartan, amlodipine maleate, terazosin hydrochloride, bevantolol hydrochloride or ramipril.
The present invention further includes an isolated polypeptide comprising an amino acid sequence that comprises CDR-L1 , CDR-L2 and CDR-L3 of the variable region the LPD1282 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO:7; as well a polypeptide comprising any 1 , 2 or 3 CDRs of any of the immunoglobulin chains disclosed herein. Also included is an isolated polynucleotide encoding any of the polypeptides set forth herein, e.g. , a polypeptide comprising CDR-H1 , CDR-H2 and CDR-H3 of the variable region the LPD1462 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO: 2; and/or a polypeptide comprising CDR-L1 , CDR-L2 and CDR-L3 of the variable region the LPD1282 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO: 7. A composition comprising: an isolated
polynucleotide encoding any polypeptide set forth herein, e.g., comprising CDR-H1 , CDR-H2 and CDR-H3 of the variable region the LPD1 62 heavy chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO: 2; and/or an isolated polynucleotide encoding encoding a polypeptide comprising CDR-L1 , CDR-L2 and CDR-L3 of the variable region the LPD1282 light chain immunoglobulin which comprises the amino acid sequence of SEQ ID NO: 7 also forms part of the present invention. The scope of the present invention also includes an isolated vector comprising any of the foregoing polynucleotides (e.g., a plasmid vector); as well as an isolated host cell comprising any of the foregoing
polynucleotides (e.g. , wherein the polynucletide is in a vector); e.g.. a Chinese hamster ovary cell, a Pichia cell or a P.pastoris cell.
The present invention also provides a method for reducing total cholesterol level; low density lipoprotein cholesterol level; a po lipo rotein B level; total cholesterol/high density lipoprotein ratio; or low density lipoprotein/high density lipoprotein ratio; or for treating or preventing hypercholesterolemia (e.g., primary hypercholesterolemia, e.g.. wherein the subject has elevated serum LDL, e , , wherein the subject has previously taken one or more LDL lowering drugs and.for example, has not achieved normal levels of LDL), hyperlipidemia, hypertriglyceridaemia, sitosterolemia, atherosclerosis, arteriosclerosis, coronary heart disease, vascular inflammation or xanthoma, in a subject, comprising administering, to said subject, a therapeutically effective amount of the antibody or antigen-binding fragment thereof; optionally in association with a further chemotherapeutic agent. For example, in an embodiment of the invention, the further chemotherapeutic agent is a cardiovascular agent, an adrenergic blocker, an antihypertensive agent, an angiotensin system inhibitor, an angiotensin-converting enzyme inhibitor, a coronary vasodilator, a diuretic, an adrenergic stimulant or an HMG-CoA reductase inhibitor; or the further chemotherapeutic agent is JB2010.7161 ezetimibe, lovastatin, atorvastatin, pravastatin, rosuvastatin, fluvastatin, rivastatin, simvastatin, an azetidinone, bunoloi hydrochloride, acebutoloi, alprenolol hydrochloride, atenolol, carteoiol hydrochioride, celiprolol hydrochloride; cetamolol hydrochloride, labetalol hydrochloride, esmolol hydrochioride, levobetaxoloi hydrochloride, levobunolol
hydrochloride, nadolol, practolo!, propranolol hydrochloride, sotalol hydrochloride, timolol, timolol maleate, bisoprolol; bisoprolol fumarate, nebivalol, cicioprolol hydrochloride, dexpropranolol hydrochloride, diacetolol hydrochloride, dilevalol hydrochloride, exaprolol hydrochloride, flestolo! sulfate, meta!ol hydrochloride, metoprolo! 2-Propanol, metoprolol tartrate, pamatolol sulfate, penbutolol sulfate, practolol, tiprenolol hydrochloride, tolamolol fenspiride hydrochloride, proroxan, alfuzosin hydrochloride, labetalol hydrochioride, bretylium tosylate, dihydroergtamine mesylate, carvedilol, labetalol, bretylium tosylate, phentolamine mesylate, solypertine tartrate, zolertine hydrochloride, candesartan cilexetil, telmisartan, candesartan; losartan potassium, benazepril hydrochloride, captopril, fosinopril, moexipril hydrochloride, perindopril erbumine, quinapril, ramipril, enalapril maleate, lisinopril, delapril, spirapril, delapril hydrochloride, libenzapril, pentopril, perindopril 1 H-lndole-2-carboxylic acid, quinaprilat, spirapril hydrochloride, spirapriiat, teprotide, zofenopril, am!odipine besylate, cientiazem maleate, isradipine, nimodipine, felodipine, nilvadipine; diltiazem hydrochloride, verapamil hydrochloride, teludipine hydrochloride, belfosdil, fostedil, ranolazine, butoprozine hydrochloride, tosifen, molsidomine, ranolazine hydrochioride, tosifen, diltiazem
hydrochloride, isosorbide dinitrate, sosorbide mononitrate, nitroglycerin, verapamil hydrochloride, chromonar, clonitate, droprenilamine, iidoflazine, prenylamine, propatyl nitrate, mioflazine hydrochloride, mixidine, molsidomine, isosorbide mononitrate, erythrityl tetranitrate, clonitrate, dipyridamole; nicorandii, pyridinecarboxamide, nifedipine; perhexiiine maleate; oxprenolol, pentrinitrol, verapamil, althiazide, benzthiazide, buthiazide,
chlorothiazide, spironolactone, triamterene, guanfacine hydrochloride, methyidopa- hydrochlorothiazide combined with Hydrochlorothiazide, methyldopa-chlorothiazide, clonidine hydrochloride, chlorthalidone, clonidine hydrochloride, clonidine, althiazide, benzthiazide, captopril, carvedilol, chlorothiazide, clonidine hydrochloride, cyclothiazide, delapril hydrochloride, dilevalol hydrochloride, delapril hydrochloride, doxazosin mesylate, fosinopril sodium, moexipril hydrochloride, monateptl maleate, metoprolol succinate, guanfacine hydrochloride, methyldopa, quinaprilat, quinapril hydrochloride, primidolo!, prazosin hydrochloride, pelanserin hydrochloride, phenoxybenzamine hydrochloride, candesartan cilexetil, telmisartan, candesartan, am!odipine maleate, terazosin hydrochloride, bevantolol hydrochioride or ramipril.
The present invention also provides a method for producing the antibody or antigen- binding fragment therof comprising introducing one or more polynucleotides into one or more JB2010.7161 host cells; which polynucleotides encodes and direct expression of said heavy and/or light chain immunoglobulins; and growing said host cells under conditions whereby said heavy and light chain immunoglobulins are expressed. For example, in an embodiment of the invention, said polynucleotide encoding and directing expression of said light chain and said polynucleotide encoding and directing expression of said heavy chain are in separate host cells.
The scope of the present invention also includes a crystalline composition comprising an a Fab/PCSK9 complex: in space group P2i2i2 comprising unit cell dimensions a=114.007 A, b= 135.131 A, c= 106.710 A and α=90°, β=90°; y=90°; e.g., wherein the Fab is derived from any antibody set forth herein (e.g. , human VH1462/VL1640/igG2), for example by papain digestion. The present invention also encompasses a crystalline composition comprising PCS 9 complexed with a Fab with a three dimensional structure characterized by structural coordinates comprising a root mean square deviation of common residue backbone atoms or alpha carbon atoms of less than about 1.5 A when superimposed on backbone atoms or alpha carbon atoms described by structural coordinates of Table 5 (e.g., wherein the crystalline composition has a three dimensional structure characterized by the structural coordinates of Table 5).
Brief Description of the Figures
Figure 1 (A & B). Relative LDL-c lowering in cynomolgous monkeys with
LPD1282/LPD1462-lgG2 (1 F11-lgG2) (A) or LPD1282/LPD1462-lgG4 (1 F11-lgG4) (B).
Figure 2. Three dimensional representation of a human PCSK9/Fab (SEQ ID NO: 18 and 19) complex.
Figure 3. Three dimensional representation of the binding region between PCS 9. and the Fab. The region is characterized by a lasso and post arrangement and a
hydrophobic lock and key arrangement as shown.
Figure 4. Close up of the polar interactions between the PCSK9 lasso and the Fab tyrosine 33 post.
Figure 5. Close up of the hydrophobic lock and key interactions.
Detailed Description of the Invention
The antibodies of the present invention are particularly advantageous. Mouse antibodies possessing superior PCSK9 inhibitory activity must be humanized before use in human subjects. Typically, however, the binding affinity associated with a mouse antibody is reduced when moved into a human framework. As a result, the frameworks typically must be modified so as to restore binding affinity to levels comparable to that of the parental mouse JB2010.7161 antibody. If the binding energy associated with binding between antibody CDRs and an antigen is derived mainiy from a few CDR residues, then the optimization process is usually straight-forward. If the interaction between the antigen and CDRs is extensive, e.g., involving multiple residues, then optimization can be a very difficult and complex process.
Optimization of the humanized anti-PCSK9 antibodies of the present invention was very difficult. The reason for this difficulty is likely due to a complex interface between the CDRs and the antigen. Dozens of modifications to the initially humanized antibodies were made before identification of a suitable antibody with binding affinity near that of the parental mouse antibody, 1462/1640. Furthermore, 1462/1640 exhibits an enhanced level of affninty for PCSK9 due to a mutation introduced into a Sight chain CDR at residue 93, T93Q.
Changing antibody CDR amino acids from the sequence that was generated in vivo, in general, would be expected to have a negative effect on binding. The T93Q mutation, however, surprising and unexpectedly increased binding.
The antibodies of the present invention are also extraordinary in that they bind to PCSK9 in a rather unusual place-at the furin processing site of PCSK9; accordingly, the scope of the present invention also includes any antibody or antigen-binding fragment thereof that binds to PCSK9 at the linear epitope EDGTRFHRQASKC (amino acids 21 1 -223 of SEQ ID NO:8) or at the furin processing site; along with a composition thereof comprising such an antibody or fragment in association with a further therapeutic agent (e.g., any of those discussed herein) or a pharmaceutical composition comprising such an antibody or fragment combined with a pharmaceutically acceptable carrier (e.g., any of those discussed herein) as well as method for treating any of the medical conditions discussed herein. The epitope set forth above appears in each of these species of PCSK9. This facilitates animal model experimentation with the antibody or an antigen-binding fragment thereof of the present invention in mice and chimpanzees.
In addition, the LPD1282/LPD1462 {i.e., antibody 1 F11 ) antibody has been
demonstrated to be a highly effective agent for lowering LDL in animal models, exhibiting up to 70% LDL reduction under the conditions tested.
In an embodiment of the invention, the antibody or antigen-binding fragment thereof of the present invention cross-reacts with human, mouse and chimpanzee PCSK9.
The present invention also includes a polypeptide (e.g., an oligopeptide) consisting of or consisting essentially of the amino acid sequence EDGTRFHRQASKC (amino acids 211- 223 of SEQ ID NO:8) optionally fused to a heterologous protein or further comprising one or several additional PCSK9 residues (e.g. , 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10) that are naturally contiguous with the N- or C-terminal end of EDGTRFHRQASKC (amino acids 211-223 of JB2010.7161
SEQ ID NO:8), A method for producing an anti-PCSK9 antibody or antigen-btnding fragment thereof comprsing immunizing a host animal with such a peptide also form part of the present invention.
An antibody or antigen-binding fragment thereof characterized as
"LPD1282/LPD1462" , which is also known as 1 F11 , or the like comprises the LPD1282 and LPD1462 variabie domain chain sequences. "LPD1282/LPD1462-lgG2" or the like indicates that the LPD1282/LPD1462 antibody heavy chain is conjugated to an lgG2 constant domain, e.g., wherein the light chain is conjugated to a kappa light chain constant domain. Other antibodies or antigen-binding fragments thereof with other chain combinations may also be named using this convention (e.g. , LPD1282/LPD1462-lgG4).
The term "subject" or "patient" or the like includes any mammal such as a human, chimpanzee, monkey (e.g., cynomolgous monkey), rat, mouse, dog, cat, horse, cow, goat or sheep. The term also includes humans that are HIV-positive and receiving highly active antiretrovirai therapy (HAART; e.g. , CCR5 receptor antagonist, entry inhibitor, nucleoside and nucleotide reverse transcriptase inhibitor ( RTI), Non-nucieoside reverse transcriptase inhibitors (NNRTI), protease inhibitor, integrase inhibitor, and/or maturation inhibitor); is intolerant of HMG Co-A reductase inhibitor therapy; suffers from acute coronary syndrome; is on immunosuppressive therapy (e.g., wherein the subject has received an organ transplant); is diabetic; and/or, will, in the future, receive percutaneous coronary intervention.
Molecular Biology
In accordance with the present invention there may be employed conventional molecular biology, microbiology, and recombinant DNA techniques within the skill of the art. Such techniques are explained fully in the literature. See, e.g., Sambrook, Fritsch &
Maniatis, Molecular Cloning: A Laboratory Manual, Second Edition (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York (herein "Sambrook, et a/., 1989"); DNA Cloning: A Practical Approach. Volumes I and II (D.N. Glover ed. 1985);
Oligonucleotide Synthesis (M.J. Gait ed. 1984); Nucleic Acid Hybridization (B.D. Hames & S.J. Higgins eds. (1985)); Transcription And Translation (B.D. Hames & S.J. Higgins, eds. (1984)); Animal Ceil Culture (R.I. Freshney, ed. (1986)); Immobilized Cells And Enzymes (IRL Press, (1986)); B. Perbal, A Practical Guide To Molecular Cloning (1984); F.M. Ausubel, et al. (eds,), Current Protocols in Molecular Biology, John Wiley & Sons, Inc. (1994).
Polynucleotides discussed herein form part of the present invention. A
"polynucleotide", "nucleic acid " or "nucleic acid molecule" DNA and RNA, single or double stranded. JB2010.7161
The polynucleotides of the present invention may, in an embodiment of the invention, be flanked by natural regulatory (expression control) sequences, or may be associated with heterologous sequences, including promoters, internal ribosome entry sites (IRES) and other ribosome binding site sequences, enhancers, response elements, suppressors, signal sequences, polyadenylation sequences, introns, 5'- and 3'- non-coding regions, and the like.
The polynucleotides of the present invention may be operably associated with a promoter. A "promoter" or "promoter sequence" is, in an embodiment of the invention, a DNA regulatory region capable of binding an RNA polymerase in a cell (e.g., directly or through other promoter-bound proteins or substances) and initiating transcription of a coding sequence. A promoter sequence is, in general, bounded at its 3' terminus by the
transcription initiation site and extends upstream (5' direction) to include the minimum number of bases or elements necessary to initiate transcription at any level. Within the promoter sequence may be found a transcription initiation site (conveniently defined, for example, by mapping with nuclease S1 ), as well as protein binding domains (consensus sequences) responsible for the binding of RNA polymerase. The promoter may be operably associated with other expression control sequences, including enhancer and repressor sequences or with a nucleic acid of the invention. Promoters which may be used to control gene expression include, but are not limited to, cytomegalovirus (CMV) promoter (U.S.
Patent Nos. 5,385,839 and 5,168,062), the SV40 early promoter region (Benoist, et at. , ( 981) Nature 290:304-310), the promoter contained in the 3' long terminal repeat of Rous sarcoma virus (Yamamoto, et al., (1980) Cell 22:787-797), the herpes thymidine kinase promoter (Wagner, et al., (1981) Proc. Natl. Acad. Sci. USA 78:1441 -1445), the regulatory sequences of the metallothionein gene (Brinster, et aL, (1982) Nature 296:39-42);
prokaryotic expression vectors such as the β-lactamase promoter (Villa-Komaroff, et al., (1978) Proc. Natl. Acad. Sci. USA 75:3727-3731 ), or the tac promoter (DeBoer, et ah, (1983) Proc. Natl. Acad. Sci. USA 80:21-25); see also "Useful proteins from recombinant bacteria" in Scientific American (1 80) 242:74-94; and promoter elements from yeast or other fungi such as the Gal 4 promoter, the ADC (alcohol dehydrogenase) promoter, PGK
(phosphoglycerol kinase) promoter or the alkaline phosphatase promoter.
The terms "vector", "cloning vector" and "expression vector" include a vehicle (e.g., a ptasmid) by which a DNA or RNA sequence can be introduced into a host cell, so as to transform the host and, optionally, promote expression and/or replication of the introduced sequence.
The term "host cell" includes any eel! of any organism that is selected, modified, transfected, transformed, grown, or used or manipulated in any way, for the production of a substance by the cell, for example the expression or replication, by the cell, of a gene, a DNA JB2010.7161 or RNA sequence, a protein or an enzyme. A host eel! can be a eukaryotic cell or prokaryotic cell. A eukaryotic cell can be, for example, a Chinese hamster ovary cell (e.g., CHO-K1 or DXB1 1), a HeLa cell, an NIH 3T3 cell, or a yeast or fungal cell, such as S.cerevisiae, any Pichia cell, Pichia pasforis, Pichia flnlandica, Pichia trehalophila, Pichia koc!amae, Pichia membranaefaciens, Pichia minuta {Ogataea minuta, Pichia lindneri), Pichia opuntiae, Pichia thermotolerans, Pichia salictaria, Pichia guercuum, Pichia pijperi, Pichia stiptis, Pichia methanolica, Pichia, Saccharomyces cerevisiae, Saccharomyces, ΗβηεβηυΙβ polymorpha, Kluyveromyces, Kluyveromyces lactis, Candida albicans, Aspergillus nidulans, Aspergil!us niger, Aspergillus oryzae, Trichoderma reesei, Chrysosporium lucknowense, Fusarium, Fusa/it/m gramineum, Fusarium venenatum or Neuraspora crassa. A prokaryotic cell can be, for example, a bacterial cell such as E.coli (e.g., BL21 or BL21 DE3); see U.S. Patent Nos. 4,952,496, 5,693,489 and 5,869,320 and in Davan!oo, P., et a!., (1984) Proc. Natl. Acad. Sci. USA 81 , 2035-2039; Studier, F. W., er a/. , (1986) J. Moi. Bioi. 189: 113-130; Rosenberg, A. H., et ai , (1987) Gene 56: 125-135; and Dunn, J. J., ef a/., (1988) Gene 68: 259 which are herein incorporated by reference.
The present invention contemplates any superficial or slight modification to the amino acid or nucleotide sequences which correspond to the immunoglobulin chains of the antibodies or antigen-binding fragments thereof of the invention. Antibodies and antigen- binding fragments thereof comprising one or more of such modified chains form part of the present invention. In particular, the present invention contemplates sequence-conservative variants and function-conservative variants. "Sequence-conservative variants" of immunoglobulin chains are those in which a change of one or more nucleotides in a given codon results in no alteration in the amino acid encoded at that position. Function- conservative variants of the immunoglobulin chains of the invention are also contemplated by the present invention. "Function-conservative variants" are those in which one or more amino acid residues in a protein have been changed without altering the overall conformation and function of the polypeptide, including, but, by no means, limited to, replacement of an amino acid with one having similar properties. Amino acids with similar properties are well known in the art. For example, polar/hydrophilic amino acids which may be interchangeable include asparagine, glutamine, serine, cysteine, threonine, lysine, arginine, histidine, aspartic acid and glutamic acid; nonpolar/hydrophobic amino acids which may be interchangeable include glycine, alanine, valine, leucine, isoleucine, proline, tyrosine, phenylalanine, tryptophan and methionine; acidic amino acids which may be interchangeable include aspartic acid and glutamic acid and basic amino acids which may be interchangeable include histidine, lysine and arginine. Conservative substitutions of an amino acid sequence refer to those wherein an amino acid of one subtype (e.g., polar/hydrophilic) is replaced with another JB2010.7161 amino acid of the same subtype; and, in an embodiment of the invention, wherein the conservatively substituted polypeptide retains essentially the same level of biological activity (e.g., binding affinity of a substituted anti-PCSK9 antibody for PCSK9).
The present invention includes nucleic acids encoding immunoglobulin chains of the present invention as well as nucleic acids which hybridize thereto. In an embodiment of the invention, the nucleic acids hybridize under low stringency conditions, more preferably under moderate stringency conditions and most preferably under high stringency conditions and, in an embodiment of the invention, exhibit PCSK9 binding activity when part if an antibody or antigen-binding fragment thereof. A nucleic acid molecule is "hybridizabie" to another nucleic acid moiecu!e, when a single stranded form of the nucleic acid molecule can anneal to the other nucleic acid molecule under the appropriate conditions of temperature and solution ionic strength (see Sambrook, et a/., supra). The conditions of temperature and ionic strength determine the "stringency" of the hybridization. An example, of a non-stringent wash condition under which a membrane comprising hybridized nucleic acids may be washed of excess, non-hybridizing nucleic acids is 2XSSC at 65°C; whereas a stringent wash would be 0.1 X SSC at 65°C. Alternatively, a stringent wash can include a series of washes at 65°C in decreasing salt concentrations (e.g., 3XSSC/0.2% SDS, then 1 x
SSC/0.2% SDS). A hybridization condition may be 6XSSC; 0.2% SDS; IXDenhard s blocking solution, or 1 % w/v milk; 10-50 ng/ml probe (denatured first); 65°C incubation, with agitation, for 18-24 hours. A recipe for 20X SSC per liter is NaC1 175.3 g (3 molar final in
20X) Sodium Citrate 88.2 g (0.3 molar final in 20X) (Adjust pH to 7.0 with a few drops of 10 N NaOH).
Also included in the present invention are nucleic acids comprising immunoglobulin chain nucleotide sequences and immunoglobulin chain polypeptides comprising amino acid sequences which are at least about 70% identical, preferably at least about 80% identical, more preferably at least about 90% identical and most preferably at least about 95% identical (e.g., 95%, 96%, 97%, 98%, 99%, 100%) to the reference immunoglobulin chain nucleotide and immunoglobulin chain amino acid sequences of the present invention (i.e., as discussed herein) when the comparison is performed by a BLAST algorithm wherein the parameters of the algorithm are selected to give the largest match between the respective sequences over the entire length of the respective reference sequences. Immunoglobulin chain polypeptides comprising amino acid sequences which are at least about 70% similar, preferably at least about 80% similar, more preferably at least about 90% similar and most preferably at least about 95% similar (e.g. , 95%, 96%, 97%, 98%, 99%, 100%) to the reference immunoglobulin chain amino acid sequences of of the present invention when the comparison is performed with a BLAST algorithm wherein the parameters of the algorithm are selected to give the JB2010.7161 largest match between the respective sequences over the entire length of the respective reference sequences, are also included in the present invention.
Sequence identity refers to exact matches between the nucleotides or amino acids of two sequences which are being compared. Sequence similarity refers to both exact matches between the amino acids of two polypeptides which are being compared in addition to matches between nonidentical, biochemically related amino acids. Biochemically related amino acids which share similar properties and may be interchangeable are discussed above.
The term "oligopeptide" refers to a peptide, generally of no more than about 100 amino acids (e.g., 10, 20, 30, 40, 50, 60, 70, 80, or 90).
The following references regarding the BLAST algorithm are herein incorporated by reference: BLAST ALGORITHMS: Altschul, S.F., et ai, (1990) J. ol. Biol. 215:403-410; Gish, W., et ai., (1993) Nature Genet. 3:266-272; Madden, T.L., et ai, (1996) Meth. Enzymol. 266:131-141; Altschul, S.F., et ai, (1997) Nucleic Acids Res. 25:3389-3402; Zhang, J., et ai., (1997) Genome Res. 7:649-656; Wootton, J.C., et ai., (1993) Comput. Chem. 17:149-163; Hancock, J.M. et ai., (1994) Comput. App!. Biosci. 10:67-70; ALIGNMENT SCORING SYSTEMS: Dayhoff, M.O., et ai, "A model of evolutionary change in proteins." in Atlas of Protein Sequence and Structure, (1978) vol. 5, suppl. 3. M.O. Dayhoff (ed.), pp. 345-352, Natl. Biomed. Res. Found., Washington, DC; Schwartz, R.M., et ai., "Matrices for detecting distant relationships." in Atlas of Protein Sequence and Structure, (1978) vol. 5, suppl. 3." M.O. Dayhoff (ed.), pp. 353-358, Natl. Biomed. Res. Found., Washington, DC; Altschul, S.F., (1991) J. Mol. Biol. 219:555-565; States, D.J., et ai., (1991) Methods 3:66-70; Henikoff, S., et ai, (1992) Proc. Natl. Acad. Sci. USA 89:10915-10919; Altschul, S.F., et ai., (1993) X Mol. Evol. 36:290-300; ALIGNMENT STATISTICS: Karlin, S., et ai., (1990) Proc. Natl. Acad. Sci. USA 87:2264-2268; Karlin, S., et ai., (1993) Proc. Natl. Acad. Sci. USA 90:5873-5877;
Dembo, A., et al„ (1994) Ann. Prob. 22:2022-2039; and Altschul, S.F. "Evaluating the statistical significance of multiple distinct local alignments." in Theoretical and Computational Methods in Genome Research (S. Suhai, ed.), (1997) pp. 1-14, Plenum, New York. Antibodies
The present invention includes methods and compositions comprising anti-PCSK9 antibodies and antigen-binding fragments thereof (e.g., LPD1282/LPD1462; 1 F11). The term "anti-PCSK9 antibody" or the like refers to a full antibody that binds specifically to PCSK9 (e.g., human PCSK9); for example, monoclonal antibodies, polyclonal antibodies, bispecific antibodies, chimeric antibodies, recombinant antibodies, anti-idiotypic antibodies, humanized antibodies and bispecific antibodies. The term "antigen-binding fragment" of an antibody JB2010.7161 encompasses a fragment or a derivative of an antibody, typically including at least a portion of the antigen-binding or variable regions (e.g. , one or more CDRs) of the parental antibody, that retains at least some of the binding specificity of the parental antibody. Examples of antigen-binding fragments of an antibody include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments; dsFv; (dsFv)2, ds diabodies; dsFv-dsFv'; single-chain antibody molecules, e.g., sc-Fv, sc-Fv dimers (bivalent diabodies); and bispecific diabodies. Thus, the invention includes any antibody or antigen-binding fragment thereof comprising one or more of the light chain and/or heavy chain immunoglobulin CDRs set forth herein. In an embodiment of the invention, the antibody or fragment comprises all 3 light chain and/or all 3 heavy chain CDRs.
The scope of the present invention includes embodiments wherein any of the antibodies and antigen-binding fragments that are discussed anywhere herein are further characterized by possessing one or more functional characteristics such as inhibiting the ability of PCSK9 to associate with LDL (low density lipoprotein) receptor, i.e., by competing with LDL receptor for PCSK9 binding; or lowering LDL levels in rhesus monkeys (e.g., under the conditions described beiow in Example 2), e.g., to a similar degree; or binding to the
PCSK9 furin processing site, e.g., at the specific PCSK9 peptide epitope discussed herein; or binding to PCSK9 with a KD of about 10'8 or a higher affinity (e.g., 109 M or 1010 M) (any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic).
The scope of the present invention also includes any antibody or antigen-binding fragment thereof that binds to PCSK9 at the linear epitope EDGTRFHRQASKC (amino acids 21 1-223 of SEQ ID NO:8) or at the PCSK9 furin processing site; along with a composition thereof comprising such an antibody or fragment in association with a further therapeutic agent (e.g., any of those discussed herein) or a pharmaceutical composition comprising such an antibody or fragment combined with a pharmaceutically acceptable carrier (e.g., any of those discussed herein) as well as method for treating any of the medical conditions discussed herein (any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic). In an embodiment of the invention, the antibody or antigen-binding fragment thereof has a linear epitope in PCSK9 including residues EDGTRFHRQASKC (amino acids 211-223 of SEQ ID NO:8); optionally, excluding residue D212; optionally including residues S188, R251 and/or C255 (any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic). Accordingly, the present invention also encompasses any antibody or antigen-binding fragment thereof that contacts PCSK9 in a similar manner. In an JB2010.7161 embodiment of the invention, the antibody or antigen-binding fragment thereof of the present invention contacts the following specific atoms in the PCSK9 antigen:
Atom Residue res #
CB SER 188
OG SER 188
N GLU 211
CB GLU 211
CG GLU 211
CD GLU 211
OE1 GLU 211
OE2 GLU 211
0 GLU 211
CA GLY 213
0 GLY 213
N THR 214
CA THR 214
CB THR 214
OG1 THR 214
CG2 THR 214
N ARG 215
CA ARG 215
CB ARG 215
CG ARG 215
CD ARG 215
NE ARG 215
CZ ARG 215
NH1 ARG 215
NH2 ARG 215
C ARG 215
O ARG 215
N PHE 216
CA PHE 216
CB PHE 216
CG PHE 216
CD1 PHE 216
CE1 PHE 216
CZ PHE 216
CE2 PHE 216
CD2 PHE 216
0 PHE 216
N HIS 217
CA HIS 217
CB HIS 217
CG HIS 217
ND1 HIS 217
CE1 HIS 217
NE2 HIS 217
CD2 HIS 217
C HIS 217
0 HIS 217
N ARG 218 JB2010.7161
CA ARG 218
CB ARG 218
CG ARG 218
CD ARG 218
NH2 ARG 218
C ARG 218
0 ARG 218
N GLN 219
CA GLN 219
CB GLN 219
CG GLN 219
CD GLN 219
0E1 GLN 219
NE2 GLN 219
0 GLN 219
N ALA 220
CA ALA 220
CB ALA 220
0 A A 220
N SER 221
ce SER 221
OG SER 221
0 SER 221
CA LYS 222
CD L.YS 222
CE LYS 222
NZ LYS 222
0 LYS 222
CB CYS 223
SG CYS 223
CZ ARG 251
NH1 ARG 251
NH2 ARG 251
CB CYS 255
SG CYS 255
(any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic). In an embodiment of the invention, the following specific atoms in the heavy chain of the antibody or antigen-binding fragment thereof of the present invention contact PCSK9:
Residue
Atom Residue #
O THR 30
CA ASP 31
CB ASP 31
CG ASP 31
OD1 ASP 31
OD2 ASP 31
C ASP 31
O ASP 31 JB2Q10.7161
CA TYR 32
OH TYR 32
CE2 TYR 32
CD2 TYR 32
C TYR 32
N TYR 33
CB TYR 33
CG TYR 33
CD1 TYR 33
CE1 TYR 33
CZ TYR 33
OH TYR 33
CE2 TYR 33
CD2 TYR 33
O TYR 33
CB ASN 35
CG ASN 35
OD1 ASN 35
ND2 ASN 35
CG2 VAL 37
CD1 TRP 47
CB ASP 50
CG ASP 50
OD1 ASP 50
OD2 ASP 50
CA ILE 51
C ]L,E 5Ί
N ASN 52
CB ASN 52
CG ASN 52
OD1 ASN 52
ND2 ASN 52
CD PRO 53
CB ASN 54
CG ASN 54
OD1 ASN 54
ND2 ASN 54
C ASN 54
O ASN 54
CB ASN 55
CG ASN 55
OD1 ASN 55
ND2 ASN 55
CA GLY 57
C GLY 57
O GLY 57
O ALA 58
CG1 !LE 59
CD1 ILE 59
NZ LYS 74
OG1 THR 97
CG2 THR 97 JB2010.7161
CA SER 98
C SER 98
0 SER 98
N GLY 99
CA GLY 99
C GLY 99
0 GLY 99
N ILE 100
CA ILE 100
CG1 ILE 100
CD1 ILE 100
N ILE 101
CB ILE 101
CG1 ILE 01
CD1 ILE 101
0 ILE 101
CB ASP 107
NE1 TRP 109
CH2 TRP 109
CZ2 TRP 109
(any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic), in an embodiment of the invention, the heavy chain tyrosine 32 contacts PCSK9, for example at the specific tyrosine 32 atom set forth in the table above (any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic). In an embodiment of the invention, tyrosine 32 interacts with PCSK9 in a lasso-post arrangement; wherein, the post, tyrosine 32, is situated inside of a flexible loop comprising PCSK9 residues 2 0-222 (any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic). In an embodiment of the invention, the foi!owing specific atoms in the light chain of the antibody or antigen-binding fragment thereof of the present invention contact PCSK9:
Residue
Atom Residue #
ND2 ASN 32
CB VAL 34
CG1 VAL 34
cz TYR 36
OH TYR 36
CE2 TYR 36
CB ALA 46
OH TYR 55
OE1 GLN 89
NE2 GLN 89
CB TYR 91
CG TYR 91
CD1 TYR 91 JB2010.7161
CE1 91
CE2 TYR 91
CD2 TYR 91
O TYR 91
C LYS 92
0 LYS 92
CA THR 93
C THR 93
N TYR 94
CD1 94
CE1 TYR 94
cz TYR 94
OH TYR 94
CE1 TYR 96
CZ TYR 96
OH TYR 96
CE2 TYR 96
CD2 TYR 96
CZ PHE 98
PHE 98
(any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic). In an embodiment of the invention, five tyrosines, 36, 55, 91 , 94 and 96, of the light chain of an antibody or antigen-binding fragment thereof of the present invention make hydrophobic interactions with PCSK9; for example, between PCS 9 and the specific atoms of the five tyrosines (any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this
characteristic). For example, antibodies and immunoglobulin chains of the present invention include those wherein the light chain variable domain is LPD1640 comprising the following amino acid sequence wherein the five tyrosines are numbered:
D I QMT QS P S S LS AS VGDRVT I TC KASQNVGTAVV WY36QQKPG APKALIH SASYRY55S
GVPSRFSGSGSGTDFTLT I SSLQPEDFATYYC QQ Y ¾ j,KQ Y 9 P Y FGQGTKVE I KR
(SEQ ID NO: 5); or antibodies of the present invention include those wherein the light chain variable domain is LPD1282 comprising the following amino acid sequence wherein the five tyrosines are numbered:
DIQMTQS PSS LSASVGDRVT I TCKASQNVGTNVVWY36QQKPGKAPKALIHSASYRY55SGVPSRFSGSG S GTDFTLT I SSLQPEDFATYYCQQY91RTY9 PY96TFGQGTKVE I KR
(SEQ ID NO: 7). The scope of the present invention encompasses antibodies and antigen- binding fragments thereof comprising tyrosines at amino acid positions 36, 55, 91 , 94 and 96 wherein the light chain residue numbering is as set forth above for SEQ ID NO: 5 or 7, i.e., wherein residue 1 is the first residue of the mature light chain variable region (any antibody or JB2010.7161 antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic).
Any antibody or antigen-binding fragment thereof that, when converted to a Fab antigen-binding fragment format, binds to human PCSK9 in a manner characterized by a three dimensional structure which structure is characterized by atoms positioned in space as described in a set of structural coordinates that has a RMSD of conserved residue backbone atoms (N, Ca, C, O) or of alpha carbon atoms (Ca) only of less than about 1.5 A when superimposed-using backbone atoms or alpha carbon atoms --on the relevant structure coordinates of Table 5 are considered within the scope of the present invention. In an embodiment, the root mean square deviation is about 1 .5 A or about 1.0 A or about 0.75 A or about 0.5 A or about 0.25 A or about 0.10 A; forms part of the present invention. In an embodiment of the invention, the coordinates are exactly as set forth in Table 5.
Furthermore, any antibody or antigen-binding fragment thereof that, when converted to a Fab antigen-binding fragment format, is, itself, characterized by a three dimensional structure, which structure is characterized by atoms positioned in space as described in the portion of the structural coordinates set forth in Table 5 (or a set of structural coordinates coordinates that has a RMSD of conserved residue backbone atoms (N, Ca, C, O) or of a!pha carbon atoms (Ca) only of less than about 1.5 A (e.g., 1.0 A, 0.75 A, 0.5 A, 0.25 A, 0.1 A) when superimposed-using backbone atoms or alpha carbon atoms -on the relevant structure coordinates of Table 5) that relates to the Fab moiety is part of the present invention (any antibody or antigen-binding fragment thereof described anywhere herein may, in an embodiment of the invention, be further characterized as possessing this characteristic).
The anti-PCSK9 antibodies and antigen-binding fragments thereof used in the present invention include antibodies and fragments which were raised against or bind to the whole PCSK9 protein as well as antibodies raised against or that bind to particular short epitopes within PCSK9.
Specific isolated anti-human PCSK9 antibody immunoglobulin sequences of the present invention are set forth below. CDR sequences for each immunoglobulin chain are underscored.
The present invention includes isolated polypeptides (e.g. , antibodies and antigen- binding fragments thereof) comprising one or more (e.g., 3) CDRs taken from any light and/or heavy chain immunoglobulin set forth herein as defined by the convention set forth in Kabat, "Sequences of Proteins of Immunological Interest" (National Institutes of Health, Bethesda, Md., 1987 and 1991 ) or in Chothia et al. , J. Mol. Biol. 196:901 (1987); Nature 342:878 (1989); and J. Mol. Biol. 186:651 (1989) (Kabat or Chothia) or Al-Lazikani et al., J. Mol. Biol. 273: 927-948 (1997). JB2010.7161
The present invention includes anti-PCSK9 antibodies and antigen-binding fragments thereof which bind specifically to PCSK9, for example, human PCSK9. In an embodiment of the invention, an anti-human PCSK9 antibody binds to human PCSK9 without any detectable binding to any other species of PCSK9 (e.g., no detectable binding to a rat PCSK9). in an embodiment of the invention, specific anti-PCSK9 binding refers to binding of the antibody to PCSK9 or an antigenic fragment thereof with a KD of about 10"8 M or greater affinity. In an embodiment of the invention, an anti-PCSK9 antibody or antigen-binding fragment of the present invention binds to human PCSK9 with a KD of about 6, 6.4, 7, 8, 9, 10 or 10.7 n . In an embodiment of the invention, an antibody or antigen-binding fragment thereof of the present invention inhibits human PCSK9-mediated functional effects in a HepG2 celi-based LDL-c uptake assay with an IC50 for human PCSK9 of about 9.8 nM. In an embodiment of the invention, an anti-PCSK9 antibody or antigen-binding fragment thereof of the present invention binds to human, cynomoigous monkey, rat and mouse PCSK9. In an embodiment of the invention, an anti-PCSK9 antibody or antigen-binding fragment of the present invention does not bind signigicantiy to the Fc Gamma Receptor (e.g. , wherein the antibody comprises the kappa and lgG2 constant domains), in an embodiment of the invention, an anti-PCSK9 antibody or antigen-binding fragment thereof of the present invention has an in vivo half life of about 1 , 2, 3, 4, 5, 6, 7, 8, 9, or 10 days.
Any suitable method for generating antibodies may be used. For example, a recipient may be immunized with PCSK9 or an immunogenic fragment thereof. Any suitable method of immunization can be used. Such methods can include adjuvants, other
immunostimuiants, repeated booster immunizations, and the use of one or more
immunization routes. Any suitable source of PCSK9 can be used as the immunogen for the generation of the antibodies and fragments of the compositions and methods disclosed herein. Such forms include, but are not limited whole protein, peptide(s), and epitopes generated through recombinant, synthetic, chemical or enzymatic degradation means known in the art.
The present invention also includes an isolated polypeptide consisting of or consisting essentially of the amino acid sequence EDGTRFHRQASKC (amino acids 211 -223 of SEQ ID NO:8) optionally fused to a heterologous protein or molecule (e.g., keyhole limpet hemocyanin (KLH)) or further comprising one or several additional PCSK9 residues (e.g., 1 , 2, 3, 4, 5, 6, 7, 8, 9, 0) that are naturally contiguous with the N- or C-terminal end of EDGTRFHRQASKC (amino acids 211 -223 of SEQ ID NO:8). Multimers comprising more than one (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10) of such peptides forms part of the present invention. A method for producing an anti-PCSK9 antibody or antigen-binding fragment thereof comprsing immunizing a host animal (goat, rat, rabbit) with such a peptide also form part of JB2010.7161 the present invention. A composition comprising such a peptide, e.g. , a vaccine, including an adjuvant or carrier forms part of the present invention.
Any form of the antigen can be used to generate the antibody that is sufficient to generate a biologically active antibody. Thus, the eliciting antigen may be a single epitope, multiple epitopes, or the entire PCSK9 protein alone or in combination with one or more immunogenicity enhancing agents known in the art.
Other suitable techniques involve selection of libraries of antibodies in phage or similar vectors. See, e.g., Huse er a/, supra; and Ward et al. (1989) Nature 341 :544-546. The polypeptides and antibodies of the present invention may be used with or without modification, including chimeric or humanized antibodies. Frequently, the polypeptides and antibodies will be labeled by joining, either covalently or non-covalentiy, a substance that provides for a detectable signal, A wide variety of labels and conjugation techniques are known and are reported extensively in both the scientific and patent literature. Suitable labels include radionuclides, enzymes, substrates, cofactors, inhibitors, fluorescent moieties, chemiluminescent moieties, magnetic particles, and the like. Patents teaching the use of such labels include U.S. Patent Nos. 3,817,837; 3,850,752; 3,939,350; 3,996,345; 4,277,437; 4,275,149; and 4,366,241.
Fab fragment are known in the art. The fragments contain the region on an antibody that binds to antigens. It contains one constant and one variable domain of each of the heavy and the light chain. Fab fragments can be generated in the laboratory. The enzyme papain can be used to cleave an antibody into two Fab fragments and an Fc fragment. The enzyme pepsin cleaves below hinge region, so a F(ab')2 fragment and a pFc' fragment is formed. The F(ab')2 fragment can be split into two Fab' fragments by mild reduction.
"Disulfide stabilized Fv fragments" and "dsFv" include molecules having a variable heavy chain (VH) and a variable light chain (VL) which are linked by a disulfide bridge.
The "Fv region" comprises the variable regions from both the heavy and light chains, but lacks the constant regions.
The term "single-chain Fv" or "scFv" antibody refers to antibody fragments comprising the VH and VL domains of an antibody, wherein these domains are present in a single polypeptide chain. Generally, the Fv polypeptide further comprises a
polypeptide linker between the VH and VL domains which enables the VH and VL chains to pair and form a binding site (e.g., 5-12 residues long). For a review of scFv, see
Pluckthun (1994) THE PHARMACOLOGY OF MONOCLONAL ANTIBODIES, vol. 113, Rosenburg JB2010.7161 and Moore eds. Springer-Verlag, New York, pp. 269-315. See also, International Patent Application Publication No. WO 88/01649 and U.S. Pat. Nos. 4,946, 778 and 5,260,203.
A domain antibody is either the variable domain of an antibody heavy chain (VH domain) or the variable domain of an antibody light chain (VL domain). Each domain antibody contains three of the six naturally occurring complementarity determining regions (CDRs) from an antibody.
A "bivalent antibody" comprises two antigen-binding sites. In some instances, the two binding sites have the same antigen specificities. However, bivalent antibodies may be bispecific. For example, the present invention comprises scfv dimers and dsfv dimers, each of which scfv and dsfv moieties may have a common or different antigen binding specificity.
In an embodiment of the invention, a (dsfv)2 comprises three peptide chains: two VH moieties linked by a peptide linker and bound by disulfide bridges to two linked VL moieties. In an embodiment of the invention, a bispecific ds diabody comprises a VHr Vl_2 (tethered by a peptide linker) linked, by a disulfide bridge between the VHi and VLi, to a VL1-VH2 moiety (also tethered by a peptide linker), in an embodiment of the invention, a bispecific dsfv-dsfv' also comprises three peptide chains: a VH-|-VH2 moiety wherein the heavy chains are linked by a peptide linker (e.g., a long flexible linker) and are bound to VLi and VL2 moieties, respectively, by disulfide bridges; wherein each disulfide paired heavy and light chain has a different antigen specificity, in an
embodiment of the invention, an scfv dimer (a bivalent diabody) comprises a VH-VL moiety wherein the heavy and light chains are bound to by a peptide linker and dimerized with another such moiety such that VHs of one chain coordinate with the VLs of another chain and form two identical binding sites. In an embodiment of the invention a bispecific diabody comprises VHrVL2 moiety (linked by a peptide linker) associated with a VL1-VH2 (linked by a peptide linker), wherein the VH-i and VLi coordinate and the VH2 and VL2 coordinate and each coordinated set has diverse antigen specificities.
The term "monoclonal antibody", as used herein, refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific, being directed against a single antigenic epitope. In contrast, conventional (polyclonal) antibody preparations typically include a multitude of antibodies directed against (or specific for) different epitopes. Monoclonal antibodies to be used in accordance with the JB2010.7161 present invention may be made recombinantly or by the hybridoma method first described by Kohler et al. (1975) Nature 256: 495, or may be made by recombinant DNA methods {see, e.g., U.S. Pat. No. 4,816,567). The "monoc!ona! antibodies" may also be isolated from phage antibody libraries using the techniques described in Clackson et al. (1991) Nature 352: 624-628 and Marks ef al. (1991 ) J. Mol. Biol. 222: 581-597. See also Presta (2005) J. Allergy Clin. Immunol. 116:731.
Any suitable method can be used to elicit an antibody with the desired biologic properties to inhibit PCSK9. Monoclonal antibodies (mAbs) may be prepared from various mammalian hosts, such as mice, rats, other rodents, humans, other primates, ere.
Description of techniques for preparing such monoclonal antibodies may be found in, e.g., Stites ef al. (eds.) BASIC AND CLINICAL IMMUNOLOGY (4th ed.) Lange Medical
Publications, Los Altos, CA, and references cited therein; Harlow and Lane (1988)
ANTIBODIES: A LABORATORY MANUAL CSH Press; Goding (1986) MONOCLONAL ANTIBODIES: PRINCIPLES AND PRACTICE (2d ed.) Academic Press, New York, NY. Thus, monoclonal antibodies may be obtained by a variety of techniques familiar to researchers skilled in the art. Typicaily, spleen cells from an animal immunized with a desired antigen are immortalized, commonly by fusion with a myeloma cell. See Kohler and Milstein (1976) Eur. J. Immunol. 6:51 -519. Alternative methods of immortalization include tra sformation with Epstein Barr Virus, oncogenes, or retroviruses, or other methods known in the art. See, e.g., Doyle et al. (eds. 1994 and periodic supplements) CELL AND TISSUE CULTURE: LABORATORY PROCEDURES, John Wiley and Sons, New York, NY. Colonies arising from single immortaiized cells are screened for production of antibodies of the desired specificity and affinity for the antigen, and yield of the monoclonal antibodies produced by such cells may be enhanced by various techniques, including injection into the peritoneal cavity of a vertebrate host. Alternatively, one may isolate DNA sequences that encode a monoclonal antibody or an antigen binding fragment thereof by screening a DNA library from human B cells according, e.g., to the genera! protocol outlined by Huse et a!. (1989) Science 246:1275-1281.
Antibodies of the present invention include "chimeric" antibodies
(immunoglobulins) in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, so long as they exhibit the desired biological activity JB2010.7161
(U.S. Pat. No. 4,816,567; and Morrison et al., (1984) Proc. Natl. Acad. Sci.USA 81 : 6851- 6855). For example, variable domains are obtained from an antibody from an
experimental animal (the "parental antibody"), such as a mouse, and the constant domain sequences are obtained from human antibodies, so that the resulting chimeric antibody will be less likely to elicit an adverse immune response in a human subject than the parental mouse antibody.
A recombinant antibody or antigen-binding fragment thereof of the invention is, in an embodiment of the invention, an antibody which is produced recombinantly, e.g., expressed from a polynucleotide which has been introduced into an organism (e.g., a plasmid containing a polynucleotide encoding the antibody or fragment transformed into a bacterial cell (e.g., E.coli) or a mammalian cell (e.g., CHO cell)), followed by isolation of the antibody or fragment from the organism. Recombinant immunoglobulins may be produced by the methods set forth in Cabilly U.S. Patent No. 4,816,567.
The present invention comprises methods for expressing any antibody or antigen- binding fragment thereof or polypeptide of the present invention, For example, an embodiment of the present invention comprises a process for producing an
immunoglobulin molecule or an immunologically functional immunoglobulin fragment comprising at least the variable domains of the immunoglobulin heavy and/or light chains, in a host cell (e.g., a single host cell), such as a CHO cell (e.g., CHO-K1 or DXB11 cell), comprising the steps of (i) transforming said host cell with a first polynucleotide encoding an immunoglobulin heavy chain and a second polynucleotide encoding an
immunoglobulin light chain, and (ii) expressing said first polynucleotide and said second polynucleotide so that said immunoglobulin heavy and light chains are produced as separate molecules in said transformed host cell. In an embodiment of the invention, the polynucleotides are operably linked to a promoter such as a CMV promoter. The present invention also comprises a process for producing an immunoglobulin molecule or an immunologically functional immunoglobulin fragment comprising introducing transforming a first haploid yeast host cell (e.g., Pichia such as Pichia pastoris) with a first
polynucleotide encoding at least the variable domain of the immunoglobulin heavy chain or light chain and transforming a second haploid yeast host cell (e.g., Pichia such as Pichia pastoris) with a second polynucleotide encoding the other chain, allowing the haploid cells to form polyploids, such as diploids, (e.g., via mating), selecting the polyploids from the haploids, and growing the polyploids under conditions wherein the JB2010.7161 heavy and light chains are expressed in the polyploids and, optionally, secreted into the culture medium.
In an embodiment of the invention, polynucleotides introduced into a host cell remain ectopic whereas in another embodiment of the invention, the polynucleotide is integrated into the chromosomal DNA of the host cell
In an embodiment of the invention, a method for producing an antibody or fragment or polypeptide further comprises isolating the chains that are expressed from the host cell and/or culture medium.
As used herein, the term "diabodies" refers to small antibody fragments with two antigen-binding sites, which fragments comprise a heavy chain variable domain (VH) connected to a light chain variable domain (VL) in the same polypeptide chain (VH-VL or VL-VH). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites. Diabodies are described more fully in, e.g., EP 404,097; WO 93/1 1161 ; and Holliger et al. (1993) Proc. Natl. Acad. Sci. USA 90: 6444-6448. For a review of engineered antibody variants generally see Holliger and Hudson (2005) Nat. Biotechnol. 23:1126-1 36.
A humanized antibody typically comprises a FR region having, substantially, the amino acid sequence of a human immunoglobulin and CDRs having, substantially, the amino acid sequence of a non-human immunoglobulin. These non-human amino acid residues are referred to as "import" residues, which are typically taken from an "import" antibody or antibody domain, e.g., a variable domain of an antibody. An import antibody typically! has a desired affinity and/or specificity, or other desirable biological activity. The humanized antibody typically also will comprise at least a portion of a human immunoglobulin constant domain. For example, an embodiment of the invention includes humanized anti-PCSK9 (e.g., anti-human PCSK9) antibodies comprising mouse immunoglobulin CDRs and human immunoglobulin framework regions fused to a human immunoglobulin constant domain. See the following U.S. patents which are herein incorporated by reference: 5,585,089; 5,693,761 ; 5,693,762; and, 6,180,370.
The present invention also includes isolated polypeptides comprising the amino acid sequences of any of the immunoglobulin chains set forth herein as well as variants thereof, e.g., as discussed herein, along with isolated polynucleotides encoding said polypeptides and variants, vectors comprising the polynucleotides and isolated host cells comprising the polynucleotides and vectors (e.g., CHO cells, bacterial cells such as E. coli and fungal cells such as S.cerevisiae and Pichia such as Pichia pastoris). Such polypeptides, variants and JB2010.7161 polynucleotides, etc., may be used, for example, as intermediates in the generation of an anti-PCSK9 antibody or antigen-binding fragment thereof. Methods for making the polypeptides are also included: comprising introducing the polynucleotide or vector into a host cell and culturing the host cell under conditions whereby the polypeptide is expressed and, optionally, secreted and, optionally, isolating the polypeptide.
in an embodiment of the invention, the heavy chain and/or light chain immunoglobulin sequences of the anti-PCSK9 antibodies of the present invention are set forth below. CDR sequences are underscored. The present invention also includes antibodies and antigen- binding fragments thereof comprising the CDRs of the heavy and/or light chain
immunoglobulins set forth below as well as isolated polypeptides comprising such CDRs (e.g., 3 light chain CDRs and/or 3 heavy chain CDRs); polynucleotides encoding such polypeptides; vectors comprising such polynucleotides and isolated host cells comprising such vectors. The present invention also includes antibodies and antigen-binding fragments thereof comprising any combination of the heavy and light chain immunoglobulins set forth herein. For example, antibodies and antigen-binding fragments thereof (e.g., a humanized antibody) comprising the light chain LPD1282 (e.g., fused to a kappa light chain constant domain) and the heavy chain LPD1462 (e.g., fused to a gamma-2 or 4 heavy chain constant domain) are within the scope of the present invention. An antibody comprising a light chain variable region of LPD1282 and a heavy chain variable region of LPD1462 is designated as LPD1282/LPD1462.
Heavy chain sequences
LPD1462 humanized 1 F1 1 !gG1;
MAVLGLLFCLVTFPSCVLSQVQLVQSGAEVKKPGASVKVSCKVSGYTFTDYY NWVRQAPGQGLEWIG DINPNNGGAIYNQKFKGRATLTVDKSTSTAYMELRSLRSDDTAVYYCTSGIITEIAEDFWGQGTLVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSLGTQTYICNVNHKPSNTKVD KVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTL MISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNG EY KCKVSNKALPAPIEKTISKA GQPREPQVYTLPP3RDELT NQVSLTCLVKGFYPSDIAVEWESNGQP ENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
(SEQ ID NO: 1 )
LPD1462 variable domain:
QVQLVQSGAEVKKPGASVKVSCKVS GYTFTDYYMN VRQAPGQGLEWIG
DINPNNGGAIYNQ F G RATLTVDKSTSTAYMELRSLRSDDTAVYYCTS GIITEIAEDF GQGTLVTVSS
(SEQ ID NO: 2)
LPD1259 humanized lgG1 CDR-swap (= version 1 ):
QVQLVQSGAEV KPGASVKVSCKASGYTFTDYYMNWVRQAPGQGLE MGDINPNNGGAIYNQ FKGRV TMTTDTS STAYMELRSLRSDD AVYYCARGIITEIAEDF GQGTLVTVSS
(SEQ ID NO: 3) JB2010.7161
Light chain sequences
LPD1640 humanized Light Chain full-length:
DMRVPAQLLGLLLL LRGARCDIQMTQSPSSLSASVGDRVTITCKASQNVGTAVVWYQQKPGKAPKA LIHSASYRYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYKQYPYTFGQGTKVEIKRTVAAPS VFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS DSTYSLSSTLTLS KADYEKHKVYACEVTHQGLSSPVTKS NRGEC
(SEQ SD 0: 4)
LPD1640 variable domain:
DIQMTQSPSSLSASVGDRVTITC ASQNVGTAVV WY36QQKPGKAPKALIH SASYRY5
GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYgiKQYgjPYggT FGQGT VEIKR
(SEG ID NO: 5)
LPD1260 humanized Light Chain CDR-swap (= version 1):
DIQMTQSPSSLSASVGDRVTITCKASQNVGTNVVWYQQKPGKAP LLIYSASYRYSGVPSRFSGSGSG TDFTLTISSLQPEDFATYYCQQYKTYPYTFGCjGTKVEIKR
(SEQ ID NO: 6)
LPD1282 humanized 1 F11 Light Chain:
DIQMTQSP5SLSASVGDRVTITCKASQNVGTNVVWYQQKPGKAPKALIHSASYRYSGVPSRFSGSGSG TDFTLTI5SLQPEDFATYYCQQY TYPYTFGQGTKVEIKR
(SEQ ID NO: 7) The present invention also encompasses an anti-PCSK9 Fab comprising the heavy chain amino acid sequence:
qvqlvqsgae vkkpgasvkv sckvsgytft dyymnwvrqa pgqglewigd inpnnggaiy
nqkfkgratl tvdkststay melrslrsdd tavyyctsgi iteiaedfwg qgtlvtvssa
stkgpsvfpl apsskstsgg taalgclvkd yfpepvtvsw nsgaltsgvh tfpavlqssg
lysLssvvtv pssslgtqty icnvnhkpsn tkvdkkvepk scdkthtaaa ypydvpdyag
ghhhhhh
(SEQ ID NO: 18) ;
and the light chain amino acid sequence:
diqmtqspss Isasvgdrvt itckasqnvg tnwwyqqkp gkapkalihs asyrysgvps
rfsgsgsgtd ftltisslqp edfatyycqq yktypytfgq gtkveikrtv aapsvfifpp
sdeqlksgta svvcllnnfy preakvqwkv dnalqsgnsq esvteqdskd styslsstlt
Iskadyek k vyacevthqg Isspvtksfn rgec
(SEQ ID NO: 19).
As discussed, an isolated polypeptide or variant thereof (as discussed herein) comprising the amino acid sequence of SEQ ID NO: 18 or 19 is part of the present invention.
The scope of the present invention includes any antibody or antigen-binding fragment thereof or light chain immunoglobulin or isolated polypeptide comprising the consensus JB2010.7161 amino acid sequence set forth below (SEQ ID NO: 20). Positions in the consensus sequence wherein the three chains differ are indicated with an X. The chain may be, at these X positions, any of the corresponding residues of the three chains, e.g. , the residue possessed by two of the three chains at that position. The present invention includes consensus sequences comprising any possible combination of the indicated residues at the X positions.
LPD1260 DIQMTQSPSSLSASVGDRVTITCKASQ VGTNVVWYQQKPGKAPKLLIYSASYRYSGVPS
LPD1282 DIQMTQSPSSLSASVGDRVTITC ASQIWGTOTV YQQKPGKAPKALIHSASYRYSGVPS
LPD1640 DIQMTQSPSSLSASVGDRVTITCKASQ VGTAWWYQQKPG APKALIHSASYRYSGVPS
consens s DIQMTQSPSSLSASVGDRVTI C ASQNVGTXWWYQQKPGKAPKXLI SASYRYSGVPS
LPD1260 RFSGSGSGTDFTLTISSLQPEDFATYYCQQYKTYPYTFGQGTKVEIKR
I,I'D1282 RFSGSGSGTDFTLTISSLQPEDFATYYCQQY TYPYTFGQGTKVEIKR
LPD1640 RFSGSGSGTDFTLTISSLQPEDFATYYCQQYKQYPYTFGQGTKVEIKR
con nsus RFSGSGSGTDFTLTISSLQPEDFATYYCQQYKXYPYTFGQGT VEIKR
The scope of the present invention inciudes any antibody or antigen-binding fragment thereof or heavy chain immunoglobulin or isolated polypeptide comprising the consensus amino acid sequence set forth below (SEQ ID NO: 21 ). Positions in the consensus sequence wherein the three chains differ are indicated with an X. The chain may be, at these X positions, any of the corresponding residues of the three chains, e.g. , the residue possessed by two of the three chains at that position. The present invention includes consensus sequences comprising any possible combination of the indicated residues at the X positions.
LPD1462 QVQLVQSGAEVK PGASVKVSCKVSGYTFTDYYMNWVRQAPGQGLEWIGDINPN GGAIY
LPD1259 QVQLVQSGAEV PGASVKVSC ASGYTFTDYYMNWVRQAPGQGLEWMGDINPNNGGAIY
consensus QVQLVQSGAEVK PGASVKVSCKXSGYTFTDYY NWVRQAPGQGLEWXGDINPNNGGAIY
LPD1462 NQKFKGRATLTVDKSTSTAYMELRSLRSDDTAVYYCTSGIITEIAEDFWGQGTLVTVSS
LPD1259 NQKF GRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARG11TEIAEDFWGQGTLVTVSS
consensus NQKFKGRXTXTXDXSTSTAYMELRSLRSDDTAVYYCXXG11TEIAEDFWGQGTLVTVSS
PCSK9
The present invention includes compositions and methods comprising antibodies and antigen-binding fragments thereof (e.g., LPD1282/LPD1462) which bind specifically to PCSK9, for example, human PCSK9. The present invention includes a complex between any isolated antibody or antigen-binding fragment thereof bound to PCSK9 (e.g. , human PCSK9) (e.g., PCSK9 such as human PCSK9 in a eel! in the body of a subject such as a human). In some embodiments of the invention, specific PCSK9 polypeptide sequences or antigenic fragments thereof from various species set forth below may be used as an antigen: JB2010.7161
HUMAN gi|31317307jref|NP_777596.2| proprotein convertase subtilisin/kexin type 9 preproprotein [Homo sapiens]
GTVSSRRSW PLPLLLLLLLLLGPAGARAQEDEDGDYSELVIALRSEEDGLAEAPEHGTTATFHRCA D PWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPHV DYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLVEVYLLDTSIQSDHREIEGRVMVTDFENVPE EDGTRFHRQASKCDSHGTHLAGVVSGRDAGVA GASMRSLRVLNCQG GTVSGTLIGLEFIRKSQLVQPV GPLVVLLPLAGGYSRVL AACQRLARAGVVLVT AGNF DDACLYSPAS PEVITVGATNAQDQPVTLG LGTNFGRCVDLFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSA KDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFS RSG RRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLT GCSSHWEVEDLGTH PPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGW TLTGCSALPGfSHVLGAYAVDNTC VRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ
(SEQ ID NO: 8)
CHIMP gi|1 4556790|ref|XP_001 54126.1 j PREDICTED: proprotein convertase subtilisin/kexin type 9 [Pan troglodytes]
MGTVSSRRSW PLPLLLLLLLLLGPAGARAQEDEDGLAEAPEHGTTATFHRCAKDPWRLPGTYV VLKEE THLSQSERTARRLQAQAARRGYLT ILHVFHGLLPGFLV MSGDLLELALKLPHVDYIEEDSSVFAQSIP WNLERI PPRYRADEYQPPDGGSLVEVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQAS CDS HGTHLAGVVSGRDAGVAKGASMRSLRVLNCQGKGTVSGTLIGLEFI KSQLVQPVGPLVVLLPLAGGYSR VLNAACQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVDLFAPG EDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSA DVINEAWFPEDQRV LTPNLVAALPPSTHGAG QLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSG RRGERMEAQGG LVCRAHNAFGGEGVYAIARCCLLPQANCSIHTAPPAEAGMGTRVHCHQQGHVLTGCSSHWEVEDLGTHK PPMLRPRGQPNQCVGHREASIHASCCRAPGLEC VKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVL GAYAVDNTCVVRSRDVSTAGSTSEEAVAAVAICCRSRHLAQASQELQ
(SEQ ID NO: 9) MOUSE g i1239563521 ref ! N P_705793.11 proprotein convertase subtilisin/kexin type 9 [Mus musculus]
GTHCSA LRWPLLPLLPPLLLLLLLLCPTGAGAQDEDGDYEEL LALPSQEDGLADEAAHVATATFRRC SKEAWRLPGTYIVVLMEETQRLQIEQTAHRLQTRAARRGYVI VLHIFYDLFPGFLV SSDLLGLAL L PHVEYIEEDSFVFAQSIP NLERIIPAWHQTEEDRSPDGSSQVEVYLLDTSIQGAHREIEGRVTITDFNS VPEEDGTRFHRQASKCDSHGTHLAG VSGRDAGVAKGTSLHSLRVLNCQG GTVSGTLIGLEFIRKSQLI QPSGPLVVLLPLAGGYSRILNAACRHLARTGVVLVAAAGNFRDDACLYSPASAPEVITVGATNAQDQPVT LGTLGTNFGRCVDLFAPGKDIIGASSDCSTCFMSQSGTSQAAAHVAGIVARMLSREPTLTLAELRQRLIH FSTKDVIN AWFPEDQQVLTPNLVATLPPSTHETGGQLLCRTV SAHSGPTRTATATARCAPEEELLSCS SFSRSGRRRGDWIEAIGGQQVCKALNAFGGEGVYAVARCCLVPRANCSIHNTPAARAGLETHVHCHQKDH VLTGCSFHWEVEDLSVRRQPALRSRRQPGQCVGHQAASVYASCCHAPGLEC IKEHGISGPSEQVTVACE JB2010.7161
AGWTLTGCNVLPGASLTLGAYSVDNLCVARVHDTARA.DRTSGEATVAAAICCRSRPSAKASWVQ
(SEQ ID NO: 10)
RAT gi|77020250|ref|NP_954862,2| proprotein convertase subtilisin/kexin type 9 [Rattus norvegicus]
MGIRCST LRWPLSPQLLLLLLLCPTGSRAQDEDGDYEELMLALPSQEDSLVDEASHVATATFRRCS EA WRLPGTYVVVLMEETQRLQVEQTAHRLQTWAARRGYVI VLHVFYDLFPGFLVKMSSDLLGLAL LPHVE YIEEDSLVFAQSIPWNLERI IPAWQQTEEDSSPDGSSQVEVYLLDTSIQSGHREIEGRV ITDFNSVPEE DGTRFHRQASKCDSHGfHLAGVVSGRDAGVA GTSLHSLRVLNCQGKGTVSGTLIGLEFIRKSQLIQPSG
PLVVLLPLAGGYSRILNTACQRLARTGVVLVAAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTL GTNFGRCVDLFAPG DIIGASSDCSTCY SQSGTSQAAAHVAGIVAM LNRDPALTLAELRQRLILFSTK DVINMAWFPEDQRVLTPNRVATLPPSTQETGGQLLCRTVWSAHSGPTRTATATARCAPEEELLSCSSFSR SGRRRGDRIEAIGGQQVC ALNAFGGEGVYAVARCCLLPRVNCSIHWTPAARAGPQTPVHCHQKDHVLTG CSFHWEVENLRAQQQPLLRSRHQPGQCVGHQEASVHASCCHAPGLECKIKEHGIAGPAEQVTVACEAGWT LTGCNVLPGASLPLGAYSVDNVCVARIRDAGRADRTSEEATVAAAICCRSRPSAKASWVHQ
(SEQ ID NO: 1 1)
Therapeutic Methods, Administration and Pharmaceutical Formulations
The present invention provides methods for treating or preventing disorders of cholesterol or lipid homeostasis that are mediated, at least in part, by PCSK9, and disorders and complications associated therewith, e.g., hypercholesterolemia, hyperlipidemia, hypertriglyceridaemia, atherosclerosis, primary heterogeneous familial hypercholesterolemia, arteriosclerosis, coronary heart disease, vascular inflammation and elevated serum LDL by administering a therapeutically effective amount of an anti-PCSK9 antibody (e.g., as set forth herein, e.g. , LPD1462/LPD1282; 1 F11) or antigen-binding fragment thereof optionally in association with a further therapeutic agent such as a HMG Co-A reductase inhibitor such as atorvastatin or simvastatin or rosuvastatin and thereby antagonizing PCS 9 and, thus, lowering serum LDL in the subject. Disorders and complications associated with disorders of cholesterol or lipid homeostasis include, for example, heart attacks (cardiac arrest) and death, e.g., sudden cardiac death (SCD). In an embodiment of the invention, the antibody or fragment is administered to reduce serum LDL levels by at least about 25% or 50% (e.g. , about 25-50%) (for at least about 20 to 30 days following a dose).
In an embodiment of the invention, a subject with a disorder of cholesterol or lipid homeostasis that are mediated, at least in part, by PCSK9, or a disorder or complication associated therewith is administered a therapeutically effective amount of the anti-PCSK9 antibody or antigen-binding fragment thereof to lower the serum LDL wherein the subject is HIV-positive and receiving highly active antiretroviral therapy (HAART; e.g. , CCR5 receptor antagonist, entry inhibitor, nucleoside and nucleotide reverse transcriptase inhibitor (NRTI), JB2010.7161
Non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitor, integrase inhibitor, and/or maturation inhibitor); is intolerant of H G Co-A reductase inhibitor therapy; suffers from acute coronary syndrome; is on immunosuppressive therapy (e.g., wherein the subject has received an organ transplant); is diabetic; and/or, will, in the future, receive percutaneous coronary intervention.
The term hypercholesterolemia includes, e.g. , familial and non-familial
hypercholesterolemia. Familial hypercholesterolemia (FHC) is an autosomal dominant disorder characterized by elevation of serum cholesterol bound to low density lipoprotein (LDL). Familial hypercholesterolemia includes both heterozygous FHC and homozygous FHC; methods for treating or preventing any of which by administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g., LPD1462/LPD1282) form part of the present invention.
Hyperlipidemia is an elevation of lipids in the bloodstream. These lipids include cholesterol, cholesterol esters, phospholipids and triglycerides. Hyperlipidemia includes for example, type I, lla, lib, III, IV and V; methods for treating or preventing any of which by administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention {e.g. , LPD1462/LPD1282) form part of the present invention.
Sitosterolemia is a rare inherited plant sterol storage disease. In general, the metabolic defect in the affected patient causes hyperabsorption of sitosterol from the gastrointestinal tract, decreased hepatic secretion of sitosterol with subsequent decreased elimination, and altered cholesterol synthesis. Methods for treating or preventing
sitosterolemia by administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g. , LPD1462/LPD1282) form part of the present invention
Atherosclerosis includes hardening of arteries associated with deposition of fatty substances, cholesterol, cellular waste products, calcium and fibrin in the inner lining of an artery. The buildup that results is called plaque. Methods for treating or preventing atherosclerosis by administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g. , LPD1462/LPD1282) form part of the present invention
Arteriosclerosis includes the diffuse build-up and deposition of calcium in artery walls which leads to hardening. Methods for treating or preventing arteriosclerosis by
administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g., LPD1462/LPD1282) form part of the present invention JB2010.7161
The present invention also provides methods for improving blood cholesterol markers associated with increased risk of heart disease. These markers include, but are not limited to, high total cholesterol, high LDL, high total cholesterol to HDL ratio and high LDL to HDL ratio.
In general, a total cholesterol of less than 200 mg/dL is considered desirable, 200-239 mg/dL is considered borderline high and 240 mg/dL and above is considered high. For example, the present invention comprises methods for reducing total cholesterol, e.g. , to less than or equal to about 200 mg/dL by administering a therapeutically effective amount of anti- PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g.,
LPD1462/LPD1282).
In general, a blood LDL level of less than 100 mg/dL is considered optimal; 100-129 mg/dL is considered near optimal/above optimal, 130-159 mg/dL is considered borderline high, 160- 89 mg/dL is considered high and 190 mg/dL and above is considered very high. For example, the present invention comprises methods for reducing LDL, e.g. , to less than about 100 mg/dL by administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g., LPD1462/LPD1282).
In general, HDL levels considered normal are at least 35 - 40 mg/dL. For example, the present invention comprises methods for increasing HDL, e.g., to greater than or equal to about 35-40 mg/dL by administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g.,
LPD1462/LPD1282).
Another indicator of heart disease risk is the ratio of total cholesterol to HDL. In general, a very low risk of heart disease correlates with a ratio of <3.4 (men) or <3.3
(women); a low risk is associated with a ratio of 4.0 (men) or 3.8 (women), an average risk is associated with a ratio of 5.0 (men) or 4.5 (women), a moderate risk is associated with a ratio of 9.5 (men) or 7.0 (women) and a high risk is associated with a ratio of >23 (men) or >11 (women). For example, the present invention comprises methods for reducing the ratio of total cholesterol to HDL, e.g., to less than about 4.5 or 5.0 by administering a therapeutically effective amount of anti-PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g., LPD1462/LPD1282).
A further indicator of heart disease risk is the ratio of LDL to HDL. In general, a very low risk is associated with a ratio of 1 (men) or 1.5 (women), an average risk is associated with a ratio of 3.6 (men) or 3.2 (women), a moderate risk is associated with a ratio of 6.3 (men) or 5.0 (women) and a high risk is associated with a ratio of 8 (men) or 6.1 (women). For example, the present invention comprises methods for the ratio of LDL to HDL, e.g., to less than or equal to about 3.2 or 3.6 by administering a therapeutically effective amount of JB2010.7161 anti-PCSK9 antibody or antigen binding fragment thereof of the present invention (e.g. , LPD1462/LPD1282).
in an embodiment of the invention, anti-PCSK9 antibodies and antigen-binding fragments thereof of the invention (e.g., LPD1462/LPD1282) are formulated into a pharmaceuticai formulation which comprises a pharmaceutically acceptable carrier. For general information concerning formulations, see, e.g., Gilman, et al., (eds.) (1990), The Pharmacological Bases of Therapeutics, 8th Ed., Pergamon Press; A. Gennaro (ed.),
Remington's Pharmaceutical Sciences, 18th Edition, (1990), Mack Publishing Co., Easton, Pennsylvania.; Avis, et al., (eds.) (1993) Pharmaceutical Dosage Forms; Parenteral
Medications Dekker, New York; Lieberman, et al., (eds.) (1990) Pharmaceutical Dosage Forms: Tablets Dekker, New York; and Lieberman, et al., (eds.) (1990), Pharmaceutical Dosage Forms: Disperse Systems Dekker, New York, Kenneth A. Walters (ed.) (2002)
Dermatoiogical and Transdermal Formulations (Drugs and the Pharmaceutical Sciences). Vol 1 19, Marcel Dekker.
In an embodiment of the invention, an anti-PCSK9 antibody or antigen-binding fragment thereof of the invention (e.g. , LPD1462/LPD1282) is formulated with a
pharmaceutically acceptable carrier that includes a buffer (e.g. , water and a buffer). In an embodiment of the invention, in an anti-PCSK9 antibody or fragment of the invention (e.g., LPD1462/LPD1282), for example, such a formulation (or any other pharmaceuticai formulation including an anti-PCSK9 antibody or fragment of the invention and a
pharmaceutically acceptable carrier) is adminsitered to lower serum LDL in a mammalian subject, such as a human, suffering from elevated LDL (e.g,. a subject suffering from heterogeneous familial hypercholesterolemia), at a dosage of about 0.5, 0.75, 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19 or 20 mg/kg of body weight, e.g., in a volume of about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19 or 20 ml, e.g., at a rate of once every week, 2 weeks, 3 weeks, 4 weeks, month or 6 weeks, e.g, subcutaneously, e.g, by injection device such as a needle and syringe or an injection pump. In an embodiment of the invention, the formulation is lyophilized or aqueous.
The anti-PCSK9 antibodies and antigen-binding fragments thereof of the present invention (e.g. , LPD1462/LPD1282) can be formulated according to known methods to prepare pharmaceutically useful compositions, whereby the antibody or fragment is combined in admixture with a pharmaceutically acceptable carrier, e.g., following antibody immunoglobulin synthesis, for example, as discussed herein. Carriers, excipients or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate and other organic acids; antioxidants including JB2010.7161 ascorbic acid; low molecular weight polypeptides; proteins, such as serum albumin, gelatin or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone, amino acids such as glycine, giutamine, asparagine, arginine or lysine; monosaccharides, disaccharides and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt-forming counterions such as sodium; and/or nonionic surfactants such as Tween, Pluronics or PEG. The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes, prior to or following lyophilization and reconstitution. Therapeutic or pharmaceutical compositions or formulations herein generally are placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle.
The route of administration of the antibodies and antigen-binding fragments thereof of the invention (e.g. , LPD1462/LPD1282) are, in an embodiment of the invention, by a parenteral route (e.g. , intravenous, subcutaneous, intraarterial, intratumoral, intramuscular, intraperitoneal).
Dosages and desired anti-PCSK9 concentrations of pharmaceutical compositions of the present invention may vary depending on the particular use envisioned. The
determination of the appropriate dosage or route of administration is well within the skill of an ordinary physician. Animal experiments provide reliable guidance for the determination of effective doses for human therapy. Interspecies scaling of effective doses can be performed following the principles laid down by Mordenti, J. and Chappell, W. "The use of interspecies scaling in toxicokinetics" In Toxicokinetics and New Drug Development, Yacobi et a/., Eds., Pergamon Press, New York 1989, pp. 42 96.
When used to treat a disorder in a subject (e.g., as discussed herein), a
therapeutically effective dosage or amount of anti-PCSK9 antibody or antigen-binding fragment thereof (e.g., LPD1462/LPD1282) is administered to the subject. In an embodiment of the invention, a therapeutically effective dosage is a dosage sufficient to decrease serum LDL to any detectable degree, e.g., by about 25% to about 50%. In an embodiment of the invention, a therapeutically effective dosage of anti-PCSK9 antibody or antigen-binding fragment thereof (e.g., as set forth herein, e.g., LPD1462/LPD1282) for treatment of hypercholesterolemia, heterogeneous familial hypercholesterolemia, hyperlipidemia, hypertriglyceridaemia, sitosteroiemia, atherosclerosis, arteriosclerosis, coronary heart disease, vascular inflammation or xanthoma or for treatment of any blood marker of heart disease risk (e.g., as discussed herein) is about 0.5, 0.75, 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19 or 20 mg/kg of body weight, e.g., in a volume of about 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19 or 20 ml, e.g., at a rate of once every week, 2 JB2010.7161 weeks, 3 weeks, 4 weeks, month or 6 weeks, e.g, which can be administered
subcutaneously, e.g, by injection device such as a needle and syringe or an injection pump.
When possible, administration and dosage of an agent (e.g. , further therapeutic agents discussed herein) is done according to the schedule listed in the product information sheet of the agents, in the Physicians' Desk Reference 2003 (Physicians' Desk Reference, 57th Ed); Medical Economics Company; ISBN; 1563634457; 57th edition (November 2002), as well as therapeutic protocols well known in the art.
A physician or clinician may monitor the blood cholesterol HDL or LDL levels or other marker levels associated with a cholesterol or lipid homeostasis disorder or disorder or complication associated therewith, in a subject being treated or about to be treated with an anti-PCSK9 antibody or antigen-binding fragment thereof (e.g., LPD1462/LPD1282), and make adjustments to the subject's treatment regimen as needed to reach a positive medical outcome. Further chemotherapeutic agents
The present invention provides methods and compositions for treating disorders of lipid and cholesterol metabolism (e.g., any set forth herein) by administering an anti-PCSK9 antibody or antigen-binding fragment thereof. Any antibody or antigen-binding fragment thereof of the present invention (e.g. , LPD1462/LPD1282; 1 F11 ) that is described anywhere herein may, in an embodiment of the invention, be provided in a composition in association with; or, administered to a subject (e.g. , a human) in association with, any additional or further chemotherapeutic agent (e.g., any that is discussed herein). In an embodiment of the invention, the further chemotherapeutic agent is a cardiovascular agent, an adrenergic blocker, an antihypertensive agent, an angiotensin system inhibitor, an angiotensin- converting enzyme (ACE) inhibitor, a coronary vasodilator, a diuretic or an adrenergic stimulant. In an embodiment of the invention, the further therapeutic agent is a cholesterol lowering medication such as an HMG-CoA reductase inhibitor.
The scope of the present invention also encompasses methods for treating or preventing a disorder of cholesterol or lipid homeostasis or any disorder or complication associated therewith by administering a therapeutically effective amount of the anti-PCSK9 antibody or antigen-binding fragment thereof (e.g. , LPD1462/LPD1282); wherein, the subject also suffers from a further medical condition such as, for example, hypertension, angina, cardiac arrhythmia, renal disease, congestive heart disease, myocardial infarction, enlarged heart, alcoholic cardiomyopathy, congenital heart disease, ischemic cardiomyopathy, hypertensive cardiomyopathy, valvular cardiomyopathy, inflammatory cardiomyopathy, myocardiodystrophy, dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic JB2010.7161 right ventricular cardiomyopathy, restrictive cardiomyopathy, noncompaction
cardiomyopathy, thrombosis or pericarditis; comprising further administering a further chemotherapeutic agent that treats or prevents such a further medical condition. Some of such further chemotherapeutic agents are discussed herein.
Cardiovascular agents which may used in connection with the present invention include those for treatment or prevention of lipid and/or cholesterol disorders or hypertension and other cardiovascular disorders and diseases. Disorders of lipid or cholesteroi metabolism may be caused or aggravated by hypertension. Hypertension is defined as persistently high blood pressure. Generally, adults are classified as being hypertensive when systolic blood pressure is persistently above 140 mmHg or when diastolic blood pressure is above 90 mmHg. Long-term risks for cardiovascular mortality increase in a direct relationship with persistent blood pressure. Examples of
antihypertensive agents which may be used in the present invention include e.g., calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-!! receptor antagonists, diuretics, adrenergic blockers including beta-adrenergic receptor blockers and alpha-adrenergic receptor blockers or diuretics.
Other cardiac drugs that may be provided in association with an anti-PCSK9 antibody or antigen-binding fragment thereof includes anti-anginal agents, such as adrenergic stimulants or coronary vasodilators and HMG-CoA reductase inhibitors.
HMG-CoA reductase inhibitors inhibit the HMG-CoA reductase enzyme and, thus, reduce production of cholesterol in the body of a subject. HMG-CoA reductase inhibitors
JB2010.7161 include, e.g., iovastatin, atorvastatin, ravastatin, rosuvastatin, fluvastatin, rivastatin and
simvastatin (
Figure imgf000038_0001
Adrenergic blockers include those compounds which are β-receptor inhibitors and/or a-receptor inhibitors. Adrenergic blockers which are p-receptor inhibitors include a class of drugs that antagonize the cardiovascular effects of catecholamines in hypertension, angina pectoris, and cardiac arrhythmias, p-adrenergic receptor blockers include, but are not limited to, bunolol hydrochloride (1(2H)-Naphthalenone, 5-[3-{1 ,1-dimethylethyl)amino]-2- hydroxypropoxy]-3,4-dihydro-, hydrochloride, CAS RN 31969-05-8 which can be obtained from Parke-Davis); acebutolol (±N-[3-Acetyl-4-[2~hydroxy-3-[(1
methylethyl)amino]propoxy]phenyl]- butanamide, or (±)-3'-Acetyl-4'-[2-hydroxy -3- (isopropylamino) propoxy] butyranilide);
acebutolol hydrochloride (such as N-[3-acetyl-4-[2-hydroxy-3-[1-methyl- ethyle)amino]propoxy]phenyl]-,monohydrocochloride, (±-;-3'-Acetyl-4'-[2-hydroxy-3- (isopropylamino)propoxyjbutyranilide monohydrochloride, for example, SECTRAL Capsules available from Wyeth-Ayerst); alprenolol hydrochloride (2-Propanol, 1-[(1-methy!ethyi)amino]- 3~[2-(2-propenyl)phenoxy]-,hydrochloride, CAS RN 13707-88-5 see Netherlands Patent Application No. 6,605,692); atenolol (such as benzeneacetamide 4-[2'-hydroxy-3'-[(1- methylethyl)ammo]propoxy3- , for example, TENORMIN I.V. Injection available from
AstraZeneca); carteolol hydrochloride (such as 5-[3-[(1 ,1-dimethylethyl)amino]-2- hydroxypropoxy]-3,4-dihydro-2(1 H)-quinolinone monohydrochloride, for example, Cartrol Filmtab Tablets available from Abbott); Celipro!ol hydrochloride (3-[3-Acetyl-4-[3-(ferf- JB2010.7161 butylamino)-2-hydroxypropoxyl]phenyl]-1 )1-diethyiurea monohydrochloride, CAS RN 57470- 78-7, also see in US Patent No. 4,034,009); cetamolol hydrochloride (Acetamide, 2-[2-[3- [{1 ,1-dimethylethyl)amino]-2-hydroxypropoxy]-phenoxy]-N-methyi-,monohydrochioride, CAS RN 77590-95-5, see also US Patent No. 4,059,622); labetalol hydrochloride (such as 5-[1- hydroxy-2-[(1-methyl-3-phenyIpropyl) amino] ethyljsalicyiamide monohydrochloride, for example, NORMODYNE Tablets available from Schering; esmolol hydrochloride ( (±)-Methyl p-[2-hydroxy-3-(isopropylamino) propoxy] hydrocinnamate hydrochloride, for example, BREVIBLOC Injection available from Baxter); levobetaxolol hydrochloride (such as (S)-1-[p- [2-(cyclopropylmethoxy)ethyl]phenoxy]-3-(isopropylamino)-2-propanol hydrochloride, for example, BETAXON Ophthalmic Suspension available from Alcon); levobunolol
hydrochloride (such as (-)-5-[3-(tert-Butylamino)-2-hydroxypropoxy]-3,4-dihydro-1 (2H)- naphthalenone hydrochloride, for example, BETAGAN Liquififm with C CAP Compliance Cap available from Allergan); nadolol (such as 1-(tert-butylamino)-3-[(5,6,7,8-tetrahydro-cis-6,7- dihydroxy-1-naphtbyl)oxy]-2-propanol, for example, Nadolol Tablets available from ylan); practolol (Acetamide, N-[4-[2-hydroxy-3-[1-methylethyl)amino]-propoxy]phenyl]-, CAS RN
6673-35-4, see also US Patent No3,408,387); propranolol hydrochloride (l-(lsopropylamino)- 3-(1-naphthy!oxy)-2-propanol hydrochloride CAS RN 318-98-9); sotalol hydrochloride (such as d,l-N-[4-[1-hydroxy-2-I(1-methylethyl)amino]ethyl]-phenyl]methane-suifonamide monohydrochloride, for example, BETAPACE AF Tablets available from Berlex);timolol (2- Propanol, 1-[(1 ,1-dimethylethyl)amino]-3-[[4-4(4-morpholinyl)-1 ,2,5-thiadiazol-3-yl]oxy]-
,hemihydrate, (S)-, CAS RN 91524-16-2); timolol maleate (S)-1-[(1 , 1-dimethylethyl) amino]- 3-[[4- (4-morpholinyl)-1 , 2, 5-thiadiazol -3- yl] oxy]-2-propanoi ( Z )-2-butenedioate (1 :1) salt, CAS RN 26921-17-5); bisoprolol (2-Propanol, 1 -[4-{[2-(1 -methylethoxy)ethoxy]- methyl]phenoxyl]-3-[(1-methylethy[)amino]-, {+), CAS RN 66722-44-9); bisoprolol fumarate (such as (±)-1 -[4-[[2-(1 -Methylethoxy) ethoxy]methyl]phenoxy]-3-[(1 -methylethy!)amino]-2- propanol (E) -2-butenedioate (2;1) (salt), for example, ZEBETA Tablets available from Lederle Consumer); nebivalol (2H-1-Benzopyran-2-methanol, aa'-(iminobis(methylene)]bis[6- fluoro-3,4-dihydro-, CAS RN 99200-09-6 see also US Patent No. 4,654,362); cicloprolol hydrochloride, such 2-Propanol, 1-[4-[2-(cyclopropylmethoxy)ethoxy]phenoxy3-3-[1- methylethyl)amino]-, hydrochloride, A.A.S. RN 63686-79-3); and dexpropranolol hydrochloride (2-Propanol, 1-[1-methylethyl)-amino]-3-(1-naphthalenyloxy)-hydroch!oride (CAS RN 13071- 11-9); diacetolol hydrochloride (Acetamide, N-I3-acetyl-4-[2-hydroxy-3-[(1-rnethyl- ethyl)amtno]propoxy][phenyl]-,monohydrochloride CAS RN 69796-04-9);dilevalol
hydrochloride (Benzamide, 2-hydroxy-5-[1-hydroxy-2-[1-methyl-3-phenylpropyl)amino]ethyl]- , monohydrochloride, CAS RN 75659-08-4); exaprolol hydrochloride (2-Propanol, 1-(2- cyclohexylphenoxy)-3-[(1-methyiethyl)amino3-,hydrochloride CAS RN 59333-90-3); flestolol JB2010.7161 sulfate (Benzoic acid, 2-fluro-,3-[[2-[aminocarbonyl)amino]-1-dimethylethyl]amino]-2- hydroxypropyl ester, (±)- sulfate {1 :1) (salt), CAS RN 88844-73-9; metaloi hydrochloride (Methanesulfonamide, N-E4-[1-hydroxy-2-(methylamino)propyl]phenyl]-,monohydrochloride CAS RN 7701-65-7);metoproloi 2-Propanol, 1-[4-(2-methoxyethyl)phenoxy]-3-[1- methylethyi)amino]-; CAS RN 37350-58-6);metoprolol tartrate (such as 2-Propanol, 1-[4-(2- methoxyethyl)phenoxy]-3-[(1-methylethyl)amino]-, for example, LOPRESSOR® available from Novartis); pamatolol sulfate (Carbamic acid, [2-[4-[2-hydroxy-3-[(1- methylethyl)amino]propoxyl]phenyl]-ethyl]-, methyl ester, (±) sulfate (salt) (2:1), CAS RN 59954-01-7); penbutolol sulfate (2-Propanol, 1-(2-cyclopentylphenoxy)-3-[1 ,1 - dimethy!ethyl)amino]1 , (S)-, sulfate (2:1) (salt), CAS RN 38363-32-5); practolol (Acetamide, N-[4-[2-hydroxy-3-[(1 -methylethyl)amino]-propoxy]phenyl]-, CAS RN 6673-35-4;) tiprenolol hydrochloride (Propanol, 1-[(1-methylethyl)amino]-3-[2-(methylthio)-phenoxy]-, hydrochloride, (±), CAS RN 39832-43-4); tolamolol (Benzamide, 4-[2-[[2-hydroxy-3-(2-methylphenoxy)- propy!]amino]ethoxylj-, CAS RN 38103-61-6).
Adrenergic receptors which are a-receptor inhibitors act to block vasoconstriction induced by endogenous catecholamines. The resulting fail in peripheral resistance leads to a fall in mean blood pressure.
Suitable adrenergic receptors which are a-receptor inhibitors include, but are not limited to, fenspiride hydrochloride (which may be prepared as disclosed in US Patent No. 3,399,192 herein incorporated by reference); proroxan (CAS RN: 33743-96-3); alfuzosin hydrochloride (CAS RN: 81403-68-1); and labetalol hydrochloride as described above or combinations thereof.
Adrenergic blockers with a- and β-receptor inhibitor activity which may be used with the present invention include, but are not limited to, bretylium tosylate (CAS RN: 61-75-6); dihydroergtamine mesylate (such as ergotaman-3', 6', 18-trione,9,-10-dihydro-12'-hydroxy-2'- methyl-S'-fphenylmethylJ-.tS alpha))-, monomethanesulfonate, for example, DHE 45 Injection available from Novartis); carvediiol (such as (±)-1-(Carbazol-4-yloxy)-3-[[2-(o- methoxyphenoxy)ethyl]amino]-2-propanol, for example, COREG Tablets available from SmithKline Beecham);. labetalol (such as 5-[1-hydroxy-2-[(1-methyl-3-phenylpropyl) amino] ethyljsalicylamide monohydrochloride, for example, NOR ODYNE Tablets available from Schering); bretylium tosylate (Benzenemethanaminium, 2-bromo-N-ethyl-N,N-dimethyh salt with 4-methylbenzenesulfonic acid (1 :1) CAS RN 61-75-6); phento!amine mesylate (Phenol, 3-Ef(4,5-dihydro-1H-imidazol-2-yl)methyl](4-methylphenyl)amino]-, monomethanesulfonate (salt) CAS RN 65-28-1); soiypertine tartrate (5H-1 ,3-Dioxolo[4,5-fJindoie, 7-[2-[4-(2- methoxyphenyl)-1-piperazinyl]ethyl]-, (2R,3R)-2,3-dihydroxybutanedioate (1 :1) CAS RN JB2010.7161
5591-43-5); zolertine hydrochloride (Piperazine, 1 -phenyl-4-[2-(1 H-tetrazol-5-yi)ethyl]~, monohydrochloride (SCI, 9CI) CAS RN: 7241-94-3)
An angiotensin system inhibitor is an agent that interferes with the function, synthesis or catabo!ism of angiotensin II. These agents, which may be used in the present invention, include, but are not limited to, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II antagonists, angiotensin II receptor antagonists, agents that activate the catabolism of angiotensin II and agents that prevent the synthesis of angiotensin I from which angiotensin II is ultimately derived. The renin-angiotensin system is involved in the regulation of hemodynamics and water and electrolyte balance. Factors that lower blood volume, renal profusion, or the concentration of Na+ in plasma tend to activate the system, while factors that increase these parameters tend to suppress its function. Angiotensin I and angiotensin II are synthesized by the enzymatic renin-angiotensin pathway. The synthetic process is initiated when the enzyme renin acts on angiotensinogen, a pseudoglobuiin in blood plasma, to produce the cecapeptide angiotensin I. Angiotensin I is converted by angiotensin- converting enzyme (ACE) to angiotensin li. The latter is an active pressor substance which has been implicated as a causative agent in several forms of hypertension in various mammalian species.
Angiotensin II receptor antagonists are compounds which interfere with the activity of angiotensin II by binding to angiotensin II receptors and interfering with its activity.
Angiotensin II receptor antagonists which may be used in the present invention are well known and include peptide compounds and non-peptide compounds. Non-limiting examples of angiotensin II receptor antagonists include: candesartan cilexetil (1 H-Benzimidazole-7- carboxylic acid, 2-ethoxy-1-[[2'-(1 H-tetrazo!-5-yl)[1 ,1,-biphenyl]-4-yl3methyl]-, 1- [[(cyclohexyloxy)carbonyl]oxy]ethyl ester ) CAS RN 145040-37-5); telmisartan( [1 ,1 - Biphenyl]-2-carboxylic acid, 4'-[(1 ,4'-dimethyi-2'-propyl[2,6'-bi-1 H-benzimidazol]-1'-yl)methyl]- CAS RN 144701-48-4); candesartan (1 H-Benzimidazole-7-carboxylic acid, 2-ethoxy-1-[t2'- (1 H-tetrazol-5-yi)t1 ,1'-biphenyl]-4-yl]methyl]- CAS RN 139481-59-7); losartan potassium (1 H-imidazole-5~methanol, 2~butyl-4-chloro-1-[[2'-(1 H-tetrazol-5-yl)t1 ,1'-biphenyl]-4- yijtnethyl]-, monopotassium lrbesartan1 ,3-Diazaspiroj .4]non-1 -en-4-one, 2-butyl-3-FJ2'-(1 H- tetrazol-5-yl)[1 ,1'-biphenyl]-4-yl]methyl]- CAS RN 138402-11 -6).
Angiotensin-converting enzyme (ACE), is an enzyme which catalyzes the conversion of angiotensin I to angiotensin II. ACE inhibitors which may be used in the present invention include amino acids and derivatives thereof, peptides, including di- and tri- peptides and antibodies to ACE which intervene renin-angiotensin system by inhibiting the activity of ACE thereby reducing or eliminating the formation of pressor substance angiotensin II. ACE inhibitors have been used medically to treat hypertension, congestive heart failure, JB2010.7161 myocardial infarction and renal disease. Suitable ACE inhibitors include, but are not limited to, benazepril hydrochloride (such as 3-[[1-(ethoxycarbonyl)-3-phenyl-(1 S)-propyl]amino]- 2,3,4,5-tetrahydro-2-oxo-1 H -1-(3S)-benzazepine-1 -acetic acid monohydrochloride, for example, LOTREL® Capsules available from Novartis); captopril (such as 1-[(2S)-3- mercapto-2-methylpropionyl)-L-proline, for example, CAPTOPRIL Tablets available from ylan); fosinopril (such as L-proline, 4-cyclohexyl-1-[[[2-methyl-1~(1-oxopropoxy) propoxy] (4-phenylbutyl) phosphinyl] acetyl]-, sodium salt, trans - ,for example, MONOPR!L Tablets available from Bristol-Myers Squibb); moexipril hydrochloride (such as [3S-[2[R*(R*)3,3R*]]~2- [2-[[1 - (Ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1 ,2,3,4-tetrahydro-6,7- dimethoxy-3-isoquinolinecarboxylic acid, monohydrochloride, for example, U IRETIC
Tablets available from Schwarz); perindopril erbumine ( such as 2S,3aS,7aS)-1-[(S)-N-[(S)-1- Carboxybutyl]alanyl]hexahydro-2-indolinecarboxylic acid, 1 -ethyl ester, compound with tert- butylamine (1 :1), for example, ACEON Tablets available from Soivay); quinapril (such as [3S- [2[R*(R*)],3R*]3-2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1 ,2,3,4- tetrahydro-3-isoquinolinecarboxyIic acid, monohydrochloride, for example, ACCURETIC Tablets available from Parke-Davis); ramipril (such as 2-aza-bicycio [3.3.0]-octane-3- carboxylic acid derivative, for example, ALTACE Capsules available from Monarch); ena!apri! maleate (such as (S)-1-[N -[1-(ethoxycarbonyi)-3- phenylpropylj-L-alanyl]-L-proline, (Z)-2- butenedioate salt (1 :1)., for example, VASOTEC Tablets available from Merck); lisinopril (such as ( S )-1-[ N 2-(1-carboxy-3-phenylpropyl)-L-lysyl]-L-proline dihydrate, for example, PRINZIDE Tablets available from Merck); delapril (which may be prepared as disclosed in US Patent No. 4,385,051); and spirapril (which may be prepared as disclosed in US Patent No. 4,470,972); benazeprilat ( H-1-Benzazepine-1 -acetic acid, 3-[ft1 S)-1-carboxy-3- phenylpropyl]amino]-2,3,4,5-tetrahydro-2-oxo-, (3S)- CAS RN 86541-78-8); delapril hydrochloride (Glycine, N-[(1 S)-1-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyi-N-(2t3-dihydro- 1 H-inden-2-yl)-, monohydrochloride CAS RN 83435-67-0); fosinopril sodium (L-Proline, 4- cyciohexyl-1-[[(R)-[(1S)-2-methyl-1-(1-oxopropoxy)propoxy](4-phenylbutyl)phosphinyl]acetyl]- , sodium salt, (4S)- CAS RN 88889-14-9); iibenzapril (1 H-1-Benzazepine-1 -acetic acid, 3- [[(1S)-5-amino-1-carboxypentyl]amino]-2,3,4,5-tetrahydro-2-oxo-, (3S)- CAS RN 109214-55- 3); pentopril (1H-lndole-1-pentanoic acid, 2-carboxy-2,3-dihydro-.aipha.,.gamma.-dimethyl- .delta.-οχο-, .alpha.-ethyl ester, (.aipha.R,.gamma.R,2S)- CAS RN 82924-03-6); perindopril 1 H-lndole-2-carboxyIic acid, 1-[(2S)-2-[£(1 S)-1-(ethoxycarbonyl)butyl]amino]-1- oxopropyQoctahydro-, (2S,3aS,7aS)- CAS RN 82834-16-0); quinapril hydrochloride (3- Isoquinolinecarboxylic acid, 2-[(2S)-2-[[(1S)-1 -(ethoxycarbonyl)-3-phenylpropyl]amino]-1- oxopropyl]-1 ,2,3,4-tetrahydro-, monohydrochloride, (3S)- CAS RN 82586-55- ); quinaprilat (3-lsoquinolinecarboxylic acid, 2-[(2S)-2-[[(1 S)-1 -carboxy-3-phenylpropyl]amino]-1 - JB2010.7161 oxopropyl]-1 ,2,3,4-tetrahydro-, (3S)- CAS RN 82768-85-2); spirapril hydrochloride (1 ,4- Dithia-7-azaspiro[4.4]nonane-8-carboxylic acid, 7-[(2S)-2-[[(1 S)-1-(ethoxycarbonyl)-3- phenylpropyl]amino]-1-oxopropyl]-, monohydrochioride, (8S)- CAS RN 94841-17-5);
spiraprilat 1 (,4-Dithia-7-azasptro[4-4]nonane-8-carboxylic acid, 7-[(2S)-2-[[(1 S)-1-carboxy-3- phenyipropyl]amino]-1-oxopropyl]-, (8S)- CAS RN 83602-05-5); teprotide (Bradykinin potentiator BPP9a CAS RN 35115-60-7); lisinopril (L-Proiine, N2-[(1 S)-1 -carboxy-3~ phenylpropyl]-L-lysy!- CAS RN 76547-98-3); zofenopril (L-Proline, 1-[(2S)-3-(benzoyithio)-2- methyl-1 -oxopropyl]-4-(phenyithio)-, calcium salt (2:1 ), (4S)- CAS RN 81938-43-4).
"Calcium channel blockers" are a class of compounds having important therapeutic value in the control of a variety of diseases including several cardiovascular disorders such as hypertension, angina, and cardiac arrhythmias (Fleckenstein, Cir. Res. V. 52 (suppl. 1), p. 13-16 (1983); Fleckenstein, Experimental Facts and Therapeutic Prospects, John Wiley, New York (1983); McCail, D., Curr. Pract Cardiol., v. 10, p. 1-11 (1985)). Calcium channel blockers are a heterogeneous group of drugs that prevent or slow the entry of calcium into cells by regulating cellular calcium channels (Remington, The Science and Practice of Pharmacy, Nineteenth Edition, Mack Publishing Company, Eaton, PA, p. 963 (1995)).
Calcium channel blockers useful in the present invention include but are not limited to, the besylate salt of amlodipine (such as 3-ethyl-5-methyl-2-(2-aminoethoxymethyl)-4-(2- chlorophenyl)-1 ,4-dihydro-6-methyl-3,5-pyridinedicarboxylate benzenesulphonate, for example, NORVASC available from Pfizer); clentiazem maleate (1 ,5-Benzothiazepin-4(5H)- one, 3-(acetySoxy)-8-chloro-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-(2S- cis)-, (Z)-2-butenedioate (1 :1), see also U.S. Patent No. 4,567,195); isradipine (3,5- Pyridinedicarboxylic acid, 4-(4-benzofurazanyi)-1 !4-dihydro-2,6-dimethyl-,methyl 1- methylethyl ester, (±)-4(4-benzofurazanyl)-1 ,4-dihydro-2,6-dimethyl-3,5- pyridinedicarboxylate, see also US Patent 4,466,972); nimodipine (such as is isopropyl (2 - methoxyethyl) 1 , 4- dihydro - 2, 6 - dimethyl - 4 - (3 - nitrophenyl) - 3, 5 - pyridine - dicarboxylate, for example, NIMOTOP available from Bayer); felodipine (such as ethyl methy! 4-(2,3-dichlorophenyl)-1 ,4-d in yd ro-2,6-di methy 1-3,5-py rid inedicarboxy late, for example, PLENDIL Extended-Release Tablets available from AstraZeneca LP); nilvadipine (3,5- Pyridinedicarboxylic acid, 2-cyano-1 ,4-dihydro-6-methyl-4-(3-nitrophenyl)-,3-methyi 5-(1- methylethyl) ester, also see US Patent No.3,799,934); nifedipine (such as 3,5- pyridinedicarboxylic acid,1 ,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-, dimethyl ester, for example, PROCARDIA XL Extended Release Tablets available from Pfizer); diltiazem hydrochloride (such as 1 ,5-Benzothiazepin-4(5H)-one,3-(acety(oxy)-5[2- (dimethylamino)ethyl]-2,-3-dihydro-2(4-methoxyphenyl)-, monohydrochioride, (+)-cis., for example, T!AZAC Capsules available from Forest); verapamil hydrochloride (such as JB2010.7161 benzeneacetronitrile, (aipha)-[[3-[[2-(3,4-dimethoxyphenyl) ethyl] methylamino] propyl]-3,4- dimethoxy-(alpha)-(1-methylethyl) hydrochloride, for example, ISOPTIN SR Tablets available from Knoll Labs); teludipine hydrochloride (3,5-Pyridinedicarboxy!ic acid, 2- [(dimethylamino)methyl]~4-[2-[(1E)-3-(1 ,1 -dimethylethoxy)-3-oxo-1-propenyi]phenyl]-1 ,4- dihydro-6-methyl- diethyl ester, monohydrochloride) CAS RN 108700-03-4); belfosdi! (Phosphonic acid, J2-(2-phenoxyethyl)-1 ,3-propanediyl]bis-, tetrabutyl ester CAS RN
103486-79-9); fostedil (Phosphonic acid, [[4-(2-benzothiazolyl)phenyl]methyl]-, diethyl ester CAS RN 75889-62-2).
Cardiovascular agents of the present invention, which also act as "anti-anginal agents", are useful in the present invention. Angina includes those symptoms that occur when myocardial oxygen availability is insufficient to meet myocardial oxygen demand. Non- limiting examples of these agents include: ranolazine (hydrochloridel-Piperazineacetamide, N-(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-, dihydrochloride CAS RN 95635-56-6); betaxoiol hydrochloride (2-Propanol, 1-[4-[2
(cyclopropylmethoxy)ethyl]phenoxy]-3-[(1-methyiethyl)amino]-, hydrochloride CAS RN
63659-19-8); butoprozine hydrochloride (Methanone, [4-[3(dibutylamino)propoxyJphenyfJ(2- ethyl-3-indolizinyl)-, monohydrochloride CAS RN 62134-34-3); cinepazet maleatel- Piperazineacetic acid, 4-t1-oxo-3-(3,4,5-trimethoxyphenyl)-2-propenyl]-, ethyl ester, (2Z)-2- butenedioate (1 :1) CAS RN 50679-07-7); tosifen (Benzenesulfonamide, 4-methyl-N-[[ (1S)- 1 -methy!-2-phenylethylJamino]carbonyi]- CAS RN 32295-18-4); verapamilhydrochloride (Benzeneacetonitrile, .alpha.-[3-[[2-(3,4-dimethoxyphenyl)ethyl]methyiamino)propyl]-3,4- dimethoxy-.alpha.-(l-methylethyl)-, monohydrochloride CAS RN 152-11-4); molsidomine (1 ,2,3-Oxadiazolium, 5-[(ethoxycarbonyl)amino]-3-(4-morpholinyl)-, inner salt CAS RN 25717-80-0); ranolazine hydrochloride (1-Piperazineacetamide, N-(2,6-dimethylphenyl)-4-[2- hydroxy-3-(2-methoxyphenoxy)propyl]-, dihydrochloride CAS RN 95635-56-6); tosifen
(Benzenesulfonamide, 4-methyl-N-[[[(1S)-1-methyl-2-pheny!ethyl]amino]carbonyi)- CAS RN 32295-18-4).
"Coronary vasodilators" may act to reduce angina systems by increasing the oxygen supply to the heart. Coronary vasodilators useful in the present invention include, but are not limited to, diltiazem hydrochloride (such as 1 ,5-Benzothiazepin- 4(5H)-one,3-(acetyloxy)-5[2~(dimethylamino)ethyl]-2,-3-dihydro-2(4-methoxyphenyl)-, monohydrochloride, (+)-cis, for example, TIAZAC Capsules available from Forest);
isosorbide dinitrate (such as 1 ,4:3,6-dianhydro-D-giucitol 2,5-dinrtrate, for example, ISORDIL TITRADOSE Tablets available from Wyeth-Ayerst); sosorbide mononitrate (such as 1 ,4:3,6-dianhydro-D-glucitol,5-nitrate, an organic nitrate, for example, Ismo JB2010.7161
Tablets available from Wyeth-Ayerst); nitroglycerin (such as 2,3 propanetriol trinitrate, for example, NITROSTAT Tablets available from Parke-Davis); verapamil hydrochloride (such as benzeneacetonitrile, (±)~(aIpha)[3[[2-(3,4
dimethoxyphenyl)ethyl]methylamino]propyl]-3,4-dimethoxy-(alpha)- (1-methylethyi) hydrochloride, for example, COVERA HS Extended-Release Tablets available from Searle); chromonar (which may be prepared as disclosed in US Patent No. 3,282,938); clonitate (Annalen 1870 155); droprenilamine (which may be prepared as disclosed in German Patent No. 2,521 ,113); lidoflazine (which may be prepared as disclosed in US Patent No. 3,267,104); prenyiamine (which may be prepared as disclosed in US Patent No. 3152173); propatyl nitrate (which may be prepared as disclosed in French Patent No. 1 ,103,113); mioflazine hydrochloride (1-Piperazineacetamide, 3-(aminocarbonyl)-4-[4,4- bis(4-fluorophenyl)butyl]-N-(2,6-dichlorophenyl)-, dihydrochloride CAS RN 83898-67-3); mixidine (Benzeneethanamine, 3,4-dimethoxy-N-(1-methyl-2-pyrrolidinylidene)- Pyrrolidine, 2-[(3,4-dimethoxyphenethyl)imino]-1 -methyl- 1 -Methyl-2-[(3,4- dimethoxyphenethyl)imino]pyrrolidine CAS RN 27737-38-8); molsidomine (1 ,2,3-
Oxadiazolium, 5-[(ethoxycarbonyl)amino]-3-(4-morpholinyl)-, inner salt CAS RN 25717- 80-0); isosorbide mononitrate (D-Glucitol, 1 ,4:3,6-dianhydro-, 5-nitrate CAS RN 16051- 77-7); erythrityl tetranitrate (1 ,2,3,4-Butanetetrol, tetranitrate, (2R,3S)-rel- CAS RN 7297-25-8); clonitrate(1 ,2-Propanediol, 3-ch!oro-, dinitrate (7CI, 8CI, 9CI) CAS RN 2612- 33-1); dipyridamole Ethanol, 2,2, l2"l2"'-[(4,8-di-1-piperidinylpyrimido[5)4-d]pyrimidine-2,6- df'yl)dinitrilo]tetrakis- CAS RN 58-32-2); nicorandil (CAS RN 65141-46-0 3-);
pyridinecarboxamide (N-[2-(nitrooxy)ethyl]-Nisoidipine3,5-Pyridinedicarboxylic acid, 1 ,4- dihydro-2,6-dimethyi-4-(2-nitrophenyl)-, methyl 2-methylpropyl ester CAS RN 63675-72- 9); nifedipines, 5-Pyridinedicarboxylic acid, 1 ,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-, dimethyl ester CAS RN 21829-25-4); perhexiline maleate (Piperidine, 2-(2,2- dicyclohexylethyl)-, (2Z)-2-butenedioate (1 :1) CAS RN 6724-53-4); oxprenolol hydrochioride2-Propanol, 1 -[(1 -methylethyl)amino]-3-[2-(2-propenyloxy)phenoxy]-, hydrochloride CAS RN 6452-73-9); pentrinitrol (1 ,3-Propanediol, 2,2- bis[(nitrooxy)methyl]-, mononitrate (ester) CAS RN 1607-17-6); verapamil
(Benzeneacetonitrile, .alpha.-[3-[[2-(3,4-dimethoxyphenyl)ethyi]methylamino]propyl]-3,4- dimethoxy-.alpha.-(l-methylethyl)- CAS RN 52-53-9).
The term "diuretic" includes compounds that increase the excretion of solutes (mainly NaCI) and water. In general, the primary goal of diuretic therapy is to reduce extracellular fluid volume in order to lower blood pressure or rid the body of excess interstitial fluid JB2010.7161
(edema). Non-limiting examples of diuretics which may be used within the scope of this invention include althiazide (which may be prepared as disclosed in British Patent No.
902,658); benzthiazide (which may be prepared as disclosed in U.S. Patent No. 3,108,097); buthiazide (which may be prepared as disclosed in British Patent Nos. 861 ,367);
chlorothiazide (which may be prepared as disclosed in U.S. 2,809,194); spironolactone (CAS Number 52-01-7); and triamterene (CAS Number 396-01-0).
"Adrenergic stimulants" useful as cardiovascular agents in the present invention include, but are not limited to, guanfacine hydrochloride (such as N-amidino-2-(2,6- dichlorophenyl) acetamide hydrochloride, for example, TENEX Tablets available from
Robins); methyldopa-hydrochlorothiazide (such as levo-3-(3,4-dihydroxyphenyl)-2- methylalanine ) combined with Hydrochlorothiazide (such as 6-chloro-3,4-dihydro-2 H -1 ,2,4- benzothiadiazine-7- sulfonamide 1 ,1 -dioxide, for example, the combination as, for example, ALDORIL Tablets available from Merck); methyldopa-chlorothiazide (such as 6-chloro-2 H -1 , 2, 4-benzothiadiazine-7-sulfonamide 1 , 1 -dioxide and methyldopa as described above, for example, ALDOCLORr Tablets available from Merck) ; clonidine hydrochloride (such as 2- (2,6-dichlorophenylamino)-2-imidazoline hydrochloride and chlorthalidone (such as 2-chloro- 5-(1-hydroxy-3-oxo-1-isoindolinyl) benzenesulfonamide), for example, COMBIPRES Tablets available from Boehringer Ingelheim); clonidine hydrochloride (such as 2-(2,6- dichlorophenylamino)-2-imidazoline hydrochloride, for example, CATAPRES Tablets available from Boehringer ingelheim); clonidine (1 H-lmidazol-2-amine, N-(2,6- dichlorophenyl)-4,5-dihydro- CAS RN 4205-90-7).
The anti-PCSK9 antibodies and antigen-binding fragments thereof may also be administered in association with any substituted azetidinone which inhibits intestinal cholesterol absorption. Such azetidinones include ezetimibe
Figure imgf000046_0001
Patent No. 5,846,966 or RE37721); optionally in combination with any HMG CoA reductase inhibitor such as simvastatin or atorvastatin. JB2010.7161
Further chemotherapeutic agents that may be administered in association with an anti-PCSK9 antibody or antigen-binding fragment thereof or EGF-A polypeptide include fish oil, eicosaepenanoic acid, docosahexanoic acid, linoleic acid, niacin, fibrates such as fenofibrate, gemfibrozil and bile acid sequestrants such as cholestyramine, colestipol and colesevelam.
Other chemotherapeutic agents include althiazide (2H-1 ,2,4-Benzothiadiazine-7- sulfonamide, 6-chloro-3t4-dihydro-3-[(2-propenylthio)methyl]-, 1 ,1 -dioxide CAS RN 5588- 16-9); benzthiazide (2H-1 ,2,4-Benzothiadiazine-7-sulfonamide, 6-chioro-3- [[(phenylmethyl)thio]methylj-, 1 ,1 -dioxide CAS RN 91-33-8); captopril (L-Proline, 1-[(2S)-3- mercapto-2-methyl-1 -oxopropyl]- CAS RN 62571-86-2); carvedilol (2-Propanol, 1-(9H- carbazol-4-yloxy)-3-[I2-(2-methoxyphenoxy)ethyl]amino]- CAS RN 72956-09-3),
chlorothiazide (sodium 2-Propanol, 1 -(9H-carbazol-4-yloxy)-3-[[2-(2- methoxyphenoxy)ethyl]amino]- CAS RN 72956-09-3); clonidine hydrochloride (1 H-lmidazoi- 2-amine, N-(2,6-dichlorophenyl)-4,5-dihydro-, monohydrochloride CAS RN 4205-91-8); cyclothiazide {2H-1 ,2,4-Benzothiadiazine-7-sulfonamide, 3-bicyclo[2,2.1 ]hept-5-en-2-yl-6- chioro-3,4-dihydro-, 1 ,1-dioxide CAS RN 2259-96-3); delapnl hydrochloride (2H-1 , 2,4- Benzothiadiazine-7-sulfonamide, 3-bicyclo[2.2.1]hept-5-en-2-yl-6-chloro-3,4-dihydro-, 1 ,1 - dioxide CAS RN 2259-96-3); dilevalol hydrochloride {2H-1 ,2,4-Benzothiadiazine-7- sulfonamide, 3-bicyclo[2.2.1]hept-5-en-2-yl-6-chloro-3,4-dihydro-, 1 ,1-dioxide CAS RN 2259-96-3); delapril hydrochloride (Glycine, N-[(1 S)-1-(ethoxycarbonyl)-3-phenylpropyi]-L- alanyl-N-(2,3-dihydro-1 H-inden-2-yl)-, monohydrochloride CAS RN 83435-67-0); doxazosin mesylate (Piperazine, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)^-[(2,3-dihydro-1 ,4- benzodioxin-2-yl)carbonyl]-, monomethanesuifonate CAS RN 77883-43-3); fosinopnl sodium (L-Proline, 4-cyclohexyl-1-[[(R)-[(1S)-2-methyl-1-(1-oxopropoxy)propox); moexipri! hydrochloride (3-lsoquinolinecarboxylic acid, 2-[(2S)-2-[[(1 S)-1-(ethoxycarbonyl)-3- pheny!propyl]amino]-1 -oxopropyl]-1 ,2,3,4-tetrahydro-6,7-dimethoxy-, monohydrochloride, (3S)- CAS RN 82586-52-5); monatepil maleate (1-Piperazinebutanamide, N-{6,11- dihydrodibenzo(b,e)thiepin-11-yl)-4-(4-fluorophenyl)-, (±)-, (Z)-2-butenedioate (1 :1) (+)-N- (6,11-Dihydrodibenzo(b,e)thiepin-11-yl)-4-(p-fluorophenyi)-1-piperazinebutyramide maleate (1 :1) CAS RN 132046-06-1), Metoprolol succinate (Butanedioic acid, compd. with 1 -[4-(2- methoxyethyl)phenoxy]-3-[(1 -methylethy!)amino]-2-propanol (1 :2) CAS RN 98418-47-4); guanfacine hydrochloride (Benzeneacetamide, N-(aminoiminomethyl)-2,6-dichloro-, monohydrochloride CAS RN 29110-48-3; methyldopa (L-Tyrosine, 3-hyd roxy-. alpha. - methyl- CAS RN 555-30-6); quinaprilat (3-lsoquinolinecarboxylic acid, 2-[(2S)-2-[[(1S)-1- carboxy-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-, (3SJ- CAS RN 82768-85- 2); quinapril hydrochloride (3-isoquinoltnecarboxylic acid, 2-[(2S)-2-[[(1S)-1-(ethoxycarbonyl)- JB2010.7161
3-phenyIpropyljamino]-1-oxopropyS]-1 ,2,3,4-tetrahydro-, monohydrochloride, (3S)- CAS RN 82586-55-8); Primidolol (2,4(1 H,3H)-Pyrimidinedk>ne, 1-[2-t[2-hydroxy-3-(2- methylphenoxy)propyl]amino]ethyl]-5-methyl- CAS RN 67227-55-8); prazosin hydrochloride (Piperazine, 1-(4-amino-6,7-dimethoxy-2-quinazolinyi)-4-(2-furanyicarbonyl)-,
monohydrochloride CAS RN 19237-84-4); pe!anserin hydrochloride 2,4(1 H,3H)-
Quinazolinedione, 3-[3-(4-pheny!-1-piperazinyl)propyl]-, monohydrochloride CAS RN 42877- 18-9); phenoxybenzamine hydrochloride (Benzenemethanamine, N-(2-chioroethyl)-N-(1- methyl-2-phenoxyethyl)-, hydrochloride CAS RN 63-92-3); candesartan cilexetil (1 H- Benzimidazoie-7-carboxylic acid, 2-ethoxy-1-[[2'-(1 H-tetrazoi-5-yl)[1 ,1 '-biphenyl]-4-yl]methyl]- , 1-[[(cyclohexyloxy)carbonyi]oxy]ethyl ester CAS RN 145040-37-5); telmisartan (1 ,1 -
Biphenyl]-2-carboxylic acid, 4 ~[(1 ,4'-dimethyl-2'-propyl[2,6'-bi-1 H-benzimidazolj-l '-yl)methyl]- CAS RN 144701-48-4); candesartan1 H-Benzimidazole-7-carboxy!ic acid, 2-ethoxy-1 -[[2'- (1 H-tetrazol-5-yl)[1 ,1 '-biphenyl3-4-yl]methyl]- CAS RN 139481-59-7); amlodipine
besylate3,5-Pyridinedicarboxylic acid, 2-[(2-aminoethoxy)methyl]-4-(2-chiorophenyl)- ,4- dihydro-6-methyi-, 3-et yl 5-methyl ester, monobenzenesulfonate CAS RN 11 1470-99-6 Amlodipine maleate 3,5-Pyridinedicarboxylic acid, 2-[(2-aminoethoxy)methyl]-4-(2- chlorophenyl)-1 ,4-dihydro-6-methyl-, 3-ethyl 5-methyi ester, (2Z)-2-butenedioate (1 :1 ) CAS RN 88150-47-4); terazosin hydrochloride (Piperazine, 1-(4-amino-6,7-dimethoxy-2- quinazolinyl)-4-[(tetrahydro-2-furanyi)carbonyl3-t monohydrochloride CAS RN 63074-08-8); bevantoloi hydrochloride (2-Propanol, 1-[[2-(3,4-dimethoxyphenyl)ethyl]amino]-3-{3- methylphenoxy)-, hydrochloride CAS RN 42864-78-8); and ramipril (Cyclopenta[b]pyrrole-2- carboxylic acid, 1-[(2S)-2-[[(1 S)-1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1 - oxopropyljoctahydro-, (2S,3aS,6aS)~ CAS RN 87333-19-5).
The term "in association with" indicates that the components of a composition of the invention (e.g., anti-PCSK9 antibody or antigen-binding fragment thereof along with ezetimibe) can be formulated into a single composition for simultaneous delivery or formulated separately into two or more compositions (e.g., a kit). Furthermore, each component can be administered to a subject at a different time than when the other component is administered; for example, each administration may be given non- simultaneously (e.g., separately or sequentially) at several intervals over a given period of time. Moreover, the separate components may be administered to a subject by the same or by a different route (e.g., wherein an anti-PCSK9 antibody is administered parenteraily and ezetimibe is administered orally). JB2010.7161
Crystals
The present invention includes crystals comprising any antibody or antigen-binding fragment thereof of the invention compiexed with PCSK9 or a peptide epitope thereof.
Several crystallization methods are known in the art (Giege, et at., (1994) Acta Crystallogr. D50: 339-350; McPherson, (1990) Eur. J. Biochem. 189: 1-23). Such methods include microbatch, hanging drop, seeding and dialysis. Preferably, hanging-drop vapor diffusion (McPherson, (1976) J. Biol. Chem. 251 ; 6300 -6303) or microbatch methods (Chayen (1997) Structure 5: 1269-1274) are used. In each of these methods, it is important to promote continued crystal growth after nucleation by maintaining a supersaturated solution. In the microbatch method, polypeptide is mixed with precipitants to achieve supersaturation, the vessel is sealed and set aside until crystals appear. In the dialysis method, polypeptide is retained in a sealed dialysis membrane which is piaced into a solution containing precipitant. Equilibration across the membrane increases the precipitant concentration thereby causing the polypeptide to reach supersaturation levels.
Once a crystal of the present invention is grown, X-ray diffraction data can be collected. One method for determining structure with X-ray diffraction data includes use of synchrotron radiation, under standard cryogenic condition; however, alternative methods may also be used. For example, crystals can be characterized by using X-rays produced by a conventional source, such as a sealed tube or a rotating anode. Methods of characterization include, but are not limited to, precession photography, oscillation photography and diffractometer data collection.
The crysta!lizable compositions provided by this invention are amenable to X-ray crystallography for providing the three-dimensional structure of the PCSK9/antibody or fragment complex. The present invention includes crystals which effectively diffract X-rays for the determination of the atomic coordinates of the PCSK9/antibody or fragment complex to a resolution of greater than about 5.0 Angstroms (e.g. , about 4.5 A , about 4,0 A , about 3 A, about 2.5 A, about 2 A, about 1.95 A, about 1 A), preferably greater than about 4.0 Angstroms (e.g., about 3 A, about 2.5 A, about 2 A, about 1.95 A, about 1 A), more preferably greater than about 2.8 Angstr5ms (e.g., about 2.5 A, about 2 A, about 1.95 A, about 1 A) and most preferably greater than about 2.0 Angstr6ms (e.g. , about 1 .95 A, about 1.5 A, about 1.0 A).
The scope of the present invention also encompasses a crystalline complex between an anti-PCSK9 antibody or antigen-binding fragment thereof of the present invention (e.g. , a Fab comprising the heavy chain amino acid sequence set forth in SEQ ID NO: 18 and the light chain amino acid sequence set forth in SEQ ID NO: 19) in space group P2i2i2 and JB2010.7161 comprising the unit cell dimensions: a=114.007 A, b= 135.131 A, c= 106.710 A, and oc=90°, p=90°; γ=90°.
The present invention includes PCSK9/antibody or fragment complex crystals whose three-dimensional structure is described by the structure coordinates set forth in Table 5. The scope of the present invention also includes crystals that possess structural coordinates which are similar to those set forth in Table 5. Structural similarity between crystals is discussed in detail below.
The term "structure coordinates" refers to Cartesian coordinates derived from mathematical equations related to the patterns obtained on diffraction of a beam of X-rays by the atoms (scattering centers) of a molecule. The diffraction data are used to calculate electron density maps and to establish the positions of the individual atoms of the molecule.
Those of skill in the art will understand that a set of structure coordinates for an enzyme or an enzyme-complex or a portion thereof, is a relative set of points that define a shape in three dimensions. Thus, it is possible that an entirely different set of coordinates could define a similar or identical shape. Moreover, slight variations in the individual coordinates will have little effect on overall shape.
The present invention includes crystals exhibiting structural coordinates which are similar to those set forth in Table 5 but for crystallographic permutations of the structure coordinates, fractionaltzation of the structure coordinates, additions, subtractions, rotations or translations to sets of the structure coordinates or any combinations of the above.
Alternatively, modifications in the crystal structure due to mutations, additions, substitutions, and/or deletions of amino acids, or other changes in any of the components that make up the crystal may also account for variations in structure coordinates. If such variations are within an acceptable standard error as compared to the coordinates of Table 5, the resulting three-dimensional shape is considered to be the same and, accordingly, the modified crystal is considered to be within the scope of the present invention.
Various computational analyses may be used to determine whether a crystal is sufficiently similar to the crystals whose structural coordinates are set forth in Table 5 as to be considered the same. Such analyses may be carried out in current software applications, such as the Molecular Similarity application of QUANTA (Molecular Simulations Inc., San Diego, CA) version 4.1 , and as described in the accompanying User's Guide.
The Molecular Similarity application permits comparisons between different structures, different conformations of the same structure, and different parts of the same structure. In general, the procedure used in Molecular Similarity to compare structures is divided into four steps: 1) input the structures to be compared; 2) define the atom equivalences in these structures; 3) perform a fitting operation; and 4) analyze the results. Each structure is JB2010.7161 identified by a name. One structure is identified as the target {i.e., the fixed structure); all remaining structures are working structures {i.e., moving structures). Since atom
equivalency within QUANTA is defined by user input, for the purpose of this invention we will define equivalent atoms as alpha carbon atoms (Ca) or all protein backbone atoms (N, Ca, C and O) for all conserved residues between the two structures being compared. When a rigid fitting method is used, the working structure is translated and rotated to obtain an optimum fit with the target structure. The fitting operation uses a least squares fitting algorithm that computes the optimum translation and rotation to be applied to the moving structure, such that the root mean square difference of the fit over the specified pairs of equivalent atom is an absolute minimum. This number, given in Angstroms, is reported by QUANTA.
The term "root mean square deviation" (RMSD) is a commonly known term in the art which, in general, means the square root of the arithmetic mean of the squares of the deviations from the mean distance of corresponding atoms. It is a way to express the deviation or variation from a trend or object.
The term "least squares" relates to a method based on the principle that the best estimate of a value is that in which the sum of the squares of the deviations of observed values is a minimum.
For the purpose of this invention, any crystalline molecule characterized by a set of structure coordinates that has a RMSD of conserved residue backbone atoms (N, Ca, C, 0) or of alpha carbon atoms (Ca) only of less than about 1.5 A when superimposed-using backbone atoms or alpha carbon atoms -on the relevant structure coordinates of Table 5 are considered identical and are within the scope of the present invention. In an embodiment, the root mean square deviation is about 1.5 A or about 1 .0 A or about 0.75 A or about 0,5 A or about 0.25 A or about 0.10 A .
The present invention also encompasses any non-crystalline antibody or antigen- binding fragment thereof that, when converted to a Fab antigen-binding fragment format, binds to human PCSK9 in a manner characterized by a three dimensional structure which is characterized by a set of structure coordinates that has a RMSD of conserved residue backbone atoms (N, Ca, C, O) or of alpha carbon atoms (Ca) only of less than about 1 ,5 A when superimposed-using backbone atoms or alpha carbon atoms -on the relevant structure coordinates of Table 5 are considered identical and are within the scope of the present invention. In an embodiment, the root mean square deviation is about 1 .5 A or about 1.0 A or about 0.75 A or about 0.5 A or about 0.25 A or about 0.10 A . JB2010.7161
Examples
The present invention is intended to exemplify the present invention and not to be a limitation thereof. Any method or composition (including any isolated immunoglobulin chain polypeptide or antibody or antigen-binding fragment thereof comprising such a chain, or the CDRs of the chain, or combination or composition or method of use or production thereof as discussed herein) embodied in the Examples section falls within the scope of the present invention.
Example 1: Humanization and optimization of anti-PCSK9 antibodies.
The anti-PCSK9 antibodies of the present invention are the product of extensive efforts involving frequent failures to identify a humanized version of a mouse antibody with acceptable characteristics. The process involved first comparing the mouse anti-PCSK9 antibody sequence to a group of known human germline immunoglobulin sequences. This comparison included assigning the mouse variable region sequences residue numbers according to Kabat; then delineating the CDR and FR regions in the sequence, again, according to Kabat. After the CDRs and FRs were delineated, a predetermined numerical score was assigned to each specific residue position at which the mouse and human antibody germline sequences were identical. After the scores were assigned, a total of all of the residue scores was generated for each human germline sequence. Then, the human germline sequence with the highest total residue score was identified and selected as the human acceptor germline sequence to be used for further humanization. The scores assigned to the matching heavy and light chains are shown below in tables 1 and 2, respectively. Moreover, a numerical score of 1 was assigned for each FR residue position for which the mouse and human antibody germline sequences were identical but not scored according to tables 1 and 2.
The initial humanized antibody, 1259/1260, exhibited no detectable binding to human PCSK9. Typically, such an initially humanized antibody requires only a small number of mutations to the framework region to restore high affinity binding to the antigen. The antibodies in the present invention, however, were extremely sensitive to any mutations in the frameworks. The reason for this sensitivity was likely that the antibody CDRs (in the mouse parental antibody) made extensive contacts with the hPCSK9 antigen. In generally, other antibodies derive most of their avidity for an antigen through the interation of a small number of CDR residues that, in general, are concentrated in heavy chain CDR3. Thus, any given mutation in a variable domain herein is likely to severely perturb the CDR/antigen contact. Indeed, 39 mutant versions of the heavy and light chains were generated in order to reach a KD near that of the parental antibody. These mutations were followed-up by several JB2010.7161 mutations to identify asparagines in the CDRs that could be eliminated without destroying binding to hPCSK9. The presence of asparagines in the CDRs creates the potential of low antibody stability due, for example, to deamination of the residue. Mutation of asparagine 32 to alanine is one example.
Furthermore, the 1 62/1640 antibody was the result of a surprising and unexpected discovery that mutation of threonine 93 in light chain CDR3 to g!utamine increased affinity for hPCSK9 by 774pM units. In short, mutation of T93 generated a non-naturally occurring set of CDRs with high affinity for human PCSK9. This discovery is particularly surprising because CDRs, being the epitope binding moiety of an antibody that is the product of complicated in vivo selection mechanisms can be very sensitive to any changes; particularly non-conservative changes such as threonine to glutamine. Antibody 1462/1378 with light chain mutation VL N32A exhibited a KD of 5514 pM for hPCSK9 whereas 1462/1640, which had the VL N32A T93Q mutations exhibited a KD of 4740 pM for hPCSK9.
JB2010.7161
Table 1. Scores assigned to matching heavy chain immunoglobulin residues
Figure imgf000054_0001
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Table 2. Scores assigned to matching heavy chain immunoglobulin residues
Figure imgf000055_0001
>TC106.1F11.B6_VH
EVQLQQSGPELVKPGASVKISC VSGYTFTDYYMNWVKQSHG SLE IGDINPNNGGAIYNQKFKGKATLT VD SSSIAYMELRSLTSEDSAVYYCTSGIITEI EDFWGQGTTL VSSAKTTAPSVYPL
>TC106.1F11.B€__VL
DIVMTQSQKFMSTSVGDRVSVTC ASQNVGTNWWYQQKPGQSP ALIHSASYRYSGVPDRF GSGSGTDFTLTITNV
JB2010.7161
QSEDLAGFFCQQYKTYPYTFGGGTQLEIKRADAAPTVSIFPPSSEQLTSGGASWCFLNNFYPKDINVKWKIDGSERQ
Heavy Chain
† = 4 points Affects CDR (Chothia et al.) Λ - 3 points Affects CDR Δ = 2 points Interface
t Λ Λ tt f †A Δ Δ ΔΔ ΤΛΛ ΔΛ ΔΛΔ Λ Λ † Λ Δ
VH1
10 20 26 40 50 60 70 80 abc 90
EVQLQQSGPELVKPGASVKISCKVS GYTFTDYYMN WVKQSHGKSLEWIG DINPNNGGA—lYNQKFKG KATLTVDKSSSIAYMELRSLTSEDSAVYYCTS
19 4 4 2 3 3 3
DP-14 QVQLVQSGAEVKKPGASVKVSCKAS GYTFTSYGIS WVRQAPGQGLEWMG WISAYNGNT—NYAQKLQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR f t ΤΔ Δ ΑΛ Δ 4 Λ *
VH3
10 20 26 40 50 60 70 80 abc 90
1F11 EVQLQQSGPELVKPGASVKISCKVS GYTFTDYYMN WVKQSHGKSLEWIG DINPNNGGA- lYNQKFKG KATLTVDKSSSIAYMELRSLTSEDSAVYYCTS 10 4 4 2
DP-46 QVQLVESGGGWQPGRSLRLSCAAS GFTFSSYAMH WVRQAPGKGLEWVA VISYDGSNK- YYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAR
† † †i A ΛΛ Δ Δ Δ Λ Λ ^ ^ Λ Λ †
VH4
10 20 26 40 50 60 70 80 abc 90
1F11 EVQLQQSGPELVKPGASVKISCKVS GYTFTDYYMN WVKQSHGKSLEWIG DINPNNGGA--lYNQKFKG KATLTVDKSSSIAYMELRSLTSEDSAVYYCTS
15 3 33 2 4
DP-71 QVQLQESGPGLVKPSETLSLTCTVS GGSISSYYWS WIRQPPGKGLEWIG YIYYSGS TNYNPSLKS RVTISVDTSKNQFSLKLSSVTAADTAVYYCAR
† † †A Λ ΛΛ Δ †
JB2010.7161
Light Chain
† = 4 points Affects CDR (Chothia et al.) Λ = 3 points Affects CDR Δ = 2 points Interface
VLK I
5 10 20 30 40 50 60 70 80 90
XF11 DrVMTQSQKFMSTSVGDRVSVTC KASQNVG TNW WYQQKPGQSPKALIH SASYRYS GVPDRFKGSGSSTDFTLTITNVQSEDIAGFFC QQYKTYP
12 3 4 3 2
46 II 111 1 111111 11 1111111 11 11 1 1 11 111111111111 1 11 1 1
Z-012 DIQMTQSPSSLSASVGDRVTITC RASQSIS SYLN WYQQKPGKAPKLLIY AASSLQS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTP
10 " † † Δ Δ Δ Λ Δ Δ Δ
VLK II
10 20 30 40 50 60 70 80 90
1F11 DIVMTQSQKFMSTSVGDRVSVTC KASQNVG TNW WYQQKPGQSPKALIH SASYRYS GVPDRFKGSGSGTDFTLTITNVQSEDLAGFFC QQYKTYP
8 3 2 3
Z-A19 DIVMTQSPLSLPVTPGEPASISC RSSQSLLHS-NGYNYLD WYLQKPGQSPQLLIY LGSNRAS GVPDRFSGSGSGTDFTLKISRVEAEDVGVYYC MQALQTP f t Δ Δ Δ Λ Δ Δ Δ
VLK III
10 20 30 40 50 60 70 80 90
1F11 DIVMTQSQKFMSTSVGDRVSVTC KASQNVG TNW WYQQKPGQSPKALIH SASYRYS GVPDRFKGSGSGTDFTLT1TNVQSEDLAGFFC QQYKTYP
12 4 4 2 2
42 II 111 1 1 1 1 1 11111111 1 11 1 1111 111111111111 II 1 1
Z-A27 EIVLTQSPGTLSLSPGERATLSC RASQSVSS SYLA WYQQKPGQAPRLLIY GASSKAT GIPDRFSGSGSGTDFTLTISRLEPEDFAVYYC QQYGSS
† † Δ Δ A Λ Δ Δ Δ
VLK IV
10 20 30 40 50 60 70 80 90
1F11 DIVMTQSQKFMSTSVGDRVSVTC KASQNVG TNW WYQQKPGQSPKALIH SASYRYS GVPDRFKGSGSGTDFTLTITNVQSEDLAGFFC QQYKTYP
30 14 3 4 3 2 2
Z~B3 DIVMTQSPDSLAVSLGERATINC KSSQSVLYSSNNKNYLA WYQQKPGQPPKLLIY WASTRES GVPDRFSGSGSGTDFTLTISSLQAEDVAVYYC QQYYSTP
† t Δ Δ Δ Δ Δ Δ
JB2010.7161
Humanized TC1G6.1F11 Heavy chain
10 20 26 40 50 60 70 80 abc 90
1F11 EVQLQQSGPELVKPGASVKISCKVS GYTFfDYYMN WVKQSHGKSLE IG DINPNKGGAIYNQKFKG KATLTVDKSSSIAYMELRSLTSEDSAVYYCTS hu QVQLVQSGAEVKKPGASVKVSCKAS GYTFTDYYMN WVRQAPGQGLEWMG DINPNNGGAIYNQKFKG RVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR DP-14 QVQLVQSGAEVKKPGASVKVSCKAS GYTFTSYGIS WVRQAPGQGLEWMG WISAYNGNTNYAQKLQG RVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR
GIITEIAEDF WGQGTTLTVSS GIITEXAEDF WGQGTLVTVSS
Humanized TC106.1F11 Light chain
10 20 30 40 50 60 70 80 90
1F11 DIVMTQSQKFMSTSVGDRVSVTC KASQNVGTNW WYQQKPGQSPKALIH SASYRYS GVPDRFKGSGSGTDFTLTITNVQSEDLAGFFC QQYKTYP hu DIQMTQSPSSLSASVGDRVTITC KASQKVGTHW WYQQKPGKAPKLLIY SASYRYS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYKTYP Z-012 DIQMTQSPSSLSASVGDRVTITC RASQSISSYLN WYQQKPGKAPKLLIY AASSLQS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQSYSTP
1F11 YT FGGGTQLEIKRA
hu YT FGQGTKVEIKR
Table 3. Summary of humanized antibody chain optimization.
Individually changing N32Af N32Q, T93Q also provided decent binding
Figure imgf000058_0001
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Figure imgf000059_0001
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Figure imgf000060_0001
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Figure imgf000061_0001
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Figure imgf000062_0001
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Figure imgf000063_0001
JB2010.7161
Figure imgf000064_0001
JB2010.7161
Figure imgf000065_0001
JB2010.7161
Figure imgf000066_0001
* [heavy chain identity] / [light chain identity]
JB2010.7161
Comparison of anti-huPCSK9 variants VH sequences
10 20 30 40 50 60 mulFll EVQLQQSGPELVKPGASVKISCKVS GYTFTDYYMN WV QSHGKSLEWIG DINPNNGGAIYNQKFKG
LPD1259 QVQLVQSGAEVKKPGASVKVSCKAS GYTFTDYYMN WVRQAPGQGLE MG DINPNNGGAIYNQKFKG
LPD1462 QVQLVQSGAEVKKPGASVKVSCKVS GYTFTDYYMN WVRQAPGQGLEWIG DINPNNGGAIYNQKFKG
70 80 90 100 110
mulFll KATLTVDKSSS I YMELRSLTSEDSAVYYCTS GIITEIAEDF WGQGTTLTVSS
LPD1259 RVTMTTDTSTSTAYMELRSLRSDDTAVYYCAR GIITEIAEDF WGQGTLVTVSS
* * * * *
LPD1462 RATLTVDKSTSTAYMELRSLRSDDTAVYYCTS 61ITEIAEDF WGQGTLVTVSS
* differences from LPD1259
Comparison of anti-huPCSK9 variants VL sequences
10 20 30 40 50
mulFll DIVMTQSQKFMSTSVGDRVSVTC KASQNVGTNW WYQQKPGQSPKALIH SASYRYS
LPD1260 DIQ TQSPSSLSASVGDRVTITC KASQNVGTNW WYQQKPGKAPKLLIY SASYRYS
LPD1282 DIQMTQSPSSLSASVGDRVTITC KASQNVGTNW HYQQKPGKAP ALIH SASYRYS
LPD1640 DIQMTQSPSSLSASVGDRVTITC KASQNVGTAW WYQQKPGKAPKALIH SASYRYS
* *
LPD1641 DIQMTQSPSSLSASVGDRVTITC KASQNVGTQW WYQQKPGKAPKALIH SASYRYS
60 70 80 90 100
mulFll GVPDRFKGSGSGTDFTLTITNVQSEDLAGFFC QQYKTYPYT FGGGTQLEIKR
LPD1260 GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYKTYPYT FGQGT VEIKR
LPD1282 GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYKTYPYT FGQGTKVEIKR
LPD1640 GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYKQYPYT FGQGTKVEIKR
*
LPD1641 GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQYKQYPYT FGQGTKVEIKR
* differences from LPD1260 Example 2: Anti-PCSK9 is effective at lowering LDL in cynomolgus monkeys
Eighteen cynomolgus monkeys were given a single dose (1 mpk (intravenous), 3 mpk (subcutaneous) and 10 mpk (intravenous); 5, 8 and 5 monkeys/group, respectively) of antibody LPD1282/LPD1462-lgG2 (1F11-lgG2) or LPD1282/LPD1462-lgG4 (1 F11-lgG4). LDL-c levels in each monkey were assayed once a week. The data from these trials were set forth in figure 1 (A & B). The antibody was very effective in its ability to lower LDL levels in the animals tested. Specifically, the 3 mpk s.c. dose of lgG2 antibody lowered LDL-c by >25% for 29 days; the 10 mpk i.v. dose of lgG2 antibody lowered LDL-c by >25% for 54 days. The monkeys in the 10 mpk dose lgG2 group exhibited up to 70% LDL-c reduction. JB2010.7161
In parallel to the LDL-c measurements described above, plasma of LPD1282/LPD1462-lgG2 (1F11-lgG2) treated Cynomo!gus monkeys was also used for the measurement of lipoprotein a (Lp(a)), a risk factor for coronary heart disease. The
administration of a single 10 mpk dose of LPD1282/LPD1462-lgG2 (1 F11-SgG2) resulted in a dose-dependent decrease in plasma Lp(a) levels reaching Lp(a) reductions of about 45%.
Example 3: Crystal ization of PCSK9/Fab Complex
A PCSK9:Fab complex was generated by incubating a 1.5 molar excess of Fab with PCSK9, followed by purification on a size-exclusion chromatography. 9.9mg/mi PCSK9:Fab complex crystallized in 0.1 M Tris pH 8.5, 2.5M ammonium acetate at 4°C. Crystals were transferred to cryoprotectants consisting of the well solution supplemented with glycerol and flash-frozen in liquid nitrogen. A 2.8 angstrom dataset was collected at the I CA beamline (Argonne National Labs, The Advanced Photon Source) by NAXTRX, INC. Diffraction images were integrated using XDS (Kabsch W: XDS. Acta Cryst 2010, D66: 125-132) and reduced using SCALA (Evans PR: Scaling and assessment of data quality. Acta Cryst 2005, D62: 72- 82) as implemented in autoPROC (Globai Phasing Limited, Cambridge, United Kingdom). The PCSK9:Fab complex structure was solved by molecular replacement with the program Phaser (McCoy AJ, Grosse-Kunstleve RW, Adams PD, Winn D, Storoni LC, Read RJ: Phaser crystaliographic software. J. Appl. Cryst. (2007). 40, 658-674) using the published PCSK9-Fab complex structure (PDB code: 3H42) as the starting model. The complete structure was obtained with multiple rounds of model building with Coot (Emsiey P, Cowtan K: Coot: model- building tools for molecular graphics. Acta Cryst 2004, D60: 2126-2132) and refinement with REFMAC as implemented in CCP4 (Collaborative Computational Project N4: The CCP4 Suite: programs for protein crystallography. Acta Cryst 1994, D50: 760-763) and auto-BUSTER (Bricogne G, Blanc E, Brand! M, Flensburg C, Keller P, Paciorek W, Roversi P, Sharff A, Smart O, Vonrhein C, Womack T. BUSTER version 2.9. Global Phasing Limited, Cambridge, United Kingdom, 2010).
The Fab heavy chain amino acid sequence was:
qvqlvqsgae vkkpgasvkv sckvsgytft dyymnwvrga pgqglewigd inpnnggaiy
nqkfkgratl tvdkststay melrslrsdd tavyyctsgi iteiaedfwg qgtlvtvssa
stkgpsvfpl apsskstsgg taalgclvkd yfpepvtvsw nsgaltsgv tfpavlqssg
lyslssvvtv pssslgtqty icnvnhkpsn tkvdkkvepk scdkthtaaa ypydvpdyag
ghhhhhh
(SEQ ID NO: 18)
The Fab light chain amino acid sequence was:
diqmtqspss lgasvgdrvt itckasqnvg tnvvwyqqkp gkapkalihs asyrysgvps
rfsgsgsgtd ftltisslqp edfatyycqq yktypytfgq gtkveikrtv aapsvfifpp JB2010.7161 sdeqlksgta svvcllnnfy preakvqwkv dnalqsgnsq esvteqdskd styslsstlt
Iskadyekhk vyacevthqg Isspvtksfn rgec
(SEQ iD NO: 19)
The epitope of the Fab was identified by determining Solvent Accessible Surface Area for the complex and the Fab and PCSK9 components separately using the MSMS program.
The antibody had a linear epitope in PCSK9 including residues EDGTRFHRQASKC (amino acids 211-223 of SEQ ID NO:8) wherein residue D212 in this loop was not buried by the Fab. Moreover, atoms of S188, R251 and C255 were also buried by the Fab. Accordingly, the present invention also encompasses any antibody or antigen-binding fragment thereof that contacts PCSK9 in a similar manner.
Interestingly, the antibody binds right at the furin processing site in the PCSK9 catalytic domain (RFHR 215-218 and FH 216-217 is deepest in the binding site).
The solvent accessible surface area of the residues contacted by the Fab were determined. The details of the analysis are as follows in Table 4a.
Table 4a. Solvent Accessible Surface Area Analysis of PCSK9 residues contacted by
Fab
SASA
Atom Residue Chain res # (Angstroms)2
CB SER B 188 0.194
OG SER B 188 3.831
N GLU B 211 1 ,877
CB GLU B 211 9.957
CG GLU B 211 3.194
CD GLU B 211 1.113
OE1 GLU B 211 2.194
OE2 GLU B 211 2.39
0 GLU B 211 1.201
CA GLY B 213 9.276
0 GLY B 213 8.656
N THR B 214 0.32
CA THR B 214 5.218
CB THR B 214 12.502
OG1 THR B 214 14.364
CG2 THR B 214 63.104
N ARG B 215 2.252
CA ARG B 215 0.234
CB ARG B 215 23.302
CG ARG B 215 15.03
CD ARG B 215 27.559
NE ARG B 215 4.967
CZ ARG B 215 3.677
NH1 ARG B 215 56.451
NH2 ARG B 215 35.996
C ARG B 215 0.277
0 ARG B 215 4.895
N PHE B 216 2.161 JB2010.7161
CA PHE B 216 5.646
CB PHE B 216 19.758
CG PHE B 216 0.744
CD1 PHE B 216 24.844
CE1 PHE B 216 28.947
CZ PHE B 216 21.717
CE2 PHE B 216 24.433
CD2 PHE 216 18.125
0 PHE B 216 8.355
N HIS B 217 2.963
CA HIS B 217 10.111
CB HIS B 217 24.067
CG HIS B 217 1.453
ND1 HIS B 217 13.511
CE1 HIS B 217 39.592
NE2 HIS B 217 23.093
CD2 HIS B 217 22.075
C HIS B 217 1.35
0 HIS B 217 25.77
N ARG B 218 0.023
CA ARG B 218 2.007
CB ARG B 218 4,677
CG ARG B 218 0.271
CD ARG B 218 1.259
NH2 ARG B 218 2.816
C ARG B 218 1.556
0 ARG B 218 17.709
N GLN B 219 2.999
CA GLN B 219 5.934
CB GLN B 219 0.014
CG GLN B 219 13,418
CD GLN B 219 1.977
0E1 GLN B 219 15.489
NE2 GLN B 219 36.57
0 GLN B 219 2.704
N ALA B 220 2.61
CA ALA B 220 10.057
CB ALA B 220 70.497
O ALA B 220 4.422
N SER B 221 4.907
CB SER B 221 5.592
OG SER B 221 7.967
O SER B 221 13.701
CA LYS B 222 2.8
CD LYS B 222 13.474
CE LYS B 222 0.772
NZ LYS B 222 21.01
O LYS B 222 6.728
CB CYS B 223 10.067
SG CYS B 223 19.876
CZ ARG B 251 0.104
NH1 ARG B 251 5.792 JB2010.7161
NH2 ARG B 251 1.41
CB CYS B 255 0.947
SG CYS B 255 8.407
Total 953.309
In addition, the solvent accessible surface area of the residues in the Fab that were contated by the PCSK9 were determined. The details of the analysis are as follows in Table 4b.
Tabie 4b. Solvent Accessible Surface Area Analysis Fab Heavy Chain Residues Contacted by PCSK9.
SASA
Atom Residue Chain res # (Angstroms)2
O TH H 30 4.382
CA ASP H 31 4.967
CB ASP H 31 2.194
CG ASP H 31 5.648
OD1 ASP H 31 3.838
OD2 ASP H 31 2.481
C ASP H 31 0.401
O ASP H 31 23.553
CA TYR H 32 2.871
OH TYR H 32 4.798
CE2 TYR H 32 5.747
CD2 TYR H 32 0.543
C H 32 0.181
N TYR H 33 1.607
CB TYR H 33 7.321
CG TYR H 33 0.323
CD1 TYR H 33 3.422
CE1 TYR H 33 12.874
02 H 33 3.993
OH TYR H 33 39.555
CE2 TYR H 33 36.443
CD2 TYR H 33 23.811
O TYR H 33 0.809
CB ASN H 35 0.904
CG ASN H 35 0.994
OD1 ASN H 35 0.083
ND2 ASN H 35 25.93
CG2 VAL H 37 4.043
CD1 TRP H 47 1.09
CB ASP H 50 0.135
CG ASP H 50 0.738
OD1 ASP H 50 3.208
OD2 ASP H 50 2.851
CA ILE H 51 0.054
C ILE H 51 0.023
N ASN H 52 0.318
CB ASN H 52 5.382 JB2010.7161
CG ASN H 52 0.107
OD1 ASN H 52 0.582
ND2 ASN H 52 34.072
CD PRO H 53 1.819
CB ASN H 54 20.022
CG ASN H 54 2.974
OD1 ASN H 54 15.294
ND2 ASN H 54 21.41
C ASN H 54 0.063
0 ASN H 54 0.068
CB ASN H 55 17.971
CG ASN H 55 2.302
0D1 ASN H 55 23.791
ND2 ASN H 55 1.395
CA GLY H 57 5.887
C GLY H 57 1.81
0 GLY H 57 4.786
0 ALA H 58 0.091
CG1 ILE H 59 4.073
CD1 !LE H 59 37.348
NZ LYS H 74 9.482
0G1 THR H 97 4.773
CG2 THR H 97 4.862
CA SER H 98 0.139
C H 98 2.052
o SER H 98 0.606
N GLY H 99 3.262
CA GLY H 99 10.731
C GLY H 99 3.022
O GLY H 99 10.476
N ILE H 100 1.311
CA !LE H 100 3.559
CG1 ILE H 100 1.927
CD1 ILE H 100 42.957
N ILE H 101 3.028
CB ILE H 101 4.81
CG1 ILE H 101 4.517
CD1 ILE H 101 17.217
0 ILE H 101 1651
CB ASP H 107 6,077
NE1 TRP H 109 0.213
CH2 TRP H 109 0.203
CZ2 TRP H 109 0.381
Total 570.636
Table 4c. Solvent Accessible Surface Area Analysis Fab Light Chain Resid Contacted by PCSK9.
res SASA
Atom Residue Chain # (Angstroms)2
ND2 ASN L 32 2.816
CB VAL L 34 1.037 JB2010.7161
CG1 VAL L 34 2.453
cz TYR L 36 0.027
OH TYR L 36 24.157
CE2 TYR L 36 1.585
CB ALA L 46 0.353
OH TYR L 55 13.035
OE1 GLN L 89 1.996
NE2 GLN L 89 4.021
CB TYR L 91 4.361
CG TYR L 91 0.479
CD1 TYR L 91 2.513
CE1 TYR L 91 0.885
CE2 TYR L 91 2.809
CD2 TYR L 91 14.042
0 TYR L 91 12.163
C LYS L 92 0.171
0 LYS L 92 18.27
CA THR L 93 4.262
C THR L 93 0.506
N TYR I 94 0.01 1
CD1 TYR L 94 8.902
CE1 TYR L 94 19.905
CZ TYR L 94 0.609
OH TYR L 94 18.222
ΟΕΞ 1 TYR L 96 3,29
cz TYR L 96 0.445
OH TYR L 96 27.579
CE2 TYR L 96 6.16
CD2 TYR L 96 2.757
CZ PHE L 98 1.218
CE2 PHE L 98 0.007
Total 201.046
The crystal the was produced was in space group P2i2i2 and comprised the unit cell dimensions: a=114.007 A, b= 135.131 A, c= 106.710 A, and α=90°, β=90°; γ=90°.
The structural coordinates for the complex were as follows:
Table 5, Structural Coordinates of PCSK9/Fab Complex
The coordinates set forth be!ow are in pdb format. The data in each column (from left to right) correspond to the following: Column 1 : type of record
Column 2: atom serial number
Column 3: atom name
Column 4: residue name
Column 5: chain ID ( A, B, H, L ...) JB201G.7161
Column 6: residue sequence number
Column 7-9: coordinates x, y, z
Column 10: occupancy
Column 11 : B factor
Column 12: atom type
ATOM 1 N ILE B 154 : 28.317 31.253 42.547 1.00 56.19
ATOM 2 CA !LE B 154 27.916 30.874 41.186 1.00 55.71
ATOM 3 CB ILE B 154 27.760 32.116 40.221 1.00 58.17
ATOM 4 CG1 ILE B 154 26.330 32.716 40.268 1.00 58.51
ATOM 5 CD1 ILE B 154 25.051 31.683 40.096 1.00 60.57
ATOM 6 CG2 ILE B 154 28.210 31.857 38.773 1.00 57.45
ATOM 7 C ILE B 154 : 28.866 29.782 40.678 1.00 54.71
ATOM 8 O ILE B 154 30.081 29.915 40.906 1.00 54.69
ATOM 9 N PRO B 155 28.327 28.697 40.026 1.00 46.55
ATOM 10 CA PRO B 155 29.192 27.613 39.533 1.00 45.18
ATOM 11 CB PRO B 155 28.216 26.710 38.776 1.0046.28
ATOM 12 CG PRO B 155 26.919 26.967 39.376 1.00 46.35
ATOM 13 CD PRO B 155 26.912 28.416 39.705 1.00 47.61
ATOM 14 C PRO B 155 30.262 28.149 38.612 1.00 44.08
ATOM 15 O PRO B 155 29.951 28.973 37.755 1.00 44.15
ATOM 16 N TRP B 156 31.520 27.714 38.802 1 .00 40.49
ATOM 17 CA TRP B 156 32.648 28.173 37.983 1.00 39.31
ATOM 18 CB TRP B 156 33.923 27.378 38.298 1.00 36.37
ATOM 19 CG TRP B 156 34.007 26.008 37.697 1.00 33.26
ATOM 20 CD1 TRP B 156 33.706 24.823 38.298 1.00 31.38
ATOM 21 NE1 TRP B 156 33.924 23.781 37.425 1.00 29.38
ATOM 22 CE2 TRP B 156 34.404 24.284 36.244 1.00 28.24
ATOM 23 CD2 TRP B 156 34.478 25.687 36.385 1.00 29.52
ATOM 24 CE3 TRP B 156 34.940 26.458 35.299 1 ,00 28.48
ATOM 25 CZ3 TRP B 156 35.292 25.813 34.125 1.00 29.04
ATOM 26 CH2 TRP B 156 35.228 24.415 34.023 1.00 29.29
ATOM 27 CZ2 TRP B 156 34.792 23.631 35.071 1.00 28.71
ATOM 28 C TRP B 156 32.344 28.176 36.473 1.00 39.29
ATOM 29 O TRP B 156 32.636 29.160 35.783 1.00 39.17
ATOM 30 N ASN B 157 31.727 27.068 35.991 1.00 36.89
ATOM 31 CA ASN B 157 31.360 26.819 34.611 1.00 36.84
ATOM 32 CB ASN B 157 30.732 25.451 34.493 1.00 36.63
ATOM 33 CG ASN B 157 29.743 25.094 35.568 1.00 35.73
ATOM 34 OD1 ASN B 157 30.066 25.068 36.776 1.00 32.71
ATOM 35 ND2 ASN B 157 28.509 24.773 35.133 1.00 32.55
ATOM 36 C ASN B 157 30.466 27.879 33.998 1.00 37.31
ATOM 37 O ASN B 157 30.564 28.151 32.801 1.00 37.07
ATOM 38 N LEU B 158 29.597 28.476 34.822 1.00 37.32
ATOM 39 28.656 29.500 34.417 1.00 37.84
ATOM 40 CB LEU B 158 27.438 29.495 35.339 1.00 37.32
ATOM 41 CG LEU B 158 26.592 28.204 35.344 1.00 36.24
ATOM 42 CD1 LEU B 158 25.283 28.427 36.079 1.00 35.08
ATOM 43 CD2 LEU B 158 26.305 27.691 33.930 1.00 32.60
ATOM 44 C LEU B 158 29.302 30.865 34.353 1 ,00 39.13
ATOM 45 O LIEU E¾ 158 28.932 31.675 33.491 1.00 39.06 JB2010.7161
ATOM 46 N GLU B 159 30.272 31.131 35.260 1.00 41.63 N
ATOM 47 CA GLU B 159 31.005 32.401 35.270 1.0043.23 C
ATOM 48 CB GLU B 159 31.881 32.546 36.536 1.00 44.68 C
ATOM 49 C GLU B 159 31.862 32.375 34'.018 1.00 44.18 C ATOM 50 O GLU B 159 31.942 33.369 33.304 1.00 43.95 O
ATOM 51 N ARG B 160 32.440 31.189 33.731 1.00 47.75 N
ATOM 52 CA ARG B 160 33.296 30.880 32.583 1.00 50.06 C
ATOM 53 CB ARG B 160 33.760 29.408 32.614 1.00 51.23 C
ATOM 54 CG ARG B 160 35.071 29.132 31.862 1.00 52.53 C ATOM 55 CD ARG B 160 36.233 30.047 32.255 1.00 53.96 C
ATOM 56 NE ARG B 160 36.406 30.119 33.706 1.00 56.52 N
ATOM 57 CZ ARG B 160 37.268 29.387 34.403 1 .00 57.09 C
ATOM 58 NH1 ARG B 160 38.071 28.527 33.789 1.00 57.68 N
ATOM 59 NH2 ARG B 160 37.332 29.507 35.719 1.00 55.92 N ATOM 60 C ARG B 160 32.653 31.246 31.249 1.00 51.22 C
ATOM 61 O ARG B 160 33.255 32.015 30.487 1.00 50.83 O
ATOM 62 N ILE B 161 31.428 30.727 30.985 1.00 52.92 N
ATOM 63 CA ILE B 161 30.699 31.019 29.744 1.00 55.02 C
ATOM 64 CB ILE B 161 29.757 29.866 29.248 1.00 56.79 C ATOM 65 CG1 iLE B 161 28.552 29.596 30.182 1.00 56.35 C
ATOM 66 CD1 ILE B 161 27.342 30.491 29.984 1.00 56.04 C
ATOM 67 CG2 ILE B 161 30.536 28.581 28.944 1.00 56.38 C
ATOM 68 C iLE B 161 30.088 32.449 29.685 1.00 56.72 C
ATOM 69 0 ILE B 161 29.686 32.889 28.614 1.00 56.90 O ATOM 70 N THR B 162 30.027 33.160 30.823 1.00 62.49 N
ATOM 71 CA THR B 162 29.468 34.512 30.897 1.00 65.13 C
ATOM 72 CB THR B 162 28.458 34.649 32.057 1.00 73.89 C
ATOM 73 0G1 THR B 162 27.334 33.799 31.778 1.00 74.67 O
ATOM 74 CG2 THR B 162 27.982 36.084 32.261 1.00 73.38 C ATOM 75 C THR B 162 30.572 35.577 30.766 1.00 66.78 C
ATOM 76 0 THR B 162 31.411 35.703 31.667 1.00 66.92 O
ATOM 77 N PRO B 163 30.579 36.338 29.633 1.00 70.98 N
ATOM 78 CA PRO B 163 31.645 37.337 29.398 1.00 72.10 C
ATOM 79 CB PRO B 163 31.521 37.583 27.888 1.00 73.83 C ATOM 80 CG PRO B 163 30.071 37.462 27.639 1 .00 73.69 C
ATOM 81 CD PRO B 163 29.653 36.283 28.478 1.00 72.86 C
ATOM 82 C PRO B 163 31.563 38.653 30.206 1.00 73.21 C
ATOM 83 O PRO B 163 30.654 38.795 31.036 1.00 73.25 O
ATOM 84 N PRO B 164 32.490 39.641 29.986 1.00 75.37 N ATOM 85 CA PRO B 164 32.386 40.915 30.721 1.00 75.69 C
ATOM 86 CB PRO B 164 33.803 41.513 30.609 1.00 77.66 C
ATOM 87 CG PRO B 164 34.622 40.531 29.778 1.00 77.42 C
ATOM 88 CD PRO B 164 33.642 39.676 29.056 1.00 77.31 C
ATOM 89 C PRO B 164 31.341 41.841 30.073 1.00 75.80 C ATOM 90 O PRO B 164 30.142 41.773 30.375 1.00 75.87 O
ATOM 91 N SER B 178 12.478 33.686 19.780 1.00 65.27 N
ATOM 92 CA SER B 178 12.070 32.888 20.933 1.00 65.26 C
ATOM 93 CB SER B 178 11.062 33.646 21.797 1.00 68.67 C
ATOM 94 OG SER B 178 11.687 34.613 22.629 1.00 69.76 O ATOM 95 C SER B 178 11.582 31.452 20.581 1.00 65.21 C
ATOM 96 O SER B 178 1 1.414 31.111 19.399 1.00 65.44 O
ATOM 97 N LEU B 179 11.362 30.630 21.639 1.00 60.62 N
ATOM 98 CA LEU B 179 10.957 29.221 21 .653 1.00 59.74 C
ATOM 99 CB LEU B 179 9.452 28.923 21.662 1.0060.10 C JB2010.7161
ATOM 100 CG LEU B 179 9.003 27.580 22.353 1.00 61.93 C
ATOM 101 CD1 LEU B 179 9.707 27.333 23.710 1.00 61.81 C
ATOM 102 CD2 LEU B 179 9.131 26.345 21.417 1.00 62.04 C
ATOM 103 C LEU B 179 11.770 28.268 20.784 1.00 58.51 C ATOM 104 O LEU B 179 11.412 27.931 19.651 1.00 58.50 O
ATOM 105 N VAL B 180 12.870 27.819 21.381 1.00 51.89 N
ATOM 106 CA VAL B 180 13.823 26.886 20.831 1.00 50.15 C
ATOM 107 CB VAL B 180 15.260 27.402 21.046 1.00 52.16 C
ATOM 108 CG1 VAL B 180 16.297 26.408 20.527 1.00 51.97 C ATOM 109 CG2 VAL B 180 15.436 28.757 20.393 1.00 52.60 C
ATOM 110 C VAL B 180 13.600 25.571 21.549 1.00 49.32 C
ATOM 1 11 O VAL B 180 13.451 25.541 22.779 1.00 48.68 O
ATOM 112 N GLU B 181 13.572 24.489 20.765 1.00 47.42 N
ATOM 113 CA GLU B 181 13.435 23.145 21.288 1.00 46.57 C ATOM 114 CB GLU B 181 12.488 22.287 20.430 1.00 49.53 C
ATOM 115 CG GLU B 181 11.002 22.576 20.648 1.00 52.32 C
ATOM 116 CD GLU B 181 10.384 22.268 22.013 1.00 57.63 C
ATOM 117 OE1 GLU B 181 9.193 22.617 22.205 1.00 59.16 O
ATOM 1 18 OE2 GLU B 181 11 .076 21.696 22.893 1.00 59.29 O ATOM 1 19 C GLU B 181 14.816 22.537 21.354 1.00 45.08 C
ATOM 120 O GLU B 181 15.585 22.648 20.401 1.00 44.86 O
ATOM 121 N VAL B 182 15.151 21.938 22.498 1.00 38.90 N
ATOM 122 CA VAL B 182 16.428 21.261 22.698 1.00 37,50 C
ATOM 123 CB VAL B 182 17.298 21.820 23.850 1.00 38.60 C ATOM 124 CG1 VAL B 182 18.633 21.089 23.917 1.00 37.95 C
ATOM 125 CG2 VAL B 182 17.521 23.317 23.702 1.00 38,17 C
ATOM 126 C VAL B 182 16.144 19.770 22.851 1.00 36.64 C
ATOM 127 O VAL B 182 15.653 19.342 23.897 1.00 36.26 O
ATOM 128 N TYR B 183 16.426 18.983 21.806 1.00 35.33 N ATOM 129 CA TYR B 183 16.226 17.541 21.852 1.00 35.16 C
ATOM 130 CB TYR B 183 16.030 16.972 20.456 1.00 37.15 C
ATOM 131 CG TYR B 183 14.647 17.219 19.913 1.00 37.99 C
ATOM 132 CD1 TYR B 183 13,596 16.360 20.216 1.00 38.14 C
ATOM 133 CE1 TYR B 183 12.320 16.576 19.713 1.00 38,80 C ATOM 134 CZ TYR B 183 12.078 17.670 18.901 1.00 40.15 C
ATOM 135 OH TYR B 183 10.805 17.887 18.425 1.00 41.26 O
ATOM 136 CE2 TYR B 183 13.112 18.536 18.578 1.00 40.48 C
ATOM 137 CD2 TYR B 183 14.387 18.306 19.084 1.00 38.86 C
ATOM 138 C TYR B 183 17.404 16.889 22.536 1 ,00 34.78 C ATOM 139 0 TYR B 183 18.554 17.221 22.248 1.00 34.74 O
ATOM 140 N LEU B 184 17.130 15.972 23.452 1.00 36.76 N
ATOM 141 CA LEU B 184 18.169 15.282 24.204 1.00 36.72 C
ATOM 142 CB LEU B 184 18.074 15.705 25.683 1.00 37.55 C
ATOM 143 CG LEU B 184 19.070 15.124 26.706 1.00 39.48 C ATOM 144 CD1 LEU B 184 20.544 15.312 26.279 1.00 39.85 C
ATOM 145 CD2 LEU B 184 18.811 15.715 28.098 1.00 41.65 C
ATOM 146 C LEU B 184 18.144 13.765 24.003 1.00 36.29 C
ATOM 147 O LEU B 184 17.155 13.114 24.332 1.00 36.02 O
ATOM 148 N LEU B 185 19.225 13.212 23.434 1.00 37.59 N ATOM 149 CA LEU B 185 19.370 11.767 23.185 1.00 37.79 C
ATOM 150 CB LEU B 185 19.905 11.473 21.760 1.00 38.71 C
ATOM 151 CG LEU B 185 18,904 11.656 20.615 1.00 38.40 C
ATOM 152 CD1 LEU B 185 18.937 13.060 20.117 1 .00 38.50 C
ATOM 153 CD2 LEU B 185 19.226 10.757 19.472 1.00 35.37 C JB2010.7161
ATOM 154 C LEU B 185 20.300 11.219 24.253 1.00 37.59 C
ATOM 155 0 LEU B 185 21.501 11.445 24.203 1.00 37.87 0
ATOM 156 N ASP B 186 19.738 10.549 25.246 1.00 38.26 N
ATOM 157 CA ASP B 186 20.497 10.060 26.386 1.00 38.66 C ATOM 158 CB ASP B 186 20.650 11.241 27.387 1.00 42.84 C
ATOM 159 CG ASP B 186 21.888 11.208 28.269 1.00 46.27 C
ATOM 160 OD1 ASP B 186 22.652 12.172 28.242 1.00 50.92 O
ATOM 161 OD2 ASP B 186 22.085 10.210 28.994 1.00 48.76 O
ATOM 162 C ASP B 186 19.751 8.908 27.085 1.00 38.23 C ATOM 163 0 ASP B 186 18.976 8.165 26.464 1.00 38.05 O
ATOM 164 N THR B 187 20.001 8.794 28.397 1.00 36.22 N
ATOM 165 CA THR B 187 19.426 7.856 29.337 1.00 35.69 C
ATOM 166 CB THR B 187 20.325 7.762 30.606 1.00 29.22 C
ATOM 167 OG1 THR B 187 20.386 9.034 31.242 1.00 29.73 O ATOM 168 CG2 THR B 187 21.738 7.279 30.324 1.00 27.30 C
ATOM 169 C THR B 187 18.059 8.448 29.701 1.00 36.05 C
ATOM 170 O THR B 187 17.708 9.537 29.217 1.00 35.93 O
ATOM 171 N SER B 188 17.286 7.732 30.548 1.00 36.17 N
ATOM 172 CA SER B 188 15.996 8.181 31.067 1.00 36.55 C ATOM 173 CB SER B 188 15.473 7.181 32.106 1.00 42.42 C
ATOM 174 OG SER B 188 15.032 5.918 31.622 1.00 43.82 O
ATOM 175 C SER B 188 16.322 9.469 31.816 1.00 36.52 C
ATOM 176 0 SER B 188 17.484 9.705 32.165 1.00 36.24 O
ATOM 177 N ILE B 189 15.330 10.308 32.067 1.00 37.53 N ATOM 178 CA ILE B 189 15.607 11.525 32.815 1.00 38.09 C
ATOM 179 CB ILE B 189 15.785 12.810 31.931 1.00 40.74 C
ATOM 180 CG1 ILE B 189 14.517 13.555 31.678 1.00 41.66 C
ATOM 181 CD1 ILE B 189 14.558 14.830 32.473 1.00 43.52 C
ATOM 182 CG2 ILE B 189 16.614 12.660 30.656 1.00 39.57 C ATOM 183 C ILE B 189 14.585 11.662 33.943 1.00 38.44 C
ATOM 184 O ILE B 189 13.428 11.282 33.763 1.00 38.88 O
ATOM 185 N GLN B 190 14.986 12.175 35.103 1 .00 39.35 N
ATOM 186 CA GLN B 190 14.029 12.371 36.186 1.00 40.06 C
ATOM 187 CB GLN B 190 14.702 12.229 37.557 1.00 42.50 C ATOM 188 CG GLN B 190 13.712 11.940 38.675 1.00 45.13 C
ATOM 189 CD GLN B 190 14.130 12.659 39.922 1.00 49.63 C
ATOM 190 OE1 GLN B 190 15.214 12.422 40.471 1.00 50.91 O
ATOM 191 NE2 GL B 190 13.277 13.569 40.404 1.00 51.34 N
ATOM 192 C GLN B 190 13.414 13.770 35.973 1.00 40.19 C ATOM 193 0 GLN B 190 13.886 14.760 36.535 1.00 39.52 O
ATOM 194 N SE B 191 12.376 13.835 35.1 14 1.00 43.32 N
ATOM 195 CA SER B 191 11.654 15.048 34.708 1.00 44.36 C
ATOM 196 CB SER B 191 10.601 14.713 33.662 1.00 47.92 C
ATOM 197 OG SER B 191 9.747 13.687 34.137 1.0048.92 O ATOM 198 C SER B 191 11.041 15.821 35.857 1.0045.15 C
ATOM 199 O SER B 191 10.724 17.007 35.719 1.00 45.78 O
ATOM 200 N ASP B 192 10.903 15.141 36.989 1.00 48.27 N
ATOM 201 CA ASP B 192 10.361 15.595 38.252 1.00 49.04 C
ATOM 202 CB ASP B 192 10.100 14.362 39.115 1.00 54.51 C ATOM 203 CG ASP B 192 8.734 14.383 39.741 1.00 58.26 C
ATOM 204 OD1 ASP B 192 7.735 14.629 38.994 1.00 62.65 O
ATOM 205 OD2 ASP B 192 8.643 14.160 40.982 1.00 62.18 O
ATOM 206 C ASP B 192 11.306 16.496 39.013 1.00 48.59 C
ATOM 207 O ASP B 192 10.830 17.271 39.829 1.00 49.10 O JB2010.7161
ATOM 208 N HIS B 193 12.632 16.381 38.803 1.00 44.34 N
ATOM 209 CA HIS B 193 13.613 17.185 39.524 1 ,00 43.85 C
ATOM 210 CB HIS B 193 15.036 16.969 38.997 1.00 41.87 C
ATOM 211 CG HIS B 193 16.093 17.392 39.973 1.00 39.51 C ATOM 212 ND1 HIS B 193 16.858 16.466 40.648 1.00 38.24 N
ATOM 213 CE1 HIS B 193 17.672 17.164 41.424 1 ,00 36.87 C
ATOM 214 NE2 HIS B 193 17,473 18.467 41.292 1.00 37.59 N
ATOM 215 CD2 HIS B 193 16.467 18.631 40.370 1 .00 38.45 C
ATOM 216 C HIS B 193 13.242 18.659 39.495 1.00 44.58 C ATOM 217 0 HIS B 193 12.900 19.189 38.427 1.00 44.61 O
ATOM 218 N ARG B 194 13.302 19.328 40.667 1.00 46.91 N
ATOM 219 CA ARG B 194 12.936 20.747 40.774 1.00 47.56 C
ATOM 220 CB ARG B 194 12.792 21.212 42.244 1.00 51.91 C
ATOM 221 CG ARG B 194 11.804 20.384 43.137 1.00 55.16 C ATOM 222 CD ARG B 194 10.475 19.909 42.495 1.00 61.43 C
ATOM 223 NE ARG B 194 10.063 18.588 43.015 1.00 66.27 N
ATOM 224 CZ ARG B 194 9.065 17.831 42.540 1.00 67.73 C
ATOM 225 NH1 ARG B 194 8.338 18.245 41.502 1.00 67.02 N
ATOM 226 NH2 ARG B 194 8.786 16,658 43.103 1.00 67.84 N ATOM 227 C ARG B 194 13.720 21.721 39.874 1.00 46,92 C
ATOM 228 0 ARG B 194 13.260 22.845 39.648 1.00 46.79 O
ATOM 229 N GLU B 195 14,862 21.267 39.317 1.00 43.68 N
ATOM 230 CA GLU B 195 15.718 22.057 38.424 1.00 43.16 C
ATOM 231 CB GLU B 195 17.071 21.370 38.257 1.00 44.73 C ATOM 232 CG GLU B 195 18.141 21.831 39.201 1.00 47.08 C
ATOM 233 CD GLU B 195 18.792 23.148 38.833 1.00 50.73 C
ATOM 234 OE1 GLU B 195 18.300 24.188 39.328 1.00 52.55 O
ATOM 235 OE2 GLU B 195 19.798 23.142 38.080 1.00 51.77 O
ATOM 236 C GLU B 195 15.153 22.159 37.039 1.00 42.55 C ATOM 237 0 GLU B 195 15.307 23.185 36.383 1.00 42.32 O
ATOM 238 N 1LE B 196 14.555 21.060 36.570 1.00 41.35 N
ATOM 239 CA ILE B 196 14.061 20.896 35.214 1.00 41.38 C
ATOM 240 CB ILE B 196 14.931 19.801 34.521 1.00 42,69 C
ATOM 241 CG1 ILE B 196 14.941 18.468 35.337 1.00 41.24 C ATOM 242 CD1 ILE B 196 15.340 17.321 34.643 1.00 38.90 C
ATOM 243 CG2 1LE B 196 16.364 20.328 34.229 1.00 42.34 C
ATOM 244 C ILE B 196 12,573 20.594 35.129 1.00 42.14 C
ATOM 245 0 ILE B 196 12.060 20.321 34.036 1.00 41.79 O
ATOM 246 N GLU B 197 11.876 20.647 36.281 1.00 47.04 N ATOM 247 CA GLU B 197 10.434 20.385 36.388 1.0047.79 C
ATOM 248 CB GLU B 197 9.980 20.597 37.863 1.00 50.52 C
ATOM 249 CG GLU B 197 8.555 21.095 38.071 1.00 54.02 C
ATOM 250 CD GLU B 197 8.017 21.147 39.493 1.00 57.95 C
ATOM 251 OE1 GLU B 197 8.207 22.190 40.165 1.00 56.85 O ATOM 252 OE2 GLU B 197 7.391 20,147 39.926 1 ,00 59.53 O
ATOM 253 C GLU B 197 9.697 21.284 35.396 1.00 46.96 C
ATOM 254 0 GLU B 197 9.928 22.486 35.395 1.00 47.11 O
ATOM 255 N GLY B 198 8.889 20.697 34.531 1.00 44.06 N
ATOM 256 CA GLY B 198 8.118 21.450 33.548 1 ,00 43.76 C ATOM 257 C GLY B 198 8.856 21.961 32.324 1.00 44.05 C
ATOM 258 0 GLY B 198 8.215 22.409 31.369 1 ,00 43.96 O
ATOM 259 N ARG B 199 10.200 21.905 32.332 1.00 45.77 N
ATOM 260 CA ARG B 199 11.060 22.342 31.228 1.00 46.06 C
ATOM 261 CB ARG B 199 12.340 22.978 31.789 1.00 51.04 C JB2010.7161
ATOM 262 CG ARG B 199 12.102 24,354 32.372 1.00 53.37 C
ATOM 263 CD ARG B 199 13.256 24.872 33.208 1.00 57.05 C
ATOM 264 NE ARG B 199 12.860 26.116 33.880 1.00 60.73 N
ATOM 265 CZ ARG B 199 13,661 27.158 34,092 1.00 61.99 C ATOM 266 NH1 ARG B 199 13.200 28.245 34.704 1.00 61.77 N
ATOM 267 NH2 ARG B 199 14.931 27.120 33.698 1.00 63.35 N
ATOM 268 C ARG B 199 11 .428 21.176 30.296 1.00 45.99 C
ATOM 269 O ARG B 199 11.844 21.403 29.168 1.00 45.97 O
ATOM 270 N VAL B 200 1 1.281 19,930 30.773 1.0046.52 N ATOM 271 CA VAL B 200 11.633 18.715 30.045 1.00 46.65 C
ATOM 272 CB VAL B 200 12.782 17.949 30.746 1.0049.03 C
ATOM 273 CG1 VAL B 200 13.263 16.786 29.889 1.00 47.84 C
ATOM 274 CG2 VAL B 200 13.933 18,886 31.056 1 .00 49.21 C
ATOM 275 C VAL B 200 10.445 17.808 29.781 1.00 47.31 C ATOM 276 O VAL B 200 9,881 17.208 30.707 1.0047.48 O
ATOM 277 N ET B 201 10,1 11 17.668 28.506 1.00 48.82 N
ATOM 278 CA MET B 201 9.022 16.832 28.052 1.00 49.57 C
ATOM 279 CB MET B 201 8.328 17.506 26.855 1.00 53.27 C
ATOM 280 CG MET B 201 7.017 16.881 26.481 1 ,00 58.84 C ATOM 281 SD MET B 201 7.170 15.692 25.118 1.00 71.69 S
ATOM 282 CE MET B 201 5.629 14.708 25.388 1.00 69.24 C
ATOM 283 C MET B 201 9.617 15.485 27.665 1.00 48.81 C
ATOM 284 O MET B 201 10.374 15.410 26.703 1.00 49.50 O
ATOM 285 N VAL B 202 9.290 14.424 28.413 1.00 45.36 N ATOM 286 CA VAL B 202 9.771 13.075 28.131 1.00 44.08 C
ATOM 287 CB VAL B 202 9.646 12.192 29.389 1.00 46.30 C
ATOM 288 CG1 VAL B 202 9.81 1 10.716 29,050 1.00 45.75 C
ATOM 289 CG2 VAL B 202 10.646 12,613 30.450 1.00 45.52 C
ATOM 290 C VAL B 202 8.951 12.512 26.956 1.00 44.23 C ATOM 291 O VAL B 202 7.761 12.232 27.120 1.00 43.85 O
ATOM 292 N THR B 203 9.569 12,353 25.775 1.00 44.86 N
ATOM 293 CA THR B 203 8,845 11.811 24.617 1.00 45.44 C
ATOM 294 CB THR B 203 9.605 12.034 23,302 1.00 44.06 C
ATOM 295 OG1 THR B 203 10.751 11.181 23.253 1.00 43.32 O ATOM 296 CG2 THR B 203 9.986 13.495 23.077 1.00 43.96 C
ATOM 297 C THR B 203 8.610 10.338 24.845 1.00 46.14 C
ATOM 298 O THR B 203 9.286 9.743 25.683 1.00 46.86 O
ATOM 299 N ASP B 204 7.691 9.725 24. 16 1.00 48.19 N
ATOM 300 CA ASP B 204 7.495 8.300 24,335 1.00 49.21 C ATOM 301 CB ASP B 204 6.021 7.874 24.148 1.00 54.63 C
ATOM 302 CG ASP B 204 5.423 8.188 22.788 1.00 58.45 C
ATOM 303 OD1 ASP B 204 5.834 9.222 22.171 1.00 63.00 O
ATOM 304 OD2 ASP B 204 4.534 7.413 22.336 1.00 63.46 O
ATOM 305 C ASP B 204 8.524 7.427 23,582 1.00 48.50 C ATOM 306 O ASP B 204 8.417 6.203 23,589 1.00 49.20 O
ATOM 307 N PHE B 205 9.548 8.065 22.986 1.00 44.03 N
ATOM 308 CA PHE B 205 10.617 7.401 22.262 1.00 42.52 C
ATOM 309 CB PHE B 205 1 1.417 8.387 21.389 1.00 42.52 C
ATOM 310 CG PHE B 205 12.424 7.658 20.527 1.00 40.48 C ATOM 311 CD1 PHE B 205 12.068 7.172 19.276 1.00 38.94 C
ATOM 312 CE1 PHE B 205 12.984 6.464 18.502 1.00 39.12 C
ATOM 313 CZ PHE B 205 14,251 6.212 18.986 1 ,00 38.65 C
ATOM 314 CE2 PHE B 205 14.620 6.677 20.226 1.00 37.84 C
ATOM 315 CD2 PHE B 205 13.713 7.402 20.994 1.00 38.56 C JB2010.7161
ATOM 316 C PHE B 205 11.559 6.682 23.209 1.00 42.40 C
ATOM 317 0 PHE B 205 12.047 7.276 24.181 1.00 42.15 O
ATOM 318 N GLU B 206 11.844 5.409 22.881 1.0044.61 N
ATOM 319 CA GLU B 206 12.740 4.533 23.621 1.0044.45 C ATOM 320 CB GLU B 206 11.996 3.893 24.803 1.00 46.70 C
ATOM 321 CG GLU B 206 12.923 3.235 25.809 1.00 49.99 C
ATOM 322 CD GLU B 206 12.269 2.228 26.738 1.00 53.06 C
ATOM 323 OE1 GLU B 206 12.233 2.481 27.969 1.00 52.50 O
ATOM 324 OE2 GLU B 206 11.797 1.181 26.230 1.00 54.67 O ATOM 325 C GLU B 206 13.383 3.458 22.697 1.00 44.07 C
ATOM 326 0 GLU B 206 12.682 2.644 22.096 1.00 44.32 O
ATOM 327 N ASN B 207 14.714 3.482 22.571 1.00 43.38 N
ATOM 328 CA ASN B 207 15.453 2.506 21.785 1.0042.65 C
ATOM 329 CB ASN B 207 15.597 2.897 20.314 1.00 48.25 C ATOM 330 CG ASN B 207 15.859 1.707 19.406 1.0048.63 C
ATOM 331 OD AS B 207 16.781 0.900 19.621 1.00 49.03 O
ATOM 332 ND2 ASN B 207 15.048 1.569 18.364 1.00 47.20 N
ATOM 333 C ASN B 207 16.795 2.269 22.451 1.00 42.27 C
ATOM 334 O ASN B 207 17.782 2.947 22.153 1.00 42.07 O ATOM 335 N VAL B 208 16.823 1.308 23.390 1.00 40.86 N
ATOM 336 CA VAL B 208 18.045 0.991 24.129 1.0040.32 C
ATOM 337 CB VAL B 208 17.962 1.374 25.645 1.00 42.06 C
ATOM 338 CG1 VAL B 208 17.567 2.826 25.842 1.00 41.33 C
ATOM 339 CG2 VAL B 208 17.030 0.466 26.419 1.00 41.60 C ATOM 340 C VAL B 208 18.516 -0.458 23.917 1.00 40.24 C
ATOM 341 0 VAL B 208 17.675 -1.362 23.772 1 .00 40.14 O
ATOM 342 N PRO B 209 19.844 -0.7 7 23.920 1.00 38.98 N
ATOM 343 CA PRO B 209 20.304 -2.100 23.802 1.00 39.09 C
ATOM 344 CB PRO B 209 21.775 -1.942 23.407 1.00 39.53 C ATOM 345 CG PRO B 209 22.193 -0.691 23.982 1.00 39.11 C
ATOM 346 CD PRO B 209 20.986 0.206 24.079 1.00 39.79 C
ATOM 347 C PRO B 209 20.183 -2.826 25.142 1.00 39.80 C
ATOM 348 O PRO B 209 20.062 -2.203 26.200 1.00 40.14 O
ATOM 349 N GLU B 210 20.261 -4.152 25.093 1.00 45.69 N ATOM 350 CA GLU B 210 20.226 -5.034 26.257 1.00 46.83 C
ATOM 351 CB GLU B 210 20.263 -6.495 25.798 1.00 49.62 C
ATOM 352 CG GLU B 210 18.983 -6.933 25.105 1.00 53.51 C
ATOM 353 CD GLU B 210 18.912 -8.401 24.734 1.00 58.79 C
ATOM 354 OE1 GLU B 210 19.985 -9.049 24.630 1.00 59.31 O ATOM 355 OE2 GLU B 210 17.775 -8.901 24.543 1.00 60.78 O
ATOM 356 C GLU B 210 21.444 -4.742 27.135 1.00 46.45 C
ATOM 357 O GLU B 210 22.454 -4.210 26.644 1.0046.86 O
ATOM 358 N GLU B 211 21.348 -5.062 28.425 1.00 45.73 N
ATOM 359 CA GLU B 211 22.447 -4.812 29.344 1.0045.67 C ATOM 360 CB GLU B 211 21.962 -4.893 30.799 1.00 47.98 C
ATOM 361 CG GLU B 211 20.961 -3.821 31.220 1.00 49.10 C
ATOM 362 CD GLU B 211 20.626 -3.731 32.709 1.00 52.91 C
ATOM 363 OE1 GLU B 211 21.052 -4.610 33.505 1.00 52.80 O
ATOM 364 OE2 GLU B 211 19.928 -2.756 33.077 1.00 54.43 O ATOM 365 C GLU B 211 23.615 -5.780 29.082 1.0045.29 C
ATOM 366 O GLU B 21 1 23.403 -6.951 28.755 1.00 45.09 O
ATOM 367 N ASP B 212 24.841 -5.284 29.190 1.00 47.40 N
ATOM 368 CA ASP B 212 26.040 -6.106 29.006 1.00 47.60 C
ATOM 369 CB ASP B 212 27.275 -5.244 28.717 1.00 50.51 C JB2010.7161
ATOM 370 CG ASP B 212 27.435 -4.844 27.261 1.00 53.89 C
ATOM 371 OD1 ASP B 212 26.968 -5.622 26.362 1.00 54.98 0
ATOM 372 OD2 ASP B 212 28.033 -3.758 27.005 1.00 57.06 O
ATOM 373 C ASP B 212 26.243 -6.864 30.299 1.00 47.17 C ATOM 374 0 ASP B 212 25.994 -6.304 31.374 1.00 47.51 O
ATOM 375 N GLY B 213 26.658 -8.126 30.202 1.00 45.49 N
ATOM 376 CA GLY B 213 26.870 -8.953 31.380 1.00 44.30 C
ATOM 377 C GLY B 213 25.573 -9.192 32.114 1.00 43.80 C
ATOM 378 0 GLY B 213 24.498 -9.145 31.500 1.00 44.45 O ATOM 379 N THR B 214 25.650 -9.450 33.422 1.00 40.76 N
ATOM 380 CA THR B 214 24.457 -9.722 34.225 1.00 40.18 C
ATOM 381 CB THR B 214 24.355 -11.202 34.611 1.00 37.31 C
ATOM 382 OG1 THR B 214 25.269 -11.452 35.669 1.00 37.87 O
ATOM 383 CG2 THR B 214 24.600 -12.159 33.441 1.00 36.43 C ATOM 384 C THR B 214 24.407 -8.819 35.444 1.00 39.88 C
ATOM 385 0 THR B 214 25.414 -8.202 35.803 1.00 40.31 O
ATOM 386 N ARG B 215 23.232 -8.756 36.081 1.00 37.17 N
ATOM 387 CA ARG B 215 22.950 -7.937 37.253 1.00 36.38 C
ATOM 388 CB ARG B 215 21.450 -7.633 37.291 1.00 33.60 C ATOM 389 CG ARG B 215 21.018 -6.612 36.277 1.00 32.19 C
ATOM 390 CD ARG B 215 19.544 -6.680 36.110 1.00 30.82 C
ATOM 391 NE ARG B 215 19.043 -5.632 35.221 1.00 31.14 N
ATOM 392 CZ ARG B 215 17.750 -5.425 34.969 1.00 30.54 C
ATOM 393 NH1 ARG B 215 16.825 -6,205 35.518 1.00 30.01 N ATOM 394 NH2 ARG B 215 17,375 -4.441 34.161 1.00 28.49 N
ATOM 395 C ARG B 215 23.340 -8.595 38.564 1.00 36.76 C
ATOM 396 O ARG B 215 23.193 -7.950 39.614 1.00 36.62 O
ATOM 397 N PHE B 216 23.801 -9.876 38.528 1.00 36.33 N
ATOM 398 CA PHE B 216 24.132 -10.634 39.733 1.00 36.82 C ATOM 399 CB PHE B 216 24.694 -12.032 39.479 1.00 36.93 C
ATOM 400 CG PHE B 216 24.572 -12.929 40.696 1.00 37.07 C
ATOM 401 CD1 PHE B 216 23.389 -13.618 40.957 1.00 36.02 C
ATOM 402 CE1 PHE B 216 23,257 -14.402 42.092 1.00 35.44 C
ATOM 403 CZ PHE B 216 24.313 -14.525 42.970 1.00 36.21 C ATOM 404 CE2 PHE B 216 25.496 -13.852 42.735 1.00 36.66 C
ATOM 405 CD2 PHE B 2 6 25.621 -13.050 41.600 1.00 37.32 C
ATOM 406 C PHE B 216 24.842 -9.937 40.850 1.00 37.93 C
ATOM 407 O PHE B 216 28.049 -9.672 40.784 1.00 38.82 O
ATOM 408 N HIS B 217 24.063 -9.669 41.905 1.00 39.43 N ATOM 409 CA HIS B 217 24.479 -9.037 43.154 1.00 39.94 C
ATOM 410 CB HIS B 217 25.166 -10.051 44.092 1.00 39.50 C
ATOM 411 CG HIS B 217 24.245 -11.091 44.655 1.00 39.68 C
ATOM 412 ND1 HiS B 217 24.703 -12.056 45.537 1.00 39.36 N
ATOM 413 CE1 HIS B 217 23.652 -12.807 45.818 1.00 40.00 C ATOM 414 NE2 HIS B 217 22.560 -12.391 45.168 1.00 39.51 N
ATOM 415 CD2 HIS B 217 22.924 -11.299 44.429 1.00 39.53 C
ATOM 416 C HiS B 217 25.244 -7.723 42.984 1.00 40.31 C
ATOM 417 0 HIS B 217 26.156 -7.409 43.761 1.00 40.91 O
ATOM 418 N ARG B 218 24.854 -6.945 41.969 1.0041.54 N ATOM 419 CA ARG B 218 25.444 -5.635 41.715 1.00 42.05 C
ATOM 420 CB ARG B 218 25.598 -5.386 40.220 1.00 39.40 C
ATOM 421 CG ARG B 218 26.623 -6.284 39.598 1.00 40.05 C
ATOM 422 CD ARG B 218 26.768 -6.046 38.125 1.00 41.86 C
ATOM 423 NE ARG B 218 27.997 -6.668 37.634 1.00 46.15 N JB2010.7161
ATOM 424 CZ ARG B 218 29.178 -6.052 37.573 1.00 47.97 C
ATOM 425 NH1 A G B 218 29.296 -4.782 37.954 1.00 49.42 N
ATOM 426 NH2 ARG B 218 30.249 -6.697 37.114 1.00 49.30 N
ATOM 427 C ARG B 218 24.503 -4.613 42.307 1.00 42.82 C ATOM 428 O ARG B 218 23.322 -4.932 42.546 1.00 43.38 O
ATOM 429 N GLN B 219 25.019 -3.393 42.572 1.00 45.01 N
ATOM 430 CA GL B 219 24.211 -2.281 43.076 1 ,00 45.54 C
ATOM 431 CB GLN B 219 25.086 -1.079 43.475 1.00 48.00 C
ATOM 432 CG GLN B 219 25.376 -0.960 44.987 1.00 50.91 C ATOM 433 CD GLN B 219 24.295 -0.286 45.848 1.00 54.99 C
ATOM 434 OE1 GLN B 219 23.283 0.243 45.353 1.00 54.68 O
ATOM 435 NE2 GLN B 219 24.504 -0.279 47.182 1.00 56.91 N
ATOM 436 C GLN B 219 23.317 -1.922 41.899 1 ,00 45.11 C
ATOM 437 0 GLN B 219 23.806 -1.849 40.766 1.00 44.91 O ATOM 438 N ALA B 220 22.010 -1.776 42.158 1.00 43.49 N
ATOM 439 CA ALA B 220 21.004 -1.464 41.153 1.00 43.60 C
ATOM 440 CB ALA B 220 19.602 -1.585 41.745 1.00 43.60 C
ATOM 441 C ALA B 220 21.208 -0.082 40.550 1.00 43.84 C
ATOM 442 0 ALA B 220 21.212 0.910 41.285 1.00 43.82 O ATOM 443 N SER B 221 21.370 -0.018 39.212 1.00 44.09 N
ATOM 444 CA SER B 221 21.533 1.237 38.474 1.0044.95 C
ATOM 445 CB SER B 221 21.718 0.964 36.988 1.00 48.17 C
ATOM 446 OG SER B 221 22.964 0.332 36.761 1.00 50.15 O
ATOM 447 C SER B 221 20.311 2.127 38.648 1.00 45.16 C ATOM 448 0 SER B 221 19,179 1.620 38.716 1.00 44.98 O
ATOM 449 N LYS B 222 20.550 3.452 38.721 1.00 45.67 N
ATOM 450 CA LYS B 222 19.516 4,475 38.847 1.0045.97 C
ATOM 451 CB LYS B 222 20.136 5.789 39.322 1.0048.37 C
ATOM 452 CG LYS B 222 20.321 5.895 40.829 1.00 50.18 C ATOM 453 CD LYS B 222 18.993 6.054 41.647 1.00 55.62 C
ATOM 454 CE LYS B 222 18.097 7.239 41.302 1.00 57.25 C
ATOM 455 NZ LYS B 222 17.071 6.897 40.262 1.00 59.23 N
ATOM 456 C LYS B 222 18.773 4.666 37.494 1.00 45.70 C
ATOM 457 0 LYS B 222 17.563 4.986 37.492 1.00 46.03 O ATOM 458 N CYS B 223 19.512 4.467 36.355 1.00 44.08 N
ATOM 459 CA CYS B 223 19.061 4.542 34.952 1.00 44.19 C
ATOM 460 CB CYS B 223 17.784 3.736 34.731 1.0045.45 C
ATOM 461 SG CYS B 223 17.919 1.988 35,185 1.00 50.48 S
ATOM 462 C CYS B 223 18.936 5.928 34.328 1.00 43.39 C ATOM 463 O CYS B 223 18.811 6.036 33.103 1.00 43.28 O
ATOM 464 N ASP B 224 18.926 6.972 35.160 1.00 41 ,50 N
ATOM 465 CA ASP B 224 18.707 8.335 34.740 1.00 40.78 C
ATOM 466 CB ASP B 224 17.282 8.757 35.157 1.00 41.85 C
ATOM 467 CG ASP B 224 16.935 8.701 36.647 1.00 41.83 C ATOM 468 OD1 ASP B 224 15.755 8.942 36.988 1.00 40.16 O
ATOM 469 OD2 ASP B 224 17.842 8.407 37.469 1.00 42.03 O
ATOM 470 C ASP B 224 19.727 9.324 35,236 1.00 40.15 C
ATOM 471 O ASP B 224 19.563 10.522 35.025 1.00 40.56 O
ATOM 472 N SER B 225 20.781 8.842 35.873 1.00 40.31 N ATOM 473 CA SER B 225 21.849 9.670 36.406 1.00 39.38 C
ATOM 474 CB SER B 225 22.963 8.782 36.951 1 ,00 45.03 C
ATOM 475 OG SER B 225 24,060 9,551 37.417 1.00 47.03 O
ATOM 476 C SER B 225 22.412 10.681 35.389 1.00 38.48 C
ATOM 477 O SER B 225 22.483 11.873 35.686 1.00 38.57 O JB2010.7161
ATOM 478 N HIS B 226 22.803 10.198 34.201 1.00 36.20 N
ATOM 479 CA HIS B 226 23.417 10.977 33.131 1.00 34.86 C
ATOM 480 CB HIS B 226 23.990 9.987 32.106 1.00 36.21 C
ATOM 481 CG HIS B 226 24.963 10.575 31.144 1.00 36.35 C ATOM 482 ND1 HIS B 226 24.602 10.855 29.823 1.00 36.89 N
ATOM 483 CE1 HIS B 226 25.688 1 1.349 29.254 1.00 37.41 C
ATOM 484 NE2 HIS B 226 26.712 11.412 30.122 1.00 36.86 N
ATOM 485 CD2 HIS B 226 26.259 10.914 31.329 1.00 36.10 C
ATOM 486 C HIS B 226 22.485 12.051 32.493 1.00 34.55 C ATOM 487 O HIS B 226 22.840 13.239 32.476 1.00 33.97 O
ATOM 488 N GLY B 227 21.314 11.620 31.993 1.00 32.55 N
ATOM 489 CA GLY B 227 20.313 12.481 31.367 1.00 31.77 C
ATOM 490 C GLY B 227 19.828 13.583 32.284 1.00 31.39 C
ATOM 491 O GLY B 227 19.741 14.749 31.877 1.00 31.44 O ATOM 492 N THR B 228 19.549 13.236 33.541 1.00 30.99 N
ATOM 493 CA THR B 228 19.105 14.205 34.534 1.00 31.11 C
ATOM 494 CB THR B 228 18.653 13.489 35.818 1.00 32.92 C
ATOM 495 OG1 THR B 228 17.596 12.600 35.447 1.00 34.62 O
ATOM 496 CG2 THR B 228 18.176 14.449 36.907 1.00 31.65 C ATOM 497 C THR B 228 20.163 15.321 34.708 1.00 31.22 C
ATOM 498 O THR B 228 19.806 16.508 34.588 1.00 30.99 O
ATOM 499 N HIS B 229 21.452 14.942 34.954 1.00 29.35 N
ATOM 500 CA HIS B 229 22.515 15.925 35.124 1.00 29.15 C
ATOM 501 CB HIS B 229 23.861 15.272 35.415 1.00 29.44 C ATOM 502 CG HIS B 229 24.903 16.248 35.860 1.00 29.07 C
ATOM 503 ND1 HIS B 229 25.653 16.968 34.952 1.00 30.15 N
ATOM 504 CE1 HIS B 229 26.482 17.707 35.672 1.00 30.30 C
ATOM 505 NE2 HIS B 229 26.293 17.528 36.970 1.00 29.59 N
ATOM 506 CD2 HIS B 229 25.287 16.594 37.108 1.00 30.02 C ATOM 507 C HIS B 229 22.634 16.836 33.917 1.00 29.50 C
ATOM 508 O HIS B 229 22.757 18.053 34.088 1.00 30.17 O
ATOM 509 N LEU B 230 22.586 16.254 32.700 1.00 29.41 N
ATOM 510 CA LEU B 230 22.686 16.983 31.437 1.00 28.66 C
ATOM 511 CB LEU B 230 22.979 16.056 30.265 1.00 28.38 C ATOM 512 CG LEU B 230 24.336 15.426 30.354 1.00 27.97 C
ATOM 513 CD1 LEU B 230 24.541 14.497 29.270 1.00 25.94 C
ATOM 514 CD2 LEU B 230 25.407 16.468 30.318 1.00 27.70 C
ATOM 515 C LEU B 230 21.548 17.919 31.152 1.00 28.67 C
ATOM 516 0 LEU B 230 21.838 19.030 30.734 1.00 28.93 O ATOM 517 N ALA B 231 20.258 17.515 31.388 1.00 29.47 N
ATOM 518 CA ALA B 231 19.103 18.417 31.195 1.00 28.90 C
ATOM 519 CB ALA B 231 17.784 17.701 31.505 1.00 29.11 C
ATOM 520 C ALA B 231 19.304 19.606 32.158 1.00 28.35 C
ATOM 521 O ALA B 231 19.001 20.739 31.810 1.00 28.14 O ATOM 522 N GLY B 232 19.866 19.329 33.333 1.00 28.79 N
ATOM 523 CA GLY B 232 20.185 20.306 34.363 1.00 28.97 C
ATOM 524 C GLY B 232 21.195 21.300 33.857 1.00 29.18 C
ATOM 525 O GLY B 232 20.951 22.495 33.958 1.00 29.26 O
ATOM 526 N VAL B 233 22.323 20.829 33.267 1.00 30.12 N ATOM 527 CA VAL B 233 23.364 21.714 32.714 1.00 30.06 C
ATOM 528 CB VAL B 233 24.637 20.979 32.239 1 .00 32.06 C
ATOM 529 CG1 VAL B 233 25.637 21.967 31.660 1.00 30.96 C
ATOM 530 CG2 VAL B 233 25.279 20. 91 33.371 1.00 32.07 C
ATOM 531 C VAL B 233 22.784 22.619 31.623 1.00 30.51 C JB2010.7161
ATOM 532 0 VAL B 233 23.055 23.815 31.631 1.00 30.47 O
ATOM 533 N VAL B 234 21.965 22.059 30.713 1.00 31.79 N
ATOM 534 CA VAL B 234 21.327 22.805 29.627 1.00 32.68 C
ATOM 535 CB VAL B 234 20.620 21.882 28.591 1.00 34.81 C ATOM 536 CG1 VAL B 234 19.995 22.690 27.455 1.00 33.95 C
ATOM 537 CG2 VAL B 234 21.566 20.834 28.038 1.00 34.65 C
ATOM 538 C VAL B 234 20.357 23.890 30.149 1.00 33.80 C
ATOM 539 O VAL B 234 20.540 25.052 29.791 1.00 33.84 O
ATOM 540 N SER B 235 19.326 23.532 30.962 1.00 36.68 N ATOM 541 CA SER B 235 18.357 24.538 31.393 1.00 38.39 C
ATOM 542 CB SER B 235 17.166 24.539 30.439 1.00 44.65 C
ATOM 543 OG SER B 235 16.399 23.365 30.658 1.00 47.13 O
ATOM 544 C SER B 235 17.850 24.471 32.827 1.00 38.82 C
ATOM 545 0 SER B 235 16.696 24.840 33.078 1.00 38.57 O ATOM 546 N GLY B 236 18.691 24.030 33.753 1.00 40.90 N
ATOM 547 CA GLY B 236 18.337 23.953 35.169 1.00 41.69 C
ATOM 548 C GLY B 236 18.075 25.326 35.757 1.00 42.16 C
ATOM 549 O GLY B 236 18.711 26.302 35.357 1.0042.37 O
ATOM 550 N ARG B 237 17.127 25.414 36.691 1.00 42.41 N ATOM 551 C ARG B 237 16.734 26.661 37.347 1.00 42.55 C
ATOM 552 CB ARG B 237 15.541 26.433 38.286 1.00 37.16 C
ATOM 553 CG ARG B 237 14.243 26.390 37.502 1.00 37.07 C
ATOM 554 CD ARG B 237 12.958 26.098 38.277 1.00 36.74 C
ATOM 555 NE ARG B 237 1 1.844 26.084 37.323 1 .00 36.81 N ATOM 556 CZ ARG B 237 11.372 24.992 36.725 1.00 36.93 C
ATOM 557 NH1 ARG B 237 11.857 23.791 37.035 1.00 36.14 N
ATOM 558 NH2 ARG B 237 10.394 25.088 35.836 1.00 34.91 N
ATOM 559 C ARG B 237 17.878 27.376 38.046 1.00 43.46 C
ATOM 560 O ARG B 237 18.045 28.579 37.849 1.00 43.83 O ATOM 561 N ASP B 238 18.669 26.646 38.843 1.00 45.72 N
ATOM 562 CA ASP B 238 19.790 27.209 39.587 1.00 46.73 C
ATOM 563 CB ASP B 238 19.755 26.764 41.061 1.00 50.33 C
ATOM 564 CG ASP B 238 18.535 27.266 41.845 1.00 53.80 C
ATOM 565 OD1 ASP B 238 18.039 28.401 41.541 1.00 56.21 O ATOM 566 OD2 ASP B 238 18.075 26.535 42.769 1.00 56.97 O
ATOM 567 C ASP B 238 21.160 26.973 38.962 1.00 46.57 C
ATOM 568 O ASP B 238 22.042 27.832 39.106 1 ,00 47.20 O
ATOM 569 N ALA B 239 21.350 25.823 38.266 1.00 44.14 N
ATOM 570 CA ALA B 239 22.640 25.485 37.656 1.00 42.92 C ATOM 571 CB ALA B 239 23.208 24.229 38.298 1.00 43.80 C
ATOM 572 C ALA B 239 22.728 25.427 36.113 1.00 42.37 C
ATOM 573 O ALA B 239 23.826 25.263 35.589 1.00 42.62 O
ATOM 574 N GLY B 240 21.613 25.588 35.408 1.00 38.42 N
ATOM 575 CA GLY B 240 21.603 25.566 33.953 1.00 37.88 C ATOM 576 C GLY B 240 22.233 26.755 33.241 1.00 37.87 C
ATOM 577 O GLY B 240 22.398 27.834 33.827 1.00 38.02 O
ATOM 578 N VAL B 241 22.588 26.560 31.949 1.00 36.11 N
ATOM 579 CA VAL B 241 23.191 27.591 31.101 1.00 35.81 C
ATOM 580 CB VAL B 241 24.096 26.980 29.991 1.00 37.02 C ATOM 581 CG1 VAL B 241 24.618 28.039 29.052 1.00 35.93 C
ATOM 582 CG2 VAL B 241 25.254 26.181 30.578 1.00 35.60 C
ATOM 583 C VAL B 241 22.053 28.463 30.543 1.00 36.95 C
ATOM 584 O VAL B 241 22.038 29.679 30.765 1.00 36.91 O
ATOM 585 N ALA B 242 21.090 27.821 29.845 1.00 41.35 N JB2010.7161
ATOM 586 CA ALA B 242 19.911 28.417 29.222 1.00 42.63 C
ATOM 587 CB ALA B 242 19.601 27.686 27.918 1.00 42.58 C
ATOM 588 C ALA B 242 18.738 28.276 30.185 1.00 44.20 C
ATOM 589 0 ALA B 242 17.780 27.563 29.882 1.0044.90 O ATOM 590 N LYS B 243 18.800 28.930 31.344 1.0048.62 N
ATOM 591 CA LYS B 243 17.718 28.837 32.318 1.00 50.34 C
ATOM 592 CB LYS B 243 18.071 29.585 33.629 1.00 53.79 C
ATOM 593 CG LYS B 243 19.406 29.189 34.287 1.00 53.56 C
ATOM 594 CD LYS B 243 19.733 30.081 35.510 1.00 54.82 C ATOM 595 CE LYS B 243 20.913 29.636 36.368 1.00 56.08 C
ATOM 596 NZ LYS B 243 22.219 30.178 35.872 1.00 56.34 H
ATOM 597 C LYS B 243 16.387 29.329 31.669 1.00 51.20 C
ATOM 598 0 LYS B 243 16.117 30.532 31.600 1.00 51.68 O
ATOM 599 N GLY B 244 15.617 28.375 31.149 1.00 52.63 N ATOM 600 CA GLY B 244 14.345 28.610 30.480 1 .00 53.15 C
ATOM 601 C GLY B 244 14.282 28.035 29.074 1 .00 53.85 C
ATOM 602 O GLY B 244 13.679 28.647 28.177 1.00 54.48 O
ATOM 603 N ALA B 245 14.901 26.848 28.860 1.00 51.90 N
ATOM 604 CA ALA B 245 14.899 26.221 27.541 1.00 50.86 C ATOM 605 CB ALA B 245 16.307 25.814 27.142 1.00 51.23 C
ATOM 606 C ALA B 245 13.953 25.031 27.496 1.00 50.43 C
ATOM 607 O ALA B 245 13.855 24.278 28.468 1 .00 50.40 O
ATOM 608 N SER B 246 13.242 24.880 26.375 1.00 48.62 N
ATOM 609 CA SER B 246 12.286 23.806 26.175 1.00 48.13 C ATOM 610 CB SER B 246 11.235 24.227 25.157 1.00 53.41 C
ATOM 61 1 OG SER B 246 10.228 23.241 24.999 1.00 54.20 O
ATOM 612 C SER B 246 13.036 22.547 25.723 1.0047.77 C
ATOM 613 O SER B 246 13.685 22.551 24.679 1.00 48.05 O
ATOM 614 N MET B 247 12.968 21.479 26.520 1.00 45.68 N ATOM 615 CA MET B 247 13.677 20.251 26.207 1.0045.02 C
ATOM 616 CB MET B 247 14.700 19.907 27.286 1.00 47.20 C
ATOM 617 CG MET B 247 15.566 21.070 27.644 1.00 48.80 C
ATOM 618 SD MET B 247 16.771 20.643 28.863 1.00 52.62 S
ATOM 619 CE MET B 247 17.852 19.612 27.843 1.00 51.37 C ATOM 620 C ET B 247 12.783 19.093 25.984 1.00 44.41 C
ATOM 621 O MET B 247 1 1.778 18.925 26.674 1.00 44.30 O
ATOM 622 N ARG B 248 13.166 18.270 25.016 1.00 45.09 N
ATOM 623 CA ARG B 248 12.442 17.058 24.678 1.00 44.40 C
ATOM 624 CB ARG B 248 11.817 17.170 23.284 1.00 49.16 C ATOM 625 CG ARG B 248 10.634 18.102 23.284 1.00 51.36 C
ATOM 626 CD ARG B 248 0.315 18.609 21.917 1.00 57.89 C
ATOM 627 NE ARG B 248 8.908 18.991 21.831 1.00 63.58 N
ATOM 628 CZ ARG B 248 7.936 18.197 21.381 1.00 66.53 C
ATOM 629 NH1 ARG B 248 6.682 18.631 21.341 1.00 68.41 N ATOM 630 NH2 ARG B 248 8.215 16.964 20.954 1.00 68.02 N
ATOM 631 C ARG B 248 13.424 15.903 24.819 1.00 43.15 C
ATOM 632 O ARG B 248 14.496 15.963 24.224 1.00 43.06 O
ATOM 633 N SER B 249 13.108 14.900 25.660 1.00 39.44 N
ATOM 634 CA SER B 249 14.018 13.785 25.863 1.00 38.26 C ATOM 635 CB SER B 249 14.267 13.552 27.348 1.0042.04 C
ATOM 636 OG SER B 249 13.363 12.625 27.919 1.00 43.25 O
ATOM 637 C SER B 249 13.619 12.493 25.122 1.00 37.22 C
ATOM 638 O SER B 249 12.430 12.165 25.031 1.00 37.27 O
ATOM 639 N LEU B 250 14.630 11.779 24.582 1.00 34.33 N JB2010.7161
ATOM 640 CA LEU B 250 14.500 10.509 23.855 1.00 32.92 C
ATOM 641 CB LEU B 250 14.902 10.674 22.379 1.00 31.83 C
ATOM 642 CG LEU B 250 13.944 11.364 21.437 1.00 30.72 C
ATOM 643 CD1 LEU B 250 14.051 12.868 21.539 1.00 30.19 C ATOM 644 CD2 LEU B 250 14.250 10.977 20.065 1.00 30.21 C
ATOM 645 C LEU B 250 15.472 9.549 24.509 1.00 32.84 C
ATOM 646 O LEU B 250 16.661 9.881 24.622 1.00 33.06 O
ATOM 647 N ARG B 251 14.983 8.376 24.960 1.00 33.49 N
ATOM 648 CA ARG B 251 15.823 7.367 25.606 1.00 32.83 C ATOM 649 CB ARG B 251 15.009 6.504 26.568 1.00 30.40 C
ATOM 650 CG ARG B 251 15.907 5.660 27.426 1.00 30.41 C
ATOM 651 CD ARG B 251 15.139 4.857 28.424 1.00 31.19 C
ATOM 652 NE ARG B 251 16.033 4.083 29.290 1.00 31.11 N
ATOM 653 CZ ARG B 251 15.944 2.770 29.455 1.00 31.21 C ATOM 654 NH1 ARG B 251 16.805 2.133 30.247 1.00 31.71 N
ATOM 655 NH2 ARG B 251 15.005 2.077 28.818 1.00 32.33 N
ATOM 656 C ARG B 251 16.579 6.502 24.571 1.00 33.16 C
ATOM 657 0 ARG B 251 15.999 5.600 23.949 1.00 33.20 O
ATOM 658 N VAL B 252 17.871 6.790 24.376 1.00 34.28 N ATOM 659 CA VAL B 252 18.698 6.037 23.419 1.00 34.15 C
ATOM 660 CB VAL B 252 19.273 6.875 22.241 1.00 36.82 C
ATOM 661 CG1 VAL B 252 18.172 7.602 21.472 1.00 35.53 C
ATOM 662 CG2 VAL B 252 20.353 7.839 22.715 1.00 36.21 C
ATOM 663 C VAL B 252 19.782 5.264 24.147 1.00 34.29 C ATOM 664 O VAL B 252 20.463 4.448 23.517 1.00 34.11 O
ATOM 665 N LEU B 253 19.932 5.521 25.480 1.00 34.20 N
ATOM 666 CA LEU B 253 20.929 4.879 26.348 1.00 34.46 C
ATOM 667 CB LEU B 253 21.969 5.866 26.896 1.00 33.61 C
ATOM 668 CG LEU B 253 22.676 6.794 25.921 1.00 32.62 C ATOM 669 CD1 LEU B 253 23.506 7.801 26.683 1.00 30.26 C
ATOM 670 CD2 LEU B 253 23.526 6.015 24.933 1.00 29.95 C
ATOM 671 C LEU B 253 20.283 4.164 27.496 1.00 34.96 C
ATOM 672 O LEU B 253 19.463 4.752 28.203 1.00 35.25 O
ATOM 673 N ASN B 254 20.661 2.872 27.673 1.00 37.31 N ATOM 674 CA ASN B 254 20.170 1.967 28.716 1.00 37.14 C
ATOM 675 CB ASN B 254 20.443 0.505 28.313 1.00 31.05 C
ATOM 676 CG ASN B 254 21.889 0.062 28.355 1.00 30.08 C
ATOM 677 OD1 ASN B 254 22.785 0.812 28.742 1.00 28.40 O
ATOM 678 ND2 AS B 254 22.155 -1.183 27.972 1.00 27.11 N ATOM 679 C ASN B 254 20.746 2.330 30.100 1 .00 37.97 C
ATOM 680 O ASN B 254 21.466 3.316 30.227 1.00 37.99 O
ATOM 681 N CYS B 255 20.447 1.521 31.126 1 .00 41.90 N
ATOM 682 CA CYS B 255 20.898 1.723 32.501 1.00 42.96 C
ATOM 683 CB CYS B 255 20.157 0.798 33.450 1.00 44.44 C ATOM 684 SG CYS B 255 18.366 1.032 33.419 1.00 50.06 S
ATOM 685 C CYS B 255 22.406 1.708 32.731 1.00 43.06 C
ATOM 686 0 CYS B 255 22.857 2.117 33.800 1.00 43.52 O
ATOM 687 N GLN B 256 23.189 1.290 31.738 1.00 41.27 N
ATOM 688 CA GLN B 256 24.642 1.287 31.858 1.00 41.43 C ATOM 689 CB GLN B 256 25.254 -0.064 31.465 1.00 43.90 C
ATOM 690 CG GLN B 256 24.460 -1.302 31.886 1.00 46.49 C
ATOM 691 CD GLN B 256 24.839 -2.461 30.991 1.00 49.41 C
ATOM 692 OE1 GLN B 256 24.674 -2.411 29.758 1.00 50.57 O
ATOM 693 NE2 GLN B 256 25.378 -3.519 31.587 1.00 50.97 N JB2010.7161
ATOM 694 C GLN B 256 25.210 2.405 30.985 1.00 41.10 C
ATOM 695 0 GL B 256 26.430 2.512 30.861 1.00 41.47 O
ATOM 696 N GLY B 257 24.323 3.227 30.399 1.00 37.48 N
ATOM 697 CA GLY B 257 24.677 4.367 29.551 1.00 36.34 C ATOM 698 C GLY B 257 25.217 3.969 28.199 1.00 35.74 C
ATOM 699 0 GLY B 257 25.959 4.717 27.572 1.00 35.13 O
ATOM 700 N LYS B 258 24.837 2.785 27.751 1.00 35.27 N
ATOM 701 CA LYS B 258 25.222 2.185 26.495 1.00 34.81 C
ATOM 702 CB LYS B 258 25.589 0.708 26.731 1.00 39.39 C ATOM 703 CG LYS B 258 26.425 0.079 25.641 1.00 43.25 C
ATOM 704 CD LYS B 258 26.330 -1.437 25.695 1.00 49.93 C
ATOM 705 CE LYS B 258 26.025 -2.110 24.356 1.00 53.75 C
ATOM 706 NZ LYS B 258 25.555 -3.535 24.542 1.00 57.23 N
ATOM 707 C LYS B 258 24.032 2.300 25.558 1.00 34.33 C ATOM 708 O LYS B 258 22.869 2.163 25.984 1.00 33.68 O
ATOM 709 N GLY B 259 24.343 2.569 24.293 1.00 35.85 N
ATOM 710 CA GLY B 259 23.363 2.689 23.221 1.00 35.69 C
ATOM 711 C GLY B 259 23.831 1.997 21.962 1.00 35.54 C
ATOM 712 O GLY B 259 24.851 1.292 21.975 1.00 36.08 O ATOM 713 N THR B 260 23.113 2.200 20.864 1.00 33.94 N
ATOM 714 CA THR B 260 23.503 1.621 19.580 1.00 34.36 C
ATOM 715 CB THR B 260 22.554 0.491 19.145 1.00 37.89 C
ATOM 716 OG1 THR B 260 21.189 0.925 19.242 1.00 38.28 O
ATOM 717 CG2 THR B 260 22.754 -0.779 19.943 1.00 36.75 C ATOM 718 C THR B 260 23.504 2.746 18.572 1.00 34.87 C
ATOM 719 0 THR B 260 22.892 3.788 18.833 1.00 35.52 O
ATOM 720 N VAL B 261 24.192 2.556 17.424 1.00 34.11 N
ATOM 721 CA VAL B 261 24.230 3.531 16.329 1.00 33.58 C
ATOM 722 CB VAL B 261 25.313 3.179 15.297 1.00 35.64 C ATOM 723 CG1 VAL B 261 25.158 4.003 14.021 1.00 35.71 C
ATOM 724 CG2 VAL B 261 26.702 3.356 15.895 1.00 34.56 C
ATOM 725 C VAL B 261 22.829 3.556 15.709 1.00 33.98 C
ATOM 726 O VAL B 261 22.280 4.615 15.487 1.00 34.29 O
ATOM 727 N SER B 262 22.236 2.388 15.492 1.00 35.27 N ATOM 728 CA SER B 262 20.902 2.225 14.941 1.00 35.69 C
ATOM 729 CB SER B 262 20.638 0.745 14.682 1.00 40.00 C
ATOM 730 OG SER B 262 20.162 0.050 15.826 1.00 40.95 O
ATOM 731 C SER B 262 19.807 2.816 15.842 1.00 35.74 C
ATOM 732 O SER B 262 18.788 3.266 15.330 1.00 35.54 O ATOM 733 N GLY B 263 20.007 2.784 17.162 1.00 36.27 N
ATOM 734 CA GLY B 263 19.052 3.324 18.134 1.00 36.79 C
ATOM 735 C GLY B 263 19.055 4.836 18.074 1.00 36.72 C
ATOM 736 0 GLY B 263 18.008 5.472 18.099 1.00 36.90 O
ATOM 737 N THR B 264 20.253 5.408 17.950 1.00 35.00 N ATOM 738 CA THR B 264 20.503 6.833 17.819 1.00 35.04 C
ATOM 739 CB THR B 264 22.006 7.098 17.977 1.00 33.88 C
ATOM 740 OG1 THR B 264 22.440 6.518 19.218 1.00 34.18 O
ATOM 741 CG2 THR B 264 22.356 8.587 17.945 1.00 33.50 C
ATOM 742 C THR B 264 19.918 7.291 16.479 1.00 35.13 C ATOM 743 0 THR B 264 19.320 8.354 16.440 1.00 35.10 O
ATOM 744 N LEU B 265 20.069 6.478 15.397 1.00 35.83 N
ATOM 745 CA LEU B 265 19.546 6,718 14.042 1.00 36.08 C
ATOM 746 CB LEU B 265 19.918 5.584 13.091 1.00 35.89 C
ATOM 747 CG LEU B 265 21.267 5.605 12.422 1.00 36.18 C JB2010.7161
ATOM 748 CD1 LEU B 265 21.337 4.486 11.403 1.00 36.42 C
ATOM 749 CD2 LEU B 265 21.512 6.925 11.718 1.00 36.53 C
ATOM 750 C LEU B 265 18.034 6.817 14.073 1.00 36.18 C
ATOM 751 O LEU B 265 17.470 7.783 13.558 1.00 36.28 O ATOM 752 N ILE B 266 17.373 5.836 14.686 1.00 34.77 N
ATOM 753 CA ILE B 266 15.920 5.841 14.803 1.00 35.08 C
ATOM 754 CB ILE B 266 15.427 4.469 15.357 1.00 37.27 C
ATOM 755 CG1 !LE B 266 15.741 3.312 14.350 1.00 36.71 C
ATOM 756 CD1 !LE B 266 15.595 1.901 14.881 1.00 33.04 C ATOM 757 CG2 ILE B 266 13.948 4.501 15.698 1.00 35.91 C
ATOM 758 C ILE B 266 15.514 7.074 15.663 1.00 35.75 C
ATOM 759 O ILE B 266 14.451 7.667 15.450 1.00 36.08 O
ATOM 760 N GLY B 267 16.388 7.463 16.590 1.00 35.70 N
ATOM 761 CA GLY B 267 16.157 8.617 17.445 1.00 36.59 C ATOM 762 C GLY B 267 16.149 9.897 16.639 1.00 37.34 C
ATOM 763 O GLY B 267 15.236 10.714 16.798 1.00 37.23 O
ATOM 764 N LEU B 268 17.172 10.065 15.756 1.00 37.78 N
ATOM 765 CA LEU B 268 17.348 11.222 14.878 1.00 38.90 C
ATOM 766 CB LEU B 268 18.695 11.174 14.140 1.00 37.91 C ATOM 767 CG LEU B 268 19.966 11.206 14.999 1.00 38.82 C
ATOM 768 CD1 LEU B 268 21.170 10.865 14.186 1.00 37.37 C
ATOM 769 CD2 LEU B 268 20.145 12.541 15.720 1.00 38.47 C
ATOM 770 C LEU B 268 16.206 11.305 13.872 1.0040.33 C
ATOM 771 O LEU B 268 15.808 12.410 13.483 1.00 40.83 O ATOM 772 N GLU B 269 15.675 10.137 13.456 1.00 44.92 N
ATOM 773 CA GLU B 269 14.567 10.074 12.516 1.00 46.13 C
ATOM 774 CB GLU B 269 14.377 8.659 11.964 1.0048.61 C
ATOM 775 CG GLU B 269 13.316 8.636 10.885 1.00 51.25 C
ATOM 776 CD GLU B 269 12.863 7.261 10.453 1.00 55.81 C ATOM 777 OE1 GLU B 269 12.169 6.567 11.237 1.00 55.66 O
ATOM 778 OE2 GLU B 269 13.194 6.890 9.307 1.00 58.12 O
ATOM 779 C GLU B 269 13.299 10.588 13.200 1.00 46.10 C
ATOM 780 O GLU B 269 12.552 11.371 12.604 1.00 46.62 O
ATOM 781 N PHE B 270 13.080 10.176 14.455 1 .00 42.97 N ATOM 782 CA PHE B 270 11.942 10.613 15.255 1.00 43.26 C
ATOM 783 CB PHE B 270 11.983 9.943 16.633 1.00 43.18 C
ATOM 784 CG PHE B 270 10.972 10.443 17.625 1.00 41.22 C
ATOM 785 CD1 PHE B 270 9.787 9.754 17.838 1.00 40.53 C
ATOM 786 CE1 PHE B 270 8.848 10.215 18.770 1.00 39.92 C ATOM 787 CZ PHE B 270 9.095 11.364 19.485 1.00 39.71 C
ATOM 788 CE2 PHE B 270 10.271 12.062 19.287 1.0040.80 C
ATOM 789 CD2 PHE B 270 11.211 11.597 18.369 1.0041.21 C
ATOM 790 C PHE B 270 11.950 12.152 15.367 1.00 44.41 C
ATOM 791 O PHE B 270 10.884 12.750 15.360 1.00 44.64 O ATOM 792 N ILE B 271 13.139 12.782 15.461 1.00 45.76 N
ATOM 793 CA ILE B 271 13.290 14.238 15.545 1.00 46.86 C
ATOM 794 CB ILE B 271 14.689 14.632 16.093 1.00 48.73 C
ATOM 795 CG1 ILE B 271 14.847 14.173 17.550 1.00 48.33 C
ATOM 796 CD1 ILE B 271 16.245 14.146 18.009 1.00 47.33 C ATOM 797 CG2 ILE B 271 14.978 16.131 15.944 1.0047.50 C
ATOM 798 C ILE B 271 12.994 14.855 14.175 1.00 48.07 C
ATOM 799 O ILE B 271 12.435 15.946 14.116 1.00 47.94 O
ATOM 800 N ARG B 272 13.372 14.167 13.083 1.00 50.28 N
ATOM 801 CA ARG B 272 13.129 14.657 1 1.733 1.00 52.10 C JB2010.7161
ATOM 802 CB ARG B 272 13.917 13.832 10.700 1.00 52.47 C
ATOM 803 CG ARG B 272 13.665 14.194 9.241 1.00 53.21 C
ATOM 804 CD ARG B 272 13.869 15.656 8.930 1.00 54.19 C
ATOM 805 NE ARG B 272 13.772 15.924 7.498 1.00 56.48 N ATOM 806 CZ ARG B 272 13.632 17.137 6.969 1.00 57.91 C
ATOM 807 NH1 ARG B 272 13.544 18.206 7.754 1.00 59.31 N
ATOM 808 NH2 ARG B 272 13.563 17.290 5.655 1.00 57.87 N
ATOM 809 C ARG B 272 11.619 14.657 1 1.459 1.00 53.55 C
ATOM 810 O ARG B 272 11.097 15.647 10.956 1.00 53.48 O ATOM 811 N LYS B 273 10.923 13.578 11.828 1.00 56.24 N
ATOM 812 CA LYS B 273 9.484 13.473 11.650 1.00 58.21 C
ATOM 813 CB LYS B 273 9.000 12.059 12.000 1.00 62.07 C
ATOM 814 CG LYS B 273 9.413 10.973 10.995 1.00 64.28 C
ATOM 815 CD LYS B 273 8.985 9.592 11.504 1.00 67.88 C ATOM 816 CE LYS B 273 9.351 8.443 10.596 1.00 69.81 C
ATOM 817 NZ LYS B 273 9.023 7.128 1 1.227 1.00 71.24 N
ATOM 818 C LYS B 273 8.770 1 .536 12.509 1.00 58.99 C
ATOM 819 0 LYS B 273 7.794 15.131 12.055 1.00 59.59 O
ATOM 820 N SER B 274 9.280 14.788 13.732 1.00 61.43 N ATOM 821 CA SER B 274 8.766 15.769 14.689 1.00 62.54 C
ATOM 822 CB SER B 274 9.516 15.628 16.010 1.00 64.82 C
ATOM 823 OG SER B 274 8.706 15.845 17.151 1.00 65.66 O
ATOM 824 C SER B 274 8.973 17.199 14.139 1 .00 63.55 C
ATOM 825 0 SER B 274 8.293 18.134 14.567 1.00 64.31 O ATOM 826 N GLN B 275 9.940 17.365 13.216 1.00 65.65 N
ATOM 827 CA GLN B 275 10.296 18.626 12.586 1.00 66.07 C
ATOM 828 CB GLN B 275 11.790 18.613 12.219 1.00 66.19 C
ATOM 829 CG GLN B 275 12.361 19.940 11.745 1.00 64.95 C
ATOM 830 CD GLN B 275 13.648 19.801 10.947 1.00 63.19 C ATOM 831 OE1 GLN B 275 14.044 18.707 10.509 1.00 63.43 O
ATOM 832 NE2 GL B 275 14.328 20.917 10.722 1.00 61.42 N
ATOM 833 C GLN B 275 9.403 18.802 11.360 1.00 67.17 C
ATOM 834 0 GLN B 275 8.842 19.876 11.186 1.00 67.51 O
ATOM 835 N LEU B 276 9.254 17.750 10.524 1.00 71.58 N ATOM 836 CA LEU B 276 8.416 17.768 9.321 1.00 72.77 C
ATOM 837 CB LEU B 276 8.507 16.434 8.549 1.00 72.40 C
ATOM 838 CG LEU B 276 9.819 16.164 7.806 1.00 72.55 C
ATOM 839 CD1 LEU B 276 9.880 14.742 7.315 1.00 71.75 C
ATOM 840 CD2 LEU B 276 10.020 17.123 6.641 1.00 72.13 C ATOM 841 C LEU B 276 6.969 18.089 9.709 1.00 73.79 C
ATOM 842 0 LEU B 276 6.477 19.163 9.369 1.00 74.24 O
ATOM 843 N VAL B 277 6.305 17.190 10.454 1.00 78.43 N
ATOM 844 CA VAL B 277 4.933 17.411 10.931 1.00 79.20 C
ATOM 845 CB VAL B 277 4.269 16.099 11.441 1.00 83.39 C ATOM 846 CG1 VAL B 277 2.811 16.326 11.852 1.00 83.25 C
ATOM 847 CG2 VAL B 277 4.362 14.989 10.388 1.00 83.80 C
ATOM 848 C VAL B 277 5.032 18.486 12.028 1.00 79.48 C
ATOM 849 O VAL B 277 6.040 18.539 12.737 1.00 79.40 O
ATOM 850 N GLN B 278 4.001 19.340 12.150 1.00 81.39 N ATOM 851 CA GLN B 278 3.947 20.441 13.121 1.00 81 .83 C
ATOM 852 CB GLN B 278 3.125 20.125 14.416 1.00 83.82 C
ATOM 853 CG GLN B 278 2.980 18.632 14.823 1.00 85.76 C
ATOM 854 CD GLN B 278 1.560 18.051 14.826 1.00 87.74 C
ATOM 855 OE1 GLN B 278 0.620 18.560 14.187 1.00 88.31 O JB2010.7161
ATOM 856 NE2 GLN B 278 1.383 16.946 15.549 1.00 87.10 N
ATOM 857 C GLN B 278 5.305 21.189 13.340 1.00 81.28 C
ATOM 858 0 GLN B 278 5.868 21.141 14.443 1.00 81.31 O
ATOM 859 N PRO B 279 5.859 21.842 12.268 1.00 81.42 N ATOM 860 CA PRO B 279 7.129 22.578 12.427 1.00 80.65 C
ATOM 861 CB PRO B 279 7.582 22.886 10.987 1.00 82.76 C
ATOM 862 CG PRO B 279 6.546 22.322 10.079 1.00 83.36 C
ATOM 863 CD PRO B 279 5.326 22.000 10.896 1.00 83.60 C
ATOM 864 C PRO B 279 6.979 23.859 13.243 1.00 79.63 C ATOM 865 0 PRO B 279 5.868 24.380 13.443 1.00 79.75 O
ATOM 866 N VAL B 280 8.123 24.356 13.722 1.00 76.16 N
ATOM 867 CA VAL B 280 8.213 25.534 14.570 1.00 74.61 C
ATOM 868 CB VAL B 280 8.157 25.148 16.094 1.00 78.97 C
ATOM 869 CG1 AL B 280 6.721 24.998 16.585 1.00 79.39 C ATOM 870 CG2 VAL B 280 8.979 23.890 16.405 1.00 78.76 C
ATOM 871 C VAL B 280 9.453 26.367 14.225 1.00 72.96 C
ATOM 872 O VAL B 280 9.762 26.596 13.045 1.00 72.94 O
ATOM 873 N GLY B 281 10.138 26.796 15.285 1.00 67.93 N
ATOM 874 CA GLY B 281 11.347 27.596 15.251 1.00 64.37 C ATOM 875 C GLY B 281 12.616 26.777 15.228 1.00 61.35 C
ATOM 876 O GLY B 281 12.677 25.752 14.542 1.00 61.36 O
ATOM 877 N PRO B 282 13.655 27.236 15.959 1.00 53.85 N
ATOM 878 CA PRO B 282 14.937 26.530 15.933 1.00 51.83 C
ATOM 879 CB PRO B 282 15.932 27.567 16.466 1.00 53.66 C ATOM 880 CG PRO B 282 15.151 28.834 16.663 1.00 54.44 C
ATOM 881 CD PRO B 282 13.736 28.438 16.808 1.00 55.05 C
ATOM 882 C PRO B 282 14.987 25.225 16.703 1.0049.73 C
ATOM 883 O PRO B 282 14.297 25.032 17.701 1.00 49.09 O
ATOM 884 N LEU B 283 15.842 24.328 16.217 1.00 46.77 N ATOM 885 CA LEU B 283 16.052 23.002 16.765 1.00 44.46 C
ATOM 886 CB LEU B 283 15.671 21.959 15.700 1.00 45.22 C
ATOM 887 CG LEU B 283 14.624 20.931 16.106 1.00 47.02 C
ATOM 888 CD1 LEU B 283 13.303 21.607 16.548 1.00 50.11 C
ATOM 889 CD2 LEU B 283 14.351 19.972 14.980 1.00 47.51 C ATOM 890 C LEU B 283 17.489 22.803 17.155 1.00 42.49 C
ATOM 891 O LEU B 283 18.401 23.089 16.359 1.00 42.71 O
ATOM 892 N VAL B 284 17.693 22.308 18.380 1.00 34.66 N
ATOM 893 CA VAL B 284 19.009 21.973 18.905 1.00 32.06 C
ATOM 894 CB VAL B 284 19.494 22.895 20.056 1.00 34.22 C ATOM 895 CG1 VAL B 284 20.756 22.351 20.723 1.00 33.19 C
ATOM 896 CG2 VAL B 284 19.728 24.315 19.562 1.00 32.87 C
ATOM 897 C VAL B 284 18.952 20.497 19.308 1.00 30.68 C
ATOM 898 O VAL B 284 18.008 20.088 19.987 1 ,00 30.03 O
ATOM 899 N VAL B 285 19.947 19.696 18.868 1.00 29.51 N ATOM 900 CA VAL B 285 20.014 18.278 19.211 1.00 28.21 C
ATOM 901 CB VAL B 285 19.834 17.300 18.000 1.00 30.74 C
ATOM 902 CG1 VAL B 285 20.087 15.853 18.409 1.00 30.76 C
ATOM 903 CG2 VAL B 285 18.440 17.420 17.385 1.00 29.52 C
ATOM 904 C VAL B 285 21.293 18.054 19.994 1.00 27.77 C ATOM 905 O VAL B 285 22.378 18.309 19.482 1.00 27.96 O
ATOM 906 N LEU B 286 21.163 17.593 21.244 1.00 29.54 N
ATOM 907 CA LEU B 286 22.307 17.311 22.105 1.00 29.30 C
ATOM 908 CB LEU B 286 22.056 17.823 23,540 1.00 28,65 C
ATOM 909 CG LEU B 286 23,073 17.505 24.668 1.00 27.79 C JB2010.7161
ATOM 910 CD1 LEU B 286 24.519 17.697 24.239 1.00 26.95 C
ATOM 911 CD2 LEU B 286 22.797 18.345 25.861 1.00 26.68 C
ATOM 912 C LEU B 286 22.594 15.808 22.059 1.00 29.54 C
ATOM 913 0 LEU B 286 21.733 14.997 22.419 1.00 29.58 O ATOM 914 N LEU B 287 23.811 15.453 21.595 1.00 30.11 N
ATOM 915 CA LEU B 287 24.277 14.080 21.453 1.00 30.28 C
ATOM 916 CB LEU B 287 24.646 13.799 19.988 1.00 29.98 C
ATOM 917 CG LEU B 287 23.479 13.795 18.986 1.00 30.72 C
ATOM 918 CD1 LEU B 287 23.976 13.977 17.567 1.00 30.99 C ATOM 919 CD2 LEU B 287 22.603 12.558 19.137 1.00 29.04 C
ATOM 920 C LEU B 287 25.467 13.896 22.409 1.00 30.68 C
ATOM 921 O LEU B 287 26.641 14.043 22.048 1.00 30.78 O
ATOM 922 N PRO B 288 25.165 13.595 23.680 1.00 32.41 N
ATOM 923 CA PRO B 288 26.248 13,465 24.673 1.00 32.22 C ATOM 924 CB PRO B 288 25.537 13.871 25.962 1.00 33.66 C
ATOM 925 CG PRO B 288 24.102 13.363 25.752 1.00 33.61 C
ATOM 926 CD PRO B 288 23.829 13.373 24.287 1.00 33.34 C
ATOM 927 C PRO B 288 26.793 12.042 24.728 1.00 32.39 C
ATOM 928 0 PRO B 288 27.060 11 .490 25.802 1.00 32.92 O ATOM 929 N LEU B 289 26.917 1 1.444 23.557 1.00 31.45 N
ATOM 930 CA LEU B 289 27.346 10.071 23.381 1.00 31.73 C
ATOM 931 CB LEU B 289 26.135 9.213 22.979 1.00 31.73 C
ATOM 932 CG LEU B 289 25.272 9.764 21.838 1.00 31.64 C
ATOM 933 CD1 LEU B 289 25.680 9.153 20.518 1.00 30.82 C ATOM 934 CD2 LEU B 289 23.794 9.539 22.1 19 1.00 31.10 C
ATOM 935 C LEU B 289 28.434 9.965 22.344 1.00 31.83 C
ATOM 936 O LEU B 289 28.658 10.893 21.574 1.00 32.07 O
ATOM 937 N ALA B 290 29.117 8.841 22.323 1.00 31.55 N
ATOM 938 CA ALA B 290 30.177 8.596 21.367 1.00 31.88 C ATOM 939 CB ALA B 290 31.466 9.280 21.784 1.00 32.33 C
ATOM 940 C ALA B 290 30.400 7.133 21.224 1.00 32.57 C
ATOM 941 O ALA B 290 30.345 6.388 22.210 1.00 32.89 O
ATOM 942 N GLY B 291 30.591 6.746 19.971 1.00 34.71 N
ATOM 943 CA GLY B 291 30.905 5.405 19.514 1.00 35.31 C ATOM 944 C GLY B 291 32.082 5.585 18.582 1.00 35.88 C
ATOM 945 O GLY B 291 32.621 6.692 18.497 1.00 36.05 O
ATOM 946 N GLY B 292 32.483 4.527 17.875 1.00 37.54 N
ATOM 947 CA GLY B 292 33.585 4.618 16.921 1.00 37.39 C
ATOM 948 C GLY B 292 33.096 5.321 15.669 1.00 37.64 C ATOM 949 O GLY B 292 31.875 5.442 15.484 1.00 37.26 O
ATOM 950 N TYR B 293 34.021 5.786 14.791 1.00 37.65 N
ATOM 951 CA TYR B 293 33.611 6.461 13.554 1.00 38.29 C
ATOM 952 CB TYR B 293 34.808 6.747 12.606 1.00 38.69 C
ATOM 953 CG TYR B 293 34.357 7.129 11.213 1 .00 39.41 C ATOM 954 CD1 TYR B 293 33.974 8.438 10.916 1.00 41.11 C
ATOM 955 CE1 TYR B 293 33.490 8.781 9.653 1.00 41.49 C
ATOM 956 CZ TYR B 293 33.372 7.804 8.673 1.00 42.49 C
ATOM 957 OH TYR B 293 32.883 8.120 7.421 1.00 45.59 O
ATOM 958 CE2 TYR B 293 33.738 6.497 8.951 1.00 40.22 C ATOM 959 CD2 TYR B 293 34.223 6.167 10.214 1.00 38.83 C
ATOM 960 C TYR B 293 32.533 5.620 12.857 1.00 38.38 C
ATOM 961 O TYR B 293 32.715 4.416 12.724 1.00 39.52 O
ATOM 962 N SER B 294 31.414 6.239 12.460 1.00 37.36 N
ATOM 963 CA SER B 294 30.290 5.588 11.797 1 ,00 36.95 C JB2010.7161
ATOM 964 CB SER B 294 29.121 5.450 12.761 1.00 37.76 C
ATOM 965 OG SER B 294 27.942 5.046 12.081 1 .00 37.84 0
ATOM 966 C SER B 294 29.834 6.381 0.586 1.00 37.32 C
ATOM 967 O SER B 294 29.376 7.524 10.734 1.00 37.75 O ATOM 968 N ARG B 295 29.912 5,765 9.392 1.00 37.86 N
ATOM 969 CA ARG B 295 29.487 6.370 8. 24 1 ,00 37.54 C
ATOM 970 CB ARG B 295 29.735 5.409 6.946 1.00 41.77 C
ATOM 971 CG ARG B 295 29.201 5.900 5.619 1.00 42.55 C
ATOM 972 CD ARG B 295 29.870 5.241 4.445 1.00 46.07 C ATOM 973 NE ARG B 295 29.533 5.958 3.218 1.00 48.72 N
ATOM 974 CZ ARG B 295 29.466 5.403 2.017 1.00 48.86 C
ATOM 975 NH1 ARG B 295 29.708 4.107 1.863 1.00 49.61 N
ATOM 976 NH2 ARG B 295 29.137 6.134 0.959 1.00 48.38 N
ATOM 977 C ARG B 295 28.024 6.825 8.154 1.00 36.42 C ATOM 978 O ARG B 295 27.761 7.970 7.787 1.00 36.88 O
ATOM 979 N VAL B 296 27.093 5.951 8.578 1.00 31.24 N
ATOM 980 CA VAL B 296 25.650 6.248 8.638 1.00 30.59 C
ATOM 981 CB VAL B 296 24.745 4.975 8.731 1.00 32.25 C
ATOM 982 CG1 VAL B 296 24.891 4.239 10.059 1.00 31.16 C ATOM 983 CG2 VAL B 296 23.292 5.297 8.449 1.00 30.86 C
ATOM 984 C VAL B 296 25.299 7.319 9.669 1.00 30.70 C
ATOM 985 O VAL B 296 24.435 8.157 9.406 1 .00 30.47 O
ATOM 986 N LEU B 297 25.970 7.299 10.838 1.00 31.76 N
ATOM 987 CA LEU B 297 25.681 8.268 11.883 1.00 31.85 C ATOM 988 CB LEU B 297 26.233 7.822 13.249 1.00 32.13 C
ATOM 989 CG LEU B 297 25.585 8.436 14.513 1.00 31.08 C
ATOM 990 CD1 LEU B 297 24.117 8. 57 14.594 1.00 30.53 C
ATOM 991 CD2 LEU B 297 26.202 7.867 15.748 1.00 29,54 C
ATOM 992 C LEU B 297 26.147 9.641 11.460 1.00 32.26 C ATOM 993 O LEU B 297 25.442 10.611 11.707 1.00 31.53 O
ATOM 994 N ASN B 298 27.299 9.720 10.769 1.00 32.34 N
ATOM 995 CA AS B 298 27.797 10.992 10.261 1.00 33.54 C
ATOM 996 CB ASN B 298 29.278 10.897 9.911 1.00 35.69 C
ATOM 997 CG ASN B 298 30.177 10.842 11.145 1.00 38.39 C ATOM 998 OD1 ASN B 298 29.742 10.585 12.275 1.00 39.51 O
ATOM 999 ND2 AS B 298 31.460 11.089 10.968 1.00 40.72 N
ATOM 1000 C ASN B 298 26.900 11.461 9.101 1.00 33.90 C
ATOM 1001 O ASN B 298 26.568 12.644 9.004 1.00 33.71 O
ATOM 1002 N ALA B 299 26.433 10.506 8.278 1.00 36.33 N ATOM 1003 CA ALA B 299 25.523 10.762 7. 70 1.00 36.99 C
ATOM 1004 CB ALA B 299 25.282 9.488 6.387 1.00 37.15 C
ATOM 1005 C ALA B 299 24.194 11.336 7.706 1.00 37.83 C
ATOM 1006 O ALA B 299 23.774 12.377 7.197 1.00 38.31 O
ATOM 1007 N ALA B 300 23.558 10.702 8.743 1.00 36.35 N ATOM 1008 CA ALA B 300 22.297 1 .175 9.346 1.00 37.40 C
ATOM 1009 CB ALA B 300 21.831 10.202 10.418 1.00 38.27 C
ATOM 1010 C ALA B 300 22.450 12,572 9.962 1.00 38.29 C
ATOM 101 1 O ALA B 300 21.535 13.398 9.909 1.00 38.11 O
ATOM 1012 N CYS B 301 23.615 12.830 10.547 1.00 41.05 N ATOM 1013 CA CYS B 301 23.904 14.113 11.148 1.00 42.56 C
ATOM 1014 CB CYS B 301 25.116 14.026 12.067 1.00 42.91 C
ATOM 1015 SG CYS B 301 24.818 13.044 13.570 1.00 46.44 S
ATOM 1016 C CYS B 301 24.048 15.172 10.065 1.00 43.01 C
ATOM 1017 O CYS B 301 23.576 16.281 10.267 1.00 43.38 O JB2010.7161
ATOM 1018 N GLN B 302 24.603 14.816 8.892 1.00 45.47 N
ATOM 1019 CA GLN B 302 24.725 15.730 7.755 1.00 46.30 C
ATOM 1020 CB GLN B 302 25.589 15.115 6.652 1.00 48.92 C
ATOM 1021 CG GLN B 302 25.900 16.087 5.524 1.00 51.37 C ATOM 1022 CD GLN B 302 26.545 15.404 4.354 1.00 55.04 C
ATOM 1023 OE1 GLN B 302 25.947 14.502 3.733 1.00 58.26 O
ATOM 1024 NE2 GL B 302 27.775 15.817 4.019 1.00 54.16 N
ATOM 1025 C GLN B 302 23.347 16.125 7.194 1.0046.52 C
ATOM 1026 O GLN B 302 23.139 17.290 6.858 1.00 46.16 O ATOM 1027 N ARG B 303 22.419 15.154 7.091 1.0049.00 N
ATOM 1028 CA ARG B 303 21.069 15.395 6.584 1.00 49.54 C
ATOM 1029 CB ARG B 303 20.307 14.092 6.338 1.00 53.09 C
ATOM 1030 CG ARG B 303 20.792 13.379 5.081 1.00 55.50 C
ATOM 1031 CD ARG B 303 20.621 11.883 5.199 1.00 58.43 C ATOM 1032 NE ARG B 303 20.845 11.210 3.921 1.00 60.43 N
ATOM 1033 CZ ARG B 303 19.896 10.939 3.030 1.00 61 .44 C
ATOM 1034 NH1 ARG B 303 18.636 11.286 3.263 1.00 61.92 N
ATOM 1035 NH2 ARG B 303 20.200 10.320 1.898 1.00 62.60 N
ATOM 1036 C ARG B 303 20.322 16.316 7.506 1.00 49.24 C ATOM 1037 O ARG B 303 19.790 17.320 7.049 1.00 49.91 O
ATOM 1038 N LEU B 304 20.338 16.020 8.803 1.00 47.38 N
ATOM 1039 CA LEU B 304 19.704 16.823 9.840 1.0047.11 C
ATOM 1040 CB LEU B 304 19.977 16.149 11.185 1.00 46.94 C
ATOM 1041 CG LEU B 304 18.808 15.779 12.116 1.0047.60 C ATOM 1042 CD1 LEU B 304 17.413 15.908 11.473 1.00 46.94 C
ATOM 1043 CD2 LEU B 304 19.010 14.424 12.645 1.00 47.08 C
ATOM 1044 C LEU B 304 20.259 18.261 9.835 1 .00 47.25 C
ATOM 1045 O LEU B 304 19.488 19.200 10.002 1.00 47.42 O
ATOM 1046 N ALA B 305 21.586 18.427 9.621 1.00 46.56 N ATOM 1047 CA ALA B 305 22.274 19.720 9.571 1.00 46.26 C
ATOM 1048 CB ALA B 305 23.781 19.527 9.598 1.00 46.48 C
ATOM 1049 C ALA B 305 21.862 20.467 8.320 1.0046.56 C
ATOM 1050 O ALA B 305 21.602 21.666 8.393 1.0046.83 O
ATOM 1051 N ARG B 306 21.779 19.765 7.176 1.00 48.86 N ATOM 1052 CA ARG B 306 21.350 20.374 5.923 1.00 49.08 C
ATOM 1053 CB ARG B 306 21.623 19.474 4.712 1.00 54.77 C
ATOM 1054 CG ARG B 306 22.922 19.833 3.989 1.00 58.49 C
ATOM 1055 CD ARG B 306 23.771 18.593 3.746 1.00 64.89 C
ATOM 1056 NE ARG B 306 25.115 18.845 3.196 1.00 68.11 N ATOM 1057 CZ ARG B 306 26.148 19.348 3.876 1.00 69.63 C
ATOM 1058 NH1 ARG B 306 26.001 19.730 5.143 1.00 69.04 N
ATOM 1059 NH2 ARG B 306 27.329 19.498 3.286 1.00 70.29 N
ATOM 1060 C ARG B 306 19.879 20.757 6.045 1.00 48.35 C
ATOM 1061 O ARG B 306 19.501 21.792 5.498 1.00 48.65 O ATOM 1062 N ALA B 307 19.073 19.974 6.822 1.00 45.09 N
ATOM 1063 CA ALA B 307 17.653 20.238 7.080 1.00 44.33 C
ATOM 1064 CB ALA B 307 16.951 18.982 7.565 1.00 44.77 C
ATOM 1065 C ALA B 307 17.409 21.399 8.071 1.00 44.06 C
ATOM 1066 O ALA B 307 16.249 21.701 8.390 1.0044.24 O ATOM 1067 N GLY B 308 18.494 22.015 8.554 1.00 44.62 N
ATOM 1068 CA GLY B 308 18.459 23.156 9.464 1.00 43.74 C
ATOM 1069 C GLY B 308 18.652 22.960 10.956 1.00 43.38 C
ATOM 1070 O GLY B 308 18.662 23.953 11.694 1.00 43.46 O
ATOM 1071 N VAL B 309 18.787 21.694 11.428 1.00 43.37 N JB2010.7161
ATOM 1072 CA VAL B 309 18.966 21.373 12.852 1 .00 42.26 C
ATOM 1073 CB VAL B 309 18.553 19.912 13.171 1.00 45.23 C
ATOM 1074 CG1 VAL B 309 18.512 19.668 14.673 1.00 45.69 C
ATOM 1075 CG2 VAL B 309 17.207 19.564 12.549 1.00 43.80 C ATOM 1076 C VAL B 309 20.401 21.677 13.334 1.00 41.42 C
ATOM 1077 O VAL B 309 21.346 21.428 12.595 1.00 41.48 O
ATOM 1078 N VAL B 310 20.554 22.218 14,573 1.00 39.32 N
ATOM 1079 CA VAL B 310 21.862 22.506 15.202 1.00 37.79 C
ATOM 1080 CB VAL B 310 21.871 23.814 16.042 1.00 39.88 C ATOM 1081 CG1 VAL B 310 23.200 23.998 16.774 1.00 38.47 C
ATOM 1082 CG2 VAL B 310 21.551 25.024 15.175 1.00 39.76 C
ATOM 1083 C VAL B 310 22.213 21.274 16.065 1.00 37.16 C
ATOM 1084 O VAL B 310 21.541 21.004 17.066 1.00 37.73 O
ATOM 1085 N LEU B 31 1 23.230 20.518 15.658 1.00 33.36 N ATOM 1086 CA LEU B 311 23.647 19.317 16.377 1.00 31.86 C
ATOM 1087 CB LEU B 311 23.817 18.133 15.418 1.00 31.75 C
ATOM 1088 CG LEU B 311 22.518 17.535 14.896 1.00 32.50 C
ATOM 1089 CD1 LEU B 311 22.139 18.138 13.571 1.00 33.15 C
ATOM 1090 CD2 LEU B 311 22.636 16.058 14.738 1.00 32.03 C ATOM 1091 C LEU B 311 24.911 19.570 17.170 1.00 31.07 C
ATOM 1092 O LEU B 311 25.903 20.055 16.630 1.00 30.54 O
ATOM 1093 N VAL B 312 24.858 19.272 18.467 1.00 30.30 N
ATOM 1094 CA VAL B 312 25.977 19.453 19.388 1.00 29.91 C
ATOM 1095 CB VAL B 312 25,682 20.509 20.494 1.00 31.65 C ATOM 1096 CG1 VAL B 312 26.902 20.742 21.398 1.00 29.57 C
ATOM 1097 CG2 VAL B 312 25.211 21.823 19.877 1.00 31.21 C
ATOM 1098 C VAL B 312 26.287 18.081 19.958 1.00 30.22 C
ATOM 1099 O VAL B 312 25.360 17.364 20.363 1.00 30.59 O
ATOM 1100 N THR B 313 27.576 17.703 19.966 1.00 30.82 N ATOM 1101 CA THR B 313 27.995 16.403 20.467 1.00 30.83 C
ATOM 1102 CB THR B 313 28.119 15.362 19.309 1.00 38.00 C
ATOM 1103 OG1 THR B 313 28.224 14.049 19.852 1.00 38.91 O
ATOM 1104 CG2 THR B 313 29.329 15.602 18.419 1.00 37.80 C
ATOM 1105 C THR B 313 29.263 16.489 21.285 1.00 30.65 C ATOM 1106 O THR B 313 30,080 17.411 21.088 1.00 30.86 O
ATOM 1107 N ALA B 314 29.444 15.482 22.175 1.00 30.33 N
ATOM 1108 CA ALA B 314 30.629 15.300 23.006 1.00 29.78 C
ATOM 1109 CB ALA B 314 30.368 14.195 24.019 1.00 30.00 C
ATOM 1110 C ALA B 314 31.792 14.871 22.090 1.00 29.78 C ATOM 1111 O ALA B 314 31.580 14.048 21.173 1.00 29.66 O
ATOM 11 12 N ALA B 315 33.020 15.391 22.331 1 .00 28.44 N
ATOM 1113 CA ALA B 315 34.180 14.974 21.525 1.00 28.07 C
ATOM 1114 CB ALA B 315 35.353 15.911 21.760 1.00 28.15 C
ATOM 1115 C ALA B 315 34.595 13.518 21.846 1.00 28.08 C ATOM 1116 0 ALA B 315 35.171 12.827 20.995 1.00 27.81 O
ATOM 1117 N GLY B 316 34.278 13.063 23.063 1.00 27.97 N
ATOM 11 18 CA GLY B 316 34.637 11.735 23.560 1.00 28.49 C
ATOM 1119 C GLY B 316 35.602 11.907 24.727 1.00 29.31 C
ATOM 1120 O GLY B 316 36.307 12.926 24.799 1.00 28.70 O ATOM 1121 N ASN B 317 35.593 10.944 25.679 1.00 29.99 N
ATOM 1122 CA ASN B 317 36.401 10.959 26.893 1.00 31.25 C
ATOM 1123 CB ASN B 317 35.499 10.678 28.092 1.0029.52 C
ATOM 1124 CG ASN B 317 34.383 11.666 28.316 1.00 29.74 C
ATOM 1125 OD1 ASN B 317 34.465 12.854 27.991 1.00 29.91 O JB2010.7161
ATOM 1126 ND2 AS B 317 33.318 11.208 28.923 1.00 29.03 N
ATOM 1127 C ASN B 317 37.505 9.911 26.797 1.00 32.46 C
ATOM 1128 O ASN B 317 37.790 9.195 27.773 1.00 33.25 O
ATOM 1129 N PHE B 318 38.155 9.823 25.631 1.00 34.04 N ATOM 1130 CA PHE B 318 39.172 8.797 25.444 1 .00 35.13 C
ATOM 1131 CB PHE B 318 38.806 7.889 24.262 1.00 34.13 C
ATOM 1 132 CG PHE B 318 37.374 7.403 24.312 1.00 33.75 C
ATOM 133 CD1 PHE B 318 37.013 6.338 25.118 1.00 33.12 C
ATOM 1134 CE1 PHE B 318 35.688 5.893 25.161 1.00 33.52 C ATOM 1135 CZ PHE B 318 34.718 6.534 24.415 1.00 32.98 C
ATOM 1136 CE2 PHE B 318 35.062 7.587 23.607 1.00 31.62 C
ATOM 1137 CD2 PHE B 318 36.384 8.027 23.562 1.00 32.85 C
ATOM 1138 C PHE B 318 40.607 9.265 25.381 1.00 36.38 C
ATOM 1139 0 PHE B 318 41.470 8.431 25.125 1.00 37.43 O ATOM 1140 N ARG B 319 40.890 10.566 25.630 1.00 39.85 N
ATOM 1141 CA ARG B 319 42.242 11.150 25.556 1.00 40.82 C
ATOM 1142 CB ARG B 319 43.118 10.707 26.743 1.00 49.83 C
ATOM 1 143 CG ARG B 319 44.142 11.774 27.110 1.00 54.00 C
ATOM 1 144 CD ARG B 319 45.191 11.297 28.093 1.00 61.76 C ATOM 1 145 NE ARG B 319 44.779 11.481 29.490 1.00 68.02 N
ATOM 1146 CZ ARG B 319 45.117 10.666 30.492 1.00 72.17 C
ATOM 1147 NH1 ARG B 319 45.873 9.592 30.263 1.00 72.63 N
ATOM 1148 NH2 ARG B 319 44.703 10.918 31.731 1 .00 73.93 N
ATOM 1149 C ARG B 319 42.844 10.740 24.199 1.00 40.44 C ATOM 1150 O ARG B 319 44.005 10.312 24.100 1.00 40.31 O
ATOM 1151 N ASP B 320 41.998 10.856 23.156 1.00 39.08 N
ATOM 1152 CA ASP B 320 42.261 10.427 21.795 1.00 38.92 C
ATOM 1153 CB ASP B 320 41.591 9.040 21.630 1.00 40.61 C
ATOM 1154 CG ASP B 320 42.061 8.165 20.487 1.00 41.51 C ATOM 1155 OD1 ASP B 320 42.972 8.605 19.729 1.00 44.06 O
ATOM 1156 OD2 ASP B 320 41.519 7.043 20.336 1.00 39.19 O
ATOM 1157 C ASP B 320 41.765 1 1.429 20.731 1.00 38.82 C
ATOM 1158 O ASP B 320 41.102 12.412 21.052 1.00 38.65 O
ATOM 1159 N ASP B 321 42.130 11.185 19.462 1.00 39.08 N ATOM 1160 CA ASP B 321 41.736 11.988 18.301 1.00 38.58 C
ATOM 1161 CB ASP B 321 42.565 11.527 17.094 1.0042.56 C
ATOM 1162 CG ASP B 321 42.475 12.341 15.823 1.00 44.20 C
ATOM 1163 OD1 ASP B 321 41.499 13.107 15.669 1.00 45.68 O
ATOM 1164 OD2 ASP B 321 43.375 12.194 14.963 1.00 48.16 O ATOM 1165 C ASP B 321 40.217 11.775 18.074 1.00 37.68 C
ATOM 1166 O ASP B 321 39.775 10.646 17.853 1.00 37.1 1 O
ATOM 1167 N ALA B 322 39.425 12.862 18.180 1 ,00 36.81 N
ATOM 1168 CA ALA B 322 37.955 12.842 18.046 1.00 36.40 C
ATOM 1169 CB ALA B 322 37.356 14.196 18.400 1.00 36.57 C ATOM 1170 C ALA B 322 37.459 12.377 16.683 1.00 35.94 C
ATOM 1171 O ALA B 322 36.313 11.964 16.569 1.00 35.91 O
ATOM 1172 N CYS B 323 38.327 12.423 15.672 1.00 33.90 N
ATOM 1173 CA CYS B 323 38.054 12.019 14.305 1.00 33.91 C
ATOM 1174 CB CYS B 323 39.157 12.499 13.363 1.00 34.67 C ATOM 1175 SG CYS B 323 39.368 14.310 13.336 1.00 39.12 S
ATOM 1176 C CYS B 323 37.776 10.528 14.159 1.00 33.21 C
ATOM 1177 O CYS B 323 37.162 10.127 13.173 1.00 33.46 O
ATOM 1178 N LEU B 324 38.179 9.714 15.151 1.00 31.93 N
ATOM 1179 CA LEU B 324 37.959 8.268 15.183 1.00 31.15 C JB2010.7161
ATOM 1180 CB LEU B 324 39.060 7.564 16.010 1.00 30.82 C
ATOM 1181 CG LEU B 324 40.540 7.909 15.710 1.00 31.14 C
ATOM 1182 CD1 LEU B 324 41.442 7.359 16.785 1.00 31.21 C
ATOM 1183 CD2 LEU B 324 40.990 7.390 14.355 1.00 29.04 C ATOM 1184 C LEU B 324 36.582 7.938 15.791 1.00 31.09 C
ATOM 1185 O LEU B 324 36.186 6.759 15.829 1 .00 31.21 O
ATOM 1186 N TYR B 325 35.851 8.965 16.264 1 .00 29.92 N
ATOM 1187 CA TYR B 325 34.566 8.761 16.918 1.00 29.47 C
ATOM 1188 CB TYR B 325 34.652 9.244 18.382 1.00 29.77 C ATOM 1189 CG TYR B 325 35.793 8.567 19.113 1.00 29.83 C
ATOM 1190 CD1 TYR B 325 35.603 7.356 19.775 1.00 28.38 C
ATOM 1191 CE1 TYR B 325 36.665 6.695 20.388 1.00 28.71 C
ATOM 1 192 CZ TYR B 325 37.938 7.245 20.336 1.00 28.77 C
ATOM 1 193 OH TYR B 325 39.001 6.609 20.921 1.00 28.92 O ATOM 1 194 CE2 TYR B 325 38.148 8.450 19.690 1.00 28.14 C
ATOM 1195 CD2 TYR B 325 37.081 9.098 19.078 1 .00 28.60 C
ATOM 1196 C TYR B 325 33.414 9.391 16.206 1.00 29.29 C
ATOM 1197 O TYR B 325 33.609 10.294 15.392 1.00 29.71 O
ATOM 1198 N SER B 326 32.206 8.933 16.519 1.00 27.99 N ATOM 1199 CA SER B 326 30.969 9.477 15.961 1.00 27.60 C
ATOM 1200 CB SER B 326 30.442 8.589 14.850 1.00 26.03 C
ATOM 1201 OG SER B 326 31.204 8.880 13.702 1.00 24.73 O
ATOM 1202 C SER B 326 29,901 9.682 17.076 1.00 27.94 C
ATOM 1203 O SER B 326 29.838 8.860 18.006 1.00 27.70 O ATOM 1204 N PRO B 327 29.084 10.777 17.028 1.00 30.58 N
ATOM 1205 CA PRO B 327 28.997 1 1.812 15.970 1.00 30.62 C
ATOM 1206 CB PRO B 327 27.618 12.452 16,213 1.00 31.77 C
ATOM 1207 CG PRO B 327 26.927 11.586 17.246 1.00 31.68 C
ATOM 1208 CD PRO B 327 28.045 11.002 18.046 1.00 31.42 C ATOM 1209 C PRO B 327 30.128 12.834 15.939 1.00 30.65 C
ATOM 1210 O PRO B 327 30.132 13.683 15.061 1.00 30.75 O
ATOM 1211 N ALA B 328 31.091 12.738 16.878 1.00 31.66 N
ATOM 1212 CA ALA B 328 32.244 13.621 17.047 1.00 31.94 C
ATOM 1213 CB ALA B 328 33.196 13.012 18.047 1.00 32.42 C ATOM 1214 C ALA B 328 33.007 14.049 15.782 1.00 32.51 C
ATOM 1215 O ALA B 328 33.384 15.212 15.664 1.00 32.57 O
ATOM 1216 N SER B 329 33.248 13.107 14.848 1.00 33.98 N
ATOM 1217 CA SER B 329 33.985 13.361 13.612 1.00 33.71 C
ATOM 1218 CB SER B 329 34.650 12.086 13.115 1.00 32.49 C ATOM 1219 OG SER B 329 33.709 11.043 12.958 1.00 31.06 O
ATOM 1220 C SER B 329 33.168 14.003 12.494 1.00 34.00 C
ATOM 1221 O SER B 329 33.765 14.531 11.547 1.00 34.17 O
ATOM 1222 N ALA B 330 31.825 13.951 12.578 1.00 32.87 N
ATOM 1223 CA ALA B 330 30.965 14.542 11.554 1.00 33.13 C ATOM 1224 CB ALA B 330 29.491 14,298 1.876 1.00 33.53 C
ATOM 1225 C ALA B 330 31.266 16.040 11.459 1.00 33.48 C
ATOM 1226 O ALA B 330 31.110 16.747 12.460 1.00 33.33 O
ATOM 1227 N PRO B 331 31.752 16.525 10.281 1.00 37.56 N
ATOM 1228 CA PRO B 331 32.087 17.970 10.135 1.00 38.14 C ATOM 1229 CB PRO B 331 32.537 18.091 8.674 1.00 38.47 C
ATOM 1230 CG PRO B 331 32.851 16.735 8.243 1.00 38.59 C
ATOM 1231 CD PRO B 331 32.009 15.794 9.021 1.00 38.87 C
ATOM 1232 C PRO B 331 30.939 18.948 10.379 1.00 38.84 C
ATOM 1233 0 PRO B 331 31.149 20,054 10.879 1.00 38.89 O JB2010.7161
ATOM 1234 N GLU B 332 29.731 18.532 10.018 1.00 42.13 N
ATOM 1235 CA GLU B 332 28.538 19.337 10.113 1.00 43.69 C
ATOM 1236 CB GLU B 332 27.633 19.052 8.898 1.00 45.86 C
ATOM 1237 CG GLU B 332 27.527 17.575 8.561 1.00 50.49 C ATOM 1238 CD GLU B 332 28.577 16.892 7.687 1.00 54.62 C
ATOM 1239 OE1 GLU B 332 29.164 15.890 8.157 1.00 55.64 O
ATOM 1240 OE2 GLU B 332 28.783 17.326 6.526 1.00 55.59 O
ATOM 1241 C GLU B 332 27.805 19.321 11.483 1.00 43.84 C
ATOM 1242 O GLU B 332 26.600 19.570 11.531 1.00 45.26 O ATOM 1243 N VAL B 333 28.528 19.038 12.591 1.00 40.06 N
ATOM 1244 CA VAL B 333 28.027 19.015 13.973 1.00 39.46 C
ATOM 1245 CB VAL B 333 27.715 17.603 14.568 1.00 42.94 C
ATOM 1246 CG1 VAL B 333 26.910 16.724 13.619 1.00 42.82 C
ATOM 1247 CG2 VAL B 333 28.971 16.888 15.036 1.00 43.96 C ATOM 1248 C VAL B 333 29.021 19.793 14.845 1.00 39.20 C
ATOM 1249 O VAL B 333 30.198 19.879 14.492 1.00 40.65 O
ATOM 1250 N ILE B 334 28.574 20.361 15.971 1.00 35.18 N
ATOM 1251 CA ILE B 334 29.479 21.091 16.851 1.00 33.66 C
ATOM 1252 CB ILE B 334 28.821 22.350 17.445 1.00 35.06 C ATOM 1253 CG1 ILE B 334 28.395 23.306 16.320 1.00 35.27 C
ATOM 1254 CD1 ILE B 334 27.131 24.096 16.621 1.00 37.09 C
ATOM 1255 CG2 ILE B 334 29.749 23.047 18.418 1.00 33.32 C
ATOM 1256 C ILE B 334 30.023 20.086 17.877 1.00 33.38 C
ATOM 1257 O ILE B 334 29.273 19.564 18.711 1.00 33.33 O ATOM 1258 N THR B 335 31.329 19.785 17.763 1.00 31.67 N
ATOM 1259 CA THR B 335 32.041 18.840 18.613 1.00 30.93 C
ATOM 1260 CB THR B 335 32.912 17.918 17.770 1.00 34.38 C
ATOM 1261 OG1 THR B 335 32.089 17.318 16.772 1.00 34.47 O
ATOM 1262 CG2 THR B 335 33.561 16.828 18.581 1.00 33.54 C ATOM 1263 C THR B 335 32.736 19.590 19.730 1.00 30.82 C
ATOM 1264 O THR B 335 33.565 20.451 19.483 1.00 30.69 O
ATOM 1265 N VAL B 336 32.350 19.271 20.974 1.00 31.95 N
ATOM 1266 CA VAL B 336 32.835 19.935 22.181 1.00 31.54 C
ATOM 1267 CB VAL B 336 31.652 20.552 22.964 1.00 32.92 C ATOM 1268 CG1 VAL B 336 32.146 21.601 23.934 1.00 32.70 C
ATOM 1269 CG2 VAL B 336 30.603 21.144 22.029 1.00 30.68 C
ATOM 1270 C VAL B 336 33.732 19.078 23.101 1.00 32.18 C
ATOM 1271 O VAL B 336 33.351 17.973 23.549 1.00 32.27 O
ATOM 1272 N GLY B 337 34.910 19.626 23.382 1.00 31.72 N ATOM 1273 CA GLY B 337 35.882 19.016 24.267 1.00 31.60 C
ATOM 1274 C GLY B 337 35.673 19.590 25.650 1.00 32.21 C
ATOM 1275 O GLY B 337 35.009 20.616 25.810 1.00 32.64 O
ATOM 1276 N ALA B 338 36.232 18.938 26.664 1.00 30.34 N
ATOM 1277 CA ALA B 338 36.089 19.402 28.026 1.00 30.15 C ATOM 1278 CB ALA B 338 35.599 18.265 28.908 1.00 30.06 C
ATOM 1279 C ALA B 338 37.370 20.024 28.599 1.00 30.48 C
ATOM 1280 O ALA B 338 38.457 19.451 28.480 1.00 30.89 O
ATOM 1281 N THR B 339 37.218 21.208 29.223 1.00 30.08 N
ATOM 1282 CA THR B 339 38.252 21.951 29.936 1.00 30.54 C ATOM 1283 CB THR B 339 38.529 23,325 29.309 1.00 38.09 C
ATOM 1284 OG1 THR B 339 37.336 24.120 29.263 1.00 38.64 O
ATOM 1285 CG2 THR B 339 39.190 23.223 27.944 1.00 38.79 C
ATOM 1286 C THR B 339 37.788 22.045 31.402 1.00 30.53 C
ATOM 1287 O THR B 339 36.596 21.886 31 .674 1.00 31.12 O JB2010.7161
ATOM 1288 N ASN B 340 38.708 22.277 32.334 1.00 31.32 N
ATOM 1289 CA AS B 340 38.372 22.389 33.746 1.00 31.54 C
ATOM 1290 CB AS B 340 39.307 21.535 34.603 1.00 34.18 C
ATOM 1291 CG ASN B 340 40.776 21.838 34.447 1.00 35.52 C ATOM 1292 OD1 ASN B 340 41.186 22.974 34.160 1.00 37.72 O
ATOM 1293 ND2 ASN B 340 41.610 20.822 34.638 1.00 35.46 N
ATOM 1294 C AS B 340 38.342 23.844 34.217 1.00 31.66 C
ATOM 1295 O ASN B 340 38.423 24.761 33.385 1.00 31.35 O
ATOM 1296 N ALA B 341 38.219 24.064 35.558 1.00 33.36 N ATOM 1297 CA ALA B 341 38.164 25.412 36.137 1.00 33.84 C
ATOM 1298 CB ALA B 341 37.782 25.358 37.609 1.00 34.30 C
ATOM 1299 C ALA B 341 39.427 26.252 35.919 1.00 34.64 C
ATOM 1300 O ALA B 341 39.378 27.473 36.071 1.00 35.12 O
ATOM 1301 N GLN B 342 40.546 25.606 35.549 1.00 36.03 N ATOM 302 CA GLN B 342 41.813 26.273 35.287 1 .00 36.75 C
ATOM 1303 CB GLN B 342 42.988 25.471 35.868 1.00 37.91 C
ATOM 1304 CG GLN B 342 43.132 25.503 37.388 1.00 39.44 C
ATOM 1305 CD GLN B 342 43.023 26.880 38.003 1.0042.11 C
ATOM 1306 OE1 GLN B 342 42.074 27.166 38.748 1.00 44.71 O ATOM 1307 NE2 GLN B 342 43.977 27.774 37.719 1.00 42.23 N
ATOM 1308 C GLN B 342 41.984 26.472 33.786 1 .00 37.45 C
ATOM 1309 O GLN B 342 43.091 26.800 33.342 1 ,00 37.79 O
ATOM 1310 N ASP B 343 40.879 26.290 32.997 1.00 38.20 N
ATOM 1311 CA ASP B 343 40.839 26.415 31.531 1.00 38.72 C ATOM 1312 CB ASP B 343 41.151 27.855 31.087 1.00 42.54 C
ATOM 1313 CG ASP B 343 40.000 28.832 31.265 1.00 45.47 C
ATOM 1314 OD1 ASP B 343 38.828 28.423 31.066 1.0047.22 O
ATOM 1315 OD2 ASP B 343 40.268 30.011 31.592 1.00 48.90 O
ATOM 1316 C ASP B 343 41.757 25.388 30.837 1.00 38.33 C ATOM 1317 O ASP B 343 42.211 25.608 29.724 1.00 37.80 O
ATOM 1318 N GLN B 344 42.009 24.257 31.501 1.00 37.08 N
ATOM 1319 CA GLN B 344 42.881 23.205 30.988 1.00 37.15 C
ATOM 1320 CB GLN B 344 44.067 22.931 31.944 1.00 37.39 C
ATOM 1321 CG GLN B 344 44.919 24.153 32.225 1.00 35.75 C ATOM 1322 CD GLN B 344 45.209 24.973 30.988 1.00 36.63 C
ATOM 1323 OE1 GLN B 344 44.942 26.186 30.938 1.00 36.72 O
ATOM 1324 NE2 GLN B 344 45.761 24.335 29.956 1.00 34.82 N
ATOM 1325 C GLN B 344 42.132 21.935 30.619 1.00 37.50 C
ATOM 1326 O GLN B 344 41.114 21.658 31.242 1.00 37.31 O ATOM 1327 N PRO B 345 42.620 21.164 29,610 1.00 38.91 N
ATOM 1328 CA PRO B 345 41.919 19.940 29.196 1.00 39.54 C
ATOM 1329 CB PRO B 345 42.857 19.353 28.147 1.00 40.92 C
ATOM 1330 CG PRO B 345 43,528 20.533 27.595 1.00 41.38 C
ATOM 1331 CD PRO B 345 43.815 21.375 28.775 1.00 40.36 C ATOM 1332 C PRO B 345 41.672 18.960 30.327 1.00 40.26 C
ATOM 1333 O PRO B 345 42.540 18.764 31.184 1.0040.83 O
ATOM 1334 N VAL B 346 40.477 18.365 30.352 1.00 39.92 N
ATOM 1335 CA VAL B 346 40.154 17.414 31.399 1.00 40.65 C
ATOM 1336 CB VAL B 346 38.642 17.125 31.521 1.00 39.84 C ATOM 1337 CG1 VAL B 346 38.368 16.11 1 32.614 1.00 38.31 C
ATOM 1338 CG2 VAL B 346 37.885 18.398 31.803 1.00 38.10 C
ATOM 1339 C VAL B 346 41.031 16.166 31.236 1.00 42.38 C
ATOM 1340 O VAL B 346 41.061 15.535 30.175 1.00 42.35 O
ATOM 1341 N THR B 347 41.812 15.893 32.274 1.00 50.88 N JB2010.7161
ATOM 1342 CA THR B 347 42.719 14.762 32.397 1.00 53.53 C
ATOM 1343 CB THR B 347 44.161 15.265 32.569 1.00 56.91 C
ATOM 1344 OG1 THR B 347 44.590 15.882 31.352 1.00 56.54 O
ATOM 1345 CG2 THR B 347 45.109 14.165 32.945 1.00 57.61 C ATOM 1346 C THR B 347 42.146 14.088 33.623 1.00 55.62 C
ATOM 1347 O THR B 347 42.431 14.508 34.744 1.00 56.04 O
ATOM 1348 N LEU B 348 41 ,256 13.121 33.419 1.00 62.22 N
ATOM 1349 CA LEU B 348 40.609 12.455 34.533 1.00 64.77 C
ATOM 1350 CB LEU B 348 39.204 13.040 34.793 1.00 65.06 C ATOM 1351 CG LEU B 348 38.970 13.689 36.183 1.00 65.97 C
ATOM 1352 CD1 LEU B 348 37.490 13.921 36.439 1.00 66.58 C
ATOM 1353 CD2 LEU B 348 39.734 15.016 36,363 1.00 65.69 C
ATOM 1354 C LEU B 348 40.619 10.951 34.326 1.00 66.52 C
ATOM 1355 O LEU B 348 40.087 10.433 33.322 1.00 66.96 O ATOM 1356 N GLY B 349 41.266 10.280 35.283 1.00 69.75 N
ATOM 1357 CA GLY B 349 41 ,481 8.844 35.270 1.00 70.85 C
ATOM 1358 C GLY B 349 42.704 8.622 34.407 1.00 71.89 C
ATOM 1359 O GLY B 349 43.605 9.478 34.387 1.00 71.76 O
ATOM 1360 N THR B 350 42.739 7.486 33.666 1.00 74.93 N ATOM 1361 CA THR B 350 43.845 7.160 32.740 1.00 75.54 C
ATOM 1362 CB THR B 350 44.235 5.659 32.793 1.00 86.32 C
ATOM 1363 OG1 THR B 350 43.063 4.850 32.649 1.00 87.59 O
ATOM 1364 CG2 TH B 350 45.001 5.286 34.063 1.00 86.74 C
ATOM 1365 C THR B 350 43.447 7.657 31.325 1.00 75.08 C ATOM 1366 0 THR B 350 44.091 7.313 30.315 1.00 75.64 O
ATOM 1367 N LEU B 351 42,360 8.479 31.280 1.00 71.36 N
ATOM 1368 CA LEU B 351 41.786 9.071 30.079 1.00 69.43 C
ATOM 1369 CB LEU B 351 40.544 8.270 29.637 1.00 69.52 C
ATOM 1370 CG LEU B 351 40.775 6.804 29.227 1.00 70.02 C ATOM 1371 CD1 LEU B 351 39.454 6.107 28.942 1.00 70.15 C
ATOM 1372 CD2 LEU B 351 41.721 6.690 28.028 1.00 69.89 C
ATOM 1373 C LEU B 351 41.473 10.571 30.292 1.00 67.68 C
ATOM 1374 O LEU B 351 42.126 11.231 31.115 1.00 68.03 O
ATOM 1375 N GLY B 352 40.496 11.089 29.546 1.00 58.19 N ATOM 1376 CA GLY B 352 40.099 12.485 29.580 1.00 53.74 C
ATOM 1377 C GLY B 352 39.613 12.942 28.222 1.00 50.86 C
ATOM 1378 O GLY B 352 39.370 12.114 27.342 1.00 50.84 O
ATOM 1379 N THR B 353 39.468 14.257 28.035 1.00 43.70 N
ATOM 1380 CA THR B 353 38.967 14.814 26.791 1.00 40.62 C ATOM 1381 CB THR B 353 38.776 16.332 26.888 1.00 38.06 C
ATOM 1382 OG1 THR B 353 37.990 16.781 25.777 1.00 36.29 O
ATOM 1383 CG2 THR B 353 40.092 17.100 26.972 1.00 37.35 C
ATOM 1384 C THR B 353 39.672 14.410 25.504 1.00 39.09 C
ATOM 1385 O THR B 353 40.907 14.335 25.449 1.00 38.87 O ATOM 1386 N ASN B 354 38.871 14.212 24.441 1.00 36.49 N
ATOM 1387 CA ASN B 354 39.383 13.926 23.115 1.00 34.87 C
ATOM 1388 CB AS B 354 38.311 13.281 22.276 1.00 29.14 C
ATOM 1389 CG ASN B 354 38.277 11 ,786 22.358 1.00 27.59 C
ATOM 1390 OD1 ASN B 354 39.044 11.142 23.073 1.00 28.51 O ATOM 1391 ND2 ASN B 354 37.381 11.193 21.609 1.00 25.14 N
ATOM 1392 C ASN B 354 39.901 15.259 22.501 1.00 34.48 C
ATOM 1393 O AS B 354 39.620 16.328 23.042 1.00 34.18 O
ATOM 1394 N PHE B 355 40.669 15.211 21.418 1.00 36.32 N
ATOM 1395 CA PHE B 355 41.244 16.435 20.820 1.00 36.65 C JB2010.7161
ATOM 1396 CB PHE B 355 42.656 16.694 21.440 1.00 38.49 C
ATOM 1397 CG PHE B 355 43.427 15.421 21.700 1.00 38.85 C
ATOM 1398 CD1 PHE B 355 43.540 14.909 22.985 1.00 38.60 C
ATOM 1399 CE1 PHE B 355 44.195 13.688 23.220 1.00 38.10 C ATOM 1400 CZ PHE B 355 44.723 12.973 22.168 1.00 37.81 C
ATOM 1401 CE2 PHE B 355 44.610 13.458 20.881 1.00 39.12 C
ATOM 1402 CD2 HE B 355 43.944 14.670 20.644 1.00 39.74 C
ATOM 1403 C PHE B 355 41.331 16.338 19.264 1.00 36.88 C
ATOM 1404 O PHE B 355 40.697 15.470 18.645 1.00 36.71 O ATOM 1405 N GLY B 356 42.112 17.224 18.654 1.00 35.93 N
ATOM 1406 CA GLY B 356 42.293 17.201 17.215 1.00 36.01 C
ATOM 1407 C GLY B 356 41.402 18.107 16.404 1.00 36.20 C
ATOM 1408 O GLY B 356 40.569 18.850 16.935 1 .00 36.29 O
ATOM 1409 N ARG B 357 41.600 18.030 15.086 1.00 34.81 N ATOM 1410 CA ARG B 357 40.907 18.802 14.073 1.00 34.86 C
ATOM 1411 CB ARG B 357 41.476 18.528 12.667 1.00 34.52 C
ATOM 1412 CG ARG B 357 41.577 17.060 12.332 1.00 35.79 C
ATOM 1413 CD ARG B 357 41.830 16.810 10.874 1.00 39.50 C
ATOM 1414 NE ARG B 357 41.433 15.446 10.526 1.00 43.33 N ATOM 1 15 CZ ARG B 357 40.322 15.135 9.861 1.00 44.48 C
ATOM 1416 NH1 ARG B 357 39.495 16.093 9.446 1.00 44.60 N
ATOM 1417 NH2 ARG B 357 40.029 13.868 9.602 1.00 46.54 N
ATOM 1418 C ARG B 357 39.414 18.649 14.105 1.00 34.60 C
ATOM 1419 O ARG B 357 38.742 19.549 13,635 1.00 34.76 O ATOM 1420 N CYS B 358 38.879 17,533 14.634 1.00 35.86 N
ATOM 1421 CA CYS B 358 37.423 17.317 14.674 1.00 35.43 C
ATOM 1422 CB CYS B 358 37.054 15.847 14.523 1.00 37.22 C
ATOM 1423 SG CYS B 358 37.538 15.144 12.934 1.00 38.72 S
ATOM 1424 C CYS B 358 36.685 17.979 15.805 1.00 34.84 C ATOM 1425 O CYS B 358 35.470 17.949 15.824 1 .00 34.91 O
ATOM 1426 N VAL B 359 37.410 18.596 16.725 1.00 34.34 N
ATOM 1427 CA VAL B 359 36.859 19.325 17.865 1.00 33.94 C
ATOM 1428 CB VAL B 359 37.771 19.220 19.116 1.00 36.16 C
ATOM 1429 CG1 VAL B 359 37.251 20.094 20.251 1.00 35.76 C ATOM 1430 CG2 VAL B 359 37.904 17.770 19.582 1.00 35.69 C
ATOM 1431 C VAL B 359 36.672 20.769 17.402 1.00 33.89 C
ATOM 1432 O VAL B 359 37.587 21.357 16.817 1.00 34.43 O
ATOM 1433 N ASP B 360 35.493 21.321 17.622 1.00 33.22 N
ATOM 1434 CA AS B 360 35.216 22.686 17.227 1.00 33.06 C ATOM 1435 CB ASP B 360 33.750 22.855 16.850 1.00 35.54 C
ATOM 1436 CG ASP B 360 33.441 22.029 15.621 1.00 37.22 C
ATOM 1437 OD1 ASP B 360 33.944 22.383 14.521 1.00 38.62 O
ATOM 1438 OD2 ASP B 360 32.722 21.009 15.754 1.00 40.25 O
ATOM 1439 C ASP B 360 35.692 23.686 18.255 1.00 32.63 C ATOM 1440 O ASP B 360 36.269 24.717 17.894 1.00 33.14 O
ATOM 1441 N LEU B 361 35.490 23.370 19.539 1.00 31.40 N
ATOM 1442 CA LEU B 361 35.875 24.217 20.669 1.00 30.67 C
ATOM 1443 CB LEU B 361 34.951 25.481 20.735 1.00 30.36 C
ATOM 1444 CG LEU B 361 33.483 25.324 21.226 1 .00 30.90 C ATOM 1445 CD1 LEU B 361 32.822 26.660 21.348 1.00 29.56 C
ATOM 1446 CD2 LEU B 361 32.644 24.423 20.315 1.00 29.22 C
ATOM 1447 C LEU B 361 35.803 23.406 21.964 1.00 30.13 C
ATOM 1448 O LEU B 361 35.408 22.243 21.949 1 .00 30.62 O
ATOM 1449 N PHE B 362 36.159 24.014 23.069 1.00 28.77 N JB2010.7161
ATOM 1450 CA PHE B 362 36.090 23.371 24.366 1.00 28.79 C
ATOM 1451 CB PHE B 362 37.474 23.354 25.017 1.00 30.27 C
ATOM 1452 CG PHE B 362 38.414 22.383 24.351 1.00 30.50 C
ATOM 1453 CD1 PHE B 362 38.621 21.119 24.884 1.00 29.96 C ATOM 1454 CE1 PHE B 362 39.468 20.205 24.253 1.00 29.60 C
ATOM 1455 CZ PHE B 362 40.1 13 20.553 23.091 1.00 29.78 C
ATOM 1456 CE2 PHE B 362 39.918 21.806 22.539 1.00 30.05 C
ATOM 1457 CD2 PHE B 362 39.075 22.723 23.172 1.00 30.55 C
ATOM 1458 C PHE B 362 35.079 24.140 25.221 1.00 28.82 C ATOM 1459 0 PHE B 362 34.790 25.290 24.916 1.00 28.79 O
ATOM 1460 N ALA B 363 34.529 23.522 26.251 1.00 29.28 N
ATOM 1461 CA ALA B 363 33.570 24.188 27.122 1.00 30.01 C
ATOM 1462 CB ALA B 363 32.141 23.956 26.628 1.00 30.70 C
ATOM 1463 C ALA B 363 33.751 23.580 28.506 1.00 30.89 C ATOM 1464 0 ALA B 363 34.351 22.492 28.592 1.00 31.10 O
ATOM 1465 N PRO B 364 33.262 24.217 29.606 1.00 31.62 N
ATOM 1466 CA PRO B 364 33.459 23.606 30.937 1.00 32.12 C
ATOM 1467 CB PRO B 364 32.710 24.560 31.866 1.00 32.92 C
ATOM 1468 CG PRO B 364 32.752 25.866 31.162 1.00 32.41 C ATOM 1469 CD PRO B 364 32.565 25.515 29.716 1.00 32.25 C
ATOM 1470 C PRO B 364 32.929 22.1 1 30.988 1.00 32.72 C
ATOM 1471 O PRO B 364 31.770 21.948 30.627 1.00 33.29 O
ATOM 1472 N GLY B 365 33.792 21.214 31.357 1.00 32.09 N
ATOM 1473 CA GLY B 365 33.422 19.798 31.416 1.00 32.18 C ATOM 1474 C GLY B 365 34.028 18.980 32.539 1.00 32.49 C
ATOM 1475 O GLY B 365 34.181 17.767 32.422 1.00 32.56 O
ATOM 1476 N GLU B 366 34.400 19.627 33.621 1.00 34.76 N
ATOM 1477 CA GLU B 366 34.948 18.945 34.783 1.00 34.96 C
ATOM 1478 CB GLU B 366 36.458 19.067 34.850 1.00 37.10 C ATOM 1479 CG GLU B 366 37.039 18.243 35.980 1.00 39.92 C
ATOM 1480 CD GLU B 366 38.537 18.319 36.176 1.00 43.33 C
ATOM 1481 OE1 GLU B 366 39.287 18.198 35.181 1.00 43.00 O
ATOM 1482 OE2 GLU B 366 38.964 18.480 37.342 1.00 47.03 O
ATOM 1483 C GLU B 366 34.339 19.576 36.003 1.00 34.57 C ATOM 1484 0 GLU B 366 34.197 20.799 36.050 1.00 34.54 O
ATOM 1485 N ASP B 367 33.961 18.750 36.984 1.00 35.28 N
ATOM 1486 CA ASP B 367 33.390 19.221 38.241 1.00 35.42 C
ATOM 1487 CB ASP B 367 34.526 19.843 39.070 1.00 37.34 C
ATOM 1488 CG ASP B 367 34.135 20.442 40.380 1.00 39.37 C ATOM 1489 OD1 ASP B 367 33.401 19.761 41.155 1.00 42.59 O
ATOM 1490 OD2 ASP B 367 34.562 21.589 40.653 1.00 41.43 O
ATOM 1491 C ASP B 367 32.190 20.177 38.008 1.00 35.19 C
ATOM 1492 0 ASP B 367 32.149 21.306 38.550 1.00 35.99 O
ATOM 1493 N ILE B 368 31.218 19.713 37.189 1.00 31.81 N ATOM 1494 CA !LE B 368 30.034 20.498 36.835 1.00 31.52 C
ATOM 1495 CB ILE B 368 29.658 20.329 35.318 1.00 33.75 C
ATOM 1496 CG1 ILE B 368 30.825 20.642 34.338 1.00 33.73 C
ATOM 1497 CD1 ILE B 368 31.461 22.025 34.424 1.00 32.03 C
ATOM 1498 CG2 ILE B 368 28.354 21.035 34.925 1.00 31.81 C ATOM 1499 C ILE B 368 28.861 20.193 37.748 1.00 31.80 C
ATOM 1500 O ILE B 368 28.399 19.058 37.744 1.00 32.62 O
ATOM 1501 N ILE B 369 28.364 21.195 38.506 1.00 30.80 N
ATOM 1502 CA ILE B 369 27.200 21.038 39.362 1.00 30.88 C
ATOM 1503 CB ILE B 369 27.052 22.166 40.448 1.00 33.96 C JB2010.7161
ATOM 1504 CG1 ILE B 369 25.989 21.832 41.495 1.00 33.58 C
ATOM 1505 CD1 ILE B 369 26.376 20.940 42.486 1.00 34.38 C
ATOM 1506 CG2 ILE B 369 26.669 23.507 39.865 1.00 34.33 C
ATOM 1507 C ILE B 369 25.970 20.947 38.448 1.00 31.28 C ATOM 1508 O ILE B 369 25.824 21.719 37.485 1.00 31.82 O
ATOM 1509 N GLY B 370 25.111 19.998 38.761 1.00 31.92 N
ATOM 1510 CA GLY B 370 23.872 19.742 38.048 1.00 32.25 C
ATOM 1511 C GLY B 370 22.976 18.823 38.852 1.00 32.61 C
ATOM 1512 O GLY B 370 23.421 18.219 39.847 1.00 32.56 O ATOM 1513 N ALA B 371 21.703 18.715 38.414 1.00 31.49 N
ATOM 1514 CA ALA B 371 20.683 17.885 39.045 1.00 32.25 C
ATOM 1515 CB ALA B 371 19.408 17.872 38.198 1.00 32.22 C
ATOM 1516 C ALA B 371 21.158 16.449 39.302 1.00 33.17 C
ATOM 1517 O ALA B 371 21.835 15.850 38.457 1.00 33.41 O ATOM 1518 N SE B 372 20.836 15.926 40.479 1.00 35.35 N
ATOM 1519 CA SER B 372 21.145 14.564 40.866 1.00 36.69 C
ATOM 1520 CB SER B 372 21.864 14.515 42.207 1.00 40.78 C
ATOM 1521 OG SER B 372 21.844 13.189 42.716 1.00 41.26 O
ATOM 1522 C SER B 372 19.806 13.863 40.949 1.00 37.80 C ATOM 1523 O SER B 372 18.864 14.372 41.554 1 .00 37.93 O
ATOM 1524 N SER B 373 19.708 12.700 40.325 1.0042.62 N
ATOM 1525 CA SER B 373 18.470 11.934 40.315 1.0043.73 C
ATOM 1526 CB SER B 373 18.509 10.912 39.191 1.00 45.30 C
ATOM 1527 OG SER B 373 19.668 10.111 39.341 1.00 45.46 O ATOM 1528 C SER B 373 18.137 1 1.278 41.673 1.00 44.71 C
ATOM 1529 O SER B 373 17.048 10.733 41.814 1.00 45.28 O
ATOM 1530 N ASP B 374 19.052 11.351 42.669 1.0047.72 N
ATOM 1531 CA ASP B 374 18.858 10.783 44.011 1.0049.25 C
ATOM 1532 CB ASP B 374 20.089 11.012 44.892 1.00 51.53 C ATOM 1533 CG ASP B 374 21.305 10.196 44.501 1.00 53.34 C
ATOM 1534 OD1 ASP B 374 21.187 9.325 43.587 1.00 55.14 O
ATOM 1535 OD2 ASP B 374 22.372 10.411 45.105 1.00 56.96 O
ATOM 1536 C ASP B 374 17.595 1.308 44.695 1.0049.85 C
ATOM 1537 0 ASP B 374 16.805 10.502 45.203 1.00 50.71 O ATOM 1538 N CYS B 375 17.406 12.650 44.698 1.00 48.63 N
ATOM 1539 CA CYS B 375 16.233 13.312 45.252 1.00 48.94 C
ATOM 1540 CB CYS B 375 16.426 13.681 46.717 1.00 50.35 C
ATOM 1541 SG CYS B 375 17.319 15.228 46.978 1.00 53.78 S
ATOM 1542 C CYS B 375 15.872 14.519 44.394 1.00 48.34 C ATOM 1543 0 CYS B 375 16.756 15.119 43.785 1.00 48.53 O
ATOM 1544 N SER B 376 14.570 14.870 44.331 1.00 45.65 N
ATOM 1545 CA SER B 376 14.058 15.980 43.522 1.00 44.66 C
ATOM 1546 CB SER B 376 12.551 16.132 43.702 1.00 47.37 C
ATOM 1547 OG SER B 376 12.224 16.902 44.849 1.00 47.93 O ATOM 1548 C SER B 376 14.761 17.323 43.723 1.00 44.04 C
ATOM 1549 O SER B 376 14.547 18.211 42.900 1.00 43.90 O
ATOM 1550 N THR B 377 15.563 17.491 44.803 1.00 40.75 N
ATOM 1551 CA THR B 377 16.257 18.758 45.086 1.00 40.70 C
ATOM 1552 CB THR B 377 15.598 19.546 46.272 1.00 46.21 C ATOM 1553 OG1 THR B 377 15.956 18.958 47.528 1.00 45.99 O
ATOM 1554 CG2 THR B 377 14.089 19.667 46.161 1.00 45.54 C
ATOM 1555 C THR B 377 17.763 18.543 45.301 1.00 40.93 C
ATOM 1556 O THR B 377 18.450 19.417 45.846 1.00 40.88 O
ATOM 1557 N CYS B 378 18.269 17.386 44.852 1.00 43.59 N JB2010J161
ATOM 1558 CA CYS B 378 19.663 16.983 44.969 1.00 43.84 C
ATOM 1559 CB CYS B 378 19.767 15.466 45.028 1.0046.78 C
ATOM 1560 SG CYS B 378 19.296 14.755 46.625 1.00 53.56 S
ATOM 1561 C CYS B 378 20.551 17.551 43.885 1.00 42,82 C ATOM 1562 0 CYS B 378 20.081 17.832 42.786 1.00 42.51 O
ATOM 1563 N PHE B 379 21.848 17.697 44.194 1.00 41.19 N
ATOM 1564 CA PHE B 379 22.849 18.208 43.269 1.0040.56 C
ATOM 1565 CB PHE B 379 23.161 19.679 43.544 1.00 43.19 C
ATOM 1566 CG PHE B 379 22.142 20.605 42.949 1 .00 44.35 C ATOM 1567 CD1 PHE B 379 22.329 21.146 41.685 1.0044.68 C
ATOM 1568 CE1 PHE B 379 21.369 21.993 41.127 1.00 46.06 C
ATOM 1569 CZ PHE B 379 20.226 22.304 41.841 1.0047.36 C
ATOM 1570 CE2 PHE B 379 20.017 21.762 43.089 1.00 44.85 C
ATOM 1571 CD2 PHE B 379 20.971 20.915 43.640 1.00 45.41 C ATOM 1572 C PHE B 379 24.126 17.413 43.306 1.00 39.73 C
ATOM 1573 O PHE B 379 24.608 17.047 44.380 1.00 39.73 O
ATOM 1574 N VAL B 380 24.703 17.166 42.125 1.00 37.33 N
ATOM 1575 CA VAL B 380 25.955 16.420 42.037 1.00 35.90 C
ATOM 1576 CB VAL B 380 25,710 14.896 41.845 1.00 37.74 C ATOM 1577 CG1 VAL B 380 25.090 14.570 40.475 1.00 37.02 C
ATOM 1578 CG2 VAL B 380 26.973 14.093 42.089 1.00 36.53 C
ATOM 1579 C VAL B 380 26.842 7.029 40.979 1.00 35.35 C
ATOM 1580 O VAL B 380 26.338 17.580 40.011 1.00 34.78 O
ATOM 1581 N SER B 381 28.152 16.938 41.181 1 ,00 34.29 N ATOM 1582 CA SER B 381 29.186 17.397 40.267 1.00 33.36 C
ATOM 1583 CB SER B 381 30.409 17.837 41.049 1.00 37.29 C
ATOM 1584 OG SER B 381 30.833 19.118 40.625 1.00 39.57 O
ATOM 1585 C SER B 381 29.575 16.238 39.356 1.00 32.67 C
ATOM 1586 O SER B 381 29.857 15.135 39.835 1.00 32.08 O ATOM 1587 N GLN B 382 29.572 16.474 38.042 1.00 35.51 N
ATOM 1588 CA GLN B 382 29.952 15,445 37.057 1 .00 35.63 C
ATOM 1589 CB GLN B 382 28.726 14.806 36.364 1.00 38.84 C
ATOM 1590 CG GLN B 382 28.091 13.674 37.187 1.00 43.37 C
ATOM 1591 CD GLN B 382 26.919 12.958 36.500 1.00 52.08 C ATOM 1592 OE1 GLN B 382 26.920 12.664 35.268 1.00 54.95 O
ATOM 1593 NE2 GLN B 382 25.877 12.633 37.292 1.00 54.12 N
ATOM 1594 C GLN B 382 30.994 15.982 36.083 1.00 34.30 C
ATOM 1595 O GLN B 382 31.132 17.202 35.933 1.00 34.47 O
ATOM 1596 N SER B 383 31.746 15.074 35.454 1.00 30.89 N ATOM 1597 CA SER B 383 32.796 15.415 34.500 1.00 30.05 C
ATOM 1598 CB SER B 383 34.180 15.143 35.100 1.00 33.35 C
ATOM 1599 OG SER B 383 34.502 15.969 36.212 1.00 33.76 O
ATOM 1600 C SER B 383 32.648 14.636 33.193 1.00 29.82 C
ATOM 1601 O SER B 383 32.263 13.477 33,206 1.00 29.98 O ATOM 1602 N GLY B 384 32.981 15.274 32.078 1 ,00 30.69 N
ATOM 1603 CA GLY B 384 32.942 14.646 30.766 1.00 30.26 C
ATOM 1604 C GLY B 384 32.682 15.595 29.626 1.00 30.31 C
ATOM 1605 O GLY B 384 32.329 16.758 29.842 1.00 30.29 O
ATOM 1606 N THR B 385 32.847 15.087 28,395 1.00 31.03 N ATOM 1607 CA THR B 385 32.593 15.875 27.199 1.00 30.45 C
ATOM 1608 CB THR B 385 33.438 15.415 26.014 1.00 28.29 C
ATOM 1609 OG1 THR B 385 33.099 14.068 25,686 1.00 27.30 O
ATOM 1610 CG2 THR B 385 34.957 15,580 26.261 1.00 27.71 C
ATOM 1611 C THR B 385 31.056 16.058 26.984 1.00 31 ,10 C JB2010.7161
ATOM 1612 O THR B 385 30.648 16.961 26.238 1.00 31.17 O
ATOM 1613 N SER B 386 30.217 15.240 27.687 1.00 31.22 N
ATOM 1614 CA SER B 386 28.756 15.321 27.689 1.00 31.62 C
ATOM 1615 CB SER B 386 28.176 14.220 28.563 1.00 36.50 C ATOM 1616 OG SER B 386 28.069 13.010 27.834 1.00 38.36 O
ATOM 1617 C SER B 386 28.367 16.644 28.325 1.00 31.50 C
ATOM 1618 O SER B 386 27.543 17.375 27.786 1.00 31.25 O
ATOM 1619 N GLN B 387 28.977 16.946 29.489 1.00 31.13 N
ATOM 1620 CA GLN B 387 28.768 18.154 30.263 1.00 31.03 C ATOM 1621 CB GLN B 387 29.575 18.096 31.567 1.00 32.62 C
ATOM 1622 CG GLN B 387 28.853 17.439 32.731 1.00 34.21 C
ATOM 1623 CD GLN B 387 28.674 15.944 32.605 1.00 36.04 C
ATOM 1624 OE1 GL B 387 29.602 15.183 32.249 1.00 38.45 O
ATOM 1625 NE2 GLN B 387 27.468 15.485 32.920 1.00 34.91 N ATOM 1626 C GLN B 387 29.185 19.337 29.460 1.00 30.83 C
ATOM 1627 0 GLN B 387 28.511 20.363 29.51 1 1.00 31.25 O
ATOM 1628 N ALA B 388 30.301 19.207 28.715 1.00 30.62 N
ATOM 1629 CA ALA B 388 30.849 20.272 27.876 1.00 30. 0 C
ATOM 1630 CB ALA B 388 32.206 19.872 27.330 1.00 30.75 C ATOM 1631 C ALA B 388 29.877 20.582 26.750 1.00 29.94 C
ATOM 1632 O ALA B 388 29.502 21.729 26.583 1.00 29.44 O
ATOM 1633 N ALA B 389 29.421 19.547 26.024 1.00 31.33 N
ATOM 1634 CA ALA B 389 28.453 19.676 24.940 1.00 31.11 C
ATOM 1635 CB ALA B 389 28.156 18.314 24.330 1.00 30.76 C ATOM 1636 C ALA B 389 27. 68 20.357 25.445 1.00 31.27 C
ATOM 1637 0 ALA B 389 26.676 21.262 24.783 1.00 32.01 O
ATOM 1638 N ALA B 390 26.663 19.985 26.622 1.00 30.87 N
ATOM 1639 CA ALA B 390 25.463 20.580 27.214 1.00 30.98 C
ATOM 1640 CB ALA B 390 25.135 19.900 28.531 1.00 31.01 C ATOM 1641 C ALA B 390 25.625 22.088 27.414 1.00 31.43 C
ATOM 1642 O ALA B 390 24.632 22.816 27.292 1.00 31.67 O
ATOM 1643 N HIS B 391 26.864 22.567 27.707 1.00 32.37 N
ATOM 1644 CA HIS B 391 27.111 24.001 27.869 1.00 33.22 C
ATOM 1645 CB HIS B 391 28.525 24.291 28.402 1.00 33.95 C ATOM 1646 CG HIS B 391 28.655 24.077 29.876 1.00 36.59 C
ATOM 1647 ND1 HIS B 391 28.895 22.804 30.413 1.00 37.63 N
ATOM 1648 CE1 HIS B 391 28.953 22.976 31.726 1.00 38.29 C
ATOM 1649 NE2 HIS B 391 28.750 24.259 32.063 1.00 39.60 N
ATOM 1650 CD2 HIS B 391 28.564 24.971 30.889 1.00 37.59 C ATOM 1651 C HIS B 391 26.902 24.691 26.512 1.00 33.42 C
ATOM 1652 O HIS B 391 26.240 25.739 26.444 1.00 33.88 O
ATOM 1653 N VAL B 392 27.441 24.078 25.429 1.00 32.39 N
ATOM 1654 CA VAL B 392 27.322 24.593 24.084 1.00 31.84 C
ATOM 1655 CB VAL B 392 28.376 24.015 23.130 1.00 35.16 C ATOM 1656 CG1 VAL B 392 28.177 24.519 21.705 1.00 33.80 C
ATOM 1657 CG2 VAL B 392 29.769 24.382 23.610 1.00 34.05 C
ATOM 1658 C VAL B 392 25.887 24.504 23.600 1.00 32.06 C
ATOM 1659 O VAL B 392 25.427 25.439 22.947 1.00 32.51 O
ATOM 1660 N ALA B 393 25.161 23.435 23.967 1.00 31.25 N ATOM 1661 CA ALA B 393 23.743 23.248 23.613 1.00 31.15 C
ATOM 1662 CB ALA B 393 23.239 21.899 24.115 1 .00 31.57 C
ATOM 1663 C ALA B 393 22.930 24.399 24.233 1.00 31.15 C
ATOM 1664 O ALA B 393 22.107 25.001 23.542 1.00 30.93 O
ATOM 1665 N GLY B 394 23.224 24.730 25.496 1.00 28.92 N J82010.7161
ATOM 1666 CA GLY B 394 22.594 25.836 26.214 1.00 28.90 C
ATOM 1667 C GLY B 394 22.941 27.159 25.569 1.00 28.80 C
ATOM 1668 O GLY B 394 22.045 27.960 25.331 1.00 28.47 O
ATOM 1669 N ILE B 395 24.243 27.382 25.230 1.00 28.11 N ATOM 1670 CA ILE B 395 24.681 28.608 24.564 1.00 28.23 C
ATOM 1671 CB ILE B 395 26.219 28.673 24.332 1.00 30.37 C
ATOM 1672 CG1 ILE B 395 26.973 28.850 25.651 1.00 30.30 C
ATOM 1673 CD1 ILE B 395 28.479 28.604 25.561 1.00 29.55 C
ATOM 1674 CG2 ILE B 395 26.586 29.824 23.394 1.00 29.94 C ATOM 1675 C ILE B 395 23.853 28.770 23.263 1.00 28.84 C
ATOM 1676 0 ILE B 395 23.197 29.797 23.104 1.00 28.22 O
ATOM 1677 N ALA B 396 23.847 27.738 22.379 1.00 31.41 N
ATOM 1678 CA ALA B 396 23.096 27.731 21.125 1.00 32.70 C
ATOM 1679 CB ALA B 396 23.254 26.398 20.411 1.00 32.94 C ATOM 1680 C ALA B 396 21.612 28.052 21.356 1.00 33.87 C
ATOM 1681 O ALA B 396 21.065 28.907 20.658 1.00 34.27 O
ATOM 1682 N ALA B 397 20.976 27.407 22.359 1.00 36.93 N
ATOM 1683 CA ALA B 397 19.571 27.619 22.737 1 ,00 37.93 C
ATOM 1684 CB ALA B 397 19.229 26.787 23.962 1.00 37.84 C ATOM 1685 C ALA B 397 19.310 29.103 23.017 1.00 38.83 C
ATOM 1686 O ALA B 397 18.273 29.638 22.622 1.00 39.41 O
ATOM 1687 N MET B 398 20.261 29.777 23.671 1.00 40.11 N
ATOM 1688 CA MET B 398 20.148 31.202 23.982 1.00 40.74 C
ATOM 1689 CB MET B 398 21.106 31.576 25.096 1.00 42.73 C ATOM 1690 CG MET B 398 20.795 30.859 26.365 1.0042.35 C
ATOM 1691 SD MET B 398 21.662 31.705 27.645 1.00 46.72 S
ATOM 1692 CE MET B 398 23.127 30.773 27.705 1.0047.02 C
ATOM 1693 C MET B 398 20.349 32.070 22.737 1.00 41.34 C
ATOM 1694 O MET B 398 19.550 32.965 22.483 1.00 42.31 O ATOM 1695 N MET B 399 21.368 31.775 21.932 1.00 40.12 N
ATOM 1696 CA MET B 399 21.645 32.478 20.694 1.00 40.69 C
ATOM 1697 CB MET B 399 22.882 31.893 20.045 1.00 42.85 C
ATOM 1698 CG MET B 399 24.150 32.117 20.791 1.0043.83 C
ATOM 1699 SD MET B 399 25.374 31.448 19.680 1.00 49.74 S ATOM 1700 CE MET B 399 26.796 32.021 20.392 1.00 52.28 C
ATOM 1701 C MET B 399 20.479 32.353 19.710 1.00 41.21 C
ATOM 1702 O MET B 399 20.246 33.277 18.935 1.00 41.57 O
ATOM 1703 N LEU B 400 19.771 31.218 19.719 1 .00 41.79 N
ATOM 1704 CA LEU B 400 18.656 30.986 18.81 1 1.00 42.56 C ATOM 1705 CB LEU B 400 18.495 29.496 18.473 1.00 42.93 C
ATOM 1706 CG LEU B 400 19.584 28.804 17.665 1.00 42.85 C
ATOM 1707 CD1 LEU B 400 19.409 27.319 17.740 1.00 42.29 C
ATOM 1708 CD2 LEU B 400 19.581 29.231 16.225 1.00 41.60 C
ATOM 1709 C LEU B 400 17.343 31.532 19.352 1.00 43.24 C ATOM 1710 O LEU B 400 16.378 31.677 18.584 1.0042.72 O
ATOM 1711 N SER B 401 17.271 31.798 20.670 1.00 45.20 N
ATOM 1712 CA SER B 401 16.029 32.355 21.196 1.0046.54 C
ATOM 1713 CB SER B 401 15.858 32.072 22.681 1.00 49.19 C
ATOM 1714 OG SER B 401 16.896 32.672 23.430 1.00 49.96 O ATOM 1715 C SER B 401 16.029 33.850 20.858 1.00 47.30 C
ATOM 1716 0 SER B 401 14.981 34.398 20.517 1.00 47.76 O
ATOM 1717 N ALA B 402 17.221 34.482 20.876 1.00 47.74 N
ATOM 1718 CA ALA B 402 17.374 35.878 20.501 1.00 48.80 C
ATOM 1719 CB ALA B 402 18.719 36.433 20.970 1.00 49.23 C JB2010.7161
ATOM 1720 C ALA B 402 17.238 35.950 18.973 1.00 49.59 C
ATOM 1721 O ALA B 402 16.235 36.484 18.534 1.00 50.46 O
ATOM 1722 N GLU B 403 18.176 35.356 18.178 1.00 51.18 N
ATOM 1723 CA GLU B 403 18.170 35.343 16.708 1.00 51.74 C ATOM 1724 CB GLU B 403 19.555 35.747 16.156 1.00 54.29 C
ATOM 1725 CG GLU B 403 19.885 37.227 16.308 1.00 57.07 C
ATOM 1726 CD GLU B 403 21.318 37.590 16.677 1.00 61.43 C
ATOM 1727 OE1 GLU B 403 22.244 37.214 15.920 1.00 63.75 O
ATOM 1728 OE2 GLU B 403 21.513 38.266 17.718 1 ,00 62.61 O ATOM 1729 C GLU B 403 17.712 33.977 16.125 1.00 51.80 C
ATOM 1730 O GLU B 403 18.573 33.164 15.792 1.00 51.55 O
ATOM 1731 N PRO B 404 16.382 33.703 15.962 1.00 50,85 N
ATOM 1732 CA PRO B 404 15.949 32.382 15.447 1.00 50.90 C
ATOM 1733 CB PRO B 404 14.427 32.418 15.607 1.00 52.08 C ATOM 1734 CG PRO B 404 14.151 33.540 16.572 1.00 51.80 C
ATOM 1735 CD PRO B 404 15.214 34.539 16.306 1.00 51.82 C
ATOM 1736 C PRO B 404 16.357 32.014 14.027 1.00 51.34 C
ATOM 1737 O PRO B 404 16.498 30.831 13.713 1.00 51.29 O
ATOM 1738 N GLU B 405 16.548 33.020 13.170 1.00 56.93 N ATOM 1739 CA GLU B 405 16.951 32.796 11.784 1.00 57.90 C
ATOM 1740 CB GLU B 405 16.703 34.048 10.922 1.00 60.93 C
ATOM 1741 CG GLU B 405 15.275 34.186 10.404 1.00 65.32 C
ATOM 1742 CD GLU B 405 15.132 35.115 9.204 1.00 71.38 C
ATOM 1743 OE1 GLU B 405 15.065 36.352 9.409 1.00 73.45 O ATOM 1744 OE2 GLU B 405 15.090 34.604 8.056 1.00 72.89 O
ATOM 1745 C GLU B 405 18.414 32.295 11.659 1.00 57.31 C
ATOM 1746 O GLU B 405 18.796 31.839 10.579 1.00 57.49 O
ATOM 1747 N LEU B 406 19.219 32.358 12.758 1.00 53.77 N
ATOM 1748 CA LEU B 406 20.615 31.908 12.771 1.00 52.59 C ATOM 1749 CB LEU B 406 21.169 31.843 14.191 1.00 52.14 C
ATOM 1750 CG LEU B 406 21.880 33.027 14.777 1.00 51.95 C
ATOM 1751 CD1 LEU B 406 22.479 32.637 16.108 1.00 51.04 C
ATOM 1752 CD2 LEU B 406 23.003 33.521 13.878 1.00 52.05 C
ATOM 1753 C LEU B 406 20.773 30.534 12.157 1.00 51.68 C ATOM 1754 0 LEU B 406 20.170 29.564 12.611 1 .00 51.65 O
ATOM 1755 N THR B 407 21.594 30.450 11.129 1.00 49.45 N
ATOM 1756 CA THR B 407 21.863 29.185 10.467 1.00 48.52 C
ATOM 1757 CB THR B 407 22.322 29.442 9.014 1.00 54.68 C
ATOM 1758 OG1 THR B 407 23.499 30.245 9.020 1.00 55.21 O ATOM 1759 CG2 THR B 407 21.248 30.112 8.167 1.00 54.39 C
ATOM 1760 C THR B 407 22.924 28.447 11.291 1.00 47.80 C
ATOM 1761 O THR B 407 23.564 29.056 12.159 1.00 47.67 O
ATOM 1762 N LEU B 408 23.123 27.151 11.024 1.00 45.39 N
ATOM 1763 CA LEU B 408 24.142 26.399 11.744 1.00 44.58 C ATOM 1764 CB LEU B 408 24.090 24.907 11.367 1.00 44.20 C
ATOM 1765 CG LEU B 408 25.319 24.055 11.647 1.00 44.18 C
ATOM 1766 CD1 LEU B 408 25.666 23.998 13.141 1.00 43.22 C
ATOM 1767 CD2 LEU B 408 25.131 22,665 11.097 1.00 45.48 C
ATOM 1768 C LEU B 408 25.542 27.026 11.522 1.00 44.23 C ATOM 1769 0 LEU B 408 26.285 27.207 12.494 1.00 43.96 O
ATOM 1770 H ALA B 409 25.883 27.375 10.260 1.00 43.16 N
ATOM 1771 CA ALA B 409 27.172 27.982 9.907 1.00 42.78 C
ATOM 1772 CB ALA B 409 27.265 28.171 8.403 1.00 43.38 C
ATOM 1773 C ALA B 409 27.395 29.317 10.636 1.00 42.75 C JB2010.7161
ATOM 1774 O ALA B 409 28.501 29.575 11.102 1.00 42.80 O
ATOM 1775 N GLU B 410 26.341 30.138 10.765 1.00 43.61 N
ATOM 1776 CA GLU B 10 26.411 31.417 11.457 1.00 43.75 C
ATOM 1777 CB GLU B 410 25.151 32.230 11.230 1.00 46.64 C ATOM 1778 CG GLU B 410 25.038 32.866 9.860 1.00 49.84 C
ATOM 1779 CD GLU B 410 23.686 33.530 9.700 1.00 55.12 C
ATOM 1780 OE1 GLU B 410 22.685 32.796 9.526 1.00 57.53 O
ATOM 1781 OE2 GLU B 410 23.622 34.779 9.784 1.00 56.56 O
ATOM 1782 C GLU B 410 26.638 31.202 12.931 1.00 42.87 C ATOM 1783 O GLU B 410 27.507 31.854 13.515 1.00 43.02 O
ATOM 1784 N LEU B 41 1 25.869 30.265 13.528 1.00 41.07 N
ATOM 1785 CA LEU B 411 25.967 29.871 14.930 1.0040.19 C
ATOM 1786 CB LEU B 411 24.945 28.775 15.234 1.00 40.22 C
ATOM 1787 CG LEU B 411 24.450 28.718 16.659 1.00 39.86 C ATOM 1788 CD1 LEU B 41 1 23.076 28.142 16.714 1.00 39.92 C
ATOM 1789 CD2 LEU B 411 25.390 27.909 17.532 1.00 40.65 C
ATOM 1790 C LEU B 411 27.389 29.373 15.228 1.00 39.99 C
ATOM 1791 O LEU B 411 28.012 29.896 16.152 1.00 39.63 O
ATOM 1792 N ARG B 412 27.916 28.396 14.425 1.00 40.13 N ATOM 1793 CA ARG B 412 29.274 27.870 14.587 1.00 39.82 C
ATOM 1794 CB ARG B 412 29.613 26.825 13.520 1.00 39.97 C
ATOM 1795 CG ARG B 412 30.992 26.176 13.723 1.00 40.57 C
ATOM 1796 CD ARG B 412 31.442 25.301 12.563 1.00 43,57 C
ATOM 1797 NE ARG B 412 30.618 24.093 12.429 1.00 46.36 N ATOM 1798 CZ ARG B 412 29.633 23.946 11.542 1.00 48.08 C
ATOM 1799 NH1 ARG B 412 29.355 24.921 10.677 1.00 47.77 N
ATOM 1800 NH2 ARG B 412 28.921 22.823 11.510 1.00 50.08 N
ATOM 1801 C ARG B 412 30.319 28.996 14.598 1.00 39.65 C
ATOM 1802 O ARG B 412 31.134 29.063 15.520 1.00 39.44 O ATOM 1803 N GLN B 413 30.282 29.885 13.585 1.00 39.49 N
ATOM 1804 CA GL B 413 31.202 31.020 13.444 1.00 38.75 C
ATOM 1805 CB GL B 413 30.946 31.758 12.128 1.00 38.86 C
ATOM 1806 CG GLN B 13 31.319 30.943 10.894 1.00 38.63 C
ATOM 1807 CD GLN B 413 32.755 31.101 10.464 1.00 38.55 C ATOM 1808 OE1 GLN B 413 33.580 31.737 11.146 1.00 39.82 O
ATOM 1809 NE2 GLN B 413 33.094 30.516 9.320 1.00 36.96 N
ATOM 1810 C GLN B 413 31.101 31.961 14.644 1.00 38.89 C
ATOM 181 1 O GLN B 413 32.126 32.461 15.113 1.00 39.11 O
ATOM 1812 N ARG B 414 29.879 32.174 15.160 1.00 39.35 N ATOM 1813 CA ARG B 414 29.649 33.027 16.322 1.00 40.00 C
ATOM 1814 CB ARG B 414 28.151 33.328 16.486 1.00 45.04 C
ATOM 1815 CG ARG B 414 27.750 34.654 15.859 1.00 47.55 C
ATOM 1816 CD ARG B 414 26.323 34.622 15.389 1.00 54.74 C
ATOM 1817 NE ARG B 414 25.788 35.952 15.072 1.00 61.39 N ATOM 1818 CZ ARG B 414 25.841 36.538 13.870 1.00 64.51 C
ATOM 1819 NH1 ARG B 414 25.309 37.739 13.689 1.00 66.31 N
ATOM 1820 NH2 ARG B 414 26.438 35.928 12.845 1.00 65.41 N
ATOM 1821 C ARG B 414 30.262 32.390 17.578 1.00 39.75 C
ATOM 1822 O ARG B 414 30.915 33.089 18.355 1 .00 39.68 O ATOM 1823 N LEU B 415 30.094 31.056 17.742 1.00 38.85 N
ATOM 1824 CA LEU B 415 30.643 30.282 18.854 1.00 38.51 C
ATOM 1825 CB LEU B 415 30.237 28.812 18.750 1.00 38.36 C
ATOM 1826 CG LEU B 415 28.858 28.432 19.260 1.00 38.24 C
ATOM 1827 CD1 LEU B 415 28.638 26.957 19.073 1.00 36.13 C JB2010.7161
ATOM 1828 CD2LEUB415 28.677 28.81420.733 1.0037.22 C
ATOM 1829 C LEU B 415 32.167 30.370 18.902 1.0038.43 C
ATOM 1830 O LEU B 415 32.729 30.507 19.991 1.0038.76 O
ATOM 1831 N ILEB416 32.828 30.291 17.721 1.0037.43 N ATOM 1832 CA ILE B 416 34.284 30.368 17.536 1.0036.87 C
ATOM 1833 CB ILE B 416 34.709 29.837 16.129 1.0038.18 C
ATOM 1834 CG1 ILEB416 34.34428.342 15.969 1.0037.59 C
ATOM 1835 CD1 ILE B 416 34.485 27.760 14.598 1.0037.42 C
ATOM 1836 CG2ILEB416 36.188 30.092 15.840 1.0036.14 C ATOM 1837 C ILE B 416 34.743 31.801 17.784 1.0037.40 C
ATOM 18380 ILEB416 35.710 32.011 18.515 1.0037.27 O
ATOM 1839 N H1SB417 34.054 32.779 17.195 1.0039.76 N
ATOM 1840 CA HISB417 34.42734.175 17.361 1.0040.92 C
ATOM 1841 CB HISB417 33.56535.062 16.479 1.0043.05 C ATOM 1842 CG HISB417 33.906 36.513 16.558 1.0044.38 C
ATOM 1843 ND1 HISB417 34.91637.057 15.788 1.0045.97 N
ATOM 1844 CE1 HISB417 34.94538.340 16.096 1.0048.40 C
ATOM 1845 NE2HISB417 34.01638.648 17.009 1.0048.19 N
ATOM 1846 CD2H1SB417 33.341 37.492 17.301 1.0046.53 C ATOM 1847 C HISB417 34.38734.661 18.798 1.0041.21 C
ATOM 1848 O HIS B 417 35.347 35.284 19.241 1.0041.24 O
ATOM 1849 N PHEB418 33.28634.368 19.522 1.0041.96 N
ATOM 1850 CA PHE B 418 33.048 34.79620.898 1.0042.07 C
ATOM 1851 CB PHE B 418 31.55735.04321.112 1.0043.63 C ATOM 1852 CG PHE B418 31.13436.25320.321 1.0044.73 C
ATOM 1853 CD1 PHE B 418 31.53237.532 20.708 1.0046.04 C
ATOM 1854 CE1 PHEB418 31.165 38.653 19.963 1.0047.25 C
ATOM 1855 CZ PHE B 418 30.39638.500 18.829 1.0047.75 C
ATOM 1856 CE2PHEB418 30.00037.238 18.425 1.0047.01 C ATOM 1857 CD2PHEB418 30.372 36.116 19.169 1.0045.87 C
ATOM 1858 C PHE B 418 33.706 34.01522.043 1.0041.85 C
ATOM 1859 O PHE B 418 33.616 34.42723.206 1.0042.28 O
ATOM 1860 N SERB 419 34.382 32.92021.721 1.0039.67 N
ATOM 1861 CA SERB 419 35.049 32.09022.709 1.0039.12 C ATOM 1862 CB SERB419 35.262 30.69622.133 1.0040.85 C
ATOM 1863 OG SERB 419 36.10030.740 20.987 1.0041.24 O
ATOM 1864 C SERB 419 36.401 32.681 23.163 1.0038.79 C
ATOM 1865 O SERB 419 37.009 33.45222.417 1.0038.93 O
ATOM 1866 N ALA B 420 36.872 32.286 24.380 1.0037.80 N ATOM 1867 CA ALA B 420 38.16632.647 24.979 1.0037.51 C
ATOM 1868 CB ALA B 420 38.22832.172 26.420 1.0037.60 C
ATOM 1869 C ALA B 420 39.22431.908 24.150 1.0037.79 C
ATOM 1870 O ALA B 420 39.063 30.71323.868 1.0038.19 O
ATOM 1871 N LYS B 421 40.277 32.621 23.733 1.0037.78 N ATOM 1872 CA LYS B 421 41.34332.096 22.868 1.0037.81 C
ATOM 1873 CB LYS B 421 41.481 32.988 21.607 1.0039.08 C
ATOM 1874 CG LYS B 421 40.179 33.59821.092 1.0039.35 C
ATOM 1875 CD LYS B 421 39.780 33.121 19.687 1.0039.77 C
ATOM 1876 CE LYS B 421 38.338 33.450 19.349 1.0040.89 C ATOM 1877 NZ LYS B 421 38.020 34.903 19.487 1.0039.05 N
ATOM 1878 C LYS B 421 42.683 32.00623.583 1.0038.06 C
ATOM 1879 O LYS B 421 42.973 32.85924.413 1.0038.21 O
ATOM 1880 N ASP B 422 43,507 31.00623.255 1.0040.82 N
ATOM 1881 CA ASP B 422 44.829 30.801 23.867 1.0041.70 C JB2010.7161
ATOM 1882 CB ASP B 422 45.878 31.775 23.307 1.0046.66 C
ATOM 1883 CG ASP B 422 46.661 31.131 22.196 1.00 50.94 C
ATOM 1884 OD1 ASP B 422 46.215 31.237 21.003 1.00 55.08 0
ATOM 1885 OD2 ASP B 422 47.697 30.481 22.503 1.00 53.58 O ATOM 1886 C ASP B 422 44.876 30.689 25.407 1.00 41.14 C
ATOM 1887 O ASP B 422 45.860 31 ,084 26.023 1 ,00 41.22 O
ATOM 1888 N VAL B 423 43.822 30.134 26.016 1.00 39.57 N
ATOM 1889 CA VAL B 423 43.702 29.947 27.466 1.00 38.98 C
ATOM 1890 CB VAL B 423 42.251 30.196 27.957 1.0041.32 C ATOM 1891 CG1 VAL B 423 41 .928 31.679 27.976 1.00 39.47 C
ATOM 1892 CG2 VAL B 423 41 ,237 29.427 27.104 1.00 42.00 C
ATOM 1893 C VAL B 423 44.211 28.551 27.880 1.00 38.82 C
ATOM 1894 O VAL B 423 44.654 28.361 29.023 1.00 38.71 O
ATOM 1895 N ILE B 424 44.118 27.580 26.947 1.00 36.97 N ATOM 1896 CA ILE B 424 44.555 26.204 27.139 1.00 36.34 C
ATOM 1897 CB ILE B 424 43.836 25.252 26.117 1.00 36.22 C
ATOM 1898 CG1 ILE B 424 42.303 25.206 26.304 1.00 34.62 C
ATOM 1899 CD1 ILE B 424 41.532 24.699 25.159 1.00 30.94 C
ATOM 1900 CG2 ILE B 424 44.437 23.848 26.151 1.00 35.32 C ATOM 1901 C ILE B 424 46.081 26.142 26.921 1.00 37.30 C
ATOM 1902 O ILE B 424 46.599 26.725 25.951 1 ,00 37.17 O
ATOM 1903 N ASN B 425 46.791 25.408 27.797 1.00 39.51 N
ATOM 1904 CA ASN B 425 48.221 25.173 27.645 1.00 39.74 C
ATOM 1905 CB ASN B 425 48.873 24.887 29.002 1.00 38.72 C ATOM 1906 CG AS B 425 50.212 24.201 28.967 1.00 36.90 C
ATOM 1907 OD1 ASN B 425 50.972 24.297 28.011 1.00 36.28 O
ATOM 1908 ND2 ASN B 425 50.523 23.502 30.035 1.00 36.27 N
ATOM 1909 C ASN B 425 48.242 23.948 26.724 1.00 40.57 C
ATOM 1910 O ASN B 425 47.732 22.873 27.101 1.00 40.66 O ATOM 1911 N GLU B 426 48.793 24.130 25.506 1.00 41.97 N
ATOM 1912 CA GLU B 426 48.841 23.116 24.456 1.00 42.73 C
ATOM 1913 CB GLU B 426 49.414 23.676 23.156 1.00 44.82 C
ATOM 1914 CG GLU B 426 48.881 25.046 22.777 1.0047.79 C
ATOM 1915 CD GLU B 426 47.832 25.074 21.685 1.00 50.96 C ATOM 1916 OE1 GLU B 426 47.554 26.177 21.165 1.00 50.28 O
ATOM 1917 OE2 GLU B 426 47.283 24.000 21.349 1.00 55.54 O
ATOM 1918 C GLU B 426 49.541 21.846 24.855 1.00 42.86 C
ATOM 1919 0 GLU B 426 49.263 20.802 24.254 1.00 43.13 O
ATOM 1920 N ALA B 427 50.422 21.916 25.887 1.00 43.09 N ATOM 1921 CA ALA B 427 51.179 20,773 26.418 1.00 43.00 C
ATOM 1922 CB ALA B 427 52.129 21.226 27.506 1.00 43.10 C
ATOM 1923 C ALA B 427 50.293 19.645 26.949 1.00 43.06 C
ATOM 1924 O ALA B 427 50,771 18.516 27.059 1.00 44.27 O
ATOM 1925 N TRP B 428 49.020 19.922 27.281 1.00 41.39 N ATOM 1926 CA TRP B 428 48.135 18.877 27.791 1.00 40.80 C
ATOM 1927 CB TRP B 428 46.923 19.469 28.511 1.00 38.73 C
ATOM 1928 CG TRP B 428 47.230 20.173 29.803 1.00 36.49 C
ATOM 1929 CD1 TRP B 428 47.284 21.519 30.003 1.00 35.37 C
ATOM 1930 NE1 TRP B 428 47.541 21.794 31.331 1.00 33.63 N ATOM 1931 CE2 TRP B 428 47.665 20.613 32.016 1.00 31.02 C
ATOM 1932 CD2 TRP B 428 47.463 19.566 31.086 1.00 32.10 C
ATOM 1933 CE3 TRP B 428 47.533 18.238 31.540 1.00 29.82 C
ATOM 1934 CZ3 TRP B 28 47.802 18.002 32.879 1.00 28.77 C
ATOM 1935 CH2 TRP B 428 47.969 19.063 33.782 1.00 29.57 C JB2010J161
ATOM 1936 CZ2 TRP B 428 47.916 20.374 33.372 1.00 28.78 C
ATOM 1937 C TRP B 428 47.690 17.908 26.697 1.00 41.11 C
ATOM 1938 O TRP B 428 47.067 16.881 27.005 1.00 41.37 O
ATOM 1939 N PHE B 429 48.022 18.227 25.425 1.00 39.04 N ATOM 1940 CA PHE B 429 47.701 17.429 24.243 1.00 39.04 C
ATOM 1941 CB PHE B 429 47.101 18.322 23.144 1 .00 39.96 C
ATOM 1942 CG PHE B 429 45.892 19.133 23.504 1.00 39.77 C
ATOM 1943 CD1 PHE B 429 44.708 18.513 23.889 1.00 39.59 C
ATOM 1944 CE1 PHE B 429 43.580 19.263 24.205 1.00 40.11 C ATOM 1945 CZ PHE B 429 43.624 20.639 24.120 1.00 40.98 C
ATOM 1946 CE2 PHE B 429 44.784 21.268 23.725 1.00 39.98 C
ATOM 1947 CD2 PHE B 429 45.918 20.513 23.416 1.00 39.50 C
ATOM 1948 C PHE B 429 48.950 16.838 23.639 1.00 39.52 C
ATOM 1949 O PHE B 429 50.003 17.489 23.678 1.00 39.18 O ATOM 1950 N PRO B 430 48.846 15.657 22.974 1.00 42.11 N
ATOM 1951 CA PRO B 430 50.011 15.104 22.278 1.00 42.59 C
ATOM 1952 CB PRO B 430 49.435 13.894 21.552 1.00 43.87 C
ATOM 1953 CG PRO B 430 48.255 13.498 22.365 1.00 43.15 C
ATOM 1954 CD PRO B 430 47.669 14.778 22.814 1.00 43.75 C ATOM 1955 C PRO B 430 50.556 16.129 21.281 1.00 43.92 C
ATOM 1956 O PRO B 430 49.792 16.874 20.660 1.00 43.68 O
ATOM 1957 N GLU B 431 51.893 16.185 21.175 1.00 49.11 N
ATOM 1958 CA GLU B 431 52.670 17.086 20.336 1.00 50.18 C
ATOM 1959 CB GLU B 431 54.131 16.627 20.333 1.00 52.66 C ATOM 1960 CG GLU B 431 55.106 17.661 19.809 1.00 56.44 C
ATOM 1961 CD GLU B 431 56.502 17.132 19.551 1.00 61.76 C
ATOM 1962 OE1 GLU B 431 57.389 17.951 19.207 1.00 64.00 O
ATOM 1963 OE2 GLU B 431 56.712 15.902 19.693 1.00 63.68 O
ATOM 1964 C GLU B 431 52.121 17.227 18.922 1.00 49.92 C ATOM 1965 0 GLU B 431 51.899 18.337 18.450 1.00 50.01 O
ATOM 1966 N ASP B 432 51.890 16.101 18.262 1.00 50.62 N
ATOM 1967 CA ASP B 432 51.366 16.010 16.897 1.00 50.88 C
ATOM 1968 CB ASP B 432 51.337 14.534 16.453 1.00 54.61 C
ATOM 1969 CG ASP B 432 50.902 13.556 17.554 1.00 58.29 C ATOM 1970 OD1 ASP B 432 51.665 13.402 18.564 1.00 62.00 O
ATOM 1971 OD2 ASP B 432 49.805 12.940 17.412 1.00 62.00 O
ATOM 1972 C ASP B 432 49.976 16.633 16.751 1.00 49.73 C
ATOM 1973 O AS B 432 49.573 16.915 15.631 1.00 49.96 O
ATOM 1974 N GLN B 433 49,255 16.860 17.872 1.00 45.67 N ATOM 1975 CA GLN B 433 47.886 17.399 17.919 1.00 44.41 C
ATOM 1976 CB GLN B 433 47.005 16.497 18.811 1.00 44.62 C
ATOM 1977 CG GLN B 433 46.842 15.061 18.342 1.00 44.43 C
ATOM 1978 CD GLN B 433 45.922 14.907 17.168 1.0044.24 C
ATOM 1979 OE1 GL B 433 45.140 15.788 16.821 1.00 47.18 O ATOM 1980 NE2 GLN B 433 45.997 13.771 16.520 1.00 43.33 N
ATOM 1981 C GLN B 433 47.732 18.851 18.392 1.00 43.67 C
ATOM 1982 O GLN B 433 46.644 19.405 18.275 1.00 43.50 O
ATOM 1983 N ARG B 434 48.771 19.456 18.956 1.00 42.47 N
ATOM 1984 CA ARG B 434 48.688 20.826 19.467 1.00 42.25 C ATOM 1985 CB ARG B 434 50.000 21.264 20.130 1 .00 39.80 C
ATOM 1986 CG ARG B 434 50.564 20.177 21.036 1.00 40.42 C
ATOM 1987 CD ARG B 434 51.677 20.616 21.948 1.00 40.89 C
ATOM 1988 NE ARG B 434 51.809 19.613 23.001 1.00 43.13 N
ATOM 1989 CZ ARG B 434 52.931 18.983 23.326 1.00 42.41 C JB2010.7161
ATOM 1990 NH1 A G B 434 54.070 19.276 22.710 1.00 41.84 N
ATOM 1991 NH2 ARG B 434 52.927 18.065 24.281 1.00 41.70 N
ATOM 1992 C ARG B 434 48.230 21.803 18.410 1.00 42.31 C
ATOM 1993 O ARG B 434 47.388 22.650 18.698 1.00 43.00 O ATOM 1994 N VAL B 435 48.739 21.650 17.177 1.00 43.08 N
ATOM 1995 CA VAL B 435 48.421 22.483 16.019 1.00 42.24 C
ATOM 1996 CB VAL B 435 49.526 22.328 14.933 1.00 45.00 C
ATOM 1997 CG1 VAL B 435 49.192 21.270 13.873 1.00 45.14 C
ATOM 1998 CG2 VAL B 435 49.823 23.649 14.284 1.00 44.07 C ATOM 1999 C VAL B 435 46.991 22.269 15.468 1.00 41.94 C
ATOM 2000 O VAL B 435 46.379 23.226 14.992 1.00 42.12 O
ATOM 2001 N LEU B 436 46.482 21.017 15.513 1.00 41.86 N
ATOM 2002 CA LEU B 436 45.167 20.618 14.997 1.00 41.03 C
ATOM 2003 CB LEU B 436 45.152 19.112 14.633 1.00 41.00 C ATOM 2004 CG LEU B 436 46.338 18.546 13.828 1.0042.37 C
ATOM 2005 CD1 LEU B 436 46.271 17.033 13.754 1.00 40.94 C
ATOM 2006 CD2 LEU B 436 46.414 19.142 12.429 1.00 42.08 C
ATOM 2007 C LEU B 436 44.055 20.872 15.972 1.00 40.32 C
ATOM 2008 O LEU B 436 42.885 20.839 15.576 1.00 40.23 O ATOM 2009 N THR B 437 44.396 21.089 17.256 1.00 38.95 N
ATOM 2010 CA THR B 437 43.397 21.285 18.311 1.00 38.00 C
ATOM 2011 CB THR B 437 43.782 20.539 19.603 1.00 31.1 1 C
ATOM 2012 OG1 THR B 37 44.170 19.197 19.266 1.00 30.31 O
ATOM 2013 CG2 THR B 437 42.649 20.513 20.626 1.00 29.20 C ATOM 2014 C THR B 437 43.055 22.741 18.487 1.00 37.50 C
ATOM 2015 O THR B 437 43.958 23.530 18.757 1.00 37.98 O
ATOM 2016 N PRO B 438 41.772 23.134 18.318 1.00 33.61 N
ATOM 2017 CA PRO B 438 41.422 24.554 18.493 1.00 33.35 C
ATOM 2018 CB PRO B 438 39.967 24.613 18.028 1.00 33.68 C ATOM 2019 CG PRO B 438 39.444 23.258 18.313 1.00 34.07 C
ATOM 2020 CD PRO B 438 40.577 22.325 17.986 1.00 34.14 C
ATOM 2021 C PRO B 438 41.572 25.030 19.941 1.00 33.40 C
ATOM 2022 O PRO B 438 40.963 24.474 20.863 1 .00 33.98 O
ATOM 2023 N ASN B 439 42.382 26.070 20.145 1.00 35.15 N ATOM 2024 C A ASN B 439 42.568 26.641 21.482 1.00 35.37 C
ATOM 2025 CB ASN B 439 43.920 27.334 21.604 1.00 37.82 C
ATOM 2026 CG ASN B 439 44.415 27.399 23.012 1.00 38.75 C
ATOM 2027 OD1 ASN B 439 43.661 27.682 23.952 1.00 41.16 O
ATOM 2028 ND2 ASN B 439 45.696 27.132 23.196 1.00 39.15 N ATOM 2029 C ASN B 439 41.410 27.616 21.757 1.00 35.24 C
ATOM 2030 O ASN B 439 41.629 28.809 21.945 1.00 34.76 O
ATOM 2031 N LEU B 440 40.170 27.089 21 .751 1.00 34.88 N
ATOM 2032 CA LEU B 440 38.959 27.868 21.980 1.00 35.23 C
ATOM 2033 CB LEU B 440 38.027 27.804 20.772 1.00 34.38 C ATOM 2034 CG LEU B 440 38.592 28.219 19.440 1.00 33.76 C
ATOM 2035 CD1 LEU B 440 37.680 27.755 18.313 1.00 31.28 C
ATOM 2036 CD2 LEU B 440 38.822 29.693 19.399 1.00 33.67 C
ATOM 2037 C LEU B 440 38.200 27.355 23.163 1.00 35.87 C
ATOM 2038 O LEU B 440 38.010 26.147 23.291 1.00 36.19 O ATOM 2039 N VAL B 441 37.750 28.256 24.035 1.00 36.25 N
ATOM 2040 CA VAL B 441 36.946 27.844 25.186 1.00 36.75 C
ATOM 2041 CB VAL B 441 37.673 27.910 26.548 1.00 39.43 C
ATOM 2042 CG1 VAL B 441 36.692 27.778 27.702 1.00 38.58 C
ATOM 2043 CG2 VAL B 441 38.748 26.832 26.635 1.00 39.50 C JB2010.7161
ATOM 2044 C VAL B 4 1 35.665 28.650 25.1 13 1.00 37.43 C
ATOM 2045 O VAL B 441 35.726 29.881 25.103 1.00 37.61 O
ATOM 2046 N ALA B 442 34.524 27.947 25.010 1.00 35.44 N
ATOM 2047 CA ALA B 442 33.189 28.510 24.880 1.00 36.31 C ATOM 2048 CB ALA B 442 32.132 27.421 24.946 1.00 36.51 C
ATOM 2049 C ALA B 442 32.861 29.630 25.845 1.00 37.33 C
ATOM 2050 O ALA B 442 33.308 29.648 26.990 1.00 37.35 O
ATOM 2051 N ALA B 443 32.082 30.583 25.339 1.00 41.06 N
ATOM 2052 CA ALA B 443 31.572 31.770 26.015 1.00 42.74 C ATOM 2053 CB ALA B 443 32.666 32.823 26.136 1.00 43.12 C
ATOM 2054 C ALA B 443 30.422 32.297 25.168 1.00 44.00 C
ATOM 2055 O ALA B 443 30.312 31.942 23.988 1.00 44.19 O
ATOM 2056 N LEU B 444 29.574 33.133 25.766 1.00 47.69 N
ATOM 2057 CA LEU B 444 28.432 33.752 25.112 1.00 49.59 C ATOM 2058 CB LEU B 444 27.401 34.067 26.185 1.00 49.28 C
ATOM 2059 CG LEU B 444 26.268 33.108 26.371 1 .00 49.49 C
ATOM 2060 CD1 LEU B 444 25.778 33.189 27.778 1.00 50.43 C
ATOM 2061 CD2 LEU B 444 25.138 33.370 25.376 1.00 47.83 C
ATOM 2062 C LEU B 444 28.799 35.090 24.474 1.00 51.54 C ATOM 2063 O LEU B 444 29.595 35.815 25.071 1.00 52.09 O
ATOM 2064 N PRO B 445 28.189 35.495 23.322 1.00 57.41 N
ATOM 2065 CA PRO B 445 28.465 36.845 22.777 1.00 58.82 C
ATOM 2066 CB PRO B 445 27.685 36.862 21.453 1.00 60.28 C
ATOM 2067 CG PRO B 445 27.396 35.442 21.152 1.00 59.55 C ATOM 2068 CD PRO B 445 27.198 34.794 22.487 1.00 59.16 C
ATOM 2069 C PRO B 445 27.877 37.841 23.791 1.00 60.24 C
ATOM 2070 O PRO B 445 26.724 37.630 24.193 1.00 61.00 O
ATOM 2071 N PRO B 446 28.640 38.854 24.297 1.00 62.13 N
ATOM 2072 CA PRO B 446 28.086 39.748 25.355 1.00 62.43 C ATOM 2073 CB PRO B 446 29.276 40.629 25.749 1.00 64.66 C
ATOM 2074 CG PRO B 446 30.221 40.576 24.552 1.00 64.26 C
ATOM 2075 CD PRO B 446 30.042 39.200 23.965 1.00 64.26 C
ATOM 2076 C PRO B 446 26.832 40.572 25.046 1.00 62.59 C
ATOM 2077 O PRO B 446 26.347 40.606 23.914 1.00 63.05 O ATOM 2078 N GLN B 454 29.678 42.175 10.580 1.00 70.29 N
ATOM 2079 CA GLN B 454 31.056 41.728 10.805 1.00 70.06 C
ATOM 2080 CB GLN B 454 31.312 41.465 12.303 1.00 72.14 C
ATOM 2081 CG GLN B 454 32.773 41.686 12.717 1.00 75.16 C
ATOM 2082 CD GLN B 454 33.053 41.573 14.210 1.00 79.00 C ATOM 2083 OE1 GLN B 454 32.189 41.816 15.076 1.00 79.99 O
ATOM 2084 NE2 GLN B 454 34.295 41.214 14.544 1.00 79.71 N
ATOM 2085 C GLN B 454 31.443 40.498 9.931 1.00 68.85 C
ATOM 2086 O GLN B 454 30.564 39.725 9.503 1.00 68.74 O
ATOM 2087 N LEU B 455 32.769 40.343 9.651 1.00 60.94 N ATOM 2088 CA LEU B 455 33.278 39.226 8.847 1.00 58.74 C
ATOM 2089 CB LEU B 455 34.316 39.688 7.796 1.00 58.04 C
ATOM 2090 CG LEU B 455 34.962 38.590 6.952 1.00 57.22 C
ATOM 2091 CD1 LEU B 455 33.961 37.898 6.088 1.00 57.38 C
ATOM 2092 CD2 LEU B 455 36.056 39.127 6.114 1.00 56.01 C ATOM 2093 C LEU B 455 33.826 38.115 9.735 1.00 57.13 C
ATOM 2094 O LEU B 455 34.843 38.300 10.399 1.00 56.45 O
ATOM 2095 N PHE B 456 33.137 36.964 9.733 1.00 51.92 N
ATOM 2096 CA PHE B 456 33.499 35.779 10.517 1.00 50.19 C
ATOM 2097 CB PHE B 456 32.242 35.158 11.151 1.00 51.54 C JB2010.7161
ATOM 2098 CG PHE B 456 31.509 36.019 12.149 1.00 52.22 C
ATOM 2099 CD1 PHE B 56 31.842 35.986 13.495 1.0053.30 C
ATOM 2100 CE1 PHE B 456 31.152 36.771 14.420 1.00 53.83 C
ATOM 2101 CZ PHE B 456 30.124 37.583 14.004 1.00 52.84 C ATOM 2102 CE2 PHE B 456 29.783 37.626 12.675 1.00 52.12 C
ATOM 2103 CD2 PHE B 456 30.466 36.837 11.751 1.00 52.74 C
ATOM 2104 C PHE B 456 34.222 34.726 9.651 1.00 48.49 C
ATOM 2105 O PHE B 456 33.700 34.340 8.601 1.00 47.71 O
ATOM 2106 N CYS B 457 35.422 34.281 10.107 1.00 45.94 N ATOM 2107 CA CYS B 457 36.305 33.277 9.471 1.00 44.40 C
ATOM 2108 CB CYS B 457 37.525 33.947 8.834 1.00 45.10 C
ATOM 2109 SG CYS B 457 37.182 34.940 7.359 1.0045.65 S
ATOM 2110 C CYS B 457 36.777 32.195 10.462 1 .00 42.94 C
ATOM 2111 O CYS B 457 37.166 32.522 11.586 1 .00 42.44 O ATOM 2112 N ARG B 458 36.830 30.928 10.022 1.00 39.69 N
ATOM 2113 CA ARG B 458 37.371 29.850 10.851 1.00 38.08 C
ATOM 2114 CB ARG B 458 36.281 28.937 11.447 1.00 36.51 C
ATOM 2115 CG ARG B 458 35.740 27.897 10.493 1.00 34.77 C
ATOM 2116 CD ARG B 458 34.358 27.508 10.875 1.00 33.03 C ATOM 2117 NE ARG B 458 33.710 26.791 9.780 1.00 32.98 N
ATOM 2118 CZ ARG B 458 33.753 25.471 9.602 1.00 31.96 C
ATOM 2119 NH1 ARG B 58 34.420 24.699 10.448 1.00 29.94 N
ATOM 2120 NH2 ARG B 458 33.123 24.915 8.578 1.00 32.98 N
ATOM 2121 C ARG B 458 38.414 29.065 10.050 1.00 37.50 C ATOM 2122 O ARG B 458 38.324 28.991 8.821 1.00 37.60 O
ATOM 2123 N THR B 459 39.394 28.497 10.741 1.00 35.33 N
ATOM 2124 CA THR B 459 40.422 27.693 10.117 1.00 35.10 C
ATOM 2125 CB THR B 459 41.745 27.893 10.862 1.00 38.75 C
ATOM 2126 OG1 THR B 459 41.952 29.281 11.1 11 1.00 39.05 O ATOM 2127 CG2 THR B 459 42.933 27.305 10.126 1.00 38.17 C
ATOM 2128 C THR B 459 39.979 26.205 10.139 1.00 35.06 C
ATOM 2129 O THR B 459 39.530 25.704 11.172 1.00 35.40 O
ATOM 2130 N VAL B 460 40.085 25.510 9.001 1.00 35.20 N
ATOM 2131 CA VAL B 460 39.765 24.089 8.908 1.00 34.64 C ATOM 2132 CB VAL B 460 38.361 23.621 8.403 1.00 35.04 C
ATOM 2133 CG1 VAL B 460 37.493 24.756 7.900 1.00 35.25 C
ATOM 2134 CG2 VAL B 460 38.430 22.479 7.413 1.00 33.46 C
ATOM 2135 C VAL B 460 40.954 23.306 8.398 1*00 35.07 C
ATOM 2136 O VAL B 460 41.476 23.613 7.331 1.00 34.54 O ATOM 2137 N TRP B 461 41.423 22.341 9.201 1.00 38.10 N
ATOM 2138 CA TRP B 461 42.537 21.485 8.849 1.00 38.76 C
ATOM 2139 CB TRP B 461 43.343 21.122 10.083 1.00 35.73 C
ATOM 2140 CG TRP B 461 44.168 22.236 10.626 1.00 33.66 C
ATOM 2141 CD1 TRP B 461 43.730 23.327 11.319 1.00 31.32 C ATOM 2142 NE1 TRP B 461 44.798 24.112 11.689 1.00 29.95 N
ATOM 2143 CE2 TRP B 461 45.953 23.539 11.223 1.00 29.52 C
ATOM 2144 CD2 TRP B 461 45.592 22.342 10.565 1.00 31.33 C
ATOM 2145 CE3 TRP B 461 46.599 21.552 9.994 1.00 30.17 C
ATOM 2146 CZ3 TRP B 461 47.914 21.963 10.11 1 1.00 30.52 C ATOM 2147 CH2 TRP B 461 48.248 23.146 10.790 1.00 29.48 C
ATOM 2148 CZ2 TRP B 461 47.282 23.946 11.357 1.00 29.30 C
ATOM 2149 C TRP B 461 41.985 20.212 8.272 1.00 40.58 C
ATOM 2150 O TRP B 461 40.959 19.693 8.739 1.00 41.43 O
ATOM 2151 N SER B 462 42.672 19.685 7.277 1.00 44.85 N JB2010.7161
ATOM 2152 CA SER B 462 42.321 18.429 6.632 1 .00 46.58 C
ATOM 2153 CB SER B 462 42.975 18.396 5.256 1.00 50.27 C
ATOM 2154 OG SER B 462 44.383 18.523 5.409 1.00 49.03 O
ATOM 2155 C SER B 462 42.974 17.339 7.455 1.00 48.42 C ATOM 2156 O SER B 462 43.774 17.632 8.366 1 ,00 48.39 O
ATOM 2157 N ALA B 463 42.714 16.074 7.091 1.00 51.38 N
ATOM 2158 CA ALA B 463 43,398 14.961 7.740 1.00 53.26 C
ATOM 2159 CB ALA B 463 42.672 13.667 7.435 1.00 53.45 C
ATOM 2160 C ALA B 463 44.800 14.936 7.099 1.00 54.91 C ATOM 2161 O ALA B 463 45.034 15.622 6.099 1.00 54.84 O
ATOM 2162 N HIS B 464 45.721 14.162 7.655 1.00 59.77 N
ATOM 2163 CA HIS B 464 47.059 14.004 7.083 1.00 62.28 C
ATOM 2164 CB HIS B 464 47.904 13.143 8.027 1.00 63.97 C
ATOM 2165 CG HIS B 464 49.376 13.343 7.902 1.00 66.10 C ATOM 2166 ND1 HIS B 464 50.204 12.319 7.481 1.00 67.57 N
ATOM 2167 CE1 HIS B 464 51.432 12.817 7.521 1.00 68.05 C
ATOM 2168 NE2 HIS B 464 51.438 14.088 7.934 1.00 68.20 N
ATOM 2169 CD2 HIS B 464 50.129 14.433 8.184 1.00 67.31 C
ATOM 2170 C HIS B 464 46.866 13.286 5.718 1.00 63.46 C ATOM 2171 O HIS B 464 45.974 12.434 5.584 1.00 63.28 O
ATOM 2172 N SER B 465 47.662 13.667 4.711 1.00 66.57 N
ATOM 2173 CA SER B 465 47.572 13.112 3.355 1.00 67.92 C
ATOM 2174 CB SER B 465 48.374 13.969 2.381 1.00 69.23 C
ATOM 2175 OG SER B 465 49.764 13.851 2.643 1.00 68.62 O ATOM 2176 C SER B 465 48.057 11.667 3.248 1.00 69.12 C
ATOM 2177 0 SER B 465 47.491 10.875 2.480 1.00 69.25 O
ATOM 2178 N GLY B 466 49.111 11.361 3.994 1.00 71.70 N
ATOM 2179 CA GLY B 466 49.768 10.066 3.954 1.00 73.75 C
ATOM 2180 C GLY B 466 51.140 10.244 3.320 1.00 75.24 C ATOM 2181 O GLY B 466 51.471 11.359 2.885 1.00 75.36 O
ATOM 2182 N PRO B 467 51.974 9.179 3.226 1.00 77.25 N
ATOM 2183 CA PRO B 467 53.333 9.356 2.678 1.00 77.79 C
ATOM 2184 CB PRO B 467 54.169 8.312 3.431 1.00 79.61 C
ATOM 2185 CG PRO B 467 53.167 7.416 4.144 1.00 79.57 C ATOM 2186 CD PRO B 467 51.781 7.801 3.703 1.00 79.11 C
ATOM 2187 C PRO B 467 53.548 9.312 1.168 1.00 78.14 C
ATOM 2188 O PRO B 467 54.592 9.789 0.725 1.00 78.40 O
ATOM 2189 N THR B 468 52.593 8.757 0.389 1.00 78.87
ATOM 2190 CA TH B 468 52.647 8.650 -1.082 1.00 79.57 C ATOM 2191 CB THR B 468 51.272 8.183 -1.602 1.00 90.26 C
ATOM 2192 OG1 THR B 468 50.875 7.000 -0.902 1.00 91.76 O
ATOM 2193 CG2 THR B 468 51.243 7.945 -3.120 1.00 90.27 C
ATOM 2194 C THR B 468 53.055 9.995 -1.727 1.00 79.72 C
ATOM 2195 0 THR B 468 52.622 11.049 -1.251 1.00 79.85 O ATOM 2196 N ARG B 469 53.896 9.965 -2.789 1.00 80.19 N
ATOM 2197 CA ARG B 469 54.334 11.196 -3.470 1.00 80.00 C
ATOM 2198 CB ARG B 469 55.497 10.934 -4.443 1.00 80.36 C
ATOM 2199 C ARG B 469 53.167 11.947 -4.157 1.00 79.60 C
ATOM 2200 O ARG B 469 53.183 13.179 -4.205 1.00 79.65 O ATOM 2201 N MET B 470 52.151 11 .212 -4.652 1.00 77.38 N
ATOM 2202 CA MET B 470 50.988 11.813 -5.309 1.00 76.73 C
ATOM 2203 CB MET B 470 50.611 1 .009 -6.565 1.00 79.16 C
ATOM 2204 C ET B 470 49.775 12.011 -4.360 1.00 76.25 C
ATOM 2205 O MET B 470 48.682 12.333 -4.834 1.00 76.24 O JB2010.7161
ATOM 2206 N ALA B 471 49.981 11.834 -3.023 1 .00 74.44 N
ATOM 2207 CA ALA B 471 48.956 11.977 -1.974 1.00 73.49 C
ATOM 2208 CB ALA B 471 49.463 11.443 -0.641 1.00 73.96 C
ATOM 2209 C ALA B 471 48.473 13.411 -1.813 1.00 72.98 C ATOM 2210 O ALA B 471 49.267 14.358 -1.885 1.00 72.88 O
ATOM 2211 N THR B 472 47.154 13.560 -1.598 1.00 70.89 N
ATOM 2212 CA THR B 472 46.505 14.856 -1 .443 1.00 69.86 C
ATOM 2213 CB THR B 472 45.763 15.260 -2.723 1.00 77.68 C
ATOM 2214 OG1 THR B 472 44.842 14.227 -3.086 1.00 77.31 O ATOM 2215 CG2 THR B 472 46.700 15.583 -3.870 1.00 77.28 C
ATOM 2216 C THR B 472 45.559 14.939 -0.262 1.00 69.13 C
ATOM 2217 O THR B 472 44.754 14.037 -0.027 1.00 68.92 O
ATOM 2218 N ALA B 473 45.648 16.064 0.451 1.00 67.73 N
ATOM 2219 CA ALA B 473 44.832 16.440 1.603 1.00 66.75 C ATOM 2220 CB ALA B 473 45.716 17.096 2.658 1.00 67.33 C
ATOM 2221 C ALA B 473 43.758 17.441 1.110 1.00 65.98 C
ATOM 2222 O ALA B 473 44.090 18.346 0.345 1.00 66.14 O
ATOM 2223 N ILE B 474 42.485 17.271 1.514 1.00 62.47 N
ATOM 2224 CA ILE B 474 41.411 18.178 1.102 1.00 61.45 C ATOM 2225 CB ILE B 474 40.346 17.499 0.190 1.00 64.91 C
ATOM 2226 CG1 ILE B 474 40.978 16.896 -1.068 1.00 66.08 C
ATOM 2227 CD1 ILE B 474 40.446 15.473 -1.364 1.00 68.49 C
ATOM 2228 CG2 ILE B 474 39.218 18.461 -0.203 1.00 64.62 C
ATOM 2229 C ILE B 474 40.790 18.807 2.342 1.00 60.34 C ATOM 2230 O ILE B 474 40.365 18.087 3.240 1.00 60.37 O
ATOM 2231 N ALA B 475 40.735 20.146 2.385 1.00 57.14 N
ATOM 2232 CA ALA B 475 40.136 20.904 3.477 1.00 55.84 C
ATOM 2233 CB ALA B 475 41.148 21.869 4.070 1.00 56.22 C
ATOM 2234 C ALA B 475 38.914 21.641 2.907 1.00 55.10 C ATOM 2235 O ALA B 475 39.061 22.512 2.051 1.00 55.21 O
ATOM 2236 N ARG B 476 37.706 21.239 3.348 1.00 53.80 N
ATOM 2237 CA ARG B 476 36.422 21.781 2.899 1.00 52.98 C
ATOM 2238 CB ARG B 476 35.452 20.646 2.545 1.00 57.32 C
ATOM 2239 CG ARG B 476 35.853 19.824 1.338 1.00 59.08 C ATOM 2240 CD ARG B 476 34.920 18.655 1.194 1.00 63.23 C
ATOM 2241 NE ARG B 476 35.412 17.649 0.249 1.00 67.39 N
ATOM 2242 CZ ARG B 476 36.216 16.634 0.568 1.00 69.07 C
ATOM 2243 NH1 ARG B 476 36.666 16.495 1.815 1.00 68.81 N
ATOM 2244 NH2 ARG B 476 36.594 15.761 -0.360 1.00 69.31 N ATOM 2245 C ARG B 476 35.756 22.701 3.914 1.00 52.07 C
ATOM 2246 O ARG B 476 36.048 22.625 5.104 1.00 52.40 O
ATOM 2247 N CYS B 477 34.834 23.551 3.426 1.00 48.60 N
ATOM 2248 CA CYS B 477 34.025 24.510 4.180 1.0047.18 C
ATOM 2249 CB CYS B 477 34.064 25.882 3.507 1.00 46.99 C ATOM 2250 SG CYS B 477 35.717 26.592 3.352 1.00 45.41 S
ATOM 2251 C CYS B 477 32.606 23.998 4.230 1.00 46.87 C
ATOM 2252 O CYS B 477 32.260 23.050 3.515 1.00 46.88 O
ATOM 2253 N ALA B 478 31.765 24.648 5.035 1.00 47.78 N
ATOM 2254 CA ALA B 478 30.357 24.319 5.117 1.00 47.78 C ATOM 2255 CB ALA B 478 29.739 25.048 6.294 1 .00 48.30 C
ATOM 2256 C ALA B 478 29.743 24.827 3.768 1.0048.48 C
ATOM 2257 O ALA B 478 30.277 25.787 3.177 1 .00 48.26 O
ATOM 2258 N PRO B 479 28.656 24.215 3.233 1.00 51.82 N
ATOM 2259 CA PRO B 479 28.110 24.684 1.940 1.00 52.05 C JB2010.7161
ATOM 2260 CB PRO B 479 26.904 23.764 1.706 1.00 53.87 C
ATOM 2261 CG PRO B 479 26.559 23.244 3.048 1.00 53.79 C
ATOM 2262 CD PRO B 479 27.880 23.069 3.736 1.00 53.76 C
ATOM 2263 C PRO B 479 27.761 26.171 1.839 1.00 51.93 C ATOM 2264 0 PRO B 479 27.866 26.748 0.762 1.00 52.20 O
ATOM 2265 N ASP B 480 27.369 26.792 2.955 1.00 53.42 N
ATOM 2266 CA ASP B 480 27.032 28.210 2.959 1.00 53.67 C
ATOM 2267 CB ASP B 480 25.665 28.496 3.622 1 ,00 56.93 C
ATOM 2268 CG ASP B 480 25.511 28.088 5.067 1.00 59.11 C ATOM 2269 OD1 ASP B 480 26.056 27.016 5.447 1.00 63.02 O
ATOM 2270 OD2 ASP B 480 24.826 28.838 5.832 1.00 62.86 O
ATOM 2271 C ASP B 480 28.186 29.098 3.427 1.00 53.04 C
ATOM 2272 0 ASP B 480 27.970 30.229 3.853 1.00 52.72 O
ATOM 2273 N GLU B 481 29.425 28.575 3.312 1.00 51.44 N ATOM 2274 CA GLU B 481 30.667 29.267 3.656 1.00 51.11 C
ATOM 2275 CB GLU B 481 31.510 28.443 4.637 1.00 52.30 C
ATOM 2276 CG GLU B 481 31.261 28.728 6.101 1.00 52.12 C
ATOM 2277 CD GLU B 481 32.035 27.832 7.055 1.00 52.14 C
ATOM 2278 OE1 GLU B 481 32.555 26.776 6.622 1.00 49.95 O ATOM 2279 OE2 GLU B 481 32.111 28.190 8.252 1.00 51.94 O
ATOM 2280 C GLU B 481 31.473 29.463 2.372 1.00 51.04 C
ATOM 2281 O GLU B 481 31.260 28.748 1.382 1.00 50.92 O
ATOM 2282 N GLU B 482 32.412 30.415 2.404 1.00 49.29 N
ATOM 2283 CA GLU B 482 33.280 30.746 1.288 1.00 49.32 C ATOM 2284 CB GLU B 482 33.172 32.254 0.946 1.00 51.66 C
ATOM 2285 CG GLU B 482 31.790 32.761 0.565 1.00 53.03 C
ATOM 2286 CD GLU B 482 31.364 32.572 -0.881 1.00 57.68 C
ATOM 2287 OE1 GLU B 482 32.183 32.096 -1.704 1.00 59.24 O
ATOM 2288 OE2 GLU B 482 30.195 32.907 -1.190 1.00 61.30 O ATOM 2289 C GLU B 482 34.712 30.424 1.687 1.00 49.13 C
ATOM 2290 O GLU B 482 35.160 30.857 2.744 1.00 49.43 O
ATOM 2291 N LEU B 483 35.436 29.680 0.849 1.00 47.43 N
ATOM 2292 CA LEU B 483 36.835 29.362 1.114 1.0047.37 C
ATOM 2293 CB LEU B 483 37.249 28.109 0.320 1.00 47.25 C ATOM 2294 CG LEU B 483 38.642 27.572 0.604 1.00 47.52 C
ATOM 2295 CD1 LEU B 483 38.568 26.180 1.131 1.00 47.92 C
ATOM 2296 CD2 LEU B 483 39.472 27.565 -0.647 1.00 48.55 C
ATOM 2297 C LEU B 483 37.645 30.597 0.673 1.00 47.47 C
ATOM 2298 0 LEU B 483 37.933 30.745 -0.506 1.00 47.63 O ATOM 2299 N LEU B 484 37.963 31.500 1.597 1.0046.80 N
ATOM 2300 CA LEU B 484 38.700 32.711 1.240 1.00 47.23 C
ATOM 2301 CB LEU B 484 38.405 33.894 2.173 1.0046.83 C
ATOM 2302 CG LEU B 484 36.946 34.390 2.221 1.00 46.04 C
ATOM 2303 CD1 LEU B 484 36.862 35.773 2.855 1.00 43.79 C ATOM 2304 CD2 LEU B 484 36.282 34.375 0.835 1.00 43.57 C
ATOM 2305 C LEU B 484 40.180 32.504 1.021 1.00 47.79 C
ATOM 2306 O LEU B 484 40.785 33.253 0.268 1.00 48.01 O
ATOM 2307 N SER B 485 40.769 31.498 1.667 1.00 49.07 N
ATOM 2308 CA SER B 485 42.181 31.155 1.507 1.00 49.53 C ATOM 2309 CB SER B 485 43.096 32.023 2.362 1.00 53.87 C
ATOM 2310 OG SER B 485 43.467 31.420 3.593 1.00 54.07 O
ATOM 2311 C SER B 485 42.452 29.671 1.676 1.00 50.19 C
ATOM 2312 O SER B 485 41.601 28.913 2.147 1.00 49.93 O
ATOM 2313 N CYS B 486 43.638 29.267 1.237 1.00 52.46 N JB2010.7161
ATOM 2314 CA CYS B 486 44.104 27.899 1.260 1 .00 53.57 C
ATOM 2315 CB CYS B 486 43.693 27.210 -0.033 1.00 54.72 C
ATOM 2316 SG CYS B 486 44.437 25.584 -0,267 1.00 58.42 S
ATOM 2317 C CYS B 486 45.620 27.867 1.461 1.00 53.67 C ATOM 2318 0 CYS B 486 46.352 28.446 0.663 1.00 54.05 O
ATOM 2319 N SE B 487 46.083 27.219 2.543 1.00 52.78 N
ATOM 2320 CA SER B 487 47.502 27.071 2.861 1.00 52.96 C
ATOM 2321 CB SER B 487 47.951 28,034 3.954 1.00 56.36 C
ATOM 2322 OG SER B 487 47.596 27.620 5.261 1.00 56.75 O ATOM 2323 C SER B 487 47.826 25.614 3.169 1.00 53.41 C
ATOM 2324 0 SER B 487 46.915 24.786 3.219 1.00 53.67 O
ATOM 2325 N SER B 488 49.111 25.272 3.298 1.00 53.67 N
ATOM 2326 CA SER B 488 49.497 23.891 3.551 1.00 53.92 C
ATOM 2327 CB SER B 488 49.856 23.182 2.246 1.00 56,83 C ATOM 2328 OG SER B 488 51.138 23.530 1.748 1.00 56.75 O
ATOM 2329 C SER B 488 50.603 23.794 4.592 1.00 54.52 C
ATOM 2330 O SER B 488 51.272 24.794 4.869 1.00 54.45 O
ATOM 2331 N PHE B 489 50.768 22.608 5.214 1.00 56.25 N
ATOM 2332 CA PHE B 489 51.799 22.420 6.233 1.00 57.17 C ATOM 2333 CB PHE B 489 51.338 22.900 7.617 1.00 58.61 C
ATOM 2334 CG PHE B 489 52.313 22.641 8.734 1.00 58.42 C
ATOM 2335 CD1 PHE B 489 53.521 23.318 8.793 1.00 58.07 C
ATOM 2336 CE1 PHE B 489 54.425 23.077 9.827 1.00 58.55 C
ATOM 2337 CZ PHE B 489 54.116 22.168 10.815 1.00 58.71 C ATOM 2338 CE2 PHE B 489 52.917 21.493 10.777 1.00 58.80 C
ATOM 2339 CD2 PHE B 489 52.017 21.727 9.734 1.00 59.16 C
ATOM 2340 C PHE B 489 52.289 21.004 6.295 1.00 57.94 C
ATOM 2341 O PHE B 489 51.483 20.079 6.240 1.00 57.83 O
ATOM 2342 N SER B 490 53.618 20.849 6.424 1.00 59.48 N ATOM 2343 CA SER B 490 54.315 19.577 6.513 1.00 60.73 C
ATOM 2344 CB SER B 490 54.960 19.235 5.174 1.0065.32 C
ATOM 2345 OG SER B 490 55.423 17.895 5.123 1.00 65.56 O
ATOM 2346 C SER B 490 55.374 19.667 7.611 1.00 61.88 C
ATOM 2347 0 SER B 490 56,139 20.645 7.672 1.00 61.84 O ATOM 2348 N ARG B 491 55.409 18.641 8.488 1.00 65.66 N
ATOM 2349 CA ARG B 491 56.360 18.549 9.599 1.00 67.00 C
ATOM 2350 CB ARG B 491 55.928 17.475 10.613 1.00 66.09 C
ATOM 2351 CG ARG B 491 54.973 18.049 11.655 1.00 67.41 C
ATOM 2352 CD ARG B 491 54.468 17,056 12.694 1.00 68.34 C ATOM 2353 NE ARG B 491 53.056 16.693 12.489 1.00 69.16 N
ATOM 2354 CZ ARG B 491 52.007 17.381 12.949 1.00 68.95 C
ATOM 2355 NH1 ARG B 491 52.187 18.503 13.644 1.00 68.24 N
ATOM 2356 NH2 ARG B 491 50.773 16.956 12.712 1.00 67.62 N
ATOM 2357 C ARG B 491 57.844 18.411 9.142 1.00 67.88 C ATOM 2358 O ARG B 491 58.754 18.869 9.852 1.00 68.01 O
ATOM 2359 N SER B 492 58.072 17.812 7.949 1.00 70.21 N
ATOM 2360 CA SER B 492 59.401 17.632 7.357 1.00 71.44 C
ATOM 2361 CB SER B 492 59.474 16.323 6.576 1.00 74.19 C
ATOM 2362 OG SER B 492 58.575 16.305 5.478 1.00 74.62 O ATOM 2363 C SER B 492 59.749 18.805 6.436 1.00 72.34 C
ATOM 2364 O SER B 492 60.933 19.1 15 6.254 1.00 72.75 O
ATOM 2365 N GLY B 493 58.712 19.432 5.867 1.00 73.60 N
ATOM 2366 CA GLY B 493 58.840 20.557 4.949 1.00 74.10 C
ATOM 2367 C GLY B 493 58.687 20.136 3.502 1.00 74.47 C JB2010.7161
ATOM 2368 0 GLY B 493 58.468 20.984 2.632 1.00 74.64 O
ATOM 2369 N LYS B 494 58.800 18.810 3.243 1.00 73.79 N
ATOM 2370 CA LYS B 494 58.694 18.175 1.928 1.00 73.93 C
ATOM 2371 CB LYS B 494 59.188 16.708 1.978 1.00 77.01 C ATOM 2372 CG LYS B 494 60.699 16.544 1.843 1.00 77.84 C
ATOM 2373 CD LYS B 494 61.393 16.447 3.195 1 ,00 79.63 C
ATOM 2374 CE LYS B 494 62.685 17.235 3.252 1.00 80.46 C
ATOM 2375 NZ LYS B 494 63.797 16.560 2.521 1.00 81.72 N
ATOM 2376 C LYS B 494 57.274 18.263 1.375 1.00 73.68 C ATOM 2377 0 LYS B 494 56.500 17.301 1.476 1.00 73.66 O
ATOM 2378 N ARG B 495 56.939 19.429 0.777 1.00 71.64 N
ATOM 2379 CA ARG B 495 55.624 19.702 0.167 1.00 71.26 C
ATOM 2380 CB ARG B 495 54.672 20.482 1.110 1.00 70.49 C
ATOM 2381 CG ARG B 495 55.273 21.722 1.735 1.00 70.38 C ATOM 2382 CD ARG B 495 54.310 22.502 2.595 1.00 70.18 C
ATOM 2383 NE ARG B 495 54.929 23.774 2.957 1.00 70.48 N
ATOM 2384 CZ ARG B 495 54.719 24.918 2.314 1.00 70.12 C
ATOM 2385 NH1 ARG B 495 55.347 26.023 2.695 1.00 69.89 N
ATOM 2386 NH2 ARG B 495 53.871 24.970 1.292 1.00 69.72 N ATOM 2387 C ARG B 495 55.710 20.356 -1.217 1.00 70.82 C
ATOM 2388 O ARG B 495 56.664 21.074 -1.510 1.00 70.65 O
ATOM 2389 N ARG B 496 54.706 20.086 -2.060 1.00 69.42 N
ATOM 2390 CA ARG B 496 54.595 20.623 -3.409 1.00 69.24 C
ATOM 2391 CB ARG B 496 54.268 19.495 -4.405 1.00 71.24 C ATOM 2392 CG ARG B 496 55.455 18.604 -4.786 1.00 72.25 C
ATOM 2393 CD ARG B 496 55.249 17.844 -6.100 1.00 74.12 C
ATOM 2394 NE ARG B 496 54.127 16.895 -6.072 1 .00 75.78 N
ATOM 2395 CZ ARG B 496 52.938 17.101 -6.644 1.00 77.26 C
ATOM 2396 NH1 ARG B 496 52.690 18.237 -7.296 1.00 78.06 N ATOM 2397 NH2 ARG B 496 51.985 16.179 -6.559 1.00 77.51 N
ATOM 2398 C ARG B 496 53.524 21.740 -3.450 1.00 68.83 C
ATOM 2399 O ARG B 496 52.838 21.915 -4.466 1.00 69.04 O
ATOM 2400 N GLY B 497 53.398 22.479 -2.345 1.00 66.71 N
ATOM 2401 CA GLY B 497 52.429 23.562 -2.200 1.00 65.86 C ATOM 2402 C GLY B 497 50.970 23.135 -2.121 1.00 65.26 C
ATOM 2403 O GLY B 497 50.664 21.975 -1.828 1.00 65.04 O
ATOM 2404 N GLU B 498 50.059 24.088 -2.392 1.00 63.61 N
ATOM 2405 CA GLU B 498 48.603 23.902 -2.335 1.00 63.10 C
ATOM 2406 CB GLU B 498 48.064 24.331 -0.951 1.00 63.75 C ATOM 2407 CG GLU B 498 48.063 25.826 -0.660 1.00 61.91 C
ATOM 2408 CD GLU B 498 49.406 26.517 -0.503 1.00 60.86 C
ATOM 2409 OE1 GLU B 498 50.259 26.024 0.274 1.00 59.86 O
ATOM 2410 OE2 GLU B 498 49.600 27.566 -1.159 1.00 61.36 O
ATOM 2411 C GLU B 498 47.841 24.631 -3.447 1.00 63.40 C ATOM 2412 O GLU B 498 48.378 25.561 -4.051 1.00 63.27 O
ATOM 2413 N ARG B 499 46.587 24.228 -3.703 1.00 64.30 N
ATOM 2414 CA ARG B 499 45.758 24.864 -4.726 1.00 65.18 C
ATOM 2415 CB ARG B 499 46.012 24.247 -6.120 1.00 71.04 C
ATOM 2416 CG ARG B 499 45.365 22.894 -6.381 1.00 73.16 C ATOM 2417 CD ARG B 499 45.718 22.331 -7.746 1.00 76.96 C
ATOM 2418 NE ARG B 499 45.023 21.063 -7.972 1.00 79.88 N
ATOM 2419 CZ ARG B 499 43.871 20.941 -8.629 1.00 81.79 C
ATOM 2420 NH1 ARG B 499 43.283 22.009 -9.161 1.00 82.44 N
ATOM 2421 NH2 ARG B 499 43.305 19.747 -8.773 1.00 82.29 N JB2O10.7161
ATOM 2422 C ARG B 499 44.263 24.925 -4.364 1.00 65.29 C
ATOM 2423 O ARG B 499 43.771 24.086 -3.612 1.00 65.09 O
ATOM 2424 N MET B 500 43.550 25.922 -4.897 1.00 65.62 N
ATOM 2425 CA ET B 500 42.115 26.082 -4.654 1.00 66.14 C ATOM 2426 CB MET B 500 41.734 27.544 -4.353 1.00 67.39 C
ATOM 2427 CG MET B 500 42.721 28.245 -3.448 1.00 67.09 C
ATOM 2428 SD MET B 500 42.061 29.739 -2.697 1.00 65.94 S
ATOM 2429 CE ET B 500 43.546 30.646 -2.422 1.00 66.00 C
ATOM 2430 C ET B 500 41.381 25.522 -5.862 1.00 66.84 C ATOM 2431 O ET B 500 41.187 26.220 -6.850 1.00 66.94 O
ATOM 2432 N GLU B 501 41.034 24.234 -5.793 1.00 71.89 N
ATOM 2433 CA GLU B 501 40.346 23.456 -6.827 1.00 73.31 C
ATOM 2434 CB GLU B 501 40.763 21.974 -6.694 1.00 75.93 C
ATOM 2435 CG GLU B 501 40.299 21.049 -7.810 1.00 78.69 C ATOM 2436 CD GLU B 501 39.356 19.932 -7.389 1.00 81.99 C
ATOM 2437 OE1 GLU B 501 39.712 19.158 -6.467 1.00 83.17 O
ATOM 2438 OE2 GLU B 501 38.265 19.823 -7.995 1.00 82.03 O
ATOM 2439 C GLU B 501 38.831 23.627 -6.685 1.00 73.76 C
ATOM 2440 O GLU B 501 38.339 23.811 -5.576 1.00 74.05 O ATOM 2441 N ALA B 502 38.091 23.577 -7.798 1.00 76.46 N
ATOM 2442 CA ALA B 502 36.639 23.744 -7.784 1.00 76.98 C
ATOM 2443 CB ALA B 502 36.210 24.630 -8.936 1.00 77.69 C
ATOM 2444 C ALA B 502 35.909 22.406 -7.823 1.00 77.42 C
ATOM 2445 O ALA B 502 35.207 22.096 -8.790 1.00 77.66 O ATOM 2446 N GLN B 503 36.076 21.615 -6.753 1.00 79.97 N
ATOM 2447 CA GLN B 503 35.468 20.286 -6.594 1.00 80.40 C
ATOM 2448 CB GLN B 503 36.105 19.544 -5.404 1.00 82.53 C
ATOM 2449 CG GLN B 503 35.676 18.100 -5.232 1.00 84.12 C
ATOM 2450 CD GLN B 503 36.207 17.519 -3.943 1.00 86.45 C ATOM 2451 OE1 GLN B 503 37.383 17.136 -3.857 1.00 86.94 O
ATOM 2452 NE2 GLN B 503 35.351 17.432 -2.910 1.00 85.97 N
ATOM 2453 C GLN B 503 33.945 20.336 -6.473 1.00 80.20 C
ATOM 2454 O GLN B 503 33.412 21.079 -5.649 1.00 80.13 O
ATOM 2455 N GLY B 504 33.281 19.540 -7.312 1.00 78.91 N ATOM 2456 CA GLY B 504 31.833 19.390 -7.389 1.00 78.24 C
ATOM 2457 C GLY B 504 30.988 20.584 -6.989 1.00 77.75 C
ATOM 2458 O GLY B 504 30.197 20.488 -6.045 1.00 77.95 O
ATOM 2459 N GLY B 505 31.176 21.701 -7.691 1.00 74.94 N
ATOM 2460 CA GLY B 505 30.417 22.929 -7.474 1.00 74.00 C ATOM 2461 C GLY B 505 30.976 23.952 -6.508 1.00 73.53 C
ATOM 2462 O GLY B 505 30.700 25.148 -6.657 1.00 73.75 O
ATOM 2463 N LYS B 506 31.740 23.503 -5.501 1.00 71.03 N
ATOM 2464 CA LYS B 506 32.298 24.423 -4.513 1.00 70.01 C
ATOM 2465 CB LYS B 506 31.639 24.223 -3.136 1.00 72.46 C ATOM 2466 C LYS B 506 33.809 24.338 -4.420 1.00 69.32 C
ATOM 2467 0 LYS B 506 34.391 23.279 -4.641 1.00 69.30 O
ATOM 2468 N LEU B 507 34.438 25.466 -4.092 1.00 66.92 N
ATOM 2469 CA LEU B 507 35.881 25.613 -3.945 1.00 66.12 C
ATOM 2470 CB LEU B 507 36.165 27.083 -3.640 1.00 66.38 C ATOM 2471 CG LEU B 507 37.049 27.840 -4.600 1.00 67.63 C
ATOM 2472 CD1 LEU B 507 36.211 28.507 -5.705 1.00 68.19 C
ATOM 2473 CD2 LEU B 507 37.826 28.902 -3.846 1.00 68.86 C
ATOM 2474 C LEU B 507 36.427 24.755 -2.793 1 .00 65.11 C
ATOM 2475 O LEU B 507 35.857 24.760 -1.698 1.00 65.09 O JB2010.7161
ATOM 2476 N VAL B 508 37.519 24.010 -3.045 1 .00 61.61 N
ATOM 2477 CA VAL B 508 38.193 23.183 -2.033 1 .00 60.38 C
ATOM 2478 CB VAL B 508 38.009 21.641 -2.126 1 .00 63.21 C
ATOM 2479 CG1 VAL B 508 36.544 21.240 -2.075 1 .00 63.38 C ATOM 2480 CG2 VAL B 508 38.707 21 .054 -3.345 1 .00 62.75 C
ATOM 2481 C VAL B 508 39.651 23.587 -1.981 1 .00 59.70 C
ATOM 2482 O VAL B 508 40.138 24.262 -2.876 1.00 59.53 O
ATOM 2483 N CYS B 509 40.338 23.169 -0.946 1.00 59.27 N
ATOM 2484 CA CYS B 509 41.733 23.467 -0.737 1.00 58.77 C ATOM 2485 CB CYS B 509 41.877 24.200 0.596 1.00 59.03 C
ATOM 2486 SG CYS B 509 43.577 24.420 1.169 1.00 58.35 S
ATOM 2487 C CYS B 509 42.505 22.125 -0.768 1.00 59.12 C
ATOM 2488 O CYS B 509 42.383 21.329 0.164 1 .00 59.07 O
ATOM 2489 N ARG B 510 43.249 21.850 -1.870 1 .00 59.85 N ATOM 2490 CA ARG B 510 44.050 20.624 -2.018 1 .00 60.23 C
ATOM 2491 CB ARG B 510 43.972 20.039 -3.433 1 .00 65.80 C
ATOM 2492 CG ARG B 510 42.609 19.592 -3.923 1.00 67.86 C
ATOM 2493 CD ARG B 510 42.747 18.693 -5.154 1 .00 69.19 C
ATOM 2494 HE ARG B 510 43.027 17.308 -4.770 1 .00 69.62 N ATOM 2495 CZ ARG B 510 42.092 16.397 -4.504 1 .00 70.34 C
ATOM 2496 NH1 ARG B 510 40.803 16.714 -4.588 1 .00 69.81 N
ATOM 2497 NH2 ARG B 510 42.438 15.162 -4.158 1 .00 70.34 N
ATOM 2498 C ARG B 510 45.511 20.937 -1.756 1.00 60.27 C
ATOM 2499 0 ARG B 510 46.022 21 .914 -2.300 1.00 60.08 O ATOM 2500 N ALA B 511 46.193 20.100 -0.956 1.00 61.36 N
ATOM 2501 CA ALA B 511 47.629 20,230 -0.653 1.00 61.82 C
ATOM 2502 CB ALA B 51 1 47.872 20.303 0.843 1.00 62.16 C
ATOM 2503 C ALA B 511 48.352 19.023 -1.262 1.00 62.42 C
ATOM 2504 O ALA B 51 1 47.780 17.936 -1.327 1.00 62.27 O ATOM 2505 N HIS B 512 49.587 19.221 -1 .744 1 .00 66.79 N
ATOM 2506 CA HIS B 512 50.351 18.154 -2.389 1.00 67.92 C
ATOM 2507 CB HiS B 512 50.684 18.542 -3.842 1 .00 69.88 C
ATOM 2508 CG HIS B 512 49.485 18.867 -4.683 1.00 71 .38 C
ATOM 2509 ND1 HIS B 512 48.602 17.882 -5.097 1 .00 72.41 N ATOM 2510 CE1 HIS B 512 47.676 18.506 -5.808 1 .00 73.23 C
ATOM 251 1 NE2 HIS B 512 47.914 19.819 -5.881 1 .00 73.20 N
ATOM 2512 CD2 HIS B 512 49.071 20.060 -5.171 1.00 72.71 C
ATOM 2513 C HIS B 512 51.612 17.786 -1 .639 1.00 68.22 C
ATOM 2514 O HIS B 512 52.337 18.672 -1.186 1.00 68.07 O ATOM 2515 N ASN B 513 51.882 16.479 -1 .520 1.00 70.55 N
ATOM 2516 CA ASN B 513 53.079 16.000 -0.832 1.00 71 .51 C
ATOM 2517 CB ASN B 513 52.802 14.671 -0.098 1.00 69.76 C
ATOM 2518 CG ASN B 513 53.936 14.196 0.795 1.00 69.80 C
ATOM 2519 OD1 ASN B 513 54.520 14.955 1 .591 1 .00 69.04 O ATOM 2520 ND2 ASN B 513 54.272 12.919 0.683 1.00 70.62 N
ATOM 2521 C ASN B 513 54.275 15.867 -1.802 1.00 72.19 C
ATOM 2522 O ASN B 513 54.1 15 15.337 -2.904 1.00 72.24 O
ATOM 2523 N ALA B 514 55.466 16.356 -1 .393 1.00 75.63 N
ATOM 2524 CA ALA B 514 56.673 16.255 -2.219 1.00 76.20 C ATOM 2525 CB ALA B 514 57.667 17.345 -1 .861 1 .00 76.75 C
ATOM 2526 C ALA B 514 57.319 14.886 -2.051 1.00 76.64 C
ATOM 2527 O ALA B 514 57.137 14.243 -1 .010 1 .00 76.77 O
ATOM 2528 N PHE B 515 58.080 14.453 -3.082 1.00 80.11 N
ATOM 2529 CA PHE B 515 58.803 13.180 -3.148 1 .00 80.31 C JB2010.7161
ATOM 2530 CB PHE B 515 59.830 13.210 -4.295 1.00 82.36 C
ATOM 2531 C PHE B 515 59.503 12.879 -1.830 1.00 80.38 C
ATOM 2532 O PHE B 515 60.322 13.682 -1.364 1.00 80.37 O
ATOM 2533 N GLY B 516 59.139 11.749 -1.230 1.00 81.00 N ATOM 2534 CA GLY B 516 59.697 11.308 0.042 1.00 80.95 C
ATOM 2535 C GLY B 516 59.400 12.258 1.184 1.00 80.88 C
ATOM 2536 O GLY B 516 60.312 12.902 1.720 1.00 81.07 O
ATOM 2537 N GLY B 517 58.115 12.351 1.523 1.00 80.34 N
ATOM 2538 CA GLY B 517 57.597 13.195 2.595 1.00 79.68 C ATOM 2539 C GLY B 517 56.645 12.415 3.475 1.00 79.22 C
ATOM 2540 O GLY B 517 55.982 11.489 2.991 1.00 79.27 O
ATOM 2541 N GLU B 518 56.575 12.779 4.774 1.00 77.21 N
ATOM 2542 CA GLU B 518 55.699 12.109 5.738 1.00 76.44 C
ATOM 2543 CB GLU B 518 56.071 12.479 7,195 1.00 79.07 C ATOM 2544 CG GLU B 518 55.311 13.634 7.855 1.00 81.97 C
ATOM 2545 CD GLU B 518 55.450 15.042 7.288 1.00 85.53 C
ATOM 2546 OE1 GLU B 518 56.301 15.260 6.392 1.00 86.46 O
ATOM 2547 OE2 GLU B 518 54.696 15.932 7.752 1.00 86.25 O
ATOM 2548 C GLU B 518 54.203 12.297 5.417 1.00 75.08 C ATOM 2549 0 GLU B 518 53.402 11.401 5.685 1.00 75.58 O
ATOM 2550 N GLY B 519 53.866 13.440 4.816 1.00 68.68 N
ATOM 2551 CA GLY B 519 52.509 13.807 4.425 1.00 65.83 C
ATOM 2552 C GLY B 519 52.239 15.284 4.583 1.00 63.77 C
ATOM 2553 O GLY B 519 53.088 16.023 5.085 1.00 63.72 O ATOM 2554 N VAL B 520 51.059 15.727 4.155 1.00 58.12 N
ATOM 2555 CA VAL B 520 50.656 17.141 4.230 1.00 56.09 C
ATOM 2556 CB VAL B 520 50.854 17.927 2.889 1.00 58.61 C
ATOM 2557 CG1 VAL B 520 52.320 18.213 2.615 1.00 58.35 C
ATOM 2558 CG2 VAL B 520 50.190 17.225 1.705 1.00 57.62 C ATOM 2559 C VAL B 520 49.236 17.362 4.750 1.00 54.72 C
ATOM 2560 O VAL B 520 48.350 16.531 4.548 1.00 54.34 O
ATOM 2561 N TYR B 521 49.030 18.525 5.379 1.00 52.96 N
ATOM 2562 CA TYR B 521 47.746 19.015 5.866 1.00 51.37 C
ATOM 2563 CB TYR B 521 47.814 19.508 7.321 1.00 51.30 C ATOM 2564 CG TYR B 521 48.055 18.429 8.348 1.00 51.00 C
ATOM 2565 CD1 TYR B 521 47.045 17.538 8.704 1.00 50.75 C
ATOM 2566 CE1 TYR B 521 47.261 16.550 9.662 1.00 51.64 C
ATOM 2567 CZ TYR B 521 48.491 16.465 10.298 1.00 51.80 C
ATOM 2568 OH TYR B 521 48.720 15.491 11.249 1.00 53.18 O ATOM 2569 CE2 TYR B 521 49.501 17.350 9.968 1.0049.63 C
ATOM 2570 CD2 TYR B 521 49.279 18.323 9.000 1.00 49.96 C
ATOM 2571 C TYR B 521 47.402 20.201 4.976 1.00 50.57 C
ATOM 2572 0 TYR B 521 48.279 21.003 4.641 1.00 50,31 O
ATOM 2573 N ALA B 522 46.138 20.286 4.576 1.0049.97 N ATOM 2574 CA ALA B 522 45.592 21.369 3.786 1.00 48.90 C
ATOM 2575 CB ALA B 522 44.594 20.826 2.765 1.00 49.18 C
ATOM 2576 C ALA B 522 44.878 22.201 4.852 1.00 48.44 C
ATOM 2577 O ALA B 522 44.108 21.663 5.658 1.00 48.69 O
ATOM 2578 N iLE B 523 45.177 23.488 4.901 1.00 46.25 N ATOM 2579 CA ILE B 523 44.586 24.403 5.869 1.00 45.22 C
ATOM 2580 CB ILE B 523 45.688 25.088 6.706 1.00 47.18 C
ATOM 2581 CG1 ILE B 523 46.670 24.043 7.264 1.00 47.21 C
ATOM 2582 CD1 ILE B 523 48.067 24.345 7.091 1.00 45.41 C
ATOM 2583 CG2 ILE B 523 45.095 25.910 7.835 1.00 46.94 C JB2010.7161
ATOM 2584 C ILE B 523 43.715 25.383 5.090 1.00 44.76 C
ATOM 2585 O !LE B 523 44.214 26.153 4.265 1.00 44.99 O
ATOM 2586 N ALA B 524 42.410 25.339 5.337 1.00 44.44 N
ATOM 2587 CA ALA B 524 41.476 26.210 4.650 1.00 43.94 C ATOM 2588 CB ALA B 524 40.343 25.383 4.077 1.00 44.17 C
ATOM 2589 C ALA B 524 40.903 27.280 5.561 1.00 43.95 C
ATOM 2590 O ALA B 524 40.579 26.998 6.716 1.00 44.21 O
ATOM 2591 N ARG B 525 40.735 28.506 5.036 1.00 43.53 N
ATOM 2592 CA ARG B 525 40.099 29.571 5.793 1.00 42.94 C ATOM 2593 CB ARG B 525 40.860 30.883 5.680 1.00 42.61 C
ATOM 2594 CG ARG B 525 40.534 31.832 6.813 1.00 42.85 C
ATOM 2595 CD ARG B 525 41.338 31.590 8.083 1.00 42.32 C
ATOM 2596 NE ARG B 525 41.238 32.765 8.951 1.00 42.51 N
ATOM 2597 CZ ARG B 525 40.756 32.784 10.189 1.00 42.27 C ATOM 2598 NH1 ARG B 525 40.342 31.665 10.766 1.00 43.54 N
ATOM 2599 NH2 ARG B 525 40.706 33.918 10.868 1.00 43.96 N
ATOM 2600 C ARG B 525 38.668 29.666 5.259 1.00 42.79 C
ATOM 2601 O ARG B 525 38.458 29.944 4.081 1.00 42.40 O
ATOM 2602 N CYS B 526 37.688 29.358 6.108 1.00 43.85 N ATOM 2603 CA CYS B 526 36.272 29.351 5.731 1.00 44.23 C
ATOM 2604 CB CYS B 526 35.639 28.002 6.046 1.00 44.59 C
ATOM 2605 SG CYS B 526 36.468 26.609 5.244 1.00 45.22 S
ATOM 2606 C CYS B 526 35.555 30.483 6.399 1.00 44.66 C
ATOM 2607 O CYS B 526 35.608 30.615 7.626 1.00 44.76 O ATOM 2608 N CYS B 527 34.909 31.319 5.593 1.00 43.81 N
ATOM 2609 CA CYS B 527 34.253 32.513 6.091 1.00 44.79 C
ATOM 2610 CB CYS B 527 35.054 33.743 5.674 1.00 45.95 C
ATOM 2611 SG CYS B 527 36.839 33.580 5.907 1.0045.55 S
ATOM 2612 C CYS B 527 32.814 32.666 5.713 1.00 45.67 C ATOM 2613 0 CYS B 527 32.330 31.968 4.829 1.00 45.37 O
ATOM 2614 N LEU B 528 32.128 33.592 6.385 1.00 47.78 N
ATOM 2615 CA LEU B 528 30.755 33.919 6.061 1.00 50.01 C
ATOM 2616 CB LEU B 528 29.837 33.956 7.284 1.00 49.00 C
ATOM 2617 CG LEU B 528 29.497 32.629 7.959 1.00 49.07 C ATOM 2618 CD1 LEU B 528 28.695 32.867 9.191 1.00 47.94 C
ATOM 2619 CD2 LEU B 528 28.747 31.678 7.027 1.00 47.61 C
ATOM 2620 C LEU B 528 30.831 35.287 5.399 1.00 51.96 C
ATOM 2621 O LEU B 528 31.1 12 36.301 6.060 1.00 52.45 O
ATOM 2622 N LEU B 529 30.660 35.306 4.077 1.00 58.47 N ATOM 2623 CA LEU B 529 30.709 36.539 3.298 1.00 60.54 C
ATOM 2624 CB LEU B 529 31.933 36.573 2.364 1.00 60.25 C
ATOM 2625 CG LEU B 529 32.382 37.930 1.810 1.00 60.15 C
ATOM 2626 CD1 LEU B 529 32.562 38.981 2.902 1.00 59.37 C
ATOM 2627 CD2 LEU B 529 33.647 37.782 1.001 1.00 59.57 C ATOM 2628 C LEU B 529 29.371 36.668 2.566 1.00 62.19 C
ATOM 2629 O LEU B 529 29.131 36.029 1.526 1.00 62.29 O
ATOM 2630 N PRO B 530 28.451 37.433 3.189 1.00 67.36 N
ATOM 2631 CA PRO B 530 27.123 37.607 2.589 1.00 68,51 C
ATOM 2632 CB PRO B 530 26.323 38.297 3.701 1.00 70.58 C ATOM 2633 CG PRO B 530 27.349 39.088 4.468 1.00 70.35 C
ATOM 2634 CD PRO B 530 28.595 38.229 4.431 1.00 69.73 C
ATOM 2635 C PRO B 530 27.216 38.450 1.321 1.00 69.45 C
ATOM 2636 O PRO B 530 27.937 39.464 1.292 1.00 69.59 O
ATOM 2637 N GLN B 531 26.494 38.001 0.273 1.00 70.43 N JB2010.7161
ATOM 2638 CA GLN B 531 26.426 38.622 -1.057 1.00 71.31 C
ATOM 2639 CB GLN B 531 25.653 39.960 -1.037 1.00 73.97 C
ATOM 2640 CG GLN B 531 24.799 40.171 -2.290 1.00 76.23 C
ATOM 2641 CD GLN B 531 24.233 41.573 -2.405 1.00 78.91 C ATOM 2642 OE1 GLN B 531 24.519 42.302 -3.375 1.00 80.16 O
ATOM 2643 NE2 GLN B 531 23.410 41.978 -1.429 1.00 78.59 N
ATOM 2644 C GLN B 531 27.819 38.744 -1.683 1.00 70.77 C
ATOM 2645 O GLN B 531 28.237 39.817 -2.123 1.00 70.70 O
ATOM 2646 N ALA B 532 28.536 37.620 -1.694 1.00 66.90 N ATOM 2647 CA ALA B 532 29.878 37.520 -2.232 1 .00 66.23 C
ATOM 2648 CB ALA B 532 30,799 36.912 -1.201 1 .00 66.95 C
ATOM 2649 C ALA B 532 29.894 36.671 -3.468 1.00 65.85 C
ATOM 2650 O ALA B 532 29.225 35.639 -3.522 1.00 65.41 O
ATOM 2651 N ASN B 533 30.670 37.109 -4.458 1.00 63.84 N ATOM 2652 CA ASN B 533 30.876 36.422 -5.723 1.00 63.79 C
ATOM 2653 CB ASN B 533 30.377 37.281 -6.908 1.00 67.55 C
ATOM 2654 CG ASN B 533 30.138 36.531 -8.209 1.00 67.96 C
ATOM 2655 OD1 ASN B 533 30.767 35.502 -8.503 1.00 68.40 O
ATOM 2656 ND2 ASN B 533 29.218 37.044 -9.032 1.00 68.51 N ATOM 2657 C ASN B 533 32.386 36.191 -5.763 1.00 63.85 C
ATOM 2658 O AS B 533 33.159 37.112 -6.065 1.00 63.71 O
ATOM 2659 N CYS B 534 32.810 34.973 -5.376 1.00 62.91 N
ATOM 2660 CA CYS B 534 34.228 34.598 -5.330 1.00 63.18 C
ATOM 2661 CB CYS B 534 34.593 34.012 -3.968 1.00 63.64 C ATOM 2662 SG CYS B 534 34.258 35.116 -2.566 1.00 64.12 S
ATOM 2663 C CYS B 534 34.636 33.673 -6.483 1.00 63.42 C
ATOM 2664 0 CYS B 534 33.818 32.889 -6.958 1.00 63.15 O
ATOM 2665 N SER B 535 35.895 33.782 -6.939 1.00 63.52 N
ATOM 2666 CA SER B 535 36.438 32.973 -8.039 1.00 64.64 C ATOM 2667 CB SER B 535 35.984 33.508 -9.403 1.00 70.56 C
ATOM 2668 OG SER B 535 35.960 34.928 -9.502 1.00 71.49 O
ATOM 2669 C SER B 535 37.965 32.835 -7.969 1.00 65.10 C
ATOM 2670 O SER B 535 38.640 33.711 -7.420 1 ,00 65.03 O
ATOM 2671 N VAL B 536 38.497 31.724 -8.512 1.00 65.54 N ATOM 2672 CA VAL B 536 39.939 31.445 -8.521 1.00 66.42 C
ATOM 2673 CB VAL B 536 40.364 30.030 -8.027 1.00 69.07 C
ATOM 2674 CG1 VAL B 536 41.870 29.961 -7.776 1.00 68.56 C
ATOM 2675 CG2 VAL B 536 39.618 29.641 -6.773 1.00 68.82 C
ATOM 2676 C VAL B 536 40.577 31.779 -9.860 1.00 67.28 C ATOM 2677 O VAL B 536 40.238 31.205 -10.900 1.00 67.13 O
ATOM 2678 N HIS B 537 41.537 32.690 -9.806 1.00 71.82 N
ATOM 2679 CA HIS B 537 42.282 33.120 -10.963 1.00 73.25 C
ATOM 2680 CB HIS B 537 42.382 34.652 -10.986 1.00 74.71 C
ATOM 2681 CG HIS B 537 41.080 35.344 -11.273 1.00 75.65 C ATOM 2682 ND1 HIS B 537 41 .037 36.514 -12.009 1.00 76.64 N
ATOM 2683 CE1 HIS B 537 39.759 36.851 -12.072 1.00 77.11 C
ATOM 2684 NE2 HIS B 537 38.986 35.969 -11.432 1.00 76.60 N
ATOM 2685 CD2 HIS B 537 39.816 35.006 -10.917 1.00 76.33 C
ATOM 2686 C HIS B 537 43.630 32.432 -10.878 1.00 74.22 C ATOM 2687 0 HIS B 537 44.404 32.693 -9.956 1.00 74.32 O
ATOM 2688 N THR B 538 43.877 31.495 -11.805 1.00 77.01 N
ATOM 2689 CA THR B 538 45.116 30.721 -11.857 1.00 78.34 C
ATOM 2690 CB THR B 538 44.812 29.242 -12.209 1.00 85.85 C
ATOM 2691 OG1 THR B 538 43.638 28.789 -11.527 1.00 85.27 O JB2010.7161
ATOM 2692 CG2 THR B 538 45.967 28.311 -11.885 1.00 86.38 C
ATOM 2693 C THR B 538 46.115 31.372 -12.831 1.00 79.19 C
ATOM 2694 O THR B 538 45.705 32,031 -13.794 1.00 79.34 O
ATOM 2695 N ALA B 539 47.419 31.187 -12.571 1.00 81.18 N ATOM 2696 CA ALA B 539 48.504 31.695 -13.406 1.00 82.27 C
ATOM 2697 CB ALA B 539 49.1 13 32.940 -12.787 1.00 82.74 C
ATOM 2698 C ALA B 539 49.567 30.595 -13.547 1.00 83.28 C
ATOM 2699 0 ALA B 539 50.249 30.310 -12.559 1.00 83.57 O
ATOM 2700 N PRO B 540 49.728 29.953 -14.741 1.00 84.90 N ATOM 2701 CA PRO B 540 50.755 28.896 -14.888 1.00 85,48 C
ATOM 2702 CB PRO B 540 50.595 28.452 -16.345 1.00 87.23 C
ATOM 2703 CG PRO B 540 49.217 28.873 -16.732 1.00 86.88 C
ATOM 2704 CD PRO B 540 49,002 30.161 -16.011 1.00 86.75 C
ATOM 2705 C PRO B 540 52.172 29.407 -14.601 1.00 86.29 C ATOM 2706 O PRO B 540 52.364 30.619 -14.666 1.00 86.29 O
ATOM 2707 N PRO B 541 53.170 28.550 -14.263 1.00 89.05 N
ATOM 2708 CA PRO B 541 54.517 29.080 -13.960 1.00 90.08 C
ATOM 2709 CB PRO B 541 55.352 27.830 -13.673 1.00 91.35 C
ATOM 2710 CG PRO B 541 54.363 26.787 -13.328 1.00 90.77 C ATOM 2711 CD PRO B 541 53.133 27.082 -14.124 1.00 90.38 C
ATOM 2712 C PRO B 541 55.095 29.943 -15,072 1.00 91.24 C
ATOM 2713 0 PRO B 541 55.194 29.508 -16.230 1.00 91.62 O
ATOM 2714 N ALA B 542 55.425 31.197 -14.712 1.00 94.96 N
ATOM 2715 CA ALA B 542 55.957 32.220 -15.61 1 1.00 96.01 C ATOM 2716 CB ALA B 542 55.825 33.595 -14.968 1.00 96.64 C
ATOM 2717 C ALA B 542 57.404 31.971 -16.015 1.00 96.90 C
ATOM 2718 0 ALA B 542 57.746 32.145 -17.191 1.00 97.12 O
ATOM 2719 N GLU B 543 58.251 31.573 -15.028 1.00 99.93 N
ATOM 2720 CA GLU B 543 59.699 31.313 -15.134 1.00100.82 C ATOM 2721 CB GLU B 543 60.064 30.320 -16.262 1.00102.55 C
ATOM 2722 CG GLU B 543 59.623 28.888 -15.996 1.00103.87 C
ATOM 2723 CD GLU B 543 60.484 28.041 -15.070 1.00105.57 C
ATOM 2724 OE1 GLU B 543 61.230 28.609 -14.235 1.00105.85 O
ATOM 2725 OE2 GLU B 543 60.403 26.795 -15,179 1.00106.06 O ATOM 2726 C GLU B 543 60.511 32.616 -15.207 1.00101 .05 C
ATOM 2727 0 GLU B 543 61.743 32.582 -15.164 1.00101.12 O
ATOM 2728 N ALA B 544 59.800 33.763 -15.289 1.00101.57 N
ATOM 2729 CA ALA B 544 60.334 35.124 -15.351 1.00101.74 C
ATOM 2730 CB ALA B 544 59.196 36.116 -15.551 1.00102.50 C ATOM 2731 C ALA B 544 61.078 35.451 -14.066 1.00101.72 C
ATOM 2732 O ALA B 544 60.730 34.922 -13.009 1.00101.81 O
ATOM 2733 N SER B 545 62.095 36.328 -14.157 1.00101.31 N
ATOM 2734 CA SER B 545 62.915 36.754 -13.020 1.00100,89 C
ATOM 2735 CB SER B 545 63.937 37.798 -13.462 1.00105.30 C ATOM 2736 OG SER B 545 65.004 37.896 -12.531 1.00105.91 O
ATOM 2737 C SER B 545 62.056 37.285 -11.862 1.00100.43 C
ATOM 2738 O SER B 545 62.345 36.975 -10.702 1.00100.43 O
ATOM 2739 N MET B 546 60.983 38.048 -12.194 1.00 98.19 N
ATOM 2740 CA ET B 546 60.018 38.648 -11.263 1.00 97.41 C ATOM 2741 CB MET B 546 59.044 39.561 -12.025 1.00 99.79 C
ATOM 2742 C MET B 546 59.235 37,595 -10,468 1.00 96.79 C
ATOM 2743 O MET B 546 59.015 37.775 -9.269 1.00 96.77 O
ATOM 2744 N GLY B 547 58.833 36.521 -11.149 1.00 93.37 N
ATOM 2745 CA GLY B 547 58.080 35.41 1 -10.577 1.00 92.04 C JB2010.7161
ATOM 2746 C GLY B 547 56.702 35.272 -11.187 1.00 91.12 C
ATOM 2747 0 GLY B 547 56.297 36.120 -11.990 1 ,00 91.29 O
ATOM 2748 N THR B 548 55.972 34.193 -10.820 1.00 87.04 N
ATOM 2749 CA THR B 548 54.609 33.965 -11.322 1 ,00 85.72 C ATOM 2750 CB THR B 548 54.215 32.491 -11.294 1.00 83.58 C
ATOM 2751 OG THR B 548 55.281 31.71 -11.834 1.00 83.14 O
ATOM 2752 CG2 THR B 548 52.947 32.222 -12.080 1.00 83.07 C
ATOM 2753 C THR B 548 53.665 34.872 -10.538 1.00 85.12 C
ATOM 2754 O THR B 548 53.797 34.984 -9.317 1.00 85.14 O ATOM 2755 N ARG B 549 52.752 35.555 -11.243 1.00 81.89 N
ATOM 2756 CA ARG B 549 51.829 36.496 -10.628 1.00 80.81 C
ATOM 2757 CB ARG B 549 52.340 37.930 -10.822 1.00 81.46 C
ATOM 2758 CG ARG B 549 53.591 38.291 -10.053 1.00 81.96 C
ATOM 2759 CD ARG B 549 53,897 39.748 -10.295 1.00 84.00 C ATOM 2760 HE ARG B 549 55.170 40.159 -9.700 1.00 86.15 N
ATOM 2761 CZ ARG B 549 55.626 41.410 -9.686 1.00 86.73 C
ATOM 2762 NH1 ARG B 549 54.912 42.394 -10.231 1.00 86.59 N
ATOM 2763 NH2 ARG B 549 56.796 41.689 -9.125 1.00 87.07 N
ATOM 2764 C ARG B 549 50.432 36.402 -11.204 1.00 79.96 C ATOM 2765 0 ARG B 549 50.275 36.058 -12.373 1.00 79.95 O
ATOM 2766 N VAL B 550 49.418 36.738 -10.380 1.00 77.30 N
ATOM 2767 CA VAL B 550 47.999 36.769 -10.744 1.00 75.98 C
ATOM 2768 CB VAL B 550 47.274 35.394 -10.737 1.00 79.16 C
ATOM 2769 CG1 VAL B 550 47.301 34.733 -9.369 1.00 79.77 C ATOM 2770 CG2 VAL B 550 45.855 35.490 -11.282 1.00 78.47 C
ATOM 2771 C VAL B 550 47.304 37.894 -9.976 1.00 75.32 C
ATOM 2772 O VAL B 550 47.451 38.002 -8.759 1.00 75.08 O
ATOM 2773 N HIS B 551 46.600 38.760 -10.717 1.00 74.87 N
ATOM 2774 CA HIS B 551 45.899 39.939 -10.226 1.00 73.98 C ATOM 2775 CB HIS B 551 46,456 41.163 -10.987 1.00 75.03 C
ATOM 2776 CG HIS B 551 45.804 42.474 -10.673 1.00 75.55 C
ATOM 2777 ND1 HIS B 551 46.206 43.246 -9.593 1.00 76.61 N
ATOM 2778 CE1 HIS B 551 45.436 44.324 -9.617 1.00 76.47 C
ATOM 2779 NE2 HIS B 551 44.581 44.293 -10.640 1.00 76.50 N ATOM 2780 CD2 HIS B 551 44.818 43.126 -11.332 1.00 75.56 C
ATOM 2781 C HIS B 551 44.376 39.824 -10.416 1.00 73.27 C
ATOM 2782 0 HIS B 551 43.912 39.251 -11.416 1.00 73.24 O
ATOM 2783 N CYS B 552 43.604 40.380 -9.448 1.00 71.70 N
ATOM 2784 CA CYS B 552 42.138 40.429 -9.490 1.00 70.77 C ATOM 2785 CB CYS B 552 41.541 40.522 -8.082 1.00 69.58 C
ATOM 2786 SG CYS B 552 42.053 39.199 -6.948 1.00 68.99 S
ATOM 2787 C CYS B 552 41.862 41.701 -10.308 1.00 70.41 C
ATOM 2788 0 CYS B 552 41.715 42,787 -9.736 1.00 70.54 O
ATOM 2789 N HIS B 553 41.867 41.570 -11.656 1.00 71.79 N ATOM 2790 CA HIS B 553 41.681 42.676 -12.607 1.00 70.99 C
ATOM 2791 CB HIS B 553 42.066 42.274 -14.042 1.00 72.84 C
ATOM 2792 CG HIS B 553 41.315 41.090 -14.573 1.00 74.09 C
ATOM 2793 ND1 HIS B 553 41.888 39.823 -14.604 1.00 75.84 N
ATOM 2794 CE1 HIS B 553 40.964 39.022 -15.118 1.00 75.76 C ATOM 2795 NE2 HIS B 553 39.848 39.691 -15.422 1.00 75.40 N
ATOM 2796 CD2 HIS B 553 40.062 41.013 -15.084 1.00 74.98 C
ATOM 2797 C HIS B 553 40.331 43.366 -12.566 1 ,00 70.18 C
ATOM 2798 0 HIS B 553 40.292 44.589 -12.674 1.00 70.23 O
ATOM 2799 N GLN B 554 39.233 42.600 -12.409 1.00 67.50 N JB2010.7161
ATOM 2800 CA GLN B 554 37.873 43.126 -12.369 1.00 66.51 C
ATOM 2801 CB GLN B 554 36.858 41.997 -12.299 1.00 68.00 C
ATOM 2802 CG GLN B 554 36.678 41.299 -13.632 1.00 68.92 C
ATOM 2803 CD GLN B 554 36.898 39.820 -13.516 1.00 71.31 C ATOM 2804 OE1 GLN B 554 37.877 39.350 -12.909 1.00 73.83 O
ATOM 2805 NE2 GLN B 554 35.994 39.049 -14.104 1.00 71.22 N
ATOM 2806 C GLN B 554 37.660 44.125 -11.256 1.00 65.77 C
ATOM 2807 O GLN B 554 38.247 43.982 -10.187 1.00 65.63 O
ATOM 2808 N GLN B 555 36.848 45.161 -11.520 1.00 65.66 N ATOM 2809 CA GLN B 555 36.556 46.219 -10.548 1.00 65.12 C
ATOM 2810 CB GLN B 555 35.899 47.457 -11.210 1.00 67.33 C
ATOM 2811 CG GLN B 555 36.794 48.213 -12.203 1.00 68.29 C
ATOM 2812 CD GLN B 555 38.056 48.807 -11.598 1.00 69.00 C
ATOM 2813 OE1 GLN B 555 39.134 48.167 -11.561 1.00 67.63 O ATOM 2814 NE2 GLN B 555 37.941 50.051 -11.124 1.00 68.96 N
ATOM 2815 C GLN B 555 35.700 45.704 -9.403 1.00 64.48 C
ATOM 2816 O GLN B 555 34.694 45.021 -9.636 1.00 64.33 O
ATOM 2817 N GLY B 556 36.120 46.035 -8.183 1.00 61.80 N
ATOM 2818 CA GLY B 556 35.426 45.632 -6.967 1.00 60.75 C ATOM 2819 C GLY B 556 35.742 44.220 -6.514 1.00 60.01 C
ATOM 2820 O GLY B 556 35.109 43.721 -5.576 1.00 59.94 O
ATOM 2821 N HIS B 557 36.719 43.575 -7.195 1.00 57.86 N
ATOM 2822 CA HIS B 557 37.222 42.237 -6.920 1.00 57.23 C
ATOM 2823 CB H!S B 557 37.547 41.475 -8.206 1.00 58.41 C ATOM 2824 CG HIS B 557 36.346 40.916 -8.886 1.00 59.11 C
ATOM 2825 ND1 HIS B 557 36.363 39.651 -9.440 1.00 60.16 N
ATOM 2826 CE1 HIS B 557 35.155 39.474 -9.962 1.00 60.77 C
ATOM 2827 NE2 HIS B 557 34.373 40.543 -9.768 1.00 60.13 N
ATOM 2828 CD2 H!S B 557 35.126 41.472 -9.089 1.00 59.70 C ATOM 2829 C HIS B 557 38.463 42.410 -6.087 1.00 56.87 C
ATOM 2830 O HIS B 557 39.474 42.949 -6.558 1.00 57.10 O
ATOM 2831 N VAL B 558 38.378 41.973 -4.833 1.00 53.61 N
ATOM 2832 CA VAL B 558 39.458 42.090 -3.864 1.00 52.74 C
ATOM 2833 CB VAL B 558 39.019 42.997 -2.672 1.00 55.30 C ATOM 2834 CG1 VAL B 558 37.555 42.815 -2.308 1.00 54.80 C
ATOM 2835 CG2 VAL B 558 39.914 42.872 -1.468 1.00 55.20 C
ATOM 2836 C VAL B 558 40.105 40.729 -3.523 1.00 52.38 C
ATOM 2837 O VAL B 558 39.419 39.708 -3.480 1.00 52.35 O
ATOM 2838 N LEU B 559 41.438 40.712 -3.361 1.00 50.85 N ATOM 2839 CA LEU B 559 42.210 39.507 -3.043 1.00 50.58 C
ATOM 2840 CB LEU B 559 43.689 39.734 -3.342 1.00 49.73 C
ATOM 2841 CG LEU B 559 44.607 38.552 -3.233 1.00 49.07 C
ATOM 2842 CD1 LEU B 559 44.471 37.663 -4.434 1.00 48.63 C
ATOM 2843 CD2 LEU B 559 46.042 39.015 -3.094 1.00 49.11 C ATOM 2844 C LEU B 559 42.028 39.108 -1.585 1.00 50.65 C
ATOM 2845 O LEU B 559 42.357 39.888 -0.674 1.00 50.46 O
ATOM 2846 N THR B 560 41.493 37.895 -1.372 1.00 49.95 N
ATOM 2847 CA THR B 560 41.256 37.366 -0.031 1.00 50.39 C
ATOM 2848 CB THR B 560 39.826 36.862 0.160 1.00 44.40 C ATOM 2849 OG1 THR B 560 39.491 35.933 -0.867 1.00 43.46 O
ATOM 2850 CG2 THR B 560 38.810 37.989 0.224 1.0043.25 C
ATOM 2851 C THR B 560 42.345 36.402 0.430 1.00 51.36 C
ATOM 2852 O THR B 560 42.583 36.308 1.634 1.00 51.00 O
ATOM 2853 N GLY B 561 43.009 35.736 -0.519 1.00 54.82 N JB2G10.7161
ATOM 2854 CA GLY B 561 44.082 34.794 -0.230 1.00 57.16 C
ATOM 2855 C GLY B 561 44.795 34.222 -1.436 1.00 59.02 C
ATOM 2856 O GLY B 561 44.194 34.032 -2.498 1.00 58.70 O
ATOM 2857 N CYS B 562 46.087 33.922 -1.261 1.00 66.80 N ATOM 2858 CA CYS B 562 46.947 33.344 -2.296 1.00 69.27 C
ATOM 2859 CB CYS B 562 48.255 34.124 -2.398 1.00 71.87 C
ATOM 2860 SG CYS B 562 48.052 35.862 -2.889 1.00 74.75 S
ATOM 2861 C CYS B 562 47.204 31.837 -2.082 1.00 70.30 C
ATOM 2862 O CYS B 562 46.983 31.311 -0.988 1.00 70.71 O ATOM 2863 N SER B 563 47.656 31.149 -3.137 1.00 70.44 N
ATOM 2864 CA SER B 563 47.993 29.723 -3.126 1.00 71.93 C
ATOM 2865 CB SER B 563 46.764 28.856 -3.373 1.00 72.92 C
ATOM 2866 OG SER B 563 46.065 28.611 -2.170 1.00 72.43 O
ATOM 2867 C SER B 563 49.004 29.463 -4.219 1.00 73.35 C ATOM 2868 0 SER B 563 48.867 30.017 -5.306 1.00 73.32 O
ATOM 2869 N SER B 564 50.013 28.629 -3.943 1.00 76.75 N
ATOM 2870 CA SER B 564 51.022 28.281 -4.942 1.00 78.64 C
ATOM 2871 CB SER B 564 52.266 29.156 -4.820 1.00 81.53 C
ATOM 2872 OG SER B 564 53.201 28.631 -3.893 1.00 81.79 O ATOM 2873 C SER B 564 51.373 26.807 -4.870 1.00 80.09 C
ATOM 2874 O SER B 564 51.687 26.314 -3.788 1.00 80.17 O
ATOM 2875 N HIS B 565 51.296 26.105 -6.014 1.00 83.57 N
ATOM 2876 CA HIS B 565 51.621 24.681 -6.120 1.00 85.44 C
ATOM 2877 CB HIS B 565 50.351 23.802 -6.180 1.00 86.15 C ATOM 2878 CG HIS B 565 49.913 23.381 -7.549 1 ,00 86.44 C
ATOM 2879 ND1 HIS B 565 49.546 24.306 -8.507 1.00 86.55 N
ATOM 2880 CE1 HIS B 565 49.206 23.600 -9.573 1.00 86.46 C
ATOM 2881 NE2 HIS B 565 49.320 22.290 -9.353 1.00 86.36 N
ATOM 2882 CD2 HIS B 565 49.767 22.136 -8.062 1.00 86.71 C ATOM 2883 C HIS B 565 52.578 24.432 -7.283 1.00 86.75 C
ATOM 2884 O HiS B 565 52.578 25.194 -8.250 1.00 86,90 O
ATOM 2885 N TRP B 566 53.390 23.374 -7.187 1.00 88.77 N
ATOM 2886 CA TRP B 566 54.373 23.032 -8.212 1.00 90.59 C
ATOM 2887 CB TRP B 566 55.712 23.719 -7.890 1.00 88.53 C ATOM 2888 CG TRP B 566 56.224 23.436 -6.508 1.00 88.17 C
ATOM 2889 CD1 TRP B 566 57.057 22.423 -6.140 1.00 88.17 C
ATOM 2890 NE1 TRP B 566 57.307 22.481 -4.787 1.00 87.71 N
ATOM 2891 CE2 TRP B 566 56.623 23.541 -4.249 1.00 87.47 C
ATOM 2892 CD2 TRP B 566 55.928 24.170 -5.306 1.00 87.89 C ATOM 2893 CE3 TRP B 566 55.132 25.292 -5.015 1.00 87.60 C
ATOM 2894 CZ3 TRP B 566 55.066 25.744 -3.705 1.00 87.46 C
ATOM 2895 CH2 TRP B 566 55.762 25.095 -2.676 1.00 86,83 C
ATOM 2896 CZ2 TRP B 566 56.545 23.994 -2.924 1.00 87.12 C
ATOM 2897 C TRP B 566 54.559 21.516 -8.389 1.00 92.26 C ATOM 2898 O TRP B 566 54.200 20.744 -7.499 1.00 92.56 O
ATOM 2899 N GLU B 567 55.101 21.099 -9.556 1.00 96.31 N
ATOM 2900 CA GLU B 567 55.413 19.705 -9.899 1.00 98.35 C
ATOM 2901 CB GLU B 567 54.939 19.372 -11 ,326 1.00100.20 C
ATOM 2902 CG GLU B 567 53.559 18.749 -11.400 1.00101.11 C ATOM 2903 CD GLU B 567 52,423 19.746 -11.298 1.00102.11 C
ATOM 2904 OE1 GLU B 567 51.951 19.997 -10.164 1.00102.67 O
ATOM 2905 OE2 GLU B 567 52.008 20.280 -12.353 1.00102.12 O
ATOM 2906 C GLU B 567 56.938 19.523 -9,806 1.00 99,66 C
ATOM 2907 O GLU B 567 57.441 18.395 -9.783 1.00 99.88 O JB2010.7161
ATOM 2908 N VAL B 568 57.656 20.665 -9.750 1.00101.48 N
ATOM 2909 CA VAL B 568 59.113 20.826 -9.684 1.00103.05 C
ATOM 2910 CB VAL B 568 59.539 22.331 -9.854 1.00107.01 C
ATOM 2911 CG1 VAL B 568 60.976 22.458 -10.359 1.00106.96 C ATOM 2912 CG2 VAL B 568 58.588 23.089 -10.791 1.00106.73 C
ATOM 2913 C VAL B 568 59.744 20.134 -8.443 1.00104.20 C
ATOM 2914 0 VAL B 568 59.057 19.870 -7.453 1.00104.05 O
ATOM 2915 N GLU B 569 61.053 19.822 -8.535 1.00106.23 N
ATOM 2916 CA GLU B 569 61.861 19.159 -7.508 1.00107.72 C ATOM 2917 CB GLU B 569 63.216 18.700 -8.099 1.00109.51 C
ATOM 2918 CG GLU B 569 63.118 17.866 -9.369 1.00110.40 C
ATOM 2919 CD GLU B 569 62.823 16.388 -9.184 1.00111.93 C
ATOM 2920 OE1 GLU B 569 61.758 16.050 -8.615 1.00112.18 O
ATOM 2921 OE2 GLU B 569 63.659 15.563 -9.622 1.00112.44 O ATOM 2922 C GLU B 569 62.092 20.065 -6.295 1.00108.56 C
ATOM 2923 O GLU B 569 61.801 19.655 -5.170 1.00108.48 O
ATOM 2924 N ASP B 570 62.622 21.291 -6.533 1.00108.05 N
ATOM 2925 CA ASP B 570 62.933 22.300 -5.514 1.00109.08 C
ATOM 2926 CB ASP B 570 64.286 21.968 -4.840 1.00111.60 C ATOM 2927 CG ASP B 570 64.422 22.375 -3.375 1.00112.91 C
ATOM 2928 OD1 ASP B 570 65.513 22.154 -2.797 1.00114.14 O
ATOM 2929 OD2 ASP B 570 63.438 22.917 -2.807 1.00114.01 O
ATOM 2930 C ASP B 570 62.934 23.736 -6.106 1.00109.47 C
ATOM 2931 O ASP B 570 62.599 23.914 -7.283 1.00109.58 O ATOM 2932 N LEU B 571 63.297 24.754 -5.281 1.00107.35 N
ATOM 2933 CA LEU B 571 63.349 26.177 -5.656 1.00107.66 C
ATOM 2934 CB LEU B 571 62.819 27.089 -4.519 1.00107.78 C
ATOM 2935 CG LEU B 571 63.575 27.099 -3.176 1.00107.90 C
ATOM 2936 CD1 LEU B 571 63.720 28.518 -2.637 1.00107.36 C ATOM 2937 CD2 LEU B 571 62.894 26.200 -2.145 1.00107.57 C
ATOM 2938 C LEU B 571 64.734 26.639 -6.148 1.00107.66 C
ATOM 2939 0 LEU B 571 64.834 27.598 -6.917 1.00107.64 O
ATOM 2940 N GLN B 584 51.502 46.502 -5.817 1.00 88.83 N
ATOM 2941 CA GLN B 584 50.419 46.074 -6.708 1.00 88.89 C ATOM 2942 CB GLN B 584 50.933 45.124 -7.817 1.Q0 90.44 C
ATOM 2943 CG GLN B 584 52.050 45.701 -8.712 1.00 91.36 C
ATOM 2944 CD GLN B 584 53.475 45.453 -8.225 1.00 92.86 C
ATOM 2945 OE1 GLN B 584 53.744 45.206 -7.039 1.00 93.49 O
ATOM 2946 NE2 GLN B 584 54.433 45.522 -9.142 1.00 93.03 N ATOM 2947 C GLN B 584 49.263 45.449 -5.880 1.00 88.29 C
ATOM 2948 0 GLN B 584 49.342 44.279 -5.491 1.00 88.23 O
ATOM 2949 N PRO B 585 48.199 46.232 -5.571 1.00 83.06 N
ATOM 2950 CA PRO B 585 47.093 45.694 -4.759 1.00 82.46 C
ATOM 2951 CB PRO B 585 46.268 46.940 -4.404 1.00 84.18 C ATOM 2952 CG PRO B 585 47.129 48.115 -4,773 1.00 84.40 C
ATOM 2953 CD PRO B 585 47.949 47.642 -5.921 1.00 84.56 C
ATOM 2954 C PRO B 585 46.249 44.653 -5.483 1.00 81.73 C
ATOM 2955 O PRO B 585 46.091 44.730 -6.702 1.00 81.37 O
ATOM 2956 N ASN B 586 45.707 43.685 -4.711 1.00 76.02 N ATOM 2957 CA ASN B 586 44.872 42.560 -5.161 1.00 75.41 C
ATOM 2958 CB AS B 586 43.439 42.984 -5.507 1.00 67.36 C
ATOM 2959 CG ASN B 586 42.850 43.927 -4.480 1.00 66.58 C
ATOM 2960 OD1 ASN B 586 42.732 43.620 -3.282 1.00 65.30 O
ATOM 2961 ND2 ASN B 586 42.487 45.114 -4.927 1.00 66.00 N JB2010.7161
ATOM 2962 C AS B 586 45.561 41.652 -6.198 1.00 75.48 C
ATOM 2963 O ASN B 586 44.944 41.179 -7.159 1.00 75.17 O
ATOM 2964 N GLN B 587 46.867 41.406 -5.952 1.00 75.37 N
ATOM 2965 CA GLN B 587 47.771 40.593 -6.762 1.00 75.77 C ATOM 2966 CB GLN B 587 48.596 41.511 -7.682 1.00 77.05 C
ATOM 2967 CG GLN B 587 49.370 40.777 -8.771 1.00 77.33 C
ATOM 2968 CD GLN B 587 50.505 41.600 -9.320 1.00 77.36 C
ATOM 2969 OE1 GLN B 587 51.415 42.028 -8.590 1.00 76.63 O
ATOM 2970 NE2 GLN B 587 50.480 41.818 -10.626 1.00 76.94 N ATOM 2971 C GLN B 587 48.697 39.703 -5.886 1.00 75.88 C
ATOM 2972 0 GLN B 587 49.258 40.174 -4.888 1.00 75.70 O
ATOM 2973 N CYS B 588 48.840 38.417 -6.288 1.00 76.72 N
ATOM 2974 CA CYS B 588 49.661 37.376 -5.651 1.00 77.12 C
ATOM 2975 CB CYS B 588 49.004 36.007 -5.795 1.00 76.84 C ATOM 2976 SG CYS B 588 47.486 35.776 -4.839 1.00 75.32 S
ATOM 2977 C CYS B 588 51.042 37.344 -6.275 1.00 78.16 C
ATOM 2978 O CYS B 588 51.168 37.476 -7.496 1.00 78.21 O
ATOM 2979 N VAL B 589 52.071 37.098 -5.453 1.00 81.28 N
ATOM 2980 CA VAL B 589 53.450 36.994 -5.933 1.00 82.14 C ATOM 2981 CB VAL B 589 54.367 38.201 -5.585 1.00 86.38 C
ATOM 2982 CG1 VAL B 589 54.048 39.397 -6.474 1.00 86.47 C
ATOM 2983 CG2 VAL B 589 54.288 38.581 -4.102 1.00 86.30 C
ATOM 2984 C VAL B 589 54.047 35.623 -5.603 1.00 82.75 C
ATOM 2985 O VAL B 589 54.615 35.423 -4.526 1.00 82.96 O ATOM 2986 N GLY B 590 53.875 34.685 -6.531 1.00 84.26 N
ATOM 2987 CA GLY B 590 54.358 33.316 -6.392 1.00 85.16 C
ATOM 2988 C GLY B 590 55.740 33.064 -6.953 1.00 85.81 C
ATOM 2989 O GLY B 590 56.349 33.954 -7.556 1.00 85.93 O
ATOM 2990 N HIS B 591 56.245 31.837 -6.753 1.00 87.71 N ATOM 2991 CA HIS B 591 57.560 31.434 -7.246 1.00 87.96 C
ATOM 2992 CB HIS B 591 58.072 30.175 -6.530 1.00 89.13 C
ATOM 2993 CG HIS B 591 59.559 30.007 -6.623 1.00 90.45 C
ATOM 2994 ND1 HIS B 591 60.169 29.558 -7.790 1.00 91.31 N
ATOM 2995 CE1 HIS B 591 61.465 29.535 -7.528 1.00 91.78 C ATOM 2996 NE2 HIS B 591 61.723 29.934 -6.279 1 ,00 91.75 N
ATOM 2997 CD2 HIS B 591 60.515 30.241 -5.693 1.00 91.22 C
ATOM 2998 C HIS B 591 57.477 31.186 -8.736 1.00 87.64 C
ATOM 2999 O HIS B 591 56.501 30.601 -9.202 1.00 87.29 O
ATOM 3000 N ARG B 592 58.508 31.634 -9.474 1.00 88.66 N ATOM 3001 CA ARG B 592 58.654 31.511 -10.933 1.00 88.43 C
ATOM 3002 CB ARG B 592 60.011 32.068 -11.395 1.00 91.97 C
ATOM 3003 CG ARG B 592 61.185 31.755 -10.466 1.00 93.65 C
ATOM 3004 CD ARG B 592 62.404 32.592 -10.810 1.00 97.07 C
ATOM 3005 NE ARG B 592 63.185 32.010 -11.907 1.00 99.77 N ATOM 3006 CZ ARG B 592 64.227 32.602 -12.488 1.00100.88 C
ATOM 3007 NH1 ARG B 592 64.624 33.808 -12.092 1.00101.32 N
ATOM 3008 NH2 ARG B 592 64.877 31 .995 -13.472 1.00100.99 N
ATOM 3009 C ARG B 592 58.426 30.092 -11.470 1.00 87.64 C
ATOM 3010 O ARG B 592 57.856 29.923 -12.553 1.00 87.56 O ATOM 3011 N GLU B 593 58.850 29.084 -10.691 1.00 86.51 N
ATOM 3012 CA GLU B 593 58.717 27.663 -11.009 1.00 85.58 C
ATOM 3013 CB GLU B 593 59.825 26.870 -10.292 1.00 87.81 C
ATOM 3014 CG GLU B 593 61.220 27. 32 -10.843 1.00 88.88 C
ATOM 3015 CD GLU B 593 62.366 26.612 -9.994 1.00 90.22 C JB2010.7161
ATOM 3016 OE1 GLU B 593 62.983 27.423 -9.264 1.00 90.44 O
ATOM 3017 OE2 GLU B 593 62.650 25.394 -10.062 1.00 91.09 0
ATOM 3018 C GLU B 593 57.320 27.111 -10.642 1.00 84.60 C
ATOM 3019 O GLU B 593 56.904 26.084 -11.194 1.00 84.65 O ATOM 3020 N ALA B 594 56.604 27.795 -9.710 1.00 79.49 N
ATOM 3021 CA ALA B 594 55.274 27.415 -9.216 1.00 77.89 C
ATOM 3022 CB ALA B 594 55.184 27.711 -7.729 1.00 78.50 C
ATOM 3023 C ALA B 594 54.117 28.102 -9.930 1 .00 76.77 C
ATOM 3024 O ALA B 594 54.303 29.163 -10.513 1.00 76.59 O ATOM 3025 N SER B 595 52.919 27.501 -9.868 1.00 73.12 N
ATOM 3026 CA SER B 595 51.695 28.062 -10.438 1.00 72.12 C
ATOM 3027 CB SER B 595 50.741 26.959 -10.896 1.00 75.26 C
ATOM 3028 OG SER B 595 51.388 25.857 -11.509 1.00 75.51 O
ATOM 3029 C SER B 595 51.049 28.821 -9.280 1.00 71.42 C ATOM 3030 O SER B 595 51.114 28.338 -8.150 1.00 71.31 O
ATOM 3031 N ILE B 596 50.441 29.996 -9.538 1.00 70.73 N
ATOM 3032 CA ILE B 596 49.795 30.795 -8.491 1.00 69.99 C
ATOM 3033 CB !LE B 596 50.542 32.116 -8.133 1.00 73.71 C
ATOM 3034 CG1 ILE B 596 49.947 32.816 -6.903 1.00 74.21 C ATOM 3035 CD1 ILE B 596 50.799 32.768 -5.658 1.00 75.24 C
ATOM 3036 CG2 ILE B 596 50.638 33.072 -9.302 1.00 74.55 C
ATOM 3037 C ILE B 596 48.275 30.910 -8.656 1.00 69.25 C
ATOM 3038 O ILE B 596 47.787 31.141 -9.761 1.00 69.32 O
ATOM 3039 N HIS B 597 47.538 30.706 -7.547 1.00 67.64 N ATOM 3040 CA HIS B 597 46.075 30.743 -7.455 1.00 66.81 C
ATOM 3041 CB HIS B 597 45.519 29.399 -6.959 1.00 67.27 C
ATOM 3042 CG HIS B 597 46.210 28.207 -7.539 1.00 67.71 C
ATOM 3043 ND1 HIS B 597 45.629 27.457 -8.539 1.00 68.36 N
ATOM 3044 CE1 HIS B 597 46.498 26.497 -8.816 1.00 68.31 C ATOM 3045 NE2 HIS B 597 47.595 26.596 -8.062 1.00 68.23 N
ATOM 3046 CD2 H1S B 597 47.421 27.677 -7.238 1.00 67.76 C
ATOM 3047 C HIS B 597 45.674 31.849 -6.497 1.00 66.09 C
ATOM 3048 O HIS B 597 46.177 31.913 -5.372 1.00 66.02 O
ATOM 3049 N ALA B 598 44.783 32.728 -6.948 1.00 63.84 N ATOM 3050 CA ALA B 598 44.309 33.849 -6.153 1.00 62.86 C
ATOM 3051 CB ALA B 598 44.632 35.149 -6.858 1.00 63.48 C
ATOM 3052 C ALA B 598 42.823 33.754 -5.945 1.00 62.40 C
ATOM 3053 O ALA B 598 42.083 33.352 -6.850 1.00 62.27 O
ATOM 3054 N SER B 599 42.377 34.126 -4.751 1.00 61.90 N ATOM 3055 CA SER B 599 40.958 34.132 -4.437 1.00 61.05 C
ATOM 3056 CB SER B 599 40.717 33.607 -3.025 1.00 61.08 C
ATOM 3057 OG SER B 599 39.365 33.762 -2.632 1.00 60.21 O
ATOM 3058 C SER B 599 40.513 35.586 -4.594 1.00 60.78 C
ATOM 3059 O SER B 599 40.996 36.466 -3.878 1.00 60.38 O ATOM 3060 N CYS B 600 39.650 35.845 -5.578 1.00 64.31 N
ATOM 3061 CA CYS B 600 39.148 37.192 -5.861 1.00 64.47 C
ATOM 3062 CB CYS B 600 39.469 37.618 -7.293 1.00 66.19 C
ATOM 3063 SG CYS B 600 41.227 37.507 -7.728 1.00 68.52 S
ATOM 3064 C CYS B 600 37.665 37.204 -5.589 1.00 64.12 C ATOM 3065 O CYS B 600 36.912 36.457 -6.220 1.00 64.27 O
ATOM 3066 N CYS B 601 37.257 38.024 -4.612 1.00 62,68 N
ATOM 3067 CA CYS B 601 35.872 38.151 -4.174 1.00 62.41 C
ATOM 3068 CB CYS B 601 35.733 37.829 -2.682 1.00 63.13 C
ATOM 3069 SG CYS B 601 36.021 36.091 -2.241 1.00 64.17 S JB2010.7161
ATOM 3070 C CYS B 601 35.297 39.512 -4.472 1.00 62.08 C
ATOM 3071 0 CYS B 601 35.930 40.538 -4.211 1.00 61.64 O
ATOM 3072 N HIS B 602 34.069 39.518 -4.967 1.00 62.51 N
ATOM 3073 CA HIS B 602 33.345 40.745 -5,182 1.00 62.47 C ATOM 3074 CB HIS B 602 32.826 40.929 -6.617 1.00 63.59 C
ATOM 3075 CG HIS B 602 31.839 42.056 -6.694 1 ,00 65.07 C
ATOM 3076 ND1 HIS B 602 32.220 43.371 -6.446 1.00 65.53 N
ATOM 3077 CE1 HIS B 602 31.113 44.084 -6.533 1 ,00 66.01 C
ATOM 3078 NE2 HIS B 602 30,054 43.313 -6.801 1 .00 66.23 N ATOM 3079 CD2 HIS B 602 30,502 42.018 -6.886 1.00 65.94 C
ATOM 3080 C HIS B 602 32.201 40.698 -4.182 1.00 62.16 C
ATOM 3081 O HIS B 602 31.334 39.823 -4.266 1.00 62.15 O
ATOM 3082 N ALA B 603 32.219 41.614 -3.215 1.00 62.66 N
ATOM 3083 CA ALA B 603 31.200 41.685 -2.181 1.00 62.34 C ATOM 3084 CB ALA B 603 31.536 40.737 -1.033 1.00 63.20 C
ATOM 3085 C ALA B 603 31.166 43.102 -1.689 1.00 62.14 C
ATOM 3086 O ALA B 603 32.203 43.614 -1.276 1.00 61.88 O
ATOM 3087 N PRO B 604 29.981 43.744 -1.725 1.00 64.06 N
ATOM 3088 CA PRO B 604 29.861 45.144 -1.305 1.00 63.85 C ATOM 3089 CB PRO B 604 28.413 45.247 -0.855 1.00 65.98 C
ATOM 3090 CG PRO B 604 27.706 44.388 -1.885 1.00 66.43 C
ATOM 3091 CD PRO B 604 28.680 43.250 -2.225 1 .00 66.17 C
ATOM 3092 C PRO B 604 30,888 45.852 -0.418 1.00 63.45 C
ATOM 3093 O PRO B 604 31.762 46.528 -0.969 1.00 64.30 O ATOM 3094 N GLY B 605 30.793 45.751 0.897 1.00 60.05 N
ATOM 3095 CA GLY B 605 31.725 46.479 1.759 1.00 58.93 C
ATOM 3096 C GLY B 605 33.072 45.841 2.023 1.00 58.13 C
ATOM 3097 O GLY B 605 33.765 46.266 2.946 1.00 58.44 O
ATOM 3098 N LEU B 606 33.462 44.831 1.244 1.00 54.47 N ATOM 3099 CA LEU B 606 34.716 44.137 1.476 1.00 54.00 C
ATOM 3100 CB LEU B 606 34.802 42.813 0.688 1.00 53.72 C
ATOM 3101 CG LEU B 606 35.943 41.869 1.058 1.00 52.83 C
ATOM 3102 CD1 LEU B 606 35.850 41 ,425 2.531 1 ,00 51.59 C
ATOM 3103 CD2 LEU B 606 35.967 40.674 0.122 1.00 52.38 C ATOM 3104 C LEU B 606 35.955 44.974 1.296 1.00 54.09 C
ATOM 3105 O LEU B 606 36.233 45.423 0.192 1.00 54.24 O
ATOM 3106 N GLU B 607 36.716 45.144 2.379 1.00 55.04 N
ATOM 3107 CA GLU B 607 37.954 45.906 2.384 1.00 55.42 C
ATOM 3108 CB GLU B 607 37.782 47.162 3.260 1.00 57.38 C ATOM 3109 CG GLU B 607 39.035 48.016 3.363 1.00 58.87 C
ATOM 3 10 CD GLU B 607 39.038 49.093 4.430 1.00 60.85 C
ATOM 3111 OE1 GLU B 607 38.094 49.119 5.255 1.00 61.65 O
ATOM 3112 OE2 GLU B 607 39.983 49.920 4.436 1.00 61.21 O
ATOM 3113 C GLU B 607 39.086 45.011 2.911 1.00 55.44 C ATOM 3114 0 GLU B 607 39.032 44.606 4.071 1.00 55.60 O
ATOM 3115 N CYS B 608 40.106 44.711 2.074 1.00 54.14 N
ATOM 3116 CA CYS B 608 41.252 43.877 2.462 1.00 54.04 C
ATOM 3117 CB CYS B 608 41.272 42.564 1.690 1.00 54.04 C
ATOM 3118 SG CYS B 608 39.741 41.610 1.802 1.00 53.76 S ATOM 3119 C CYS B 608 42.591 44.580 2.358 1.00 54.18 C
ATOM 3120 O CYS B 608 42.816 45.325 1.411 1.00 54.34 O
ATOM 3121 N LYS B 609 43.495 44.306 3.300 1.00 54.86 N
ATOM 3122 CA LYS B 609 44.852 44.864 3.327 1.00 55.43 C
ATOM 3123 CB LYS B 609 44.982 46.016 4.346 1.00 56.81 C JB2010J161
ATOM 3124 CG LYS B 609 44.900 45.609 5.805 1.00 57.46 C
ATOM 3125 CD LYS B 609 44.750 46.814 6.731 1.00 59.08 C
ATOM 3126 CE LYS B 609 45.905 46.964 7.704 1.00 60.80 C
ATOM 3127 NZ LYS B 609 45.625 47.985 8.760 1.00 62.27 N ATOM 3128 C LYS B 609 45.914 43.777 3.572 1 .00 55.76 C
ATOM 3129 O LYS B 609 45.605 42.720 4.135 1.00 56.22 O
ATOM 3130 N VAL B 610 47.155 44.036 3. 50 1.00 54.85 N
ATOM 3131 CA VAL B 610 48.258 43.105 3.357 1.00 55.05 C
ATOM 3132 CB VAL B 610 49.068 42.824 2.062 1.00 57.33 C ATOM 3133 CG1 VAL B 610 50.383 42.112 2.348 1.00 57.13 C
ATOM 3134 CG2 VAL B 610 48.243 42.004 1.085 1.00 56.76 C
ATOM 3135 C VAL B 610 49.106 43.601 4.536 1.00 55.93 C
ATOM 3136 O VAL B 610 49.336 44.803 4.686 1.00 55.91 O
ATOM 3137 N LYS B 611 49.514 42.670 5.394 1.00 58.35 N ATOM 3138 CA LYS B 611 50.359 42.932 6.540 1.00 59.67 C
ATOM 3139 CB LYS B 611 49.598 42.751 7.846 1.00 62.48 C
ATOM 3140 CG LYS B 611 48.894 44.000 8.315 1.00 62.55 C
ATOM 3141 CD LYS B 611 48.464 43.842 9.738 1.00 62.02 C
ATOM 3142 CE LYS B 611 49.373 44.550 10.701 1.00 61.73 C ATOM 3143 NZ LYS B 611 48.814 44.504 12.076 1.00 63.02 N
ATOM 3144 C LYS B 611 51.493 41.950 6.454 1.00 60.89 C
ATOM 3145 0 LYS B 611 51.277 40.797 6.083 1.00 61 .07 O
ATOM 3146 N GLU B 612 52.704 42.401 6.769 1.00 65.52 N
ATOM 3147 CA GLU B 612 53.890 41.559 6.716 1.00 67.20 C ATOM 3148 CB GLU B 612 54.738 41.890 5.479 1.00 69.75 C
ATOM 3149 CG GLU B 612 54.102 41.580 4.134 1.00 72.07 C
ATOM 3150 CD GLU B 612 54.824 42.139 2.912 1.00 74.93 C
ATOM 3151 OE1 GLU B 612 55.927 42.719 3.075 1.00 75.72 O
ATOM 3152 OE2 GLU B 612 54.281 41.993 1.788 1.00 75.17 O ATOM 3153 C GLU B 612 54.745 41.777 7.932 1.00 67.85 C
ATOM 3154 0 GLU B 612 54.802 42.893 8.450 1.0067.69 O
ATOM 3155 N HIS B 613 55.425 40.709 8.375 1 .00 70.43 N
ATOM 3156 CA HIS B 613 56.382 40.719 9.485 1.00 71.72 C
ATOM 3157 CB HIS B 613 55.762 40.455 10.861 1.00 72.33 C ATOM 3158 CG HIS B 613 56.748 40.654 11.974 1.00 73.36 C
ATOM 3159 ND1 HIS B 613 57.589 39.633 12.387 1.00 73.70 N
ATOM 3160 CE1 HIS B 613 58.322 40.143 13.362 1.00 73.23 C
ATOM 3161 NE2 HIS B 613 58.015 41.420 13.589 1.00 72.77 H
ATOM 3162 CD2 HIS B 613 57.018 41.762 12.703 1.00 73.57 C ATOM 3163 C HIS B 613 57.513 39.749 9.181 1 .00 72.40 C
ATOM 3164 O HIS B 613 57.266 38.577 8.884 1.00 72.35 O
ATOM 3165 N GLY B 614 58.735 40.269 9.237 1.00 75.34 N
ATOM 3166 CA GLY B 614 59.949 39.516 8.956 1.00 76.68 C
ATOM 3167 C GLY B 614 60.985 39.550 10.059 1.00 77.54 C ATOM 3168 O GLY B 614 60.958 40.446 10.909 1.00 77.67 O
ATOM 3169 N ILE B 615 61.894 38.540 10.052 1.00 78.87 N
ATOM 3170 CA ILE B 615 63.027 38.317 10.979 1.00 79.84 C
ATOM 3171 CB ILE B 615 62.652 38.108 12.493 1.00 82.96 C
ATOM 3172 CG1 ILE B 615 61.263 37.475 12.710 1.00 83.14 C ATOM 3173 CD1 ILE B 615 61.280 36.003 12.683 1.00 83.42 C
ATOM 3174 CG2 ILE B 615 62.849 39.380 13.327 1.00 83.28 C
ATOM 3175 C ILE B 615 63.943 37.177 10.458 1.00 80.22 C
ATOM 3176 O ILE B 615 63.423 36.183 9.944 1.00 80.09 O
ATOM 3177 N PRO B 616 65.289 37.276 10.591 1.00 79.85 N JB2010.7161
ATOM 3178 CA PRO B 616 66.159 36.200 10.088 1.00 80.08 C
ATOM 3179 CB PRO B 616 67.370 36.971 9,541 1.00 82.01 C
ATOM 3180 CG PRO B 616 67.277 38.388 10.173 1.00 81.86 C
ATOM 3181 CD PRO B 616 66.107 38.379 11.126 1.00 81.64 C ATOM 3182 C PRO B 616 66.561 35.181 11.164 1.00 80.04 C
ATOM 3183 O PRO B 616 66.838 34.014 10.864 1.00 79.99 O
ATOM 3184 N GLN B 619 65.988 31.467 12.228 1.00 97.95 N
ATOM 3185 CA GLN B 619 64.818 31.710 13.070 1.00 98.18 C
ATOM 3186 CB GLN B 619 64.133 33.018 12.679 1.00 99.99 C ATOM 3187 CG GLN B 619 64.286 34.089 13.749 1.00100.87 C
ATOM 3188 CD GLN B 619 63.267 33.998 14.875 1.00101.55 C
ATOM 3189 OE1 GLN B 619 62.669 32.942 15.169 1.00102.03 O
ATOM 3190 NE2 GLN B 619 63.053 35.124 15.539 1.00101 ,11 N
ATOM 3191 C GLN B 619 63.804 30.562 13.091 1.00 97.94 C ATOM 3192 O GLN B 619 63.628 29.897 12.072 1.00 98.16 O
ATOM 3193 N GLU B 620 63.127 30.340 14.243 1 .00 94.15 N
ATOM 3194 CA GLU B 620 62.138 29.257 14.416 1.00 93.93 C
ATOM 3195 CB GLU B 620 61.942 28.898 15.905 1.00 95.67 C
ATOM 3196 CG GLU B 620 61.685 27.415 16.152 1.00 97.17 C ATOM 3197 CD GLU B 620 60.234 26.966 16.211 1.00 99.16 C
ATOM 3198 OE1 GLU B 620 59.530 27,346 17.176 1.00100.08 O
ATOM 3199 OE2 GLU B 620 59.804 26.223 15.297 1.00 99.16 O
ATOM 3200 C GLU B 620 60.786 29.473 13.694 1.00 93.26 C
ATOM 3201 O GLU B 620 60.458 28.710 12.779 1.00 93.37 O ATOM 3202 N GLN B 621 59.998 30.485 14.115 1.00 87.28 N
ATOM 3203 CA GLN B 621 58.700 30.777 13.504 1.00 85.89 C
ATOM 3204 CB GLN B 621 57.568 29.950 14.133 1.00 87.11 C
ATOM 3205 CG GLN B 621 57.182 30.349 15.556 1.00 87.24 C
ATOM 3206 CD GLN B 621 55.691 30.342 15.770 1.00 88.14 C ATOM 3207 OE1 GLN B 621 54.969 29.432 15.332 1.00 88.09 O
ATOM 3208 NE2 GL B 621 55.197 31.356 16.468 1.00 88.26 N
ATOM 3209 C GLN B 621 58.366 32.253 13.525 1.00 84.75 C
ATOM 3210 O GLN B 621 58.694 32.950 14.491 1.00 84.85 O
ATOM 3211 N VAL B 622 57.697 32.724 12.461 1.00 78.75 N ATOM 3212 CA VAL B 622 57.306 34,129 12.334 1.00 77.09 C
ATOM 3213 CB VAL B 622 58.078 34.874 11.203 1.00 80.68 C
ATOM 3214 CG1 VAL B 622 57.753 34.324 9.821 1.00 81.02 C
ATOM 3215 CG2 VAL B 622 57.883 36.383 11.268 1.00 80.40 C
ATOM 3216 C VAL B 622 55.775 34.302 12.354 1.00 75.68 C ATOM 3217 O VAL B 622 55.052 33.525 11.726 1.00 75,34 O
ATOM 3218 N THR B 623 55.307 35.301 13.119 1.00 70.40 N
ATOM 3219 CA THR B 623 53.901 35.617 13.343 1.00 68.81 C
ATOM 3220 CB THR B 623 53.567 35.230 14.814 1.00 72.33 C
ATOM 3221 OG1 THR B 623 52.862 33.992 14.833 1.00 71.66 O ATOM 3222 CG2 THR B 623 52.797 36.301 15.597 1.00 72.39 C
ATOM 3223 C THR B 623 53.515 37.052 12.933 1.00 67.86 C
ATOM 3224 O THR B 623 54.271 37.989 13.186 1.00 68.00 O
ATOM 3225 N VAL B 624 52.330 37.213 12.306 1.00 64.60 N
ATOM 3226 CA VAL B 624 51.748 38.505 11.891 1.00 63.05 C ATOM 3227 CB VAL B 624 52.143 39.034 10.477 1.00 65.35 C
ATOM 3228 CG1 VAL B 624 51.604 38.157 9.355 1.00 65.05 C
ATOM 3229 CG2 VAL B 624 51.712 40.479 10.285 1.00 64.43 C
ATOM 3230 C VAL B 624 50,250 38.441 12.146 1.0062.30 C
ATOM 3231 O VAL B 624 49.585 37.526 11.674 1.00 61.94 O JB2010.7161
ATOM 3232 N ALA B 625 49.736 39.376 12.932 1.00 61.82 N
ATOM 3233 CA ALA B 625 48.330 39.393 13.282 1.00 61.21 C
ATOM 3234 CB ALA B 625 48.172 39.301 14.786 1.00 61.54 C
ATOM 3235 C ALA B 625 47.572 40.589 12.757 1.00 60.92 C ATOM 3236 O ALA B 625 48.161 41.638 12.505 1.00 60.94 O
ATOM 3237 N CYS B 626 46.251 40.420 12.600 1.00 62.19 N
ATOM 3238 CA CYS B 626 45.316 41.446 12.181 1.00 62.00 C
ATOM 3239 CB CYS B 626 44.181 40.852 11.351 1.00 61.53 C
ATOM 3240 SG CYS B 626 44.729 39.974 9.867 1.00 60.63 S ATOM 3241 C CYS B 626 44.791 42.077 13.468 1.00 62.54 C
ATOM 3242 O CYS B 626 44.401 41.370 14.405 1.00 62.53 O
ATOM 3243 N GLU B 627 44.799 43.408 13.509 1.00 66.87 N
ATOM 3244 CA GLU B 627 44.339 44.231 14.627 1.00 67.38 C
ATOM 3245 CB GLU B 627 44.695 45.721 14.392 1.00 69.87 C ATOM 3246 CG GLU B 627 45.784 46.001 13.360 1.00 72.16 C
ATOM 3247 CD GLU B 627 45.363 45.918 11.898 1.00 75.33 C
ATOM 3248 OE1 GLU B 627 45.972 45.1 17 11.149 1.00 75.99 O
ATOM 3249 OE2 GLU B 627 44.425 46.650 11.501 1.00 75.31 O
ATOM 3250 C GLU B 627 42.824 44.075 14.779 1.00 67.07 C ATOM 3251 O GLU B 627 42.156 43.619 13.845 1.00 67.1 1 O
ATOM 3252 N GLU B 628 42.281 44.454 15.948 1.00 68.37 N
ATOM 3253 CA GLU B 628 40.844 44.369 16.237 1.00 68.37 C
ATOM 3254 CB GLU B 628 40.514 44.963 17.627 1.00 71.24 C
ATOM 3255 CG GLU B 628 39.120 44.627 18.153 1.00 74.08 C ATOM 3256 CD GLU B 628 38.845 45.018 19.599 1.00 78.48 C
ATOM 3257 OE1 GLU B 628 39.107 46.189 19.964 1 ,00 80.05 O
ATOM 3258 OE2 GLU B 628 38.358 44.152 20.366 1.00 80.14 O
ATOM 3259 C GLU B 628 40.078 45.090 15.144 1.00 67.26 C
ATOM 3260 O GLU B 628 40.464 46.193 14.738 1.00 67.45 O ATOM 3261 N GLY B 629 39.026 44.437 14.665 1.00 63.31 N
ATOM 3262 CA GLY B 629 38.176 44.945 13.597 1.00 61.57 C
ATOM 3263 C GLY B 629 38.453 44.248 12.284 1.00 60.65 C
ATOM 3264 O GLY B 629 37.591 44.193 11.400 1.00 60.63 O
ATOM 3265 N TRP B 630 39.664 43.697 12.159 1.00 58.89 N ATOM 3266 CA TRP B 630 40.072 42.977 10.967 1.00 57.94 C
ATOM 3267 CB TRP B 630 41.426 43.461 10.459 1.00 56.85 C
ATOM 3268 CG TRP B 630 41.379 44.906 10.065 1.00 57.46 C
ATOM 3269 CD1 TRP B 630 41.403 45.984 10.901 1.00 57.83 C
ATOM 3270 NE1 TRP B 630 41.321 47.148 10.177 1.00 57.93 N ATOM 3271 CE2 TRP B 630 41.249 46.839 8.844 1.00 57.67 C
ATOM 3272 CD2 TRP B 630 41.256 45.429 8.739 1.00 57.43 C
ATOM 3273 CE3 TRP B 630 41.195 44.847 7.464 1.00 56.71 C
ATOM 3274 CZ3 TRP B 630 41.108 45.674 6.358 1.00 56.82 C
ATOM 3275 CH2 TRP B 630 41.077 47.069 6.495 1.00 56.39 C ATOM 3276 CZ2 TRP B 630 41.155 47.674 7.725 1.00 56.57 C
ATOM 3277 C TRP B 630 40.051 41.502 11.233 1.00 57.10 C
ATOM 3278 O TRP B 630 40.207 41.073 12.378 1.00 57.34 O
ATOM 3279 N THR B 631 39.822 40.730 10.168 1.00 52.78 N
ATOM 3280 CA THR B 631 39.723 39.290 10.167 1.00 51.32 C ATOM 3281 CB THR B 631 38.293 38.922 9.773 1.00 51.99 C
ATOM 3282 OG1 THR B 631 37.392 39.396 10.777 1.00 51.79 O
ATOM 3283 CG2 THR B 631 38.107 37.443 9.550 1.00 50.82 C
ATOM 3284 C THR B 631 40.744 38.722 9.197 1.00 51 .00 C
ATOM 3285 O THR B 631 40.700 39.027 8.008 1.00 50.56 O JB2010.7161
ATOM 3286 N LEU B 632 41.646 37.875 9.694 1.00 50.70 N
ATOM 3287 CA LEU B 632 42.649 37.233 8.857 1.00 50.33 C
ATOM 3288 CB LEU B 632 43.651 36.477 9.731 1.00 50.25 C
ATOM 3289 CG LEU B 632 44.690 35.644 9.007 1.00 49.59 C ATOM 3290 CD1 LEU B 632 45.708 36.509 8.381 1.00 49.63 C
ATOM 3291 CD2 LEU B 632 45.386 34.745 9.961 .00 49.87 C
ATOM 3292 C LEU B 632 41.965 36.267 7.916 1.00 50.17 C
ATOM 3293 0 LEU B 632 41.327 35.330 8.379 1.00 50.24 0
ATOM 3294 N THR B 633 42.080 36.501 6.607 1.00 49.83 N ATOM 3295 CA THR B 633 41.469 35.636 5.589 1.00 49.74 C
ATOM 3296 CB THR B 633 40.691 36.455 4.545 1.00 45.88 C
ATOM 3297 OG1 THR B 633 41.587 37.376 3.927 1.00 44.87 O
ATOM 3298 CG2 THR B 633 39.477 37.182 5.136 1.00 45.09 C
ATOM 3299 C THR B 633 42.523 34.772 4.901 1.00 50.13 C ATOM 3300 O THR B 633 42.222 33.654 4.520 1.00 50.32 O
ATOM 3301 N GLY B 634 43.729 35.303 4.733 1.00 50.23 N
ATOM 3302 CA GLY B 634 44.820 34.609 4.066 1.00 50.78 C
ATOM 3303 C GLY B 634 46.140 34.710 4.793 1.00 51 .61 C
ATOM 3304 O GLY B 634 46.465 35.740 5.388 1.00 51.21 O ATOM 3305 N CYS B 635 46.904 33.626 4.746 1.00 54.23 N
ATOM 3306 CA CYS B 635 48.200 33.528 5.396 1.00 55.68 C
ATOM 3307 CB CYS B 635 48.056 32.903 6.784 1.00 55.59 C
ATOM 3308 SG CYS B 635 49.635 32.444 7.552 1.00 56.18 S
ATOM 3309 C CYS B 635 49.179 32.742 4.524 1.00 56.70 C ATOM 3310 O CYS B 635 48.820 31.683 3.995 1.00 57.08 O
ATOM 3311 N SER B 636 50.407 33.260 4.374 1.00 57.68 N
ATOM 3312 CA SE B 636 51.478 32.619 3.603 1.00 59.41 C
ATOM 3313 CB SER B 636 51.220 32.699 2.099 1.00 63.69 C
ATOM 3314 OG SER B 636 51.226 34.035 1.626 1.00 63.68 O ATOM 3315 C SER B 636 52.816 33.230 3.959 1.00 60.57 C
ATOM 3316 O SER B 636 52.876 34.130 4.793 1.00 60.88 O
ATOM 3317 N ALA B 637 53.886 32.737 3.340 1.00 63.32 N
ATOM 3318 CA ALA B 637 55.247 33,223 3.559 1.00 64.95 C
ATOM 3319 CB ALA B 637 56.132 32.073 3.994 1.00 65.56 C ATOM 3320 C ALA B 637 55.782 33.814 2.267 1.00 66.19 C
ATOM 3321 O ALA B 637 55.192 33.591 1.205 1.00 66.44 O
ATOM 3322 N LEU B 638 56.895 34.562 2.343 1.00 68.82 N
ATOM 3323 CA LEU B 638 57.511 35.129 1.145 1.00 70.17 C
ATOM 3324 CB LEU B 638 58.206 36.469 1.425 1.00 70.44 C ATOM 3325 CG LEU B 638 57.325 37.716 1.355 1.00 71.03 C
ATOM 3326 CD1 LEU B 638 58.138 38.978 1.643 1.00 70.92 C
ATOM 3327 CD2 LEU B 638 56.598 37.827 0.001 1.00 70.95 C
ATOM 3328 C LEU B 638 58.498 34.111 0.551 1.00 71.25 C
ATOM 3329 O LEU B 638 59.251 33.474 1.314 1.00 71.34 O ATOM 3330 N PRO B 639 58.499 33.935 -0.803 1.00 71.69 N
ATOM 3331 CA PRO B 639 59.419 32.953 -1.424 1.00 71.83 C
ATOM 3332 CB PRO B 639 58.928 32.875 -2.882 1.00 73.61 C
ATOM 3333 CG PRO B 639 57.562 33.554 -2.893 1.00 73.64 C
ATOM 3334 CD PRO B 639 57.658 34.596 -1.824 1.00 73.30 C ATOM 3335 C PRO B 639 60.909 33.327 -1.329 1.00 71.98 C
ATOM 3336 0 RO B 639 61.736 32.557 -0.821 1.00 72.17 O
ATOM 3337 N SER B 642 63.922 30.173 2.266 1.00102.54 N
ATOM 3338 CA SER B 642 64.126 28.911 1.553 1.00102.51 C
ATOM 3339 CB SER B 642 65.576 28.781 1.095 1.00106.12 C JB2010.7161
ATOM 3340 OG SER B 642 65.809 29.507 -0.102 1.00107.12 O
ATOM 3341 C SER B 642 63.695 27.667 2.349 1.00102.15 C
ATOM 3342 0 SER B 642 63.402 26.623 1.746 1.00102.22 O
ATOM 3343 N HIS B 643 63.649 27.783 3.697 1.00 97.98 N ATOM 3344 CA HIS B 643 63.269 26.687 4.591 1.00 97.25 C
ATOM 3345 CB HIS B 643 64.363 26.453 5.655 1.00 98.90 C
ATOM 3346 CG HIS B 643 64.136 25.250 6.520 1.00101.21 C
ATOM 3347 ND1 HiS B 643 63.918 23.993 5.973 1.00102.92 N
ATOM 3348 CE1 HIS B 643 63.758 23.178 7.004 1.00103.54 C ATOM 3349 NE2 HIS B 643 63.865 23.829 8.164 1.00103.74 N
ATOM 3350 CD2 HiS B 643 64.113 25.150 7.868 1.00103.05 C
ATOM 3351 C HIS B 643 61.851 26.834 5.202 1.00 96.00 C
ATOM 3352 O HIS B 643 61.705 27.213 6.368 1.00 96.03 O
ATOM 3353 N VAL B 644 60.806 26.523 4.400 1.00 88.17 N ATOM 3354 CA VAL B 644 59.409 26.606 4.848 1.00 86.20 C
ATOM 3355 CB VAL B 644 58.501 27.638 4.118 1.00 89.28 C
ATOM 3356 CG1 VAL B 644 58.803 29.061 4.574 1.00 88.83 C
ATOM 3357 CG2 VAL B 644 58.585 27.508 2.596 1.00 89.07 C
ATOM 3358 C VAL B 644 58.740 25.251 5.027 1.00 84.56 C ATOM 3359 O VAL B 644 58.657 24.459 4.088 1.00 84.29 O
ATOM 3360 N LEU B 645 58.273 24.996 6.250 1.00 77.53 N
ATOM 3361 CA LEU B 645 57.578 23.772 6.632 1.00 75.38 C
ATOM 3362 CB LEU B 645 57.677 23.595 8.165 1.00 75.55 C
ATOM 3363 CG LEU B 645 58.820 22.711 8.732 100 75.68 C ATOM 3364 CD1 LEU B 645 60.212 23.322 8.502 1.00 75.26 C
ATOM 3365 CD2 LEU B 645 58.633 22.489 10.215 1.00 75.25 C
ATOM 3366 C LEU B 645 56.112 23.898 6.181 1.00 73.53 C
ATOM 3367 0 LEU B 645 55.490 22.916 5.767 1.00 73.40 O
ATOM 3368 N GLY B 646 55.607 25.125 6.246 1.00 66.85 N ATOM 3369 CA GLY B 646 54.255 25.504 5.873 1.00 63.83 C
ATOM 3370 C GLY B 646 53.772 26.714 6.645 1.00 62.06 C
ATOM 3371 O GLY B 646 54.445 27.191 7.566 1.00 61.80 O
ATOM 3372 N ALA B 647 52.595 27.218 6.278 1.00 58.17 N
ATOM 3373 CA ALA B 647 51.989 28.367 6.951 1.00 56.19 C ATOM 3374 CB ALA B 647 52.102 29.605 6.077 1.00 56.84 C
ATOM 3375 C ALA B 647 50.513 28.073 7.291 1.00 54.76 C
ATOM 3376 O ALA B 647 49.873 27.285 6.586 1.00 54.27 O
ATOM 3377 N TYR B 648 49,980 28.693 8.368 1.00 50.14 N
ATOM 3378 CA TYR B 648 48.583 28.494 8.792 1.00 48.49 C ATOM 3379 CB TYR B 648 48.360 27.119 9.488 1.0048.43 C
ATOM 3380 CG TYR B 648 49.334 26.811 10.605 1.00 47.29 C
ATOM 3381 CD1 TY B 648 50.478 26.055 10.369 1.00 47.36 C
ATOM 3382 CE1 TYR B 648 51.394 25.787 11.388 1.00 47.07 C
ATOM 3383 CZ TYR B 648 51.166 26.276 12.663 1.00 45.95 C ATOM 3384 OH TYR B 648 52.061 25.992 13.674 1.00 45.65 O
ATOM 3385 CE2 TYR B 648 50.021 27.014 12.923 1.0044.78 C
ATOM 3386 CD2 TYR B 648 49.116 27.277 11.895 1.0045.25 C
ATOM 3387 C TYR B 648 48.042 29.626 9.658 1.0047.40 C
ATOM 3388 O TYR B 648 48,804 30.328 10.309 1.00 46.98 O ATOM 3389 N ALA B 649 46.719 29.786 9.664 1.00 47.15 N
ATOM 3390 CA ALA B 649 46.019 30.787 10.456 1.00 46.58 C
ATOM 3391 CB ALA B 649 44.765 31.231 9.730 1.00 47.37 C
ATOM 3392 C ALA B 649 45.629 30.214 1 1.817 1.00 46.15 C
ATOM 3393 O ALA B 649 45.219 29.051 11.927 1.00 46.34 O JB2010.7161
ATOM 3394 N VAL B 650 45,750 31.030 12.855 1.00 44.74 N
ATOM 3395 CA VAL B 650 45.373 30.661 14.224 1.00 44.16 C
ATOM 3396 CB VAL B 650 46.603 30.359 15.146 1.00 46.30 C
ATOM 3397 CG1 VAL B 650 46.155 29.812 16.494 1.0044.69 C ATOM 3398 CG2 VAL B 650 47.577 29.393 14.482 1.00 44.90 C
ATOM 3399 C VAL B 650 44.588 31.894 14.643 1.00 44.31 C
ATOM 3400 O VAL B 650 45.189 32.893 15.040 1.00 44.03 O
ATOM 3401 N ASP B 651 43.255 31.859 14.469 1.00 46.53 N
ATOM 3402 CA ASP B 651 42.373 32.999 14.750 1.00 47.35 C ATOM 3403 CB ASP B 651 42.384 33.367 16.246 1.00 50.53 C
ATOM 3404 CG ASP B 651 41.324 34.359 16.652 1 .00 52.00 C
ATOM 3405 OD1 AS B 651 40.256 34.391 15.997 1.00 53.87 O
ATOM 3406 OD2 ASP B 651 41.554 35.105 17.631 1.00 54.61 O
ATOM 3407 C ASP B 651 42.798 34.180 13.810 1.00 47.78 C ATOM 3408 O ASP B 651 42.732 34.012 12.592 1.00 47.81 O
ATOM 3409 N ASN B 652 43.281 35.322 14.341 1.00 48.04 N
ATOM 3410 CA ASN B 652 43.707 36.435 13.484 1.0048.42 C
ATOM 3411 CB ASN B 652 43.183 37.753 14.015 1.00 50.35 C
ATOM 3412 CG ASN B 652 41.752 38.009 13.643 1.00 50.70 C ATOM 3413 OD1 ASN B 652 41.119 37.266 12.859 1.00 51.37 O
ATOM 3414 ND2 AS B 652 41.211 39.082 14.206 1.00 51.48 N
ATOM 3415 C ASN B 652 45.219 36.483 13.282 1.00 48.74 C
ATOM 3416 O AS B 652 45.756 37.467 12.784 1.00 48.04 O
ATOM 3417 N THR B 653 45.898 35.408 13.656 1.00 50.30 N ATOM 3418 CA THR B 653 47.335 35.346 13.552 1.00 51.00 C
ATOM 3419 CB THR B 653 47.930 34.993 14.930 1.00 53.38 C
ATOM 3420 OG1 THR B 653 47.599 36.029 15.861 1.00 53.32 O
ATOM 3421 CG2 THR B 653 49.432 34.806 14.897 1.00 53.09 C
ATOM 3422 C THR B 653 47.754 34.423 12.443 1.00 52.01 C ATOM 3423 O THR B 653 47.322 33.268 12.382 1.00 52.52 O
ATOM 3424 N CYS B 654 48.588 34.941 11.554 1.00 53.72 N
ATOM 3425 CA CYS B 654 49.147 34.154 10.475 1.00 54.88 C
ATOM 3426 CB CYS B 654 49.369 34.992 9.224 1.00 55.55 C
ATOM 3427 SG CYS B 654 50.488 34.228 8.028 1.00 55.79 S ATOM 3428 C CYS B 654 50.470 33.589 11.020 1.00 56.01 C
ATOM 3429 0 CYS B 654 51.329 34.346 11.507 1.00 56.19 O
ATOM 3430 N VAL B 655 50.605 32.258 10.964 1.00 55.20 N
ATOM 3431 CA VAL B 655 51.774 31.555 11.451 1.00 56.32 C
ATOM 3432 CB VAL B 655 51.385 30.515 12.540 1.00 59.15 C ATOM 3433 CG1 VAL B 655 52.601 29.733 13.038 1.00 58.78 C
ATOM 3434 CG2 VAL B 655 50.672 31.181 13.704 1.00 58.25 C
ATOM 3435 C VAL B 655 52.515 30.922 10.280 1.00 57.77 C
ATOM 3436 O VAL B 655 51.910 30.224 9.467 1.00 57.89 O
ATOM 3437 N VAL B 656 53.830 31.169 10.216 1.00 61.77 N ATOM 3438 CA VAL B 656 54.755 30.626 9.225 1.00 63.68 C
ATOM 3439 CB VAL B 656 55.355 31.744 8.333 1.00 66.73 C
ATOM 3440 CG1 VAL B 656 56.562 31.247 7.545 1.00 66.20 C
ATOM 3441 CG2 VAL B 656 54.297 32.315 7.392 1.00 67.10 C
ATOM 3442 C VAL B 656 55.817 29.799 10.001 1.00 65.28 C ATOM 3443 O VAL B 656 56.416 30.296 10.967 1.00 65.57 O
ATOM 3444 N ARG B 657 56.028 28.543 9.587 1.00 69.23 N
ATOM 3445 CA ARG B 657 56.969 27.643 10.249 1.00 71.43 C
ATOM 3446 CB ARG B 657 56.272 26.320 10.602 1 .00 73.42 C
ATOM 3447 CG ARG B 657 54.945 26.449 11.362 1.00 73.99 C JB2010.7161
ATOM 3448 CD ARG B 657 55.069 26.898 12.806 1.00 74.54 C
ATOM 3449 NE ARG B 657 56.272 26.387 13.459 1.00 75.10 N
ATOM 3450 CZ ARG B 657 56.388 25.185 14.013 1.00 76.00 C
ATOM 3451 NH1 ARG B 657 55.366 24.336 13.999 1.00 75.65 N ATOM 3452 NH2 ARG B 657 57.533 24.817 14.578 1.00 77.39 N
ATOM 3453 C ARG B 657 58.263 27.366 9.471 1.00 72.89 C
ATOM 3454 O ARG B 657 58.255 27.314 8.240 1.00 72.89 O
ATOM 3455 N SER B 658 59.368 27.157 10.221 1.00 76.51 N
ATOM 3456 CA SER B 658 60.724 26.856 9.736 1.00 78.24 C ATOM 3457 CB SER B 658 61.410 28.142 9.287 1.00 82.02 C
ATOM 3458 OG SER B 658 61.552 29.053 10.364 1.00 82.21 O
ATOM 3459 C SER B 658 61.554 26.177 10.863 1.00 79.54 C
ATOM 3460 O SER B 658 60.999 25.879 11.932 1.00 79.96 O
ATOM 3461 N ARG B 659 62.879 25.940 10.626 1.00 81 .25 N ATOM 3462 CA ARG B 659 63.822 25.346 11.595 1.00 82.60 C
ATOM 3463 CB ARG B 659 63.975 23.825 11.416 1.00 86.96 C
ATOM 3464 CG ARG B 659 62.829 23.021 12.028 1.00 89.32 C
ATOM 3465 CD ARG B 659 63.078 21.525 1 1.977 1.00 92.74 C
ATOM 3466 NE ARG B 659 62.329 20.875 10.900 1.00 94.29 N ATOM 3467 CZ ARG B 659 62.816 20.625 9.688 1.00 95.33 C
ATOM 3468 NH1 ARG B 659 64.061 20.973 9.378 1.00 95.40 N
ATOM 3469 NH2 ARG B 659 62.064 20.021 8.776 1.00 95.41 N
ATOM 3470 C ARG B 659 65.190 26.063 11.645 1.00 82.64 C
ATOM 3471 O ARG B 659 66.089 25.805 10.839 1.00 83.00 O ATOM 3472 N ALA B 671 66.209 35.075 6.755 1.00 86.67 N
ATOM 3473 CA ALA B 671 65.054 35.940 6.521 1.00 86.82 C
ATOM 3474 CB ALA B 671 65.315 36.866 5.340 1.00 87.48 C
ATOM 3475 C ALA B 671 63.729 35.159 6.331 1.00 86.72 C
ATOM 3476 O ALA B 671 63.566 34.419 5.353 1.00 87.05 O ATOM 3477 N VAL B 672 62.794 35.314 7.296 1.00 82.98 N
ATOM 3478 CA VAL B 672 61.474 34.665 7.278 1.00 82.28 C
ATOM 3479 CB VAL B 672 61.257 33.568 8.367 1.00 86.15 C
ATOM 3480 CG1 VAL B 672 60.356 32.454 7.842 1.00 85.93 C
ATOM 3481 CG2 VAL B 672 62.570 32.996 8.905 1.00 86.52 C ATOM 3482 C VAL B 672 60.412 35.752 7.405 1.00 81.71 C
ATOM 3483 O VAL B 672 60.409 36.463 8.409 1.00 81.70 O
ATOM 3484 N THR B 673 59.523 35.888 6.397 1.00 77.59 N
ATOM 3485 CA THR B 673 58.443 36.886 6.410 1.00 76.72 C
ATOM 3486 CB THR B 673 58.639 37.976 5.325 1.00 86.99 C ATOM 3487 OG1 THR B 673 59.839 38.692 5.603 1.00 87.86 O
ATOM 3488 CG2 THR B 673 57.480 38.982 5.272 1.00 87.13 C
ATOM 3489 C THR B 673 57.057 36.243 6.345 1.00 75.66 C
ATOM 3490 O THR B 673 56.767 35.491 5.404 1.00 75.66 O
ATOM 3491 N ALA B 674 56.203 36.554 7.343 1.00 70.24 N ATOM 3492 CA ALA B 674 54.824 36.065 7.388 1.00 68.59 C
ATOM 3493 CB ALA B 674 54.384 35.817 8.824 1.00 69.15 C
ATOM 3494 C ALA B 674 53.953 37.133 6.731 1.00 67,41 C
ATOM 3495 O ALA B 674 53.998 38.300 7.128 1.00 67.18 O
ATOM 3496 N VAL B 675 53.206 36.733 5.691 1.00 65.14 N ATOM 3497 CA VAL B 675 52.306 37.588 4.902 1.00 63.90 C
ATOM 3498 CB VAL B 675 52.605 37.482 3.382 1.00 66.96 C
ATOM 3499 CG1 VAL B 675 51.607 38.286 2.552 1 .00 66.63 C
ATOM 3500 CG2 VAL B 675 54.031 37.911 3.077 1.00 66.88 C
ATOM 3501 C VAL B 675 50.840 37.251 5.224 1.00 63.05 C JB2010.7161
ATOM 3502 O VAL B 675 50.390 36.120 4.999 1.00 63.01 O
ATOM 3503 N ALA B 676 50.103 38.242 5.730 1.00 61.45 N
ATOM 3504 CA ALA B 676 48.696 38.090 6.087 1.00 60.67 C
ATOM 3505 CB ALA B 676 48.511 38.374 7.570 1.00 61.54 C ATOM 3506 C ALA B 676 47.795 39.013 5.290 1.00 60.02 C
ATOM 3507 O ALA B 676 48.153 40.162 5.040 1.00 60.12 O
ATOM 3508 N ILE B 677 46.615 38.522 4.922 1.00 57.78 N
ATOM 3509 CA ILE B 677 45.601 39.311 4.231 1.00 57.04 C
ATOM 3510 CB ILE B 677 45.125 38.661 2.893 1.00 60.06 C ATOM 3511 CG1 ILE B 677 46.250 38.695 1.827 1.00 59.45 C
ATOM 3512 CD1 ILE B 677 46.020 37.827 0.587 1.00 58.81 C
ATOM 3513 CG2 ILE B 677 43.859 39.357 2.356 1.00 60.46 C
ATOM 3514 C ILE B 677 44.489 39.491 5.278 1.00 56.75 C
ATOM 3515 O ILE B 677 43.938 38.493 5.755 1.00 56.70 O ATOM 3516 N CYS B 678 44.212 40.748 5.678 1.00 56.71 N
ATOM 3517 CA CYS B 678 43.189 41.073 6.676 1.00 56.45 C
ATOM 3518 CB CYS B 678 43.749 41.980 7.765 1.00 58.05 C
ATOM 3519 SG CYS B 678 45.291 41.405 8.502 1.00 60.60 S
ATOM 3520 C CYS B 678 42.034 41.739 5.983 1.00 55.85 C ATOM 3521 O CYS B 678 42.262 42.691 5.249 1.00 56.33 O
ATOM 3522 N CYS B 679 40.802 41.291 6.236 1.00 53.24 N
ATOM 3523 CA CYS B 679 39.616 41.884 5.640 1.00 52.71 C
ATOM 3524 CB CYS B 679 38.938 40.923 4.674 1.00 53.41 C
ATOM 3525 SG CYS B 679 40.024 40.323 3.362 1.00 53.45 S ATOM 3526 C CYS B 679 38.635 42.471 6.656 1.00 52.81 C
ATOM 3527 O CYS B 679 38.755 42.238 7.856 1.00 52.92 O
ATOM 3528 N ARG B 680 37.676 43.253 6.169 1.00 51.94 N
ATOM 3529 CA ARG B 680 36.666 43.934 6.965 1.00 52.11 C
ATOM 3530 CB ARG B 680 37.173 45.356 7.211 1 .00 54.43 C ATOM 3531 CG ARG B 680 36.835 45.904 8.563 1.00 56.37 C
ATOM 3532 CD ARG B 680 37.797 46.992 9.006 1.00 59.33 C
ATOM 3533 NE ARG B 680 37.745 48.181 8.148 1.00 60.77 N
ATOM 3534 CZ ARG B 680 38.210 49.381 8.490 1.00 61.06 C
ATOM 3535 NH1 ARG B 680 38.758 49.575 9.687 1.00 61.00 N ATOM 3536 NH2 ARG B 680 38.130 50.396 7.639 1.00 60.38 N
ATOM 3537 C ARG B 680 35.376 43.955 6.139 1.00 51.94 C
ATOM 3538 O ARG B 680 35.447 43.687 4.937 1.00 51.70 O
ATOM 3539 N SER B 681 34.206 44.248 6.755 1.00 50.99 N
ATOM 3540 CA SER B 681 32.918 44.309 6.033 1 .00 51.20 C ATOM 3541 CB SER B 681 32.312 42.921 5.846 1.00 53.97 C
ATOM 3542 OG SER B 681 31.399 42.903 4.761 1.00 54.15 O
ATOM 3543 C SER B 681 31.905 45.245 6.699 1.00 51.35 C
ATOM 3544 O SER B 681 31.940 46.460 6.467 1.00 51.96 O TER 3545 SER B 681
ATOM 3546 N THR A 61 29.207 -2.333 -6.445 1.00 71.46 N
ATOM 3547 CA THR A 61 29.389 -0.955 -5.962 1 .00 71.34 C
ATOM 3548 CB THR A 61 28.571 0.084 -6.777 1.00 81.70 C
ATOM 3549 OG1 THR A 61 27.352 -0.483 -7.277 1.00 82.09 O
ATOM 3550 CG2 THR A 61 29.382 0.718 -7.904 1.00 82.43 C ATOM 3551 C THR A 61 29.174 -0.794 -4.447 1.00 70.33 C
ATOM 3552 O THR A 61 29.945 -0.067 -3.808 1.00 70.55 O
ATOM 3553 N ALA A 62 28.126 -1.466 -3.888 1.00 63.31 N
ATOM 3554 CA ALA A 62 27.761 -1.435 -2.470 1.00 61.73 C
ATOM 3555 CB ALA A 62 26.515 -2.261 -2.219 1.00 62.21 C JB2010.7161
ATOM 3556 C ALA A 62 28.896 -1.910 -1.587 1.00 60.68 C
ATOM 3557 O ALA A 62 29.497 -2.950 -1.836 1 .00 61.01 O
ATOM 3558 N THR A 63 29.199 -1.1 11 -0.565 1.00 55.83 N
ATOM 3559 CA THR A 63 30.273 -1.324 0.404 1.00 53.73 C ATOM 3560 CB THR A 63 31.118 -0.036 0.528 1.00 58.03 C
ATOM 3561 OG1 THR A 63 30.310 1.129 0.290 1.00 58.41 O
ATOM 3562 CG2 THR A 63 32.292 -0.022 -0.427 1.00 57.98 C
ATOM 3563 C THR A 63 29.743 -1 .766 1.762 1.00 52.47 C
ATOM 3564 O THR A 63 28.592 -1.497 2.105 1.00 52.33 O ATOM 3565 N PHE A 64 30.580 -2.460 2.531 1.00 47.35 N
ATOM 3566 CA PHE A 64 30.218 -2.879 3.873 1.00 45.45 C
ATOM 3567 CB PHE A 64 30.400 -4.382 4.070 1.00 46.06 C
ATOM 3568 CG PHE A 64 30.278 -4.844 5.504 1.00 44.59 C
ATOM 3569 CD1 PHE A 64 29.038 -4.881 6.139 1.00 43.16 C ATOM 3570 CE1 PHE A 64 28.930 -5.299 7.475 1.00 42.74 C
ATOM 3571 CZ PHE A 64 30.061 -5.702 8.170 1.00 42.68 C
ATOM 3572 CE2 PHE A 64 31.296 -5.673 7.554 1 .00 42.72 C
ATOM 3573 CD2 PHE A 64 31.404 -5.248 6.221 1.00 43.04 C
ATOM 3574 C PHE A 64 31.080 -2.074 4.842 1.00 44.69 C ATOM 3575 O PHE A 64 32.289 -1.907 4.623 1.00 44.16 O
ATOM 3576 N HIS A 65 30.448 -1.555 5.902 1.00 43.94 N
ATOM 3577 CA HIS A 65 31.133 -0.755 6.917 1.00 43.41 C
ATOM 3578 CB HIS A 65 30.733 0.717 6.810 1.00 45.37 C
ATOM 3579 CG HIS A 65 30.999 1.306 5.461 1.00 46.96 C ATOM 3580 ND1 HIS A 65 32.136 2.059 5.214 1.00 48.94 N
ATOM 3581 CE1 HIS A 65 32.060 2.415 3.942 1.00 49.43 C
ATOM 3582 NE2 HIS A 65 30.964 1.923 3.360 1.00 49.53 N
ATOM 3583 CD2 HIS A 65 30.275 1.217 4.320 1.00 48.52 C
ATOM 3584 C HIS A 65 30.910 -1.312 8.312 1.00 42.72 C ATOM 3585 O HIS A 65 29.827 -1.789 8.644 1.00 42.52 O
ATOM 3586 N ARG A 66 31.957 -1.293 9.113 1.00 42.68 N
ATOM 3587 CA ARG A 66 31.915 -1.829 10.475 1.00 42.63 C
ATOM 3588 CB ARG A 66 32.457 -3.277 10.510 1.00 45.77 C
ATOM 3589 CG ARG A 66 33.874 -3.373 9.970 1.00 47.68 C ATOM 3590 CD ARG A 66 34.691 -4.461 10.600 1.00 52.86 C
ATOM 3591 NE ARG A 66 35.391 -4.008 11.802 1.00 58.01 N
ATOM 3592 CZ ARG A 66 36.709 -4.077 11.975 1.00 60.12 C
ATOM 3593 NH1 ARG A 66 37.489 -4.573 11.015 1.00 60.20 N
ATOM 3594 NH2 ARG A 66 37.261 -3.648 13.107 1.00 60.97 N ATOM 3595 C ARG A 66 32.742 -0.955 1 1.399 1.00 41.88 C
ATOM 3596 O ARG A 66 33.654 -0.253 10.939 1.00 41.37 O
ATOM 3597 N CYS A 67 32.453 -1.021 12.708 1.00 39.14 N
ATOM 3598 CA CYS A 67 33.218 -0.245 13.671 1.00 38.83 C
ATOM 3599 CB CYS A 67 32.586 -0.312 15.060 1.00 38.09 C ATOM 3600 SG CYS A 67 33.428 0.711 16.292 1.00 39.33 S
ATOM 3601 C CYS A 67 34.693 -0.707 13.675 1.00 38.30 C
ATOM 3602 O CYS A 67 34.968 -1.901 13.540 1.00 38.51 O
ATOM 3603 N ALA A 68 35.627 0.233 13.800 1.00 38.58 N
ATOM 3604 CA ALA A 68 37.064 -0.089 13.820 1.00 38.69 C ATOM 3605 CB ALA A 68 37.895 1.129 13.435 1.00 38.57 C
ATOM 3606 C ALA A 68 37.522 -0.657 15.182 1.00 39.17 C
ATOM 3607 O ALA A 68 38.621 -1.217 15.277 1.00 39.42 O
ATOM 3608 N LYS A 69 36.683 -0.521 16.225 1.00 40.90 N
ATOM 3609 CA LYS A 69 37.010 -1.011 17.554 1.00 41.62 C JB2010.7161
ATOM 3610 CB LYS A 69 36.722 0.065 18.615 1.00 44.57 C
ATOM 3611 CG LYS A 69 37.160 -0.324 20.011 1.00 46.69 C
ATOM 3612 CD LYS A 69 37.337 0.890 20.885 1.00 49.96 C
ATOM 3613 CE LYS A 69 37.873 0.551 22.256 1.00 52.60 C ATOM 3614 NZ LYS A 69 38.204 1.789 23.030 1.00 55.51 N
ATOM 3615 C LYS A 69 36.210 -2.280 17.777 1.00 41.75 C
ATOM 3616 O LYS A 69 34.978 -2.225 17.905 1.0041.79 O
ATOM 3617 N ASP A 70 36.915 -3.426 17.795 1.0043.81 N
ATOM 3618 CA ASP A 70 36.301 -4.741 17.973 1.00 44.10 C ATOM 3619 CB ASP A 70 37.294 -5,898 17.843 1.0047.66 C
ATOM 3620 CG ASP A 70 37.026 -6.714 16.591 1.00 50.06 C
ATOM 3621 OD1 ASP A 70 36.417 -7.809 16.713 1.00 50.91 O
ATOM 3622 OD2 ASP A 70 37.404 -6.244 15.480 1.00 51.92 O
ATOM 3623 C ASP A 70 35.300 -4.910 19.122 1.00 43.30 C ATOM 3624 O ASP A 70 34.169 -5.278 18.818 1.00 43.48 O
ATOM 3625 N PRO A 71 35.614 -4.598 20.409 1.00 40.55 N
ATOM 3626 CA PRO A 71 34.589 -4.729 21.467 1.00 40.12 C
ATOM 3627 CB PRO A 71 35.307 -4.203 22.711 1.00 41.05 C
ATOM 3628 CG PRO A 71 36.459 -3.420 22.207 1.00 40.63 C ATOM 3629 CD PRO A 71 36.892 -4.120 20.977 1.00 41.18 C
ATOM 3630 C PRO A 71 33.302 -3.926 21.230 1.00 40.1 1 C
ATOM 3631 O PRO A 71 32.259 -4.247 21.784 1.00 40.41 O
ATOM 3632 N TRP A 72 33.372 -2.890 20.397 1.00 41.01 N
ATOM 3633 CA TRP A 72 32.235 -2.034 20.095 1.00 40.05 C ATOM 3634 CB TRP A 72 32.701 -0.591 19.922 1.00 39.21 C
ATOM 3635 CG TRP A 72 33.286 0.040 21.162 1.00 38.78 C
ATOM 3636 CD1 TR A 72 33.443 -0.530 22.394 1.00 37.60 C
ATOM 3637 NE1 TRP A 72 34.003 0.370 23.261 1.00 37.15 N
ATOM 3638 CE2 TRP A 72 34.222 1.551 22.598 1.00 38.05 C ATOM 3639 CD2 TRP A 72 33.766 1.380 21.275 1.00 38.03 C
ATOM 3640 CE3 TRP A 72 33.864 2.457 20.379 1.00 37.63 C
ATOM 3641 CZ3 TRP A 72 34.418 3.644 20.821 1.00 36.45 C
ATOM 3642 CH2 TRP A 72 34.880 3.784 22.135 1.00 37.08 C
ATOM 3643 CZ2 TRP A 72 34.780 2.759 23.045 1.00 38.61 C ATOM 3644 C TRP A 72 31.383 -2.479 18.928 1.00 39.69 C
ATOM 3645 O TRP A 72 30.310 -1.929 18.762 1.00 39.66 O
ATOM 3646 N ARG A 73 31.834 -3.462 18.122 1.00 39.77 N
ATOM 3647 CA ARG A 73 31.093 -4.000 16.978 1.00 38.83 C
ATOM 3648 CB ARG A 73 31.963 -4.994 16,193 1.00 40.18 C ATOM 3649 CG ARG A 73 33.179 -4.440 15.453 1.00 40.08 C
ATOM 3650 CD ARG A 73 33.924 -5.579 14.765 1.00 39.63 C
ATOM 3651 NE ARG A 73 33.544 -5.748 13.361 1.0040.88 N
ATOM 3652 CZ ARG A 73 33.106 -6.877 12.798 1.00 40.55 C
ATOM 3653 NH1 ARG A 73 32.799 -6.907 11.507 1.00 38.82 N ATOM 3654 NH2 ARG A 73 32.959 -7.979 13.526 1.00 42.65 N
ATOM 3655 C ARG A 73 29.851 -4.744 17.477 1.00 38.75 C
ATOM 3656 O ARG A 73 29.862 -5.288 18.582 1.00 39.29 O
ATOM 3657 N LEU A 74 28.773 -4.771 16.678 1.00 37.90 N
ATOM 3658 CA LEU A 74 27.557 -5.495 17.041 1.00 37.02 C ATOM 3659 CB LEU A 74 26.466 -4.577 17.564 1.00 35.97 C
ATOM 3660 CG LEU A 74 26.727 -3.938 18.903 1.00 35.34 C
ATOM 3661 CD1 LEU A 74 25.707 -2.891 19.187 1.00 32.76 C
ATOM 3662 CD2 LEU A 74 26.753 -4.970 20.011 1.00 34.43 C
ATOM 3663 C LEU A 74 27.058 -6.327 15.866 1.00 37.13 C JB2010.7161
ATOM 3664 O LEU A 74 25.954 -6.062 15.374 1.00 37.91 O
ATOM 3665 N PRO A 75 27.844 -7.347 15.397 1.00 36.70 N
ATOM 3666 CA PRO A 75 27.381 -8.197 14.275 1.00 36.21 C
ATOM 3667 CB PRO A 75 28.437 -9.302 14.207 1.00 37.48 C ATOM 3668 CG PRO A 75 29.179 -9.224 15.492 1.00 37.69 C
ATOM 3669 CD PRO A 75 29.165 -7.796 15.878 1.00 37.92 C
ATOM 3670 C PRO A 75 26.024 -8.817 14.535 1.00 35.85 C
ATOM 3671 O PRO A 75 25.699 -9.075 15.698 1.00 35.20 O
ATOM 3672 N GLY A 76 25.256 -9.043 13.467 1.00 34.74 N ATOM 3673 CA GLY A 76 23.914 -9.600 13.573 1.00 35.24 C
ATOM 3674 C GLY A 76 22.836 -8.575 13.283 1.00 35.81 C
ATOM 3675 O GLY A 76 21.694 -8.942 12.988 1.00 36.04 O
ATOM 3676 N THR A 77 23.187 -7.272 13.365 1.00 35.58 N
ATOM 3677 CA THR A 77 22.259 -6.161 13.099 1.00 35.86 C ATOM 3678 CB THR A 77 21.750 -5.494 14.402 1.0042.91 C
ATOM 3679 OG1 THR A 77 21.189 -6.491 15.265 1.00 42.32 O
ATOM 3680 CG2 THR A 77 20.702 -4.439 14.142 1.00 43.08 C
ATOM 3681 C THR A 77 22.913 -5.245 12.081 1.00 35.89 C
ATOM 3682 O THR A 77 24.077 -4.918 12,248 1.00 36.44 O ATOM 3683 N TYR A 78 22.195 -4.891 10.996 1.00 34.85 N
ATOM 3684 CA TYR A 78 22.752 -4.080 9.911 1.00 35.44 C
ATOM 3685 CB TYR A 78 23.193 -4.986 8,683 1.00 34.45 C
ATOM 3686 CG TYR A 78 24.117 -6.099 9.111 1.00 33.32 C
ATOM 3687 CD1 TYR A 78 25.490 -5.889 9.209 1.00 32.26 C ATOM 3688 CE1 TYR A 78 26.336 -6.869 9.725 1.00 32.86 C
ATOM 3689 CZ TYR A 78 25.808 -8.072 10.171 1.00 33.41 C
ATOM 3690 OH TYR A 78 26.636 -9.027 10.697 1.00 36.06 O
ATOM 3691 CE2 TYR A 78 24.446 -8.303 10.093 1.00 32.34 C
ATOM 3692 CD2 TYR A 78 23.609 -7.322 9.554 1.00 33.11 C ATOM 3693 C TYR A 78 21.810 -2.972 9.463 1.00 35.96 C
ATOM 3694 O TYR A 78 20.592 -3.161 9.428 1.00 36.15 O
ATOM 3695 N VAL A 79 22.389 -1.824 9.1 18 1.00 37.37 N
ATOM 3696 CA VAL A 79 21.653 -0.693 8,589 1.00 38.36 C
ATOM 3697 CB VAL A 79 22.035 0.700 9.173 1.00 42.19 C ATOM 3698 CG1 VAL A 79 21.083 1.787 8.655 1.00 41.49 C
ATOM 3699 CG2 VAL A 79 22.086 0.684 10.704 1.00 40.87 C
ATOM 3700 C VAL A 79 21.959 -0.749 7.100 1.00 39.25 C
ATOM 3701 O VAL A 79 23.095 -0.466 6.679 1.00 38.93 O
ATOM 3702 N VAL A 80 20.945 -1.142 6.319 1.00 40.52 N ATOM 3703 CA VAL A 80 21.015 -1.237 4.867 1.00 42.09 C
ATOM 3704 CB VAL A 80 20.077 -2.350 4.288 1.00 46.38 C
ATOM 3705 CG1 VAL A 80 20.148 -2.398 2.766 1.00 46.25 C
ATOM 3706 CG2 VAL A 80 20.412 -3.725 4.873 1.00 45.62 C
ATOM 3707 C VAL A 80 20.647 0.177 4.402 1.00 43.21 C ATOM 3708 O VAL A 80 19.519 0.640 4.627 1.0042.98 O
ATOM 3709 N VAL A 81 21.641 0.880 3.839 1.00 45.50 N
ATOM 3710 CA VAL A 81 21.494 2.252 3.351 1.00 47.28 C
ATOM 3711 CB VAL A 81 22.617 3.214 3.833 1.00 50.54 C
ATOM 3712 CG1 VAL A 81 22.311 4.658 3.427 1.00 49.36 C ATOM 3713 CG2 VAL A 81 22.829 3.1 0 5.343 1.00 50.43 C
ATOM 3714 C VAL A 81 21.385 2.207 1.845 1.00 48.57 C
ATOM 3715 O VAL A 81 22.316 1.770 1.170 1.00 48.68 O
ATOM 3716 N LEU A 82 20.242 2.649 1.335 1.00 50.97 N
ATOM 3717 CA LEU A 82 19.935 2.674 -0.087 1.00 53.13 C JB2010.7161
ATOM 3718 CB LEU A 82 18.455 2.295 -0.316 1.00 52.31 C
ATOM 3719 CG LEU A 82 17.909 1.058 0.436 1.00 51.19 C
ATOM 3720 CD1 LEU A 82 16.471 0.880 0.173 1.0048.96 C
ATOM 3721 CD2 LEU A 82 18.617 -0.212 0.034 1.00 49.81 C ATOM 3722 C LEU A 82 20.289 4.031 -0.733 1.00 55.12 C
ATOM 3723 O LEU A 82 20.443 5.031 -0.022 1.00 55.48 O
ATOM 3724 N LYS A 83 20.430 4.062 -2.080 1.00 60.35 N
ATOM 3725 CA LYS A 83 20.778 5.267 -2.842 1.00 62.50 C
ATOM 3726 CB LYS A 83 20.989 4.951 -4.319 1.00 65.11 C ATOM 3727 CG LYS A 83 22.453 5.098 -4.738 1.00 66.66 C
ATOM 3728 CD LYS A 83 23.236 3.795 -4.646 1 .00 69.10 C
ATOM 3729 CE LYS A 83 23.258 3.004 -5.936 1.00 70.55 C
ATOM 3730 NZ LYS A 83 21.988 2.259 -6.174 1.00 71.87 N
ATOM 3731 C LYS A 83 19.798 6.399 -2.623 1.00 63.89 C ATOM 3732 O LYS A 83 18.633 6.125 -2.344 1.00 63.80 O
ATOM 3733 N GLU A 84 20.272 7.668 -2.693 1.00 70.34 N
ATOM 3734 CA GLU A 84 19.423 8.830 -2.415 1.00 72.78 C
ATOM 3735 CB GLU A 84 20.130 10.189 -2.532 1 .00 74.51 ' C
ATOM 3736 CG GLU A 84 19.943 11.089 -1 .308 1.00 76.74 C ATOM 3737 CD GLU A 84 18.537 11.360 -0.773 1.00 79.84 C
ATOM 3738 OE1 GLU A 84 17.937 12.384 -1.178 1.00 81.00 O
ATOM 3739 OE2 GLU A 84 18.042 10.564 0.064 1.00 80.03 O
ATOM 3740 C GLU A 84 18.016 8.841 -2.990 1.00 73.94 C
ATOM 3741 O GLU A 84 17.072 8.816 -2.203 1.00 74.46 O ATOM 3742 N GLU A 85 17.852 8.847 -4.325 1.00 78.15 N
ATOM 3743 CA GLU A 85 16.506 8.862 -4.917 1.00 79.60 C
ATOM 3744 CB GLU A 85 16.511 9.507 -6.330 1.00 82.05 C
ATOM 3745 CG GLU A 85 16.539 11.038 -6.333 1.00 84.36 C
ATOM 3746 CD GLU A 85 16.640 11.736 -7.686 1.00 87.70 C ATOM 3747 OE1 GLU A 85 17.503 11.337 -8.505 1.00 89.37 O
ATOM 3748 OE2 GLU A 85 15.863 12.694 -7.922 1.00 88.09 O
ATOM 3749 C GLU A 85 15.805 7.471 -4.853 1.00 79.60 C
ATOM 3750 O GLU A 85 15.534 6.850 -5.890 1.00 80.06 O
ATOM 3751 N THR A 86 15.524 6.988 -3.618 1.00 76.63 N ATOM 3752 CA THR A 86 14.871 5.696 -3.385 1.00 76.52 C
ATOM 3753 CB THR A 86 15.825 4.682 -2.724 1.00 77.37 C
ATOM 3754 OG1 THR A 86 16.988 4.539 -3.536 1.00 77.26 O
ATOM 3755 CG2 THR A 86 15.186 3.314 -2.522 1.00 76.59 C
ATOM 3756 C THR A 86 13.572 5.887 -2.625 1.00 76.63 C ATOM 3757 0 THR A 86 13.581 6.358 -1.488 1.00 76.54 O
ATOM 3758 N HIS A 87 12.458 5.51 -3.262 1.00 75.40 N
ATOM 3759 CA HIS A 87 11.110 5.612 -2.712 1.00 75.83 C
ATOM 3760 CB HIS A 87 10.081 5.338 -3.824 1.00 78.38 C
ATOM 3761 CG HSS A 87 8.728 5.916 -3.544 1.00 82.01 C ATOM 3762 ND1 HIS A 87 7.785 5.226 -2.790 1.00 84.50 N
ATOM 3763 CE1 HSS A 87 6.725 6.018 -2.728 1.00 85.76 C
ATOM 3764 NE2 HIS A 87 6.927 7.161 -3.394 1.00 86.17 N
ATOM 3765 CD2 HIS A 87 8.203 7.107 -3.919 1.00 84.48 C
ATOM 3766 C HiS A 87 10.918 4.637 -1.553 1.00 74.94 C ATOM 3767 0 HiS A 87 11.562 3.589 -1.525 1.00 74.91 O
ATOM 3768 N LEU A 88 10.030 4.969 -0.599 1.00 69.94 N
ATOM 3769 CA LEU A 88 9.742 4.106 0.547 1.00 69.15 C
ATOM 3770 CB LEU A 88 8.679 4.727 1.478 1.00 68.12 C
ATOM 3771 CG LEU A 88 8.125 3.849 2.620 1.00 67.87 C JB2010.7161
ATOM 3772 CD1 LEU A 88 9.155 3.606 3.712 1.00 67.33 C
ATOM 3773 CD2 LEU A 88 6.878 4.445 3.205 1.00 66.46 C
ATOM 3774 C LEU A 88 9.322 2.726 0.059 1.00 69.09 C
ATOM 3775 O LEU A 88 9.776 1.733 0.620 1.00 69.08 O ATOM 3776 N SER A 89 8.497 2.672 -1.015 1.00 70.03 N
ATOM 3777 CA SER A 89 8.001 1.450 -1.668 1.00 70.02 C
ATOM 3778 CB SER A 89 7.121 1.799 -2.861 1.00 74.97 C
ATOM 3779 OG SER A 89 5.918 2.405 -2.419 1.00 76.06 O
ATOM 3780 C SER A 89 9,140 0.537 -2.111 1.00 69.65 C ATOM 3781 O SER A 89 8.999 -0.679 -2.034 1.00 69.67 O
ATOM 3782 N GLN A 90 10.270 1.122 -2.539 1.00 69.18 N
ATOM 3783 CA GLN A 90 11.453 0.373 -2.956 1.00 69.01 C
ATOM 3784 CB GLN A 90 12.347 1.205 -3.891 1 .00 70.79 C
ATOM 3785 CG GLN A 90 11.558 1.917 -4.996 1.00 71.70 C ATOM 3786 CD GLN A 90 12.434 2.578 -6.026 1.00 72.98 C
ATOM 3787 OE1 GLN A 90 13.072 3.617 -5.780 1.00 74.14 O
ATOM 3788 NE2 GLN A 90 12.475 1.987 -7.215 1.00 73.63 N
ATOM 3789 C GLN A 90 12.221 -0.163 -1.729 1.00 68.83 C
ATOM 3790 O GLN A 90 12.729 -1.279 -1.790 1.00 68.92 O ATOM 3791 N SE A 91 12.282 0.614 -0.610 1.00 68.74 N
ATOM 3792 CA SER A 91 12.944 0.193 0.639 1.00 68.31 C
ATOM 3793 CB SER A 91 12.952 1.313 1.677 1.00 71.11 C
ATOM 3794 OG SER A 91 13.828 2.373 1.345 1.00 71.89 O
ATOM 3795 C SER A 91 12.190 -0.991 1.224 1.00 67,78 C ATOM 3796 O SER A 91 12.812 -1.926 1.733 1.00 68.08 O
ATOM 3797 N GLU A 92 10.846 -0.941 1.157 1.00 66.41 N
ATOM 3798 CA GLU A 92 9.981 -1.998 1.660 1.00 65.79 C
ATOM 3799 CB GLU A 92 8.515 -1.533 1.729 1.00 67.62 C
ATOM 3800 CG GLU A 92 8.255 -0.502 2.814 1.00 68.90 C ATOM 3801 CD GLU A 92 7.000 0.338 2.654 1.00 71.72 C
ATOM 3802 OE1 GLU A 92 6.763 0.859 1.537 1.00 74.02 O
ATOM 3803 OE2 GLU A 92 6.257 0.490 3.652 1.00 72.49 O
ATOM 3804 C GLU A 92 10.140 -3.216 0.763 1.00 64.90 C
ATOM 3805 O GLU A 92 10.218 -4.333 1.275 1.00 64.71 O ATOM 3806 N ARG A 93 10.232 -2.992 -0.572 1.00 62.19 N
ATOM 3807 CA ARG A 93 10.397 -4.044 -1.575 1.00 61.24 C
ATOM 3808 CB ARG A 93 10.281 -3.478 -3.004 1.00 64.69 C
ATOM 3809 CG ARG A 93 9.469 -4.346 -3.976 1.00 66.24 C
ATOM 3810 CD ARG A 93 9.360 -3.719 -5.361 1.00 69.53 C ATOM 3811 NE ARG A 93 8.412 -2.595 -5.401 1.00 72.38 N
ATOM 3812 CZ ARG A 93 8.679 -1.384 -5.900 1.00 73.40 C
ATOM 3813 NH1 ARG A 93 9.878 -1.115 -6.412 1.00 73.28 N
ATOM 3814 NH2 ARG A 93 7.750 -0.433 -5.886 1.00 72.88 N
ATOM 3815 C ARG A 93 11.717 -4.754 -1 .366 1.00 59.98 C ATOM 3816 O ARG A 93 11.724 -5.982 -1.313 1.00 59.89 O
ATOM 3817 N THR A 94 12.822 -3.977 -1.211 1.00 55.66 N
ATOM 3818 CA THR A 94 14.190 -4.460 -0.981 1.00 54.28 C
ATOM 3819 CB THR A 94 15.193 -3.293 -1.049 1.00 53.59 C
ATOM 3820 OG1 THR A 94 14.974 -2.556 -2.245 1.00 52.88 O ATOM 3821 CG2 THR A 94 16.640 -3.753 -1.026 1.00 53.85 C
ATOM 3822 C THR A 94 14.270 -5.229 0.352 1.00 53.89 C
ATOM 3823 O THR A 94 15.022 -6.2 1 0.458 1.00 53.64 O
ATOM 3824 N ALA A 95 13.489 -4.780 1.364 1.00 53.00 N
ATOM 3825 CA ALA A 95 13.464 -5.426 2.673 1.00 52.43 C JB2010.7161
ATOM 3826 CB ALA A 95 12.688 -4.583 3.668 1.00 52.83 C
ATOM 3827 C ALA A 95 12.849 -6.819 2.521 1.00 52.16 C
ATOM 3828 0 ALA A 95 13.442 -7.796 2.978 1.00 51.82 O
ATOM 3829 N ARG A 96 11.686 -6.897 1.825 1.00 53.15 N ATOM 3830 CA ARG A 96 10.923 -8.112 1 .509 1.00 53.05 C
ATOM 3831 CB ARG A 96 9.637 -7.739 0.754 1.00 52.78 C
ATOM 3832 CG ARG A 96 8.360 -8.039 1.524 1.00 53.63 C
ATOM 3833 CD ARG A 96 7.224 -7.038 1.275 1.00 53.95 C
ATOM 3834 NE ARG A 96 7.259 -6.408 -0.056 1.00 55.19 N ATOM 3835 CZ ARG A 96 6.984 -5.122 -0.297 1 .00 55.63 C
ATOM 3836 NH1 ARG A 96 6.640 -4.309 0.697 1.00 55.67 N
ATOM 3837 NH2 ARG A 96 7.048 -4.643 -1.533 1.00 54.51 N
ATOM 3838 C ARG A 96 1 1.808 -9.063 0.669 1.00 52.87 C
ATOM 3839 O ARG A 96 1 1.955 -10.231 1.028 1.00 52.51 O ATOM 3840 N ARG A 97 12.435 -8.537 -0.413 1.00 53.58 N
ATOM 3841 CA ARG A 97 13.333 -9.265 -1.306 1 .00 53.78 C
ATOM 3842 CB ARG A 97 13.860 -8.336 -2.408 1.00 60.57 C
ATOM 3843 CG ARG A 97 14.383 -9.077 -3.624 1 .00 63.43 C
ATOM 3844 CD ARG A 97 14.634 -8.155 -4.798 1.00 68.16 C ATOM 3845 NE ARG A 97 5.228 -8.865 -5.934 1.00 71.21 N
ATOM 3846 CZ ARG A 97 15.338 -8.363 -7.165 1.00 73.43 C
ATOM 3847 NH1 ARG A 97 14.885 -7.139 -7.437 1.00 74.51 N
ATOM 3848 NH2 ARG A 97 15.899 -9.081 -8.136 1.00 73.95 N
ATOM 3849 C ARG A 97 14.485 -9.925 -0.532 1.00 53.20 C ATOM 3850 O ARG A 97 14.864 -11.047 -0.857 1.00 53.61 O
ATOM 3851 N LEU A 98 15.022 -9.244 0.497 1.00 51.50 N
ATOM 3852 CA LEU A 98 16.112 -9,756 1.324 1.00 50.52 C
ATOM 3853 CB LEU A 98 16.726 -8.614 2.171 1.00 50.19 C
ATOM 3854 CG LEU A 98 17.806 -8.974 3.216 1.00 48.93 C ATOM 3855 CD1 LEU A 98 19.031 -9.654 2.590 1 .00 48.73 C
ATOM 3856 CD2 LEU A 98 18.252 -7.766 3.934 1.00 48.11 C
ATOM 3857 C LEU A 98 15.614 -10.886 2.221 1 ,00 50.30 C
ATOM 3858 0 LEU A 98 16.320 -11.873 2.421 1.00 50.14 O
ATOM 3859 N GLN A 99 14.404 -10.736 2.768 1.00 50.57 N ATOM 3860 CA GLN A 99 13.826 - 1.734 3.647 1.00 50.46 C
ATOM 3861 CB GLN A 99 12.548 -11 ,229 4.274 1.00 51.50 C
ATOM 3862 CG GLN A 99 12.796 -10.183 5.322 1.00 51.93 C
ATOM 3863 CD GLN A 99 11.672 -10.208 6.309 1.00 52.70 C
ATOM 3864 OE1 GLN A 99 10.543 -9.771 6.008 1.00 52.27 O ATOM 3865 NE2 GLN A 99 1 1.961 -10.739 7.504 1.00 51.75 N
ATOM 3866 C GLN A 99 13.585 -13.026 2.916 1.00 50.38 C
ATOM 3867 0 GLN A 99 13.987 -14.069 3.427 1.00 50.41 O
ATOM 3868 N ALA A 100 12.959 -12.951 1.712 1.00 51.50 N
ATOM 3869 CA ALA A 100 12.636 -14.072 0.833 1.00 51.13 C ATOM 3870 CB ALA A 100 11.886 -13.579 -0.383 1.00 51.59 C
ATOM 3871 C ALA A 100 13.908 -14.793 0.418 1 ,00 51.34 C
ATOM 3872 O ALA A 100 13.986 -16.021 0.580 1.00 51.15 O
ATOM 3873 N GLN A 101 14.923 -14.028 -0.054 1.00 53.40 N
ATOM 3874 CA GLN A 101 16.223 -14.567 -0.446 1.00 53.82 C ATOM 3875 CB GLN A 101 17.090 -13.492 -1.087 1.00 56.60 C
ATOM 3876 CG GLN A 101 16.661 -13.150 -2.497 1.00 58.16 C
ATOM 3877 CD GLN A 101 17.450 -12.013 -3.101 1.00 60.43 C
ATOM 3878 OE1 GLN A 101 18.648 -11 .805 -2.814 1.00 62.03 O
ATOM 3879 NE2 GLN A 101 16.796 -11.261 -3.978 1.00 59.75 N JB2010.7161
ATOM 3880 C GLNA101 16.973-15.187 0.734 1.0053.87 C
ATOM 3881 O GLNA101 17.752-16.115 0.531 1.0054.16 O
ATOM 3882 N ALA A 102 16.764-14.690 1.958 1.0053.24 N
ATOM 3883 CA ALA A 02 17.459-15.269 3.102 1.0053.27 C ATOM 3884 CB ALA A 102 17.511 -14.281 4.244 1.0054.17 C
ATOM 3885 C ALA A 102 16.803-16.573 3.551 1.0052.95 C
ATOM 3886 O ALA A 102 17.509-17.510 3.922 1.0052.48 O
ATOM 3887 N ALA A 103 15.453-16.621 3.514 1.0051.72 N
ATOM 3888 CA ALA A 103 14.626-17.765 3.890 1.0051.23 C ATOM 3889 CB ALA A 103 13.156-17.373 3.866 1.0051.75 C
ATOM 3890 C ALA A 103 14.899-18.930 2.915 1.0051.00 C
ATOM 3891 O ALA A 103 5.038-20.077 3.350 1.0050.53 O
ATOM 3892 N ARG A 104 15.038-18.618 1.599 1.0050.50 N
ATOM 3893 CA ARGA 104 15.362-19.604 0.561 1.0049.94 C ATOM 3894 CB ARGA 104 15.319-18.971 -0.832 1.0051.42 C
ATOM 3895 CG ARG A 104 13.922-18.978 -1.428 1.0053.17 C
ATOM 3896 CD ARG A 104 13.952-18.700 -2.911 1.0058.29 C
ATOM 3897 HE ARGA 104 13.605-17.315 -3.198 1.0061.74 N
ATOM 3898 CZ ARG A 104 12.359-16.855 -3.306 1.0064.87 C ATOM 3899 NH1 ARG A 104 11.322-17.677 -3.163 1.0065.21 N
ATOM 3900 NH2 ARG A 104 12.139-15.566 -3.547 1.0067.20 N
ATOM 3901 C ARG A 104 16.727-20.232 0.843 1.0049.32 C
ATOM 3902 O ARG A 104 16.942-21.398 0.501 1.0049.86 O
ATOM 3903 N AARGA105 17.631 -19.469 1.488 0.5046.01 N ATOM 3904 N BARGA105 17.629-19.461 1,477 0.5046.32 N
ATOM 3905 CAAARGA105 18.982-19.888 1.866 0.5045.20 C
ATOM 3906 CABARGA105 18.978-19.865 1.858 0.5045.80 C
ATOM 3907 CBAARGA105 19.969-18.716 1.743 0.5043.34 C
ATOM 3908 CBBARGA105 19.953-18.686 1.693 0.5044.23 C ATOM 3909 CGAARGA 105 20.221 -18.294 0.306 0.5041.11 C
ATOM 3910 CG BARG A 105 20.902-18.875 0.510 0.5043.65 C
ATOM 3911 CD AARG A 105 21.675-17.975 0.045 0.5037.20 C
ATOM 3912 CD BARG A 105 21.063-17.654 -0.380 0.5042.78 C
ATOM 3913 HE AARG A 105 21.816-17.306 -1.245 0.5034.81 N ATOM 3914 NE BARG A 105 19.808-17.227 -1.010 0.5042.10 N
ATOM 3915 CZ AARG A 105 22.963-16.872 -1.746 0.5032.58 C
ATOM 3916 CZ BARG A 105 19.734-16.504 -2.126 0.5042.07 C
ATOM 3917 NH1 AARG A 105 24.095-17.034 -1.073 0.5032.42 N
ATOM 3918 NH1 BARG A 105 20.842-16.127 -2.761 0.5041.65 N ATOM 3919 NH2AARGA105 22.989-16.275 -2.928 0.5030.39 N
ATOM 3920 NH2BARGA105 18.553-16.150 -2.616 0.5041.52 N
ATOM 3921 C AARG A 105 19.025-20.504 3.273 0.5045.34 C
ATOM 3922 C BARG A 105 19.024-20.473 3.276 0.5045.68 C
ATOM 3923 O AARG A 105 20.112-20.761 3.807 0.5045.25 O ATOM 3924 O BARG A 105 20.114-20.706 3.814 0.5045.57 O
ATOM 3925 N GLY A 106 17.839-20.745 3.842 1.0044.97 N
ATOM 3926 CA GLY A 106 17.660-21.344 5.167 1.0044.87 C
ATOM 3927 C GLY A 106 17.964-20.449 6.354 1.0044.93 C
ATOM 3928 O GLY A 106 18.198-20.952 7.459 1.0044.78 O ATOM 3929 N TYR A 107 17.964-19.120 6.137 1,0046.60 N
ATOM 3930 CA TYRA107 18.257-18.111 7.157 1.0046.56 C
ATOM 3931 CB TYR A 107 19.335-17.159 6.646 1.0047.28 C
ATOM 3932 CG TYR A 107 20.738-17.707 6.702 1.0046.61 C
ATOM 3933 CD1 TYR A 107 21.469-17.684 7.886 1.0046.60 C JB2Q10.7161
ATOM 3934 CE1 TYR A 107 22.781 -18.148 7.934 1.0046.70 C
ATOM 3935 CZ TYR A 107 23.372-18.649 6.786 1.0046.52 C
ATOM 3936 OH TYR A 107 24.653-19.126 6.828 1.0046.25 O
ATOM 3937 CE2 TYR A 107 22.668-18.671 5.595 1.0045.85 C ATOM 3938 CD2 TYR A 107 21,359-18.200 5.560 1.0046.36 C
ATOM 3939 C TYR A 107 17.050-17.271 7.592 1.0046.67 C
ATOM 3940 O TYR A 107 16.351 -16.663 6.759 1.0046.60 O
ATOM 3941 N LEU A 108 16.831 -17.208 8.909 1.0048.24 N
ATOM 3942 CA LEU A 108 15.756-16.390 9.457 1.0048.73 C ATOM 3943 CB LEU A 108 15.310-16.935 10.810 1.0049.13 C
ATOM 3944 CG LEU A 108 13.946-16.460 11.282 1.0049.96 C
ATOM 3945 CD1 LEU A 108 12.864-17.462 10.925 1.0049.53 C
ATOM 3946 CD2 LEU A 108 13.960-16.220 12.775 1.0049.70 C
ATOM 3947 C LEU A 108 16.258-14.926 9.585 1.0048.72 C ATOM 3948 0 LEU A 108 17.422-14.702 9.941 1.0048.60 O
ATOM 3949 N TH A109 15.397-13.949 9.232 1.0047.96 N
ATOM 3950 CA THR A 109 15.707-12.520 9.306 1.0048.27 C
ATOM 3951 CB THR A 109 16.178-11.900 7.971 1.0051.11 C
ATOM 3952 OG1 THR A 109 15.105-11.771 7.041 1.0050.94 O ATOM 3953 CG2 THR A 109 17.387-12.582 7.379 1.0051.11 C
ATOM 3954 C THR A 109 14.553-11.725 9.875 1.0048.76 C
ATOM 3955 O THR A 109 13,392-12.124 9.735 1.0048.93 O
ATOM 3956 N LYSA110 14.872-10.580 10.502 1.0049.93 N
ATOM 3957 CA LYSA 110 13.870 -9.695 11.090 1.0050.34 C ATOM 3958 CB LYSA110 13.905 -9.787 12.628 1.0055.19 C
ATOM 3959 CG LYSA 10 12.644 -9.264 13.308 1.0058.45 C
ATOM 3960 CD LYSA110 12.638 -9.598 14.812 1.0062.92 C
ATOM 3961 CE LYS A 110 11.326 -9.258 15.491 1.0064.55 C
ATOM 3962 NZ LYS A 110 11.407 -9.462 16.966 1.0067.00 N ATOM 3963 C LYS A 110 14.117 -8.276 10.638 1.0049.68 C
ATOM 3964 O LYS A 110 15.205 -7.745 10.865 1.0050.25 O
ATOM 3965 N ILEA 111 13.132 -7.661 9.982 1.0045.80 N
ATOM 3966 CA ILEA 111 13.288 -6.266 9.573 1.0044.84 C
ATOM 3967 CB ILEA 111 12.552 -5.894 8.263 1.0046.07 C ATOM 3968 CG1 ILEA 111 12.886 -6.864 7.096 1.0046.18 C
ATOM 3969 CD1 ILEA 111 14.369 -6.968 6.588 1.0045.56 C
ATOM 3970 CG2 ILEA 111 12.742 -4.419 7.898 1.0044.81 C
ATOM 3971 C ILEA 111 12.794 -5.509 10.802 1.0044.60 C
ATOM 3972 0 ILEA 111 11.598 -5.538 11.131 1.0044.69 O ATOM 3973 N LEU A 112 13.738 -4.918 11.534 1.0044.12 N
ATOM 3974 CA LEU A 112 13.432 -4,222 12.779 1.0043.34 C
ATOM 3975 CB LEU A 112 14.676 -4.148 13.679 1.0043.01 C
ATOM 3976 CG LEU A 112 15,363 -5.468 13.993 1.0042.20 C
ATOM 3977 CD1 LEU A 112 16.719 -5.231 14.621 1.0041.66 C ATOM 3978 CD2 LEU A 112 14.496 -6.353 14.857 1.0039.83 C
ATOM 3979 C LEU A 112 12.855 -2.854 12.568 1.0043.11 C
ATOM 3980 O LEU A 112 11.980 -2.451 13.322 1.0043.19 O
ATOM 3981 N HIS A 113 13.333 -2.136 11.553 1.0042.54 N
ATOM 3982 CA HIS A 113 12.886 -0.783 11.268 1.0042.24 C ATOM 3983 CB HIS A 113 13.712 0.188 12.141 1.0042.56 C
ATOM 3984 CG HIS A 113 13.199 1.589 12.173 1.0041.70 C
ATOM 3985 ND1 HIS A 113 13.718 2.568 11.336 1.0041.60 N
ATOM 3986 CE1 HISA113 13.034 3.665 11.605 1.0040.48 C
ATOM 3987 NE2HISA113 12.124 3.452 12.564 1.0040.02 N JB2010.7161
ATOM 3988 CD2 HIS A 1 13 12.221 2.131 12.933 1.00 40.24 C
ATOM 3989 C HIS A 113 13.082 -0.458 9.800 1.00 42.67 C
ATOM 3990 O HIS A 113 14.068 -0.890 9.206 1.00 42.56 O
ATOM 3991 N VAL A 114 12.141 0.294 9.214 1.00 47.96 N ATOM 3992 CA VAL A 114 12.215 0.765 7.824 1.00 49.12 C
ATOM 3993 CB VAL A 114 11.034 0.287 6.932 1.00 52.59 C
ATOM 3994 CG1 VAL A 114 11.018 1.006 5.583 1.00 51.44 C
ATOM 3995 CG2 VAL A 114 11.078 -1.230 6.729 1.00 52.02 C
ATOM 3996 C VAL A 114 12.280 2.277 7.941 1.00 50.51 C ATOM 3997 O VAL A 114 11.385 2.883 8.540 1.00 50.89 O
ATOM 3998 N PHE A 115 13.351 2.881 7.426 1.00 55.75 N
ATOM 3999 CA PHE A 115 13.514 4.326 7.518 1.00 57.48 C
ATOM 4000 CB PHE A 115 14.992 4.746 7.397 1.00 58.79 C
ATOM 4001 CG PHE A 115 15.842 4.343 8.576 1.00 60.01 C ATOM 4002 CD1 PHE A 115 15.918 5.149 9.710 1.00 60.60 C
ATOM 4003 CE1 PHE A 115 16.697 4.765 10.810 1.00 60.25 C
ATOM 4004 CZ PHE A 115 17.407 3.586 10.773 1.00 60.39 C
ATOM 4005 CE2 PHE A 115 17.347 2.779 9.656 1.00 59.53 C
ATOM 4006 CD2 PHE A 115 16.568 3.158 8.558 1.00 59.76 C ATOM 4007 C PHE A 115 12.633 5.104 6.547 1.00 58.56 C
ATOM 4008 O PHE A 115 12.805 4.978 5.333 1.00 59.46 O
ATOM 4009 N HIS A 116 11.689 5.906 7.079 1.00 62.69 N
ATOM 4010 CA HIS A 116 10.804 6.756 6.271 1.00 63.85 C
ATOM 4011 CB HIS A 116 9.450 7.028 7.002 1.00 66.38 C ATOM 4012 CG HIS A 1 16 8.620 5.804 7.345 1.00 69.29 C
ATOM 4013 ND1 HIS A 116 7.254 5.909 7.618 1.00 72.14 N
ATOM 4014 CE1 HIS A 116 6.839 4.676 7.892 1.00 72.17 C
ATOM 4015 NE2 HIS A 116 7.839 3.792 7.820 1.00 71.89 N
ATOM 4016 CD2 HIS A 116 8.981 4.498 7.478 1.00 71.51 C ATOM 4017 C HIS A 1 16 11.639 8.057 5.996 1.00 63.40 C
ATOM 4018 O HIS A 1 16 12.464 8.066 5.066 1.00 63.07 O
ATOM 4019 N GLY A 117 11.482 9.086 6.841 1.00 60.32 N
ATOM 4020 CA GLY A 117 12.239 10.335 6.727 1.00 59.87 C
ATOM 4021 C GLY A 117 13.684 10.211 7.197 1 ,00 59.43 C ATOM 4022 O GLY A 1 17 14.081 9.169 7.733 1.00 59.41 O
ATOM 4023 N LEU A 118 14.492 11.282 7.013 1.00 55.67 N
ATOM 4024 CA LEU A 118 15.925 11.339 7.385 1.00 54.59 C
ATOM 4025 CB LEU A 118 16.199 10.985 8.870 1.00 54.02 C
ATOM 4026 CG LEU A 1 18 17.657 10.849 9.338 1.00 53.60 C ATOM 4027 CD1 LEU A 18 18.269 12.202 9.645 1.00 52.47 C
ATOM 4028 CD2 LEU A 118 17.737 9.983 10.559 1.00 52.26 C
ATOM 4029 C LEU A 118 16.827 10.555 6.421 1.00 53.87 C
ATOM 4030 O LEU A 118 17.760 11.142 5.880 1.00 54.13 O
ATOM 4031 N LEU A 119 16.570 9.260 6.203 1.00 49.71 N ATOM 4032 CA LEU A 19 17.392 8.488 5.272 1.00 49.00 C
ATOM 4033 CB LEU A 119 18.726 8.023 5.897 1.00 48.88 C
ATOM 4034 CG LEU A 119 18.668 6.946 6.954 1.00 48.28 C
ATOM 4035 CD1 LEU A 119 19.482 5.759 6.530 1.00 48.31 C
ATOM 4036 CD2 LEU A 119 19.207 7.463 8.258 1.00 49.05 C ATOM 4037 C LEU A 119 16.661 7.340 4.559 1.00 48.51 C
ATOM 4038 O LEU A 119 15.707 6.791 5.125 1.00 48.77 O
ATOM 4039 N PRO A 120 17.094 6.961 3.320 1.0046.77 N
ATOM 4040 CA PRO A 120 16.429 5.846 2.623 1.00 46.14 C
ATOM 4041 CB PRO A 120 16.584 6.224 1.142 1.0048.10 C JB2O10.7161
ATOM 4042 CG PRO A 120 17.842 7.070 1.086 1 ,00 48.38 C
ATOM 4043 CD PRO A 120 18.198 7.507 2.498 1.00 48.50 C
ATOM 4044 C PRO A 120 17.076 4.493 2.951 1 .00 45.22 C
ATOM 4045 O PRO A 120 18.259 4.275 2.671 1.00 45.40 O ATOM 4046 N GLY A 121 16.311 3.597 3.553 1.00 40.94 N
ATOM 4047 CA GLY A 121 16.850 2.290 3.895 1.00 39.78 C
ATOM 4048 C GLY A 121 16.085 1.569 4.967 1.00 39.11 C
ATOM 4049 O GLY A 121 14.909 1.876 5.194 1.00 39.03 O
ATOM 4050 N PHE A 122 16.749 0.594 5.628 1 .00 39.37 N ATOM 4051 CA PHE A 122 16.147 -0.217 6.704 1.00 38.88 C
ATOM 4052 CB PHE A 122 15,185 -1.286 6.134 1.00 40.96 C
ATOM 4053 CG PHE A 122 15.807 -2.280 5,175 1.00 41.85 C
ATOM 4054 CD1 PHE A 122 15.958 -1.971 3.825 1.00 43.01 C
ATOM 4055 CE1 PHE A 122 16.527 -2.899 2.939 1.00 45.02 C ATOM 4056 CZ PHE A 122 16.929 -4.143 3.399 1 .00 44.60 C
ATOM 4057 CE2 PHE A 122 16.779 -4.465 4.731 1.0043,47 C
ATOM 4058 CD2 PHE A 122 16.216 -3.539 5.616 1.00 42.83 C
ATOM 4059 C PHE A 122 17.171 -0.859 7.664 1.00 38.26 C
ATOM 4060 O PHE A 122 18.375 -0,937 7.369 1.00 38.20 O ATOM 4061 N LEU A 123 16.672 -1.321 8.81 1 1.00 38.71 N
ATOM 4062 CA LEU A 123 17.475 -1.962 9.838 1.00 38.58 C
ATOM 4063 CB LEU A 123 17.300 -1.237 1 1.190 1 .00 39.06 C
ATOM 4064 CG LEU A 123 18.081 -1.815 12.384 1.00 39.51 C
ATOM 4065 CD1 LEU A 123 19.569 -1.631 12.215 1.00 38.1 1 C ATOM 4066 CD2 LEU A 123 17.613 -1.21 1 13.672 1.00 38.72 C
ATOM 4067 C LEU A 123 17.079 -3.434 9.913 1 .00 38.81 C
ATOM 4068 O LEU A 123 15.899 -3.767 10.085 1.00 39.17 O
ATOM 4069 N VAL A 124 18.065 -4.312 9.779 1.00 39.99 N
ATOM 4070 CA VAL A 124 17.826 -5.758 9.752 1.00 40.02 C ATOM 4071 CB VAL A 124 17.993 -6.310 8.284 1 ,0042.96 C
ATOM 4072 CG1 VAL A 124 19.394 -6.040 7.713 1.00 41.95 C
ATOM 4073 CG2 VAL A 124 17.648 -7.792 8.186 1.00 42.92 C
ATOM 4074 C VAL A 124 18.630 -6.581 10.765 1.00 39.93 C
ATOM 4075 O VAL A 124 19.801 -6.300 1 1.005 1.00 39.67 O ATOM 4076 N LYS A 125 17.973 -7.604 11.330 1.0041.56 N
ATOM 4077 CA LYS A 125 18.576 -8.594 12.200 1 .00 42.15 C
ATOM 4078 CB LYS A 125 17.748 -8.889 13.463 1.00 46.16 C
ATOM 4079 CG LYS A 125 18.628 -9.477 14.566 1.00 47.19 C
ATOM 4080 CD LYS A 125 17.875 -10.229 15.651 1.00 49.48 C ATOM 4081 CE LYS A 125 18.822 -10.508 16.803 1.00 51.92 C
ATOM 4082 HZ LYS A 125 18.619 -1 1.857 17.421 1.00 54.33 N
ATOM 4083 C LYS A 125 18.707 -9.850 11.291 1 ,0042.16 C
ATOM 4084 O LYS A 125 17.708 -10.413 10.823 1.00 41.20 O
ATOM 4085 N MET A 126 19.952 -10.225 10.998 1.00 43.60 N ATOM 4086 CA MET A 126 20,304 -1 1.345 10.137 1 ,00 43.63 C
ATOM 4087 CB MET A 126 20.180 -10.916 8.661 1.00 46.37 C
ATOM 4088 CG MET A 126 21.320 -10.086 8.176 1.00 47.26 C
ATOM 4089 SD MET A 126 21.045 -9.455 6.525 1.00 53.22 S
ATOM 4090 CE MET A 126 22.775 -8.962 6.086 1.00 49.28 C ATOM 4091 C MET A 126 21.744 -1 1.741 10.440 1.00 43.72 C
ATOM 4092 O MET A 126 22.462 -10.957 11.054 1 .00 43.53 O
ATOM 4093 N SER A 127 22.176 -12.941 9.988 1 .00 44.21 N
ATOM 4094 CA SER A 127 23.550 -13.416 10.173 1.00 44.32 C
ATOM 4095 CB SER A 127 23.649 -14.916 9.886 1.00 48.51 C JB2010.7161
ATOM 4096 OG SER A 127 24.970 -15.413 10.056 1.00 48.85 O
ATOM 4097 C SER A 127 24.443 -12.649 9.211 1.0044.19 C
ATOM 4098 O SER A 127 23.983 -12.242 8.152 1.00 43.60 O
ATOM 4099 N GLY A 128 25.705 -12.469 9.592 1.00 45.41 N ATOM 4100 CA GLY A 128 26.720 -11 ,810 8.775 1.00 46.38 C
ATOM 4101 C GLY A 128 26.931 -12.558 7.471 1.00 47.32 C
ATOM 4102 O GLY A 128 27.351 -11.971 6.471 1.00 47.12 O
ATOM 4103 N ASP A 129 26.584 -13.870 7.468 1.00 47.55 N
ATOM 4104 CA ASP A 129 26.655 -14.755 6.311 1.00 48.52 C ATOM 4105 CB ASP A 129 26.151 -16.154 6.696 1.00 51.79 C
ATOM 4106 CG AS A 129 27.008 -16.879 7.727 1.00 53.70 C
ATOM 4107 OD1 ASP A 129 28.101 -16.349 8.084 1.00 55.32 O
ATOM 4108 OD2 ASP A 129 26.598 -17.976 8.175 1.00 54.96 O
ATOM 4109 C ASP A 129 25.862 -14.201 5.124 1.00 48.61 C ATOM 4110 O ASP A 129 26.216 -14.469 3.977 1.00 48.89 O
ATOM 4111 N LEU A 130 24.818 -13.407 5.395 1.0045.31 N
ATOM 4112 CA LEU A 130 23.986 -12.807 4.353 1.00 45.55 C
ATOM 4113 CB LEU A 130 22.517 -12.752 4.793 1.00 45.33 C
ATOM 4114 CG LEU A 130 21.915 -14.097 5.207 1.00 45.54 C ATOM 4115 CD1 LEU A 130 20.810 -13.892 6.204 1.00 46.25 C
ATOM 4116 CD2 LEU A 130 21.422 -14.892 3.997 1.00 44.17 C
ATOM 4117 C LEU A 30 24.490 -11.446 3.828 1.00 46.04 C
ATOM 4118 O LEU A 130 23.775 -10.782 3.071 1.00 45.71 O
ATOM 4119 N LEU A 131 25.724 -11.044 4.204 1.0047.71 N ATOM 4120 CA LEU A 131 26.286 -9.778 3.740 1.00 48.91 C
ATOM 4121 CB LEU A 131 27.516 -9.303 4.522 1.00 48.12 C
ATOM 4122 CG LEU A 131 27.165 -8.756 5.891 1.00 48.26 C
ATOM 4123 CD1 LEU A 131 28.364 -8.687 6.777 1.00 46.73 C
ATOM 4124 CD2 LEU A 131 26.341 -7.459 5.797 1.00 47.62 C ATOM 4125 C LEU A 131 26.502 -9.721 2.254 1.00 50.04 C
ATOM 4126 O LEU A 131 25.830 -8.905 1.605 1.00 49.78 O
ATOM 4127 N GLU A 132 27.385 -10.617 1.700 1 .00 54.83 N
ATOM 4128 CA GLU A 132 27.678 -10.688 0.256 1.00 56.49 C
ATOM 4129 CB GLU A 132 28.633 -11.852 -0.101 1.00 59.67 C ATOM 4130 CG GLU A 132 30.096 -11.508 0.201 1.00 64.27 C
ATOM 4131 CD GLU A 132 31.198 -12.561 0.084 1.00 70.27 C
ATOM 4132 OE1 GLU A 132 30.875 -13.770 -0.041 1.00 73.40 O
ATOM 4133 OE2 GLU A 132 32.393 -12.171 0.128 1.00 71.23 O
ATOM 4134 C GLU A 132 26.400 -10.647 -0.590 1.00 56,19 C ATOM 4135 0 GLU A 132 26.372 -9.997 -1.640 1.00 56.34 O
ATOM 4136 N LEU A 133 25.322 -11.261 -0.068 1.00 53.45 N
ATOM 4137 CA LEU A 133 23.990 -11.308 -0.663 1.00 53.52 C
ATOM 4138 CB LEU A 133 23.108 -12.275 0.142 1.00 53.58 C
ATOM 4139 CG LEU A 33 21.782 -12,701 -0.471 1.00 54.88 C ATOM 4140 CD1 LEU A 133 21.350 -14.034 0.096 1.00 56.24 C
ATOM 4141 CD2 LEU A 133 20.685 -11.671 -0.222 1.00 56.14 C
ATOM 4142 C LEU A 133 23.363 -9.927 -0.649 1.00 53.30 C
ATOM 4143 O LEU A 133 23.026 -9.394 -1.704 1.00 53.01 O
ATOM 4144 N ALA A 134 23.177 -9.369 0.566 1.00 54.34 N ATOM 4145 CA ALA A 134 22,570 -8.065 0.837 1.00 54.20 C
ATOM 4146 CB ALA A 134 22.635 -7.770 2.323 1.00 54.76 C
ATOM 4147 C ALA A 134 23.210 -6.939 0.025 1.00 54.32 C
ATOM 4148 O ALA A 134 22.507 -6.035 -0.431 1.00 53.89 O
ATOM 4149 N LEU A 135 24.537 -7.020 -0.186 1.00 55.42 N JB2010.7161
ATOM 4150 CA LEU A 135 25.293 -6.049 -0.972 1.00 55.95 C
ATOM 4151 CB LEU A 135 26.799 -6.283 -0.811 1.00 55.07 C
ATOM 4152 CG LEU A 135 27.372 -5.949 0.567 1.00 54.77 C
ATOM 4153 CD1 LEU A 135 28.748 -6.525 0.733 1.00 52.97 C ATOM 4154 CD2 LEU A 135 27.391 -4.451 0.811 1.00 53.66 C
ATOM 4155 C LEU A 135 24.875 -6.083 -2.448 1.00 56.75 C
ATOM 4156 0 LEU A 135 24.800 -5.033 -3.098 1.00 57.21 O
ATOM 4157 N LYS A 36 24.565 -7.291 -2.965 1.00 60.97 N
ATOM 4158 CA LYS A 136 24.121 -7.497 -4.345 1.00 61.42 C ATOM 4159 CB LYS A 136 24.292 -8.961 -4.767 1.00 64.42 C
ATOM 4160 CG LYS A 136 25.677 -9.277 -5.301 1.00 66.16 C
ATOM 4161 CD LYS A 136 25.794 -10.758 -5.668 1.00 69.63 C
ATOM 4162 CE LYS A 136 25.696 -11.051 -7.163 1.00 71.66 C
ATOM 4163 NZ LYS A 136 24.294 - 1.219 -7.659 1.00 71.76 N ATOM 4164 C LYS A 136 22.688 -7.005 -4.611 1.00 61.35 C
ATOM 4165 O LYS A 136 22.359 -6.775 -5.774 1.00 61.85 O
ATOM 4166 N LEU A 137 21.851 -6.829 -3.558 1.00 61.20 N
ATOM 4167 CA LEU A 137 20.460 -6.364 -3.663 1.00 61.19 C
ATOM 4168 CB LEU A 137 19.849 -6.140 -2.277 1 ,00 61.12 C ATOM 4169 CG LEU A 137 19.260 -7.323 -1.542 1.00 60.89 C
ATOM 4170 CD1 LEU A 137 19.062 -6.970 -0.093 1.00 61.17 C
ATOM 4171 CD2 LEU A 137 17.920 -7.734 -2.124 1.00 60.68 C
ATOM 4172 C LEU A 137 20.336 -5.062 -4.440 1 .00 61.43 C
ATOM 4173 0 LEU A 137 21.260 -4.242 -4.374 1.00 61.43 O ATOM 4174 N PRO A 38 19.206 -4.828 -5.163 1.00 64.48 N
ATOM 4175 CA PRO A 138 19.069 -3.565 -5.911 1.00 64.58 C
ATOM 4176 CB PRO A 138 17.844 -3.815 -6.793 1.00 66.51 C
ATOM 4177 CG PRO A 138 17.004 -4.786 -6.006 1.00 66.41 C
ATOM 4178 CD PRO A 138 18.008 -5.687 -5.336 1.00 66.33 C ATOM 4179 C PRO A 138 18.839 -2.391 -4.964 1.00 64.55 C
ATOM 4180 O PRO A 138 18.304 -2.594 -3.865 1.00 64.60 O
ATOM 4181 N HIS A 139 19.243 -1.173 -5.394 1.00 63.59 N
ATOM 4182 CA HIS A 139 19.134 0.105 -4.661 1.00 63.25 C
ATOM 4183 CB HIS A 139 17.706 0.409 -4.144 1.00 64.48 C ATOM 4184 CG HIS A 139 16.594 0.178 -5.123 1.00 66.85 C
ATOM 4185 ND1 HIS A 139 16.440 0.975 -6.250 1.00 67.60 N
ATOM 4186 CE1 HIS A 39 15.359 0.517 -6.865 1.00 67.94 C
ATOM 4187 NE2 HIS A 139 14.803 -0.498 -6.196 1.00 68.08 N
ATOM 4188 CD2 HIS A 139 15.579 -0.722 -5.079 1.00 67.76 C ATOM 4189 C HIS A 139 20.152 0.328 -3.522 1.00 62.56 C
ATOM 4190 O HIS A 139 20.275 1.466 -3.076 1.00 62.65 O
ATOM 4191 N VAL A 140 20.872 -0.718 -3.049 1.00 59.06 N
ATOM 4192 CA VAL A 140 21.841 -0.590 -1.944 1.00 57.85 C
ATOM 4193 CB VAL A 140 22.323 -1.980 -1.418 1.00 61.01 C ATOM 4194 CG1 VAL A 40 23.382 -1.852 -0.323 1.00 60.80 C
ATOM 4195 CG2 VAL A 140 21.154 -2.814 -0.917 1.00 60.75 C
ATOM 4196 C VAL A 140 23.011 0.375 -2.249 1.00 57.04 C
ATOM 4197 O VAL A 140 23.637 0.269 -3.303 1.00 56.49 O
ATOM 4198 N ASP A 141 23.291 1.316 -1.326 1.00 55.32 N ATOM 4199 CA ASP A 141 24.411 2.242 -1.459 1.00 54.33 C
ATOM 4200 CB ASP A 141 24.053 3.648 -0.978 1.00 56.54 C
ATOM 4201 CG ASP A 141 25.098 4.712 -1.283 1.00 58.25 C
ATOM 4202 OD1 ASP A 141 26.147 4.373 -1.909 1.00 58.29 O
ATOM 4203 OD2 ASP A 141 24.879 5.886 -0.894 1.00 60.72 O JB2010.7161
ATOM 4204 C ASP A 141 25.553 1.635 -0.656 1.00 53.30 C
ATOM 4205 0 ASP A 141 26.676 1.530 -1.156 1.00 53.38 0
ATOM 4206 N TYR A 142 25.242 1.194 0.574 1.00 50.90 N
ATOM 4207 CA TYR A 42 26.145 0.517 1.513 1.00 49.75 C ATOM 4208 CB TYR A 142 27.266 1.442 2.067 1.00 51.31 C
ATOM 4209 CG TYR A 1 2 26.771 2.658 2.821 1.00 51.67 C
ATOM 4210 CD1 TYR A 142 26.347 3.798 2.142 1.00 52.32 C
ATOM 4211 CE1 TYR A 142 25.896 4.921 2.826 1.00 51.52 C
ATOM 4212 CZ TYR A 142 25.861 4.916 4.208 1.00 51 ,37 C ATOM 4213 OH TYR A 142 25.415 6.050 4.842 1.00 51.03 O
ATOM 4214 CE2 TYR A 142 26.279 3.796 4.911 1.00 50.45 C
ATOM 4215 CD2 TYR A 142 26.739 2.678 4.215 1.00 50.57 C
ATOM 4216 C TYR A 142 25.351 -0.137 2.654 1.00 48.59 C
ATOM 4217 O TYR A 142 24.158 0.117 2.824 1.00 48.89 O ATOM 4218 N ILE A 143 26.019 -0.987 3.411 1.00 44.99 N
ATOM 4219 CA ILE A 143 25.468 -1.666 4.563 1.0043.64 C
ATOM 4220 CB ILE A 143 25.234 -3.184 4.296 1.00 46.83 C
ATOM 4221 CG1 ILE A 143 24.225 -3.392 3.147 1.00 47.35 C
ATOM 4222 CD1 ILE A 143 24.089 -4.723 2.696 1.00 45.23 C ATOM 4223 CG2 ILE A 143 24.774 -3.931 5.570 1.00 46.75 C
ATOM 4224 C ILE A 143 26.458 -1.406 5.703 1.00 43.04 C
ATOM 4225 0 ILE A 143 27.677 -1.559 5.524 1.00 42.66 O
ATOM 4226 N GLU A 144 25.934 -0.984 6.867 1.00 43.50 N
ATOM 4227 CA GLU A 144 26.789 -0.748 8.016 1.0042.76 C ATOM 4228 CB GLU A 144 26.827 0.730 8.420 1.00 45.35 C
ATOM 4229 CG GLU A 144 27.988 1.028 9.351 1.00 47.33 C
ATOM 4230 CD GLU A 144 28.024 2.439 9.885 1.00 50.56 C
ATOM 4231 OE1 GLU A 144 28.220 3.369 9.071 1.00 53.28 O
ATOM 4232 OE2 GLU A 144 27.854 2.618 11.113 1.00 48.93 O ATOM 4233 C GLU A 144 26.402 -1.670 9.162 1.00 41.47 C
ATOM 4234 0 GLU A 144 25.222 -1.837 9.440 1.00 41.22 O
ATOM 4235 N GLU A 145 27.400 -2.305 9.788 1.00 38.71 N
ATOM 4236 CA GLU A 145 27.203 -3.211 10.909 1.00 37.90 C
ATOM 4237 CB GLU A 145 28.450 -4.086 11.116 1.00 38.97 C ATOM 4238 CG GLU A 145 28.350 -5.099 12.248 1.00 40.26 C
ATOM 4239 CD GLU A 145 29.675 -5.745 12.610 1.00 42.74 C
ATOM 4240 OE1 GLU A 145 30.539 -5.054 13.196 1.00 44.60 O
ATOM 4241 OE2 GLU A 145 29.857 -6.942 12.298 1.00 44.73 O
ATOM 4242 C GLU A 145 26.953 -2.340 12.129 1.00 37.33 C ATOM 4243 O GLU A 145 27.748 -1.416 12.419 1.00 37.17 O
ATOM 4244 N ASP A 146 25.843 -2.627 12.849 1.00 36.00 N
ATOM 4245 CA ASP A 146 25.482 -1.886 14.044 1.00 34.82 C
ATOM 4246 CB ASP A 146 24.179 -2.410 14.657 1.00 37.17 C
ATOM 4247 CG ASP A 146 23.487 -1.428 15.602 1.00 39.00 C ATOM 4248 OD1 ASP A 146 23.983 -0.276 15.745 1.00 39.55 O
ATOM 4249 OD2 ASP A 146 22.451 -1.810 16.204 1.00 40.22 O
ATOM 4250 C ASP A 46 26.631 -1.915 15.045 1.00 34.22 C
ATOM 4251 O ASP A 146 27.447 -2.857 15.034 1.00 33.99 O
ATOM 4252 N SER A 147 26.740 -0.851 15.859 1.00 32.75 N ATOM 4253 CA SER A 147 27.782 -0.733 16.865 1.00 32.50 C
ATOM 4254 CB SER A 147 29.109 -0.231 16.286 1.00 36.97 C
ATOM 4255 OG SER A 147 29.131 1.129 15.874 1.00 38.76 O
ATOM 4256 C SER A 147 27.308 0.085 18.047 1.00 32.40 C
ATOM 4257 O SER A 147 26.266 0.744 17.994 1.00 32.55 O JB2010.7161
ATOM 4258 N SER A 148 28.074 0.000 19.127 1.00 33.20 N
ATOM 4259 CA SER A 148 27.853 0.625 20.407 1.00 33.16 C
ATOM 4260 CB SE A 148 28.636 -0.144 21.469 1.00 35.47 C
ATOM 4261 OG SER A 148 28.064 -1.427 21.666 1.00 35.21 O ATOM 4262 C SER A 148 28.213 2.087 20.487 1.00 32.91 C
ATOM 4263 O SER A 148 29.205 2.528 19.895 1.00 34.05 O
ATOM 4264 N VAL A 149 27.401 2.837 21.247 1.00 31.59 N
ATOM 4265 CA VAL A 149 27.601 4.251 21.601 1.00 30.73 C
ATOM 4266 CB VAL A 149 26.718 5.315 20.900 1.00 32.89 C ATOM 4267 CG1 VAL A 149 26.918 5.305 19.393 1.00 32.80 C
ATOM 4268 CG2 VAL A 149 25.256 5.172 21.267 1.00 32.80 C
ATOM 4269 C VAL A 149 27.579 4.326 23.148 1.00 30.20 C
ATOM 4270 O VAL A 149 26.996 3.449 23.813 1.00 29.63 O
ATOM 4271 N PHE A 150 28.244 5.328 23.718 1.00 29.59 N ATOM 4272 CA PHE A 150 28.305 5.410 25,170 1.00 29.74 C
ATOM 4273 CB PHE A 150 29.683 4.909 25.652 1.00 31 .90 C
ATOM 4274 CG PHE A 150 30.031 3.509 25.204 1.00 32.59 C
ATOM 4275 CD1 PHE A 150 29.617 2.400 25.945 1.00 30.93 C
ATOM 4276 CE1 PHE A 150 29.922 1.102 25.527 1.00 29.04 C ATOM 4277 CZ PHE A 150 30.644 0.904 24.368 1.00 31.26 C
ATOM 4278 CE2 PHE A 150 31.065 1.994 23.614 1.00 34.25 C
ATOM 4279 CD2 PHE A 150 30.763 3.295 24.035 1.00 32.60 C
ATOM 4280 C PHE A 150 28.102 6.805 25.678 1.00 29.52 C
ATOM 4281 O PHE A 150 28.572 7.754 25.059 1.00 30.02 O ATOM 4282 N ALA A 151 27.456 6.931 26.847 1.00 27.19 N
ATOM 4283 CA ALA A 51 27.244 8.203 27.526 1.00 27.18 C
ATOM 4284 CB ALA A 151 26.545 7.975 28.866 1.00 26.77 C
ATOM 4285 C ALA A 151 28.631 8.740 27.753 1.00 27.63 C
ATOM 4286 0 ALA A 151 29.519 7.980 28.138 1.00 27.53 O ATOM 4287 N GL A 152 28.850 10.019 27.467 1.00 29.24 N
ATOM 4288 CA GLN A 152 30.162 10.625 27.665 1.00 30.10 C
ATOM 4289 CB GLN A 152 30.632 11.340 26.388 1.00 31.24 C
ATOM 4290 CG GL A 152 30.977 10.390 25.235 1.00 31.81 C
ATOM 4291 CD GL A 152 31.977 9.350 25.646 1.00 31.39 C ATOM 4292 OE1 GLN A 152 33.170 9.6 8 25.828 1.00 31.63 O
ATOM 4293 NE2 GLN A 152 31.505 8.141 25.848 1.00 31.82 N
ATOM 4294 C GLN A 152 30.203 11.530 28.920 1.00 30.89 C
ATOM 4295 O GLN A 152 31.047 12.454 28.989 1.00 31.47 O
ATOM 4296 OXT GLN A 152 29.385 11.327 29.846 1.00 53.75 O TER 4297 GLN A 152
ATOM 4298 N GLN H 1 18.365 -6.211 60.346 1.00 68.74 N
ATOM 4299 CA GLN H 1 17.462 -7.355 60.210 1.00 68.40 C
ATOM 4300 CB GLN H 1 16.514 -7.441 61.425 1.00 71.72 C
ATOM 4301 CG GLN H 1 16.425 -8.833 62.052 1.00 75.06 C ATOM 4302 CD GLN H 1 15.322 -9.708 61.484 1.00 79.05 C
ATOM 4303 OE1 GLN H 1 14.232 -9.239 61.093 1.00 80.58 O
ATOM 4304 NE2 GLN H 1 15.581 -11.018 61.443 1.00 81.46 N
ATOM 4305 C GLN H 1 16.681 -7.267 58.894 1.00 66.87 C
ATOM 4306 O GLN H 1 15.565 -6.732 58.855 1.00 67.08 O ATOM 4307 N VAL H 2 17.291 -7.780 57.812 1.00 58.52 N
ATOM 4308 CA VAL H 2 16.697 -7.771 56.477 1.00 56.61 C
ATOM 4309 CB VAL H 2 17.729 -7.866 55.326 1.00 59.34 C
ATOM 4310 CG1 VAL H 2 17.036 -8.049 53.978 1.00 58.47 C
ATOM 4311 CG2 VAL H 2 18.628 -6.640 55.294 1.00 58.90 C JB2010.7161
ATOM 4312 C VAL H 2 15.636 -8.836 56.376 1.00 55.47 C
ATOM 4313 O VAL H 2 15.905 -10.008 56.632 1.00 55.17 O
ATOM 4314 N GLN H 3 14.434 -8.428 55.986 1.00 52.36 N
ATOM 4315 CA GLN H 3 13.320 -9.337 55.824 1.00 51.14 C ATOM 4316 CB GLN H 3 12.277 -9.090 56.927 1.00 54.31 C
ATOM 4317 CG GLN H 3 12.440 -9.947 58.173 1.00 58.37 C
ATOM 4318 CD GLN H 3 11.078 -10.394 58.674 1.00 63.86 C
ATOM 4319 OE1 GLN H 3 10.635 -11.537 58.428 1.00 66.18 O
ATOM 4320 NE2 GLN H 3 10.367 -9.501 59.383 1.00 65.83 N ATOM 4321 C GLN H 3 12.671 -9.207 54.444 1.00 49.17 C
ATOM 4322 O GLN H 3 12.191 -8.119 54.077 1.00 49.09 O
ATOM 4323 N LEU H 4 12.663 -10.323 53.677 1.00 42.69 N
ATOM 4324 CA LEU H 4 1 1.978 -10.428 52.377 1.00 40.71 C
ATOM 4325 CB LEU H 4 12.848 -11.089 51.289 1.00 39.94 C ATOM 4326 CG LEU H 4 13.624 -10. 51 50.346 1.00 39.82 C
ATOM 4327 CD1 LEU H 4 14.678 -9.349 51.082 1.00 39.47 C
ATOM 4328 CD2 LEU H 4 14.345 -10.941 49.266 1.00 40.49 C
ATOM 4329 C LEU H 4 10.741 -11.264 52.750 1.00 39.52 C
ATOM 4330 O LEU H 4 10.879 -12.440 53.087 1.00 39.30 O ATOM 4331 N VAL H 5 9.556 -10.618 52.823 1.00 38.02 N
ATOM 4332 CA VAL H 5 8.303 -11.264 53.255 1.00 37.05 C
ATOM 4333 CB VAL H 5 7.625 -10.549 54.464 1.00 39.90 C
ATOM 4334 CG1 VAL H 5 6.277 -1 1.184 54.823 1.00 39.11 C
ATOM 4335 CG2 VAL H 5 8.547 -10.532 55.671 1.00 39.19 C ATOM 4336 C VAL H 5 7.339 -11.544 52.124 1.00 36.26 C
ATOM 4337 O VAL H 5 6.703 -10.626 51.607 1.00 36.37 O
ATOM 4338 N GLN H 6 7.197 -12.828 51.788 1.00 36.26 N
ATOM 4339 CA GLN H 6 6.333 -13.279 50.712 1.00 35.44 C
ATOM 4340 CB GLN H 6 6.948 -14.454 49.977 1.00 36.11 C ATOM 4341 CG GLN H 6 8.292 -14.135 49.359 1.00 35.68 C
ATOM 4342 CD GLN H 6 8.832 -15.313 48.611 1.00 35.29 C
ATOM 4343 OE1 GLN H 6 10.009 -15.648 48.722 1.00 35.36 O
ATOM 4344 NE2 GLN H 6 7.984 -15.983 47.829 1.00 34.39 N
ATOM 4345 C GLN H 6 4.907 -13.604 51.107 1.00 35.60 C ATOM 4346 0 GLN H 6 4.616 -13.978 52.254 1.00 35.41 O
ATOM 4347 N SER H 7 4.010 -13.471 50.119 1.00 37.84 N
ATOM 4348 CA SER H 7 2.586 -13.749 50.234 1.00 37.70 C
ATOM 4349 CB SER H 7 1.868 -13.309 48.962 1.00 41.61 C
ATOM 4350 OG SER H 7 2.179 -14.141 47.855 1.00 42.93 O ATOM 4351 C SER H 7 2.404 -15.252 50.504 1.00 37.69 C
ATOM 4352 O SER H 7 3.341 -16.041 50.286 1.00 37.52 O
ATOM 4353 N GLY H 8 1.225 -15.628 51.003 1.00 38.18 N
ATOM 4354 CA GLY H 8 0.898 -17.006 51.362 1.00 37.75 C
ATOM 4355 C GLY H 8 0.871 -17.970 50.203 1.00 37.86 C ATOM 4356 O GLY H 8 0.929 -17.551 49.042 1 ,00 38.33 O
ATOM 4357 N ALA H 9 0.785 -19.266 50.511 1.00 37.54 N
ATOM 4358 CA ALA H 9 0.761 -20.326 49.506 1.00 37.86 C
ATOM 4359 CB ALA H 9 0.786 -21.690 50.158 1.00 38.34 C
ATOM 4360 C ALA H 9 -0.429 -20.217 48.595 1.00 38.77 C ATOM 4361 O ALA H 9 -1.459 -19.637 48.957 1.00 39.44 O
ATOM 4362 N GLU H 10 -0.284 -20.779 47.401 1 .00 40.77 N
ATOM 4363 CA GLU H 10 -1.321 -20.726 46.408 1.00 40.99 C
ATOM 4364 CB GLU H 10 -0.922 -19.734 45.300 1.00 43.25 C
ATOM 4365 CG GLU H 10 -0.604 -18,336 45.818 1.00 44.97 C JB2010.7161
ATOM 4366 CD GLU H 10 -1.649- 7.24545.662 1.0047.42 C
ATOM 4367 OE1 GLU H 10 -1.243-16.05845.626 1.0050.48 O
ATOM 4368 OE2 GLU H 10 -2.861 -17.56245.574 1.0048.05 O
ATOM 4369 C GLU H 10 -1.643-22.102 45.846 1.0041.01 C ATOM 4370 O GLU H 10 -0.794-22.98445.810 1.0041.02 O
ATOM 4371 N VALH 11 -2.909-22.27045.440 1.0041.86 N
ATOM 4372 CA VALH 11 -3.455-23.47044.820 1.0041.75 C
ATOM 4373 CB VALH 11 -4.302-24.36845.763 1.0045.31 C
ATOM 4374 CG1 VAL H 11 -5.635-23.731 46.138 1.0045.11 C ATOM 4375 CG2 VALH 11 -4.507-25.74345.154 1.0044.78 C
ATOM 4376 C VALH 11 -4.158-23.01343.541 1.0041.53 C
ATOM 4377 O VALH 11 -5.064-22.17043.579 1.0041.95 O
ATOM 4378 N LYS H 12 -3.678-23.49342.406 1.0037.19 N
ATOM 4379 CA LYS H 12 -4.224-23.05441.148 1.0036.89 C ATOM 4380 CB LYS H 12 -3.227-22.09640.467 1.0040.46 C
ATOM 4381 CG LYS H 12 -3.002-20,76041.164 1.0041.16 C
ATOM 4382 CD LYS H 12 -4.138-19.77040.924 1.0043.18 C
ATOM 4383 CE LYS H 12 -4.056-18.53741.802 1.0044.49 C
ATOM 4384 NZ LYS H 12 -5.317-17.75741.722 1.0046.46 N ATOM 4385 C LYS H 12 -4.510-24.21940.241 1.0036.70 C
ATOM 4386 O LYS H 12 -3.950-25.291 40.441 1.0037.46 O
ATOM 4387 N LYS H 13 -5.390-24.013 39.249 1.0034.94 N
ATOM 4388 CA LYS H 13 -5.747-25.01 38.250 1.0034.34 C
ATOM' 4389 CB LYS H 13 -7.225-24.888 37.875 1.0034.82 C ATOM 4390 CG LYS H 13 -8.159-25.495 38.870 1.0033.31 C
ATOM 4391 CD LYS H 13 -8.549-26.908 38.5070.5031.12 C
ATOM 4392 CE LYS H 13 -9.192-27.567 39.692 1.0029.81 C
ATOM 4393 NZ LYS H 13 -9.850-26.57040.582 1.0028.22 N
ATOM 4394 C LYS H 13 -4.907-24.737 37.003 1.0034.36 C ATOM 43950 LYS H 13 -4.475-23.590 36.814 1.0034.42 O
ATOM 4396 N PRO H 14 -4.681 -25.71536.099 1.0035.09 N
ATOM 4397 CA PRO H 14 -3.892-25.401 34.894 1.0035.13 C
ATOM 4398 CB PRO H 14 -3.741 -26.76334.218 1.0036.01 C
ATOM 4399 CG PRO H 14 -4.013-27.768 35.309 1.0035.54 C ATOM 4400 CD PRO H 14 -5,073-27.135 36.127 1.0036.10 C
ATOM 4401 C PROH 14 -4.599-24.340 34.027 1.0035.67 C
ATOM 4402 O PROH 14 -5.823-24.374 33.882 1.0036.68 O
ATOM 4403 N GLY H 15 -3.841 -23.388 33.498 1.0036.81 N
ATOM 4404 CA GLY H 15 -4.387-22.28932.703 1.0036.68 C ATOM 4405 C GLY H 15 -4.548-21.00233.512 1.0036.92 C
ATOM 4406 O GLY H 15 -4.583-19.90232.937 1.0037.30 O
ATOM 4407 N ALA H 16 -4.642-21.130 34.860 1.0034.25 N
ATOM 4408 CA ALA H 16 -4.775-20.023 35.790 1.0034.15 C
ATOM 4409 CB ALA H 16 -5.066-20.551 37.191 1.0034.86 C ATOM 4410 C ALA H 16 -3.509-19.141 35.814 1.0034.65 C
ATOM 4411 O ALAH 16 -2.532-19.403 35.083 1.0034.81 O
ATOM 4412 N SER H 17 -3.539-18.09236.673 1.0034.29 N
ATOM 4413 CA SER H 17 -2.468-17.11936.862 1.0034.51 C
ATOM 4414 CB SER H 17 -2.916-15.752 36.354 1.0039.22 C ATOM 4415 OG SER H 17 -2.755-15.664 34.950 1.0041,91 O
ATOM 4416 C SER H 17 -2.130-16.981 38.321 1.0034.19 C
ATOM 4417 O SER H 17 -2.978-17.244 39.178 1.0034.75 O
ATOM 4418 N VALH 18 -0.919-16.51238.620 1.0031.41 N
ATOM 4419 CA VALH 18 -0.522-16.295 39.998 1.0030.99 C JB2010.7161
ATOM 4420 CB VAL H 18 0.025 -17.579 40.699 1.00 33.21 C
ATOM 4421 CG1 VAL H 18 1.424 -17.962 40.219 1.00 32.75 C
ATOM 4422 CG2 VAL H 18 -0.007 -17.431 42.208 1.00 33.08 C
ATOM 4423 C VAL H 18 0.363 -15.041 40.139 1.00 31.28 C ATOM 4424 O VAL H 18 1.234 -14.814 39.291 1.00 31.23 O
ATOM 4425 N LYS H 19 0.104 -14.222 41.186 1.00 32.24 N
ATOM 4426 CA LYS H 19 0.874 -13.034 41.534 1.00 32.94 C
ATOM 4427 CB LYS H 19 0.056 -11.738 41.464 1.00 34.56 C
ATOM 4428 CG LYS H 19 0.534 -10.764 40.370 1.00 35.94 C ATOM 4429 CD LYS H 19 0.801 -9.352 40.871 1.00 37.08 C
ATOM 4430 CE LYS H 19 0.331 -8.306 39.880 1.00 37.33 C
ATOM 4431 NZ LYS H 19 0.864 -6.943 40.202 1.00 38.66 N
ATOM 4432 C LYS H 19 1.383 -13.260 42.947 1.00 33.45 C
ATOM 4433 O LYS H 19 0.573 -13.430 43.873 1.00 34.45 O ATOM 4434 N VAL H 20 2.709 -13.319 43.119 1.00 31.10 N
ATOM 4435 CA VAL H 20 3.297 -13.531 44.439 1.00 30.89 C
ATOM 4436 CB VAL H 20 4.253 -14.767 44.458 1.00 33.33 C
ATOM 4437 CG1 VAL H 20 5.001 -14.892 45.787 1.00 32.49 C
ATOM 4438 CG2 VAL H 20 3.505 -16.055 44.132 1.00 32.50 C ATOM 4439 C VAL H 20 3.991 -12.230 44.838 1.00 31.28 C
ATOM 4440 O VAL H 20 4.737 -11.678 44.043 1.00 30.80 O
ATOM 4441 N SER H 21 3.745 -11.746 46.059 1.00 34.27 N
ATOM 4442 CA SER H 21 4.353 -10.514 46.569 1 .00 34.76 C
ATOM 4443 CB SER H 21 3.345 -9.717 47.397 1.00 40.20 C ATOM 4444 OG SER H 21 3.437 -9.943 48.798 1.00 41.15 O
ATOM 4445 C SER H 21 5.588 -10.859 47.404 1.00 35.29 C
ATOM 4446 O SER H 21 5.689 -11.980 47.909 1.00 35.35 O
ATOM 4447 N CYS H 22 6.509 -9.887 47.549 1.00 37.90 N
ATOM 4448 CA CYS H 22 7.751 -9.987 48.302 1.00 38.59 C ATOM 4449 CB CYS H 22 8.867 -10.463 47.381 1.00 40.41 C
ATOM 4450 SG CYS H 22 10.521 -10.452 48.125 1.00 40.84 S
ATOM 4451 C CYS H 22 8.052 -8.609 48.869 1.00 39.33 C
ATOM 4452 O CYS H 22 8.573 -7.753 48.150 1.00 39.20 O
ATOM 4453 N LYS H 23 7.710 -8.372 50.138 1.00 39.81 N ATOM 4454 CA LYS H 23 7.959 -7.084 50.776 1.00 40.65 C
ATOM 4455 CB LYS H 23 6.859 -6.747 51.793 1.00 44,57 C
ATOM 4456 CG LYS H 23 6.829 -5.276 52.194 1.00 46.83 C
ATOM 4457 CD LYS H 23 5.506 -4.882 52.861 1.00 51.00 C
ATOM 4458 CE LYS H 23 5.621 -3.662 53.763 1.00 52.40 C ATOM 4459 NZ LYS H 23 5.689 -2.374 52.993 1.00 54.11 N
ATOM 4460 C LYS H 23 9.362 -7.039 51.401 1.0040.85 C
ATOM 4461 O LYS H 23 9.719 -7.920 52.192 1.00 40.78 O
ATOM 4462 N VAL H 24 10.153 -6.007 51.034 1.00 40.79 N
ATOM 4463 CA VAL H 24 11.516 -5.801 51.549 1.00 41.07 C ATOM 4464 CB VAL H 24 12.520 -5.376 50.451 1.00 44.26 C
ATOM 4465 CG1 VAL H 24 13.900 -5.088 51.036 1.0043.62 C
ATOM 4466 CG2 VAL H 24 12.613 -6.425 49.362 1.00 44.33 C
ATOM 4467 C VAL H 24 1 1.543 -4.806 52.704 1.00 41.36 C
ATOM 4468 O VAL H 24 10.912 -3.749 52.635 1.00 41.13 O ATOM 4469 N SER H 25 12.305 -5.150 53.757 1.00 42.50 N
ATOM 4470 CA SER H 25 12.533 -4.327 54.947 1.00 42.85 C
ATOM 4471 CB SER H 25 11 ,501 -4.642 56.022 1.00 44.78 C
ATOM 4472 OG SER H 25 11.948 -5.687 56.865 1.00 45.31 O
ATOM 4473 C SER H 25 13.956 -4.612 55.452 1.00 43.10 C JB2010.7161
ATOM 4474 0 SER H 25 14.435 -5.741 55.323 1.00 43.21 O
ATOM 4475 N GLY H 26 14.621 -3.610 56.005 1.0044.19 N
ATOM 4476 CA GLY H 26 15.966 -3.814 56.531 1.00 44.18 C
ATOM 4477 C GLY H 26 17.079 -3.262 55.671 1.00 44.51 C ATOM 4478 O GLY H 26 18.245 -3.290 56.091 1.00 44.83 O
ATOM 4479 N TYR H 27 16.721 -2.773 54.452 1.00 43.70 N
ATOM 4480 CA TYR H 27 17.619 -2.151 53.473 1.00 43.68 C
ATOM 4481 CB TYR H 27 18.573 -3.177 52.768 1.0045.07 C
ATOM 4482 CG TYR H 27 17.975 -4.014 51.647 1.00 45.84 C ATOM 4483 CD 1 TYR H 27 17.632 -3.438 50.424 1.0045.51 C
ATOM 4484 CE1 TYR H 27 17.091 -4.197 49.393 1.00 45.17 C
ATOM 4485 CZ TYR H 27 16.928 -5.560 49.556 1.00 45.76 C
ATOM 4486 OH TYR H 27 16.399 -6.293 48.522 1.00 46.88 O
ATOM 4487 CE2 TYR H 27 17.275 -6.162 50.755 1.00 45.55 C ATOM 4488 CD2 TYR H 27 17.811 -5.389 51.787 1.00 46.05 C
ATOM 4489 C TYR H 27 16.814 -1.270 52.496 1.00 43.50 C
ATOM 4490 O TYR H 27 15.587 -1.435 52.399 1.00 43.73 O
ATOM 4491 N THR H 28 17.491 -0.335 51.784 1.00 43.40 N
ATOM 4492 CA THR H 28 16.818 0.532 50.808 1.00 44.00 C ATOM 4493 CB THR H 28 17.704 1.730 50.394 1.00 53.83 C
ATOM 4494 OG1 THR H 28 18.086 2.469 51.548 1.00 56.35 O
ATOM 4495 CG2 THR H 28 17.003 2.659 49.413 1.00 54.29 C
ATOM 4496 C THR H 28 16.421 -0.327 49.580 1.00 43.85 C
ATOM 4497 O THR H 28 17.291 -0.724 48.782 1.00 43.61 O ATOM 4498 N PHE H 29 15.109 -0.604 49.441 1.00 41.13 N
ATOM 4499 CA PHE H 29 14.524 -1.406 48.361 1.00 40.53 C
ATOM 4500 CB PHE H 29 13.029 -1.084 48.221 1.00 41.34 C
ATOM 4501 CG PHE H 29 12.296 -1.857 47.157 1.00 40.96 C
ATOM 4502 CD1 PHE H 29 12.194 -3.245 47.226 1.00 40.17 C ATOM 4503 CE1 PHE H 29 11.512 -3.960 46.241 1.00 37.42 C
ATOM 4504 CZ PHE H 29 10.901 -3.289 45.206 1.00 38.49 C
ATOM 4505 CE2 PHE H 29 10.978 -1.915 45.125 1.00 40.05 C
ATOM 4506 CD2 PHE H 29 11.677 -1.199 46.099 1.00 40.81 C
ATOM 4507 C PHE H 29 15.216 -1.251 47.018 1.00 40.40 C ATOM 4508 O PHE H 29 15.551 -2.256 46.383 1.0040.69 O
ATOM 4509 N THR H 30 15.447 -0.003 46.609 1.00 40.02 N
ATOM 4510 CA THR H 30 16.053 0.385 45.333 1.00 39.83 C
ATOM 4511 CB THR H 30 15.612 1.813 44.968 1.00 41.35 C
ATOM 4512 OG1 THR H 30 15.852 2.691 46.083 1.00 41.01 O ATOM 4513 CG2 THR H 30 14.148 1.886 44.522 1.00 39.88 C
ATOM 4514 C THR H 30 17.573 0.150 45.188 1.00 40.07 C
ATOM 4515 O THR H 30 18.1 13 0.316 44.089 1.00 40.18 O
ATOM 4516 N ASP H 31 18.261 -0.230 46.271 1.00 41.78 N
ATOM 4517 CA ASP H 31 19.703 -0.470 46.231 1.0042.27 C ATOM 4518 CB ASP H 31 20.246 -0.617 47.659 1.00 46.00 C
ATOM 4519 CG ASP H 31 20.648 0.649 48.368 1.00 47.93 C
ATOM 4520 OD1 ASP H 31 20.579 1.727 47.743 1.00 51.68 O
ATOM 4521 OD2 ASP H 31 21.037 0.561 49.552 1.00 50.02 O
ATOM 4522 C ASP H 31 20.096 -1.742 45.487 1.00 42.08 C ATOM 4523 O ASP H 31 21.140 -1.768 44.828 1.00 42.31 O
ATOM 4524 N TYR H 32 19.308 -2.821 45.653 1.00 40.03 N
ATOM 4525 CA TYR H 32 19.637 -4.106 45.075 1.00 39.39 C
ATOM 4526 CB TYR H 32 19.890 -5.116 46.208 1.00 41.21 C
ATOM 4527 CG TYR H 32 20.814 -4.595 47.292 1.00 42.82 C JB2010.7161
ATOM 4528 CD1 TYR H 32 20.389 -4.504 48.617 1.00 43.77 C
ATOM 4529 CE1 TYR H 32 21.230 -4.018 49.617 1.00 43.50 C
ATOM 4530 CZ TYR H 32 22.517 -3.611 49.296 1.00 43.78 C
ATOM 4531 OH TYR H 32 23.374 -3.136 50.268 1.00 43.95 O ATOM 4532 CE2 TYR H 32 22.954 -3.675 47.981 1.00 43.19 C
ATOM 4533 CD2 TYR H 32 22.112 -4.181 46.993 1.00 43.02 C
ATOM 4534 C TYR H 32 18.596 -4.627 44.139 1.00 38.80 C
ATOM 4535 O TYR H 32 17.408 -4.394 44.367 1.00 39.01 O
ATOM 4536 N TYR H 33 19.037 -5,361 43.088 1.00 36.02 N ATOM 4537 CA TYR H 33 18.130 -5.976 42.123 1.00 35.58 C
ATOM 4538 CB TYR H 33 18.879 -6.545 40.903 1.00 35.25 C
ATOM 4539 CG TYR H 33 19.663 -5.542 40.087 1.00 36.97 C
ATOM 4540 CD1 TYR H 33 19.037 -4.743 39.133 1.00 36.59 C
ATOM 4541 CE1 TYR H 33 19.764 -3.839 38.354 1.00 36.38 C ATOM 4542 CZ TYR H 33 21.139 -3.753 38.500 1.00 37.33 C
ATOM 4543 OH TYR H 33 21.877 -2.860 37.746 1.00 38.79 O
ATOM 4544 CE2 TYR H 33 21.784 -4.554 39.429 1.00 37.67 C
ATOM 4545 CD2 TYR H 33 21.047 -5.443 40.211 1.00 38.05 C
ATOM 4546 C TYR H 33 17.405 -7.115 42.835 1.00 35.36 C ATOM 4547 O TYR H 33 17.909 -7.647 43.822 1.00 35.46 O
ATOM 4548 N MET H 34 16.249 -7.510 42.321 1.00 36.65 N
ATOM 4549 CA MET H 34 15.470 -8.585 42.899 1.00 36.16 C
ATOM 4550 CB MET H 34 14.109 -8.043 43.369 1.00 38.96 C
ATOM 4551 CG MET H 34 13.228 -9.080 44.033 1.00 41.05 C ATOM 4552 SD MET H 34 13.861 -9.731 45.595 1.00 45.60 S
ATOM 4553 CE MET H 34 13.785 -8.264 46.613 1.00 42.62 C
ATOM 4554 C MET H 34 15.308 -9.732 41.904 1.00 35.50 C
ATOM 4555 O MET H 34 14.761 -9.538 40.826 1.00 35.07 O
ATOM 4556 N ASN H 35 15.784 -10.923 42.282 1.00 34.95 N ATOM 4557 CA ASN H 35 15.671 -12.139 41.490 1 .00 34.11 C
ATOM 4558 CB ASN H 35 16.905 -13.010 41.649 1.00 37.99 C
ATOM 4559 CG ASN H 35 18.158 -12.355 41.154 1.00 38.92 C
ATOM 4560 OD1 ASN H 35 18.476 -12.378 39.955 1.00 39.35 O
ATOM 4561 ND2 AS H 35 18.895 -11.753 42.069 1.00 38.99 N ATOM 4562 C ASN H 35 14.463 -12.915 41.977 1.00 33.60 C
ATOM 4563 O ASN H 35 13.965 -12.689 43.081 1.00 32.95 O
ATOM 4564 N TRP H 36 13.982 -13.818 41.124 1.00 32.06 N
ATOM 4565 CA TRP H 36 12.883 -14.709 41.388 1.00 31.15 C
ATOM 4566 CB TRP H 36 11.611 -14.259 40.698 1.00 27.96 C ATOM 4567 CG TRP H 36 10.886 -13.178 41.455 1.00 28.09 C
ATOM 4568 CD1 TRP H 36 10.967 -11.834 41.232 1.00 27.78 C
ATOM 4569 NE1 TRP H 36 10.137 -11.156 42.101 1 ,00 26.66 N
ATOM 4570 CE2 TRP H 36 9.498 -12.059 42.914 1.00 26.32 C
ATOM 4571 CD2 TRP H 36 9.944 -13.349 42.538 1.00 27.23 C ATOM 4572 CE3 TRP H 36 9.437 -14.461 43.226 1.00 27.48 C
ATOM 4573 CZ3 TRP H 36 8.522 -14.253 44.253 1.00 29.03 C
ATOM 4574 CH2 TRP H 36 8.087 -12.962 44.592 1.00 28.89 C
ATOM 4575 CZ2 TRP H 36 8.556 -11.852 43.928 1.00 27.21 C
ATOM 4576 C TRP H 36 13.399 -16.038 40.902 1.00 31.20 C ATOM 4577 O TRP H 36 13.795 -16.163 39.738 1.00 31.13 O
ATOM 4578 N VAL H 37 13.500 -16.995 41.838 1.00 31.53 N
ATOM 4579 CA VAL H 37 14.020 -18.348 41.654 1.00 31.40 C
ATOM 4580 CB VAL H 37 15.340 -18.547 42.490 1.00 34.90 C
ATOM 4581 CG1 VAL H 37 15.858 -19.976 42.428 1 .00 35.64 C JB2010.7161
ATOM 4582 CG2 VAL H 37 16.439 -17.591 42.043 1.00 34.68 C
ATOM 4583 C VAL H 37 12.931 -19.286 42.121 1.00 31.06 C
ATOM 4584 O VAL H 37 12.152 -18.911 42.977 1.00 31.89 O
ATOM 4585 N ARG H 38 12.869 -20.502 41.588 1.00 31.77 N ATOM 4586 CA ARG H 38 11.877 -21.485 42.017 1.00 31.14 C
ATOM 4587 CB ARG H 38 10.630 -21.480 41.120 1.00 33.02 C
ATOM 4588 CG ARG H 38 10.881 -22.112 39.776 1.00 32.16 C
ATOM 4589 CD ARG H 38 9.613 -22.386 39.041 1.00 30.77 C
ATOM 4590 NE ARG H 38 9.922 -23.071 37.789 1.00 31.18 N ATOM 4591 CZ ARG H 38 9.024 -23.326 36.849 1.00 29.23 C
ATOM 4592 NH1 ARG H 38 7.760 -22.943 37.007 1.00 27.88 N
ATOM 4593 NH2 ARG H 38 9.386 -23.949 35.731 1.00 26.85 N
ATOM 4594 C ARG H 38 12.470 -22.901 42.183 1.00 30.94 C
ATOM 4595 O ARG H 38 13.512 -23.245 41.600 1.00 30.33 O ATOM 4596 N GLN H 39 11.795 -23.709 42.998 1.00 31.50 N
ATOM 4597 CA GLN H 39 12.233 -25.055 43.233 1.00 31.55 C
ATOM 4598 CB GLN H 39 13.047 -25.086 44.520 1.00 32.09 C
ATOM 4599 CG GLN H 39 1 .628 -26.430 44.824 1.00 30.32 C
ATOM 4600 CD GLN H 39 14.544 -26.334 45.986 1.00 30.33 C ATOM 4601 OE1 GLN H 39 14.276 -25.645 46.973 1.00 30.12 O
ATOM 4602 NE2 GL H 39 15.664 -27.016 45.891 1.00 32.56 N
ATOM 4603 C GLN H 39 11.056 -26.046 43.262 1 .00 32.29 C
ATOM 4604 O GLN H 39 10.214 -25.977 44.169 1.00 32.64 O
ATOM 4605 N ALA H 40 10.997 -26.966 42.273 1.00 32.91 N ATOM 4606 CA ALA H 40 9.939 -27.980 42.260 1.00 33.97 C
ATOM 4607 CB ALA H 40 9.857 -28.665 40.915 1.00 34.69 C
ATOM 4608 C ALA H 40 10.240 -28.998 43.353 1.00 35.27 C
ATOM 4609 O ALA H 40 11.423 -29.265 43.641 1.00 34.93 O
ATOM 4610 N PRO H 41 9.190 -29.546 44.015 1.00 39.91 N ATOM 461 CA PRO H 41 9.428 -30.503 45.116 1.00 40.81 C
ATOM 4612 CB PRO H 41 8.027 -31.048 45.423 1.0041.99 C
ATOM 4613 CG PRO H 41 7.168 -30.596 44.280 1.00 41.52 C
ATOM 4614 CD PRO H 41 7.743 -29.319 43.832 1.00 41.14 C
ATOM 4615 C PRO H 41 10.482 -31.595 44.857 1.0041.48 C ATOM 4616 0 PRO H 41 10.370 -32.369 43.893 1.00 41.96 O
ATOM 4617 N GLY H 42 11.514 -31.608 45.707 1.00 40.30 N
ATOM 4618 CA GLY H 42 12.601 -32.576 45.618 1.00 40.34 C
ATOM 4619 C GLY H 42 13.591 -32.355 44.483 1.00 40.79 C
ATOM 4620 O GLY H 42 14.492 -33.170 44.274 1.00 40.68 O ATOM 4621 N GLN H 43 13.457 -31.237 43.761 1.00 41.79 N
ATOM 4622 CA GLN H 43 14.333 -30.913 42.646 1.00 41.63 C
ATOM 4623 CB GLN H 43 13.502 -30.722 41.374 1.00 44.35 C
ATOM 4624 CG GLN H 43 12.765 -31.983 40.967 1.00 48.55 C
ATOM 4625 CD GLN H 43 11.630 -31.651 40.029 1.00 55.63 C ATOM 4626 OE1 GLN H 43 11.817 -31.034 38.949 1.00 56.93 O
ATOM 4627 NE2 GLN H 43 10,409 -32.063 40.426 1.00 57.43 N
ATOM 4628 C GLN H 43 15.241 -29.707 42.933 1.0040.59 C
ATOM 4629 O GLN H 43 15.239 -29.154 44.039 1.00 39.90 O
ATOM 4630 N GLY H 44 16.014 -29.331 41.919 1.00 38.58 N ATOM 4631 CA GLY H 44 16.950 -28.216 41 ,965 1.00 38.45 C
ATOM 4632 C GLY H 44 16.337 -26.849 41.749 1.00 38.10 C
ATOM 4633 O GLY H 44 15. 17 -26.685 41.803 1.00 38.17 O
ATOM 4634 N LEU H 45 17.206 -25.860 41.476 1.00 36.20 N
ATOM 4635 CA LEU H 45 16.833 -24.462 41.304 1.00 35.58 C JB2010.7161
ATOM 4636 CB LEU H 45 17.777 -23.566 42.1 11 1.00 34.68 C
ATOM 4637 CG LEU H 45 17.954 -23.939 43.573 1.00 34.33 C
ATOM 4638 CD1 LEU H 45 19.227 -23.335 44.133 1.00 33.58 C
ATOM 4639 CD2 LEU H 45 16.7 1 -23.602 44.395 1 .00 32.03 C ATOM 4640 C LEU H 45 16.741 -23.975 39.885 1.00 35.57 C
ATOM 4641 O LEU H 45 17.533 -24.361 39.034 1.00 36.16 O
ATOM 4642 N GLU H 46 15.774 -23.108 39.637 1.00 33.52 N
ATOM 4643 CA GLU H 46 15.550 -22.500 38.341 1.00 33.02 C
ATOM 4644 CB GLU H 46 14.368 -23.171 37.660 1.00 34.37 C ATOM 4645 CG GLU H 46 14.021 -22.646 36.285 1 .00 37.24 C
ATOM 4646 CD GLU H 46 13.144 -23.618 35.523 1.00 42.30 C
ATOM 4647 OE1 GLU H 46 13.455 -23.877 34.337 1.0042.37 O
ATOM 4648 OE2 GLU H 46 12.164 -24.140 36.114 1.00 44.02 O
ATOM 4649 C GLU H 46 15.301 -21.004 38.564 1.00 32.57 C ATOM 4650 O GLU H 46 14.476 -20.623 39.401 1.00 32.00 O
ATOM 4651 N TRP H 47 16.047 -20.164 37.825 1.00 32.73 N
ATOM 4652 CA TRP H 47 15.942 -18.720 37.885 1.00 31.59 C
ATOM 4653 CB TRP H 47 17.293 -18.123 37.505 1.00 31.62 C
ATOM 4654 CG TRP H 47 17.357 -16.624 37.496 1.00 31.89 C ATOM 4655 CD1 TRP H 47 17.512 -15.802 38.575 1.00 31.63 C
ATOM 4656 NE1 TRP H 47 17.580 -14.489 38.167 1.00 31.70 N
ATOM 4657 CE2 TRP H 47 17.483 -14.445 36.798 1.00 32.74 C
ATOM 4658 CD2 TRP H 47 17.353 -15.777 36.342 1.00 31.58 C
ATOM 4659 CE3 TRP H 47 17.210 -16.009 34.967 1.00 31 ,29 C ATOM 4660 CZ3 TRP H 47 17.213 -14.927 34.100 1.00 31.61 C
ATOM 4661 CH2 TRP H 47 17.325 -13.613 34.577 1.00 32.11 C
ATOM 4662 CZ2 TRP H 47 17.483 -13.347 35.920 1.00 32.82 C
ATOM 4663 C TRP H 47 14.851 -18.282 36.905 1.00 31.22 C
ATOM 4664 O TRP H 47 14.912 -18.650 35.732 1.00 30.72 O ATOM 4665 N ILE H 48 13.844 -17.517 37.389 1.00 29.39 N
ATOM 4666 CA ILE H 48 12.743 -16.998 36.571 1.00 29.17 C
ATOM 4667 CB ILE H 48 11.443 -16.864 37.395 1.00 31.66 C
ATOM 4668 CG1 ILE H 48 10.980 -18.237 37.899 1.00 30.54 C
ATOM 4669 CD1 ILE H 48 10.244 -18.166 39.191 1.00 29.61 C ATOM 4670 CG2 ILE H 48 10.328 -16.150 36.583 1.00 30.56 C
ATOM 4671 C ILE H 48 13.123 -15.678 35.858 1.00 29.63 C
ATOM 4672 O ILE H 48 12.859 -15.514 34.668 1.00 29.38 O
ATOM 4673 N GLY H 49 13.720 -14.759 36.606 1.00 32.15 N
ATOM 4674 CA GLY H 49 14.138 -13.460 36.103 1.00 32.43 C ATOM 4675 C GLY H 49 14.577 -12.510 37.196 1 ,00 33.00 C
ATOM 4676 O GLY H 49 14.602 -12.875 38.370 1.00 33.64 O
ATOM 4677 N ASP H 50 14.941 -11.287 36.817 1.00 34.93 N
ATOM 4678 CA ASP H 50 15.342 -10.245 37.758 1.00 35.13 C
ATOM 4679 CB ASP H 50 16.870 -10.187 38.024 1.00 37.15 C ATOM 4680 CG ASP H 50 17.756 -9.693 36.906 1.00 38.66 C
ATOM 4681 OD1 ASP H 50 17.282 -8.883 36.083 1.00 41 .87 O
ATOM 4682 OD2 ASP H 50 18.936 -10.105 36.860 1.00 39.44 O
ATOM 4683 C ASP H 50 14.731 -8.886 37.413 1.00 35.42 C
ATOM 4684 O ASP H 50 14.233 -8.691 36.294 1.00 35.21 O ATOM 4685 N ILE H 51 14.764 -7.959 38.375 1.00 33.12 N
ATOM 4686 CA ILE H 51 14.203 -6.639 38.191 1.00 33.13 C
ATOM 4687 CB ILE H 51 12.681 -6.612 38.585 1.00 35.44 C
ATOM 4688 CG1 ILE H 51 11.980 -5.323 38.107 1.00 34.68 C
ATOM 4689 CD1 ILE H 51 10.639 -5.481 37.730 1.00 33.37 C JB2010.7161
ATOM 4690 CG2 ILE H 51 12.451 -6.860 40.091 1.00 35,10 C
ATOM 4691 C ILE H 51 15.050 -5.549 38.867 1.00 33.61 C
ATOM 4692 O ILE H 51 15.658 -5.761 39.924 1.00 33.17 O
ATOM 4693 N ASN H 52 15.106 -4.380 38.211 1.00 36.13 N ATOM 4694 CA ASN H 52 15.794 -3.206 38.719 1.00 35.88 C
ATOM 4695 CB ASN H 52 16.431 -2.395 37.602 1.00 35.87 C
ATOM 4696 CG ASN H 52 17.133 -1.171 38.115 1.00 36.70 C
ATOM 4697 OD1 ASN H 52 16.794 -0.618 39.169 1.00 38.52 O
ATOM 4698 ND2 AS H 52 18.132 -0.716 37.392 1.00 37.81 N ATOM 4699 C ASN H 52 14.660 -2.448 39.405 1.00 35.33 C
ATOM 4700 O ASN H 52 13.697 -2.060 38.732 1.00 35.02 O
ATOM 4701 N PRO H 53 14.722 -2.294 40.755 1.00 35.99 N
ATOM 4702 CA PRO H 53 13,602 -1.623 41.467 1 .00 35.84 C
ATOM 4703 CB PRO H 53 13.841 -1.933 42.943 1.00 37.28 C ATOM 4704 CG PRO H 53 15.266 -2.402 43.022 1.00 37.53 C
ATOM 4705 CD PRO H 53 15.796 -2.730 41.677 1.00 37.47 C
ATOM 4706 C PRO H 53 13.490 -0.136 41.183 1.00 35.76 C
ATOM 4707 O PRO H 53 12.461 0.468 41.490 1.00 35.23 O
ATOM 4708 N ASN H 54 14.544 0.441 40.553 1 .00 35.74 N ATOM 4709 CA ASN H 54 14.558 1.848 40.204 1.00 35.61 C
ATOM 4710 CB ASN H 54 15.965 2.325 39.923 1.00 31.91 C
ATOM 4711 CG ASN H 54 16.777 2.344 41.176 1.00 33.76 C
ATOM 4712 OD1 ASN H 54 17.737 1.594 41.329 1.00 39.09 O
ATOM 4713 ND2 AS H 54 16.410 3.186 42.119 1.00 33.45 N ATOM 4714 C ASN H 54 13.592 2.176 39.083 1.00 35.42 C
ATOM 4715 O ASN H 54 12.747 3.050 39.249 1.00 35.56 O
ATOM 4716 N ASN H 55 13.690 1.457 37.966 1.00 35.33 N
ATOM 4717 CA ASN H 55 12.869 1 .672 36.791 1.00 35.14 C
ATOM 4718 CB ASN H 55 13.796 1.946 35.610 1.00 37.96 C ATOM 4719 CG ASN H 55 14.549 0.761 35.073 1.00 41.14 C
ATOM 4720 OD1 AS H 55 14.868 0.695 33.878 1.00 43.72 O
ATOM 4721 ND2 AS H 55 14.857 -0.205 35.914 1.00 44.14 N
ATOM 4722 C ASN H 55 11.840 0.567 36.462 1.00 34.70 C
ATOM 4723 O ASN H 55 10.960 0.795 35,628 1.00 35.15 O ATOM 4724 N GLY H 56 11.959 -0.602 37.090 1.00 31.80 N
ATOM 4725 CA GLY H 56 11.069 -1.723 36.820 1 ,00 31.01 C
ATOM 4726 C GLY H 56 11.526 -2.491 35.589 1.00 31.10 C
ATOM 4727 O GLY H 56 10.724 -3.177 34.949 1.00 30.58 O
ATOM 4728 N GLY H 57 12.820 -2.375 35.260 1.00 32,33 N ATOM 4729 CA GLY H 57 13.425 -3.027 34.098 1.00 32.32 C
ATOM 4730 C GLY H 57 13.715 -4.484 34,370 1.00 32,32 C
ATOM 4731 O GLY H 57 14.598 -4.784 35.174 1.00 32.90 O
ATOM 4732 N ALA H 58 12.956 -5.395 33.735 1.00 30.56 N
ATOM 4733 CA ALA H 58 13.077 -6.834 33.956 1.00 30.36 C ATOM 4734 CB ALA H 58 11.709 -7.455 34.213 1.00 29.63 C
ATOM 4735 C ALA H 58 13.807 -7.593 32.860 1.00 30.96 C
ATOM 4736 O ALA H 58 13.745 -7.234 31.679 1.00 31.12 O
ATOM 4737 N ILE H 59 14.539 -8.632 33.280 1.00 31.91 N
ATOM 4738 CA ILE H 59 15.252 -9.549 32.403 1.00 31.68 C ATOM 4739 CB ILE H 59 16.784 -9.523 32.573 1.00 32.42 C
ATOM 4740 CG1 !LE H 59 17.317 -8.143 32.167 1.00 31.40 C
ATOM 4741 CD1 ILE H 59 18.760 -7.920 32.404 1.00 31.91 C
ATOM 4742 CG2 ILE H 59 17.437 -10.637 31.756 1.00 30.36 C
ATOM 4743 C ILE H 59 14.609 -10.890 32.721 1.00 32.11 C JB2010.7161
ATOM 4744 O ILE H 59 14.363-11.177 33.896 1.0032.90 O
ATOM 4745 N TYR H 60 14.260- 1.66831.695 1.0032.48 N
ATOM 4746 CA TYR H 60 13.601 -12.93631.941 1.0032.29 C
ATOM 4747 CB TYR H 60 12.193-12.949 31.322 1.0031.67 C ATOM 4748 CG TYR H 60 11.248-11.91731.880 1.0031.25 C
ATOM 4749 CD1 TYR H 60 10.417-12.211 32.964 1.0031.40 C
ATOM 4750 CE1TYRH 60 9.528-11.26033.473 1.0031.06 C
ATOM 4751 CZ TYR H 60 9.451 -10.00632.879 1.0030.95 C
ATOM 4752 OH TYR H 60 8.597 -9.02733.334 1.0031.15 O ATOM 4753 CE2 TYR H 60 10.254 -9.70731.794 1.0029.14 C
ATOM 4754 CD2 TYR H 60 11.138-10.664 31.296 1.0030.46 C
ATOM 4755 C TYR H 60 14.347-14.09931.382 1.0032.47 C
ATOM 4756 O TYR H 60 15.019-13.981 30.356 1.0032.02 O
ATOM 4757 N ASN H 61 14.178-15.248 32.040 1.0034.06 N ATOM 4758 CA ASN H 61 14.689-16.501 31.573 1.0034.98 C
ATOM 4759 CB ASN H 61 14.575-17.547 32.661 1.0032.75 C
ATOM 4760 CG ASN H 61 14.974-18.94532.251 1.0031.32 C
ATOM 4761 OD1 ASN H 61 14.862-19.369 31.095 1.0031.54 O
ATOM 4762 ND2 ASN H 61 15.442-19.69033.206 1.0028.47 N ATOM 4763 C ASN H 61 13.692-16.80730.446 1.0036.49 C
ATOM 4764 O ASN H 61 12.486-16.894 30.700 1.0036.32 O
ATOM 4765 N GLN H 62 14.203-16.921 29.208 1.0040.25 N
ATOM 4766 CA GLN H 62 3.490-17.192 27.957 1.0042.61 C
ATOM 4767 CB GLN H 62 14.472-17.47326.806 1.0046.63 C ATOM 4768 CG GLN H 62 15.748-18.281 27.194 1.0051.33 C
ATOM 4769 CD GLN H 62 16.927-17.406 27.621 1.0055.11 C
ATOM 4770 OE1 GLN H 62 16.868-16.611 28.597 1.0053.73 O
ATOM 4771 NE2GL H 62 18.031 -17.54826.891 1.0056.37 N
ATOM 4772 C GLN H 62 12.427-18.266 28.057 1.0043.04 C ATOM 4773 O GLN H 62 11.409-18.168 27.384 1.0043.45 O
ATOM 4774 N LYS H 63 12.625-19.251 28.929 1.0043.48 N
ATOM 4775 CA LYS H 63 11.675-20.32829.180 1.0044.75 C
ATOM 4776 CB LYS H 63 12.313-21.339 30.150 1.0046.81 C
ATOM 4777 CG LYS H 63 11.330-22.346 30.717 1.0048.47 C ATOM 4778 CD LYS H 63 12.005-23.381 31.519 1.0050.88 C
ATOM 4779 CE LYS H 63 10.991 -24.339 32.050 1.0051.93 C
ATOM 4780 NZ LYS H 63 11.656-25.40632.830 1.0054.83 N
ATOM 4781 C LYS H 63 10.302-19.807 29.7 1 1.0045.59 C
ATOM 4782 O LYS H 63 9.295-20.496 29.545 1.0045.76 O ATOM 4783 N PHE H 64 10.280-18.607 30.358 1.0048.96 N
ATOM 4784 CA PHE H 64 9.099-17.937 30.942 1.0049.93 C
ATOM 4785 CB PHE H 64 9.288-17.70532.444 1.0049.86 C
ATOM 4786 CG PHE H 64 9.790-18.855 33.269 1.0050.13 C
ATOM 4787 CD1 PHE H 64 8.928-19.84933.695 1.0048.57 C ATOM 4788 CE1 PHE H 64 9.391 -20.892 34.474 1.0048.76 C
ATOM 4789 CZ PHE H 64 10.710-20.942 34.850 1.0048.36 C
ATOM 4790 CE2 HEH 64 11.571 -19.952 34.461 1.0048.71 C
ATOM 4791 CD2PHEH 64 11.114-18.906 33.680 1.0049.25 C
ATOM 4792 C PHE H 64 8.782-16.549 30.311 1.0051.38 C ATOM 4793 0 PHE H 64 7.921 -15.809 30.853 1.0052.00 O
ATOM 4794 N LYS H 65 9.485-16.16329.204 1.0054.08 N
ATOM 4795 CA LYS H 65 9.177-14.88228.574 1.0054.14 C
ATOM 4796 CB LYS Ή 65 10.224-14.500 27.508 1.0056.96 C
ATOM 4797 C LYS H 65 7.733-14.99627.993 1.0053.83 C JB2010.7161
ATOM 4798 O LYS H 65 7.327 -16.055 27.483 1.00 53.61 O
ATOM 4799 N GLY H 66 6.960 -13.934 28.168 1.00 53.49 N
ATOM 4800 CA GLY H 66 5.580 -13.887 27.700 1.00 52.48 C
ATOM 4801 C GLY H 66 4.595 -14.583 28.614 1.00 51.60 C ATOM 4802 O GLY H 66 3.393 -14.606 28.304 1.00 52.39 O
ATOM 4803 N A G H 67 5.090 -15.167 29.736 1.00 45.58 N
ATOM 4804 CA ARG H 67 4.244 -15.851 30.720 1.00 44.16 C
ATOM 4805 CB ARG H 67 4.558 -17.336 30.799 1.00 43.50 C
ATOM 4806 CG ARG H 67 3.705 -18.163 29.869 1.00 42.99 C ATOM 4807 CD ARG H 67 3.310 -19.486 30.465 1.00 42.63 C
ATOM 4808 NE ARG H 67 4.445 -20.270 30.957 1.00 41.04 N
ATOM 4809 CZ ARG H 67 4.412 -21.002 32.067 1.0040.29 C
ATOM 4810 NH1 ARG H 67 3.312 -21.049 32.807 1.0040.06 N
ATOM 4811 NH2 ARG H 67 5.475 -21.692 32.443 1.00 40.01 N ATOM 4812 C ARG H 67 4.426 -15.251 32.069 1.00 43.18 C
ATOM 4813 O ARG H 67 3.473 -15.137 32.837 1.00 42.46 O
ATOM 4814 N ALA H 68 5.666 -14.889 32.374 1.00 42.75 N
ATOM 4815 CA ALA H 68 6.018 -14.294 33.647 1.00 42.13 C
ATOM 4816 CB ALA H 68 7.318 -14.893 34.174 1.00 42.56 C ATOM 4817 C ALA H 68 6.150 -12.803 33.492 1.00 41.57 C
ATOM 4818 O ALA H 68 6.651 -12.322 32.475 1.00 42.01 O
ATOM 4819 N THR H 69 5.694 -12.072 34.489 1.00 38.81 N
ATOM 4820 CA THR H 69 5.789 -10.622 34.527 1.00 37.94 C
ATOM 4821 CB THR H 69 4.430 -9.928 34.216 1.00 37.21 C ATOM 4822 OG1 THR H 69 4.004 -10.287 32.903 1.00 37.48 O
ATOM 4823 CG2 THR H 69 4.520 -8.423 34.275 1.00 35.86 C
ATOM 4824 C THR H 69 6.350 -10.300 35.894 1.00 37.70 C
ATOM 4825 O THR H 69 5.813 -10.743 36.921 1.00 37.65 O
ATOM 4826 N LEU H 70 7.441 -9.569 35.908 1.00 36.37 N ATOM 4827 CA LEU H 70 8.068 -9.155 37.147 1.00 36.33 C
ATOM 4828 CB LEU H 70 9.577 -9.457 37.097 1.00 36.52 C
ATOM 4829 CG LEU H 70 10.125 -10.718 37.807 1.00 36.35 C
ATOM 4830 CD1 LEU H 70 9.231 -11.930 37.668 1 ,00 35.06 C
ATOM 4831 CD2 LEU H 70 11.478 -11.063 37.286 1.00 35.67 C ATOM 4832 C LEU H 70 7.810 -7.663 37.224 1.00 36.30 C
ATOM 4833 O LEU H 70 8.031 -6.955 36.238 1.00 36.51 O
ATOM 4834 N THR H 71 7.277 -7.189 38.360 1.00 35.94 N
ATOM 4835 CA THR H 71 6.992 -5.772 38.586 1.00 35.73 C
ATOM 4836 CB THR H 71 5.491 -5.424 38.394 1.00 33.76 C ATOM 4837 OG1 THR H 71 4.685 -6.130 39.340 1.00 33.22 O
ATOM 4838 CG2 THR H 71 4.999 -5.606 36.961 1.00 32.02 C
ATOM 4839 C THR H 71 7.443 -5.411 39.981 1.00 36.60 C
ATOM 4840 O THR H 71 7.740 -6.299 40.786 1.00 37.10 O
ATOM 4841 N VAL H 72 7.504 -4.110 40.270 1.00 39,56 N ATOM 4842 CA VAL H 72 7.852 -3.602 41.597 1.00 40.54 C
ATOM 4843 CB VAL H 72 9.337 -3.188 41.807 1.00 43.89 C
ATOM 4844 CG1 VAL H 72 10.262 -4.404 41.864 1.00 42.94 C
ATOM 4845 CG2 VAL H 72 9.802 -2.153 40.782 1.00 42.96 C
ATOM 4846 C VAL H 72 6.905 -2.474 41.956 1.00 41.56 C ATOM 4847 O VAL H 72 6.095 -2.056 41.121 1.00 41.80 O
ATOM 4848 N ASP H 73 6.989 -2.012 43.212 1.00 43.60 N
ATOM 4849 CA ASP H 73 6.249 -0.885 43.746 1.00 44.88 C
ATOM 4850 CB ASP H 73 4.883 -1.263 44.341 1.00 47.82 C
ATOM 4851 CG ASP H 73 4.072 -0.063 44.843 1.00 50.09 C JB20107161
ATOM 4852 OD1 ASP H 73 4.453 1.094 44.541 1.00 52.99 0
ATOM 4853 OD2 ASP H 73 3.068 -0.280 45.541 1.00 52.46 0
ATOM 4854 C ASP H 73 7.181 -0.214 44.743 1.00 45.05 C
ATOM 4855 O ASP H 73 7.290 -0.653 45.893 1.00 45.03 O ATOM 4856 N LYS H 74 7.892 0.829 44.262 1.00 44.09 N
ATOM 4857 CA LYS H 74 8.876 1 .623 45.009 1.00 44.46 C
ATOM 4858 CB LYS H 74 9.363 2.794 44.140 1.00 46.36 C
ATOM 4859 CG LYS H 74 10.723 2.61 1 43,495 1.00 47.03 C
ATOM 4860 CD LYS H 74 10.764 3.251 42.097 1.00 49.55 C ATOM 4861 CE LYS H 74 11 .207 4.696 42.049 1.00 49.1 1 C
ATOM 4862 NZ LYS H 74 12.699 4.833 42.128 1.00 51.92 N
ATOM 4863 C LYS H 74 8,272 2.172 46.307 1.00 44.71 C
ATOM 4864 O LYS H 74 8.929 2.151 47.354 1.00 44.47 O
ATOM 4865 N SER H 75 7.008 2.645 46.219 1.00 45.91 N ATOM 4866 CA SER H 75 6.244 3.239 47.307 1.00 46.63 C
ATOM 4867 CB SER H 75 4.935 3.820 46.773 1.00 50.56 C
ATOM 4868 OG SER H 75 3.783 3.062 47.107 1 .00 52.14 O
ATOM 4869 C SER H 75 6.002 2.275 48.471 1.00 46.54 C
ATOM 4870 O SER H 75 5.903 2.702 49.625 1.00 46.52 O ATOM 4871 N THR H 76 5.913 0.974 48.167 1.00 48.04 N
ATOM 4872 CA THR H 76 5.664 -0.031 49.190 1.00 47.46 C
ATOM 4873 CB THR H 76 4.250 -0.603 49.032 1.00 55.80 C
ATOM 4874 OG1 THR H 76 3.818 -1.1 19 50.287 1.00 56.91 O
ATOM 4875 CG2 THR H 76 4.157 -1.663 47.976 1.00 55.67 C ATOM 4876 C THR H 76 6.812 -1.019 49.444 1.00 46.86 C
ATOM 4877 O THR H 76 6.665 -1.888 50.314 1.00 46.89 O
ATOM 4878 N SER H 77 7.964 -0.872 48.715 1.00 43.60 N
ATOM 4879 CA SER H 77 9.149 -1.760 48.813 1.00 43.18 C
ATOM 4880 CB SER H 77 9.832 -1.620 50.176 1.00 46.46 C ATOM 4881 OG SER H 77 10.520 -0.388 50.289 1.00 47.06 O
ATOM 4882 C SER H 77 8.732 -3.226 48.562 1.00 42.36 C
ATOM 4883 O SER H 77 9.132 -4.141 49.290 1.00 42.38 O
ATOM 4884 N THR H 78 7.900 -3.426 47.543 1.0040.07 N
ATOM 4885 CA THR H 78 7,345 -4.721 47.192 1 .00 39.43 C ATOM 4886 CB THR H 78 5.841 -4.743 47.543 1.00 43.96 C
ATOM 4887 OG1 THR H 78 5.679 -4.333 48.893 1.00 44.36 O
ATOM 4888 CG2 THR H 78 5.212 -6.108 47.392 1.00 43.71 C
ATOM 4889 C THR H 78 7.608 -5.120 45.744 1.00 38.97 C
ATOM 4890 O THR H 78 7.375 -4.335 44.816 1.00 38.96 O ATOM 4891 N ALA H 79 8.066 -6.367 45.563 1.00 38.68 N
ATOM 4892 CA ALA H 79 8.307 -6.962 44.252 1 .00 38.65 C
ATOM 4893 CB ALA H 79 9.651 -7.682 44.230 1.00 38.91 C
ATOM 4894 C ALA H 79 7.164 -7.950 44.005 1.00 38.43 C
ATOM 4895 O ALA H 79 6.607 -8.510 44.954 1.00 38.06 O ATOM 4896 N TYR H 80 6.801 -8.138 42.738 1.00 39.56 N
ATOM 4897 CA TYR H 80 5.755 -9.077 42.361 1.00 39.75 C
ATOM 4898 CB TYR H 80 4.451 -8.381 41.929 1.00 41.50 C
ATOM 4899 CG TYR H 80 3.877 -7.440 42.957 1.00 42.25 C
ATOM 4900 CD1 TYR H 80 4.126 -6.070 42.891 1 .00 43.81 C ATOM 4901 CE1 TYR H 80 3.610 -5.194 43.845 1.00 45.50 C
ATOM 4902 CZ TYR H 80 2.828 -5.687 44.878 1.00 47.13 C
ATOM 4903 OH TYR H 80 2.327 -4.822 45,819 1 ,00 50.47 O
ATOM 4904 CE2 TYR H 80 2.565 -7.049 44.963 1.0045.06 C
ATOM 4905 CD2 TYR H 80 3.080 -7.914 43.997 1.00 43.03 C JB2010.7161
ATOM 4906 C TYR H 80 6.231 -9.937 41.228 1.00 39.61 C
ATOM 4907 O TYR H 80 7.072 -9.507 40.443 1.00 39.90 O
ATOM 4908 N MET H 81 5.693 -11.165 41.155 1.00 40,49 N
ATOM 4909 CA MET H 81 5.921 -12.126 40.098 1.00 40.76 C ATOM 4910 CB MET H 81 6.877 -13.250 40.476 1.00 44.10 C
ATOM 4911 CG MET H 81 7.023 -14.272 39.345 1.00 46.08 C
ATOM 4912 SD MET H 81 7.005 -15.957 39.951 1.00 52.30 S
ATOM 4913 CE MET H 81 5.265 -16.251 40.216 1.00 50.75 C
ATOM 4914 C MET H 81 4.582 -12.705 39.71 1 1.00 40.40 C ATOM 4915 O MET H 81 3.904 -13.334 40.527 1.00 39.80 O
ATOM 4916 N GLU H 82 4.209 -12.483 38.462 1.00 40.17 N
ATOM 4917 CA GLU H 82 2.989 -13.014 37.912 1.00 40.31 C
ATOM 4918 CB GLU H 82 2.191 -11.919 37.188 1.0042.84 C
ATOM 4919 CG GLU H 82 0.901 -12.425 36.566 1.00 46.03 C ATOM 4920 CD GLU H 82 0.120 -11.362 35.825 1.00 50.45 C
ATOM 4921 OE1 GLU H 82 0.116 -11.386 34.573 1.00 51.84 O
ATOM 4922 OE2 GLU H 82 -0.482 -10.494 36.498 1.00 51.93 O
ATOM 4923 C GLU H 82 3.381 -14.1 11 36.939 1.00 39.36 C
ATOM 4924 O GLU H 82 4.218 -13.878 36.070 1.00 39.31 O ATOM 4925 N LEU H 83 2.797 -15.294 37.073 1.00 35.96 N
ATOM 4926 CA LEU H 83 3.070 -16.375 36.121 1.00 35,08 C
ATOM 4927 CB LEU H 83 3.801 -17.555 36.769 1.00 33.73 C
ATOM 4928 CG LEU H 83 4.336 -18.646 35.833 1.00 32.25 C
ATOM 4929 CD1 LEU H 83 5.306 -18.082 34.806 1.00 29.34 C ATOM 4930 CD2 LEU H 83 4.946 -19.799 36.642 1.00 27.95 C
ATOM 4931 C LEU H 83 1.716 -16.769 35.563 1.00 35.35 C
ATOM 4932 O LEU H 83 0.827 -17.132 36.328 1.00 35.78 O
ATOM 4933 N ARG H 84 1.531 -16.606 34.257 1.00 36.94 N
ATOM 4934 CA ARG H 84 0.265 -16.896 33.590 1.00 37.22 C ATOM 4935 CB ARG H 84 -0.053 -15.81 32.560 1.00 38.41 C
ATOM 4936 CG ARG H 84 -0.244 -14.445 33.162 1.00 38.93 C
ATOM 4937 CD ARG H 84 -0.398 -13.405 32.070 1.00 37.60 C
ATOM 4938 NE ARG H 84 0.795 -13.281 31.224 1.00 37.61 N
ATOM 4939 CZ ARG H 84 1.883 -12.589 31.559 1.00 37.93 C ATOM 4940 NH1 ARG H 84 1.948 -11.967 32.734 1.00 35.84 N
ATOM 4941 NH2 ARG H 84 2.921 -12.527 30.729 1.00 37.18 N
ATOM 4942 C ARG H 84 0.270 -18.269 32.924 1.00 37.57 C
ATOM 4943 O ARG H 84 1.343 -18.865 32.815 1.00 37.43 O
ATOM 4944 N SER H 85 -0.940 -18.761 32.469 1.00 40.08 N ATOM 4945 CA SER H 85 -1.170 -20.052 31.798 1.00 40.28 C
ATOM 4946 CB SER H 85 -0.710 -20.016 30.342 1.00 44.33 C
ATOM 4947 OG SER H 85 -0.907 -18.746 29.748 1.00 46.34 O
ATOM 4948 C SER H 85 -0.385 -21.107 32.544 1.00 40.47 C
ATOM 4949 O SER H 85 0.529 -21.743 31.978 1.00 40.81 O ATOM 4950 N LEU H 86 -0.682 -21.240 33.841 1.00 37.74 N
ATOM 4951 CA LEU H 86 0.042 -22.178 34.694 1.00 37.31 C
ATOM 4952 CB LEU H 86 -0.400 -22.040 36.171 1.00 35,82 C
ATOM 4953 CG LEU H 86 -0.108 -20.710 36.907 1.00 33.72 C
ATOM 4954 CD1 LEU H 86 -0.741 -20.698 38.234 1.00 31.78 C ATOM 4955 CD2 LEU H 86 1.344 -20.487 37.133 1.00 30.33 C
ATOM 4956 C LEU H 86 -0.068 -23.613 34.197 1.00 37.44 C
ATOM 4957 O LEU H 86 -1.147 -24.039 33.798 1.00 37.39 O
ATOM 4958 N ARG H 87 1.078 -24.323 34.153 1.00 39.75 N
ATOM 4959 CA ARG H 87 1.204 -25.737 33.761 1.00 40.02 C JB2010.7161
ATOM 4960 CB ARG H 87 2.538 -26.025 33.040 1.0046.07 C
ATOM 4961 CG ARG H 87 3.162-24.97532.138 1.0049.17 C
ATOM 4962 CD ARG H 87 3.961 -25.643 31.016 1.0055.18 C
ATOM 4963 NE ARG H 87 4.710-24,698 30.166 1,0062.43 N ATOM 4964 CZ ARG H 87 4.178-23.758 29.366 1.0065.67 C
ATOM 4965 NH1 ARG H 87 4.967-22.976 28.635 1.0066,58 N
ATOM 4966 NH2ARGH 87 2.857-23.58029.313 1,0066.85 N
ATOM 4967 C ARG H 87 1.278-26.475 35.088 1.0039.32 C
ATOM 4968 O ARG H 87 1.607-25.840 36.076 1.0039.93 O ATOM 4969 N SER H 88 1.034-27.795 35.145 1.0039.07 N
ATOM 4970 CA SER H 88 1.152-28.496 36.437 1.0038.47 C
ATOM 4971 CB SER H 88 0.481 -29.861 36.399 1.0042.09 C
ATOM 4972 OG SER H 88 1.313-30.78935,726 1.0042.47 O
ATOM 4973 C SER H 88 2.625-28.617 36.848 1.0037.93 C ATOM 4974 O SER H 88 2.914-28.680 38.033 1,0037.45 O
ATOM 4975 N ASP H 89 3.561 -28.593 35.871 1.0039.35 N
ATOM 4976 CA ASP H 89 4.978-28.652 36.176 1.0039.09 C
ATOM 4977 CB ASP H 89 5.802-29.252 35.029 1.0043.14 C
ATOM 4978 CG ASP H 89 5.857-28.444 33.753 1.0046.42 C ATOM 4979 OD1 ASP H 89 5.177-27.395 33.682 1.0050.34 O
ATOM 4980 OD2ASPH 89 6,591 -28.859 32.817 1.0049.07 O
ATOM 4981 C ASP H 89 5.495-27.302 36.652 1.0038.27 C
ATOM 4982 O ASP H 89 6.700-27.137 36.840 1.0038.94 O
ATOM 4983 N ASP H 90 4,581 -26.340 36.867 1.0034.36 N ATOM 4984 CA ASP H 90 4.891 -25.026 37.414 1.0033.25 C
ATOM 4985 CB ASP H 90 3.992 -23.924 36.830 1.0034.96 C
ATOM 4986 CG ASP H 90 4.457-23.330 35.508 1.0036.50 C
ATOM 4987 OD1 ASP H 90 5.701 -23,326 35.242 1,0038.06 O
ATOM 4988 OD2 ASP H 90 3.597-22.862 34.742 1.0039.01 O ATOM 4989 C ASP H 90 4.752 -25.094 38.933 1.0032.30 C
ATOM 4990 O ASP H 90 4.973-24.081 39.597 1.0032.26 O
ATOM 4991 N THR H 91 4.387-26.292 39.487 1.0031.70 N
ATOM 4992 CA THR H 91 4.248-26.58340.934 1.0030.50 C
ATOM 4993 CB THR H 91 3.627-27.97541.179 1.0031.21 C ATOM 4994 OG1 THR H 91 2.343-28.01940.548 1.0031.96 O
ATOM 4995 CG2THRH 91 3.497-28.32042.672 1.0029,18 C
ATOM 4996 C THR H 91 5.648-26.47941.537 1.0030,09 C
ATOM 4997 0 THR H 91 6.565-27.19241.099 1.0030.40 O
ATOM 4998 N ALA H 92 5.820-25,56442.501 1.0027.54 N ATOM 4999 CA ALA H 92 7.113-25.29343.101 1.0027.08 C
ATOM 5000 CB ALA H 92 8.039-24.71542.023 1.0027.16 C
ATOM 5001 C ALAH 92 6.985-24.26244.214 1.0027.49 C
ATOM 5002 O ALAH 92 5.937-23.61344.370 1.0027,34 O
ATOM 5003 N VAL H 93 8.095 -24.08744.956 1.0028.68 N ATOM 5004 CA VAL H 93 8.236 -23.08245.992 1.0029.08 C
ATOM 5005 CB VAL H 93 9.024-23.575 47.217 1.0031.38 C
ATOM 5006 CG1VALH 93 9.225-22.44848.214 1.0030.97 C
ATOM 5007 CG2VALH 93 8.315-24.73347.882 1.0029.73 C
ATOM 5008 C VAL H 93 8.960-21.95045.245 1.0029.78 C ATOM 5009 O VAL H 93 10.013-22.19044.646 1.0030.76 O
ATOM 5010 N TYRH 94 8.366-20.75045.237 1.0029.08 N
ATOM 5011 CA TYRH 94 8.860-19.551 44.566 1.0029.17 C
ATOM 5012 CB TYRH 94 7.700-18.821 43.850 1.0029.17 C
ATOM 5013 CG TYRH 94 7.230-19.591 42.633 1.0030.73 C JB2010.7161
ATOM 5014 CD1TYRH 94 7.592-19.19241.346 1.0029.47 C
ATOM 5015 CE1 TYRH 94 7.202-19.92640.228 1.0027.65 C
ATOM 5016 CZ TYRH 94 6.464-21.091 40.392 1.0028.93 C
ATOM 5017 OH TYRH 94 6.084-21.844 39.310 1.0031.00 O ATOM 5018 CE2 TYRH 94 6.101 -21.51341.656 1.0028.56 C
ATOM 5019 CD2TYRH 94 6.483-20.76642.768 1.0030.16 C
ATOM 5020 C TYRH 94 9.538-18.65045.585 1.0029.49 C
ATOM 5021 O TYRH 94 8.953-18.332 46.622 1.0029.34 O
ATOM' 5022 N TYRH 95 10.772-18.24845.295 1.0028.90 N ATOM 5023 CA TYRH 95 11.537-17.38946.162 1.0029.15 C
ATOM 5024 CB TYRH 95 12.858-18.06446.529 1.0028.29 C
ATOM 5025 CG TYRH 95 12.748-19.29747.385 1.0027.68 C
ATOM 5026 CD1 TYRH 95 12.695-19.20348.772 1.0027.06 C
ATOM 5027 CE1TYRH 95 12.620-20.34049.567 1.0026.75 C ATOM 5028 CZ TYRH 95 12.635-21.59448.980 1.0027.72 C
ATOM 5029 OH TYRH 95 12.547-22.72249.765 1.0029.10 O
ATOM 5030 CE2TYRH 95 12.736-21.71347.607 1.0026.18 C
ATOM 5031 CD2 TYR H 95 12.795-20.56946.819 1.0027.03 C
ATOM 5032 C TYRH 95 11.928-16.10845.463 1.0030.36 C ATOM 5033 O TYR H 95 12.384-16.141 44.309 1.0030.54 O
ATOM 5034 N CYS H 96 11.827-14.98346.188 1.0032.42 N
ATOM 5035 CA CYS H 96 12.353-13.72445.717 1.0033.74 C
ATOM 5036 CB CYS H 96 1.451 -12.54246.050 1.0035.01 C
ATOM 5037 SG CYS H 96 11.029-12.40247.800 1.0041.45 S ATOM 5038 C CYS H 96 13.708-13.65946.469 1.0033.69 C
ATOM 5039 O CYS H 96 13.801 -14.04047.641 1.0033.77 O
ATOM 5040 N THR H 97 14.770-13.26245.776 1.0034.56 N
ATOM 5041 CA THR H 97 16.100-13.17446.370 1.0034.49 C
ATOM 5042 CB THR H 97 16.868-14.50346.337 1.0030.99 C ATOM 5043 OG1 THR H 97 18.158-14.28946.930 1.0031.12 O
ATOM 5044 CG2THRH 97 16.996-15.11444.939 1.0027.91 C
ATOM 5045 C THR H 97 16.881 -11.998 45.837 1.0035.36 C
ATOM 5046 O THR H 97 16.789-11.69844.650 1.0035.40 O
ATOM 5047 N SER H 98 17.628-11.31846.726 1.0034.13 N ATOM 5048 CA SER H 98 18.456-10.17946.385 1.0035.08 C
ATOM 5049 CB SER H 98 17.777 -8.87546.767 1.0035.74 C
ATOM 5050 OG SER H 98 17.731 -8.69648.167 1.0035.51 O
ATOM 5051 C SER H 98 19.816-10.34047.047 1.0036.31 C
ATOM 5052 O SER H 98 20.009-11.26847.840 1.0036.87 O ATOM 5053 N GLY H 99 20.764 -9.48046.684 1.0037.34 N
ATOM 5054 CA GLY H 99 22.105 -9.55347.238 1.0038.31 C
ATOM 5055 C GLY H 99 23.055 -8,47846.772 1.0039.06 C
ATOM 5056 O GLY H 99 22.700 -7.611 45.959 1.0039.08 O
ATOM 5057 N !LE H 100 24.281 -8.54747.305 1.0038.95 N ATOM 5058 CA ILE H 100 25.340 -7.59947.020 1.0040.13 C
ATOM 5059 CB ILE H 100 25.140 -6.25647.805 1.0042.20 C
ATOM 5060 CG1 ILEH 100 26.069 -5.121 47.313 1.0042.37 C
ATOM 5061 CD1 ILE H 100 25.744 -4.59545.877 1.0043.04 C
ATOM 5062 CG2ILEH 100 25.130 -6.42649.330 1.0040.23 C ATOM 5063 C ILE H 100 26.728 -8.18647.196 1.0041.35 C
ATOM 5064 O ILE H 100 27.060 -8.671 48.274 1.0041.53 O
ATOM 5065 N ILE H 101 27.525 -8.156 46.129 1.0044.91 N
ATOM 5066 CA ILE H 101 28.906 -8.59446.151 1.0046.66 C
ATOM 5067 CB ILE H 101 29.304 -9.331 44.856 1.0048.93 C JB2010.7161
ATOM 5068 CG1 ILE H 101 28.684 -10.741 44.774 1.00 48.02 C
ATOM 5069 CD1 ILE H 101 28.863 -11.484 43.376 1.00 46.04 C
ATOM 5070 CG2 ILE H 101 30.830 -9.364 44.707 1.00 48.63 C
ATOM 5071 C ILE H 101 29.645 -7.249 46.324 1.00 48.39 C ATOM 5072 O ILE H 101 29.673 -6.407 45.409 1.00 49.10 O
ATOM 5073 N THR H 102 30.154 -7.018 47.527 1.00 53.02 N
ATOM 5074 CA THR H 102 30.862 -5.802 47.911 1.00 54.64 C
ATOM 5075 CB THR H 102 29.844 -4.709 48.295 1.00 57.94 C
ATOM 5076 OG1 THR H 102 30.542 -3.493 48.467 1.00 58.87 O ATOM 5077 CG2 THR H 102 29.063 -5.030 49.554 1.00 57.98 C
ATOM 5078 C THR H 102 31.909 -6.182 48.982 1.00 55.73 C
ATOM 5079 O THR H 102 32.287 -7.365 49.048 1.00 55.75 O
ATOM 5080 N GLU H 103 32.384 -5.213 49.815 1.00 60.61 N
ATOM 5081 CA GLU H 103 33.353 -5.551 50.865 1.00 61.61 C ATOM 5082 CB GLU H 103 33.831 -4.314 51.662 1.00 64.25 C
ATOM 5083 CG GLU H 103 34.914 -4.619 52.703 1.00 67.99 C
ATOM 5084 CD GLU H 103 36.021 -5.604 52.336 1.00 72.61 C
ATOM 5085 OE1 GLU H 103 36.476 -5.599 51.165 1.00 73.35 O
ATOM 5086 OE2 GLU H 103 36.436 -6.380 53.232 1.00 73.54 O ATOM 5087 C GLU H 103 32.709 -6.598 51.766 1.00 60.94 C
ATOM 5088 O GLU H 103 33.245 -7.702 51.904 1.00 60.83 O
ATOM 5089 N ILE H 104 31.520 -6.266 52.303 1.00 58.77 N
ATOM 5090 CA ILE H 104 30.728 -7.160 53.134 1.00 57.69 C
ATOM 5091 CB ILE H 104 30.207 -6.434 54.412 1.00 60.80 C ATOM 5092 CG1 ILE H 104 31.348 -5.716 55.219 1.00 61.34 C
ATOM 5093 CD1 ILE H 104 32.692 -6.537 55.580 1.00 61.00 C
ATOM 5094 CG2 ILE H 104 29.350 -7.346 55.296 1.00 60.83 C
ATOM 5095 C ILE H 104 29.619 -7.698 52.217 1.00 56.89 C
ATOM 5096 O ILE H 104 28.593 -7.031 52.022 1.00 56.88 O ATOM 5097 N ALA H 105 29.864 -8.890 51.615 1.00 54.42 N
ATOM 5098 CA ALA H 105 28.935 -9.570 50.701 1.00 53.29 C
ATOM 5099 CB ALA H 105 29.660 - 0.615 49.872 1.00 53.60 C
ATOM 5100 C ALA H 105 27.785 -10.202 51.460 1.00 52.34 C
ATOM 5101 O ALA H 105 28.001 -10.855 52.469 1.00 52.43 O ATOM 5102 N GLU H 106 26.559 -9.992 50.988 1.00 50.41 N
ATOM 5103 CA GLU H 106 25.353 -10.515 51.629 1.00 49.37 C
ATOM 5104 CB GLU H 106 24.671 -9.418 52.455 1.00 50.89 C
ATOM 5105 CG GLU H 106 25.547 -8.694 53.455 1.00 52.55 C
ATOM 5106 CD GLU H 106 24.775 -7.645 54.233 1.00 55.73 C ATOM 5107 OE1 GLU H 106 23.922 -8.046 55.063 1.00 57.24 O
ATOM 5108 OE2 GLU H 106 25.009 -6.430 54.008 Ί .00 56.45 O
ATOM 5109 C GLU H 106 24.351 -10.980 50.591 1.00 48.34 C
ATOM 5110 O GLU H 106 24.347 -10.485 49.465 1 .00 48.32 O
ATOM 51 11 N ASP H 107 23.480 -11.914 50.986 1.00 46.83 N ATOM 51 12 CA ASP H 107 22.401 -12.427 50.147 1.00 45.62 C
ATOM 5113 CB ASP H 107 22.777 -13.754 49.468 1.00 47.87 C
ATOM 5114 CG ASP H 107 22.576 -15.008 50.291 1.00 49.03 C
ATOM 5115 OD1 ASP H 107 22.962 -15.008 51.486 1.00 51.82 O
ATOM 5116 OD2 ASP H 107 22.045 -15.991 49.744 1.00 48.51 O ATOM 5117 C ASP H 107 21.160 -12.533 51.018 1.00 44.28 C
ATOM 5118 0 ASP H 107 21.269 -12.875 52.189 1.00 44.54 O
ATOM 5119 N PHE H 108 20.000 -12.195 50.470 1.0040.84 N
ATOM 5120 CA PHE H 108 18.733 -12.221 51.184 1.00 39.40 C
ATOM 5121 CB PHE H 108 18.199 -10.794 51.403 1.00 41.16 C JB2010.7161
ATOM 5122 CG PHE H 108 19.290 -9.805 51.729 1.0042.98 C
ATOM 5123 CD1 PHE H 108 19.928 -9.82852.967 1.0043.66 C
ATOM 5124 CE1 HEH 108 20.954 -8.924 53.263 1.0044.22 C
ATOM 5125 CZ PHE H 108 21.364 -8.01652.312 1.0044.60 C ATOM 5126 CE2 PHE H 108 20.759 -7.997 51.067 1.0045.37 C
ATOM 5127 CD2 PHE H 108 9.729 -8.89250.777 1.0044.02 C
ATOM 5128 C PHE H 108 17.750-13.03550.392 1.0038.33 C
ATOM 5129 0 PHE H 108 17.775-13.001 49.164 1.0038.44 O
ATOM 5130 N TRPH 109 16.893-13.788 51.093 1.0034.79 N ATOM 5131 CA TRPH 109 15.877-14.625 50.482 1.0032.79 C
ATOM 5132 CB TR H 109 16.317-16.073 50.541 1.0030.93 C
ATOM 5133 CG TRP H 109 17.423-16.43849.596 1.0030.32 C
ATOM 5134 CD1 TRPH 109 18.756-16.17549.740 1.0028.01 C
ATOM 5135 NE1 TRP H 109 19.464-16.73648.706 1.0026.73 N ATOM 5136 CE2 TRPH 109 18.595-17.40547.879 1.0026.51 C
ATOM 5137 CD2 TRPH 109 17.298-17.25248.421 1.0028.55 C
ATOM 5138 CE3 TRP H 109 16.211 -17.84047.758 1.0026.57 C
ATOM 5139 CZ3 TRP H 109 16.450-18.53646.587 1.0028.11 C
ATOM 5140 CH2 TRP H 109 17.752-18.67846.074 1.0026.55 C ATOM 5141 CZ2 TRPH 109 18.836-18.13246.709 1.0026.03 C
ATOM 5142 C TRPH 109 14.522-14.48551.170 1.0032.49 C
ATOM 51430 TRPH 109 14.437-14.15252.349 1.0031.70 O
ATOM 5144 N GLY H 110 13.466-14.755 50.423 1.0032.00 N
ATOM 5145 CA GLY H 110 12.127-14.72550.969 1.0031.63 C ATOM 5146 C GLY H 110 11.931 -16.05551.652 1.0031.48 C
ATOM 51470 GLY H 110 12.811 -16.93051.585 1.0030.61 O
ATOM 5148 N GLN H 111 10.788-16.241 52.319 1.0032.17 N
ATOM 5149 CA GLN H 111 10.565-17.52952.973 1.0032. 5 C
ATOM 5150 CB GLN H 111 9.540-17.382 54.111 1.0032.48 C ATOM 5151 CG GLN H 111 8.073-17.27353.657 1.0033.06 C
ATOM 5152 CD GLN H 111 7.616-15.865 53.394 1.0035.58 C
ATOM 5153 OE1 GLN H 111 8.374-14.985 52.939 1.0037.87 O
ATOM 5154 NE2 GLN H 111 6.347-15.62853.662 1.0035.46 N
ATOM 5155 C GLN H 111 10.092-18.558 51.913 1.0032.38 C ATOM 5156 0 GLN H 111 9.980-19.75052.213 1.0032.74 O
ATOM 5157 N GLY H 112 9.793-18.074 50.708 1.0030.97 N
ATOM 5158 CA GLY H 112 9.284-18.90749.636 1.0030.95 C
ATOM 5159 C GLY H 112 7.770-18.99949.666 1.0031.30 C
ATOM 5160 O GLY H 112 7.147-18.808 50.721 1.0030.98 O ATOM 5161 N THR H 113 7.172-19.27948.492 1.0033.14 N
ATOM 5162 CA THR H 113 5.730-19.44548.321 1.0034.00 C
ATOM 5163 CB THR H 113 5.064-18.20047.678 1.0039.72 C
ATOM 5164 OG1 THR H 113 5.278-17.07848.523 1.0041.05 O
ATOM 5165 CG2 THR H 113 3,559-18.36747.493 1.0039.55 C ATOM 5166 C THR H 113 5.442-20.71947.532 1.0033.87 C
ATOM 5167 0 THR H 113 5.842-20.81546.380 1.0033.36 O
ATOM 5168 N LEU H 114 4.716-21.66848.137 1.0033.36 N
ATOM 5169 CA LEU H 114 4.348-22.88747.440 1.0033.18 C
ATOM 5170 CB LEU H 114 4.008-24.03248.414 1.0032.10 C ATOM 5171 CG LEU H 114 3.429-25.29947.784 1.0032.52 C
ATOM 5172 CD1 LEU H 114 4.495-26.11346.981 1.0032.96 C
ATOM 5173.CD2 LEU H 114 2.729-26.14548.814 1.0031.61 C
ATOM 5174 C LEU H 114 3.157-22.57946.531 1.0033.46 C
ATOM 5175 O LEU H 114 2.122-22.07746.992 1.0033.61 O JB2010.7161
ATOM 5176 N VALH 115 3.321 -22.85745.234 1.0033.02 N
ATOM 5177 CA VALH 115 2.275-22.67444.236 1.0032.90 C
ATOM 5178 CB VALH 115 2.607-21.60643.157 1.0035.77 C
ATOM 5179 CG1 VALH 115 1.467-21.45642.147 1.0035.48 C ATOM 5180 CG2 VALH 115 2.957-20.25543.795 1.0035.38 C
ATOM 5181 C VALH 115 2.031 -24.07443.665 1.0033.24 C
ATOM 5182 O VALH 115 2.902-24.651 43.008 1.0033.16 O
ATOM 5183 N THRH 116 0.869-24.641 43.989 1.0034.85 N
ATOM 5184 CA THR H 116 0.509-25.95743.503 1.0035.27 C ATOM 5185 CB THR H 116 -0.159-26.80344.601 1.0036.94 C
ATOM 5186 OG1 THR H 116 0.649-26.75745.773 1.0036.22 O
ATOM 5187 CG2 THR H 116 -0,360-28.25444.174 1.0035.44 C
ATOM 5188 C THR H 116 -0.398-25.77342.288 1.0035.86 C
ATOM 51890 THR H 116 -1.443-25.12942.417 1,0036.38 O ATOM 5190 N VALH 117 0.011 -26.31341.120 1.0034.74 N
ATOM 5191 CA VALH 117 -0.774-26.25939.897 1.0035.49 C
ATOM 5192 CB VALH 117 -0.083-25.582 38.683 1.0038,05 C
ATOM 5193 CG1 VALH 117 -1.092-25.343 37.561 1.0036.70 C
ATOM 5194 CG2 VALH 117 0.637-24.284 39.073 1.0037.66 C ATOM 5195 C VALH 117 -1.184-27.70539.584 1.0036.66 C
ATOM 5196 O VALH 117 -0.330-28.566 39.326 1.0036.06 O
ATOM 5197 N SER H 118 -2.501 -27.963 39.615 1,0040.15 N
ATOM 5198 CA SER H 118 -3.073-29.278 39.369 1.0041.03 C
ATOM 5199 CB SER H 118 -2.808-30,161 40.589 1.0043.44 C ATOM 5200 OG SER H 118 -3.598-31.33440.645 1.0043.97 O
ATOM 5201 C SER H 118 -4.590-29.206 39.095 1.0041.66 C
ATOM 5202 O SER H 118 -5.283-28.303 39.601 1.0041.95 O
ATOM 5203 N SER H 119 -5.103-30.210 38.339 1.0042.75 N
ATOM 5204 CA SER H 119 -6.521 -30.412 38.008 1.0042.86 C ATOM 5205 CB SER H 119 -6.675-31.610 37.085 1.0046.76 C
ATOM 5206 OG SER H 119 -5.866-31.48235.932 1.0048.92 O
ATOM 5207 C SER H 119 -7.303-30.747 39.276 1.0043.18 C
ATOM 5208 O SER H 119 -8.541 -30.649 39.268 1.0044.08 O
ATOM 5209 N ALA H 120 -6.588-31.18640.358 1.0040.98 N ATOM 5210 CA ALA H 120 -7.178-31.57941.629 1.0041.20 C
ATOM 5211 CB ALA H 120 -6.133-32.20742.530 1.0041.61 C
ATOM 5212 C ALA H 120 -7.875-30.42642.325 1.0041.51 C
ATOM 5213 O ALA H 120 -7.539-29.261 42.100 1.0041.99 O
ATOM 5214 N SER H 121 -8.865-30.75743.154 1.0042.89 N ATOM 5215 CA SER H 121 -9.667-29.80043.910 1.0043.14 C
ATOM 5216 CB SER H 121 -11.147-30.11743.737 1.0046.93 C
ATOM 5217 OG SER H 121 -11.435-30.48442.397 1.0048.04 O
ATOM 5218 C SER H 121 -9.272-29.92745.363 1.0042.82 C
ATOM 52190 SER H 121 -8.983-31.03445.796 1.0043.44 O ATOM 5220 N THR H 122 -9.224-28.82946.121 1.0041.94 N
ATOM 5221 CA THR H 122 -8.813-28.96547.515 1.0041.52 C
ATOM 5222 CB THR H 122 -8.398-27.66348.220 1.0039.57 C
ATOM 5223 OG1 THR H 122 -9.047-27.56549.492 1.0038.83 O
ATOM 5224 CG2 THR H 122 -8.519-26.41447.348 1.0038.63 C ATOM 5225 C THR H 122 -9.681 -29.95748.267 1.0041.75 C
ATOM 5226 0 THR H 122 -10.901 -29.89448.165 1.0041.91 O
ATOM 5227 N LYS H 123 -9.039-30.938 48.924 1.0042.28 N
ATOM 5228 CA LYS H 123 -9.709-32.02849.640 1.0042.34 C
ATOM 5229 CB LYS H 123 -9.748-33.27548.732 1.0044.49 C JB2010.7161
ATOM 5230 CG LYS H 123 -10.679 -34.360 49.230 1.00 45.57 C
ATOM 5231 CD LYS H 123 -10.496 -35.692 48.507 1.00 47.72 C
ATOM 5232 CE LYS H 123 -1 1.262 -36,796 49.228 1.0049.42 C
ATOM 5233 NZ LYS H 123 -10,689 -37.163 50.577 1.00 51.60 N ATOM 5234 C LYS H 123 -8.991 -32.357 50.948 1.00 41.90 C
ATOM 5235 O LYS H 123 -7.755 -32.376 50.989 1.00 41 ,91 O
ATOM 5236 N GLY H 124 -9.778 -32.609 51.991 1.00 40.43 N
ATOM 5237 CA GLY H 124 -9.295 -32.986 53.317 1.00 40.19 C
ATOM 5238 C GLY H 124 -8.870 -34.450 53.342 1.00 40.25 C ATOM 5239 0 GLY H 124 -9.370 -35.263 52.541 1.00 39.78 O
ATOM 5240 N PRO H 125 -7.925 -34.847 54.229 1.00 40.21 N
ATOM 5241 CA PRO H 125 -7.482 -36.245 54.211 1.00 40.07 C
ATOM 5242 CB PRO H 125 -6.140 -36.184 54.929 1 ,00 41.43 C
ATOM 5243 CG PRO H 125 -6.324 -35.100 55.933 1.00 41 .68 C ATOM 5244 CD PRO H 125 -7.183 -34.066 55.245 1.00 41.27 C
ATOM 5245 C PRO H 125 -8.404 -37.229 54.903 1.00 39.77 C
ATOM 5246 0 PRO H 125 -9.165 -36.871 55.815 1.00 38.97 O
ATOM 5247 N SER H 126 -8.291 -38.485 54.463 1.00 39.77 N
ATOM 5248 CA SER H 126 -8.972 -39.616 55.048 1.00 40.54 C ATOM 5249 CB SER H 126 -9.378 -40.620 53.974 1.00 45.57 C
ATOM 5250 OG SER H 126 -10.620 -40.281 53.367 1.0047.93 O
ATOM 5251 C SER H 126 -7.890 -40.169 56.012 1 ,00 40.47 C
ATOM 5252 0 SER H 126 -6.758 -40.475 55.575 1.00 41.10 O
ATOM 5253 N VAL H 127 -8.193 -40.198 57.331 1.00 38.55 N ATOM 5254 CA VAL H 127 -7.207 -40.650 58.316 1.00 38.28 C
ATOM 5255 CB VAL H 127 -6.957 -39.612 59.469 1.00 41.68 C
ATOM 5256 CG1 VAL H 127 -5.831 -40.060 60.399 1.00 42.88 C
ATOM 5257 CG2 VAL H 127 -6.634 -38.229 58.900 1.00 41.41 C
ATOM 5258 C VAL H 127 -7.520 -42.075 58.773 1.00 37.82 C ATOM 5259 O VAL H 127 -8.504 -42.293 59.473 1.00 37.19 O
ATOM 5260 N PHE H 128 -6.698 -43.054 58.334 1.00 37.96 N
ATOM 5261 CA PHE H 128 -6.897 -44.469 58.693 1.00 37.97 C
ATOM 5262 CB PHE H 128 -6.894 -45,378 57.448 1 ,00 38.56 C
ATOM 5263 CG PHE H 128 -7.894 -44.977 56.401 1.00 39.12 C ATOM 5264 CD1 PHE H 128 -9.254 -44.918 56.699 1.00 39.77 C
ATOM 5265 CE1 PHE H 128 -10.187 -44.524 55.731 1.00 37.84 C
ATOM 5266 CZ PHE H 128 -9.767 -44.203 54.461 1.00 38.59 C
ATOM 5267 CE2 PHE H 128 -8.418 -44.244 54.149 1.00 39.97 C
ATOM 5268 CD2 PHE H 128 -7.483 -44.644 55.118 1 .00 39.73 C ATOM 5269 C PHE H 128 -5.856 -44.949 59.685 1.00 37.91 C
ATOM 5270 O PHE H 128 -4.705 -44.542 59.556 1.00 37.67 O
ATOM 5271 N PRO H 129 -6.210 -45.822 60.663 1.00 38.44 N
ATOM 5272 CA PRO H 129 -5.182 -46.318 61.601 1.00 38.45 C
ATOM 5273 CB PRO H 129 -6.011 -46.978 62,713 1.00 39,86 C ATOM 5274 CG PRO H 129 -7.245 -47.470 62.014 1.00 39.14 C
ATOM 5275 CD PRO H 129 -7.535 -46.415 60.957 1.00 39.73 C
ATOM 5276 C PRO H 129 -4.269 -47.374 60.991 1.00 38.59 C
ATOM 5277 O PRO H 129 -4.677 -48.158 60.126 1.00 38.45 O
ATOM 5278 N LEU H 130 -3.035 -47.405 61.472 1.00 37.24 N ATOM 5279 CA LEU H 130 -2.037 -48.412 61.122 1.00 37.65 C
ATOM 5280 CB LEU H 130 -0.727 -47.793 60.595 1.00 36.89 C
ATOM 5281 CG LEU H 130 -0.791 -47.165 59.209 1.00 35.49 C
ATOM 5282 CD1 LEU H 130 0.492 -46.467 58.878 1.00 35.07 C
ATOM 5283 CD2 LEU H 130 -1.055 -48.191 58.171 1.00 35.20 C JB2010.7161
ATOM 5284 C LEU H 30 -1.890 -49.097 62.481 1.00 38.65 C
ATOM 5285 O LEU H 130 -1.083 -48.695 63.324 1.00 38.40 O
ATOM 5286 N ALA H 131 -2.789 -50.062 62.710 1.00 40.73 N
ATOM 5287 CA ALA H 131 -2.959 -50.812 63.932 1.00 42.92 C ATOM 5288 CB ALA H 131 -4.1 7 -51.696 63.834 1.00 43.35 C
ATOM 5289 C ALA H 131 -1.769 -51.610 64.428 1.00 44.78 C
ATOM 5290 O ALA H 131 -1.168 -52.362 63.653 1.00 45.28 O
ATOM 5291 N PRO H 132 -1.419 -51.466 65.736 1.00 50.50 N
ATOM 5292 CA PRO H 132 -0.319 -52.273 66.278 1.00 52.22 C ATOM 5293 CB PRO H 132 -0.073 -51.684 67.667 1.00 53.34 C
ATOM 5294 CG PRO H 132 -1.292 -50.942 68.010 1.00 52.73 C
ATOM 5295 CD PRO H 132 -2.049 -50.625 66.777 1.00 51.89 C
ATOM 5296 C PRO H 132 -0.799 -53.721 66.319 1.00 54.12 C
ATOM 5297 0 PRO H 132 -1.850 -54.022 66.901 1.00 54.24 O ATOM 5298 N SER H 133 -0.074 -54.596 65.616 1.00 59.56 N
ATOM 5299 CA SER H 133 -0.390 -56.016 65.512 1.00 61.66 C
ATOM 5300 CB SER H 133 -0.627 -56.370 64.043 1.00 67.07 C
ATOM 5301 OG SER H 133 -1.210 -57.653 63.870 1.00 69.07 O
ATOM 5302 C SER H 133 0.784 -56.832 66.074 1.00 62.67 C ATOM 5303 O SER H 133 1.775 -56.249 66.520 1.00 63.05 O
ATOM 5304 N SER H 134 0.677 -58.182 66.050 1.00 65.34 N
ATOM 5305 CA SER H 134 1.762 -59.078 66.467 1.00 66.17 C
ATOM 5306 CB SER H 134 1.264 -60.514 66.629 1.00 68.11 C
ATOM 5307 OG SER H 134 0.579 -60.991 65.482 1.00 68.00 O ATOM 5308 C SER H 134 2.835 -58.977 65.351 1 .00 66.66 C
ATOM 5309 O SER H 134 4.025 -59.150 65.625 1.00 67.11 O
ATOM 5310 N LYS H 135 2.382 -58.630 64.103 1.00 67.19 N
ATOM 531 1 CA LYS H 135 3.159 -58.415 62.870 1.00 67.61 C
ATOM 5312 CB LYS H 135 2.248 -58.589 61.635 1.00 70.13 C ATOM 5313 C LYS H 135 3.888 -57.022 62.866 1.00 67.97 C
ATOM 5314 0 LYS H 135 4.746 -56.762 62.006 1.00 67.50 O
ATOM 5315 N SER H 136 3.538 -56.150 63.850 1.00 68.33 N
ATOM 5316 CA SER H 136 4.120 -54.822 64.065 1.00 68.40 C
ATOM 5317 CB SER H 136 3.127 -53.712 63.728 1.00 70.88 C ATOM 5318 OG SER H 136 2.316 -53.364 64.835 1.00 70.60 O
ATOM 5319 C SER H 136 4.736 -54.653 65.483 1.00 68.63 C
ATOM 5320 O SER H 136 5.051 -53.525 65.860 1.00 68.81 O
ATOM 5321 N THR H 137 4.920 -55.777 66.253 1.00 68.87 N
ATOM 5322 CA THR H 137 5.549 -55.800 67.595 1.00 68.83 C ATOM 5323 CB THR H 137 4.649 -56.367 68.708 1.00 78.28 C
ATOM 5324 OG1 THR H 137 4.312 -57.723 68.423 1.00 79.55 O
ATOM 5325 CG2 THR H 137 3.414 -55.544 68.953 1.00 78.24 C
ATOM 5326 C THR H 137 6.883 -56.554 67.523 1.00 68.41 C
ATOM 5327 0 THR H 137 6.918 -57.700 67.077 1.00 68.50 O ATOM 5328 N SER H 138 7.971 -55.893 67.948 1.00 68.49 N
ATOM 5329 CA SER H 138 9.355 -56.390 67.943 1.00 68.20 C
ATOM 5330 CB SER H 138 10.213 -55.529 67.007 1.00 72.61 C
ATOM 5331 OG SER H 138 11.591 -55.863 67.001 1.00 73.19 O
ATOM 5332 C SER H 138 9.909 -56.406 69.384 1.00 67.56 C ATOM 5333 0 SER H 138 10.585 -55.465 69.827 1.00 67.76 O
ATOM 5334 N GLY H 139 9.591 -57.484 70.100 1.00 66.36 N
ATOM 5335 CA GLY H 139 9.981 -57.669 71.493 1.00 64.49 C
ATOM 5336 C GLY H 139 9.037 -56.870 72.363 1.00 63.43 C
ATOM 5337 O GLY H 139 7.816 -57.105 72.343 1.00 63.40 O JB2010.7161
ATOM 5338 N GLY H 140 9.600 -55.911 73.097 1.00 58.87 N
ATOM 5339 CA GLY H 140 8.819 -55.044 73.970 1.00 57.08 C
ATOM 5340 C GLY H 140 8.259 -53.831 73.253 1.00 56.04 C
ATOM 5341 O GLY H 140 7.432 -53.114 73.821 1.00 56.27 O ATOM 5342 N THR H 141 8.704 -53.595 71.996 1.00 51.81 N
ATOM 5343 CA THR H 141 8.296 -52.480 71.146 1.00 50.39 C
ATOM 5344 CB THR H 141 9.512 -51.922 70.421 1 ,00 48.78 C
ATOM 5345 OG1 THR H 141 10.373 -51.373 71.401 1.00 48.99 O
ATOM 5346 CG2 THR H 141 9.168 -50.828 69.433 1.00 48.95 C ATOM 5347 C THR H 141 7.178 -52.869 70.194 1.00 49.72 C
ATOM 5348 0 THR H 141 7.182 -53.963 69.647 1.00 50.09 O
ATOM 5349 N ALA H 142 6.234 -51.955 69.991 1.00 47.37 N
ATOM 5350 CA ALA H 142 5.084 -52.109 69.110 1.00 46.20 C
ATOM 5351 CB ALA H 142 3.807 -52.198 69.941 1.00 46.49 C ATOM 5352 C ALA H 142 5.019 -50.887 68.205 1.00 45.46 C
ATOM 5353 0 ALA H 142 5.051 -49.758 68.698 1.00 45,62 O
ATOM 5354 N ALA H 143 4.941 -51.096 66.898 1.00 42.89 N
ATOM 5355 CA ALA H 143 4.842 -49.984 65.963 1.00 42.36 C
ATOM 5356 CB ALA H 143 5.633 -50.269 64.692 1.00 42.68 C ATOM 5357 C ALA H 143 3.377 -49.750 65.629 1.00 42.23 C
ATOM 5358 O ALA H 143 2.619 -50.685 65.367 1.00 42.73 O
ATOM 5359 N LEU H 144 2.974 -48.504 65.670 1.00 43.06 N
ATOM 5360 CA LEU H 144 1.622 -48.105 65.320 1.00 42.54 C
ATOM 5361 CB LEU H 144 0.651 -48.041 66.530 1.00 42.39 C ATOM 5362 CG LEU H 144 0.937 -47.062 67.692 1.00 41.93 C
ATOM 5363 CD 1 LEU H 144 0.364 -45.679 67.428 1.0042.12 C
ATOM 5364 CD2 LEU H 144 0.277 -47.541 68,926 1.00 41.53 C
ATOM 5365 C LEU H 144 1.750 -46.786 64.599 1.00 42.34 C
ATOM 5366 0 LEU H 144 2.808 -46.152 64.640 1.00 42.24 O ATOM 5367 N GLY H 145 0.693 -46.390 63.933 1.00 42.41 N
ATOM 5368 CA GLY H 145 0.685 -45,135 63.211 1.00 41.96 C
ATOM 5369 C GLY H 145 -0.655 -44.892 62.580 1.00 41.44 C
ATOM 5370 O GLY H 145 -1.624 -45.589 62.880 1.00 40.99 O
ATOM 5371 N CYS H 146 -0.725 -43.886 61.728 1.00 41.32 N ATOM 5372 CA CYS H 146 -1.933 -43.608 60.980 1.00 41.14 C
ATOM 5373 CB CYS H 146 -2.973 -42.790 61.745 1.00 43.82 C
ATOM 5374 SG CYS H 146 -2.500 -41.082 62.046 1.00 51.35 S
ATOM 5375 C CYS H 146 -1.615 -43.082 59.579 1.00 38.98 C
ATOM 5376 0 CYS H 146 -0.629 -42.376 59.397 1.00 38.06 O ATOM 5377 N LEU H 147 -2.390 -43.559 58.584 1.00 35.03 N
ATOM 5378 CA LEU H 147 -2.274 -43.273 57.160 1.00 33.53 C
ATOM 5379 CB LEU H 147 -2.683 -44.528 56.374 1.00 32.83 C
ATOM 5380 CG LEU H 147 -2.680 -44.405 54.872 1.00 32.20 C
ATOM 5381 CD1 LEU H 147 -1.269 -44.465 54.315 1.00 30.70 C ATOM 5382 CD2 LEU H 147 -3.513 -45.468 54.265 1.00 31.15 C
ATOM 5383 C LEU H 147 -3.159 -42.122 56.777 1.00 33.17 C
ATOM 5384 0 LEU H 147 -4.387 -42.260 56.807 1.00 33.47 O
ATOM 5385 N VAL H 148 -2.541 -40,980 56.431 1.00 31.62 N
ATOM 5386 CA VAL H 148 -3.218 -39.743 56.030 1.00 30.88 C ATOM 5387 CB VAL H 148 -2.395 -38.529 56.510 1.00 33.37 C
ATOM 5388 CG1 VAL H 148 -3.013 -37.207 56.079 1.00 33.39 C
ATOM 5389 CG2 VAL H 148 -2.212 -38.569 58.014 1.00 32.03 C
ATOM 5390 C VAL H 148 -3.358 -39.832 54.520 1.00 31.14 C
ATOM 5391 O VAL H 148 -2.436 -39.491 53.775 1.00 31.01 O JB2010.7161
ATOM 5392 N LYS H 149 -4.501 -40.351 54.065 1.00 35.35 N
ATOM 5393 CA LYS H 149 -4.733 -40.583 52.640 1.00 35.64 C
ATOM 5394 CB LYS H 149 -5.229 -42.040 52.423 1.00 36.58 C
ATOM 5395 CG LYS H 149 -4.956 -42.584 51.024 1.00 35.92 C ATOM 5396 CD LYS H 149 -5.470 -43.986 50.768 1.00 34.65 C
ATOM 5397 CE LYS H 149 -4.829 -44.589 49.535 1.00 34.60 C
ATOM 5398 NZ LYS H 149 -5.570 -44.286 48.272 1.00 33.84 N
ATOM 5399 C LYS H 149 -5.703 -39.611 51.993 1.00 36.65 C
ATOM 5400 O LYS H 149 -6.601 -39.074 52.654 1.00 36.56 O ATOM 5401 N ASP H 150 -5.514 -39.427 50.666 1.00 40.25 N
ATOM 5402 CA ASP H 150 -6.321 -38.673 49.718 1.00 41.18 C
ATOM 5403 CB ASP H 150 -7.567 -39.506 49.341 1.00 43.09 C
ATOM 5404 CG ASP H 150 -7.266 -40.827 48.636 1.00 45.22 C
ATOM 5405 OD1 AS H 150 -6.204 -40.921 47.946 1.0046.44 O ATOM 5406 OD2 ASP H 150 -8.088 -41.762 48.756 1.0047.88 O
ATOM 5407 C ASP H 150 -6.662 -37.218 50.062 1.00 41.50 C
ATOM 5408 O ASP H 150 -7.846 -36.873 50.250 1.00 42.08 O
ATOM 5409 N TYR H 151 -5.624 -36.367 50.119 1.00 38.45 N
ATOM 5410 CA TYR H 151 -5.769 -34.941 50.426 1.00 38.12 C ATOM 5411 CB TYR H 151 -5,261 -34.632 51.837 1.00 38.09 C
ATOM 5412 CG TYR H 151 -3.756 -34.726 52.008 1.00 39.05 C
ATOM 5413 CD1 TYR H 151 -2.941 -33.614 51.810 1.00 38.24 C
ATOM 5414 CE1 TYR H 151 -1.558 -33.691 51.965 1.00 39.24 C
ATOM 5415 CZ TYR H 151 -0.977 -34.884 52.359 1.0040.25 C ATOM 5416 OH TYR H 151 0.382 -34.941 52.525 1.00 39.93 O
ATOM 5417 CE2 TYR H 151 -1.768 -36.004 52.578 1.00 39.95 C
ATOM 5418 CD2 TYR H 151 -3.150 -35.919 52.406 1.00 39.59 C
ATOM 5419 C TYR H 151 -5.057 -34.057 49.403 1.00 37,73 C
ATOM 5420 O TYR H 151 -4.088 -34.485 48.767 1.00 37.25 O ATOM 5421 N PHE H 152 -5.524 -32.812 49.267 Ί .00 38.52 N
ATOM 5422 CA PHE H 152 -4.946 -31.844 48.342 1.00 38.48 C
ATOM 5423 CB PHE H 152 -5.490 -32.068 46.934 1.0040.18 C
ATOM 5424 CG PHE H 152 -4.894 -31.160 45.888 1.00 41.34 C
ATOM 5425 CD1 PHE H 152 -5.509 -29.959 45.555 1.0041.88 C ATOM 5426 CE1 PHE H 152 -4.956 -29.116 44.596 1.00 40.85 C
ATOM 5427 CZ PHE H 152 -3.793 -29.472 43.957 1.00 41.32 C
ATOM 5428 CE2 PHE H 152 -3.171 -30.664 44.262 1.00 42.11 C
ATOM 5429 CD2 PHE H 152 -3.718 -31.506 45.232 1 .00 42.28 C
ATOM 5430 C PHE H 152 -5.227 -30.396 48.776 1.00 38.21 C ATOM 5431 0 PHE H 152 -6.345 -30.105 49.193 1.00 38.37 O
ATOM 5432 N PRO H 153 -4.262 -29.460 48.637 1.00 37.63 N
ATOM 5433 CA PRO H 153 -2.856 -29.654 48.216 1.00 37.14 C
ATOM 5434 CB PRO H 153 -2.503 -28.276 47.627 1.00 38.46 C
ATOM 5435 CG PRO H 153 -3.271 -27.302 48.533 1.00 38.66 C ATOM 5436 CD PRO H 153 -4.512 -28.051 49.023 1.00 38.89 C
ATOM 5437 C PRO H 153 -2.019 -29.955 49.467 1.00 36.80 C
ATOM 5438 0 PRO H 153 -2.564 -30.281 50.530 1.00 35.92 O
ATOM 5439 N GLU H 154 -0.707 -29.803 49.362 1.00 38.45 N
ATOM 5440 CA GLU H 154 0.140 -29.971 50.534 1.00 39.17 C ATOM 5441 CB GLU H 154 1.586 -30.256 50.110 1.00 40.07 C
ATOM 5442 CG GLU H 154 1.844 -31.704 49.778 1.00 39.86 C
ATOM 5443 CD GLU H 154 2.575 -32.452 50.870 1.00 41.40 C
ATOM 5444 OE1 GLU H 154 1.935 -32.791 51.899 1.00 39.34 O
ATOM 5445 OE2 GLU H 154 3.792 -32.707 50.690 1.0040.96 O JB2010.7161
ATOM 5446 C GLU H 154 0.086 -28.627 51.292 1.00 39.78 C
ATOM 5447 0 GLU H 154 -0.203 -27.593 50.684 1.00 40.94 O
ATOM 5448 N PRO H 155 0.329 -28.583 52.606 1.00 39.89 N
ATOM 5449 CA PRO H 155 0.748 -29.659 53.508 1.00 40.30 C ATOM 5450 CB PRO H 155 1.955 -29.007 54.198 1.00 41.14 C
ATOM 5451 CG PRO H 155 1.613 -27.484 54.206 1.00 40.60 C
ATOM 5452 CD PRO H 155 0.400 -27.298 53.313 1.00 40.40 C
ATOM 5453 C PRO H 155 -0.277 -30.062 54.572 1.00 40.39 C
ATOM 5454 0 PRO H 155 -1.321 -29.429 54.753 1.00 40.68 O ATOM 5455 N VAL H 156 0.070 -31.125 55.299 1.00 40.76 N
ATOM 5456 CA VAL H 156 -0.656 -31.620 56.464 1.00 41.17 C
ATOM 5457 CB VAL H 156 -1.372 -33.006 56.338 1.00 44.37 C
ATOM 5458 CG1 VAL H 156 -2.552 -32.955 55.402 1.00 44.61 C
ATOM 5459 CG2 VAL H 156 -0.421 -34.115 55.932 1.00 44.73 C ATOM 5460 C VAL H 156 0.428 -31.633 57.547 1.00 41 .27 C
ATOM 5461 O VAL H 156 1.621 -31.640 57.222 1.00 41.37 O
ATOM 5462 N THR H 157 0.024 -31.609 58.815 1.00 42.73 N
ATOM 5463 CA THR H 157 0.944 -31.688 59.945 1.0043.31 C
ATOM 5464 CB THR H 157 1.066 -30.372 60.692 1.00 51.85 C ATOM 5465 OG1 THR H 157 -0.225 -30.013 61.169 1.00 53.32 O
ATOM 5466 CG2 THR H 157 1.645 -29.269 59.837 1.00 52.43 C
ATOM 5467 C THR H 157 0.372 -32.766 60.823 1.00 43.04 C
ATOM 5468 0 THR H 157 -0.837 -32.769 61.075 1.00 43.16 O
ATOM 5469 N VAL H 158 1.218 -33.702 61.258 1.00 42.04 N ATOM 5470 CA VAL H 158 0.762 -34.783 62.119 1.00 41.33 C
ATOM 5471 CB VAL H 158 0.904 -36.199 61.497 1.00 44.48 C
ATOM 5472 CG1 VAL H 158 0.205 -37.244 62.370 1.00 43.66 C
ATOM 5473 CG2 VAL H 158 0.386 -36.247 60.062 1.00 43.70 C
ATOM 5474 C VAL H 158 1.489 -34.716 63.443 1.00 41.19 C ATOM 5475 0 VAL H 158 2.714 -34.555 63.468 1.00 41.13 O
ATOM 5476 N SER H 159 0.742 -34.872 64.538 1.00 39.19 N
ATOM 5477 CA SER H 159 1.321 -34.918 65.872 1.00 38.85 C
ATOM 5478 CB SER H 159 1.085 -33,620 66.628 1.00 44.06 C
ATOM 5479 OG SER H 159 -0.294 -33.309 66.665 1.0045.99 O ATOM 5480 C SER H 159 0.690 -36.100 66.576 1.00 38.25 C
ATOM 5481 O SER H 159 -0.3 7 -36.612 66.088 1.00 38.11 O
ATOM 5482 N TRP H 160 1.298 -36.569 67.678 1.00 37.81 N
ATOM 5483 CA TRP H 160 0.777 -37.699 68.436 1.00 37.51 C
ATOM 5484 CB TRP H 160 1.727 -38.897 68.409 1.00 35.41 C ATOM 5485 CG TRP H 160 1.727 -39.594 67.084 1.00 33.57 C
ATOM 5486 CD1 TRP H 160 2.497 -39.291 65.999 1.00 32.52 C
ATOM 5487 NE1 TRP H 160 2.168 -40.108 64.941 1.00 32.10 N
ATOM 5488 CE2 TRP H 160 1.152 -40.946 65.323 1.00 32.47 C
ATOM 5489 CD2 TRP H 160 0.853 -40.654 66.675 1.00 32.41 C ATOM 5490 CE3 TRP H 160 -0.164 -41.391 67.324 1.00 31.63 C
ATOM 5491 CZ3 TRP H 160 -0.822 -42.391 66.618 1.00 30.74 C
ATOM 5492 CH2 TRP H 160 -0.489 -42.670 65.284 1.00 32.74 C
ATOM 5493 CZ2 TRP H 160 0,499 -41.962 64.615 1.00 33.08 C
ATOM 5494 C TRP H 160 0.491 -37.258 69.832 1.00 38.37 C ATOM 5495 0 TRP H 160 1.337 -36.589 70.445 1.00 38.65 O
ATOM 5496 N ASN H 161 -0.733 -37.608 70.333 1.00 41.10 N
ATOM 5497 CA ASN H 161 -1.268 -37.291 71.666 1.00 41.33 C
ATOM 5498 CB ASN H 161 -0.608 -38.115 72.754 1.00 39.01 C
ATOM 5499 CG ASN H 161 -0.959 -39.565 72.709 1.0040.08 C JB2010.7161
ATOM 5500 OD1 ASN H 161 -1.800 -40.012 71.921 1.0042.08 O
ATOM 5501 ND2 ASN H 161 -0.316 -40.332 73.572 1.00 40.37 N
ATOM 5502 C ASN H 161 -1.160 -35.818 71.967 1.00 41.97 C
ATOM 5503 O ASN H 161 -0.749 -35.429 73.063 1.00 41.89 O ATOM 5504 N SER H 162 -1.520 -35.003 70.969 1.00 43.03 N
ATOM 5505 CA SER H 162 -1.504 -33.546 71.006 1.00 44.28 C
ATOM 5506 CB SER H 162 -2.604 -32.994 71.916 1.00 48.12 C
ATOM 5507 OG SER H 162 -3.879 -33.486 71.532 1.00 49.19 O
ATOM 5508 C SER H 162 -0.129 -32.962 71.300 1,00 44.82 C ATOM 5509 O SER H 162 -0.040 -31.882 71.884 1.00 45.65 O
ATOM 5510 N GLY H 163 0.926 -33.660 70.866 1.00 43.69 N
ATOM 5511 CA GLY H 163 2.300 -33.212 71.054 1.00 43.54 C
ATOM 5512 C GLY H 163 3.008 -33.848 72.227 1.00 43.65 C
ATOM 5513 0 GLY H 163 4.231 -33.740 72.342 1.0044.06 O ATOM 5514 N ALA H 164 2.253 -34.537 73.097 1.0043.46 N
ATOM 5515 CA ALA H 164 2.803 -35.215 74.268 1.00 42.83 C
ATOM 5516 CB ALA H 164 1.691 -35.699 75.172 1.00 43.09 C
ATOM 5517 C ALA H 164 3.708 -36.377 73.871 1.00 42.66 C
ATOM 5518 O ALA H 164 4.661 -36.664 74.599 1.00 43.15 O ATOM 5519 N LEU H 165 3.425 -37.024 72.709 1.00 41 .20 N
ATOM 5520 CA LEU H 165 4.184 -38.144 72.164 1.00 40.42 C
ATOM 5521 CB LEU H 165 3.241 -39.285 71.782 1.00 40.23 C
ATOM 5522 CG LEU H 165 3.914 -40.565 71.280 1.00 40.86 C
ATOM 5523 CD1 LEU H 165 4.868 -41.160 72.341 1.00 40.45 C ATOM 5524 CD2 LEU H 165 2.879 -41.586 70.766 1.00 39.93 C
ATOM 5525 C LEU H 165 5.088 -37.717 70.984 1.00 40.26 C
ATOM 5526 O LEU H 165 4.611 -37.453 69.880 1.00 39.93 O
ATOM 5527 N THR H 166 6.406 -37.655 71.232 1.0041.78 N
ATOM 5528 CA THR H 166 7.389 -37.249 70.213 1.00 41.15 C ATOM 5529 CB THR H 166 8.031 -35.911 70.593 1.00 41.57 C
ATOM 5530 OG1 THR H 166 8.403 -35.966 71.971 1.00 42.01 O
ATOM 5531 CG2 THR H 166 7.110 -34.738 70.358 1.00 40.82 C
ATOM 5532 C THR H 166 8.462 -38.311 69.950 1.00 40.78 C
ATOM 5533 0 THR H 166 8.880 -38.465 68.803 1.00 40.56 O ATOM 5534 N SER H 167 8.920 -39.026 71.006 1.0041.78 N
ATOM 5535 CA SER H 167 9.944 -40.069 70.886 1.00 41.46 C
ATOM 5536 CB SER H 167 10.249 -40.690 72.247 1.00 44.40 C
ATOM 5537 OG SER H 167 10.852 -39.749 73.121 1.00 44.64 O
ATOM 5538 C SER H 167 9.542 -41.146 69.873 1.00 41.40 C ATOM 5539 O SER H 167 8.408 -41.644 69.907 1.00 42.04 O
ATOM 5540 N GLY H 168 10.455 -41.443 68.955 1.00 40.97 N
ATOM 5541 CA GLY H 168 10.275 -42.456 67.920 1.00 40.88 C
ATOM 5542 C GLY H 168 9.265 -42.202 66.819 1.00 40.90 C
ATOM 5543 0 GLY H 168 8.962 -43.122 66.050 1.00 41.22 O ATOM 5544 N VAL H 169 8.745 -40.962 66.724 1.00 40.23 N
ATOM 5545 CA VAL H 169 7.762 -40.552 65.715 1.00 39.61 C
ATOM 5546 CB VAL H 169 6.932 -39.295 66.150 1.00 41.28 C
ATOM 5547 CG1 VAL H 169 6.112 -38.715 65.009 1.00 41.01 C
ATOM 5548 CG2 VAL H 169 6.024 -39.614 67.324 1.0040.95 C ATOM 5549 C VAL H 169 8.502 -40.353 64.393 1.00 39.60 C
ATOM 5550 O VAL H 169 9.623 -39.843 64.387 1.00 39.71 O
ATOM 5551 N HIS H 170 7.876 -40.775 63.288 1.00 40.37 N
ATOM 5552 CA HIS H 170 8.407 -40.649 61.956 1 .00 39.81 C
ATOM 5553 CB HIS H 170 9.025 -41.970 61.496 1.00 41.60 C JB2010.7161
ATOM 5554 CG HIS H 170 10.439 -42.184 61.953 1.00 43.22 C
ATOM 5555 ND1 HIS H 170 10.836 -43.381 62.528 1.00 44.20 N
ATOM 5556 CE1 HIS H 170 12.122 -43.243 62.797 1 .00 42.49 C
ATOM 5557 NE2 HIS H 170 12.572 -42.049 62.430 1.00 43.71 N ATOM 5558 CD2 HIS H 170 11.513 -41.364 61.878 1.00 43.57 C
ATOM 5559 C HIS H 170 7.263 -40.274 61.054 1.00 39.79 C
ATOM 5560 O HIS H 170 6.354 -41.090 60.853 1.00 40.30 O
ATOM 5561 N THR H 171 7.267 -39.026 60.542 1.00 36.48 N
ATOM 5562 CA THR H 171 6.234 -38.583 59.620 1.00 35.19 C ATOM 5563 CB THR H 171 5.600 -37.260 60.010 1.00 31.80 C
ATOM 5564 OG1 THR H 171 5.032 -37.414 61.304 1.00 31.78 O
ATOM 5565 CG2 THR H 171 4.498 -36.837 59.045 1.00 30.94 C
ATOM 5566 C THR H 171 6.936 -38.578 58.296 1.00 35.08 C
ATOM 5567 O THR H 171 7.919 -37.860 58.105 1.00 35.43 O ATOM 5568 N PHE H 172 6.473 -39.434 57.406 1.00 31.58 N
ATOM 5569 CA PHE H 172 7.060 -39.593 56.110 1.00 31.17 C
ATOM 5570 CB PHE H 172 6.659 -40.955 55.544 1.00 32.20 C
ATOM 5571 CG PHE H 172 7.342 -42.086 56.257 1.00 31.20 C
ATOM 5572 CD1 PHE H 172 6.758 -42.681 57.369 1.00 29.49 C ATOM 5573 CE1 PHE H 172 7.400 -43.713 58.043 1.00 29.23 C
ATOM 5574 CZ PHE H 172 8.640 -44.147 57.617 1.00 30.02 C
ATOM 5575 CE2 PHE H 172 9.242 -43.563 56.526 1.00 29.22 C
ATOM 5576 CD2 PHE H 172 8.588 -42.539 55.839 1.00 31.36 C
ATOM 5577 C PHE H 172 6.685 -38.501 55.129 1.00 31.66 C ATOM 5578 0 PHE H 172 5.551 -37.989 55.149 1.00 31.55 O
ATOM 5579 N PRO H 173 7.623 -38.166 54.210 1 .00 33.02 N
ATOM 5580 CA PRO H 173 7.295 -37.211 53.151 1.00 33.36 C
ATOM 5581 CB PRO H 173 8.549 -37.245 52.275 1.00 33.80 C
ATOM 5582 CG PRO H 173 9.603 -37.676 53.156 1.00 33.34 C ATOM 5583 CD PRO H 173 8.996 -38.677 54.045 1.00 33.60 C
ATOM 5584 C PRO H 173 6.079 -37.748 52.370 1.00 34.09 C
ATOM 5585 0 PRO H 173 5.968 -38.978 52.158 1.00 34.99 O
ATOM 5586 N ALA H 174 5.143 -36.857 51.981 1.00 35.84 N
ATOM 5587 CA ALA H 174 3.949 -37.267 51.237 1.00 36.26 C ATOM 5588 CB ALA H 174 3.010 -36.088 51.087 1.00 36.88 C
ATOM 5589 C ALA H 174 4.327 -37.787 49.858 1.00 36.52 C
ATOM 5590 O ALA H 174 5.438 -37.508 49.399 1.00 36.79 O
ATOM 5591 N VAL H 175 3.424 -38.558 49.206 1.00 37.51 N
ATOM 5592 CA VAL H 175 3.603 -39.072 47.841 1.00 38.03 C ATOM 5593 CB VAL H 175 3.808 -40.600 47.678 1.00 41.33 C
ATOM 5594 CG1 VAL H 175 5.153 -41.042 48.234 1.00 40.26 C
ATOM 5595 CG2 VAL H 175 2.650 -41.406 48.264 1.00 41.47 C
ATOM 5596 C VAL H 175 2.455 -38.578 46.983 1.00 38,57 C
ATOM 5597 0 VAL H 175 1.340 -38.433 47.483 1.00 38.68 O ATOM 5598 N LEU H 176 2.721 -38.316 45.706 1.00 40.23 N
ATOM 5599 CA LEU H 176 1.671 -37.866 44.820 1.0041.44 C
ATOM 5600 CB LEU H 176 2.128 -36.695 43.929 1.00 41.23 C
ATOM 5601 CG LEU H 176 1.023 -36.000 43.096 1.00 41.83 C
ATOM 5602 CD1 LEU H 176 -0.203 -35.580 43.971 1.0040.65 C ATOM 5603 CD2 LEU H 176 1.595 -34.816 42.347 1.00 38.24 C
ATOM 5604 C LEU H 176 1.163 -39.054 44.019 1.00 42.31 C
ATOM 5605 O LEU H 176 1.903 -39.642 43.211 1.00 42.59 O
ATOM 5606 N GLN H 177 -0.105 -39.422 44.284 1.00 43.34 N
ATOM 5607 CA GLN H 177 -0.818 -40.542 43.655 1.00 43.78 C JB2010.7161
ATOM 5608 CB GLN H 177 -2.041 -40.932 44.507 1.00 45.34 C
ATOM 5609 CG GLN H 177 -1.677 -41.510 45.861 1.0047.20 C
ATOM 5610 CD GLN H 177 -2.849 -41.520 46.813 1.00 52.34 C
ATOM 5611 OE1 GLN H 177 -3.379 -42.585 47.179 1.00 54.03 O ATOM 5612 NE2 GLN H 177 -3.281 -40.339 47.259 1.00 53.08 N
ATOM 5613 C GLN H 177 -1.258 -40.205 42.239 1.0043.33 C
ATOM 5614 0 GLN H 177 -1.396 -39.038 41.910 1.00 43.36 O
ATOM 5615 N SER H 178 -1.515 -41.215 41.408 1.00 44.66 N
ATOM 5616 CA SER H 178 -1.973 -41.012 40.036 1.00 45.12 C ATOM 5617 CB SER H 178 -2.138 -42.341 39.326 1.00 51.63 C
ATOM 5618 OG SER H 178 -1.273 -42.323 38.202 1.00 54.90 O
ATOM 5619 C SER H 178 -3.254 -40.188 39.946 1.00 45.01 C
ATOM 5620 O SER H 178 -3.491 -39.542 38.936 1.00 44.98 O
ATOM 5621 N SER H 179 -4.059 -40.180 41.020 1.0043.45 N ATOM 5622 CA SER H 179 -5.281 -39.401 41.127 1.00 42.95 C
ATOM 5623 CB SER H 179 -6.101 -39.900 42.308 1.00 45.76 C
ATOM 5624 OG SER H 179 -5.343 -39.907 43.505 1.00 46.43 O
ATOM 5625 C SER H 179 -4.986 -37.894 41.311 100 42.78 C
ATOM 5626 0 SER H 179 -5.899 -37.077 41.218 1.00 42.52 O ATOM 5627 N GLY H 180 -3.734 -37.541 41.592 1.00 42.23 N
ATOM 5628 CA GLY H 180 -3.330 -36.158 41.817 1.00 42.03 C
ATOM 5629 C GLY H 180 -3.564 -35.730 43.250 1.00 42.15 C
ATOM 5630 O GLY H 180 -3.528 -34.534 43.561 1.00 42.00 O
ATOM 5631 N LEU H 181 -3.810 -36.713 44.137 1.0041.07 N ATOM 5632 CA LEU H 181 -4.025 -36.492 45.561 1.00 40.92 C
ATOM 5633 CB LEU H 181 -5.291 -37.210 46.081 1.00 40.28 C
ATOM 5634 CG LEU H 181 -6.651 -36.699 45.564 1.00 40.61 C
ATOM 5635 CD1 LEU H 181 -7.789 -37.501 46.143 1.00 40.93 C
ATOM 5636 CD2 LEU H 181 -6.857 -35.215 45.842 1.00 38.97 C ATOM 5637 C LEU H 181 -2.787 -36.989 46.299 1.00 40.94 C
ATOM 5638 0 LEU H 181 -2.084 -37.889 45.804 1.00 41.24 O
ATOM 5639 N TYR H 182 -2.499 -36.386 47.470 1.00 40.23 N
ATOM 5640 CA TYR H 182 -1.349 -36.777 48.267 1.00 39.58 C
ATOM 5641 CB TYR H 182 -0.702 -35.569 48.945 1.00 40.66 C ATOM 5642 CG TYR H 182 -0.147 -34.567 47.970 1.00 39.74 C
ATOM 5643 CD1 TYR H 182 1.169 -34.650 47.530 1.00 39.27 C
ATOM 5644 CE1 TYR H 182 1.686 -33.736 46.616 1.00 38.20 C
ATOM 5645 CZ TYR H 182 0.883 -32.712 46.142 1.00 39.01 C
ATOM 5646 OH TYR H 182 1.389 -31 ,806 45.241 1.00 39.50 O ATOM 5647 CE2 TYR H 182 -0.433 -32.610 46.566 1.00 38.18 C
ATOM 5648 CD2 TYR H 182 -0.936 -33.529 47.482 1.00 38.30 C
ATOM 5649 C TYR H 182 -1.745 -37.807 49.285 1.00 39.40 C
ATOM 5650 O TYR H 182 -2.929 -37.986 49.575 1.00 39.80 O
ATOM 5651 N SER H 183 -0.753 -38.486 49.831 1.00 38.17 N ATOM 5652 CA SER H 183 -0.954 -39.502 50.840 1.00 37.90 C
ATOM 5653 CB SER H 183 -1.294 -40.837 50.188 1.00 44.16 C
ATOM 5654 OG SER H 183 -1.621 -41.796 51.176 1.00 47.34 O
ATOM 5655 C SER H 183 0.318 -39.618 51.643 1.00 37.07 C
ATOM 5656 0 SER H 183 1.403 -39.533 51.070 1.00 37.05 O ATOM 5657 N LEU H 184 0.193 -39.787 52.969 1.00 36.77 N
ATOM 5658 CA LEU H 184 1.323 -39.950 53.887 1.00 36.09 C
ATOM 5659 CB LEU H 184 2.054 -38.617 54.264 1.00 35.69 C
ATOM 5660 CG LEU H 184 1.473 -37.626 55.305 1.00 34.71 C
ATOM 5661 CD1 LEU H 184 1.737 -38.072 56.732 1.00 31.95 C JB2010.7161
ATOM 5662 CD2 LEU H 184 2.169 -36.304 55.183 1.00 32.48 C
ATOM 5663 C LEU H , 184 1.019 -40.788 55.105 1.00 35.91 C
ATOM 5664 0 LEU H 184 -0.124 -40.903 55.513 1.00 35.56 O
ATOM 5665 N SER H 185 2.067 -41.331 55.711 1.00 38.03 N ATOM 5666 CA SER H 185 2.014 -42.115 56.929 1.00 38.53 C
ATOM 5667 CB SER H 185 2.640 -43.478 56.686 1.00 45.62 C
ATOM 5668 OG SER H 185 1.752 -44.260 55.910 1.00 50.12 O
ATOM 5669 C SER H 185 2.805 -41.418 58.009 1.00 38.06 C
ATOM 5670 O SER H 185 3.828 -40.803 57.723 1.00 38.33 O ATOM 5671 N SER H 186 2.330 -41.501 59.242 1.00 36.36 N
ATOM 5672 CA SER H 186 3.023 -41.008 60.421 1.00 36.19 C
ATOM 5673 CB SER H 186 2.267 -39.906 61.138 1.00 39.07 C
ATOM 5674 OG SER H 186 2.988 -39.544 62.307 1.00 39.07 O
ATOM 5675 C SER H 186 3.078 -42.248 61.257 1.00 36.44 C ATOM 5676 0 SER H 186 2.092 -42.979 61.346 1.00 36.86 O
ATOM 5677 N VAL H 187 4.230 -42.534 61.824 1.00 35.85 N
ATOM 5678 CA VAL H 187 4.426 -43.763 62.579 1.00 35.28 C
ATOM 5679 CB VAL H 187 5.194 -44.701 61.599 1.00 38.47 C
ATOM 5680 CG1 VAL H 187 6.512 -45.229 62.140 1.00 38.49 C ATOM 5681 CG2 VAL H 187 4.307 -45.795 61.036 1.00 38.13 C
ATOM 5682 C VAL H 187 5.146 -43.472 63.907 1.00 35.38 C
ATOM 5683 0 VAL H 187 5.846 -42.454 64.026 1.00 35.23 O
ATOM 5684 N VAL H 188 4.963 -44.370 64.904 1.00 34.50 N
ATOM 5685 CA VAL H 188 5.574 -44.285 66.239 1.00 34.10 C ATOM 5686 CB VAL H 188 4.799 -43.317 67.177 1.00 36.55 C
ATOM 5687 CG1 VAL H 188 3.408 -43.836 67.504 1.00 36.24 C
ATOM 5688 CG2 VAL H 188 5.577 -43.014 68.446 1.00 35.79 C
ATOM 5689 C VAL H 188 5.773 -45.673 66.855 1.00 33.91 C
ATOM 5690 O VAL H 188 4.960 -46.587 66.644 1.00 33.56 O ATOM 5691 N THR H 189 6.861 -45.817 67.620 1.00 32.94 N
ATOM 5692 CA THR H 189 7.211 -47.039 68.341 1.00 32.71 C
ATOM 5693 CB THR H 189 '8.608 -47.516 68.025 1.00 34.27 C
ATOM 5694 OG1 THR H 189 9.535 -46.463 68.314 1.00 34.37 O
ATOM 5695 CG2 THR H 189 8.733 -48.01 66.586 1.00 33.87 C ATOM 5696 C THR H 189 6.942 -46.742 69.798 1.00 33.03 C
ATOM 5697 0 THR H 189 7.429 -45.757 70.372 1.00 32.91 O
ATOM 5698 N VAL H 190 6.084 -47.564 70.358 1.00 33.89 N
ATOM 5699 CA VAL H 190 5.573 -47.450 71.709 1.00 34.54 C
ATOM 5700 CB VAL H 190 4.067 -46.998 71.641 1.00 37.67 C ATOM 5701 CG1 VAL H 190 3.916 -45.665 70.910 1.00 36.78 C
ATOM 5702 CG2 VAL H 190 3.183 -48.052 70.983 1.00 37.37 C
ATOM 5703 C VAL H 190 5.747 -48.799 72.436 1.00 34.99 C
ATOM 5704 O VAL H 190 5.915 -49.818 71.761 1.00 34.56 O
ATOM 5705 N PRO H 191 5.745 -48.832 73.792 1.00 36.18 N ATOM 5706 CA PRO H 191 5.857 -50.120 74.485 1.00 36.94 C
ATOM 5707 CB PRO H 191 5.944 -49.737 75.957 1.00 38.66 C
ATOM 5708 CG PRO H 191 6.022 -48.255 76.022 1.00 38.66 C
ATOM 5709 CD PRO H 191 5.564 -47.709 74.736 1.00 37.74 C
ATOM 5710 C PRO H 191 4.596 -50.945 74.240 1.00 38.39 C ATOM 5711 O PRO H 191 3.491 -50.385 74.264 1.00 38.10 O
ATOM 5712 N SER H 192 4.762 -52.271 73.991 1.00 42.35 N
ATOM 5713 CA SER H 192 3.668 -53.216 73.734 1.00 43.99 C
ATOM 5714 CB SER H 192 4.218 -54.605 73.461 1.00 48.10 C
ATOM 5715 OG SER H 192 5.089 -54.552 72.350 1.00 50.49 O JB2010.7161
ATOM 5716 C SER H 192 2.714 -53.307 74.902 1.00 44.82 C
ATOM 5717 O SER H 192 1.500 -53.383 74.709 1.00 45.71 O
ATOM 5718 N SER H 193 3.265 -53.308 76.115 1.00 45.48 N
ATOM 5719 CA SER H 193 2.505 -53.406 77.343 1.00 46.08 C ATOM 5720 CB SER H 193 3.455 -53.585 78.522 1.00 52.05 C
ATOM 5721 OG SER H 193 4.320 -52.470 78.694 1.00 54.08 O
ATOM 5722 C SER H 193 1.560 -52.220 77.575 1.00 46.18 C
ATOM 5723 O SER H 193 0.684 -52.315 78.427 1.00 46.34 O
ATOM 5724 N SER H 194 1.733 -51.116 76.837 1.00 47.14 N ATOM 5725 CA SER H 194 0.909 -49.918 77.002 1.0047.97 C
ATOM 5726 CB SER H 194 1.714 -48.646 76.754 1.00 50.64 C
ATOM 5727 OG SER H 194 2.110 -48.572 75.396 1.00 50.71 O
ATOM 5728 C SER H 194 -0.322 -49.941 76.129 1.00 48.36 C
ATOM 5729 O SER H 194 -1.208 -49.112 76.328 1.00 48.48 O ATOM 5730 N LEU H 195 -0.391 -50.874 75.165 1.00 49.60 N
ATOM 5731 CA LEU H 195 -1.563 -50.994 74.303 1.00 50.20 C
ATOM 5732 CB LEU H 195 -1.290 -51.941 73.120 1.00 48.95 C
ATOM 5733 CG LEU H 195 -0.043 -51.651 72.274 1.00 48.35 C
ATOM 5734 CD1 LEU H 195 0.314 -52.823 71.407 1.00 46.81 C ATOM 5735 CD2 LEU H 195 -0.177 -50.362 71.465 1.00 46.82 C
ATOM 5736 C LEU H 195 -2.726 -51.497 75.199 1.00 51.22 C
ATOM 5737 O LEU H 195 -2.515 -52.283 76.148 1.00 51.51 O
ATOM 5738 N GLY H 196 -3.924 -50.989 74.949 1.00 54.03 N
ATOM 5739 CA GLY H 196 -5.056 -51.364 75.782 1.00 54.57 C ATOM 5740 C GLY H 196 -5.159 -50.385 76.930 1 .00 54.72 C
ATOM 5741 O GLY H 196 -6.229 -49.789 77.144 1.00 55.83 O
ATOM 5742 N THR H 197 -4.029 -50.167 77.645 1.00 51.43 N
ATOM 5743 CA THR H 197 -3.959 -49.211 78.757 1.00 50.67 C
ATOM 5744 CB THR H 197 -3.040 -49.688 79.886 1.00 54.18 C ATOM 5745 OG1 THR H 197 -2.413 -48.558 80.486 1.00 54.49 O
ATOM 5746 CG2 THR H 197 -1.996 -50.700 79.423 1.00 54.12 C
ATOM 5747 C THR H 197 -3.838 -47.727 78.318 1.00 50.19 C
ATOM 5748 0 THR H 197 -4.698 -46.929 78.689 1.00 50.56 O
ATOM 5749 N GLN H 198 -2.790 -47.360 77.541 1.00 46.29 N ATOM 5750 CA GLN H 198 -2.573 -45.990 77.048 1.00 45.20 C
ATOM 5751 CB GLN H 198 -1.074 -45.657 76,966 1.00 46.60 C
ATOM 5752 CG GLN H 198 -0.699 -44.395 76.166 1.00 46.10 C
ATOM 5753 CD GLN H 198 -0.834 -43.087 76.908 1.00 45.88 C
ATOM 5754 OE1 GLN H 198 -0.258 -42.885 77.982 1.00 46.73 O ATOM 5755 NE2 GLN H 198 -1.575 -42.154 76.339 1.00 43.65 N
ATOM 5756 C GLN H 198 -3.272 -45.746 75.710 1.00 44.90 C
ATOM 5757 O GLN H 198 -3.260 -46.607 74.835 1.00 44.53 O
ATOM 5758 N THR H 199 -3.864 -44.549 75.562 1.00 44.61 N
ATOM 5759 CA THR H 199 -4.582 -44.105 74.378 1.0044.51 C ATOM 5760 CB THR H 199 -5.822 -43.271 74.804 1.00 50.95 C
ATOM 5761 OG1 THR H 199 -6.879 -44.1 0 75.179 1.00 50.37 O
ATOM 5762 CG2 THR H 199 -6.323 -42.339 73.716 1.00 50.30 C
ATOM 5763 C THR H 199 -3.624 -43.396 73.432 1.00 44.67 C
ATOM 5764 0 THR H 199 -2.958 -42.430 73.840 1.00 44.83 O ATOM 5765 N TYR H 200 -3.551 -43.881 72.162 1.00 43.84 N
ATOM 5766 CA TYR H 200 -2.691 -43.289 71.129 1.00 43.76 C
ATOM 5767 CB TYR H 200 -1.695 -44.303 70.532 1.00 42.64 C
ATOM 5768 CG TYR H 200 -0.713 -44.826 71.555 1.00 42.17 C
ATOM 5769 CD1 TYR H 200 -0.821 -46.119 72.057 1.00 41.42 C JB2010.7161
ATOM 5770 CE1 TYR H 200 0.060 -46.596 73.022 1.00 43.03 C
ATOM 5771 CZ TYR H 200 1.060 -45.769 73.506 1.00 44.30 C
ATOM 5772 OH TYR H 200 1.931 -46.207 74.473 1.00 44.64 O
ATOM 5773 CE2 TYR H 200 1.177 -44.473 73.027 1.00 42.68 C ATOM 5774 CD2 TYR H 200 0.295 -44.012 72.058 1.00 41 .82 C
ATOM 5775 C TYR H 200 -3.5Θ8 -42.671 70.073 1.00 44.12 C
ATOM 5776 0 TYR H 200 -4.346 -43.376 69.438 1.00 44.64 O
ATOM 5777 N ILE H 201 -3.478 -41.341 69.924 1.00 45.25 N
ATOM 5778 CA ILE H 201 -4.261 -40.568 68.978 1.00 45.08 C ATOM 5779 CB ILE H 201 -5.259 -39.629 69.716 1.0048.08 C
ATOM 5780 CG1 ILE H 201 -6.301 -40.428 70.507 1.00 48.14 C
ATOM 5781 CD1 ILE H 201 -7.026 -39.622 71 .525 1.00 47.00 C
ATOM 5782 CG2 ILE H 201 -5.941 -38.620 68.748 1.00 47.65 C
ATOM 5783 C ILE H 201 -3.354 -39.747 68.120 1.00 45.19 C ATOM 5784 O ILE H 201 -2.536 -38.997 68.649 1.00 45.45 O
ATOM 5785 N CYS H 202 -3.529 -39.830 66.801 1.00 47.01 N
ATOM 5786 CA CYS H 202 -2.766 -38.969 65.913 1 .00 47.41 C
ATOM 5787 CB CYS H 202 -2.269 -39.679 64.661 1.0048.99 C
ATOM 5788 SG CYS H 202 -3.563 -40.439 63.666 1.00 51.00 S ATOM 5789 C CYS H 202 -3.625 -37.786 65.575 1.00 46.88 C
ATOM 5790 O CYS H 202 -4.827 -37.925 65.317 1.00 46.61 O
ATOM 5791 N ASN H 203 -3.002 -36.622 65.595 1.00 43.51 N
ATOM 5792 CA ASN H 203 -3.641 -35.361 65.318 1.00 42.92 C
ATOM 5793 CB ASN H 203 -3.364 -34.364 66.447 1.00 44.17 C ATOM 5794 CG ASN H 203 -3.356 -35.013 67.808 1.00 44.22 C
ATOM 5795 OD1 ASN H 203 -2.293 -35.182 68.423 1.00 45.30 O
ATOM 5796 ND2 ASN H 203 -4.523 -35.429 68.304 1.0042.41 N
ATOM 5797 C AS H 203 -3.167 -34.866 63.973 1.00 43.03 C
ATOM 5798 0 AS H 203 -2.014 -34.447 63.813 1.00 42.92 O ATOM 5799 N VAL H 204 -4.073 -34.951 63.002 1.00 41.20 N
ATOM 5800 CA VAL H 204 -3.857 -34.549 61.622 1.0042.13 C
ATOM 5801 CB VAL H 204 -4.389 -35.643 60.654 1.00 45.04 C
ATOM 5802 CG1 VAL H 204 -4.129 -35.286 59.192 1.00 44.39 C
ATOM 5803 CG2 VAL H 204 -3.775 -36.994 60.988 1.00 44.18 C ATOM 5804 C VAL H 204 -4.504 -33.178 61.406 1.00 42.92 C
ATOM 5805 O VAL H 204 -5.590 -32.917 61.919 1.00 43.23 O
ATOM 5806 N ASN H 205 -3.838 -32.304 60.660 1.00 42.67 N
ATOM 5807 CA ASN H 205 -4.355 -30.975 60.419 1.00 43.85 C
ATOM 5808 CB ASN H 205 -3.832 -30.016 61.513 1.00 52.11 C ATOM 5809 CG ASN H 205 -4.085 -28.529 61.357 1.00 54.54 C
ATOM 5810 OD1 ASN H 205 -5.200 -28.051 61.082 1.00 56.73 O
ATOM 5811 ND2 ASN H 205 -3.023 -27.759 61.568 1.00 56.17 N
ATOM 5812 C ASN H 205 -4.013 -30.537 59.003 1.00 43.84 C
ATOM 5813 O ASN H 205 -2.849 -30.424 58.635 1.00 44.02 O ATOM 5814 N HIS H 206 -5.047 -30.344 58.198 1.00 44.82 N
ATOM 5815 CA HIS H 206 -4.917 -29.910 56.828 1.00 45.25 C
ATOM 5816 CB HIS H 206 -5.631 -30.894 55.875 1.00 45.95 C
ATOM 5817 CG H!S H 206 -5.406 -30.614 54.416 1.00 45.29 C
ATOM 5818 ND1 HIS H 206 -6.469 -30.466 53.541 1.0044.62 N ATOM 5819 CE1 HIS H 206 -5.926 -30.210 52.361 1.0044.66 C
ATOM 5820 NE2 HIS H 206 -4.588 -30.204 52.426 1.00 43.63 N
ATOM 5821 CD2 HIS H 206 -4.246 -30.443 53.731 1.0043.66 C
ATOM 5822 C HIS H 206 -5.501 -28.508 56.751 1.00 45.79 C
ATOM 5823 O HIS H 206 -6.715 -28.351 56.622 1.00 45.85 O JB2010.7161
ATOM 5824 N LYS H 207 -4.636 -27.486 56.866 1.00 48.69 N
ATOM 5825 CA LYS H 207 -5.073 -26.090 56.797 1.00 49.52 C
ATOM 5826 CB LYS H 207 -3.973 -25.102 57.244 1.00 52.73 C
ATOM 5827 CG LYS H 207 -3.698 -25.153 58.757 1.00 54.37 C ATOM 5828 CD LYS H 207 -2.424 -24.390 59.192 1.00 57.42 C
ATOM 5829 CE LYS H 207 -2.105 -24.591 60.666 1.00 58.66 C
ATOM 5830 NZ LYS H 207 -0.771 -24.039 61.045 1.00 59.36 N
ATOM 5831 C LYS H 207 -5.734 -25.71 55.436 1.00 49.64 C
ATOM 5832 O LYS H 207 -6.827 -25.135 55.481 1.0049.98 O ATOM 5833 N PRO H 208 -5.177 -26.105 54.241 1.00 48.55 N
ATOM 5834 CA PRO H 208 -5.831 -25.743 52.972 1.00 48.51 C
ATOM 5835 CB PRO H 208 -4.939 -26.395 51.913 1.00 50.10 C
ATOM 5836 CG PRO H 208 -3.601 -26.500 52.539 1.00 50.11 C
ATOM 5837 CD PRO H 208 -3.896 -26.811 53.980 1.00 50.33 C ATOM 5838 C PRO H 208 -7.293 -26.141 52.793 1.00 48,80 C
ATOM 5839 O PRO H 208 -7.900 -25.719 51.808 1.00 48.87 O
ATOM 5840 N SER H 209 -7.858 -26.930 53.715 1.00 48.44 N
ATOM 5841 CA SER H 209 -9.256 -27.370 53.651 1.00 49.06 C
ATOM 5842 CB SER H 209 -9.362 -28.789 53.086 1.00 52.19 C ATOM 5843 OG SER H 209 -8.821 -29.774 53.953 1.00 53.12 O
ATOM 5844 C SER H 209 -9.907 -27.277 55.025 1.00 49.40 C
ATOM 5845 0 SER H 209 -11.010 -27.801 55.232 1.00 48.91 O
ATOM 5846 N ASN H 210 -9.208 -26.598 55.962 1.00 52.27 N
ATOM 5847 CA ASN H 210 -9.612 -26.391 57.353 1.00 53.33 C ATOM 5848 CB ASN H 210 -10.561 -25.186 57.487 1.00 62.28 C
ATOM 5849 CG ASN H 210 -10.006 -23.886 56.913 1.00 64.49 C
ATOM 5850 OD1 ASN H 210 -10.715 -23.147 56.200 1.00 66.62 O
ATOM 5851 ND2 AS H 210 -8.724 -23.575 57.202 1 ,00 66.39 N
ATOM 5852 C ASN H 210 -10.164 -27.686 57.966 1.00 53.49 C ATOM 5853 0 ASN H 210 -11.266 -27.717 58.535 1.00 54.39 O
ATOM 5854 N THR H 211 -9.381 -28.769 57.804 1.00 51 ,76 N
ATOM 5855 CA THR H 211 -9.697 -30.107 58.275 1.00 51.69 C
ATOM 5856 CB THR H 211 -9.605 -31.119 57.109 1.00 56.69 C
ATOM 5857 OG1 THR H 211 -10.355 -30.642 55.997 1 .00 56.69 O ATOM 5858 CG2 THR H 211 -10.087 -32.511 57.488 1.00 56.46 C
ATOM 5859 C THR H 211 -8.781 -30.475 59.432 1.00 51.76 C
ATOM 5860 O THR H 211 -7,564 -30.456 59.289 1.00 51.86 O
ATOM 5861 N LYS H 212 -9.374 -30.815 60.571 1.00 52.58 N
ATOM 5862 CA LYS H 212 -8.649 -31.236 61.759 1.00 52.88 C ATOM 5863 CB LYS H 212 -8.760 -30.198 62.905 1.00 57.19 C
ATOM 5864 CG LYS H 212 -7.967 -28.912 62.648 1.00 59.49 C
ATOM 5865 CD LYS H 212 -8.096 -27.819 63.750 1.00 64.42 C
ATOM 5866 CE LYS H 212 -7.237 -26.588 63.446 1.00 66.39 C
ATOM 5867 NZ LYS H 212 -7.448 -25.458 64.402 1.00 67.98 N ATOM 5868 C LYS H 212 -9.279 -32.566 62.120 1.00 52.46 C
ATOM 5869 O LYS H 212 -10.500 -32.634 62.315 1.00 52.24 O
ATOM 5870 N VAL H 213 -8.462 -33.642 62.130 1.00 52.14 N
ATOM 5871 CA VAL H 213 -8.911 -35.010 62.435 1.00 51.80 C
ATOM 5872 CB VAL H 213 -8.849 -35.947 61 ,178 1.00 53.43 C ATOM 5873 CG1 VAL H 213 -9.397 -37.336 61.474 1.00 53.01 C
ATOM 5874 CG2 VAL H 213 -9.561 -35.347 59.976 1.00 52.33 C
ATOM 5875 C VAL H 213 -8.046 -35.550 63.574 1.00 51.85 C
ATOM 5876 0 VAL H 213 -6.824 -35.424 63.501 1.00 52.15 O
ATOM 5877 N ASP H 214 -8.669 -36.136 64.612 1.00 53.48 N JB2010.7161
ATOM 5878 CA ASP H 214 -7.965 -36.736 65.751 1.00 53.86 C
ATOM 5879 CB ASP H 214 -8.387 -36.089 67.088 1.00 56.39 C
ATOM 5880 CG ASP H 214 -7.910 -34.663 67.310 1.00 57.01 C
ATOM 5881 OD1 ASP H 214 -6.703 -34.396 67.099 1.00 57.31 O ATOM 5882 OD2 ASP H 214 -8.745 -33.811 67.709 1.00 58.01 O
ATOM 5883 C ASP H 214 -8.343 -38.208 65.737 1.00 54.1 C
ATOM 5884 O ASP H 214 -9.446 -38.528 66.173 1.00 54.36 O
ATOM 5885 N LYS H 215 -7.473 -39.101 65.207 1.00 52.90 N
ATOM 5886 CA LYS H 215 -7.797 -40.534 65.117 1.00 53.22 C ATOM 5887 CB LYS H 215 -7.483 -41.088 63.703 1.00 56.11 C
ATOM 5888 CG LYS H 215 -7.893 -42.553 63.414 1.00 57.35 C
ATOM 5889 CD LYS H 215 -9.403 -42.846 63.265 1.00 58.11 C
ATOM 5890 CE LYS H 215 -10.060 -42.078 62.133 1.00 60.19 C
ATOM 5891 NZ LYS H 215 -1 1.487 -42.445 61.939 1.00 60.89 N ATOM 5892 C LYS H 215 -7.161 -41.380 66.213 1.00 53.16 C
ATOM 5893 0 LYS H 215 -5.976 -41.244 66.472 1.00 53.39 O
ATOM 5894 N LYS H 216 -7.953 -42.249 66.849 1.00 53.65 N
ATOM 5895 CA LYS H 216 -7.477 -43.146 67.897 1.00 54.12 C
ATOM 5896 CB LYS H 216 -8.567 -43.416 68.955 1.00 58.22 C ATOM 5897 CG LYS H 216 -8.021 -43.973 70.274 1 .00 60.25 C
ATOM 5898 CD LYS H 216 -9.120 -44.242 71.299 1.00 62.93 C
ATOM 5899 CE LYS H 216 -8.660 -45.084 72.473 1.00 64.24 C
ATOM 5900 NZ LYS H 216 -9.798 -45.529 73.343 1.00 65.23 N
ATOM 5901 C LYS H 216 -7.038 -44.441 67.227 1.00 54.02 C ATOM 5902 O LYS H 216 -7.794 -45.024 66.445 1.00 54.32 O
ATOM 5903 N VAL H 217 -5.805 -44.869 67.501 1.00 53.53 N
ATOM 5904 CA VAL H 217 -5.255 -46.094 66.930 1.00 53.75 C
ATOM 5905 CB VAL H 217 -3.773 -45.938 66.476 1.00 54.72 C
ATOM 5906 CG1 VAL H 217 -3.304 -47.164 65.703 1.00 53.88 C ATOM 5907 CG2 VAL H 217 -3.584 -44.684 65.635 1.00 54.18 C
ATOM 5908 C VAL H 217 -5.458 -47.205 67.967 1.00 54.41 C
ATOM 5909 O VAL H 217 -4.896 -47.135 69.069 1.00 54.34 O
ATOM 5910 N GLU H 218 -6.297 -48.198 67.641 1.00 58.00 N
ATOM 5911 CA GLU H 218 -6.541 -49.298 68.576 1.00 59.39 C ATOM 5912 CB GLU H 218 -8.042 -49.466 68.893 1.00 61.87 C
ATOM 5913 CG GLU H 218 -8.506 -48.459 69.931 1.00 63.95 C
ATOM 5914 CD GLU H 218 -9.886 -48.680 70.514 1.00 66.94 C
ATOM 5915 OE1 GLU H 218 -9.996 -49.452 71.498 1.00 67.96 O
ATOM 5916 OE2 GLU H 218 -10.853 -48.071 69.997 1.00 67.64 O ATOM 5917 C GLU H 218 -5.881 -50.586 68.089 1.00 59.79 C
ATOM 5918 0 GLU H 218 -5.735 -50.736 66.869 1.00 59.81 O
ATOM 5919 N PRO H 219 -5.455 -51.506 69.002 1.00 58.97 N
ATOM 5920 CA PRO H 219 -4.796 -52.744 68.551 1.00 59.69 C
ATOM 5921 CB PRO H 219 -4.318 -53.396 69.851 1.00 60.67 C ATOM 5922 CG PRO H 219 -4.426 -52.346 70.885 1.00 60.16 C
ATOM 5923 CD PRO H 219 -5.538 -51.468 70.473 1.00 59.98 C
ATOM 5924 C PRO H 219 -5.681 -53.690 67.744 1.00 60.57 C
ATOM 5925 0 PRO H 219 -6.884 -53.795 68.007 1.00 60.36 O
ATOM 5926 N LYS H 220 -5.054 -54.371 66.753 1.00 63.14 N ATOM 5927 CA LYS H 220 -5.625 -55.344 65.804 1.00 64.45 C
ATOM 5928 CB LYS H 220 -5.754 -56.762 66.412 1.00 68.34 C
ATOM 5929 CG LYS H 220 -4.394 -57.444 66.582 1.00 69.74 C
ATOM 5930 CD LYS H 220 -4.422 -58.965 66.354 1.00 72.01 C
ATOM 5931 CE LYS H 220 -3.063 -59.528 65.941 1.00 73.29 C JB2010.7161
ATOM 5932 NZ LYS H 220 -2.020 -59.383 67.000 1.00 72.76 N
ATOM 5933 C LYS H 220 -6.879 -54.888 65.029 1.00 64.63 C
ATOM 5934 O LYS H 220 -7.977 -54.800 65.584 1.00 65.10 O TER 5935 LYS H 220
ATOM 5936 N ASP L 1 22.210 -21.472 26.568 1.00 56.85 N
ATOM 5937 CA ASP L 1 22.330 -21.465 28.026 1.00 56.71 C
ATOM 5938 CB ASP L 1 21.135 -22.182 28.681 1.00 57.15 C
ATOM 5939 CG ASP L 1 19.767 -21.565 28.475 1.00 56.62 C
ATOM 5940 OD1 ASP L 1 18.823 -21.992 29.165 1.00 57.04 O ATOM 5941 OD2 ASP L 1 19.639 -20.650 27.616 1.00 55.70 O
ATOM 5942 C ASP L 1 23.584 -22.187 28.427 1.00 56.90 C
ATOM 5943 O ASP L 1 24.000 -23.116 27.730 1.00 57.33 O
ATOM 5944 N ILE L 2 24.185 -21.795 29.554 1.00 52.23 N
ATOM 5945 CA ILE L 2 25.383 -22.493 30.003 1.00 51.70 C ATOM 5946 CB ILE L 2 26.464 -21.565 30.606 1.00 52.39 C
ATOM 5947 CG1 ILE L 2 26.870 -20.458 29.592 1.00 51.26 C
ATOM 5948 CD1 ILE L 2 27.608 -19.281 30.157 1.00 49.94 C
ATOM 5949 CG2 ILE L 2 27.677 -22.399 31.050 1.00 51.52 C
ATOM 5950 C ILE L 2 24.966 -23.628 30.924 1.00 51.93 C ATOM 5951 O ILE L 2 24.290 -23.395 31.925 1.00 52.00 O
ATOM 5952 N GLN L 3 25.345 -24.857 30.579 1.00 51.79 N
ATOM 5953 CA GLN L 3 25.024 -26.020 31.397 1.00 52.27 C
ATOM 5954 CB GLN L 3 25.036 -27.271 30.524 1.00 55.08 C
ATOM 5955 CG GLN L 3 24.306 -28.464 31.126 1.00 58.73 C ATOM 5956 CD GLN L 3 24.497 -29.727 30.290 1 ,00 63.45 C
ATOM 5957 OE1 GLN L 3 23,522 -30.336 29.801 1.00 65.29 O
ATOM 5958 NE2 GLN L 3 25.763 -30.151 30.100 1.00 63.83 N
ATOM 5959 C GLN L 3 26.044 -26.133 32.544 1 .00 51.64 C
ATOM 5960 O GLN L 3 27.250 -26.016 32.310 1.00 51.78 O ATOM 5961 N MET L 4 25.559 -26.317 33.778 1 .00 47.22 N
ATOM 5962 CA MET L 4 26.415 -26.483 34.948 1.00 47.02 C
ATOM 5963 CB MET L 4 26.090 -25.492 36.094 1 ,00 48.37 C
ATOM 5964 CG MET L 4 26.228 -24.009 35.752 1.00 47.31 C
ATOM 5965 SD MET L 4 27.893 -23.449 35.315 1.0047.54 S ATOM 5966 CE MET L 4 28.636 -23.200 36.902 1.00 44.49 C
ATOM 5967 C MET L 4 26.249 -27.940 35.415 1.00 47.54 C
ATOM 5968 O MET L 4 25.136 -28.358 35.764 1.00 48.06 O
ATOM 5969 N THR L 5 27.347 -28.717 35.393 1.00 47.71 N
ATOM 5970 CA THR L 5 27.347 -30.123 35.795 1.00 47.70 C ATOM 5971 CB THR L 5 27.842 -31.010 34.637 1.00 54.99 C
ATOM 5972 OG1 THR L 5 26.905 -30.933 33.566 1.00 54.57 O
ATOM 5973 CG2 THR L 5 27.993 -32,462 35.034 1.00 55.48 C
ATOM 5974 C THR L 5 28.113 -30.302 37.105 1.00 47.80 C
ATOM 5975 O THR L 5 29.334 -30.135 37,155 1.00 47.96 O ATOM 5976 N GLN L 6 27.384 -30.636 38.163 1.00 46.99 N
ATOM 5977 CA GLN L 6 27.948 -30.854 39.490 1.00 46.64 C
ATOM 5978 CB GLN L 6 26.979 -30.388 40.561 1.00 46.69 C
ATOM 5979 CG GLN L 6 27.473 -29.192 41.290 1.00 46.69 C
ATOM 5980 CD GLN L 6 26.398 -28.724 42.214 1.00 47.74 C ATOM 5981 OE1 GLN L 6 25.462 -28.038 41.814 1.0048.86 O
ATOM 5982 NE2 GLN L 6 26.506 -29.097 43.474 1.00 47.32 N
ATOM 5983 C GLN L 6 28.221 -32.306 39,703 1.00 46.53 C
ATOM 5984 0 GLN L 6 27.469 -33.152 39.223 1.00 46.90 O
ATOM 5985 N SER L 7 29.290 -32.610 40.434 1.00 47.89 N JB2010.7161
ATOM 5986 CA SERL 7 29.648-33.99240.747 1.0047.55 C
ATOM 5987 CB SER L 7 30.461 -34.63739.624 1.0053.00 C
ATOM 5988 OG SER L 7 31.854-34.461 39.816 1.0054.36 O
ATOM 5989 C SER L 7 30.363-34.06342.106 1.0046.96 C ATOM 5990 O SER L 7 31.159-33.16642.425 1.0046.83 O
ATOM 5991 N PRO L 8 30.063-35.101 42.932 1.0044.47 N
ATOM 5992 CA PRO L 8 29.095-36.18742.675 1.0043.81 C
ATOM 5993 CB PRO L 8 29.527-37.26843.671 1.0044.49 C
ATOM 5994 CG PRO L 8 30.105-36.50444.831 1.0044.40 C ATOM 5995 CD PRO L 8 30.683-35.22944.271 1.0044.80 C
ATOM 5996 C PRO L 8 27.667 -35.68242.902 .0043.24 C
ATOM 5997 O PRO L 8 27.487-34.581 43.407 1.0043.02 O
ATOM 5998 N SER L 9 26.660-36.461 42.531 1.0045.08 N
ATOM 5999 CA SER L 9 25.290-36.03242.750 1.0044.98 C ATOM 6000 CB SER L 9 24.317-36.86941.929 1.0053.47 C
ATOM 6001 OG SER L 9 24.234-38.19642.429 1.0055.85 O
ATOM 6002 C SERL 9 24.990-36.11844.248 1.0044.31 C
ATOM 6003 O SERL 9 24.023-35.51744.723 1.0044.36 O
ATOM 6004 N SERL 10 25.835-36.851 44.983 1.0042.97 N ATOM 6005 CA SERL 10 25.761 -37.02546.431 1.0043.00 C
ATOM 6006 CB SE L 10 24.482-37.75046.858 1.0046.65 C
ATOM 6007 OG SERL 10 24.473-39.11346.472 1.0046.34 O
ATOM 6008 C SERL 10 26.978-37.75846.977 1.0042.84 C
ATOM 6009 O SERL 10 27.524-38.63246.301 1.0042.42 O ATOM 6010' N LEU L 11 27.369-37.41948.218 1.0043.95 N
ATOM 6011 CA LEU L 11 28.477 -38.05648.924 1.0044.60 C
ATOM 6012 CB LEU L 11 29.840-37.37648.655 1.0043.65 C
ATOM 6013 CG LEU L 11 30.050-35.97749.201 1.0043.43 C
ATOM 6014 CD1 LEU L 11 30.710-36.005 50.555 1.0042.72 C ATOM 6015 CD2 LEU L 11 30.855-35.14848.245 1.0042.84 C
ATOM 6016 C LEU L 11 28.212-38.224 50.426 1.0045.27 C
ATOM 6017 O LEU L 11 27.590-37.361 51.054 1.0045.55 O
ATOM 6018 N SERL 12 28.693-39.339 51.000 1.0049.17 N
ATOM 6019 CA SERL 12 28.548-39.60052.434 1.0049.59 C ATOM 6020 CB SERL 12 28.161 -41.05052.686 1.0055.29 C
ATOM 6021 OG SERL 12 29.090-41.919 52.060 1.0056.49 O
ATOM 6022 C SERL 12 29.896-39.301 53.079 1.0049.19 C
ATOM 6023 O SER L 12 30.920-39.742 52.555 1.0049.39 O
ATOM 6024 N ALA L 13 29.910-38.553 54.190 1.0046.40 N ATOM 6025 CA ALA L 13 31.151 -38.225 54.867 1.0046.48 C
ATOM 6026 CB ALA L 13 31.737-36.958 54.279 1.0047.13 C
ATOM 6027 C ALA L 13 31.007-38.11056.400 1.0046.95 C
ATOM 6028 O ALA L 13 29.897-37.961 56.921 1.0047.43 O
ATOM 6029 N SERL 14 32.135-38.210 57.121 1.0047.06 N ATOM 6030 CA SERL 14 32.155-38.129 58.578 1.0047.44 C
ATOM 6031 CB SERL 14 33.177-39.108 59.144 1.0049.65 C
ATOM 6032 OG SERL 14 33.166-40.34958.452 1.0049.68 O
ATOM 6033 C SERL 14 32.501 -36.713 58.977 1.0047.79 C
ATOM 6034 O SERL 14 33.000-35.961 58.140 1.0048.05 O ATOM 6035 N VAL L 15 32.217-36.31960.235 1.0050.60 N
ATOM 6036 CA VAL L 15 32.562-34.97360.720 1.0051.01 C
ATOM 6037 CB VAL L 15 31.920-34.67562.107 1.0053.74 C
ATOM 6038 CG1VALL 15 32.622-33.52462.838 1.0053.21 C
ATOM 6039 CG2VALL 15 30.434-34.38061.957 1.0054.09 C JB2010.7161
ATOM 6040 C VALL 15 34.117-34.92060.742 1.0051.52 C
ATOM 6041 0 VALL 15 34.762-35.919 61.115 1.0052.11 O
ATOM 6042 N GLY L 16 34.688-33.802 60.298 1.0049.65 N
ATOM 6043 CA GLY L 16 36.135-33.64360.244 1.0049.60 C ATOM 6044 C GLY L 16 36.734-34.025 58.898 1.0049.74 C
ATOM 6045 O GLY L 16 37.899-33.697 58.644 1.0050.19 O
ATOM 6046 N ASP L 17 35.957-34.706 58.011 1.0046.62 N
ATOM 6047 CA ASP L 17 36.428-35.063 56.670 1.0046.94 C
ATOM 6048 CB ASP L 17 35.444-36.009 55.954 1,0048.31 C ATOM 6049 CG ASP L 17 35.505-37.49956.264 1.0049.58 C
ATOM 6050 OD1AS L 17 36.164-37.889 57.279 1.0050.77 O
ATOM 6051 OD2ASPL 17 34,885-38.287 55.506 1.0050.35 O
ATOM 6052 C ASP L 17 36.594-33.780 55.795 1.0047.49 C
ATOM 6053 O ASP L 17 36.003-32.717 56.074 1.0046.93 O ATOM 6054 N ARG L 18 37.424-33.90354.739 1.0050.29 N
ATOM 6055 CA ARG L 18 37.638-32.845 53.774 1.0050.82 C
ATOM 6056 CB ARG L 18 39.102-32.72653.347 1.0055.70 C
ATOM 6057 CG ARG L 18 39.294-31.683 52.250 1.0057.09 C
ATOM 6058 CD ARG L 18 40,645-31.76951.588 1.0059.25 C ATOM 6059 NE ARG L 18 41.103-30.430 51.205 1.0061.18 N
ATOM 6060 CZ ARG L 18 41.328-30.03549.950 1.0061.70 C
ATOM 6061 NH1 ARGL 18 41.164-30.88448.935 1.0060.94 N
ATOM 6062 NH2 ARG L 18 41.727-28.78949.701 1.0062.16 N
ATOM 6063 C ARG L 18 36.783-33.281 52.608 1.0050.66 C ATOM 6064 O ARG L 18 36.908-34.416 52.149 1.0051.17 O
ATOM 6065 N VALL 19 35.885-32.409 52.152 1.0049.11 N
ATOM 6066 CA VALL 19 35.008-32.749 51.033 1.0048.70 C
ATOM 6067 CB VALL 19 33.506-32,966 51.407 1.0052.67 C
ATOM 6068 CG1VALL 19 33.332-34.141 52.371 1.0053.11 C ATOM 6069 CG2 VAL L 19 32.872-31.706 51.979 1.0052.81 C
ATOM 6070 C VALL 19 35.177-31.771 49.920 1.0048.30 C
ATOM 6071 O VALL 19 35.312-30.571 50.161 1.0047.96 O
ATOM 6072 N THR L 20 35.201 -32.28248.700 1.0046.55 N
ATOM 6073 CA THR L 20 35.312-31.41447.546 1.0046.73 C ATOM 6074 CB THR L 20 36.756-31.28346.976 1.0057.01 C
ATOM 6075 OG1THRL 20 37.040-32.34946.069 1.0057.18 O
ATOM 6076 CG2THRL 20 37.840-31.14448.050 1.0055.86 C
ATOM 6077 C THR L 20 34.227-31.75246.525 1.0046.73 C
ATOM 6078 O THR L 20 34.106-32.904 46.100 1.0046.55 O ATOM 6079 N ILE L 21 33.435-30.73646.152 1.0046.14 N
ATOM 6080 CA ILE L 21 32.352-30.82245.166 1.0046.26 C
ATOM 6081 CB ILE L 21 31.046-30.14845.704 1.0049.00 C
ATOM 6082 CG1 ILEL 21 30.549-30.817 47.000 1.0048.32 C
ATOM 6083 CD11LEL 21 29.896-29.88047.932 1.0048.21 C ATOM 6084 CG2 ILE L 21 29.937-30.09544.635 1.0048.85 C
ATOM 6085 C ILE L 21 32.865-30.13743.891 1.0046.47 C
ATOM 6086 O ILE L 21 33.395-29.03643.950 1.0046.17 O
ATOM 6087 N THR L 22 32.694-30.795 42.751 1.0049.56 N
ATOM 6088 CA THR L 22 33.118-30.30641.438 1.0050.44 C ATOM 6089 CB THR L 22 33.889-31.44440.734 1.0054.95 C
ATOM 6090 OG1 THR L 22 35.285 -31.20340.889 1.0054.79 O
ATOM 6091 CG2THRL 22 33.508-31.646 39.262 1.0054.61 C
ATOM 6092 C THR L 22 31,930-29.718 40.647 1.0051.14 C
ATOM 6093 O THR L 22 30.801 -30.19740.781 1.0051.53 O JB2010.7161
ATOM 6094 N CYS L 23 32.196-28.692 39.833 1,0050.38 N
ATOM 6095 CA CYS L 23 31.207-28.039 38.995 1.0051.14 C
ATOM 6096 CB CYS L 23 30.596-26.828 39.691 1.0050.93 C
ATOM 6097 SG CYS L 23 29.281 -26.022 38.735 1.0052.84 S ATOM 6098 C CYS L 23 31.826-27.660 37.670 1.0051.69 C
ATOM 6099 O CYS L 23 32.752-26.84637.611 1.0052.15 O
ATOM 6100 N LYSL 24 31.316-28.247 36.605 1.0053.93 N
ATOM 6101 CA LYSL 24 31.806-27.961 35.275 1.0054.47 C
ATOM 6102 CB LYS L 24 32.116-29.258 34.517 1.0059.23 C ATOM 6103 CG LYSL 24 33.580-29.381 34.094 1.0061.73 C
ATOM 6104 CD LYSL 24 34.556-29.488 35.299 1.0066.24 C
ATOM 6105 CE LYS L 24 34.743-30.882 35.877 1.0067.90 C
ATOM 6106 NZ LYSL 24 35.248-31.87534.875 1.0069.79 N
ATOM 6107 C LYSL 24 30.836-27.105 34.501 1.0054.17 C ATOM 6108 O LYSL 24 29.637-27.378 34.510 1.0054.15 O
ATOM 6109 N ALA L 25 31.357-26.079 33.817 1.0052.91 N
ATOM 6110 CA ALA L 25 30.574-25.175 32.977 1.0052.26 C
ATOM 6111 CB ALA L 25 31.050-23.745 33.167 1.0052.76 C
ATOM 6112 C ALAL 25 30.740-25.596 31.517 1.0051.83 C ATOM 6113 O ALAL 25 31.843-25.954 31.104 1.0052.27 O
ATOM 6114 N SER L 26 29.652-25.57530.743 1.0051.04 N
ATOM 6115 CA SER L 26 29.668-25.93829.326 1.0050.38 C
ATOM 6116 CB SER L 26 28.246-26.22028.840 1.0053.14 C
ATOM 6117 OG SER L 26 27.532-25.048 28.477 1.0052.96 O ATOM 6118 C SER L 26 30.382-24.87428.424 1.0050.46 C
ATOM 6119 0 SER L 26 30.699-25.166 27.264 1.0050.04 O
ATOM 6120 N GLN L 27 30.619-23.65728.965 1.0051.58 N
ATOM 6121 CA GLN L 27 31.266-22.52728.287 1.0051.81 C
ATOM 6122 CB GLN L 27 30.193-21.58027.689 1.0054.30 C ATOM 6123 CG GLN L 27 29.623-22.051 26.347 1.0057.45 C
ATOM 6124 CD GLN L 27 28.101 -22.12226.304 1.0061.11 C
ATOM 6125 OE1 GLN L 27 27.415-21.091 26.177 1.0061.77 O
ATOM 6126 NE2GLN L 27 27.533-23.34526.397 1.0061.28 N
ATOM 6127 C GLN L 27 32.090-21.75529.303 1.0051.14 C ATOM 6128 0 GLN L 27 31.780-21.855 30.489 1.0050.86 O
ATOM 6129 N ASN L 28 33.113-20.951 28.864 1.0052.46 N
ATOM 6130 CA ASN L 28 33.903-20.14429.820 1.0051.45 C
ATOM 6131 CB ASN L 28 34.967-19.25229.154 1.0055.57 C
ATOM 6132 CG ASN L 28 35.947-18.572 30.134 1.0057.24 C ATOM 6133 OD1 ASN L 28 35.585-18.02431.182 1.0058.39 O
ATOM 6134 ND2ASNL 28 37.241 -18.581 29.816 1.0060.49 N
ATOM 6135 C ASN L 28 32.909-19.291 30.600 1.0050.28 C
ATOM 6136 O ASN L 28 31.907-18.837 30.038 1.0050.84 O
ATOM 6137 N VAL L 29 33.165-19.10631.889 1.0045.24 N ATOM 6138 CA VAL L 29 32.290-18.373 32.793 1.0044.06 C
ATOM 6139 CB VAL L 29 31.470-19.46533.572 1.0047.07 C
ATOM 6140 CG1 VAL L 29 31.261 -19.15735.035 1.0047.35 C
ATOM 6141 CG2VALL 29 30.153-19,788 32.876 1.0046.45 C
ATOM 6142 C VAL L 29 33.133-17.37633.650 1.0043.44 C ATOM 6143 O VAL L 29 32.585-16.616 34.473 1.0042.83 O
ATOM 6144 N GLY L 30 34.455-17.372 33.387 1.0042.12 N
ATOM 6145 CA GLY L 30 35.440-16.549 34.084 1.0040.99 C
ATOM 6146 C GLY L 30 35.441 -17.007 35.521 1.0040.51 C
ATOM 6147 O GLY L 30 35.707-18,181 35.792 1,0040.80 O JB2010.7161
ATOM 6148 N THR L 31 35.081 -16.118 36.442 1.0038.61 N
ATOM 6149 CA THR L 31 34.967-16.498 37.841 1.0037.83 C
ATOM 6150 CB THR L 31 36.071 -15.881 38.693 1.0037.80 C
ATOM 6151 OG1 THRL 31 35.913-14.466 38.723 1.0038.78 O ATOM 6152 CG2THR L 31 37.476-16.297 38.271 1.0037.41 C
ATOM 6153 C THR L 31 33.584-16.080 38.321 1.0037.83 C
ATOM 6154 0 THR L 31 33.424-15.772 39.495 1.0037.69 O
ATOM 6155 N ASN L 32 32.579-16.034 37.418 1.0039.84 N
ATOM 6156 CA ASN L 32 31.214-15.646 37.784 1.0039.91 C ATOM 6157 CB ASN L 32 30.497-14.961 36.630 1.0047.46 C
ATOM 6158 CG ASN L 32 31.172-13.721 36.132 1.0049.20 C
ATOM 6159 OD1 ASN L 32 31.568-13.647 34.966 1.0053.55 O
ATOM 6160 ND2AS L 32 31.326-12.720 36.987 1.0049.76 N
ATOM 6161 C ASN L 32 30.460-16.883 38.222 1.0039.24 C ATOM 6162 0 ASN L 32 29.530-17.329 37.546 1.0038.51 O
ATOM 6163 N VAL L 33 30.901 -17.460 39.350 1.0039.99 N
ATOM 6164 CA VAL L 33 30.340-18.662 39.948 1.0039.37 C
ATOM 6165 CB VAL L 33 31.244-19.898 39.694 1.0042.16 C
ATOM 6166 CG1 VAL L 33 31.022-21.022 40.708 1.0042.02 C ATOM 6167 CG2VALL 33 31.027-20.421 38.290 1.0042.01 C
ATOM 6168 C VAL L 33 30.010-18.401 41.414 1.0038.91 C
ATOM 6169 O VAL L 33 30.835-17.85742.152 1.0039.90 O
ATOM 6170 N VAL L 34 28.789-18.751 41.810 1.0036.44 N
ATOM 6171 CA VAL L 34 28.279-18.63043.177 1.0035.84 C ATOM 6172 CB VAL L 34 27.084-17.621 43.262 1.0039.53 C
ATOM 6173 CG1VALL 34 25.958-17.96942.293 1.0037.69 C
ATOM 6174 CG2VALL 34 26.562-17.45544.688 1.0039.60 C
ATOM 6175 C VAL L 34 27.979-20.07043.734 1.0035.64 C
ATOM 61760 VAL L 34 27.652-20.98342.961 1.0035.53 O ATOM 6177 N TRP L 35 28.150-20.27545.047 1.0034.01 N
ATOM 6178 CA TRP L 35 27.897-21.57945.694 1.0033.88 C
ATOM 6179 CB TRP L 35 29.176-22.17246.304 1.0031.62 C
ATOM 6180 CG TRP L 35 30.116-22.75245.288 1.0032.66 C
ATOM 6181 CD1TRPL 35 31.178-22.128 44.692 1.0033.43 C ATOM 6182 NE1 TRP L 35 31.787-22.981 43.793 1.0033.02 N
ATOM 6183 CE2TRPL 35 31.132-24.18643.809 1.0032.45 C
ATOM 6184 CD2TRP L 35 30.070-24.07844.740 1.0032.54 C
ATOM 6185 CE3TRPL 35 29.216-25.17544.923 1.0031.79 C
ATOM 6186 CZ3TRPL 35 29.453-26.331 44.204 1.0033.40 C ATOM 6187 CH2TRP L 35 30.526-26.42343.306 1.0034.47 C
ATOM 6188 CZ2TRPL 35 31.375-25.35743.086 1.0033.47 C
ATOM 6189 C TRP L 35 26.832-21.38746.751 1.0033.58 C
ATOM 6190 O TRP L 35 26.909-20.44047.551 1.0033.70 O
ATOM 6191 N TYR L 36 25.801 -22.22946.723 1.0033.53 N ATOM 6192 CA TYR L 36 24.706-22.10547.693 1.0033.31 C
ATOM 6193 CB TYR L 36 23.341 -21.88447.015 1.0033.22 C
ATOM 6194 CG TYR L 36 23.193-20.62246.198 1.0032.66 C
ATOM 6195 CD1TY L 36 23.388-20.63644.826 1.0033.32 C
ATOM 6196 CE1TYRL 36 23.211 -19.48844.059 1.0033.23 C ATOM 6197 CZ TYR L 36 22.843-18.301 44.667 1.0032.01 C
ATOM 6198 OH TYR L 36 22.687-17.17843.882 1.0033.10 O
ATOM 6199 CE2TYRL 36 22.629-18.26546.032 1.0030.99 C
ATOM 6200 CD2TYRL 36 22.785-19.42946.786 1.0032.50 C
ATOM 6201 C TYR L 36 24.603-23.33748.545 1.0033.80 C JB2010.7161
ATOM 6202 O TYR L 36 24.955 -24.438 48.103 1.00 34.28 O
ATOM 6203 N GLN L 37 24.082 -23.160 49.757 1.00 34.69 N
ATOM 6204 CA GLN L 37 23.865 -24.258 50.686 1.00 34.82 C
ATOM 6205 CB GLN L 37 24.685 -24.095 51.967 1.00 35.20 C ATOM 6206 CG GLN L 37 24.378 -25.212 52.940 1.00 36.67 C
ATOM 6207 CD GLN L 37 24.841 -24.909 54.311 1.00 38.23 C
ATOM 6208 OE1 GL L 37 24.286 -24.022 54.984 1.00 38.57 O
ATOM 6209 NE2 GLN L 37 25.873 -25.654 54.749 1.00 37.92 N
ATOM 6210 C GLN L 37 22.374 -24.341 51.020 1.00 34.83 C ATOM 6211 0 GLN L 37 21.748 -23.354 51.458 1.00 34.67 O
ATOM 6212 N GLN L 38 21.819 -25.526 50.847 1.00 33.45 N
ATOM 6213 CA GLN L 38 20.428 -25.664 51.158 1.00 33.41 C
ATOM 6214 CB GLN L 38 19.576 -25.771 49.887 1.00 34.64 C
ATOM 6215 CG GLN L 38 18.186 -25.214 50.119 1.00 33.82 C ATOM 6216 CD GLN L 38 17.210 -25.598 49.057 1.00 34.80 C
ATOM 6217 OE1 GLN L 38 17.546 -26.241 48.041 1.00 36.47 O
ATOM 6218 NE2 GLN L 38 15.962 -25.212 49.280 1.00 34.82 N
ATOM 6219 C GLN L 38 20.152 -26.789 52.091 1.00 33.67 C
ATOM 6220 O GLN L 38 20.590 -27.917 51.873 1.00 32.86 O ATOM 6221 N LYS L 39 19.388 -26.466 53.118 1.00 36.79 N
ATOM 6222 CA LYS L 39 18.915 -27.391 54.130 1.00 38.34 C
ATOM 6223 CB LYS L 39 19.180 -26.834 55.532 1.00 40.15 C
ATOM 6224 CG LYS L 39 20.615 -27.089 55.927 1.00 41.30 C
ATOM 6225 CD LYS L 39 20.952 -26.528 57.264 1.0043.61 C ATOM 6226 CE LYS L 39 22.320 -27.017 57.658 1.00 45.71 C
ATOM 6227 NZ LYS L 39 22.632 -26.733 59.093 1.00 48.25 N
ATOM 6228 C LYS L 39 17.411 -27.642 53.870 1.00 39.22 C
ATOM 6229 O LYS L 39 16.725 -26.733 53.390 1.00 39.57 O
ATOM 6230 N PRO L 40 16.886 -28.860 54.155 1.00 41.15 N ATOM 6231 CA PRO L 40 15.446 -29.130 53.907 1.00 41.47 C
ATOM 6232 CB PRO L 40 15.242 -30.525 54.487 1.00 43.33 C
ATOM 6233 CG PRO L 40 16.614 -31.158 54.408 1.0043.44 C
ATOM 6234 CD PRO L 40 17.573 -30.046 54.709 1.00 42.40 C
ATOM 6235 C PRO L 40 14.506 -28.117 54.553 1.00 41.90 C ATOM 6236 0 PRO L 40 14.731 -27.696 55.689 1.00 42.06 O
ATOM 6237 N GLY L 41 13.493 -27.704 53.787 1.00 42.50 N
ATOM 6238 CA GLY L 41 12.500 -26.722 54.211 1.00 42.27 C
ATOM 6239 C GLY L 41 13.043 -25.320 54.424 1.00 42.43 C
ATOM 6240 O GLY L 41 12.424 -24.51 1 55.123 1.00 42.71 O ATOM 6241 N LYS L 42 14.215 -25.020 53.849 1.00 41.74 N
ATOM 6242 CA LYS L 42 14.845 -23.705 53.990 1.00 41.40 C
ATOM 6243 CB LYS L 42 16.068 -23.754 54.943 1.00 45.27 C
ATOM 6244 CG LYS L 42 15.787 -24.137 56.401 1.00 48.00 C
ATOM 6245 CD LYS L 42 15.184 -23.007 57.259 1.00 54.05 C ATOM 6246 CE LYS L 42 15.133 -23.352 58.748 1.00 58.44 C
ATOM 6247 NZ LYS L 42 14.054 -24.333 59.099 1.00 60.51 N
ATOM 6248 C LYS L 42 15.258 -23.152 52.625 1.0040.29 C
ATOM 6249 0 LYS L 42 15.492 -23.917 51.678 1.00 39.82 O
ATOM 6250 N ALA L 43 15.330 -21.817 52.532 1.00 36.19 N ATOM 6251 CA ALA L 43 15.762 -21.131 51.333 1.00 35.56 C
ATOM 6252 CB ALA L 43 15.529 -19.644 51.494 1.00 36.11 C
ATOM 6253 C ALA L 43 17.263 -21.370 51.223 1.00 35.48 C
ATOM 6254 O ALA L 43 17.931 -21.506 52.263 1.00 35.06 O
ATOM 6255 N PRO L 44 17.840 -21.401 50.005 1.00 33.19 N JB2010.7161
ATOM 6256 CA PRO L 44 19.301 -21.561 49.907 1.00 33.73 C
ATOM 6257 CB PRO L 44 19.545 -21.629 48.394 1.00 34.29 C
ATOM 6258 CG PRO L 44 18.173 -21.960 47.790 1.00 33.06 C
ATOM 6259 CD PRO L 44 17.218 -21.257 48.672 1.00 33.28 C ATOM 6260 C PRO L 44 20.054 -20.382 50.556 1.00 34.65 C
ATOM 6261 O PRO L 44 19.468 -19.329 50.880 1.00 34.57 O
ATOM 6262 N LYS L 45 21.347 -20.565 50.792 1.00 38.85 N
ATOM 6263 CA LYS L 45 22.181 -19.522 51.389 1.00 39.67 C
ATOM 6264 CB LYS L 45 22.438 -19.813 52.879 1.00 45.77 C ATOM 6265 CG LYS L 45 23.384 -18.821 53.564 1.00 49.42 C
ATOM 6266 CD LYS L 45 23.602 -19.119 55.060 1.00 52.87 C
ATOM 6267 CE LYS L 45 24.984 -19.662 55.385 1.00 56.40 C
ATOM 6268 N2 LYS L 45 25.206 -19.859 56.861 1.00 57.24 N
ATOM 6269 C LYS L 45 23.479 -19.474 50.608 1.00 39.39 C ATOM 6270 O LYS L 45 24.154 -20.496 50.497 1.00 39.67 O
ATOM 6271 N ALA L 46 23.833 -18.303 50.068 1 .00 38.49 N
ATOM 6272 CA ALA L 46 25.079 -18.139 49.295 1.00 38.18 C
ATOM 6273 CB ALA L 46 25.068 -16.815 48.536 1.00 38.68 C
ATOM 6274 C ALA L 46 26.281 -18.213 50.213 1.00 37.91 C ATOM 6275 0 ALA L 46 26.315 -17.545 51.240 1.00 38.05 O
ATOM 6276 N LEU L 47 27.244 -19.042 49.856 1.00 39.06 N
ATOM 6277 CA LEU L 47 28.466 -19.244 50.636 1.00 39.93 C
ATOM 6278 CB LEU L 47 28.803 -20.751 50.768 1.00 38.95 C
ATOM 6279 CG LEU L 47 27.769 -21.683 51.394 1.00 38.15 C ATOM 6280 CD1 LEU L 47 28.170 -23.097 51.187 1.00 38.31 C
ATOM 6281 CD2 LEU L 47 27.583 -21.433 52.887 1.00 36.24 C
ATOM 6282 C LEU L 47 29.632 - 8.496 49.988 1.00 40.92 C
ATOM 6283 0 LEU L 47 30.196 -17.588 50.592 1.00 41.18 O
ATOM 6284 N ILE L 48 29.964 -18.880 48.749 1.00 44.28 N ATOM 6285 CA ILE L 48 31.033 -18.307 47.936 1.00 45.02 C
ATOM 6286 CB ILE L 48 31.926 -19.462 47.374 1.00 47.96 C
ATOM 6287 CG1 ILE L 48 32.438 -20.457 48.447 1.00 48.50 C
ATOM 6288 CD1 ILE L 48 33.626 -20.029 49.325 1.00 50.10 C
ATOM 6289 CG2 ILE L 48 33.026 -18.971 46.451 1.00 47.55 C ATOM 6290 C ILE L 48 30.409 -17.507 46.779 1.00 45.24 C
ATOM 6291 0 ILE L 48 29.334 -17.870 46.296 1.00 45.27 O
ATOM 6292 N HIS L 49 31.103 -16.438 46.338 1.00 45.01 N
ATOM 6293 CA HIS L 49 30.802 -15.568 45.193 1.00 45.03 C
ATOM 6294 CB HIS L 49 30.154 -14.225 45.605 1.00 45.28 C ATOM 6295 CG HIS L 49 31.071 -13.194 46.196 1.00 46.33 C
ATOM 6296 ND1 HIS L 49 30.934 -12.768 47.513 1.00 47.80 N
ATOM 6297 CE1 HIS L 49 31.875 -11.850 47.694 1.00 46.74 C
ATOM 6298 NE2 HIS L 49 32.582 -11.648 46.580 1.00 45.90 N
ATOM 6299 CD2 HIS L 49 32.075 -12.490 45.618 1.00 46.18 C ATOM 6300 C HIS L 49 32.130 -15.364 44.435 1.00 45.12 C
ATOM 6301 O HIS L 49 33.197 -15.688 44.973 1.00 45.08 O
ATOM 6302 N SER L 50 32.089 -14.851 43.200 1.00 45.08 N
ATOM 6303 CA SER L 50 33.310 -14.620 42.424 1.00 45.32 C
ATOM 6304 CB SER L 50 34.062 -13.404 42.958 1.00 47.10 C ATOM 6305 OG SER L 50 33.218 -12.267 42.935 1.00 47.36 O
ATOM 6306 C SER L 50 34.227 -15.859 42.360 1.00 45.50 C
ATOM 6307 O SER L 50 35.449 -15.727 42.261 1.00 45.66 O
ATOM 6308 N ALA L 51 33.617 -17.059 42.407 1.00 44.44 N
ATOM 6309 CA ALA L 51 34.251 -18.382 42.379 1.0044.12 C JB2010J161
ATOM 6310 CB ALA L 51 35.088 -18.570 41.116 1.00 44.39 C
ATOM 6311 C ALA L 51 35.057 -18.790 43.636 1.0044.07 C
ATOM 6312 O ALA L 51 35.193 -19.991 43.876 1.0044.06 O
ATOM 6313 N SER L 52 35.562 -17.809 44.435 1.00 43.12 N ATOM 6314 CA SER L 52 36.412 -18.060 45.601 1.00 43.05 C
ATOM 6315 CB SER L 52 37.862 -18.247 45.136 1.00 48.02 C
ATOM 6316 OG SER L 52 38.362 -17.144 44.385 1.00 49.01 O
ATOM 6317 C SER L 52 36.361 -16.984 46.710 1.00 42.91 C
ATOM 6318 O SER L 52 37.338 -16.833 47.444 1.00 42.66 O ATOM 6319 N TYR L 53 35.259 -16.250 46.850 1.0042.91 N
ATOM 6320 CA TYR L 53 35.173 -15.239 47.907 1.00 43.64 C
ATOM 6321 CB TYR L 53 35.124 -13.803 47.343 1.00 45.60 C
ATOM 6322 CG TYR L 53 36.444 -13.333 46.762 1.00 47.95 C
ATOM 6323 CD1 TYR L 53 37.263 -12.449 47.463 1.00 49.33 C ATOM 6324 CE1 TYR L 53 38.486 -12.028 46.941 1.00 51.54 C
ATOM 6325 CZ TYR L 53 38.901 -12.494 45.701 1.00 52.74 C
ATOM 6326 OH TYR L 53 40.109 -12.102 45.166 1.00 54.08 O
ATOM 6327 CE2 TYR L 53 38.102 -13.375 44.988 1.00 51.57 C
ATOM 6328 CD2 TYR L 53 36.883 -13.785 45.517 1.00 49.77 C ATOM 6329 C TYR L 53 33.978 -15.537 48.792 1.00 43.54 C
ATOM 6330 O TYR L 53 32.869 -15.680 48.286 1.00 43.97 O
ATOM 6331 N ARG L 54 34.191 -15.649 50.107 1.00 44.12 N
ATOM 6332 CA ARG L 54 33.099 -15.967 51.017 1.00 44.02 C
ATOM 6333 CB ARG L 54 33.630 -16.556 52.337 1.00 45.36 C ATOM 6334 CG ARG L 54 34.415 -17.871 52.169 1.00 45.41 C
ATOM 6335 CD ARG L 54 34.801 -18.543 53.479 1.00 45.27 C
ATOM 6336 NE ARG L 54 35.031 - 7.588 54.562 1.0045.59 N
ATOM 6337 CZ ARG L 54 36.214 -17.075 54.889 1.0045.25 C
ATOM 6338 NH1 ARG L 54 37.313 -17.438 54.228 1.00 46.53 N ATOM 6339 NH2 ARG L 54 36.312 -16.200 55.884 1.00 43.46 N
ATOM 6340 C ARG L 54 32.170 -14.788 51.288 1.00 43.62 C
ATOM 6341 O ARG L 54 32.622 - 3.642 51.275 1.00 43.47 O
ATOM 6342 N TYR L 55 30.874 -15.070 51.547 1.00 42.55 N
ATOM 6343 CA TYR L 55 29.885 -14.047 51.888 1.00 42.49 C ATOM 6344 CB TYR L 55 28.454 -14.551 51.626 1.00 43.15 C
ATOM 6345 CG TYR L 55 27.971 -14.345 50.211 1.00 40.73 C
ATOM 6346 CD1 TYR L 55 27.107 -13.306 49.898 1.00 39.08 C
ATOM 6347 CE1 TYR L 55 26.661 -13.102 48.595 1.00 39.34 C
ATOM 6348 CZ TYR L 55 27.069 -13.960 47.586 1.00 40.25 C ATOM 6349 OH TYR L 55 26.619 -13.753 46.300 1.00 41.11 O
ATOM 6350 CE2 TYR L 55 27.914 -15.022 47.881 1.00 39.64 C
ATOM 6351 CD2 TYR L 55 28.372 -15.197 49.185 1.00 39.59 C
ATOM 6352 C TYR L 55 30.061 -13.712 53.363 1.00 43.19 C
ATOM 6353 0 TYR L 55 30.784 -14.419 54.051 1.0043.16 O ATOM 6354 N SER L 56 29.404 -12.660 53.856 1.00 47.71 N
ATOM 6355 CA SER L 56 29.488 -12.258 55.259 1.00 48.97 C
ATOM 6356 CB SER L 56 28,743 -10.944 55.479 1.00 52.35 C
ATOM 6357 OG SER L 56 28.905 -10.432 56.790 1 ,00 53.47 O
ATOM 6358 C SER L 56 28.913 -13.364 56.168 1.0049.79 C ATOM 6359 0 SER L 56 27.770 -13.801 55.961 1.00 50.71 O
ATOM 6360 N GLY L 57 29.717 -13.822 57.136 1.00 49.68 N
ATOM 6361 CA GLY L 57 29.326 -14.858 58.088 1.00 49.76 C
ATOM 6362 C GLY L 57 29.752 -16.262 57.722 1.00 50.00 C
ATOM 6363 O GLY L 57 29.681 -17.156 58.566 1.00 50.19 O JB2010.7161
ATOM 6364 N VAL L 58 30.190 -16.477 56.469 1.00 48.13 N
ATOM 6365 CA VAL L 58 30.605 -17.800 56.001 1.00 48.12 C
ATOM 6366 CB VAL L 58 30.515 -17.984 54.457 1.00 50.39 C
ATOM 6367 CG1 VAL L 58 30.712 -19.447 54.060 1.00 50.48 C ATOM 6368 CG2 VAL L 58 29.188 -17.471 53.908 1.00 49.49 C
ATOM 6369 C VAL L 58 31.980 -18.207 56.600 1.00 48.56 C
ATOM 6370 O VAL L 58 32.961 -17.470 56.413 1.0048.80 O
ATOM 6371 N PRO L 59 32.041 -19.376 57.315 1.00 48.30 N
ATOM 6372 CA PRO L 59 33.300 -19.828 57.939 1.00 48.02 C ATOM 6373 CB PRO L 59 32.870 -21.084 58.696 1.00 49.71 C
ATOM 6374 CG PRO L 59 31.408 -20.958 58.854 1.00 49.95 C
ATOM 6375 CD PRO L 59 30.942 -20.312 57.625 1.00 50.04 C
ATOM 6376 C PRO L 59 34.403 -20.188 56.966 1.00 48.07 C
ATOM 6377 O PRO L 59 34.091 -20.726 55.905 1.00 48.20 O ATOM 6378 N SER L 60 35.696 -19.958 57.357 1.00 47.98 N
ATOM 6379 CA SER L 60 36.9 1 -20.228 56.556 1.00 47.81 C
ATOM 6380 CB SER L 60 38.159 -19.667 57.236 1.00 52.01 C
ATOM 6381 OG SER L 60 38.809 -20.542 58.146 1.00 52.78 O
ATOM 6382 C SER L 60 37.085 -21.690 56.096 1.00 47.74 C ATOM 6383 0 SER L 60 37.919 -22.014 55.235 1.00 47.83 O
ATOM 6384 N ARG L 61 36.264 -22.562 56.673 1.00 47.49 N
ATOM 6385 CA ARG L 61 36.141 -23.993 56.411 1.00 46.91 C
ATOM 6386 CB ARG L 61 35.009 -24.444 57.334 1.0046.33 C
ATOM 6387 CG ARG L 61 34.720 -25.909 57.486 1.00 45.30 C ATOM 6388 CD ARG L 61 33.383 -26.090 58.181 1.00 42.83 C
ATOM 6389 NE ARG L 61 33.1 14 -25.021 59.142 1.00 40.16 N
ATOM 6390 CZ ARG L 61 31.920 -24.722 59.641 1.00 39.72 C
ATOM 6391 NH1 ARG L 61 30.856 -25.431 59.300 1.00 38.03 N
ATOM 6392 NH2 ARG L 61 31.786 -23.726 60.509 1.00 41.31 N ATOM 6393 C ARG L 61 35.721 -24.139 54.918 1.00 46.94 C
ATOM 6394 O ARG L 61 36.228 -25.017 54.212 1.00 46.82 O
ATOM 6395 N PHE L 62 34.798 -23.240 54.450 1.00 45.76 N
ATOM 6396 CA PHE L 62 34.282 -23.212 53.084 1.00 45.44 C
ATOM 6397 CB PHE L 62 32.859 -22.607 53.032 1.00 46.91 C ATOM 6398 CG PHE L 62 31.808 -23.370 53.797 1.00 47,13 C
ATOM 6399 CD1 PHE L 62 31.219 -24.509 53.255 1.00 45.95 C
ATOM 6400 CE1 PHE L 62 30.255 -25.221 53.969 1.00 44.62 C
ATOM 6401 CZ PHE L 62 29.864 -24.788 55.218 1.00 44.33 C
ATOM 6402 CE2 PHE L 62 30.427 -23.655 55.765 1.00 45.45 C ATOM 6403 CD2 PHE L 62 31.404 -22.951 55.059 1.00 46.95 C
ATOM 6404 C PHE L 62 35.198 -22.420 52.160 1.00 45.13 C
ATOM 6405 O PHE L 62 35.434 -21.229 52.384 1.00 45.05 O
ATOM 6406 N SER L 63 35.689 -23.070 51 ,107 1.00 42.27 N
ATOM 6407 CA SER L 63 36.546 -22.423 50.142 1.00 41.87 C ATOM 6408 CB SER L 63 38.021 -22.695 50.454 1.00 44.94 C
ATOM 6409 OG SER L 63 38.673 -23.608 49.580 1.00 44.80 O
ATOM 6410 C SER L 63 36.164 -22.884 48.745 1.0041.88 C
ATOM 6411 O SER L 63 35.832 -24.055 48.548 1.00 41.65 O
ATOM 6412 N GLY L 64 36.201 -21.949 47.799 1.00 42.15 N ATOM 6413 CA GLY L 64 35.912 -22.211 46.404 1.00 41.93 C
ATOM 6414 C GLY L 64 37.149 -21.904 45.599 1.00 41.92 C
ATOM 6415 O GLY L 64 38.019 -21.177 46.078 1.00 42.11 O
ATOM 6416 N SER L 65 37.254 -22.454 44.385 1.00 43.26 N
ATOM 6417 CA SER L 65 38.413 -22.218 43.532 1.00 43.66 C JB2010.7161
ATOM 6418 CB SER L 65 39.617 -23.025 44.023 1.00 47.22 C
ATOM 6419 OG SER L 65 39.558 -24.379 43.604 1.00 47.15 O
ATOM 6420 C SER L 65 38.124 -22.542 42.055 1.00 43.94 C
ATOM 6421 O SER L 65 37.341 -23.441 41.749 1.00 44.29 O ATOM 6422 N GLY L 66 38.778 -21.826 41.159 1.0042.77 N
ATOM 6423 CA GLY L 66 38.620 -22.062 39.739 1.00 43.01 C
ATOM 6424 C GLY L 66 38.334 -20.824 38.928 1.00 43.61 C
ATOM 6425 O GLY L 66 38.107 -19.725 39.467 1.00 43.03 O
ATOM 6426 N SER L 67 38.369 -21.028 37.605 1.00 47.58 N ATOM 6427 CA SER L 67 38.092 -20.040 36.573 1.00 49.01 C
ATOM 6428 CB SER L 67 39.209 - 9.002 36.442 1.00 55.53 C
ATOM 6429 OG SER L 67 40.476 -19.594 36.212 1.00 57.40 O
ATOM 6430 C SER L 67 37.843 -20.773 35.264 1.00 49.24 C
ATOM 6431 O SER L 67 38.337 -21.891 35.075 1.00 49.83 O ATOM 6432 N GLY L 68 37.048 -20.158 34.400 1.00 49.15 N
ATOM 6433 CA GLY L 68 36.725 -20.723 33.105 1.00 49.84 C
ATOM 6434 C GLY L 68 35.631 -21.758 33.153 1.00 50.48 C
ATOM 6435 0 GLY L 68 34.450 -21.417 33.087 1.00 50.56 O
ATOM 6436 N THR L 69 36.005 -23.029 33.239 1.00 52.49 N ATOM 6437 CA THR L 69 34.995 -24.087 33.237 1.00 53.25 C
ATOM 6438 CB THR L 69 35.014 -24.851 31.898 1.00 60.09 C
ATOM 6439 OG1 THR L 69 36.348 -25.281 31.635 1.00 62.23 O
ATOM 6440 CG2 THR L 69 34.494 -24.036 30.733 1.00 59.76 C
ATOM 6441 C THR L 69 35.123 -25.068 34.386 1.00 53.36 C ATOM 6442 O THR L 69 34.238 -25.898 34.542 1.00 53.85 O
ATOM 6443 N ASP L 70 36.209 -25.009 35.174 1.00 54.55 N
ATOM 6444 CA ASP L 70 36.414 -25.968 36.269 1.00 54.28 C
ATOM 6445 CB ASP L 70 37.664 -26.830 36.043 1.00 58.24 C
ATOM 6446 CG ASP L 70 37.716 -27.402 34.641 1.00 61.54 C ATOM 6447 OD1 ASP L 70 38.246 -26.708 33.738 1.00 64.93 O
ATOM 6448 OD2 ASP L 70 37.203 -28.534 34.438 1.00 63.54 O
ATOM 6449 C ASP L 70 36.431 -25.305 37.604 1.00 53.41 C
ATOM 6450 O ASP L 70 37.334 -24.533 37.911 1.00 53.31 O
ATOM 6451 N PHE L 71 35.404 -25.604 38.397 1.00 50.17 N ATOM 6452 CA PHE L 71 35.201 -25.042 39.725 1.00 49.47 C
ATOM 6453 CB PHE L 71 33.974 -24.116 39.708 1.00 51.00 C
ATOM 6454 CG PHE L 71 34.086 -22.998 38.693 1.00 50.77 C
ATOM 6455 CD1 PHE L 71 34.677 -21.781 39.034 1.00 50.21 C
ATOM 6456 CE1 PHE L 71 34.796 -20.761 38.100 1.00 48.73 C ATOM 6457 CZ PHE L 71 34.339 -20.954 36.813 1.00 50.48 C
ATOM 6458 CE2 PHE L 71 33.756 -22.151 36.453 1.00 50.21 C
ATOM 6459 CD2 PHE L 71 33.627 -23.171 37.391 1.00 49.56 C
ATOM 6460 C PHE L 71 35.022 -26.139 40.754 1.0048.86 C
ATOM 6461 O PHE L 71 34.523 -27.212 40.414 1.0049.08 O ATOM 6462 N THR L 72 35.463 -25.882 42.000 1.00 45.72 N
ATOM 6463 CA THR L 72 35.342 -26.804 43.123 1.00 45.67 C
ATOM 6464 CB THR L 72 36.629 -27.649 43.384 1.00 55.18 C
ATOM 6465 OG1 THR L 72 37.719 -26.792 43.707 1.00 56.02 O
ATOM 6466 CG2 THR L 72 36.989 -28.607 42.256 1.00 54.40 C ATOM 6467 C THR L 72 34.981 -26.052 44.398 1.00 45.58 C
ATOM 6468 O THR L 72 35.434 -24.923 44.599 1.0045.53 O
ATOM 6469 N LEU L 73 34.178 -26.690 45.259 1.0043.61 N
ATOM 6470 CA LEU L 73 33.791 -26.187 46.568 1.00 43.91 C
ATOM 6471 CB LEU L 73 32.269 -26.178 46.789 1.00 43.61 C JB2010.7161
ATOM 6472 CG LEU L 73 31.787 -25.738 48.188 1.00 42.87 C
ATOM 6473 CD1 LEU L 73 32.052 -24.243 48.448 1.00 41.69 C
ATOM 6474 CD2 LEU L 73 30.320 -26.026 48.360 1.00 42.64 C
ATOM 6475 C LEU L 73 34.452 -27.130 47.547 1.00 44.46 C ATOM 6476 O LEU L 73 34.296 -28,350 47.438 1.00 44.01 O
ATOM 6477 N THR L 74 35.202 -26.559 48.496 1.00 47.69 N
ATOM 6478 CA THR L 74 35.931 -27.312 49.498 1.00 48.44 C
ATOM 6479 CB THR L 74 37.462 -27.235 49.259 1.00 55.13 C
ATOM 6480 OG THR L 74 37.743 -27.702 47.936 1.00 55.72 O ATOM 6481 CG2 THR L 74 38.266 -28.080 50.250 1.00 55.22 C
ATOM 6482 C THR L 74 35.516 -26.966 50.910 1.0048.94 C
ATOM 6483 O THR L 74 35.572 -25.802 51.327 1.00 49.20 O
ATOM 6484 N ILE L 75 35.090 -28.004 51.641 1.00 50.46 N
ATOM 6485 CA ILE L 75 34.751 -27.917 53.051 1.00 51.27 C ATOM 6486 CB ILE L 75 33.341 -28.446 53.487 1.00 52.71 C
ATOM 6487 CG1 ILE L 75 32.199 -28.003 52.520 1.00 52.80 C
ATOM 6488 CD1 ILE L 75 30.804 -28.695 52.674 1.00 52.64 C
ATOM 6489 CG2 ILE L 75 33.080 -28.049 54.945 1.00 51.73 C
ATOM 6490 C ILE L 75 35.871 -28.767 53.620 1.00 52.02 C ATOM 6491 O ILE L 75 35.865 -29.989 53.431 1.00 52.25 O
ATOM 6492 N SER L 76 36.877 -28.118 54.215 1.00 55.10 N
ATOM 6493 CA SER L 76 38.008 -28.814 54.825 1.00 55.71 C
ATOM 6494 CB SER L 76 39.256 -27.944 54.741 1.00 56.80 C
ATOM 6495 OG SER L 76 39,034 -26.697 55.377 1.00 54.97 O ATOM 6496 C SER L 76 37.560 -28.980 56.277 1.00 56.22 C
ATOM 6497 O SER L 76 37.178 -27.974 56.883 1.00 57.07 O
ATOM 6498 N SER L 77 37.550 -30.209 56.830 1.00 55.64 N
ATOM 6499 CA SER L 77 37.063 -30.441 58.206 1.00 55.10 C
ATOM 6500 CB SER L 77 37.941 -29.759 59.258 1.00 59.19 C ATOM 6501 OG SER L 77 37.344 -29.806 60.544 1.00 60.15 O
ATOM 6502 C SER L 77 35.559 -30.065 58.336 1.00 54.34 C
ATOM 6503 O SER L 77 35,197 -28.990 58.842 1.00 54.33 O
ATOM 6504 N LEU L 78 34.705 -30.973 57.836 1.00 51.78 N
ATOM 6505 CA LEU L 78 33.238 -30.914 57.806 1.00 51.20 C ATOM 6506 CB LEU L 78 32.780 -32.188 57.064 1.00 50.91 C
ATOM 6507 CG LEU L 78 31.367 -32.325 56.492 1.00 50.98 C
ATOM 6508 CD1 LEU L 78 31.110 -31.348 55.349 1.00 51.38 C
ATOM 6509 CD2 LEU L 78 31.210 -33.695 55.901 1.00 51.24 C
ATOM 6510 C LEU L 78 32.623 -30.843 59.226 1.00 50.94 C ATOM 6511 0 LEU L 78 33.069 -31.552 60.123 1.00 51.31 O
ATOM 6512 N GLN L 79 31.610 -29.994 59.432 1.00 51.20 N
ATOM 6513 CA GLN L 79 30.949 -29.853 60.739 1.00 51.10 C
ATOM 6514 CB GLN L 79 30.917 -28.388 61.178 1.00 52.91 C
ATOM 6515 CG GLN L 79 32.303 -27.787 61.335 1.00 54.51 C ATOM 6516 CD GLN L 79 33.108 -28.408 62.443 1 .00 55.63 C
ATOM 6517 OE1 GL L 79 32.937 -28.053 63.617 1.00 56.61 O
ATOM 6518 NE2 GLN L 79 34.002 -29.340 62.093 1.00 54.86 N
ATOM 6519 C GLN L 79 29.540 -30.441 60.744 1.00 50.74 C
ATOM 6520 O GLN L 79 28.983 -30.614 59.665 1.00 50.68 O ATOM 6521 N PRO L 80 28.926 -30.763 61.911 1.00 50.81 N
ATOM 6522 CA PRO L 80 27.555 -31.311 61.890 1.00 50.26 C
ATOM 6523 CB PRO L 80 27.182 -31.414 63.383 1.00 52.07 C
ATOM 6524 CG PRO L 80 28.155 -30.529 64.104 1.00 52.53 C
ATOM 6525 CD PRO L 80 29.420 -30.658 63.300 1.00 52.84 C JB2010J161
ATOM 6526 C PRO L 80 26.560 -30.443 61.113 1.00 49.13 C
ATOM 6527 O PRO L 80 25.747 -30.985 60.363 1.0048.89 0
ATOM 6528 N GLU L 81 26.657 -29.108 61.252 1 .00 45.92 N
ATOM 6529 CA GLU L 81 25.779 -28.146 60.568 1.0045.07 C ATOM 6530 CB GLU L 81 25.809 -26.760 61.255 1.00 46.99 C
ATOM 6531 CG GLU L 81 27. 63 -26.064 61.302 1.00 49.87 C
ATOM 6532 CD GLU L 81 28.074 -26.312 62.498 1.00 55.34 C
ATOM 6533 OE1 GLU L 81 29.196 -25.752 62.498 1.00 57.55 O
ATOM 6534 OE2 GLU L 81 27.681 -27.050 63.434 1.00 55.65 O ATOM 6535 C GLU L 81 25.991 -28.038 59.037 1.00 43.58 C
ATOM 6536 O GLU L 81 25.227 -27.338 58.372 1.0043.34 O
ATOM 6537 N ASP L 82 27.002 -28.747 58.488 1.00 39.81 N
ATOM 6538 CA ASP L 82 27.364 -28.743 57.066 1.00 38.29 C
ATOM 6539 CB ASP L 82 28.891 -28.745 56.898 1.00 40.15 C ATOM 6540 CG ASP L 82 29.552 -27.564 57,581 1.00 40.53 C
ATOM 6541 OD1 ASP L 82 28.819 -26.599 57.962 1.00 42.85 O
ATOM 6542 OD2 ASP L 82 30.781 -27.597 57.752 1.00 37.44 O
ATOM 6543 C ASP L 82 26.732 -29.799 56.196 1.00 37.24 C
ATOM 6544 O ASP L 82 26.961 -29.820 54.989 1.00 37.45 O ATOM 6545 N PHE L 83 25.961 -30.686 56.779 1.00 37.68 N
ATOM 6546 CA PHE L 83 25.327 -31.713 55.975 1.00 36.49 C
ATOM 6547 CB PHE L 83 25.027 -32.974 56.796 1.00 37.55 C
ATOM 6548 CG PHE L 83 26.300 -33.645 57.260 1.00 37.22 C
ATOM 6549 CD1 PHE L 83 26.935 -34.597 56.465 1.00 37.78 C ATOM 6550 CE1 PHE L 83 28.125 -35.210 56.892 1.00 39.15 C
ATOM 6551 CZ PHE L 83 28.678 -34.879 58.1 18 1.00 37.38 C
ATOM 6552 CE2 PHE L 83 28.069 -33.923 58.910 1.00 37,72 C
ATOM 6553 CD2 PHE L 83 26.877 -33.312 58.485 1.00 37.40 C
ATOM 6554 C PHE L 83 24.116 -31.017 55.399 1.00 35.60 C ATOM 6555 O PHE L 83 23.238 -30.560 56.143 1.00 35.59 O
ATOM 6556 N ALA L 84 24.155 -30.826 54.064 1.00 33.80 N
ATOM 6557 CA ALA L 84 23.175 -30.112 53.263 1.00 32.88 C
ATOM 6558 CB ALA L 84 23.371 -28.610 53.472 1.00 33.61 C
ATOM 6559 C ALA L 84 23.395 -30.443 51.799 1.00 32.44 C ATOM 6560 O ALA L 84 24.182 -31.322 51.472 1.00 32.28 O
ATOM 6561 N THR L 85 22.672 -29.749 50.924 1.00 33.93 N
ATOM 6562 CA THR L 85 22.781 -29.859 49.485 1.00 33.75 C
ATOM 6563 CB THR L 85 21.406 -30.043 48.814 1.00 36.16 C
ATOM 6564 OG1 THR L 85 20.890 -31.323 49.189 1.00 37.98 O ATOM 6565 CG2 THR L 85 21.465 -29.971 47.293 1.00 34.24 C
ATOM 6566 C THR L 85 23.487 -28.594 49.068 1.00 33.83 C
ATOM 6567 O THR L 85 23.167 -27.500 49.557 1.00 33.64 O
ATOM 6568 N TYR L 86 24.470 -28.748 48.181 1.00 35.00 N
ATOM 6569 CA TYR L 86 25.237 -27.625 47.680 1.00 35.32 C ATOM 6570 CB TYR L 86 26.742 -27.813 47.992 1.00 35.87 C
ATOM 6571 CG TYR L 86 26.986 -27.771 49.485 1.00 34.56 C
ATOM 6572 CD1 TYR L 86 26.843 -28.913 50.266 1.00 34.62 C
ATOM 6573 CE1 TYR L 86 27.002 -28.867 51.653 1.00 36.49 C
ATOM 6574 CZ TYR L 86 27.292 -27.661 52.270 1.00 36.32 C ATOM 6575 OH TYR L 86 27.445 -27.595 53.630 1.00 35.42 O
ATOM 6576 CE2 TYR L 86 27.412 -26.509 51.511 1.00 35.47 C
ATOM 6577 CD2 TYR L 86 27.239 -26.566 50.133 1.00 34.34 C
ATOM 6578 C TYR L 86 24.948 -27.434 46.229 1.00 35.92 C
ATOM 6579 0 TYR L 86 24.757 -28.420 45.521 1.00 36.14 O JB2010.7161
ATOM 6580 N TYR L 87 24.866 -26.177 45.787 1.00 36.01 N
ATOM 6581 CA TYR L 87 24.608 -25.867 44.383 1.00 36.79 C
ATOM 6582 CB TYR L 87 23.206 -25.252 44.193 1.00 36.76 C
ATOM 6583 CG TYR L 87 22.035 -26.162 44.451 1.00 37.00 C ATOM 6584 CD1 TYR L 87 21.310 -26.077 45.636 1.00 35.97 C
ATOM 6585 CE1 TYR L 87 20.196 -26.874 45.859 1.00 34.84 C
ATOM 6586 CZ TYR L 87 19.780 -27.766 44.883 1.00 36.00 C
ATOM 6587 OH TYR L 87 18.697 -28.590 45.114 1.00 36.03 O
ATOM 6588 CE2 TYR L 87 20.474 -27.855 43.691 1.00 36.88 C ATOM 6589 CD2 TYR L 87 21.589 -27.047 43.477 1.00 36.94 C
ATOM 6590 C TYR L 87 25.584 -24.833 43.886 1.00 37.38 C
ATOM 6591 O TYR L 87 25.830 -23.853 44.590 1.00 37.27 O
ATOM 6592 N CYS L 88 26.085 -25.002 42.659 1.00 40.93 N
ATOM 6593 CA CYS L 88 26.938 -24.001 42.018 1.00 42.62 C ATOM 6594 CB CYS L 88 28.123 -24.636 41.291 1.00 45.72 C
ATOM 6595 SG CYS L 88 27.658 -25.811 39.983 1.00 52.13 S
ATOM 6596 C CYS L 88 26.021 -23.263 41.042 1.00 42.21 C
ATOM 6597 O CYS L 88 25.048 -23.837 40.545 1.00 42.20 O
ATOM 6598 N GLN L 89 26.311 -22.015 40.753 1.00 40.17 N ATOM 6599 CA GLN L 89 25.515 -21.282 39.777 1.00 39.81 C
ATOM 6600 CB GLN L 89 24.377 -20.507 40.458 1.00 41.13 C
ATOM 6601 CG GLN L 89 23.473 -19.682 39.509 1.00 40.14 C
ATOM 6602 CD GLN L 89 23.135 -18.326 40.080 1.00 39.80 C
ATOM 6603 OE1 GLN L 89 22.678 -18.199 41.212 1.00 38.03 O ATOM 6604 NE2 GLN L 89 23.362 -17.278 39.31 1 1.00 38.89 N
ATOM 6605 C GLN L 89 26.416 -20.339 39.018 1.00 39.72 C
ATOM 6606 O GLN L 89 27.340 -19.781 39.600 1.00 39.49 O
ATOM 6607 N GLN L 90 26.168 -20.161 37.728 1.00 39.65 N
ATOM 6608 CA GLN L 90 26.938 -19.207 36.927 1.00 39.94 C ATOM 6609 CB GLN L 90 27.333 -19.746 35.522 1.00 40.31 C
ATOM 6610 CG GLN L 90 26.178 -20.008 34.535 1.00 41.32 C
ATOM 661 1 CD GLN L 90 25.651 -18.791 33.795 1.00 41.40 C
ATOM 6612 OE1 GLN L 90 26.367 -17.817 33.566 1.00 41.70 O
ATOM 6613 NE2 GL L 90 24.382 -18.826 33.403 1.00 40.08 N ATOM 6614 C GLN L 90 26.1 17 -17.949 36.815 1.00 39.91 C
ATOM 6615 O GLN L 90 24.893 -18.001 36.896 1.00 40.31 O
ATOM 6616 N TYR L 91 26.773 -16.832 36.610 1.00 42.16 N
ATOM 6617 CA TYR L 91 26.113 -15.549 36.424 1.00 42.57 C
ATOM 6618 CB TYR L 91 25.816 -14.846 37.756 1.00 43.87 C ATOM 6619 CG TYR L 91 27.014 -14.605 38.638 1.00 44.54 C
ATOM 6620 CD1 TYR L 91 27.434 -15.564 39.554 1.00 45.40 C
ATOM 6621 CE1 TYR L 91 28.526 -15.337 40.389 1.00 46.27 C
ATOM 6622 CZ TYR L 91 29.200 -14.129 40.324 1.00 46.44 C
ATOM 6623 OH TYR L 91 30.280 -13.883 41.140 1.0047.42 O ATOM 6624 CE2 TYR L 91 28.787 -13.158 39.427 1.0045.72 C
ATOM 6625 CD2 TYR L 91 27.700 -13.399 38.596 1.00 44.80 C
ATOM 6626 C TYR L 91 26.904 -14.710 35.429 1.00 42.85 C
ATOM 6627 0 TYR L 91 26.881 -13.473 35.461 1.00 43.21 O
ATOM 6628 N LYS L 92 27.603 -15.417 34.523 1.00 43.34 N ATOM 6629 CA LYS L 92 28.413 -14.836 33.469 1.00 43.40 C
ATOM 6630 CB LYS L 92 29.357 -15.919 32,888 1.00 46.23 C
ATOM 6631 CG LYS L 92 30.074 -15.560 31.574 1.00 47.10 C
ATOM 6632 CD LYS L 92 31.042 -1 .408 31.743 1.00 49.55 C
ATOM 6633 CE LYS L 92 31.846 -14.082 30.521 1.00 50.74 C JB2010.7161
ATOM 6634 NZ LYS L 92 32.784 -12.973 30.837 1.00 52.36 N
ATOM 6635 C LYS L 92 27.457 -14.322 32.407 1.00 42.96 C
ATOM 6636 0 LYS L 92 27.618 -13.208 31.900 1.00 43.96 O
ATOM 6637 N THR L 93 26.442 -15.141 32.115 1.00 40.59 N ATOM 6638 CA THR L 93 25.413 -14.951 31.107 1.00 39.38 C
ATOM 6639 CB THR L 93 25.820 -15.877 29.934 1.00 48.83 C
ATOM 6640 OG1 THR L 93 26.305 -15.086 28.865 1.00 50.32 O
ATOM 6641 CG2 THR L 93 24.731 -16.848 29.463 1.00 49.52 C
ATOM 6642 C THR L 93 24.004 - 5.212 31.659 1.00 38.07 C ATOM 6643 0 THR L 93 23.853 -15.855 32.698 1.00 38.40 O
ATOM 6644 N TYR L 94 22.982 -14.722 30.945 1.00 35.62 N
ATOM 6645 CA TYR L 94 21.575 -14.957 31.245 1.00 34.10 C
ATOM 6646 CB TYR L 94 20.769 -13.714 30.947 1.00 33.22 C
ATOM 6647 CG TYR L 94 20.811 -12.655 32.015 1.00 31.94 C ATOM 6648 CD1 TYR L 94 21.254 -11.372 31.728 1.00 31.62 C
ATOM 6649 CE1 TYR L 94 21.256 -10.376 32.697 1.00 30.55 C
ATOM 6650 CZ TYR L 94 20.809 -10.660 33.971 1.00 30.11 C
ATOM 6651 OH TYR L 94 20.807 -9.676 34.914 1.00 30.54 O
ATOM 6652 CE2 TYR L 94 20.355 -11.928 34.278 1.00 30.32 C ATOM 6653 CD2 TYR L 94 20.333 -12.908 33.293 1.00 30.17 C
ATOM 6654 C TYR L 94 21.039 -16.142 30.363 1.00 33.68 C
ATOM 6655 O TYR L 94 21 .445 -16.278 29.204 1.00 34.00 O
ATOM 6656 N PRO L 95 20.114 -16.990 30.849 1.00 33.52 N
ATOM 6657 CA PRO L 95 19.551 -16.990 32.206 1.00 33.51 C ATOM 6658 CB PRO L 95 18.325 -17.900 32.061 1.00 33.90 C
ATOM 6659 CG PRO L 95 18.746 -18.906 31.009 1.00 33.21 C
ATOM 6660 CD PRO L 95 19.608 -18.126 30.044 1.00 33.76 C
ATOM 6661 C PRO L 95 20.589 -17.590 33.151 1.00 33.59 C
ATOM 6662 O PRO L 95 21.468 -18.349 32.704 1.00 33.52 O ATOM 6663 N TYR L 96 20.506 -17.260 34.439 1.00 32.59 N
ATOM 6664 CA TYR L 96 21.412 -17.861 35.405 1.00 32.70 C
ATOM 6665 CB TYR L 96 21.192 -17.279 36.792 1.00 33.23 C
ATOM 6666 CG TYR L 96 21.402 -15.786 36.937 1.00 33.68 C
ATOM 6667 CD1 TYR L 96 22.389 -15.122 36.210 1.00 32.41 C ATOM 6668 CE1 TYR L 96 22.627 -13.765 36.396 1.00 33.57 C
ATOM 6669 CZ TYR L 96 21.876 -13.049 37.325 1.00 34.22 C
ATOM 6670 OH TYR L 96 22.047 -11.693 37.514 1.00 34.04 O
ATOM 6671 CE2 TY L 96 20.904 -13.693 38.065 1.00 33.52 C
ATOM 6672 CD2 TYR L 96 20.687 -15.055 37.880 1.00 33.85 C ATOM 6673 C TYR L 96 21.078 -19.357 35.439 1.00 32.50 C
ATOM 6674 O TYR L 96 19.902 -19.729 35.388 1.00 32.59 O
ATOM 6675 N THR L 97 22.099 -20.211 35.478 1.00 31.55 N
ATOM 6676 CA THR L 97 21.868 -21.654 35.513 1.00 31.13 C
ATOM 6677 CB THR L 97 22.236 -22.312 34.185 1.00 34.58 C ATOM 6678 OG1 THR L 97 23.557 -21.895 33.797 1.00 34.96 O
ATOM 6679 CG2 THR L 97 21.224 -22.025 33.089 1.00 31.79 C
ATOM 6680 C THR L 97 22.587 -22.246 36.695 1.00 31.22 C
ATOM 6681 O THR L 97 23.660 -21.783 37.039 1.00 31.91 O
ATOM 6682 N PHE L 98 21.997 -23.268 37.301 1.00 30.43 N ATOM 6683 CA PHE L 98 22.488 -23.970 38.483 1 .00 30.36 C
ATOM 6684 CB PHE L 98 21.350 -24.035 39.525 1.00 31.46 C
ATOM 6685 CG PHE L 98 20.771 -22.723 39.991 1.00 30.09 C
ATOM 6686 CD1 PHE L 98 19.717 -22.129 39.310 1.00 29.35 C
ATOM 6687 CE1 PHE L 98 19.176 -20.912 39.744 1.00 30.21 C JB2O10.7161
ATOM 6688 CZ PHE L 98 19.681 -20.29540.869 1.0030.76 C
ATOM 6689 CE2 PHE L 98 20.718-20.88441.567 1.0031.50 C
ATOM 6690 CD2PHEL 98 21.257-22.09741.130 1.0030.65 C
ATOM 6691 C PHE L 98 22.912-25.412 38.194 1.0031.08 C ATOM 6692 0 PHE L 98 22.371 -26.05737.288 Ί.0031.54 O
ATOM 6693 N GLY L 99 23.848-25.931 38.992 1.0031.10 N
ATOM 6694 CA GLY L 99 24.268-27.322 38.897 1.0031.76 C
ATOM 6695 C GLY L 99 23.154-28.144 39.516 1.0032.76 C
ATOM 66960 GLY L 99 22.357-27.60440.285 1.0032.39 O ATOM 6697 N GLN L 100 23.044-29.442 39.188 1.0037.75 N
ATOM 6698 CA GLN L 100 21.957-30.268 39.732 1.0038.91 C
ATOM 6699 CB GLN L 100 21.883-31.620 39.018 1.0042.84 C
ATOM 6700 CG GLN L 100 22.723-32.744 39.657 1.0047.52 C
ATOM 6701 CD GLN L 100 24.193-32,714 39.296 1.0053.54 C ATOM 6702 OE1 GLN L 100 24.679-31.83038.544 1.0056.03 O
ATOM 6703 NE2GLNL100 24.926-33.69539.827 1.0053.33 N
ATOM 6704 C GLN L 100 21.947-30.42541.256 1.0038.63 C
ATOM 6705 O GLN L 100 20.949-30.87441.811 1.0038.90 O
ATOM 6706 N GLY L 101 23.040-30.031 41.903 1.0037.47 N ATOM 6707 CA GLY L 101 23.215-30.13043.345 1.0037.46 C
ATOM 6708 C GLY L 01 23.971 -31.37043.799 1.0037.80 C
ATOM 6709 O GLY L 101 23.979-32.40943. 21 1.0037.80 O
ATOM 6710 N THRL 102 24.600-31.26244.975 1.0038.01 N
ATOM 6711 CA THR L 102 25.355-32.33245.626 1.0038.18 C ATOM 6712 CB THR L 102 26.857-32.04845.560 1.0037.47 C
ATOM 6713 OG1 THR L 102 27.239-31.991 44.187 1.0037.34 O
ATOM 6714 CG2 THR L 102 27.686-33.09046.293 1.0036.20 C
ATOM 6715 C THR L 102 24.872-32.391 47.051 1.0038.92 C
ATOM 6716 0 THR L 102 25.002-31.40047.778 1.0039.21 O ATOM 6717 N LYS L 103 24.305-33.53647.448 1.0039.90 N
ATOM 6718 CA LYS L 103 23.816-33.74048.809 1.0040.50 C
ATOM 6719 CB LYS L 103 22.614-34.70848.783 1.0043.66 C
ATOM 6720 CG LYS L 103 22.074-35,170 50.128 1.0044.21 C
ATOM 6721 CD LYS L 103 21.181 -34.143 50.801 1.0047.30 C ATOM 6722 CE LYS L 103 20.098-34.754 51.671 1.0048.07 C
ATOM 6723 NZ LYS L 03 18.983-35.366 50.887 1.0046.44 N
ATOM 6724 C LYS L 103 24.973-34.32549.623 1.0041.09 C
ATOM 6725 0 LYS L 103 25.585-35.29749.165 1.0041.23 O
ATOM 6726 N VAL L 104 25.288-33.735 50.804 1.0041.91 N ATOM 6727 CA VAL L 104 26.344-34.228 51.701 1.0042.63 C
ATOM 6728 CB VAL L 104 27.353-33.152 52.216 1.0046.25 C
ATOM 6729 CG1 VAL L 104 28.513-33.796 52.973 1.0045.95 C
ATOM 6730 CG2VALL104 27.894-32.297 51.068 1.0046.86 C
ATOM 6731 C VAL L 104 25.605-34.958 52.828 1.0043.33 C ATOM 6732 O VAL L 104 24.945-34.337 53.664 1.0043.49 O
ATOM 6733 N GLU L 105 25.666-36.29052.785 1.0045.65 N
ATOM 6734 CA GLU L 105 25.041 -37.21853,715 1.0046.28 C
ATOM 6735 CB GLU L 105 24.630-38.47352.900 1.0049,45 C
ATOM 6736 CG GLU L 105 24.050-39.62953.716 1.0053.16 C ATOM 6737 CD GLU L 05 24.192-41.05253.185 1.0056.19 C
ATOM 6738 OE1 GLU L 105 25.316-41.45352.799 1.0058.04 O
ATOM 6739 OE2 GLU L 105 23.170-41.77753.178 1.0056.86 O
ATOM 6740 C GLU L 105 26.042-37.57054.872 1.0045.84 C
ATOM 6741 O GLU L 105 27.268-37.550 54.669 1.0046.09 O JB2010.7161
ATOM 6742 N ILEL106 25.513-37.89456.085 1.0041.84 N
ATOM 6743 CA ILE L 106 26.350-38.291 57.229 1.0040.89 C
ATOM 6744 CB ILE L 106 25.700-38.01858.619 1.0042.54 C
ATOM 6745 CG1 ILE L 106 25.286-36.53958.799 1.0041.14 C ATOM 6746 CD1 ILE L 106 23.905-36.32459.160 1.0037.55 C
ATOM 6747 CG2 ILE L 106 26.614-38.46459.762 1.0041.89 C
ATOM 6748 C ILE L 106 26.704-39.765 57.072 1.0040.69 C
ATOM 67490 ILE L 106 25.813-40.602 56.916 1.0040.09 O
ATOM 6750 N LYS L 107 28.003-40.07657.090 1.0041.25 N ATOM 6751 CA LYS L 107 28.470-41.452 57.013 1.0041.49 C
ATOM 6752 CB LYS L 107 29.890-41.52756.411 1.0045.73 C
ATOM 6753 CG LYS L 107 30.579-42.895 56.507 1.0048.18 C
ATOM 6754 CD LYS L 107 31.416-43.27855.268 1.0052.95 C
ATOM 6755 CE LYS L 107 32.535-42.31254.834 1.0056.59 C ATOM 6756 NZ LYS L 107 33.554-42.02055.906 1.0059.72 N
ATOM 6757 C LYS L 107 28,411 -41.99458.454 1.0040.56 C
ATOM 67580 LYS L 107 28.785-41.290 59.395 1.0040.70 O
ATOM 6759 N ARG L 108 27.914-43.21558.623 1.0038.36 N
ATOM 6760 CA ARG L 108 27.796-43.878 59.918 1.0037.76 C ATOM 6761 CB ARG L 108 26.458-43.47760.593 1.0037.49 C
ATOM 6762 CG ARG L 108 25.280-44.208 59.967 1.0037.62 C
ATOM 6763 CD ARG L 108 23.925-44.04560.583 1.0037.54 C
ATOM 6764 NE ARG L 108 23.807-44.38362.003 1.0037.19 N
ATOM 6765 CZ ARG L 108 23.849-45.60862.521 1.0036.68 C ATOM 6766 NH1 ARG L 108 24.092-46.656 61.753 1.0035.86 N
ATOM 6767 NH2 ARG L 108 23.699-45.78563.820 1.0037.31 N
ATOM 6768 C ARG L 108 27.887-45.42059.674 1.0037.69 C
ATOM 67690 ARG L 08 28.043-45.861 58.518 1.0037.33 O
ATOM 6770 N THRL109 27.778-46.227 60.746 1.0038.82 N ATOM 6771 CA THR L 109 27.798-47.685 60.631 1.0038.82 C
ATOM 6772 CB THR L 109 28.009-48.331 61.977 1.0049.09 C
ATOM 6773 OG1 THR L 109 27.504-47.489 63.011 1.0049.96 O
ATOM 6774 CG2 THR L 109 29.449-48.671 62.203 1.0048.97 C
ATOM 6775 C THR L 109 26.528-48.256 60.024 1.0038.44 C ATOM 67760 THR L 109 25.474-47.64660.077 1.0039.08 O
ATOM 6777 N VALL 110 26.615-49.431 59.453 1.0039.17 N
ATOM 6778 CA VALL110 25.442-50.080 58.888 1.0038.47 C
ATOM 6779 CB VALL 110 25.862-51.369 58.164 1.0041.37 C
ATOM 6780 CG1 VALL 110 24.652-52.180 57.757 1.0041.33 C ATOM 6781 CG2 VALL 110 26.708-51.038 56.945 1.0041.59 C
ATOM 6782 C VALL 110 24.459-50.37060.034 1.0038.03 C
ATOM 67830 VALL 110 24.883-50.746 61.144 1.0037.99 O
ATOM 6784 N ALA L 111 23.160-50.148 59.778 1.0035.39 N
ATOM 6785 CA ALA L 111 22.076 -50.38760.726 1.0034.25 C ATOM 6786 CB ALA L 111 21.516-49.075 61.209 1.0033.35 C
ATOM 6787 C ALA L 111 21.051 -51.126 59.921 1.0033.98 C
ATOM 6788 O ALA L 111 20.658-50.641 58.868 1,0034.44 O
ATOM 6789 N ALA L 112 20.642-52.313 60.353 1.0035.73 N
ATOM 6790 CA ALA L 112 19.625-53.079 59.606 1.0035.64 C ATOM 6791 CB ALA L 112 19.627-54.541 60.058 1.0036.44 C
ATOM 6792 C ALA L 112 18.229-52.464 59.856 1.0035.08 C
ATOM 6793 0 ALA L 112 18.014-51.93460.951 1.0034.46 O
ATOM 6794 N PRO L 113 17,260-52.521 58.908 1.0034.48 N
ATOM 6795 CA PRO L 113 15,931 -51.961 59.218 1.0034.41 C JB2010.7161
ATOM 6796 CB PRO L 113 15.288-51.767 57.845 1.0035.47 C
ATOM 6797 CG PRO L 113 15.924-52.786 56.972 1.0035.20 C
ATOM 6798 CD PRO L 113 17.297-53.10957.549 1.0035.70 C
ATOM 6799 C PRO L 113 15.084-52.895 60.071 1.0034.55 C ATOM 6800 O PRO L 113 15.164-54.11659.933 1.0034.48 O
ATOM 6801 N SERL 114 14.277-52.30460.958 1.0035.49 N
ATOM 6802 CA SER L 114 13.292-52.980 61.788 1.0036.34 C
ATOM 6803 CB SER L 114 12.979-52.138 63.014 1.0041.46 C
ATOM 6804 OG SER L 114 13.810-52.54064.082 1.0044.00 O ATOM 6805 C SER L 114 12.066-52.982 60.858 1.0037.12 C
ATOM 6806 O SER L 114 11.532-51.91660.540 1.0037.77 O
ATOM 6807 N VALL115 11.664-54.14660.375 1.0036.88 N
ATOM 6808 CA VALL 15 10.540-54.26059.449 1.0037.15 C
ATOM 6809 CB VALL 115 10.900-55.237 58.295 1.0040.01 C ATOM 6810 CG1 VALL 115 9.833-55.237 57.205 1.0040.23 C
ATOM 6811 CG2 VALL 115 12.269-54.901 57.704 1.0038.73 C
ATOM 6812 C VALL 115 9.185-54.592 60.158 1.0037.46 C
ATOM 6813 O VALL 115 9.110-55.513 60.970 1.0037.73 O
ATOM 6814 N PHE L 116 8.131 -53.82759.841 1.0038.30 N ATOM 6815 CA PHE L 116 6.769-53.96760.363 1.0038.14 C
ATOM 6816 CB PHE L 116 6.461 -52.851 61.361 1.0039.80 C
ATOM 6817 CG PHE L 116 7.456-52.62762.477 1.0041.80 C
ATOM 6818 CD1 PHE L 116 7.381 -53.360 63.657 1.0044.42 C
ATOM 6819 CE1 PHE L 116 8.280-53.127 64.713 1.0044.48 C ATOM 6820 CZ PHE L 116 9.250-52.163 64.588 1.0043.05 C
ATOM 6821 CE2 PHE L 116 9.334-51.42363.424 1.0044.33 C
ATOM 6822 CD2 PHE L 116 8.433-51.65062.374 1.0043.20 C
ATOM 6823 C PHE L 116 5.763-53.88659.197 1.0037.88 C
ATOM 6824 O PHE L 116 5.972-53.11658.263 1.0038.32 O ATOM 6825 N ILEL117 4.691 -54.687 59.240 1.0037.23 N
ATOM 6826 CA 1LEL 117 3.625-54.699 58.227 1.0036.75 C
ATOM 6827 CB 1LEL 117 3.545-56.015 57.402 1.0038.15 C
ATOM 6828 CG1 ILEL 17 2.663-55.839 56.146 1.0037.56 C
ATOM 6829 CD1 ILEL 117 2.758-56.947 55.060 1.0037.55 C ATOM 6830 CG2 ILEL 117 3.090-57.213 58.266 1.0037.70 C
ATOM 6831 C ILEL 117 2.284-54.313 58.902 1.0037.19 C
ATOM 6832 0 ILEL 117 2.024-54.66060.072 1.0037.33 O
ATOM 6833 N PHE L 118 1.443-53.58458.150 1.0037.03 N
ATOM 6834 CA PHE L 118 0.148-53.12258.602 1.0036.84 C ATOM 6835 CB PHE L 118 0.165-51.609 58.830 1.0037.15 C
ATOM 6836 CG PHE L 118 1.129-51.131 59.891 1.0037.23 C
ATOM 6837 CD1 PHE L 18 2.381 -50.62659.542 1.0036.66 C
ATOM 6838 CE1 PHE L 18 3.259-50.150 60.525 1.0035.24 C
ATOM 6839 CZ PHE L 118 2.891 -50.191 61.855 1.0035.05 C ATOM 6840 CE2 PHE L 118 1.658-50.682 62.220 1.0034.64 C
ATOM 6841 CD2 PHE L 118 0.774-51.14661.239 1.0035.80 C
ATOM 6842 C PHE L 118 -0.931 -53.475 57.602 1.0037.30 C
ATOM 6843 0 PHE L 118 -0.892-52.986 56.459 1.0037.13 O
ATOM 6844 N PRO L 19 -1.936-54.293 58.024 1.0039.26 N ATOM 6845 CA PRO L 119 -3.060-54.609 57.121 1.0039.24 C
ATOM 6846 CB PRO L 119 -3.809-55.730 57.855 1.0040.33 C
ATOM 6847 CG PRO L 119 -2.978-56.111 59.010 1.0040.18 C
ATOM 6848 CD PRO L 119 -2.137-54.925 59.343 1.0040.60 C
ATOM 6849 C PRO L 119 -3.967-53.384 56.976 1.0039.28 C JB2010.7161
ATOM 6850 O PRO L 119 -3.879 -52.465 57.826 1.00 39.08 O
ATOM 6851 N PRO L 120 -4.840 -53.333 55.923 1.00 39.98 N
ATOM 6852 CA PRO L 120 -5.753 -52.182 55.792 1.00 40.21 C
ATOM 6853 CB PRO L 120 -6.550 -52.485 54.516 1.00 41.60 C ATOM 6854 CG PRO L 120 -5.826 -53.554 53.831 1.00 41.86 C
ATOM 6855 CD PRO L 120 -5.073 -54.319 54.850 1.0041.59 C
ATOM 6856 C PRO L 120 -6.713 -52.166 56.967 1.00 40.34 C
ATOM 6857 0 PRO L 120 -7.106 -53.240 57.460 1.0040.53 O
ATOM 6858 N SER L 121 -7.081 -50.966 57.425 1.00 38.91 N ATOM 6859 CA SER L 121 -8.048 -50.844 58.503 1.00 39.71 C
ATOM 6860 CB SER L 121 -8.062 -49.417 59.040 1.00 40.84 C
ATOM 6861 OG SER L 121 -8.478 -48.494 58.050 1.00 40.41 O
ATOM 6862 C SER L 121 -9.452 -51.219 57.945 1.00 40.60 C
ATOM 6863 0 SER L 121 -9.710 -51.072 56.736 1.00 39.46 O ATOM 6864 N ASP L 122 -10.350 -51.699 58.835 1.00 45.82 N
ATOM 6865 CA ASP L 122 -11.740 -52.058 58.483 1.0047.79 C
ATOM 6866 CB ASP L 122 -12.507 -52.584 59.716 1.00 51.29 C
ATOM 6867 CG ASP L 122 -11.881 -53.836 60.321 1.00 53.82 C
ATOM 6868 OD1 ASP L 122 -1 1.859 -54.885 59.627 1.00 55.46 O ATOM 6869 OD2 ASP L 122 -1 1.401 -53.764 61.490 1.00 56.53 O
ATOM 6870 C ASP L 122 -12.420 -50.820 57.883 1.00 47.96 C
ATOM 6871 O ASP L 122 -13.120 -50.925 56.878 1.00 47.95 O
ATOM 6872 N GLU L 123 -12.118 -49.653 58.466 1.00 46.98 N
ATOM 6873 CA GLU L 123 -12,569 -48.335 58.069 1.00 47.62 C ATOM 6874 CB GLU L 123 -11.877 -47.280 58.960 1.00 50.15 C
ATOM 6875 CG GLU L 123 -12.481 -45.889 58.886 1.00 53.24 C
ATOM 6876 CD GLU L 123 -11.795 -44.818 59.724 1.00 57.96 C
ATOM 6877 OE1 GLU L 123 -11.816 -43.628 59.313 1.00 59.40 O
ATOM 6878 OE2 GLU L 123 -11.240 -45.166 60.796 1.00 58.72 O ATOM 6879 C GLU L 123 -12.311 -48.089 56.567 1.00 47.33 C
ATOM 6880 O GLU L 123 -13.230 -47.667 55.873 1.00 47.50 O
ATOM 6881 N GLN L 124 -11.084 -48.368 56.058 1.00 47.16 N
ATOM 6882 CA GLN L 124 -10.776 -48.165 54.636 1.00 46.66 C
ATOM 6883 CB GLN L 124 -9.274 -48.113 54.371 1.00 47.32 C ATOM 6884 CG GLN L 124 -8.941 -47.636 52.949 1.00 46.65 C
ATOM 6885 CD GLN L 124 -7.482 -47.723 52.586 1.00 46.49 C
ATOM 6886 OE1 GLN L 124 -6.672 -48.320 53.297 1.00 47.00 O
ATOM 6887 NE2 GLN L 124 -7.110 -47.130 51.464 1.00 46.08 N
ATOM 6888 C GLN L 124 -11.425 -49.225 53.770 1.00 47.05 C ATOM 6889 0 GLN L 124 -11980 -48.894 52.718 1.00 47.34 O
ATOM 6890 N LEU L 125 -11.351 -50.501 54.197 1.00 47.08 N
ATOM 6891 CA LEU L 125 -11.946 -51.619 53.470 1.00 47.17 C
ATOM 6892 CB LEU L 125 -11.776 -52.936 54.242 1.00 46.47 C
ATOM 6893 CG LEU L 125 -10.374 -53.530 54.267 1.00 46.17 C ATOM 6894 CD1 LEU L 125 -10.280 -54.670 55.257 1.00 44.62 C
ATOM 6895 CD2 LEU L 125 -9.933 -53.964 52.885 1.00 44.90 C
ATOM 6896 C LEU L 125 -13.425 -51.340 53.148 1.00 47.71 C
ATOM 6897 0 LEU L 125 -13.825 -51.465 51.988 1.00 47.49 O
ATOM 6898 N LYS L 126 -14.208 -50.905 54.167 1.00 50.19 N ATOM 6899 CA LYS L 126 -15.631 -50.572 54.043 1.00 50.46 C
ATOM 6900 CB LYS L 126 -16.194 -50.090 55.385 1.00 51.30 C
ATOM 6901 CG LYS L 126 -16.458 -51.251 56.342 1.00 51.91 C
ATOM 6902 CD LYS L 126 -16.398 -50.805 57.792 1.00 54.16 C
ATOM 6903 CE LYS L 126 -16.597 -51.958 58.744 1.00 56.39 C JB2010.7161
ATOM 6904 NZ LYS L 126 -16.721 -51.48860.154 1.0057.86 N
ATOM 6905 C LYS L 126 -15.870-49.55352.911 1.0050.73 C
ATOM 6906 O LYS L 126 -16.811 -49.720 52.109 1.0051.27 O
ATOM 6907 N SERL 127 -14.962-48.546 52.815 1.0050.24 N ATOM 6908 CA SERL 127 -14.966-47.485 51.807 1.0049.86 C
ATOM 6909 CB SER L 127 -14.007-46.348 52.185 1.0053.95 C
ATOM 6910 OG SER L 127 -12.688-46.49951.680 1.0054.23 O
ATOM 6911 C SERL 127 -14.666-48.029 50.416 1.0049.37 C
ATOM 6912 0 SERL 127 -14.879-47.31049.433 1.0049.89 O ATOM 6913 N GLYL128 -14.178-49.265 50.344 1.0046.00 N
ATOM 6914 CA GLY L 128 -13.877-49.92349.076 1.0045.37 C
ATOM 6915 C GLY L 28 -12.446-49.89248.566 1.0044.99 C
ATOM 69160 GLY L 128 -12.232-50.03647.354 1.0045.31 O
ATOM 6917 N THRL129 -11.449-49.71349.473 1.0042.40 N ATOM 6918 CA THR L 129 -10.024-49.68549.109 1.0041.14 C
ATOM 6919 CB THR L 129 -9.523-48.23348.824 1.0041.22 C
ATOM 6920 OG1 THR L 129 -10.246-47.71647.714 1.0041.32 O
ATOM 6921 CG2THRL129 -8.044-48.16348.451 1.0040.52 C
ATOM 6922 C THR L 29 -9.214-50.40450.156 1.0040.51 C ATOM 69230 THR L 129 -9.652-50.514 51.299 1.0040.40 O
ATOM 6924 N ALA L 130 -8.031 -50.89849.771 1.0039.56 N
ATOM 6925 CA ALA L 130 -7.133-51.577 50.693 1.0038.85 C
ATOM 6926 CB ALA L 130 -7.165-53.067 50.453 1.0039.56 C
ATOM 6927 C ALA L 130 -5.719-51.056 50.552 1.0038.00 C ATOM 6928 0 ALA L 130 -5.099-51.20449.497 1.0037.65 O
ATOM 6929 N SERL 131 -5,214-50.43751.606 1.0037.47 N
ATOM 6930 CA SER L 131 -3.850-49.94651.617 1.0037.52 C
ATOM 6931 CB SERL 131 -3.791 -48.438 51.827 1.0039.91 C
ATOM 6932 OG SER L 131 -4.221 -47.763 50.658 1.0040.07 O ATOM 6933 C SERL 131 -3.072-50.716 52.681 1.0037.32 C
ATOM 6934 O SER L 131 -3.359-50.616 53.886 1.0037.48 O
ATOM 6935 N VAL L 132 -2.105-51.519 52.216 1.0036.64 N
ATOM 6936 CA VAL L 132 -1.239-52.332 53.073 1.0036.36 C
ATOM 6937 CB VAL L 132 -0.963-53.73052.462 1.0039.67 C ATOM 6938 CG1 VAL L 132 -0.328-54.654 53.489 1.0039.77 C
ATOM 6939 CG2 VAL L 132 -2.228-54.34951.886 1.0039.19 C
ATOM 6940 C VAL L 132 0.044-51.530 53.228 1.0036.02 C
ATOM 6941 O VAL L 132 0.605-51.11452.217 1.0035.83 O
ATOM 6942 N VAL L 133 0.513-51.318 54.460 1.0035.39 N ATOM 6943 CA VAL L 133 1.726-50.521 54.689 1.0035.74 C
ATOM 6944 CB VAL L 133 1.425-49.233 55.533 1.0037.52 C
ATOM 6945 CG1 VAL L 133 2.697-48.552 56.032 1.0036.60 C
ATOM 6946 CG2VALL133 0.558-48.250 54.759 1.0037.13 C
ATOM 6947 C VAL L 133 2.884-51.296 55.284 1.0036.32 C ATOM 6948 0 VAL L 133 2.747-51.880 56.365 1.0035.98 O
ATOM 6949 N CYSL134 4.047-51.235 54.620 1.0040.83 N
ATOM 6950 CA CYS L 134 5.267-51.842 55.144 1.0041.97 C
ATOM 6951 CB CYS L 134 5.968-52.702 54.104 1.0045.15 C
ATOM 6952 SG CYS L 134 7.256-53.775 54.793 1.0051.65 S ATOM 6953 C CYS L 134 6.187-50.745 55.648 1.0040.92 C
ATOM 6954 0 CYS L 34 6.452-49.787 54.920 1.0041.22 O
ATOM 6955 N LEU L 135 6.683-50.880 56.881 1.0038.47 N
ATOM 6956 CA LEU L 135 7.592-49.90457.484 1.0037.48 C
ATOM 6957 CB LEU L 135 7.015-49.424 58.836 1.0037.59 C JB2010.7161
ATOM 6958 CG LEU L 135 7.937 -48.555 59.720 1.00 37.84 C
ATOM 6959 CD1 LEU L 135 8.004 -47.111 59.234 1.00 36.39 C
ATOM 6960 CD2 LEU L 135 7.492 -48.579 61.153 1.00 38.08 C
ATOM 6961 C LEU L 135 9.011 -50.489 57.673 1.00 36.92 C ATOM 6962 0 LEU L 135 9.129 -51.597 58.171 1.00 36.59 O
ATOM 6963 N LEU L 136 10.072 -49.749 57.251 1.00 34.10 N
ATOM 6964 CA LEU L 136 11.496 -50.091 57.446 1.00 33.50 C
ATOM 6965 CB LEU L 136 12.369 -50.023 56.192 1.00 33.77 C
ATOM 6966 CG LEU L 136 12.014 -50.817 54.968 1.00 33.04 C ATOM 6967 CD1 LEU L 136 13.250 -51.127 54.189 1.00 30.68 C
ATOM 6968 CD2 LEU L 136 11.286 -52.034 55.317 1.00 33.58 C
ATOM 6969 C LEU L 136 1 1.940 -49.018 58.398 1.00 33.57 C
ATOM 6970 O LEU L 136 11.936 -47.839 58.044 1.00 33.44 O
ATOM 6971 N ASN L 137 12.247 -49.410 59.620 1.00 34.40 N ATOM 6972 CA ASN L 137 12.580 -48.456 60.648 1.00 35.07 C
ATOM 6973 CB ASN L 137 1 1.664 -48.674 61.858 1.00 38.73 C
ATOM 6974 CG ASN L 137 11.366 -47.435 62.673 1.00 40.02 C
ATOM 6975 OD1 ASN L 137 11.037 -46.359 62.156 1.00 42.88 O
ATOM 6976 ND2 ASN L 137 11.456 -47.562 63.986 1.00 40.44 N ATOM 6977 C ASN L 137 14.048 -48.410 61.038 1.00 35.44 C
ATOM 6978 0 ASN L 137 14.667 -49.436 61.313 1.00 35.11 O
ATOM 6979 N ASN L 138 14.592 -47.194 61.055 1.00 37.10 N
ATOM 6980 CA ASN L 138 15.961 -46.868 61.423 1.00 37.73 C
ATOM 6981 CB ASN L 138 16.054 -46.681 62.916 1.00 44.07 C ATOM 6982 CG ASN L 138 15.082 -45.654 63.373 1.00 45.06 C
ATOM 6983 OD1 ASN L 138 15.075 -44.515 62.878 1.00 49.21 O
ATOM 6984 ND2 ASN L 138 14.240 -46.035 64.311 1.0045.95 N
ATOM 6985 C ASN L 138 17.047 -47.778 60.851 1.00 37.78 C
ATOM 6986 O ASN L 138 17.548 -48.681 61.530 1.00 37.49 O ATOM 6987 N PHE L 139 17.394 -47.529 59.585 1.00 37.16 N
ATOM 6988 CA PHE L 139 18.402 -48.286 58.855 1.00 37.49 C
ATOM 6989 CB PHE L 139 17.757 -49.194 57.806 1.00 38.62 C
ATOM 6990 CG PHE L 139 16.937 -48.512 56.735 1.00 37.09 C
ATOM 6991 CD1 PHE L 139 17.505 -48.172 55.514 1.00 35.66 C ATOM 6992 CE1 PHE L 139 16.743 -47.564 54.511 1.00 34.67 C
ATOM 6993 CZ PHE L 139 15.410 -47.321 54.723 1.00 34.71 C
ATOM 6994 CE2 PHE L 139 14.830 -47.652 55.929 1.00 33.94 C
ATOM 6995 CD2 PHE L 139 15.585 -48.262 56.924 1.00 34.97 C
ATOM 6996 C PHE L 139 19.412 -47.382 58.187 1.00 38.04 C ATOM 6997 O PHE L 139 19.175 -46.183 58.023 1.00 37.76 O
ATOM 6998 N TYR L 140 20.546 -47.982 57.797 1.00 39.00 N
ATOM 6999 CA TYR L 140 21.647 -47.321 57.117 1.00 39.49 C
ATOM 7000 CB TYR L 140 22.502 -46.498 58.079 1.00 39.65 C
ATOM 7001 CG TYR L 140 23.475 -45.619 57.330 1.00 40.97 C ATOM 7002 CD1 TYR L 140 24.753 -46.078 57.004 1.00 41.62 C
ATOM 7003 CE1 TYR L 140 25.633 -45,298 56.266 1.00 40.86 C
ATOM 7004 CZ TYR L 140 25.249 -44.032 55.859 1.00 41.98 C
ATOM 7005 OH TYR L 140 26.133 -43.250 55.159 1.0042.38 O
ATOM 7006 CE2 TYR L 140 23.983 -43.554 56.167 1.0041.15 C ATOM 7007 CD2 TYR L 140 23.104 -44.349 56.893 1.00 41.02 C
ATOM 7008 C TYR L 140 22.485 -48.361 56.349 1.00 39.84 C
ATOM 7009 O TYR L 140 22.766 -49.432 56.908 1.00 40.31 O
ATOM 7010 N PRO L 141 22.896 -48.098 55.071 1.00 39.96 N
ATOM 7011 CA PRO L 141 22.651 -46.903 54.228 1.00 40.14 C JB2010.7161
ATOM 7012 CB PRO L 141 23.661 -47.105 53.088 1.0040.85 C
ATOM 7013 CG PRO L 141 23.692-48.586 52.915 1.0040.51 C
ATOM 7014 CD PRO L 141 23.686-49.105 54.326 1.0040.88 C
ATOM 7015 C PRO L 141 21.196-46.770 53.729 1.0040.63 C ATOM 7016 O PRO L 141 20.377-47.65353.988 1.0039.97 O
ATOM 7017 N ARG L 142 20.889-45.684 52.989 1.0043.36 N
ATOM 7018 CA ARG L 142 19.567-45.394 52.431 1.0044.42 C
ATOM 7019 CB ARG L 142 19.594-44.034 51.738 1.0046.19 C
ATOM 7020 CG ARG L 142 18.222-43.423 51.498 1.0047.97 C ATOM 7021 CD ARG L 142 18.314-42.09650.770 1.0050.58 C
ATOM 7022 NE ARG L 142 17.392-42.08549.640 1.0052.83 N
ATOM 7023 CZ ARG L 142 16.272-41.37249.577 1.0053.43 C
ATOM 7024 NH ARGL142 15.931 -40.561 50.578 1.0054.61 N
ATOM 7025 NH2 ARG L 142 15.494-41.44448.504 1.0053.82 N ATOM 7026 C ARG L 142 19.040-46.449 51.454 1.0044.89 C
ATOM 7027 O ARG L 142 17.823-46.61351.347 1.0045.05 O
ATOM 7028 N GLU L 143 19.933-47.136 50.724 1.0048.81 N
ATOM 7029 CA GLU L 143 19.522-48.131 49.727 1.0049.90 C
ATOM 7030 CB GLU L 143 20.508-48.34248.556 1.0052.15 C ATOM 7031 CG GLU L 143 21.978-48.08348.850 1.0054.87 C
ATOM 7032 CD GLU L 143 22.412-46,62948.947 1.0057.12 C
ATOM 7033 OE1 GLU L 143 23.153-46.30549.905 1.0058.30 O
ATOM 7034 OE2 GLU L 143 22.009-45.81548.080 1.0057.38 O
ATOM 7035 C GLU L 143 19.017-49.410 50.296 1.0050.07 C ATOM 7036 O GLU L 143 19.756-50.143 50.961 1.0050.40 O
ATOM 7037 N ALA L 144 17.726-49.668 50.041 1.0049.61 N
ATOM 7038 CA ALA L 144 17.010-50.849 50.501 1.0049.58 C
ATOM 7039 CB ALA L 144 16.388-50.569 51.859 1.0049.93 C
ATOM 7040 C ALA L 144 15.919-51.23949.497 1.0049.71 C ATOM 7041 O ALA L 144 15.204-50.35449.010 1.0050.34 O
ATOM 7042 N LYS L 145 15.790-52.54849.180 1.0046.06 N
ATOM 7043 CA LYS L 145 14.754-53.01548.262 1.0045.90 C
ATOM 7044 CB LYS L 145 15.273-54.121 47.328 1.0048.16 C
ATOM 7045 C LYS L 145 13.572-53.53249.058 1.0045.74 C ATOM 7046 O LYS L 145 13.745-54.33449.977 1.0045.89 O
ATOM 7047 N VAL L 146 12.377-53.07448.709 1.0041.79 N
ATOM 7048 CA VALL 146 11.116-53.50349.315 1.0041.66 C
ATOM 7049 CB VAL L 146 10.368-52.371 50.068 1.0044.36 C
ATOM 7050 CG1 VALL 146 8.976-52.813 50.497 1.0043.93 C ATOM 7051 CG2 VALL 146 11.165-51.883 51.266 1.0044.31 C
ATOM 7052 C VAL L 146 10.315-54.05848.145 1.0042.05 C
ATOM 7053 O VAL L 146 10.013-53.34947.175 1.0041.63 O
ATOM 7054 N GLN L 147 10.004-55.33348.230 1.0046.03 N
ATOM 7055 CA GLN L 147 9.277-56.05847.200 1.0046.89 C ATOM 7056 CB GLN L 147 10.192-57.20046.720 1.0051.07 C
ATOM 7057 CG GLN L 147 9.622-58.121 45.665 1.0055.34 C
ATOM 7058 CD GLN L 147 9.658-57.47244.309 1.0061.48 C
ATOM 7059 OE1 GLN L 147 10.735-57.00943.825 1.0064.83 O
ATOM 7060 NE2 GLN L 147 8.470-57.41743.675 1.0060.31 N ATOM 7061 C GLN L 147 7.932-56.597 47.749 1.0046.29 C
ATOM 7062 O GLN L 147 7.937-57,38648.693 1.0046.34 O
ATOM 7063 N TRPL148 6.792-56.17247.167 1.0043.55 N
ATOM 7064 CA TRP L 148 5.475-56.66347.587 1.0042.97 C
ATOM 7065 CB TRP L 148 4.392-55.631 47.306 1.0039.62 C JB2010.7161
ATOM 7066 CG TRP L 148 4.388 -54.505 48.291 1.00 37.78 C
ATOM 7067 CD1 TRP L 148 4.895 -53.254 48.111 1.00 35.32 C
ATOM 7068 NE1 TRP L 148 4.711 -52.498 49.248 1.00 34.17 N
ATOM 7069 CE2 TRP L 148 4.072 -53.257 50.191 1.00 34.35 C ATOM 7070 CD2 TRP L 148 3.866 -54.538 49.630 1 .00 36.50 C
ATOM 7071 CE3 TRP L 148 3.201 -55.519 50.398 1.00 36.07 C
ATOM 7072 CZ3 TRP L 148 2.799 -55.196 51.687 1.00 36.64 C
ATOM 7073 CH2 TRP L 148 3.038 -53.922 52.224 1.00 36.43 C
ATOM 7074 C22 TRP L 148 3.648 -52.929 51.482 1.00 35.47 C ATOM 7075 C TRP L 48 5.171 -58.008 46.891 1.00 43.88 C
ATOM 7076 O TRP L 148 5.366 -58.135 45.673 1.00 43.59 O
ATOM 7077 N LYS L 149 4.743 -59.017 47.676 1.0047.44 N
ATOM 7078 CA LYS L 149 4.428 -60.362 47.200 1.00 48.36 C
ATOM 7079 CB LYS L 149 5.440 -61.406 47.752 1 ,00 51.44 C ATOM 7080 CG LYS L 149 6.898 -61.223 47.373 1.00 51.22 C
ATOM 7081 CD LYS L 149 7.410 -62.382 46.547 1.00 52.68 C
ATOM 7082 CE LYS L 149 8.927 -62.448 46.469 1 .00 54.20 C
ATOM 7083 NZ LYS L 149 9.567 -62.846 47.760 1.00 51.54 N
ATOM 7084 C LYS L 149 3.032 -60.754 47.673 1.00 49.06 C ATOM 7085 O LYS L 149 2.894 -61.283 48.786 1.00 49.98 O
ATOM 7086 N VAL L 150 2.005 -60.534 46.841 1.00 48.19 N
ATOM 7087 CA VAL L 150 0.629 -60.918 47.158 1.00 48.43 C
ATOM 7088 CB VAL L 150 -0.372 -59.984 46.466 1.00 52.36 C
ATOM 7089 CG1 VAL L 150 -1.793 -60.399 46.774 1.00 52.88 C ATOM 7090 CG2 VAL L 150 -0.144 -58.547 46.876 1.00 52.64 C
ATOM 7091 C VAL L 150 0.435 -62.377 46.691 1.00 48.66 C
ATOM 7092 O VAL L 150 0.460 -62.636 45.476 1.00 48.52 O
ATOM 7093 N ASP L 151 0.249 -63.328 47.658 1.00 49.95 N
ATOM 7094 CA ASP L 151 0.067 -64.782 47.416 1.00 49.68 C ATOM 7095 CB ASP L 151 -1.148 -65.061 46.508 1.00 51.18 C
ATOM 7096 CG ASP L 151 -2.482 -65.166 47.192 1.00 51.16 C
ATOM 7097 OD1 ASP L 151 -2.505 -65.234 48.449 1.00 49.40 O
ATOM 7098 OD2 ASP L 151 -3.516 -65.190 46.469 1.00 52.00 O
ATOM 7099 C ASP L 151 1.311 -65.351 46.759 1.00 49.51 C ATOM 7100 O ASP L 151 1.213 -66.137 45.812 1.00 49.29 O
ATOM 7101 N AS L 152 2.484 -64.911 47.239 1.00 49.78 N
ATOM 7102 CA ASN L 152 3.817 -65.273 46.753 1.0049.72 C
ATOM 7103 CB ASN L 152 4.105 -66.744 46.914 1.00 52.10 C
ATOM 7104 CG ASN L 152 5.550 -67.016 47.161 1.00 52.62 C ATOM 7105 OD1 ASN L 152 6.245 -66.217 47.809 1.00 54.87 O
ATOM 7106 ND2 ASN L 152 6.032 -68.147 46.655 1.00 52.48 N
ATOM 7107 C ASN L 152 4.132 -64.786 45.339 1.0049.54 C
ATOM 7108 O ASN L 152 5.227 -65.046 44.836 1.00 49.11 O
ATOM 7109 N ALA L 153 3.186 -64.069 44.710 1.00 49.37 N ATOM 7110 CA ALA L 153 3.347 -63.511 43.377 1.00 49.86 C
ATOM 7111 CB ALA L 153 2.012 -63.509 42.645 1.00 50.32 C
ATOM 7112 C ALA L 153 3.864 -62.080 43.552 1.00 50.31 C
ATOM 7113 0 ALA L 153 3.209 -61.269 44.223 1.00 50.34 O
ATOM 71 14 N LEU L 154 5.043 -61.769 42.979 1.00 51.93 N ATOM 71 15 CA LEU L 154 5.540 -60.426 43.164 1.00 52.49 C
ATOM 7116 CB LEU L 154 7.063 -60.272 43.252 1.00 53.02 C
ATOM 7117 CG LEU L 154 7.923 -60.563 42.050 1.00 53.76 C
ATOM 7118 CD1 LEU L 154 8.036 -59.339 41.150 1.00 54.05 C
ATOM 7119 CD2 LEU L 154 9.327 -60.997 42.499 1.00 53.50 C JB2010.7161
ATOM 7120 C LEU L 154 4.809-59.34842.382 1.0052.53 C
ATOM 7121 0 LEU L 154 4.446-59.552 41.233 1.0052.51 O
ATOM 7122 N GLNL 155 4.550-58.21843.070 1.0053.93 N
ATOM 7123 CA GLN L 155 3.815-57.041 42.624 1.0054.23 C ATOM 7124 CB GLN L 155 3.050-56.438 43.812 1.0055.17 C
ATOM 7125 CG GLN L 155 1.952-57.32044.393 1.0056.25 C
ATOM 7126 CD GLN L 155 1.075-57.92243.324 1.0058.09 C
ATOM 7127 OE1 GLN L 155 1.147-59.13043.048 1.0059.71 O
ATOM 7128 NE2 GLN L 155 0.254-57.10242.680 1.0055.85 N ATOM 7129 C GLN L 155 4.671 -55.96241.990 1.0054.33 C
ATOM 7130 O GLN L 155 5.838-55.80042.353 1.0054.50 O
ATOM 7131 N SER L 156 4.065-55.20641.052 1.0055.36 N
ATOM 7132 CA SER L 156 4.684-54.09240.326 1.0055.17 C
ATOM 7133 CB SER L 156 5.381 -54.581 39.054 1.0060.88 C ATOM 7134 OG SER L 156 6.325-55.619 39.281 1.0062.94 O
ATOM 7135 C SER L 156 3.619-53.064 39.959 1.0054.69 C
ATOM 7136 O SER L 156 2.488-53.424 39.617 1.0054.86 O
ATOM 7137 N GLY L 157 3.995-51.79740.046 1.0053.72 N
ATOM 7138 CA GLY L 157 3.149-50.660 39.698 1.0052.81 C ATOM 7139 C GLY L 157 1.914-50.421 40.537 1.0052.16 C
ATOM 7140 O GLY L 157 1.014-49.681 40.107 1.0052.37 O
ATOM 7141 N ASN L 158 1.854-51.03741.730 1.0049.94 N
ATOM 7142 CA ASN L 158 0.719-50.86442.631 1.0049.47 C
ATOM 7143 CB ASN L 158 -0.223-52.071 42.609 1.0052.50 C ATOM 7144 CG ASN L 158 0.405-53.378 43.005 1.0053.86 C
ATOM 7145 OD1 ASN L 158 1.634-53.52543.113 1.0056.51 O
ATOM 7146 ND2 ASN L 158 -0.430-54.36243.240 1.0053.79 N
ATOM 7147 C ASN L 158 1.157-50.45744.040 1.0048.81 C
ATOM 7148 0 ASN L 158 0.368-50.527 44.986 1.0048.81 O ATOM 7149 N SER L 159 2.414-50.00244.164 1.0046.79 N
ATOM 7150 CA SER L 159 2.979-49.53845.420 1.0046.00 C
ATOM 7151 CB SER L 159 3.870-50.60046.047 1.0049.18 C
ATOM 7152 OG SER L 159 5.123-50.66645.389 1.0048.39 O
ATOM 7153 C SER L 159 3.752-48.23045.220 1.0045.77 C ATOM 7154 0 SER L 159 4.198-47.94044.109 1.0045.28 O
ATOM 7155 N GLN L 160 3.896-47.44746.310 1.0046.43 N
ATOM 7156 CA GLN L 160 4.598-46.16746.357 1.0046.47 C
ATOM 7157 CB GLN L 160 3.618-45.01046.347 1.0047.83 C
ATOM 7158 CG GLN L 160 3.019-44.77844.983 1.0050.05 C ATOM 7159 CD GLN L 160 2.166-43.551 45.001 1.0052.86 C
ATOM 7160 OE1 GLN L 160 1.060-43.541 45.572 1.0055.24 O
ATOM 7161 NE2GL L160 2.668-42.48944.382 1.0054.04 N
ATOM 7162 C GLN L 160 5.479-46.10347.579 1.0046.19 C
ATOM 7163 0 GLN L 160 5.086-46.53948.661 1,0046.63 O ATOM 7164 N GLU L 161 6.675-45.555 47.419 1.0045.60 N
ATOM 7165 CA GLU L 161 7.644-45.471 48.510 1.0044.89 C
ATOM 7166 CB GLU L 161 8.944-46.09348.029 1.0047.37 C
ATOM 7167 CG GLU L 161 9.450-47.19848.908 1.0049.78 C
ATOM 7168 CD GLU L 161 10.501 -48.02748.201 1.0053.41 C ATOM 7169 OE1 GLU L 161 11.512-47.44347.738 1.0055.46 O
ATOM 7170 OE2 GLU L 161 10.315-49.26548.109 1.0054.49 O
ATOM 7171 C GLU L 161 7.932-44.068 49.005 1.0043.65 C
ATOM 7172 0 GLU L 161 7.788-43.098 48.261 1.0043.56 O
ATOM 7173 N SER L 162 8.389-43.972 50.263 1.0039.94 N JB2010.7161
ATOM 7174 CA SER L 162 8.759 -42.705 50.874 1.00 38.30 C
ATOM 7175 CB SER L 162 7.546 -42.008 51.464 1.00 40.95 C
ATOM 7176 OG SER L 162 7.882 -40.667 51.749 1.00 39.65 O
ATOM 7177 C SER L 162 9.825 -42.919 51.929 1.00 37.71 C ATOM 7178 O SER L 162 9.658 -43.745 52.817 1.00 37.95 O
ATOM 7179 N VAL L 163 10.929 -42.181 51.819 1.00 35.29 N
ATOM 7180 CA VAL L 163 12.049 -42.251 52.752 1.00 34.41 C
ATOM 7181 CB VAL L 163 13.384 -42.595 52.043 1.00 36.18 C
ATOM 7182 CG1 VAL L 163 14.475 -42.909 53.053 1.00 36.30 C ATOM 7183 CG2 VAL L 163 13.216 -43.763 51.089 1.00 35.67 C
ATOM 7184 C VAL L 163 12.149 -40.922 53.479 1.00 34.51 C
ATOM 7185 0 VAL L 163 12.016 -39.864 52.857 1.00 34.67 O
ATOM 7186 N THR L 164 12,392 -40.956 54.789 1.00 35.81 N
ATOM 7187 CA THR L 164 12.564 -39.721 55.552 1.00 35.99 C ATOM 7188 CB THR L 164 12.360 -39.959 57.066 1.00 35.31 C
ATOM 7189 OG1 THR L 164 13.312 -40.912 57.537 1.00 35.77 O
ATOM 7190 CG2 THR L 164 10.970 -40.365 57.418 1.00 34.69 C
ATOM 7191 C THR L 164 14.007 -39.212 55.323 1.00 36.55 C
ATOM 7192 0 THR L 164 14.866 -39.921 54.768 1.00 35.73 O ATOM 7193 N GLU L 165 14.269 -37.980 55.779 1.00 40.72 N
ATOM 7194 CA GLU L 165 15.602 -37.397 55.712 1.00 41.81 C
ATOM 7195 CB GLU L 165 15.502 -35.889 56.003 1.00 44.52 C
ATOM 7196 CG GLU L 165 16.240 -35.010 55.011 1.00 48.56 C
ATOM 7197 CD GLU L 165 15.761 -35.114 53.574 1.00 54.00 C ATOM 7198 OE1 GLU L 165 14.578 -34.783 53.325 1.00 57.32 O
ATOM 7199 OE2 GLU L 165 16.563 -35.518 52.697 1.00 56.54 O
ATOM 7200 C GLU L 165 16.409 -38.122 56.819 1.0041.40 C
ATOM 7201 O GLU L 165 15.799 -38.779 57.674 1.00 41.64 O
ATOM 7202 N GLN L 166 17.743 -38.044 56.800 1.00 39.37 N ATOM 7203 CA GLN L 166 18.563 -38.676 57.841 1.00 39.79 C
ATOM 7204 CB GLN L 166 20.031 -38.323 57.646 1.00 40.51 C
ATOM 7205 CG GLN L 166 20.807 -39.440 57.064 1.00 41.14 C
ATOM 7206 CD GLN L 166 22.207 -39.025 56.796 1.00 42.34 C
ATOM 7207 OE1 GLN L 166 22.478 -37.958 56.225 1.00 43.15 O ATOM 7208 NE2 GLN L 166 23.139 -39.865 57.201 1 .00 44.04 N
ATOM 7209 C GLN L 166 18.120 -38.184 59.229 1.00 40.05 C
ATOM 7210 O GLN L 166 7.969 -36.975 59.399 1.00 40.02 O
ATOM 7211 N ASP L 167 17.909 -39.097 60.204 1.00 42.94 N
ATOM 7212 CA ASP L 167 17.484 -38.708 61.557 1.00 44.05 C ATOM 7213 CB ASP L 167 17.225 -39.939 62.448 1.0046.40 C
ATOM 7214 CG ASP L 167 16.823 -39.585 63.871 1.00 47.84 C
ATOM 7215 OD1 ASP L 167 17.714 -39.548 64.753 1.00 49.84 O
ATOM 7216 OD2 ASP L 167 15.625 -39.342 64.105 1.00 48.79 O
ATOM 7217 C ASP L 167 18,479 -37.732 62.219 1.00 44.57 C ATOM 7218 0 ASP L 167 19.678 -38.007 62.248 1.00 45.38 O
ATOM 7219 N SER L 168 17.978 -36.607 62.742 1.00 46.13 N
ATOM 7220 CA SER L 168 18.784 -35.564 63.393 1.00 46.62 C
ATOM 7221 CB SER L 168 17.886 -34.462 63.952 1.00 52.26 C
ATOM 7222 OG SER L 168 17.168 -34.894 65.100 1.00 53.31 O ATOM 7223 C SER L 168 19.694 -36.106 64.496 1.00 46.63 C
ATOM 7224 0 SER L 168 20.849 -35.685 64.603 1.00 46.80 O
ATOM 7225 N LYS L 169 19.175 -37.055 65.302 1.00 46.82 N
ATOM 7226 CA LYS L 169 19.933 -37.661 66.400 1.00 46.19 C
ATOM 7227 CB LYS L 169 19.007 -38.160 67.537 1.00 49.04 C JB2010.7161
ATOM 7228 CG LYS L 169 17.799 -37.259 67.860 1.00 51.53 C
ATOM 7229 CD LYS L 169 18.003 -36.283 69.036 1.00 54.31 C
ATOM 7230 CE LYS L 169 18.562 -34.914 68.670 1.00 56.55 C
ATOM 7231 NZ LYS L 169 18.958 -34.115 69.871 1.00 58.48 N ATOM 7232 C LYS L 169 20.908 -38.769 65.917 1.00 44.87 C
ATOM 7233 0 LYS L 169 22. 14 -38.593 66.084 1.00 44.84 O
ATOM 7234 N ASP L 170 20.412 -39.872 65.289 1.0041.20 N
ATOM 7235 CA ASP L 170 21.261 -41.014 64.863 1.00 39.73 C
ATOM 7236 CB ASP L 170 20.767 -42.323 65.503 1.00 41.21 C ATOM 7237 CG ASP L 170 9.406 -42.773 65.01 1 1.0042.36 C
ATOM 7238 OD1 ASP L 170 18.720 -43.505 65.752 1.00 44.52 O
ATOM 7239 OD2 ASP L 170 19.032 -42.410 63.886 1.00 42.33 O
ATOM 7240 C ASP L 170 21.645 -41.223 63.378 1.00 38.70 C
ATOM 7241 O ASP L 170 22.276 -42.239 63.053 1.00 37.91 O ATOM 7242 N SER L 171 21.263 -40.288 62.482 1 .00 36.51 N
ATOM 7243 CA SER L 171 21.595 -40.336 61.055 1.00 35.49 C
ATOM 7244 CB SER L 171 23.095 -40.121 60.845 1.00 39.64 C
ATOM 7245 OG SER L 171 23.541 -38.984 61.571 1.00 39.25 O
ATOM 7246 C SER L 171 21.067 -41.568 60.276 1.00 35.26 C ATOM 7247 0 SER L 171 21.577 -41.885 59.196 1.00 34.81 O
ATOM 7248 N THR L 172 20.037 -42.245 60.814 1.00 33.58 N
ATOM 7249 CA THR L 172 19.424 -43.394 60.160 1.00 33.43 C
ATOM 7250 CB THR L 172 18.969 -44.480 61.172 1.00 38.08 C
ATOM 7251 OG1 THR L 172 17.960 -43.960 62.032 1.00 39.35 O ATOM 7252 CG2 THR L 172 20.131 -45.062 61.992 1.00 37.86 C
ATOM 7253 C THR L 172 18.304 -42.882 59.247 1.00 32.92 C
ATOM 7254 0 THR L 172 18.025 -41.683 59.217 1.00 32.65 O
ATOM 7255 N TYR L 173 17.695 -43.796 58.486 1.00 33.11 N
ATOM 7256 CA TYR L 173 16.612 -43.537 57.560 1.00 32.54 C ATOM 7257 CB TYR L 173 17.046 -43.949 56.149 1.00 33.73 C
ATOM 7258 CG TYR L 173 18.063 -43.035 55.509 1.00 35.40 C
ATOM 7259 CD1 TYR L 173 19.427 -43.341 55.538 1.00 34.18 C
ATOM 7260 CE1 TYR L 173 20.365 -42.500 54.944 1.00 33.34 C
ATOM 7261 CZ TYR L 173 19.940 -41.345 54.301 1.00 33.44 C ATOM 7262 OH TYR L 173 20.831 -40.486 53.712 1.00 34.91 O
ATOM 7263 CE2 TYR L 173 18.596 -41.015 54.271 1.00 32.73 C
ATOM 7264 CD2 TYR L 173 17.664 -41.873 54.844 1.00 35.54 C
ATOM 7265 C TYR L 173 15.442 -44.429 57.914 1.00 32.61 C
ATOM 7266 0 TYR L 173 15.620 -45.514 58.471 1.00 32.69 O ATOM 7267 N SER L 174 14.246 -44.004 57.548 1.00 32.14 N
ATOM 7268 CA SER L 174 13.082 -44.827 57.688 1.00 32.18 C
ATOM 7269 CB SER L 174 12.165 -44.310 58.772 1.00 37.85 C
ATOM 7270 OG SER L 174 12.583 -44.928 59.976 1.00 39.22 O
ATOM 7271 C SER L 174 12.447 -44.848 56.318 1.00 32.24 C ATOM 7272 O SER L 174 12.692 -43.948 55.534 1 .00 32.08 O
ATOM 7273 N LEU L 175 11.692 -45.889 55.995 1.00 34.78 N
ATOM 7274 CA LEU L 175 11.033 -46.033 54.698 1.00 35.19 C
ATOM 7275 CB LEU L 175 11.860 -46.952 53.782 1.00 34.70 C
ATOM 7276 CG LEU L 175 11.401 -47.130 52.360 1.00 34.41 C ATOM 7277 CD1 LEU L 175 12.551 -47.394 51.476 1.00 32.24 C
ATOM 7278 CD2 LEU L 175 10.424 -48.275 52.253 1.00 34.08 C
ATOM 7279 C LEU L 175 9.664 -46.618 54.931 1.00 35.66 C
ATOM 7280 O LEU L 175 9.510 -47.538 55.732 1.00 35.61 O
ATOM 7281 N SER L 176 8.677 -46.089 54.224 1.00 38.59 N JB2010.7161
ATOM 7282 CA SER L 176 7.294 -46.521 54.292 1.00 39.66 C
ATOM 7283 CB SER L 176 6.432 -45.414 54.883 1.00 46.07 C
ATOM 7284 OG SER L 176 5.060 -45.642 54.615 1.00 47.62 O
ATOM 7285 C SER L 176 6.825 -46.839 52.893 1.00 40.26 C ATOM 7286 0 SER L 176 6.821 -45.939 52.056 1.00 41.38 O
ATOM 7287 N SER L 177 6.451 -48.108 52.622 1.00 39.17 N
ATOM 7288 CA SER L 177 5.938 -48.540 51 .320 1 .00 39.45 C
ATOM 7289 CB SER L 177 6.682 -49.765 50.807 1.00 42.96 C
ATOM 7290 OG SER L 177 6.272 -50.091 49.490 1.00 42.77 O ATOM 7291 C SER L 177 4.455 -48.840 51.476 1.00 39.71 C
ATOM 7292 O SER L 177 4.052 -49.458 52.460 1 .00 40.73 O
ATOM 7293 N TH L 178 3.637 -48.382 50.533 1.00 37.53 N
ATOM 7294 CA THR L 178 2.198 -48.575 50.599 1.00 37.41 C
ATOM 7295 CB THR L 178 1.516 -47.229 50.861 1.00 39.57 C ATOM 7296 OG1 THR L 178 2.096 -46.643 52.024 1.00 39.53 O
ATOM 7297 CG2 THR L 178 0.007 -47.335 51.001 1.00 38.39 C
ATOM 7298 C THR L 178 1.672 -49.253 49.357 1.00 37.95 C
ATOM 7299 0 THR L 178 1.655 -48.640 48.291 1.00 37.71 O
ATOM 7300 N LEU L 179 1.226 -50.514 49.500 1.00 37.71 N ATOM 7301 CA LEU L 179 0.622 -51.259 48.403 1.00 38.36 C
ATOM 7302 CB LEU L 179 0.860 -52.768 48.572 1.00 37.34 C
ATOM 7303 CG LEU L 179 0.277 -53.661 47.474 1.00 37.16 C
ATOM 7304 CD1 LEU L 179 1.230 -53.795 46.333 1.00 36.11 C
ATOM 7305 CD2 LEU L 179 -0.023 -55.018 47.997 1.00 36.31 C ATOM 7306 C LEU L 179 -0.876 -50.930 48.451 1.00 39.03 C
ATOM 7307 O LEU L 179 -t.525 -51.212 49,460 1.00 39.15 O
ATOM 7308 N THR L 180 -1.410 -50.282 47.409 1.00 41.56 N
ATOM 7309 CA THR L 180 -2.842 -49.934 47.376 1.00 42.99 C
ATOM 7310 CB THR L 180 -3.119 -48.406 47.286 1.00 51.23 C ATOM 731 1 OG1 THR L 180 -2.474 -47.691 48.352 1.00 52.38 O
ATOM 7312 CG2 THR L 180 -4.603 -48.084 47.319 1.00 51.14 C
ATOM 7313 C THR L 180 -3.554 -50.752 46.313 1.00 43.34 C
ATOM 7314 0 THR L 180 -3.137 -50.774 45.153 1.00 43.41 O
ATOM 7315 N LEU L 181 -4.627 -51.425 46.735 1.00 45.20 N ATOM 7316 CA LEU L 181 -5.485 -52.289 45.929 1.00 45.57 C
ATOM 7317 CB LEU L 181 -5.232 -53.736 46.390 1.00 45.80 C
ATOM 7318 CG LEU L 181 -4.665 -54.746 45.388 1.00 46.69 C
ATOM 7319 CD1 LEU L 181 -3.679 -54.110 44.406 1.00 47.01 C
ATOM 7320 CD2 LEU L 181 -4.010 -55.909 46.116 1.00 46.46 C ATOM 7321 C LEU L 181 -6.961 -51.927 46.161 1.00 45.80 C
ATOM 7322 0 LEU L 181 -7.293 -51.348 47.200 1.00 45.51 O
ATOM 7323 N SER L 182 -7.845 -52.279 45.211 1.00 47.46 N
ATOM 7324 CA SER L 182 -9.287 -52.037 45.363 1.00 48.58 C
ATOM 7325 CB SER L 182 -9.996 -52.140 44.017 1.00 52.50 C ATOM 7326 OG SER L 182 -9.809 -53.400 43.393 1.00 53.30 O
ATOM 7327 C SER L 182 -9.792 -53.114 46.314 1 .00 49.16 C
ATOM 7328 0 SER L 182 -9.127 -54.153 46.410 1.00 49.36 O
ATOM 7329 N LYS L 183 -10.929 -52.901 47.031 1.00 52.00 N
ATOM 7330 CA LYS L 183 -11.432 -53.931 47.973 1.00 52.83 C ATOM 7331 CB LYS L 183 -12.718 -53.498 48.679 1.00 56.56 C
ATOM 7332 CG LYS L 183 -12.988 -54.302 49.937 1.00 57.82 C
ATOM 7333 CD LYS L 183 -14.437 -54.258 50.382 1.00 60.42 C
ATOM 7334 CE LYS L 183 -14.524 -54.836 51.779 1.00 62.97 C
ATOM 7335 HZ LYS L 183 -15.929 -55.009 52.254 1.00 63.88 N JB2010J161
ATOM 7336 C LYS L 183 -11 .622 -55.290 47.280 1.00 53.30 C
ATOM 7337 0 LYS L 183 - 1.314 -56.330 47.868 1.00 53.25 O
ATOM 7338 N ALA L 184 -12.087 -55.258 46.007 1.00 54.62 N
ATOM 7339 CA ALA L 184 -12.304 -56.420 45.151 1.00 55.06 C ATOM 7340 CB ALA L 184 -12.953 -55.990 43.843 1.00 55.64 C
ATOM 7341 C ALA L 184 -10.998 -57.194 44.878 1.00 55.56 C
ATOM 7342 0 ALA L 184 -10.959 -58.400 45.134 1.00 56.10 O
ATOM 7343 N ASP L 185 -9.939 -56.522 44.378 1.00 54.69 N
ATOM 7344 CA ASP L 185 -8.664 -57.200 44.097 1.00 54.98 C ATOM 7345 CB ASP L 185 -7.672 -56.289 43.355 1.00 58,05 C
ATOM 7346 CG ASP L 185 -8.053 -55.882 41.941 1.00 59.60 C
ATOM 7347 OD1 ASP L 185 -8.914 -56.566 41.327 1.00 62.21 O
ATOM 7348 OD2 ASP L 185 -7.481 -54.890 41.440 1.00 60.45 O
ATOM 7349 C ASP L 185 -8.026 -57.710 45.380 1.00 54.51 C ATOM 7350 O ASP L 185 -7.456 -58.797 45.382 1.00 54.63 O
ATOM 7351 N TYR L 186 -8.133 -56.933 46.473 1.00 50.39 N
ATOM 7352 CA TYR L 186 -7.592 -57.302 47.774 1.00 49.59 C
ATOM 7353 CB TYR L 186 -7.787 -56.149 48.762 1.00 47.67 C
ATOM 7354 CG TYR L 186 -7.298 -56.457 50.157 1.00 44.21 C ATOM 7355 CD1 TYR L 186 -5.941 -56.539 50.436 1.00 41.38 C
ATOM 7356 CE1 TYR L 186 -5.482 -56.805 51.718 1.00 39.98 C
ATOM 7357 CZ TYR L 186 -6.387 -56.977 52.744 1.00 38.78 C
ATOM 7358 OH TYR L 186 -5.918 -57.256 53.998 1.00 37.70 O
ATOM 7359 CE2 TYR L 186 -7.744 -56.867 52.498 1.00 39.01 C ATOM 7360 CD2 TYR L 186 -8.191 -56.627 51.205 1.00 40.94 C
ATOM 7361 C TYR L 186 -8.255 -58.598 48.295 1.00 50.34 C
ATOM 7362 0 TYR L 186 -7.604 -59.435 48.939 1.00 50.12 O
ATOM 7363 N GLU L 187 -9.550 -58.754 47.996 1.00 52.52 N
ATOM 7364 CA GLU L 187 -10.293 -59.928 48.413 1.00 53.39 C ATOM 7365 CB GLU L 187 -11.770 -59.620 48.560 1.00 55.11 C
ATOM 7366 CG GLU L 187 -11.985 -58.846 49.845 1.00 57.12 C
ATOM 7367 CD GLU L 187 -13.407 -58.523 50.257 1.00 59.54 C
ATOM 7368 OE1 GLU L 187 -14.323 -58.626 49.405 1.00 61.06 O
ATOM 7369 OE2 GLU L 187 -13.599 -58.159 51.442 1.00 60.47 O ATOM 7370 C GLU L 187 -9.977 -61.199 47.614 1.00 53.69 C
ATOM 7371 O GLU L 187 -10.115 -62.293 48.161 1.00 54.00 O
ATOM 7372 N LYS L 188 -9.492 -61.058 46.355 1.00 52.79 N
ATOM 7373 CA LYS L 188 -9.099 -62.165 45.473 1.00 52.74 C
ATOM 7374 CB LYS L 188 -8.759 -61.623 44.077 1.00 54.61 C ATOM 7375 CG LYS L 188 -9.941 -61.270 43.216 1.00 56.05 C
ATOM 7376 CD LYS L 188 -9.448 -60.689 41.926 1.00 57.88 C
ATOM 7377 CE LYS L 188 -10.446 -59.717 41.359 1.00 60.21 C
ATOM 7378 NZ LYS L 188 -9.838 -58.884 40.281 1.00 61.92 N
ATOM 7379 C LYS L 188 -7.844 -62.918 45.986 1.00 52.56 C ATOM 7380 O LYS L 188 -7.518 -63.974 45.435 1.00 52.78 O
ATOM 7381 N HIS L 189 -7.114 -62.365 46.995 1.00 52.66 N
ATOM 7382 CA HIS L 189 -5.877 -62.951 47.529 1.00 52.17 C
ATOM 7383 CB HIS L 189 -4.682 -62. 37 47.057 1.00 53.36 C
ATOM 7384 CG HIS L 189 -4.719 -61.886 45.583 1.00 54.45 C ATOM 7385 ND1 HIS L 189 -5.116 -60.663 45.071 1 .00 55.85 N
ATOM 7386 CE1 HIS L 189 -5.071 -60.788 43.752 1.00 55.68 C
ATOM 7387 NE2 HIS L 189 -4.689 -62.011 43.390 1.00 56.62 N
ATOM 7388 CD2 HIS L 189 -4.472 -62.730 44.553 1.00 55.89 C
ATOM 7389 C HiS L 189 -5.882 -63.143 49.033 1.00 51.61 C JB2010.7161
ATOM 7390 O HIS L 189 -6.697-62.52849.712 1.0051.93 O
ATOM 7391 N LYS L 190 -4.999-64.00549.565 1.0050.15 N
ATOM 7392 CA LYS L 190 -4.988-64.285 51.002 1.0049.64 C
ATOM 7393 CB LYS L 190 -5.320-65.764 51.291 1.0051.27 C ATOM 7394 C LYS L 190 -3.771 -63.814 51.782 1.0049.17 C
ATOM 7395 O LYS L 190 -3.939-63.238 52.859 1.0049.68 O
ATOM 7396 N VAL L 191 -2.561 -64.059 51.269 1.0047.10 N
ATOM 7397 CA VAL L 191 -1.336-63.666 51.971 1.0046.31 C
ATOM 7398 CB VAL L 191 -0.336-64.851 52.183 1.0050.03 C ATOM 7399 CG1 VAL L 191 -0.876-65.834 53.216 1.0050.40 C
ATOM 7400 CG2VALL191 1.045-64.36352.613 1.0050.11 C
ATOM 7401 C VAL L 191 -0.694-62.451 51.325 1.0045.42 C
ATOM 7402 O VAL L 191 -0.439-62.431 50.112 1.0045.03 O
ATOM 7403 N TYR L 192 -0.430-61.446 52.158 1.0042.22 N ATOM 7404 CA TYR L 192 0.197-60.208 51.756 1.0041.31 C
ATOM 7405 CB TYR L 192 -0.710-59.014 52.090 1.0040.99 C
ATOM 7406 CG TYR L 192 -1.865-58.92651.126 1.0040.14 C
ATOM 7407 CD1 TYR L 192 -1.799-58.109 50.002 1.0038.71 C
ATOM 7408 CE1 TYR L 192 -2.848-58.05649.088 1.0038.96 C ATOM 7409 CZ TYR L 192 -3.965-58.851 49.275 1.0038.64 C
ATOM 7410 OH TYR L 192 -4.991 -58.80048.375 1.0038.07 O
ATOM 7411 CE2TYRL 192 -4.054-59.674 50.382 1.0038.96 C
ATOM 7412 CD2TYRL192 -3.007-59.709 51.300 1.0040.07 C
ATOM 7413 C TYR L 192 1.539-60.131 52.429 1.0041.50 C ATOM 7414 O TYR L 192 1.608-60.10053.652 1.0041.66 O
ATOM 7415 N ALA L 193 2.603-60.147 51.638 1.0043.23 N
ATOM 7416 CA ALA L 193 3.964-60.099 52.149 1.0043.86 C
ATOM 7417 CB ALA L 193 4.688-61.409 51.868 1.0044.58 C
ATOM 7418 C ALA L 193 4.759-58.933 51.588 1.0044.02 C ATOM 7419 O ALA L 193 4.578-58.524 50.440 1.0043.79 O
ATOM 7420 N CYSL194 5.646-58.427 52.419 1.0044.91 N
ATOM 7421 CA CYS L 194 6.560-57.34252.150 1.0046.03 C
ATOM 7422 CB CYS L 194 6.333-56.23953.183 1.0047.50 C
ATOM 7423 SG CYS L 194 7.620-54.97753.199 1.0052.16 S ATOM 7424 C CYS L 194 7.976-57.96652.268 1.0045.66 C
ATOM 7425 0 CYS L 194 8.310-58.55453.305 1.0045.40 O
ATOM 7426 N GLU L 195 8.787-57.88051.214 1.0047.36 N
ATOM 7427 CA GLU L 195 10.134-58.465 51.255 1.0047.77 C
ATOM 7428 CB GLU L 195 10.322-59,532 50.181 1.0050.49 C ATOM 7429 CG GLU L 195 11.569-60.361 50.410 1.0052.93 C
ATOM 7430 CD GLU L 195 11.995-61.148 49.191 1.0057.07 C
ATOM 7431 OE1 GLU L 95 12.012-62.39849.284 1.0059.44 O
ATOM 7432 OE2 GLU L 195 12.298-60.52448.143 1.0058.79 O
ATOM 7433 C GLU L 195 11.264-57.425 51.241 1.0047.17 C ATOM 7434 0 GLU L 195 11.521 -56.768 50.224 1.0047.06 O
ATOM 7435 N VAL L 196 11.947-57.315 52.373 1.0043.90 N
ATOM 7436 CA VAL L 196 13.012-56.34352.560 1.0043.87 C
ATOM 7437 CB VAL L 196 12.821 -55.608 53.913 1.0046.72 C
ATOM 7438 CG1 VAL L 196 13.961 -54.63354.206 1.0045.46 C ATOM 7439 CG2 VAL L 196 11.466-54.91953.957 1.0045.59 C
ATOM 7440 C VAL L 196 14.444-56.861 52.356 1.0044.18 C
ATOM 7441 O VAL L 196 14.895-57.760 53.066 1.0043.85 O
ATOM 7442 N THR L 197 15.155-56.238 51.405 1.0044.92 N
ATOM 7443 CA THR L 197 16.549-56.512 51.067 1.0045.60 C JB201G.7161
ATOM 7444 CB THR L 197 16.690 -56.880 49.592 1.00 57.14 C
ATOM 7445 OG1 THR L 197 15.491 -57.514 49.133 1 ,00 58.73 O
ATOM 7446 CG2 THR L 197 17.874 -57.769 49.347 1.00 57.49 C
ATOM 7447 C THR L 197 17.346 -55.249 51.444 1.00 45.45 C ATOM 7448 0 THR L 197 16.990 -54.144 51.039 1.00 45.31 O
ATOM 7449 N HIS L 198 18.385 -55.416 52.249 1.00 45.36 N
ATOM 7450 CA HIS L 198 19.224 -54.337 52.731 1.00 45.85 C
ATOM 7451 CB HIS L 198 18.535 -53.640 53.906 1.00 45.49 C
ATOM 7452 CG HIS L 198 19.288 -52.455 54.409 1.00 44.85 C ATOM 7453 ND1 HIS L 198 20.175 -52.563 55.465 1.00 44.15 N
ATOM 7454 CE1 HIS L 198 20,664 -51.350 55.646 1.00 44.28 C
ATOM 7455 NE2 HIS L 198 20.154 -50.481 54.770 1.00 44.58 N
ATOM 7456 CD2 HIS L 198 19.277 -51 .175 53.973 1.00 43.96 C
ATOM 7457 C HIS L 198 20.574 -54.905 53.179 1.00 46.66 C ATOM 7458 0 HIS L 198 20.603 -56.005 53,747 1.00 46.96 O
ATOM 7459 N GLN L 199 21.683 -54.148 52.963 1.00 48.90 N
ATOM 7460 CA GLN L 199 23.034 -54.575 53.348 1.00 49.59 C
ATOM 7461 CB GLN L 199 24.146 -53.675 52.766 1.00 51.39 C
ATOM 7462 CG GLN L 199 24.739 -52.659 53.719 1.00 52.97 C ATOM 7463 CD GLN L 199 26.065 -52.157 53.205 1.00 55.76 C
ATOM 7464 OE1 GLN L 199 26.136 -51.238 52.374 1.00 56.11 O
ATOM 7465 NE2 GLN L 199 27.145 -52.754 53.696 1.00 56.20 N
ATOM 7466 C GLN L 199 23.243 -54.978 54.825 1.00 49.46 C
ATOM 7467 0 GLN L 199 24.167 -55.737 55.115 1.00 50.00 O ATOM 7468 N GLY L 200 22.372 -54.505 55.722 1.00 48.18 N
ATOM 7469 CA GLY L 200 22.405 -54.837 57.144 1 ,00 47.87 C
ATOM 7470 C GLY L 200 21.761 -56.180 57.438 1.0047.94 C
ATOM 7471 O GLY L 200 21.803 -56.655 58.578 1.00 47.59 O
ATOM 7472 N LEU L 201 21.164 -56.804 56.395 1.00 49.80 N ATOM 7473 CA LEU L 201 20.475 -58.089 56.479 1.00 50.27 C
ATOM 7474 CB LEU L 201 19.016 -58.012 55.941 1.00 49.33 C
ATOM 7475 CG LEU L 201 18.076 -57.007 56.586 1.00 48.43 C
ATOM 7476 CD1 LEU L 201 16.780 -56.915 55.823 1.00 47.68 C
ATOM 7477 CD2 LEU L 201 17.837 -57.325 58.038 1.00 46.03 C ATOM 7478 C LEU L 201 21.221 -59.208 55.760 1.00 50.87 C
ATOM 7479 0 LEU L 201 21.498 -59.102 54.544 1.00 50.80 O
ATOM 7480 N SER L 202 21.503 -60.298 56.523 1.00 52.67 N
ATOM 7481 CA SER L 202 22.173 -61.527 56.095 1.00 53.07 C
ATOM 7482 CB SER L 202 22.039 -62.590 57.188 1.00 57.31 C ATOM 7483 OG SER L 202 22.160 -62.081 58.510 1.00 57.58 O
ATOM 7484 C SER L 202 21.502 -62.029 54,795 1.00 53.54 C
ATOM 7485 0 SER L 202 22.161 -62.240 53.765 1.00 53.80 O
ATOM 7486 N SER L 203 20.169 -62.173 54.864 1.00 54,97 N
ATOM 7487 CA SER L 203 19.295 -62.602 53.781 1.00 54.75 C ATOM 7488 CB SER L 203 18.945 -64.084 53.946 1.00 58.28 C
ATOM 7489 OG SER L 203 18.095 -64.318 55.057 1.00 59.14 O
ATOM 7490 C SER L 203 18.032 -61.703 53.872 1.00 54. 1 C
ATOM 7491 O SER L 203 17.869 -61.050 54.909 1.00 54.10 O
ATOM 7492 N PRO L 204 17.134 -61.641 52.847 1.00 53.47 N ATOM 7493 CA PRO L 204 15.956 -60.774 52.962 1.00 53.26 C
ATOM 7494 CB PRO L 204 15.327 -60.826 51.563 1.00 55.17 C
ATOM 7495 CG PRO L 204 16.385 -61.361 50.675 1 .00 55.70 C
ATOM 7496 CD PRO L 204 17.139 -62.321 51.540 1.00 55.57 C
ATOM 7497 C PRO L 204 14.944 -61.207 54.005 1.00 53.00 C JB2010.7161
ATOM 74980 PRO L 204 14.600-62.38854.076 1.0053.35 O
ATOM 7499 N VALL205 14.459-60.23254.796 1.0050.26 N
ATOM 7500 CA VAL L 205 13.438-60.40555.823 1.0049.74 C
ATOM 7501 CB VAL L 205 13.625-59.4 1 56.996 1.0053.53 C ATOM 7502 CG1 VAL L 205 12.404-59.38357.921 1.0053.29 C
ATOM 7503 CG2 VAL L 205 14.890-59.731 57.783 1.0053.37 C
ATOM 7504 C VAL L 205 12.078-60.228 55.156 1.0049.20 C
ATOM 7505 O VAL L 205 11.901 -59.349 54.312 1.0049.57 O
ATOM 7506 N THRL206 11.138-61.082 55.518 1.0048.06 N ATOM 7507 CA THR L 206 9.777-61.03555.011 1.0047.58 C
ATOM 7508 CB THR L 206 9.396-62.31654,243 1.0045.00 C
ATOM 7509 OG1 THR L 206 10.220-62.429 53.085 1.0044.77 O
ATOM 7510 CG2THRL206 7.944-62.322 53.803 1.0043.84 C
ATOM 7511 C THR L 206 8.868-60.851 56.187 1.0047,62 C ATOM 7512 O THR L 206 9.037-61.517 57.207 1.0047.99 O
ATOM 7513 N LYS L 207 7.914-59.943 56.046 1.0046.48 N
ATOM 7514 CA LYSL 207 6.872-59.692 57.029 1.0046.22 C
ATOM 7515 CB LYS L 207 6.996-58.308 57.680 1.0047.09 C
ATOM 7516 CG LYSL 207 7.331 -58.33659.171 1.0047.56 C ATOM 7517 CD LYS L 207 8.652-59.070 59.509 1.0049.19 C
ATOM 7518 CE LYSL 207 9.243-58.771 60.886 1.0050.37 C
ATOM 7519 NZ LYS L 207 8.292-59.025 62.015 1.0050.64 N
ATOM 7520 C LYS L 207 5.576 -59.892 56.234 1.0046.32 C
ATOM 7521 O LYS L 207 5.436-59.36655.120 1.0045.93 O ATOM 7522 N SER L 208 4.686-60.742 56.749 1.0045.15 N
ATOM 7523 CA SER L 208 3.426-61.039 56.083 1.0045.75 C
ATOM 7524 CB SER L 208 3,557-62.252 55.158 1.0048.15 C
ATOM 7525 OG SER L 208 4.036 -63.422 55.793 1.0047.86 O
ATOM 7526 C SER L 208 2.268-61. 9857.044 1.0046.00 C ATOM 75270 SER L 208 2.449-61.167 58.265 1.0046.15 O
ATOM 7528 N PHEL209 1.072-61.34356.480 1.0045.90 N
ATOM 7529 CA PHE L 209 -0.173-61.559 57.196 1.0047.09 C
ATOM 7530 CB PHE L 209 -0.763-60.232 57.748 1.0049.18 C
ATOM 7531 CG PHE L 209 -1.315-59,250 56.732 1.0050.00 C ATOM 7532 CD1 PHE L 209 -2.643-59.31556.326 1.0050.38 C
ATOM 7533 CE1 PHE L 209 -3.145-58.415 55.378 1.0051.24 C
ATOM 7534 CZ PHE L 209 -2.330-57.43954.856 1.0051.17 C
ATOM 7535 CE2 PHE L 209 -1.015-57.359 55.255 1.0049.98 C
ATOM 7536 CD2 PHE L 209 -0.510-58.25456.193 1.0050.23 C ATOM 7537 C PHE L 209 -1.132-62.249 56.242 1.0047.82 C
ATOM 7538 O PHE L 209 -1.000-62.094 55.019 1.0047.53 O
ATOM 7539 N AS L210 -2.077-63.033 56.788 1.0051.36 N
ATOM 7540 CA ASN L 210 -3.117-63.69955.994 1.0053.05 C
ATOM 7541 CB ASN L 210 -3.218-65.212 56.315 1.0063.71 C ATOM 7542 CG ASN L 210 -4.091 -66.041 55.358 1.0066.75 C
ATOM 7543 OD1 ASN L 210 -5.267-65,731 55.085 1.0069.22 O
ATOM 7544 ND2 ASN L 210 -3.544-67.141 54.836 1.0069.09 N
ATOM 7545 C ASN L 210 -4.407-62.930 56.331 1.0053.09 C
ATOM 7546 O ASN L 210 -4.645-62.660 57.513 1.0053.35 O ATOM 7547 N ARG L 211 -5.199-62.531 55.319 1.0053.59 N
ATOM 7548 CA ARG L 211 -6.453 -61.778 55.532 1.0054.86 C
ATOM 7549 CB ARG L 211 -7.217-61.595 54.220 1.0055.71 C
ATOM 7550 CG ARG L 211 -6.627-60.601 53.246 1.0055.67 C
ATOM 7551 CD ARG L 211 -7.670-60.152 52.239 1.0056.78 C JB2010.7161
ATOM 7552 NE ARG L 211 -8.230 -61.241 51.439 1.00 57.26 N
ATOM 7553 CZ ARG L 21 1 -9.468 -61.710 51.568 1 .00 56.90 C
ATOM 7554 NH1 ARG L 211 -10.298 -61.182 52.464 1.00 56.33 N
ATOM 7555 NH2 ARG L 211 -9.888 -62.711 50:803 1.00 55.66 N
ATOM 7556 C ARG L 211 -7.403 -62.407 56.608 1.00 55.58 C
ATOM 7557 O ARG L 211 -7.909 -63.525 56.427 1.00 55.82 O
ATOM 7558 N GLY L 21 -7.600 -61.676 57.713 1.00 55.36 N
ATOM 7559 CA GLY L 212 -8.428 -62.084 58.847 1.00 55.86 C
ATOM 7560 L-Y^ L. 2- *12 -7.663 -62.866 59.897 1.00 56.11 C
ATOM 7561 O GLY L 212 -7.083 -63.909 59.589 1.00 56.57 O TER 7562 GLY L 212
HETAT 7563 0 HOH W 1 30.256 -2.590 13.960 1.00 22.29 O HETAT 7564 0 HOH W 2 -1 .548 - 44.622 48.640 1.00 34.80 O HETATM 7565 0 HOH W 3 23.390 - 44.015 52.060 1.00 33.92 O HETATM 7566 0 HOH W 18.345 4.557 30.838 1.00 33.88 O HETATM 7567 0 HOH W 5 23.568 8.135 3.808 1.00 27.23 O HETATM 7568 O HOH W 6 7.744 -: 39.725 74.544 1.00 22.81 O HETATM 7569 0 HOH W 7 19.231 - •23.735 53.752 1.00 22.35 O HETATM 7570 O HOH W 8 3.076 -: 32.403 54.334 1.00 32.08 O HETATM 7571 0 HOH W 9 9.667 ■ -8.580 40.707 1.00 23.38 O HETATM 7572 o HOH W 10 20.561 2.983 21.272 1.00 37.08 O HETATM 7573 O HOH W 11 5.396 - -38.656 44.410 1.00 35.67 O HETATM 7574 O HOH W 12 29.742 47.124 5.223 1.00 43.24 0 HETATM 7575 0 HOH W 13 7.807 - -49.659 47.259 1.00 35.13 0 HETATM 7576 O HOH W 14 12.036 -0.215 31.365 1 .00 45.96 0 HETATM 7577 O HOH W 15 37.518 -14.596 51.786 1.00 36.50 0 HETATM 7578 O HOH W 16 11.555 -46.208 70.800 1.00 26.68 0 HETATM 7579 0 HOH W 17 25.093 -16.012 53.335 1.00 43.28 0 HETATM 7580 0 HOH W 18 3.777■ -35.165 68.567 1.00 35.45 0 HETATM 7581 O HOH W 19 4.094 - -44.753 51.907 1.00 32.71 0 HETATM 7582 O HOH W 20 22.797 6.356 34.189 1.00 26.19 0 HETATM 7583 O HOH W 21 7.365 -2.380 37.931 1.00 27.82 0 HETATM 7584 O HOH W 22 8.162 -6.729 31.702 1.00 29.20 0 HETATM 7585 0 HOH W 23 43.000 46.552 -8.194 1.00 36.67 0 HETATM 7586 0 HOH W 24 2.294■ -40.854 75.953 1.00 31.03 0 HETATM 7587 0 HOH W 25 -3.231 ■ -23.299 50.487 1.00 35.05 0 HETATM 7588 0 HOH W 26 10.884 6.635 28.308 1.00 30.60 0 HETATM 7589 0 HOH W 27 14.433 -10.985 28.785 1.00 27.44 0 HETATM 7590 0 HOH W 28 20.272 -15.036 10.275 1.00 39.57 0 HETATM 7591 0 HOH W 29 2.127 -4.413 40.351 1.00 36.54 0 HETATM 7592 0 HOH W 30 12.966 -26.91 1 40.232 1.00 35.55 0 HETATM 7593 0 HOH W 31 25.338 -41.121 64.283 1.00 41.17 0 HETATM 7594 0 HOH W 32 12.476 -49.724 65.374 1.00 32.77 0 HETATM 7595 0 HOH W 33 18.823 -0.966 30.767 1.00 23.28 0 HETATM 7596 0 HOH W 34 43.933 30.345 19.1 18 1.00 42.60 o HETATM 7597 0 HOH W 35 -4.662 -19.606 46.653 1.00 45.80 0 HETATM 7598 0 HOH W 36 33.392 2.423 26.947 1.0040.29 0 HETATM 7599 0 HOH W 37 1 1.767 9.104 26.469 1.00 34.95 0 HETATM 7600 0 HOH W 38 20.501 -32.284 53.651 1.00 28.23 0 HETATM 7601 0 HOH W 39 18.552 -6.116 29.416 1.00 35.22 0 HETATM 7602 0 HOH W 40 5.589 · -34.689 45.537 1.00 37.79 0 HETATM 7603 0 HOH W 41 20.296 -14.504 45.285 1.00 46.16 0 HETATM 7604 0 HOH W 42 33.208 6.659 28.134 1.00 46.65 0 HETATM 7605 0 HOH W 43 21.351 -23.052 55.148 1.00 35.20 0 JB2010.7161
HETATM 7606 0 HOH W 44 10.819 -37.803 60.656 1.00 42.07 O
HETATM 7607 0 HOH W 45 -10.744 -29.030 37.045 1.00 37.55 O
HETATM 7608 0 HOH W 46 20.215 -37.899 52.304 1.00 33.51 0
HETATM 7609 0 HOH W 47 37.098 19.026 5.734 1.00 33.42 0
HETATM 7610 0 HOH W 48 14.772 -1.754 20.980 .00 45.45 0
HETATM 7611 0 HOH W 49 32.937 6.682 4.157 1.00 37.34 0
HETATM 7612 0 HOH W 50 4.058 - 42.377 53.156 1.00 37.35 0
HETATM 7613 0 HOH W 51 7.035 14.702 30.514 1.00 35.33 0
HETATM 7614 0 HOH W 52 -11.730 -35.601 64.417 1.00 38.86 0
HETATM 7615 0 HOH W 53 22.797 -26.150 34.134 1.00 44.92 0
HETATM 7616 0 HOH w 54 31.739 -45.128 59.899 1.00 35.87 0
HETATM 7617 o HOH w 55 -0.088 - •31.348 42.823 1.00 39.79 0
HETATM 7618 0 HOH w 56 43.215 14.831 27.475 1.00 32.86 0
HETATM 7619 o HOH w 57 4.260 - ■32.619 60.007 1.00 39.35 0
HETATM 7620 0 HOH w 58 -6.566 · ■41.864 45.006 1 .00 36.25 o
HETATM 7621 o HOH w 59 5.033 - •29.416 51.787 1.00 42.34 0
HETATM 7622 0 HOH w 60 11.967 2.765 18.113 1.00 40.16 0
HETATM 7623 0 HOH w 61 47.650 13.573 12.974 1.00 40.25 0
HETATM 7624 0 HOH w 62 -6.360 · -48.811 55.997 1.00 31.93 0
HETATM 7625 0 HOH w 63 23.976 -12.478 28.883 1.00 39.70 0
HETATM 7626 0 HOH w 64 40.457 -20.612 48.065 1.00 35.27 0
HETATM 7627 0 HOH w 65 13.913 -12.995 -4.490 1.00 43.50 0
HETATM 7628 0 HOH w 66 23.848 31.687 31.958 1.00 40,99 0
HETATM 7629 0 HOH w 67 0.622 - 5.875 28.782 1.00 42.76 0
HETATM 7630 0 HOH w 68 34.471 -0.220 7.627 1.00 40.78 o
HETATM 7631 0 HOH w 69 37.242 4.445 14.608 1.00 38.96 0
HETATM 7632 0 HOH w 70 -8.580 · -25.478 44.024 1.00 45.88 0
HETATM 7633 0 HOH w 71 7.635■ ■44.423 45.050 .00 33.58 0
HETATM 7634 0 HOH w 72 -1.121 -29.149 33.295 1.00 36.12 0
HETATM 7635 0 HOH w 73 15.632 -46.755 49.021 1.00 44.32 0
HETATM 7636 0 HOH w 74 21.789 13.121 37.733 1.00 25.92 0
HETATM 7637 o HOH w 75 17.192 35.837 13.487 1.00 49.82 0
HETATM 7638 0 HOH w 76 30.713 21.422 7.169 1.00 34.50 0
HETATM 7639 o HOH w 77 21 .959 -3.838 17.769 1.00 32.28 0
HETATM 7640 o HOH w 78 -12.358 -36.212 53.054 1.00 36.38 0
HETATM 7641 o HOH w 79 -9.873 · -34.014 43.306 1.00 39.25 0
HETATM 7642 0 HOH w 80 10.771 -39.929 49.541 1.00 40.22 0
HETATM 7643 0 HOH w 81 37.817 31.730 29.992 1.00 42.15 0
HETATM 7644 0 HOH w 82 30.902 -41.127 49.423 1.00 37.56 0
HETATM 7645 0 HOH w 83 21.672 -13.038 27.238 1.00 34.42 0
HETATM 7646 0 HOH w 84 4.762 · -18.107 51.752 1.00 26.47 0
HETATM 7647 o HOH w 85 37.142 25.997 31.149 1.00 34.71 0
HETATM 7648 o HOH w 86 5.055■ -33.854 53.426 1.00 36.89 0
HETATM 7649 0 HOH w 87 12.068 -50.382 46.836 1.00 29.28 0
HETATM 7650 0 HOH w 88 38.917 3.732 17.660 1.00 31.00 0
HETATM 7651 0 HOH w 89 39.730 29.432 13.684 1.00 45.89 0
HETATM 7652 0 HOH w 90 18.715 -36.829 54.158 1.00 28.12 0
HETATM 7653 o HOH w 91 0.024■ -46.775 46.812 1.00 37.05 0
HETATM 7654 o HOH w 92 23.482 -6.275 33.373 1.0043.29 0
HETATM 7655 o HOH w 93 -7.285 -47.286 75.759 1.00 42.94 0
HETATM 7656 o HOH w 94 31.365 41.048 -11.351 1.00 50.05 0
HETATM 7657 o HOH w 95 16.269 24.483 41.610 .00 43.74 0
HETATM 7658 0 HOH w 96 15.252 30.084 35.751 1.00 43.52 0
HETATM 7659 0 HOH w 97 6.472 -29.578 39.594 .00 36.76 o JB2010.7161
HETATM 7660 O HOH W 98 15.623 -4.354 31.437 1.00 50.36 O HETATM 7661 O HOH W 99 7.035 17.987 38.166 1.00 51.00 O HETATM 7662 O HOH W 100 13.616 -28.703 50.090 1.00 41.03 O HETATM 7663 O HOH W 101 14.515 -1.457 16.699 1.00 43.59 O HETATM 7664 O HOH W 102 -6.561 -52.773 42.731 1.00 44.65 O HETATM 7665 O HOH W 103 32.690 48.791 -1.878 1.00 34.27 O HETATM 7666 O HOH W 104 4.011 -31.830 44.782 1.00 37.61 O HETATM 7667 O HOH W 105 -12.335 -29.457 60.291 1.00 53.35 O HETATM 7668 O HOH W 106 21.435 -34.084 43.227 1.00 37.26 O HETATM 7669 O HOH W 107 22.314 -3.951 53.646 1.00 37.70 O HETATM 7670 O HOH W 108 22.798 7.633 0.485 1.00 56.34 O HETATM 7671 O HOH W 109 13.564 21.196 6.132 1.00 46.06 O HETATM 7672 O HOH W 110 10.531 -4.946 31.931 1.00 36.54 O HETATM 7673 O HOH W 111 21.541 16.192 2.243 1.00 49.47 O HETATM 7674 O HOH W 112 -1.534 -31.101 64.014 1.00 46.57 O HETATM 7675 O HOH W 113 28.391 8.867 3.156 1.00 43.82 O HETATM 7676 O HOH W 114 15.389 10.909 2.455 1.0044.45 O HETATM 7677 O HOH W 115 37.441 1.861 25.715 1.00 48.25 O HETATM 7678 O HOH W 116 24.046 -4.162 35.574 1.00 44.30 O HETATM 7679 O HOH W 117 41.769 17.624 34.528 1 .00 27.08 O HETATM 7680 O HOH W 118 14.082 -12.979 54.814 1.00 41.37 O HETATM 7681 O HOH W 119 22.312 -51.392 51.285 1.00 45.71 O HETATM 7682 O HOH W 120 -2.983 -15.157 43.267 1.00 49.19 O HETATM 7683 O HOH W 121 11.230 -13.797 55.828 1.00 38.18 O HETATM 7684 O HOH W 122 12.263 -29.866 47.789 1.00 41.35 O HETATM 7685 O HOH W 123 26.240 -40.991 49.227 1.00 53.78 O HETATM 7686 O HOH W 124 -1.997 -33.064 41.954 1.00 32.90 O HETATM 7687 O HOH W 125 -0,207 -25.110 47.446 1.00 24.85 O HETATM 7688 O HOH W 126 46.383 14.126 26.645 1.00 53.31 O HETATM 7689 O HOH W 127 13.776 -0.461 23.547 1.00 41.43 O HETATM 7690 O HOH W 128 27.368 -21.497 56.693 1.00 37.00 O HETATM 7691 O HOH W 129 7.648 -22.167 52.348 1.00 43.95 O HETATM 7692 O HOH W 130 17.599 -1.063 17.220 1.00 40.03 O HETATM 7693 O HOH W 131 33.388 -11.079 13.477 1.00 46.49 O HETATM 7694 O HOH W 132 19.941 -5.402 22.293 1.00 43.89 O HETATM 7695 O HOH W 133 -11.535 -39.745 58.181 1.00 43.22 O HETATM 7696 O HOH W 134 10.819 6.943 14.678 1.00 39.32 O HETATM 7697 O HOH W 135 14.950 -40.785 59.773 1.00 36,02 O HETATM 7698 O HOH W 136 25.627 -13.472 54.035 1.00 41.53 O HETATM 7699 O HOH W 137 12.529 -40.892 65.745 1.00 38.70 O HETATM 7700 O HOH W 138 19.779 -60.757 59.192 1.00 46.29 O HETATM 7701 O HOH W 139 13.277 9.864 28.790 1.00 37.19 O HETATM 7702 O HOH W 140 52.521 14.398 11.020 1.00 59.28 O HETATM 7703 O HOH W 141 13.540 8.311 35.029 1.00 47.14 O HETATM 7704 O HOH W 142 30.534 11.969 19.897 1.00 34.96 O HETATM 7705 O HOH W 143 27.709 1.208 13.374 1.00 36.12 O HETATM 7706 O HOH W 144 20.336 -10.453 39.120 1.00 30.48 O HETATM 7707 O HOH W 145 23.081 -19.452 30.523 1.00 48.62 O END
*************************** JB2010.7161
The present invention is not to be limited in scope by the specific embodiments described herein. Indeed, the scope of the present invention includes embodiments specifically set forth herein and other embodiments not specifically set forth herein; the embodiments specifically set forth herein are not necessarily intended to be exhaustive. Various modifications of the invention in addition to those described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the claims.
Patents, patent applications, publications, product descriptions, and protocols are cited throughout this application, the disclosures of which are incorporated herein by reference in their entireties for all purposes.

Claims

JB2010.7161 We claim:
1. An isolated antibody or antigen-binding fragment thereof:
(a) that comprises a poiypeptide comprising a light variable immunoglobulin region which comprises the amino acid sequence:
QVQLVQSGAEVK PGASV VSC VSGYTFTDYYMNWVRQAPGQGLEWIGDINPNNGGMYNQKFKGRATLTVDKSTSTAY
MELRSLRSDDTAVYYCTSGIITEIAEDFWGQGTLVTVSS (SEQ ID NO: 2); and a polypeptide comprising a heavy variable immunoglobulin region which comprises the amino acid sequence:
DIQ TQSPSSLSASVGDRVTITCKASQNVGTNVV YQQKPG APKALIHSASYRYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYKTYPYTFGQGT VEIKR (SEQ
ID NO: 7);
(b) that specifically binds to PCSK9 at an epitope comprising the amino acid sequence EDGTRFHRQASKC (amino acids 211-223 of SEQ ID NO:8);
(c) that specifically binds PCSK9 at a furin processing site; and/or
(d) that specifically binds to PCSK9 such that, upon such binding, the PCSK9 residues and/or atoms thereof indicated in the table
Atom Residue res #
CB SER 188
OG SER 188
N GLU 211
CB GLU 211
CG 0LU 211
CD GLU 211
OE1 GLU 211
OE2 GLU 211
0 GLU 211
CA GLY 213
O GLY 213
N THR 214
CA THR 214
CB THR 214
OG1 THR 214
CG2 THR 214
N ARG 215
CA ARG 215
CB ARG 215
CG ARG 215
CD ARG 215
NE ARG 215
ARG 215
NH1 ARG 215
NH2 ARG 215
C ARG 215
O ARG 215
N PHE 216 JB2010.7161
CA PHE 216
CB PHE 216
CG PHE 216
CD1 PHE 216
CE1 PHE 216 cz PHE 216
PHE 216
CD2 PHE 216
0 PHE 216
N HIS 217
CA HIS 217
CB HIS 217
CG HIS 217
ND1 HIS 217
CEEi HIS 217
NE2 HIS 217
CD2 HIS 217
C HIS 217
0 HIS 217
N ARG 218
CA ARG 218
CB ARG 218
CG ARG 218
CD ARG 218
NH2 ARG 218
C ARG 218
0 ARG 218
N GLN 219
CA GLN 219
CB GLN 219
CG GLN 219
CD GLN 219
0E1 GLN 219
NE2 GLN 219
0 GLN 219
N ALA 220
CA ALA 220
CB ALA 220
O ALA 220
N SER 221
CB SER 221
OG SER 221
O SER 221
CA LYS 222
CD LYS 222
CE LY3 222
NZ LYS 222
0 LYS 222
CB CYS 223
SG CYS 223
CZ ARG 251
NH1 ARG 251 JB2010.7161
NH2 ARG 251
CB CYS 255
SG CYS 255
are contacted and buried by the antibody or fragment; and, optionally, wherein, upon such binding, the antibody or fragment heavy chain immunogiobuiin residues and/or atoms thereof indicated in the table
Residue
Atom Residue #
0 THR 30
CA ASP 31
CB ASP 31
CG ASP 31
OD1 ASP 31
OD2 ASP 31
C ASP 31
0 ASP 31
CA TYR 32
OH TYR 32
CE2 TYR 32
TYR 32
c TYR 32
N TYR 33
CB 33
CG TYR 33
CD1 TYR 33
TYR 33
cz TYR 33
OH TYR 33
CE2 TYR 33
CD2 TYR 33
0 TYR 33
CB ASN 35
CG ASN 35
OD1 ASN 35
ND2 ASN 35
CG2 VAL 37
CD1 TRP 47
CB ASP 50
CG ASP 50
OD1 ASP 50
OD2 ASP 50
CA iLE 51
C ILE 51
N ASN 52
CB ASN 52
CG ASN 52
OD1 ASN 52
ND2 ASN 52
CD PRO 53
CB ASN 54
CG ASN 54 JB2010.7161
OD1 ASN 54
ND2 ASN 54
C ASN 54
0 ASN 54
CB ASN 55
CG ASN 55
OD1 ASN 55
ND2 ASN 55
OA GLY 57
c GLY 57
0 GLY 57
o ALA 58
CG1 ILE 59
CD1 ILE 59
NZ LYS 74
OG1 THR 97
CG2 THR 97
CA SER 98
C SER 98
0 CCD 98
N GLY 99
CA GLY 99
C GLY 99
0 GLY 99
N ILE 100
CA ILE 100
CG1 ILE 100
CD1 ILE 100
N ILE 101
CB ILE 101
CG1 ILE 101
CD1 iLE 101
0 ILE 101
CB ASP 107
NE1 TRP 109
CH2 TRP 109
CZ2 TRP 109
are contacted and buried by said PCS 9; and, optionaliy, wherein, upon such binding, the antibody or fragment light chain immunoglobulin residues and/or atoms thereof indicated in the table
Residue
Atom Residue #
ND2 ASN 32
CB VAL 34
CG1 VAL 34
CZ TYR 36
OH TYR 36
CE2 TYR 36
CB ALA 46
OH TYR 55
OE1 GLN 89 JB2010.7161
NE2 GLN 89
CB TYR 91
CG TYR 91
CD1 TYR 91
CE1 91
CE2 TYR 91
CD2 TYR 91
0 TYR 91
C LYS 92
O LYS 92
CA THR 93
C THR 93
N TYR 94
CD1 TYR 94
CE1 TYR 94
cz TYR 94
OH 94
CE1 TYR 96
CZ TYR 96
OH TYR 96
CE2 TYR 96
CD2 TYR 96
CZ PHE 98
CE2 PHE 98
are contacted and buried by said PCSK9.
2. The isolated antibody or antigen-binding fragment thereof of claim 1 comprising a polypeptide comprising a light variable immunoglobulin region which comprises the amino acid sequence:
QVQLVQSGAEVK PGASV VSC VSGYTFTDYYMNWVRQAPGQGLEWIGDINPNNGGAIYHQKFKGRATLTVD STSTAY
MELRSLRSDDTAVYYCTSGiiTEiAEDFWGQGTLVT ss (SEQ ID NO: 2); and a polypeptide comprising a heavy variable immunoglobulin region which comprises the amino acid sequence:
DIQ TQSPSSLSASVGDRVTITC ASQNVGTNVV WYQQKPG APKALIHS SYRYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQY TYPYTFGQGT VEI R (SEQ
ID NO: 7).
3. The isolated antibody or antigen-binding fragment thereof according to any one of claims 1-2 wherein the light chain is fused to a kappa immunoglobulin constant domain and wherein the heavy chain is fused to a gamma-2 immunoglobulin constant domain.
4. A composition comprising the antibody or antigen-binding fragment thereof according to any one of claims 1-3 in association with a further chemotherapeutic agent. JB2010.7161
5. The composition of claim 4 wherein the further chemotherapeutic agent is a cardiovascular agent, an adrenergic blocker, an antihypertensive agent, an angiotensin system inhibitor, an angiotensin-converting enzyme inhibitor, a coronary vasodilator, a diuretic, an adrenergic stimulant or an HMG-CoA reductase inhibitor.
6. The composition of claim 4 wherein the further chemotherapeutic agent is ezetimibe, lovastatin, atorvastatin, pravastatin, rosuvastatin, fluvastatin, rivastatin, simvastatin, an azetidinone, bunoloi hydrochloride, acebutolol, alprenolol hydrochloride, atenolol, carteolol hydrochloride, celiprolol hydrochloride; cetamoloi hydrochloride, labetalol hydrochloride, esmolol hydrochloride, levobetaxolol hydrochloride, levobunolol hydrochloride, nadolol, practoiol, propranolol hydrochloride, sotalol hydrochloride, timolol, timolol maleate, bisoprolol; bisoprolo! fumarate, nebivalol, cicloprolol hydrochloride, dexpropranolol hydrochloride, diacetolol hydrochloride, dilevalol hydrochloride, exaprolol hydrochloride, flestolol sulfate, metalol hydrochloride, metoprolol 2-Propanol, metoprolol tartrate, pamatolol sulfate, penbutolol sulfate, practoiol, tiprenolol hydrochloride, tolamolol fenspiride hydrochloride, proroxan, alfuzosin hydrochloride, labetalol hydrochloride, bretylium tosylate, dihydroergtamine mesylate, carvedilol, labetalol, bretylium tosylate, phentolamine mesylate, solypertine tartrate, zolertine hydrochloride, candesartan cilexetil, telmisartan, candesartan; losartan potassium, benazepril hydrochloride, captopril, fosinopril, moexipril hydrochloride, perindopril erbumine, quinapril, ramipril, enalapril maleate, lisinopril, deiaprii, spirapril, de!apri! hydrochloride, libenzapril, pentopril, perindopril 1 H-lndole-2-carboxylic acid, quinaprilat, spirapri! hydrochloride, spiraprilat, teprotide, zofenopril, amlodipine besylate, clentiazem maleate, isradiptne, nimodipine, felodipine, nilvadipine; diltiazem hydrochloride, verapamil hydrochloride, teludipine hydrochloride, belfosdil, fostedil, ranolazine, butoprozine hydrochloride, tosifen, molsidomine, ranolazine hydrochloride, tosifen, diltiazem hydrochloride, isosorbide dinitrate, sosorbide mononitrate, nitroglycerin, verapamil hydrochloride, chromonar, clonitate, droprenilamine, lidoflazine, preny!amine, propatyl nitrate, mioflazine hydrochloride, mixidine, molsidomine, isosorbide mononitrate, erythrityl tetranitrate, clonitrate, dipyridamole; nicorandil,
pyridinecarboxamide, nifedipine; perhexiline maleate; oxprenolol, pentrinitrol, verapamil, althiazide, benzthiazide, buthiazide, chlorothiazide, spironolactone, triamterene, guanfacine hydrochloride, methyldopa-hydrochlorothiazide combined with Hydrochlorothiazide, methyldopa-chlorothiazide, clonidine hydrochloride, chlorthalidone, clonidlne hydrochloride, clonidine, althiazide, benzthiazide, captopril, carvedilol, chlorothiazide, clonidine hydrochloride, cyclothiazide, delaprif hydrochloride, dilevalol hydrochloride, deiaprii hydrochloride, doxazosin mesylate, fosinopril sodium, moexipril hydrochloride, monatepil maleate, metoprolol succinate, guanfacine hydrochloride, meihyldopa, quinaprilat, quinapril hydrochloride, primidolol, prazosin JB2010.7161 hydrochloride, pelanserin hydrochloride, phenoxybenzamine hydrochloride, candesartan cilexetil, telmisartan, candesartan, amlodipine maieate, terazosin hydrochloride, bevantolol hydrochloride or ramiprii.
7. The composition of claim 6 wherein the further chemotherapeutic agent is ezetimibe optionally in association with simvastatin or atorvastatin.
8. The antibody or antigen-binding fragment thereof of any of claims 1-3, which is a humanized antibody.
9. The antibody or antigen-binding fragment thereof of any of claims 1-3, which is a recombinant antibody.
10. The antibody or antigen-binding fragment thereof of any of claims 1-3, which is an antibody which is a monoclonal antibody, a labeled antibody, a bivalent antibody, a polyclonal antibody, a bispecific antibody, a chimeric antibody, a recombinant antibody, an anti-idiotypic antibody, a humanized antibody or a bispecific antibody.
11. The antibody or antigen-binding fragment thereof of any of claims 1-3, which is an antigen- binding fragment which is a camelized single domain antibody, a diabody, an scfv, an scfv dimer, a dsfv, a (dsfv)2, a dsFv-dsfv', a bispecific ds diabody, an Fv, an Fab, an Fab', an F(ab')2, or a domain antibody.
12. The antibody or antigen-binding fragment thereof of any of claims 1-3 which is linked to an immunoglobulin constant domain.
13. The antibody or antigen-binding fragment thereof of claim 12 wherein the constant domain is a light chain, γ1 heavy chain, γ2 heavy chain, γ3 heavy chain or γ4 heavy chain.
14. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:
DIQMTQSPSSLSASVGORVTITC KASQNVGTNVV WYQQKPGKAPKALIH SASYRYS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQY TYPYT FGQGTKVEIKR (SEQ (D NO: 7);
and,
QVQLVQSGAEVKKPGASVKVSCKVS GYTFTDYYMN WVRQAPGQGLEWIG DINPNNGGAIYNQ F G RATLTVDKSTSTAYMELRSLRSDDTAVYYCTS GIITEIAEDF WGQGTLVTVSS (SEQ ID NO: 2). JB2010.7161
15. The polypeptide of claim 14 which is linked to an immunoglobulin constant domain.
16. An isolated polynucleotide encoding polypeptide comprising an amino acid sequence selected from the group consisting of:
DIQ TQSPSSLSASVGDRVTITC ASQNVGTNVV WYQQKPGKAPKALIH SASYRYS GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC QQY TYPYT FGQGTKVEIKR (SEQ ID NO: 7);
and,
QVQLVQSGAEVKKPGASVKVSC VS GYTFTDYYMN VRQAPGQGLEWIG DINPNNGGAIYNQKFKG RATLTVDKSISTAYMELRSLRSDDTAVYYCTS GIITEIAEDF WGQGTLVTVSS (SEQ ID NO: 2).
17. A composition comprising the polynucleotide of claim 16 and a buffer.
18. An isolated vector comprising the polynucleotide of claim 16.
19. An isolated host cell comprising the polynucleotide of claim 16.
20. The host cell of claim 19 which is a Chinese hamster ovary ceil, a Pichia ceil or a P.pastoris cell.
21. A pharmaceutical composition comprising the antibody or fragment of any of claims 1-3 in association with a pharmaceutically acceptable carrier.
22. A method for reducing:
total cholesterol level;
low density lipoprotein cholesterol level;
apolipoprotein B level;
total cholesterol/high density lipoprotein ratio; or
low density lipoprotein/high density lipoprotein ratio;
in a subject, comprising administering, to said subject, a therapeutically effective amount of an antibody or antigen-binding fragment thereof of any of claims 1-3; optionally in association with a further chemotherapeutic agent.
23. A method for treating or preventing hypercholesterolemia, hyperlipidemia,
hypertriglyceridaemia, sitosterolemia, atherosclerosis, arteriosclerosis, coronary heart disease, vascular inflammation or xanthoma, in an subject, comprising administering, to said subject, a JB2010.7161 therapeutically effective amount of an antibody or antigen-binding fragment thereof of any of claims 1-3; optionally in association with a further chemotherapeutic agent.
24, The method of claim 22 wherein the further chemotherapeutic agent is a cardiovascular agent, an adrenergic blocker, an antihypertensive agent, an angiotensin system inhibitor, an angiotensin-converting enzyme inhibitor, a coronary vasodilator, a diuretic, an adrenergic stimulant or an H G-CoA reductase inhibitor.
25. The method of claim 22 wherein the further chemotherapeutic agent is ezetimibe, lovastatin, atorvastatin, pravastatin, rosuvastatin, fluvastatin, rivastatin, simvastatin, an azetidinone, bunolol hydrochioride, acebutolol, alprenoiol hydrochloride, atenolol, carteoloi hydrochloride, celiprolol hydrochloride; cetamolol hydrochloride, labetalol hydrochloride, esmolol hydrochloride, levobetaxoloi hydrochloride, levobunolol hydrochloride, nadolol, practoloi, propranolol hydrochloride, sotalol hydrochloride, timolol, timolol maleate, bisoprolol; bisoprolol fumarate, nebivalol, cicioprolol hydrochloride, dexpropranolol hydrochloride, diacetoiol hydrochloride, dilevalol hydrochloride, exaprolol hydrochloride, flestolol sulfate, metalol hydrochloride, metoprolol 2-Propanol, metoproloi tartrate, pamatolol sulfate, penbutolo! sulfate, practoloi, tiprenolol hydrochloride, tolamolol fenspiride hydrochloride, proroxan, alfuzosin hydrochloride, labetalol hydrochloride, bretylium tosylate, dihydroergtamine mesylate, carvedilol, labetalol, bretylium tosylate, phentolamine mesylate, solypertine tartrate, zolertine hydrochloride, candesartan cilexetil, telmisartan, candesartan; losartan potassium, benazepril hydrochloride, captopril, fosinopril, moexipril hydrochloride, perindopril erbumine, quinapril, ramipril, enalaprii maleate, lisinopril, delapril, spirapril, delapril hydrochloride, libenzapril, pentopril, perindopril 1 H-lndole-2-carboxylic acid, quinaprilat, spirapril hydrochioride, spiraprilat, teprotide, zofenopril, amlodipine besylate, clentiazem maleate, isradipine, nimodipine, felodipine, nilvadipine; diltiazem hydrochloride, verapamil hydrochloride, teludipine hydrochloride, belfosdil, fostedil, ranolazine, butoprozine hydrochloride, tosifen, molsidomine, ranolazine hydrochloride, tosifen, diltiazem hydrochloride, isosorbide dinitrate, sosorbide mononitrate, nitroglyceri , verapamil hydrochioride, chromonar, clonitate, droprenilamine, lidoflazine, prenylamine, propatyl nitrate, mtoflazine hydrochloride, mixidine, molsidomine, isosorbide mononitrate, erythrity! tetranitrate, clonitrate, dipyridamole; nicorandii,
pyridinecarboxamide, nifedipine; perhexiline maleate; oxprenolol, pentrinitrol, verapamil, althiazide, benzthiazide, buthiazide, chlorothiazide, spironolactone, triamterene, guanfacine hydrochloride, methyldopa-hydrochlorothiazide combined with Hydrochlorothiazide, methyldopa-chlorothiazide, clonidine hydrochloride, chlorthalidone, clonidine hydrochloride, cionidine, althiazide, benzthiazide, captopril, carvedilol, chlorothiazide, clonidine hydrochloride, JB2010.7161 cyclothiazide, delapril hydrochloride, dilevalol hydrochloride, delaprii hydrochloride, doxazosin mesylate, fosinoprii sodium, moexipril hydrochloride, monatepil maleate, metoprolol succinate, guanfacine hydrochioride, methyidopa, quinapri!at, quinapril hydrochloride, primidoloi, prazosin hydrochloride, pelanserin hydrochloride, phenoxybenzamine hydrochloride, candesartan cilexetil, telmisartan, candesartan, amlodipine maleate, terazosin hydrochloride, bevantolol hydrochloride or ramipril.
26. The method of claim 25 wherein the further chemotherapeutic agent is ezetimibe and, optionally, simvastatin or atorvastatin.
27. The method of any of claims 22-26 wherein the antibody or antigen-binding fragment thereof is a humanized antibody.
28. The method of any of claims 22-26 wherein the antibody or antigen-binding fragment thereof is administered to the subject parenterally.
29. A method for producing an antibody or antigen-binding fragment therof of any of claims 1-3 comprising introducing one or more polynucleotides into one or more host cells; which polynucleotides encodes and direct expression of said heavy and/or light chain
immunoglobulins; and growing said host cells under conditions whereby said heavy and light chain immunoglobulins are expressed.
30. The method of claim 29 wherein said polynucleotide encoding and directing expression of said light chain and said polynucleotide encoding and directing expression of said heavy chain are in separate host cells.
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