WO2005118629A1 - BINDING MOIETIES BASED ON SHARK IgNAR DOMAINS - Google Patents

BINDING MOIETIES BASED ON SHARK IgNAR DOMAINS Download PDF

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WO2005118629A1
WO2005118629A1 PCT/AU2005/000789 AU2005000789W WO2005118629A1 WO 2005118629 A1 WO2005118629 A1 WO 2005118629A1 AU 2005000789 W AU2005000789 W AU 2005000789W WO 2005118629 A1 WO2005118629 A1 WO 2005118629A1
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Prior art keywords
atom
domain
loop
remark
ignar
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PCT/AU2005/000789
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French (fr)
Inventor
Stewart Nuttal
Victor Streltsov
Katherine Merne Griffiths
Jennifer Ann Carmichael
Peter Hudson
Robert Alexander Irving
Joseph Noozhumutry Varghese
Miles Mackay Barraclough
David Peter Simmons
Kylie Anne Henderson
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Diatech Pty Ltd
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Priority to AU2005250055A priority Critical patent/AU2005250055B2/en
Priority to CA2567655A priority patent/CA2567655C/en
Priority to US11/628,475 priority patent/US7977071B2/en
Priority to JP2007513617A priority patent/JP2008511286A/en
Priority to EP05744734A priority patent/EP1751181B1/en
Priority to DK05744734.4T priority patent/DK1751181T3/en
Publication of WO2005118629A1 publication Critical patent/WO2005118629A1/en
Priority to AU2008229687A priority patent/AU2008229687B2/en
Priority to AU2009201692A priority patent/AU2009201692B2/en
Priority to US13/157,205 priority patent/US20120003214A1/en
Priority to US15/044,731 priority patent/US20160237169A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/461—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from fish
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
    • C07K16/464—Igs containing CDR-residues from one specie grafted between FR-residues from another
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2299/00—Coordinates from 3D structures of peptides, e.g. proteins or enzymes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • 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
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]

Definitions

  • the present invention relates to immunoglobulin new antigen receptors (IgNARs) from fish and uses thereof.
  • IgNARs immunoglobulin new antigen receptors
  • the present invention relates to modified IgNAR variable domains and to domains from members of the immunoglobulin superfamily that have been modified to include structural features derived from IgNAR variable domains.
  • immunoglobulin superfamily includes immunoglobulins and numerous other cell surface and soluble molecules that mediate recognition, adhesion or binding functions in the immune system. They share partial amino acid sequence homology and tertiary structural features that were originally identified in immunoglobulin (Ig) heavy and light chains. Molecules of the IgSF are identified by a characteristic IgSF fold structure, a ⁇ - sandwich structure formed by two ⁇ -sheets, packed face-to-face and linked by a disulphide bond between the B and F strands (Bork 1994; Chothia 1998).
  • IgSF frameworks are further classified into 3-4 major categories, the Variable (V)-, Constant (C)-, I- and I2-sets, based on ⁇ -strand number, configuration and hydrogen bond patterns (Bork 1994; Cassasnovas 1998).
  • Conventional immunoglobulins have two heavy polypeptide chains linked by disulphide bonds at a hinge portion, and two light polypeptide chains, each of which is linked to a respective heavy chain by disulphide bonding. Each heavy chain comprises a variable (VH) domain at the N-terminal end and a number of constant (CH) domains.
  • Each light chain has a variable (VL) domain at the N-terminal end and a constant (CL) domain at the C-terminal end, the VL and CL domains aligning with the VH domain and the first CH domain, respectively.
  • T-cell receptors TCRs are heterodimers having ⁇ and ⁇ chains of equal size, each chain consisting of an N-terminal variable domain (V ⁇ or V ⁇ ) and a constant domain.
  • V ⁇ or V ⁇ N-terminal variable domain
  • V ⁇ N-terminal variable domain
  • constant domains typically, the variable domains on different polypeptide chains interact across hydrophobic interfaces to form binding sites designed to receive a particular target molecule.
  • each pair of VH/VL domains form an antigen binding site, the CH and CL domains not being directly involved in binding the antibody to the antigen.
  • the V ⁇ and V ⁇ domains form the binding site for target molecules, namely peptides presented by a histocompatibility antigen.
  • the amino acid sequences of variable domains vary particularly from one molecule to another. This variation in sequence enables the molecules to recognise an extremely wide variety of target molecules.
  • Variable domains are often viewed as comprising four framework regions, whose sequences are relatively conserved, connected by three hypervariable or complementarity determining loop regions (CDRs) (Kabat 1983 & 1987; Bork 1994).
  • the CDRs are held in close proximity by the framework regions and, with the CDRs from the other variable domain, contribute to the formation of the binding site.
  • chimeric antibodies have been constructed in which an animal antigen- binding variable domain is coupled to a human constant domain.
  • the isotype of the human constant domain may be selected to tailor the chimeric antibody for participation in antibody-dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity.
  • ADCC antibody-dependent cellular cytotoxicity
  • chimeric antibodies typically may contain about one third rodent (or other non-human species) sequence and consequently are often still capable of eliciting a significant antigenic response in humans.
  • IgSF molecules are dependent on their three dimensional structure, and that amino acid substitutions can change the three-dimensional structure of, for example, an antibody (Snow and Amzel 1986). Based upon molecular modelling, it has been shown that the antigen binding affinity of a humanized antibody can be increased by mutagenesis (Riechmann 1988; Queen 1989).
  • the Immunoglobulin New Antigen Receptors (IgNARs) are an unconventional subset of antibodies recently identified in fish. In domain structure, IgNAR proteins are reportedly similar to other immune effector molecules, being disulphide-bonded homodimers of two polypeptide chains having five constant domains (CN AR S) and one variable domain (V N AR) (Greenberg 1995).
  • variable domains are independent in solution and do not appear to associate across a hydrophobic interface (as seen for conventional VH/VL type antibodies) (Roux 1998).
  • IgNARs have been identified in all shark species studied to date. In particular,
  • IgNARs have been identified in the serum of nurse sharks Ginglymostoma cirratum (Greenberg 1995) and wobbegong sharks Orectolobus maculatus (Nuttall 2001). The cell-surface expression of IgNARs has also been reported (Rumfelt 2002). Research has implicated IgNARs as true molecules of the immune armoury, and as the most probable agents of the shark antigen-driven affinity-maturation antibody response (Diaz 1999; Nuttall 2002; Dooley 2003). IgNARs identified to date have been placed into three categories based on their time of appearance during the shark development and on their postulated disulphide bonding pattern within the variable domains (Diaz 2002; Nuttall 2003).
  • Type 1 VNAR topology is characterised by an extra framework disulphide linkage and, usually, cysteines in the extended loop region analogous to a conventional CDR3 loop, which it has been suggested may form intra-loop disulphide bonds.
  • Type 2 V NAR topology is characterised by cysteines in the loop regions analogous to conventional CDRl and CDR3 loops in approximately two thirds of cases, which it has been postulated may form inter-loop disulphide bonds.
  • Type 3 VNA R topology is characterised by a relatively constant sized loop region analogous to a conventional CDR3 loop of limited diversity and a characteristic conserved tryptophan residue within the loop region analogous to a CDRl loop.
  • IgNARs identified to date are reported as having minimally variable loop regions analogous to conventional CDRl and CDR2 loops, with diversity being concentrated in an elongated loop region analogous to a conventional CDR3 loop (Greenberg 1995; Nuttall 2001; Diaz 2002).
  • the elongated loop region can reportedly vary in length from 5 to 23 residues in length, though the modal classes are more in the order of 15 to 17 residues (Nuttall 2003). This is significantly larger than for conventional murine and human antibodies, but approximate to the extended CDR3 loops found in camelid single VH antibodies (Wu 1993; Muyldermans 1994).
  • Type 2 VNA R S Large bacteriophage libraries have been generated based upon the Type 2 VNAR repertoire from wobbegong sharks and used to isolate a number of Type 2 VNA R S proteins encapsulating significant variability within the framework and the loop region analogous to a conventional CDRl loop. However, the most significant diversity was within the extended loop region analogous to a conventional CDR3 loop, the extended loop region varying in both length and amino acid composition (Nuttall 2001; Nuttall 2003).
  • Various computer-modelled structures for Type 2 V A S have been reported in the literature (Roux 1998; Nuttall 2001; Diaz 2002; Nuttall 2004). Although such computer modelling can offer key insights into structure, the definitive structure remains to be determined from crystallographic analysis. In the case of VNA R S, the elucidation of the crystal structure is particularly important.
  • the present invention provides a crystal of a variable domain of a Type 2 IgNAR that effectively diffracts X-rays for the determination of the atomic coordinates of the variable domain of the IgNAR to a resolution of better than 4.0A, wherein the variable domain of the Type 2 IgNAR consists of 105 to 125 amino acid residues and comprises an amino acid sequence according to Table 1 and/or Figure 1.
  • the present invention provides a crystal of a variable domain of a Type 2 IgNAR comprising a structure defined by all or a portion of the coordinates of Appendix 1(a), (b), (c) or (d) + a root mean square deviation from the C ⁇ atoms of less than 0.5 A.
  • the present invention provides a method of homology modelling comprising the steps of: (a) aligning a representation of an amino acid sequence of an IgSF domain with the amino acid sequence of 12Y-1, 12Y-2, 12A-9 or 1A-7 as shown in Figure 1 to match homologous regions of the amino acid sequences; (b) modelling the structure of the matched homologous regions of said IgSF domain on the corresponding regions of the 12Y-1, 12Y-2, 12A-9 or 1A-7 structure as defined by Appendix 1(a), (b), (c) or (d); and (c) determining a conformation (e.g.
  • the present invention provides a method for determining the structure of a protein, which method comprises; providing the co-ordinates of Appendix 1(a), (b), (c) or (d), and either (a) positioning the co-ordinates in the crystal unit cell of said protein so as to provide a structure for said protein or (b) assigning NMR spectra Peaks of said protein by manipulating the coordinates of Appendix 1(a), (b), (c) or (d).
  • the present invention provides systems, particularly a computer system, the systems containing at least one of the following: (a) atomic coordinate data according to Appendix I, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7 or at least selected coordinates thereof; (b) structure factor data (where a structure factor comprises the amplitude and phase of the diffracted wave) for 12Y-1, 12Y-2, 12A-9 or 1A-7, said structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of an IgSF domain generated by homology modelling of the IgSF domain based on the data of Appendix I; (d) atomic coordinate data of the IgSF domain generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Appendix I; and (e) structure factor data derivable from the atomic coordinate data of (c) or (d).
  • the present invention provides a computer-readable storage medium, comprising a data storage material encoded with computer readable data, wherein the data are defined by all or a portion (e.g. selected coordinates as defined herein) of the structure coordinates of 12Y-1, 12Y-2, 12A-9 or 1A-7, or a variant of 12Y-1, 12Y-2, 12A-9 or 1A-7, wherein said variant comprises backbone atoms that have a root mean square deviation from the C ⁇ or backbone atoms (nitrogen-carbon ⁇ - carbon) of Appendix I of less than 2 A, such as not more than 1.5 A, preferably less than 1.5 A, more preferably less than 1.0 A, even more preferably less than 0.74 A, even more preferably less than 0.72 A and most preferably less than 0.5 A.
  • Appendix I of less than 2 A, such as not more than 1.5 A, preferably less than 1.5 A, more preferably less than 1.0 A, even more preferably less than 0.74 A, even more preferably less than 0.72 A and most
  • the present invention provides a computer-readable data storage medium comprising a data storage material encoded with a first set of computer-readable data comprising a Fourier transform of at least a portion (e.g. selected coordinates as defined herein) of the structural coordinates for 12Y-1, 12Y-2, 12A-9 or 1A-7 according to Appendix I; which, when combined with a second set of machine readable data comprising an X-ray diffraction pattern of a molecule or molecular complex of unknown structure, using a machine programmed with the instructions for using said first set of data and said second set of data, can determine at least a portion of the structure coordinates corresponding to the second set of machine readable data.
  • a computer-readable data storage medium comprising a data storage material encoded with a first set of computer-readable data comprising a Fourier transform of at least a portion (e.g. selected coordinates as defined herein) of the structural coordinates for 12Y-1, 12Y-2, 12A-9 or 1A-7 according to Appendix I
  • the present invention provides computer readable media with at least one of: (a) atomic coordinate data according to Appendix I recorded thereon, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, or at least selected coordinates thereof; (b) structure factor data for 12Y-1, 12Y-2, 12A-9 or 1A-7 recorded thereon, the structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of a target IgSF domain generated by homology modelling of the IgSF domain based on the data of Appendix 1; (d) atomic coordinate data of a modified IgSF domain generated by interpreting X- ray crystallographic data or NMR data by reference to the data of Appendix I; and (e) structure factor data derivable from the atomic coordinate data of (c) or (d).
  • the present invention provides a method of providing data for generating structures and/or performing rational drug design for IgSF domains, the method comprising: (i) establishing communication with a remote device containing computer-readable data comprising at least one of: (a) atomic coordinate data according to Appendix I, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, at least one sub-domain of the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, or the coordinates of a plurality of atoms of 12Y-1, 12Y-2, 12A-9 or 1A-7; (b) structure factor data for 12Y-1, 12Y-2, 12A-9 or 1A-7, said structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of a modified IgSF domain generated by homology modelling of the domain based on the data of Appendix I; (d) atomic coordinate data of a protein generated by interpreting X-
  • the present invention provides a method of altering a property of an IgNAR variable domain comprising eight ⁇ -strand regions, designated A, A', B, C, D, E, F and G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2, said method comprising modifying the IgNAR variable domain within at least one of the ⁇ -strand regions or loop regions.
  • the present invention provides a binding moiety comprising a modified IgNAR variable domain produced by a method according to any one of claims 1 to 5.
  • the present invention provides a binding moiety comprising an IgNAR variable domain comprising eight ⁇ -strand regions, designated A, A', B, C, D, E, F and G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2, wherein the IgNAR variable domain has been modified within at least one of the ⁇ -strand regions or loop regions.
  • the present invention provides a method of modifying an I- set domain, said method comprising inserting and/or substituting one or more structural features from an IgNAR variable domain into the I-set domain.
  • the present invention provides a binding moiety comprising a
  • I-set domain wherein the I-set domain has been modified by insertion and/or substitution of one or more structural features from an IgNAR variable domain into the
  • the present invention provides a method of modifying a V- set domain, said method comprising inserting and/or substituting one or more structural features from an IgNAR variable domain into the V-set domain.
  • the present invention provides a binding moiety comprising a V-set domain, wherein the V-set domain has been modified by insertion and/or substitution of one or more structural features from an IgNAR variable domain into the
  • the present invention provides a binding moiety comprising a multimer comprising:
  • the present invention provides a binding moiety according to the invention linked to a diagnostic reagent.
  • the present invention provides a binding moiety according to the invention immobilised on a solid support or coupled to a biosensor surface.
  • the present invention provides a polynucleotide encoding a binding moiety according to the invention.
  • the present invention provides a vector comprising a polynucleotide according to the present invention.
  • the present invention contemplates a host cell comprising a vector according to the invention.
  • the present invention provides a method of producing a binding moiety according to the invention which comprises culturing a host cell of the present invention under conditions enabling expression of the binding moiety according to the invention and optionally recovering the a binding moiety.
  • the present invention provides a pharmaceutical composition comprising a binding moiety according to the invention and a pharmaceutically acceptable carrier or diluent.
  • the present invention provides a method of treating a pathological condition in a subject, which method comprises administering to the subject a binding moiety according to the invention.
  • the present invention provides a method of selecting a binding moiety according to the invention with an affinity for a target molecule which comprises screening a library of polynucleotides of the present invention for expression of a binding moiety according to the invention with an affinity for the target molecule.
  • the present invention provides a polynucleotide library comprising a plurality of polynucleotides encoding binding moieties according to the invention, which polynucleotides comprise one or more modifications in the IgNAR variable domain, I-set domain or V-set domain.
  • Figure 1 Amino acid sequence alignment of VNARS 12Y-1, 12Y-2, 12A-9 and 1A-7 with 12 naturally occurring Type 2 IgNAR variable domain sequences.
  • Figure 2. 2D topology diagram of the 12Y-1, 12Y-2, 12A-9 and 1A-7 folds showing the loop regions and ⁇ -strand regions.
  • the labelled 8 strands form a sandwich of 2 sheets: front and back sheets are shown with thick and thin arrows, respectively.
  • the switch of N-terminal strand A to A', adjacent to the bulge in the C-terminal strand G, is shown as a kink between the A and A' strands.
  • FIG. 3 Detailed 2D topology diagram of the 12Y-1, 12Y-2, 12A-9 and 1A-7 folds showing the loop regions and ⁇ -strand regions.
  • the labelled 10 strands form a sandwich of 2 sheets: front and back sheets are shown with thick and thin arrows, respectively.
  • the disulfide bond is indicated as a horizontal line connecting the B and
  • VMD The CDRl analogous region (loop region 4) and CDR3 analogous region (loop region 8) are labelled.
  • Figure 5a Stereo images of superimposed 1A-7 A chain, 1A-7 C chain and 12Y-2 A chain. Figures were produced using VMD.
  • the CDRl analogous region (loop region 4) is labelled.
  • FIG. 1 CDR analogous regions in VNA R 12Y-2.
  • the 12Y-2 chain A structure in ribbon representation is overlayed with transparent molecular surface.
  • the positions of the CDRl, "CDR2" and CDR3 analogous regions are indicated.
  • FIG. 9 CDR analogous regions in VNAR 12Y-2. Overlay of the CDRl analogous region (loop region 4) of the 12Y-2 chain A and the CDRl of human VL (1HZH)
  • FIG. 10 CDR analogous regions in VNAR 12Y-2. Positioning of the CDRl analogous region (loop region 4) and the CDR3 analogous region (loop region 8) in the 12Y-2 chain A in ribbon representation. Residues Phe29 and Lys32 (possible half- cystine positions) are oriented toward the CDR3 analogous region (loop region 8), ideally placed to make inter-loop contacts.
  • FIG. 1 CDR analogous regions in VN A R 12Y-2.
  • Figure 12. CDR analogous regions in V NAR 12Y-2. Overlay of the backbone "CDR2" region (loop region 5) of the 12Y-2 chain A in liquorice representation and CDR2 of human VH (lhzh) in ribbon semitransparent representation. This figure was produced using VMD.
  • FIG. 13 Structures of the VN AR 12Y-2 2-fold symmetry dimer.
  • (a) View from the top of the CDR3 analogous region (loop region 8) and (b) side view. Each chain is shown in ribbon representation. The N and C termini, and the CDRl analogous region (loop region 4) and CDR3 analogous region (loop region 8) of each chain are labelled.
  • Figure 14. MOLSCRIPT/RASTERED3D diagram of the 12A-9 chain. The chain is shown in ribbon representation. Cysteine residues are shown as ball-and-sticks.
  • FIG 16. ELISA analysis of 12 14M-15 variants (12Y-2 with Pro90Leu) for binding to AMA1 and a control negative antigen. Comparative expression levels are also shown.
  • the CDRl analogous region (loop region 4) has been shuffled in the variants.
  • Figure 17. Amino acid sequence alignment of 14M-15 variant IgNAR clones in which the CDRl analogous region (loop region 4) has been shuffled. Five clones with affinity for the AMA-1 antigen (24A-82, 24A-72, 24A-58, 24A-75, 24A-46) and five with no affinity (24A-24, 24A-28, 24A-33, 24A-10, 24A-19) are shown.
  • Sequence differences map predominantly to the CDRl analogous region (loop region 4), with some contribution from framework residues.
  • Figure 18. Titres of total eluted phage from 12Y-2 loop library panned against different malarial strains: W2MEF (- ⁇ -), W2MEF (- ⁇ -), W2/HB/W2/3D7 (- A-), HB3 (-X-), HB3 (- * -), HB/W2/HB/3D7 (-•-). The initial titre of phage added for reading 1 pan is taken as the zero reading.
  • Figure 19 Schematic diagram of loop region 8 (analogous to CDR3) variability for IgNAR libraries. Loop region 8 varies in length and in coding sequence and randomization strategy.
  • Generations 1 to 3 are based on the existing shark libraries.
  • Generation 4 libraries were designed with reference to the structures of 12Y-1 and 12Y-2.
  • Oligonucleotides A0298, A0296, A0297, A0295, 8477, 8476, 7210, 7211, 6980 and 6981 correspond to SEQ ID Nos: 61-70, respectively.
  • FIG. 20 Schematic diagram of loop region 8 (analogous to CDR3) variability for IgNAR libraries based on the 12Y-2 structure.
  • the tip of the 12Y02 loop region 8 is modified by 6 different strategies, varying in amino acid randomisation, loop length and amino acid variation pattern.
  • Oligonucleotides KH0001RC, KH0002RC, KH0003RC, KH0004RC, KH0005RC and KH0006RC correspond to SEQ ID Nos: 71- 76, respectively.
  • FIG. 21 (a) Modelled liquorice representation of CDR3 analogous loop (loop region 8) of the 12Y-2 structure showing the position of the Leu89 and Ser97 residues, (b) Portion of the 12Y-2 nucleotide/amino acid sequences showing the CDR3 analogous region (light shade), (c) Schematic diagram of loop region 8 (analogous to CDR3) libraries based on the 12Y-2 structure, where the tip of the 12Y-2 loop region 8 has been modified by 6 different strategies, varying in amino acid randomisation, loop length, and amino acid variation pattern.
  • Figure 22 (a) ELISA analysis of 40 12Y-2 variants binding to AMA-1 and a control negative antigen, (b) Alignment of 12Y-2 variants 22A-2 (Thr39Ser; Pro90Leu) and 14M-15 (Pro90Leu). (c) Three-dimensional structure of 12Y-2 illustrating affinity- enhancing CDRl and CDR3 mutation and the framework affinity-enhancing mutation Thr39Ser. (d) FPLC traces of 12Y-2 variants 14M-15 and 22A-2. Both show identical expression and folding characteristics, (e) Biosensor traces of purified 12Y-2 variant proteins 14M-15 and 22A-2. 22A-2 shows 2-fold enhanced affinity over 14M-15 (20- fold better affinity than 12Y-2).
  • Figure 23 (a) Schematic figure of NCAM (CD56) ectodomain showing Ig superfamily and fibronectin domains, (b) Amino acid sequences of NCAM domain 1 (21H-5) and domain 1+2 (21G-1) recombinant proteins. Dual C-terminal FLAG affinity tags are not shown, (c) FPLC traces of NCAM domain 1 (21H-5) and domain 1 +2 (21 G- 1 ) recombinant proteins .
  • Figure 24 (a) Schematic figure of Myosin Light Chain Kinase showing Ig, catalytic, and Telokin domains, (b) Protein sequences of human wild type Telokin (21J-4). Dual C-terminal FLAG affinity tags are not shown, (c) FPLC trace of Telokin (21J-4) recombinant protein.
  • Figure 25 (a) Alignment of NCAM domain 1 (21H-5) and loop-graft variant 23B-2. Dual C-terminal FLAG affinity tags are not shown, (b) FPLC traces of NCAM domain 1 (21H-5) and loop-graft variant 23B-2 recombinant proteins.
  • Protein 23B-2 shows a "cleaner" profile
  • NCAM domain 1+2 (21G-1) is shown for comparison
  • the parental anti-5G-8 IgNAR (1 A-7) similarly binds, but not the wild type NCAM domain 1 or domain 1+2.
  • Figure 26 (a) Alignment of Telokin (21J-4) and loop-graft variants 23C-7 and 23F-4. Dual C-terminal FLAG affinity tags are not shown, (b) FPLC traces of recombinant proteins 21J-4, 23C-7, and 23F-4. (c) SDS-PAGE profiles of recombinant proteins 21J-4, 23C-7, and 23F-4. (d) ELISA analysis showing binding of Telokin loop-graft variants 23C-7 and 23F-4 to the target antigen (monoclonal antibody 5G-8) but not to negative control antigens. The parental anti-5G-8 IgNAR (1A-7) similarly binds, but not the wild type Telokin (21 J-4).
  • the disulphide-bonded dimer does not bind the target antigen, demonstrating both the importance of the CDR3 and that the novel dimer form presents a different interface to antigen than the monomeric protein, (e) SDS-PAGE and western blot analysis 12Y-2 variants 14M-15 and 21B-5.
  • the disulphide-bonded dimer runs as a dimeric form in the absence of reducing agent ( ⁇ -mercaptoethanol). Incorporation of Leu99Cys drives the dominant protein form to dimer.
  • Figure 28 Schematic diagram of CDRl and CDR3 variability for NCAM domain 1 libraries. CDRl and CDR3 both vary in length and in coding sequence and randomization strategy. The NCAM wild type sequence is given for comparison.
  • FIG. 29 Schematic diagram of CDRl and CDR3 variability for Telokin libraries. CDRl and CDR3 both vary in length and in coding sequence and randomization strategy. The Telokin wild type sequence is given for comparison. Framework residues N- and C-terminal to the CDR loop regions are also shown.
  • Figure 30 Immunopanning of NCAM domain 1 library by bacteriophage display against amyloid a ⁇ (1-42) peptide (panels A & B) and the Carcino Embryonic Antigen (CEA) (panels C & D). Binding to antigens (panels A & C) and comparative expression levels of individual clones (panels B & D) are shown.
  • Figure 31 Titres of eluted phage/ml from NCAM library panned against monoclonal antibody 5G8 (- ⁇ -), AMA1 (- ⁇ -), Hepatitis B virus E antigen (- A-), ab 1- 42 peptide (-x-), Carcino Embryonic Antigen (*); and, the Telokin library panned against monoclonal antibody 5G8 (•).
  • Figure 32 Fluorescent intensity graph following regeneration of V NAR 14M-15 (12Y-
  • Figure 33 The full wobbegong shark (Orectolobus maculatus) IgNAR coding sequence.
  • Figure 34 (a) Cartoon of 17T-6 protein, with 12Y-2 variable and constant domain.1. (b) Comparative FPLC traces of IgNARs 12Y-2 and 17T-6. (c) SDS PAGE of IgNARs 12Y-2 and 17T-6. (d) Biosensor traces of equal masses of IgNARs 12Y-2 and 17T-6 binding to immobilized AMAl .
  • Noloopref_cis Two solutions were selected from the top ten of each with buried Trp 31 residues and illustrating the variability of the Phe 96 in the modelling solutions.
  • Figure 36 Model of IgNAR Type 3 CDRl and CDR3 analogous regions (and some framework residues) based on the 12A-9 structure. This isotype has limited diversity. Hypervariable residues (by sequence alignment) are shown in dark grey.
  • hydrophobic residues or “nonpolar residues” as used herein is meant valine, leucine, isoleucine, methionine, phenylalanine, tyrosine, and tryptophan.
  • polar residues herein is meant serine, threonine, histidine, aspartic acid, asparagine, glutamic acid, glutamine, arginine, and lysine.
  • V NAR S targeting the apical membrane antigen- 1 (AMA1) of Plasmodium falciparum malarial parasites (Nuttall 2004).
  • AMA1 apical membrane antigen- 1 of Plasmodium falciparum malarial parasites
  • 12Y-1 SEQ ID NOs: 1 & 2
  • 12Y-2 SEQ ID NOs: 3 & 4
  • 12A-9 and 1A-7 IgNAR variable domains
  • VNAR 12A-9 (SEQ ID NOs: 9 & 10) was isolated from a library containing a broad mixture of naturally occurring Type 2 VN AR framework scaffolds derived from the wobbegong shark by biopanning against the Gingipain K protease from Porphyromonas gingivalis (Nuttall et al. 2002).
  • This IgNAR is completely natural, including the CDR3 analogous loop region (loop region 8).
  • a disulphide bridge links and stabilises the CDRl and CDR3 analogous loop regions, in this case connecting residues Cys29 and Cys89.
  • VN AR 1A-7 (SEQ ID NOs: 5 & 6) is specific for the anti-AMA-1 mouse IgG
  • CDR3 loops fit into the synthetic category, their lengths (16, 18 and 16 residues, respectively) and amino acid composition are typical of naturally occurring IgNAR antibodies.
  • 12A-9 is a naturally occurring shark IgNAR and has a loop region of length 13 residues analogous to a conventional CDR3 loop.
  • Figure 1 presents the sequence alignments of 12Y-1, 12Y-2, 12A-9, 1A-7 and twelve naturally occurring Type 2 V NAR S: 7E-22 (SEQ ID NO: 17), 7E-23 (SEQ ID NO: 18), 7E-51 (SEQ ID NO: 19), 7E-54 (SEQ ID NO: 20), 7E-56 (SEQ ID NO: 21), 7E-58 (SEQ ID NO: 22), 7E-68 (SEQ ID NO: 23), 7E-77 (SEQ ID NO: 24), 7E-80 (SEQ ID NO: 25), 7E-87 (SEQ ID NO: 26), 7E-91 (SEQ ID NO: 27), 7E-93 (SEQ ID NO: 28).
  • 12A-9 and 1A-7 VNARS were expressed in Escherichia coli and placed into crystallization trials. Successful conditions were scaled up and diffraction quality crystals obtained for both 12A-9 (space group P2 1 2 1 2) and 1 A-7 (space group I2 ⁇ 2 1 2 ⁇ ). Data sets generated for 12Y-1 and 12Y-2 crystal forms resisted solution by standard molecular replacement techniques, using a broad range of immunoglobulin superfamily proteins as template. We believed this was indicative of the unique nature of these proteins, thus the 12Y-1 structure was solved ah initio by phasing with two isomo ⁇ hous heavy atom derivatives (Lutetium (III) Acetate Hydrate: LAH, and Potassium Hexachloro Rhenium: PHR).
  • the present invention provides a crystal of a variable domain of a Type 2 IgNAR that effectively diffracts X-rays for the determination of the atomic coordinates of the variable domain of the IgNAR to a resolution of better than 4. ⁇ A, wherein the variable domain of the Type 2 IgNAR consists of 105 to 125 amino acid residues and comprises an amino acid sequence according to Table 1 and/or Figure 1.
  • the variable domain of the Type 2 IgNAR consists of 105 to 125 amino acid residues and comprises an amino acid sequence according to Table 1 and/or Figure 1.
  • reference herein to comprising an amino acid sequence according to Table 1 includes amino acid sequences having a high degree of sequence homology with the consensus sequence given in Table 1.
  • amino acid sequences will have at least 80%, more preferably at least 85% and yet more preferably at least 90% sequence identity with the consensus sequence in Table 1.
  • amino acid sequences will have at least 90%, more preferably at least 95% sequence identity with those residues in the consensus sequence in Table 1 that are totally conserved.
  • reference herein to comprising an amino acid sequence according to Figure 1 includes amino acid sequences having at least at least 80%, more preferably at least 85% and yet more preferably at least 90% sequence identity with a sequence shown in Figure 1.
  • sequence identity figures given above in respect of Table 1 and Figure 1 exclude the variable regions in Table 1 and corresponding variable regions in Figure 1.
  • the crystals effectively diffract X-rays to a resolution of better than 3. ⁇ A, more preferably better than 2.5 A.
  • the present invention provides a crystal of a variable domain of a Type 2 IgNAR comprising a structure defined by all or a portion of the coordinates of Appendix 1(a), (b), (c) or (d) + a root mean square deviation from the C ⁇ atoms of less than 0.5 A.
  • the IgNAR domain structures set out in Appendices 1(a), (b), (c) and (d) are monomer structures. This is the first time that a monomer has been observed crystallographically for an IgNAR variable domain.
  • the third column denotes the atom type, the fourth column the residue type, the fifth column the chain identification, the sixth column the residue number (the atom numbering as described in Hong (2000)), the seventh, eighth and ninth columns the X, Y, Z coordinates, respectively, of the atom in question, the tenth column the occupancy of the atom, the eleventh column the temperature factor of the atom, and the last the atom type.
  • Each of the Appendices is presented in an internally consistent format.
  • the coordinates of the atoms of each amino acid residue are listed such that the backbone nitrogen atom is first, followed by the C- ⁇ backbone carbon atom, designated CA, followed by the carbon and oxygen of the protein backbone and finally side chain residues (designated according to one standard convention).
  • Alternative file formats e.g. such as a format consistent with that of the EBI Macromolecular Structure Database (Hinxton, UK) which may include a different ordering of these atoms, or a different designation of the side-chain residues, may be used or preferred by others of skill in the art.
  • the use of a different file format to present or manipulate the coordinates of the Appendices is within the scope of the present invention.
  • IgNAR variable domains that are important for antigen binding or solubility/stability of these domains. These features can be introduced into domains of other members of the IgSF (for example, I-set or V-set domains) in order to alter binding properties or to improve solubility and/or stability.
  • the information presented in Appendix I can be used, for example, to compare structures of IgSF domains that have been modified so as to more closely resemble the structure of IgNAR variable domains. Protein structure similarity is routinely expressed and measured by the root mean square deviation (r.m.s.d.), which measures the difference in positioning in space between two sets of atoms.
  • root mean square deviation we mean the square root of the arithmetic mean of the squares of the deviations from the mean.
  • the r.m.s.d. measures distance between equivalent atoms after their optimal superposition.
  • the r.m.s.d. can be calculated over all atoms, over residue backbone atoms (i.e. the nitrogen-carbon-carbon backbone atoms of the protein amino acid residues), main chain atoms only (i.e. the nitrogen-carbon-oxygen-carbon backbone atoms of the protein amino acid residues), side chain atoms only or more usually over C- ⁇ atoms only.
  • the r.m.s.d. can be calculated over any of these, using any of the methods outlined below.
  • the atomic coordinates can then be superimposed according to this alignment and an r.m.s.d.. value calculated.
  • the program Sequoia (Bruns 1999) performs the alignment of homologous protein sequences, and the superposition of homologous protein atomic coordinates. Once aligned, the r.m.s.d.. can be calculated using programs detailed above. For sequence identical, or highly identical, the structural alignment of proteins can be done manually or automatically as outlined above. Another approach would be to generate a superposition of protein atomic coordinates without considering the sequence. It is more normal when comparing significantly different sets of coordinates to calculate the r.m.s.d. value over C- ⁇ atoms only.
  • the term portion is intended to define a sub-set of the coordinates, which may or may not represent contiguous amino acid residues in the 12Y-1, 12Y-2, 12A-9 or 1A-7 structure.
  • the invention also provides a means for homology modelling of other IgSF domains.
  • homology modelling it is meant the prediction of related IgSF domain structures based either on X-ray crystallographic data or computer-assisted de novo prediction of structure, based upon manipulation of the coordinate data of Appendix I.
  • homologous regions describes amino acid residues in two sequences that are identical or have similar (e.g. aliphatic, aromatic, polar, negatively charged, or positively charged) side-chain chemical groups.
  • the method involves comparing the amino acid sequences of the IgNAR domain of Appendix 1(a), (b), (c) or (d) with a modified IgSF domain by aligning the amino acid sequences (Dunbrack (1997)). Amino acids in the sequences are then compared and groups of amino acids that are homologous (conveniently referred to as "corresponding regions") are grouped together. This method detects conserved regions of the polypeptides and accounts for amino acid insertions or deletions. Homology between amino acid sequences can be determined using commercially available algorithms.
  • BLAST, gapped BLAST, BLASTN, PSI-BLAST and BLAST 2 sequences are widely used in the art for this purpose, and can align homologous regions of two amino acid sequences. These may be used with default parameters to determine the degree of homology between the amino acid sequence of the 12Y-1, 12Y-2, 12A-9 or 1A-7 protein and other IgSF domains, which are to be modelled. Homology modelling as such is a technique that is well known to those skilled in the art (see e.g. Greer 1985 and Blundell 1988).
  • the invention provides a method of homology modelling comprising the steps of: (a) aligning a representation of an amino acid sequence of an IgSF domain with the amino acid sequence of 12Y-1, 12Y-2, 12A-9 or 1A-9 as shown in Figure 1 to match homologous regions of the amino acid sequences; (b) modelling the structure of the matched homologous regions of said IgSF domain on the corresponding regions of the 12Y-1, 12Y-2, 12A-9 or 1A-7 structure as defined by Appendix 1(a), (b), (c) or (d); and (c) determining a conformation (e.g.
  • steps (a) to (c) are performed by computer modelling.
  • the aspects of the invention described herein which utilise the 12Y-1, 12Y-2, 12A-9 or 1A-7 structure in silico may be equally applied to models of modified IgSF domains obtained by methods of the present invention, and this application forms a further aspect of the present invention.
  • conformation may be used in a computer-based method of rational design of modified domains for diagnostic or therapeutic applications as described herein.
  • the structure of 12Y-1, 12Y-2, 12A-9 or 1A-7 can also be used to solve the crystal structure of other IgNAR domains, where X-ray diffraction data or NMR specfroscopic data of these other domains has been generated and requires interpretation in order to provide a structure.
  • One method that may be employed for these purposes is molecular replacement.
  • the unknown IgNAR domain crystal structure may be determined using the 12Y-1, 12Y-2, 12A-9 or 1A-7 structure coordinates as provided herein. This method will provide an accurate structural form for the unknown crystal more quickly and efficiently than attempting to determine such information ab initio.
  • the invention provides a method for determining the structure of a protein, which method comprises; providing the co-ordinates of Appendix 1(a), (b), (c) or (d), and either (a) positioning the co-ordinates in the crystal unit cell of said protein so as to provide a structure for said protein or (b) assigning NMR spectra Peaks of said protein by manipulating the coordinates of Appendix 1(a), (b), (c) or (d).
  • the present invention provides systems, particularly a computer system, the systems containing at least one of the following: (a) atomic coordinate data according to Appendix I, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7 or at least selected coordinates thereof; (b) structure factor data (where a structure factor comprises the amplitude and phase of the diffracted wave) for 12Y-1, 12Y-2, 12A-9 or 1A-7, said structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of an IgSF domain generated by homology modelling of the IgSF domain based on the data of Appendix I; (d) atomic coordinate data of the IgSF domain generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Appendix I; and (e) structure factor data derivable from the atomic coordinate data of (c) or (d).
  • the computer system may comprise: (i) a computer-readable data storage medium comprising data storage material encoded with the computer-readable data; (ii) a working memory for storing instructions for processing said computer- readable data; and (iii) a central-processing unit coupled to said working memory and to said computer-readable data storage medium for processing said computer-readable data and thereby generating structures and/or performing rational drug design.
  • the computer system may further comprise a display coupled to said central-processing unit for displaying said structures.
  • the invention also provides such systems containing atomic coordinate data of modified IgSF domains wherein such data has been generated according to the methods of the invention described herein based on the starting data provided by Appendix I.
  • the invention provides a computer-readable storage medium, comprising a data storage material encoded with computer readable data, wherein the data are defined by all or a portion (e.g.
  • the invention also provides a computer-readable data storage medium comprising a data storage material encoded with a first set of computer-readable data comprising a Fourier transformation of at least a portion (e.g. selected coordinates as defined herein) of the structural coordinates for 12Y-1, 12Y-2, 12A-9 or 1A-7 according to Appendix I; which, when combined with a second set of machine readable data comprising an X-ray diffraction pattern of a molecule or molecular complex of unknown structure, using a machine programmed with the instructions for using said first set of data and said second set of data, can determine at least a portion of the structure coordinates corresponding to the second set of machine readable data.
  • a computer-readable data storage medium comprising a data storage material encoded with a first set of computer-readable data comprising a Fourier transformation of at least a portion (e.g. selected coordinates as defined herein) of the structural coordinates for 12Y-1, 12Y-2, 12A-9 or 1A-7 according to Appendix I
  • the present invention provides computer readable media with at least one of: (a) atomic coordinate data according to Appendix I recorded thereon, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, or at least selected coordinates thereof; (b) structure factor data for 12Y-1, 12Y-2, 12A-9 or 1A-7 recorded thereon, the structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of a target IgSF domain generated by homology modelling of the IgSF domain based on the data of Appendix 1 ; (d) atomic coordinate data of a modified IgSF domain generated by interpreting X- ray crystallographic data or NMR data by reference to the data of Appendix I; and (e) structure factor data derivable from the atomic coordinate data of (c) or (d).
  • the atomic coordinate data can be routinely accessed to model IgSF domains or selected coordinates thereof.
  • RASMOL Syle 1995
  • structure factor data which are derivable from atomic coordinate data (see e.g. Blundell 1976), are particularly useful for calculating e.g. difference Fourier electron density maps.
  • a further aspect of the invention provides a method of providing data for generating structures and/or performing rational drug design for IgSF domains, the method comprising: (i) establishing communication with a remote device containing computer-readable data comprising at least one of: (a) atomic coordinate data according to Appendix I, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, at least one sub-domain of the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, or the coordinates of a plurality of atoms of 12Y-1, 12Y-2, 12A-9 or 1A-7; (b) structure factor data for 12Y-1, 12Y-2, 12A-9 or 1A-7, said structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of a modified IgSF domain generated by homology modelling of the domain based on the data of Appendix I; (d) atomic coordinate data of a protein generated by interpreting X-
  • a further aspect of the invention provides a method of providing data for generating structures and/or performing rational drug design for IgSF domains, the method comprising: (i) establishing communication with a remote device containing computer-readable data comprising at least one of: (a) atomic coordinate data according to Appendix I, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, at least one sub-domain of the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, or the coordinates of a plurality of atoms of 12Y-1, 12Y-2, 12A-9 or 1A-7; (b) structure factor data for 12Y-1, 12Y-2, 12A-9 or 1A-7, said structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of a modified IgSF domain generated by homology modelling of the domain based on the data of Appendix I; (d) atomic coordinate data of a protein generated by interpreting X-
  • the remote device may comprise, for example, a computer system or computer readable media of one of the previous aspects of the invention.
  • the device may be in a different country or jurisdiction from where the computer-readable data is received.
  • the communication may be via the internet, intranet, email etc.
  • the communication will be electronic in nature, but some or all of the communication pathway may be optical, for example, over optical fibres. Additionally, the communication may be through radio signals or satellite transmissions.
  • the folding topologies of the 12Y-1, 12Y-2, 12A-9 and 1A-7 structures show the characteristic immunoglobulin superfamily (IgSF) fold, identified by a ⁇ -sandwich structure formed by two ⁇ -sheets, packed face-to-face and linked by a disulfide bond between strands B and F (Bork 1994, Chothia 1998).
  • the inner-strand features are turns, coils and loops including two loop regions analogous to CDRl and CDR3 loops.
  • the structures comprise eight ⁇ -strand regions, designated A, A', B, C, D, E, F and G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2.
  • a "loop region” is a portion of peptide sequence that extends either from or between a ⁇ -strand conformation or ⁇ -strand conformations.
  • a " ⁇ -strand region” contains an extended ⁇ -strand conformation, i.e. ⁇ -strands comprising at least 4, preferably at least 5 amino acids. Loop regions are typically free of extended ⁇ -strand conformations but may include shortened ⁇ -strand conformations, i.e. ⁇ -strands comprising less than 4 amino acids. Apart from N- and C-terminal loop regions, the loop regions connect ⁇ -strands running in opposite directions. Preferably, loop region 5 contains shortened ⁇ -strand conformations.
  • loop region 8 may contain ⁇ -strand conformations, which may be either shortened or extended, and these are discussed in more detail below. Preferably, no other loop regions contain ⁇ -strand conformations.
  • ⁇ -strand conformations may be either shortened or extended, and these are discussed in more detail below.
  • no other loop regions contain ⁇ -strand conformations.
  • Detailed analysis of the 12Y-1, 12Y-2, 12A-9 and 1A-7 frameworks indicates a novel folding topology which resembles the intermediate (I-set) fold in a number of important characteristics, but also with distinct structural features found in variable (V- set) domains.
  • the structures comprise 8 ⁇ -strand regions, designated A, A', B, C, D, E, F and G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2, in which loop region 5 comprises 2 shortened ⁇ -strand regions, designated D' and C, and 3 loop regions, designated 5a, 5b and 5c, according to Figure 3.
  • Table 3 presents a breakdown of the number of amino acid residues present in the various loop and ⁇ -strand regions of Type 2 VNARS.
  • Loop region 4 is analogous to a conventional CDRl loop.
  • Loop region 8 is analogous to a conventional CDR3 loop.
  • loop region 8 can contain a variable number of amino acids ranging from about 5 to 30, a default value of 18 is used on which to base the residue numbering for subsequent regions. Consequently, the residue numbering does not necessarily correlate with the total number of amino acid residues present in the sequence. It is based on loop region 8 having a default value of 18 amino acid residues.
  • Table 3 A presents a breakdown of the number of amino acid residues present in the loop region 5 of Type 2 V NAR S.
  • Loop region 5 comprises 2 shortened ⁇ -strand regions, designated D' and C, and 3 loop regions, designated 5a, 5b and 5c.
  • V-set and I-set proteins have a typical kink in the first strand (A'), which allows the first part of the strand (A) to hydrogen bond to one part of the ⁇ -sandwich sheet and the second part (A') to the extended G strand of the other ⁇ -sheet.
  • This first- strand kink is found in the VNA R proteins as depicted in Figure 4. It starts with the highly conserved cw-proline (Pro7), the most typical residue in first-strand kinks of variable domains (Spada 1998).
  • Pro7 the highly conserved cw-proline
  • 12Y-1, 12Y-2, 12A-9 and 1A-7 also have bulges in the C terminal G strand (conserved Gly-Ala-Gly motif) and in the C strand.
  • 12Y-1, 12Y-2, 12A-9 and 1A-7 resemble I-set proteins in having a short C strand (three H-bonds) and a very short C" strand (labelled as D' in Figure 3) which atypically switches from one ⁇ -sheet to the other, such that a single hydrogen bond links it to the D strand rather than the C strand as in V-set domains.
  • the 12Y-2 chain A and B r.m.s.d. of 0.53 A for C ⁇ of 113 residues
  • the 12Y-1 framework r.m.s.d. of 0.72 A for C ⁇ of 100 residues
  • VNARS Neural Cell Adhesion Molecules
  • NCAMs Neural Cell Adhesion Molecules
  • Telokin Chothia 1997; Holden 1992
  • V H H and VNARS The low structural homology between V H H and VNARS is consistent with their very low sequence homology, and reflects convergent evolutionary solutions to the problem of achieving solvent solubility and binding affinity.
  • Figure 8 the relative positions of the three classically defined antibody CDR or hypervariable loop regions are shown. Sequence alignments show IgNAR antibody variability confined to the loop regions 4 and 8 corresponding to conventional CDRl and CDR-3 regions, and this is confirmed by our structural analysis where a loop region analogous to a typical "CDR2 loop" is missing and its bottom turn appears to be well separated from the antigen-binding face (or paratope). Sequence analysis also suggests that loop region 4 is the minor loop component, invariant in length and limited in diversity.
  • the 12Y-2 CDR3 loop is present in two crystal forms, corresponding to chains A and B, and extends from residues Phe86 to Glul03.
  • the chain A loop region 8 adopts a clear ⁇ -hairpin configuration with ⁇ -strands from Phe86-Leu89, and Leu98-Glul03, separated by a flexible loop (Pro90-Ser97).
  • the ⁇ -hairpin extends even further into loop region 8 with residues Phe86-Asp93 and Tyr96-Glul03 involved in ⁇ -strand formation (see Figure 11).
  • the ⁇ -hairpins are formed by the main chain hydrogen bonds ( ⁇ 3 A): Tyr87 (O) - PhelOO (N); Tyr87 (N) - PhelOO (O); Leu89 (N) - Leu98 (O); Leu89 (O) - Leu98 (N), and, Asp93(O) - Tyr96(O) ( Figure 11). Additional H-bonds for loop region 8 of chain B are: Asp93 (N) - Tyr96 (O); Asp93 (O) - Tyr96 (N); and, Leu91 (O) - Tyr96 (O).
  • the 12Y-2 loop region 8 extends outward and upward from the immunoglobulin framework, at the furthest point extending ⁇ 2 ⁇ A above the conserved ⁇ -sheet framework, and tipped by the bulky side-chains of tyrosine residues at positions 94 and 96 (see Figures 8 and 11).
  • extended antigen binding paratopes have been observed in but a limited number of antibodies, for example the camel anti-lysozyme VHH cAb-Lys3 (Desmyter 1996), and the H3 loop of human antibody bl2, which penetrates deeply into the HIV gpl20 binding cleft (Sapphire 2001).
  • binding of 12Y-2 to the AMA1 target is probably mediated by the rigid ⁇ -hairpin, with increased access to the antigen mediated by flexibility at the bottom of the loop structure.
  • the 12Y-1 loop region 8 is unresolved in the crystal structure and is probably highly flexible in solution around similar hinge-like residues.
  • the aromatic loop region 8 residues of 12Y-2 are replaced with Arg87 and Pro98 in 12Y-1, reducing the stability of the loop region, i.e. the Phe29 of loop region 4 is now hydrogen bonded to GlulOl (Glul03 in 12Y-2) (Tyr29(OH) - Glu 101 (O ⁇ )) leaving the hinges of the loop region 8 unsupported.
  • the most significant dimer contacts are probably mediated by the loop regions 4 and especially by the D strands, where the main-chain interactions are independent of side-chain variation.
  • the 12Y-2 dimer appears to be a true protein-protein interaction site, as the statistical probability of finding a non-specific interface of such dimensions in a crystal is ⁇ 1% (Lo Conte 1999).
  • this configuration is a general phenomenon for independent IgNAR variable domains (i.e. not tethered to constant domains), as we have also observed such dimeric species in other recombinant VNA R S (Nuttall 2002).
  • heterodimeric immune receptors such as VH/VL antibodies and V ⁇ /V ⁇ TCRs
  • the paired domains interact across a broad hydrophobic interface.
  • This non-solvent exposed region is formed by a conserved patch of residues on the AGFCC ⁇ -strands, with additional CDR3 interactions.
  • IgSF-based cell surface receptors are single domains in solution and this face of the ⁇ -sandwich takes on a more charged/polar character.
  • the hydrophobic region of inter-domain contact is immediately apparent for the TCR and antibody domains, centred around aromatic residues at the centre of the interface.
  • the surface character is altered for VHH domains, for example by mutations Leu45Arg and Gly44Glu, to give a more charged character.
  • the relatively short evolutionary time since the development of these single domain antibodies in the Camelidae mean that other solutions have also been adopted, for example the illustrated antibody where part of the loop region 8 (analogous to a conventional CDR3 loop) descends to partly cover the former V L interface, for example residues Aspl21 and Tyrl20.
  • Residues Glu46, Lys82, and Lys 104 especially are well conserved across type 2 V ARS, and in this instance form a charged pocket with a pattern of hydrogen bonds between side-chains (i.e. Glu46O ⁇ l-Lysl04 N ⁇ ) and to adjacent water molecules (i.e. Glu46O ⁇ 2 - H 2 0 - Lys82 N ⁇ ).
  • the central Tyr37 is well-conserved as an aromatic species across the immunoglobulin superfamily, and it and residues Gln84 and ArglOl also participate in forming a framework-CDR3 hydrogen bond network (Argl01(NH2) - Gln84(N ⁇ 2); Tyr87(OH) - Argl01(NH 2 ).
  • VNA R proteins Modifications to the IgNAR variable domain Analysis of the crystal structures has revealed the potential of VNA R proteins as, for example, therapeutic, diagnostic and bioarray reagents.
  • VNAR proteins have potential to act as cleft-binding antibodies in which the ⁇ -hairpin structures are extended to form paratopes capable of penetrating otherwise cryptic antigenic sites.
  • these proteins have a high degree of stability which offers significant advantages in terms of their manipulation and practical application.
  • the present invention provides a method of altering a property of an IgNAR variable domain comprising eight ⁇ -strand regions, designated A, A', B, C, D, E, F and G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2, said method comprising modifying the IgNAR variable domain within at least one of the ⁇ -strand regions or loop regions.
  • the IgNAR variable domain is modified such that a property of the IgNAR variable domains is altered.
  • a property of an ' IgNAR variable domain, I-set domain or V-set domain is altered if any characteristic or attribute of the domain differs from the corresponding property of the unmodified domain.
  • a property of an IgNAR variable domain, I-set domain or V-set domain is considered to be altered when the property exhibits at least a 5%, preferably at least 10%, more preferably at least a 20%, yet more preferably at least a 50%, and most preferably at least a 2-fold increase or decrease relative to the corresponding property in the unmodified domain.
  • the solubility of the modified IgNAR variable domain, and concomitantly the binding moiety is altered, preferably improved, relative to the corresponding unmodified IgNAR variable domain.
  • the stability of the IgNAR variable domain, and concomitantly the binding moiety is altered, preferably improved, relative to the corresponding unmodified IgNAR variable domain. Examples of altering the stability include changing one of the following properties:- thermal stability, alkaline stability, pH activity profile and resistance to proteolytic degradation.
  • the binding characteristics of the IgNAR variable domain are altered relative to the corresponding unmodified IgNAR variable domain.
  • the present invention also provides a binding moiety comprising a modified IgNAR variable domain produced by a method according to the invention.
  • the present invention also provides a binding moiety comprising an IgNAR variable domain comprising eight ⁇ -strand regions, designated A, A', B, C, D, E, F and
  • an IgNAR variable comprises 10 ⁇ -strand regions, designated A, A', B, C, C, D', D, E, F and G according to Figure 3, and eleven loop regions, designated 1, 2, 3, 4, 5a, 5b, 5c, 6, 7, 8 and 9 according to Figure 3.
  • the loop regions 5a, 5b and 5c, and ⁇ -strand regions C, C and D' have the amino acid residue numbering according to Table 3 A.
  • the C ⁇ trace of loop region 5b extends no more than 5 A above the plane formed by the C ⁇ trace of residues 22, 83 and 36 as defined in Table 1.
  • the amino acid sequence of the unmodified ⁇ -strand regions A, A', B, C, D, E, F and G and loop regions 1, 2, 3, 6, 7 and 9 comprises an amino acid sequence according to Figure 1 and/or Table 1.
  • the IgNAR is a Type 2 or Type 3 IgNAR, preferably Type 2.
  • the IgNAR is derived from a shark, preferably a wobbegong shark.
  • the unmodified IgNAR variable domain has a sequence as shown in Figure 1. More preferably, the unmodified IgNAR is 12Y-1, 12Y-2, 12A-9 or 1A-7. Suitable modifications include substitutions, insertions and deletions within at least one at least one of the ⁇ -strand regions or loop regions. A combination of deletion, insertion and substitution can be made to generate the IgNAR modified variable domain.
  • Modifications can be prepared by introducing appropriate nucleotide changes into a nucleic acid of the present invention, or by in vitro synthesis of the desired polypeptide.
  • Such mutants include, for example, deletions, insertions or substitutions of residues within the amino acid sequence.
  • the sites for mutation can be modified individually or in series, for example by (1) substituting first with conservative amino acid choices and then with more radical selections depending upon the results achieved, (2) deleting the target residue, or (3) inserting other residues adjacent to the located site.
  • modifications which are tantamount to conservative substitutions but which alter a property of the IgNAR variable domain. Examples of conservative substitutions are given in as follows:
  • unnatural amino acids or chemical amino acid analogues can be introduced as a substitution or addition into the polypeptides of the present invention.
  • Such amino acids include, but are not limited to, the D-isomers of the common amino acids, 2,4-diaminobutyric acid, ⁇ -amino isobutyric acid, 4- aminobutyric acid, 2-aminobutyric acid, 6-amino hexanoic acid, 2-amino isobutyric acid, 3 -amino propionic acid, ornithine, norleucine, norvaline, hydroxyproline, sarcosine, citrulline, homocitrulline, cysteic acid, t-butylglycine, t-butylalanine, phenylglycine, cyclohexylalanine, ⁇ -alanine, fluoro-amino acids, designer amino acids such as ⁇ -methyl amino acids, C ⁇ -methyl amino acids, N ⁇ -methyl
  • chemically modified derivates of IgNAR variable domains which may provide advantages such as increasing stability and circulating time of the polypeptide, or decreasing immunogenicity (see U.S. Patent No. 4,179,337).
  • the chemical moieties for derivatization may be selected from water-soluble polymers such as polyethylene glycol, ethylene glycol/propylene glycol copolymers. carboxymethylcellulose, dextran, polyvinyl alcohol and the like.
  • variable domains of the present invention that are differentially modified during or after synthesis, for example, by biotinylation, benzylation, glycosylation, acetylation, phosphorylation, amidation, derivatization by known protecting/blocking groups, proteolytic cleavage, linkage to an antibody molecule or other cellular ligand, etc.
  • the IgNAR variable domain may be modified at random positions within the molecule or at predetermined positions within the molecule and may include one, two, three or more attached chemical moieties. These modifications may, for example, serve to increase the stability and/or bioactivity of the modified domains of the invention.
  • the IgNAR variable domains may also be modified by having C- or N-terminal truncations. However, the scope for such modifications is limited and it is preferred that no more than 8, preferably no more than 6 and more preferably no more than 4 residues be removed. Preferably there is no truncation at the N-terminal and more preferably there is no truncation at either the N- or C-terminals. Modified domains of the present invention can be produced in a variety of ways, including production and recovery of natural proteins, production and recovery of recombinant proteins, and chemical synthesis of the proteins.
  • an isolated polypeptide of the present invention is produced by culturing a cell capable of expressing the polypeptide under conditions effective to produce the polypeptide, and recovering the polypeptide.
  • the modification comprises insertion of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,19, 20 or more amino acids.
  • the modification comprises deletion of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acids.
  • the modification involves more than mere substitution of a cysteine residue in one loop region, the cysteine residue being involved in disulphide formation with another cysteine residue in another loop region.
  • the modification is not substitution of residue 43 as shown in Table 1 or involves more than mere substitution of the residue 43.
  • the modification is made to one or more amino acid residues within the patch defined by residues 33, 37, 46, 48, 50, 51, 59, 61, 86, 94, 95, 96, 98, 99 and 101 as shown in Table 1.
  • loop region 4 or loop region 8 of the IgNAR when loop region 4 or loop region 8 of the IgNAR is modified, at least one of the ⁇ -strand regions or loop regions 1-3, 5-7 or 9 is also modified.
  • at least one of ⁇ -strand regions C, D, E or F or loop regions 5, 6 or 7 has been modified.
  • ⁇ -strand regions C or D or loop region 5 has been modified.
  • loop region 5 has been modified.
  • the modification involves point mutations within loop region 8. For example, residues Pro90 and/or PhelOO may be replaced in order to enhance flexibility of loop region 8.
  • the modification involves randomisation of loop region 8.
  • the modification involves insertion of amino acids into loop region 8.
  • the modification involves grafting a CDR loop or portion thereof from a V-set or an I-set domain onto the IgNAR variable domain.
  • the CDR3 loop of an antibody may be grafted onto the IgNAR variable domain in the vicinity of loop region 8.
  • the grafting may involve, for example, replacing amino acids from loop region 8 (for example amino acids 86 to 103 as defined in Table 1 or a portion thereof) with amino acids that constitute an antibody CDR 3 loop or portion thereof.
  • the modification may further involve replacing amino acids from loop region 4 (for example amino acids 28 to 33 as defined in Table 1 or a portion thereof) with amino acids that constitute an antibody CDR 1 loop or portion thereof.
  • loop region 8 is modified by substitution, deletion or addition, preferably by addition, of at least one amino acid within that part of the loop not capable of adopting the ⁇ -strand configuration.
  • loop region 8 is modified by substitution, deletion or addition, preferably by addition or substitution, of one or more amino acid residues at the C- and/or N-terminal ends of the loop region to facilitate the adoption of ⁇ -strand configurations at the C- and/or N-terminal ends.
  • loop region 8 is modified so as to facilitate the adoption of ⁇ -strand configurations at the C- and/or N-terminal ends of 2 to 10, preferably from 3 to 8, amino acid residues in length.
  • the modification increases or decreases the binding characteristics, e.g. the affinity, of the modified IgNAR variable domain for a predetermined target molecule compared to the unmodified IgNAR variable domain. That part of the IgNAR variable domain which normally contacts a ligand (e.g.
  • an antigen or which appear, from the studies we have undertaken, to be available for interacting with a ligand (e.g. a receptor, enzyme etc.) are typically the solvent exposed regions of the IgNAR variable domain.
  • they are generally made up of the surface exposed loops, and in particular loop regions 8 and 4 of the IgNAR variable domain.
  • the unmodified IgNAR variable domain has had one or more loop regions modified. In particular, this can be achieved by replacing one or more solvent exposed loops of the IgNAR variable domain with one or more loops from the variable domains of other members of the IgSF.
  • loop regions 4 and/or 8, or part thereof is modified, preferably replaced, by a corresponding loop structure (e.g.
  • Modifications can also be made to regions of the IgNAR variable domain that are not solvent exposed and/or which do not form part of a binding loop, e.g. the ⁇ strand regions.
  • the modification increases or decreases the propensity for the IgNAR variable domain to form homodimers compared to the unmodified IgNAR variable domains.
  • the modification increases the solubility of the IgNAR variable domain compared to the unmodified IgNAR variable domain.
  • one or more solvent exposed loops is/are modified to improve solubility.
  • Solubility may be improved by, for example, either removing disulphide bond-forming cysteines and/or replacing disulphide bond-forming cysteines from within the solvent exposed loops with amino acids such as alanine or serine. Modifications to improve solubility may be desirable where the IgNAR variable domains are being designed to function in an intracellular context and/or their method of production favours expression in a soluble form. It will also be evident to the skilled person that it may be necessary to modify the solubility characteristics of the IgNAR variable domains at the same time or even prior to making other modifications, such as, changing the binding characteristics.
  • the physicochemical properties, such as stability and solubility, of the IgNAR variable domains may be qualitatively and/or quantitatively determined using a wide range of methods known in the art.
  • Methods which may find use in the present invention for characterizing the biophysical/physicochemical properties of the binding moieties include gel electrophoresis, chromatography such as size exclusion chromatography, reversed-phase high performance liquid chromatography, mass spectrometry, ultraviolet absorbance spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy, isothermal titration calorimetry, differential scanning calorimetry, analytical ultra-centrifugation, dynamic light scattering, proteolysis, cross- linking, turbidity measurement, filter retardation assays, immunological assays, fluorescent dye binding assays, protein-staining assays, microscopy, and detection of aggregates via ELISA or other binding assay.
  • Protein stability e.g. structural integrity
  • stability and/or solubility may be measured by determining the amount of soluble protein after some defined period of time. In such an assay, the protein may or may not be exposed to some extreme condition, for example elevated temperature, low pH, or the presence of denaturant. Because unfolded and aggregated protein is not expected to maintain its function, e.g. be capable of binding to a predetermined target molecule, the amount of activity remaining provides a measure of the binding moieties stability and solubility.
  • one method of assessing solubility and/or stability is to assay a solution comprising a binding moiety for its ability to bind a target molecule, then expose the solution to elevated temperature for one or more defined periods of time, then assay for antigen binding again.
  • the modified IgNAR binding domains could be expressed in prokaryotic expression systems and the protein isolated from the cell lysate by a series of biochemical purification steps including differential centrifugation, affinity isolation chromatography using attached tags such as poly histidine, ion-exchange chromatography and gel filtration chromatography.
  • a measure of the improvement in the solubility of the modified polypeptide can be obtained by making a comparison of the amount of soluble protein obtained at the end of the purification procedure to that obtained using the unmodified polypeptide, when starting with a similar amount of expressed unfractionated product.
  • Levels of expression of product in culture can be normalised by a comparison of product band densities after polyacrylamide gel electrophoresis of equivalent aliquots of SDS detergent-solubilised cell lysate.
  • IgNAR variable domains can be unfolded using chemical denaturant, heat, or pH, and this transition be monitored using methods including, but not limited to, circular dichroism spectroscopy, fluorescence spectroscopy, absorbance spectroscopy, NMR spectroscopy, calorimetry, and proteolysis.
  • the kinetic parameters of the folding and unfolding transitions may also be monitored using these and other techniques.
  • the solubility of the IgNAR variable domains of the present invention preferably correlates with the production of correctly folded, monomeric polypeptide. The solubility of the modified IgNAR variable domains may therefore also be assessed by HPLC or FPLC.
  • soluble (non-aggregated) domains will give rise to a single peak on a HPLC or FPLC chromatograph, whereas insoluble (aggregated) domains will give rise to a plurality of peaks.
  • the ability to be able to correctly fold and form ordered crystal leads and structures is also often indicative of good solubility.
  • aliquots of the IgNAR variable domain can be stored at different temperatures, such as -20°C, 4°C, 20°C and 37°C and an activity of the IgNAR variable domain assayed at different time intervals. For example, successful maintenance of activity during storage at 37°C for 12 weeks is roughly equivalent to storage stability for 12 months at 4°C.
  • the trial can also be conducted to compare the effect of different protecting additives in the storage buffer on the stability of the protein.
  • additives can include compounds such as glycerol, sorbitol, non-specific protein such as bovine serum albumin, or other protectants that might be used to increase the shelf life of the protein.
  • the results presented herein also identify structural features in IgNAR variable domains that are important for antigen binding or solubility/stability of these domains. These features can be introduced into domains of other members of the IgSF (for example, I-set or V-set domains) in order to alter binding properties or to improve solubility and/or stability. Accordingly, in a further aspect the present invention provides a method of modifying an I- or V-set domain, said method comprising inserting and/or substituting one or more structural features from an IgNAR variable domain into the I- or V-set domain.
  • the present invention provides a binding moiety comprising an I- or V-set domain, wherein the I- or V-set domain has been modified by substitution or insertion of one or more structural features from an IgNAR variable domain into the I- or V-set domain.
  • I-set domain is meant a domain comprising nine ⁇ -strand regions, designated A, A', B, C, C, D, E, F and G, as set out and according to Chothia (1997).
  • representative I-set domain molecules include NCAM, VCAM, ICAM, Telokin, MADCAM-1, Twitchin and Titin.
  • V-set domain is meant a domain comprising ten ⁇ -strand regions, designated A, A', B, C, C, C", D, E, F and G, as , as set out and according to Chothia (1997).
  • V-set domain molecules include antibodies, T cell receptors (TCRs), CTLA-4, CD28, ICOS, CD2, CD4, Cd7, CD22, CD33, CD80, CD86, CD48 and CD58.
  • the I-set or V-set domain is modified such that a property of the domain is altered.
  • the structural feature is a loop region from an IgNAR variable domain.
  • loop region 8 and/or loop region 4 from an IgNAR variable domain may be grafted onto the I- or V-set domain.
  • the grafting may involve, for example, replacing suitable (e.g. predeteremined) amino acids of the I- or V-set domain with amino acids 86 to 103 as defined in Table 1 or a portion thereof.
  • the method comprises removing all or a portion of the CDR2 loop of the I- or V-set domain.
  • the structural feature is the solvent exposed face of an
  • the method may involve modifying amino acids of the I- or V-set domain equivalent to amino acids 32, 33, 34, 35, 55, 57 and 58 as defined in Table 1 or a portion thereof.
  • the method may involve grafting the solvent exposed face of an IgNAR variable domain (for example comprising residues 32, 33, 34, 35, 55, 57 and 58 as defined in Table 1) or a portion thereof onto the I- or V-set domain.
  • Grafting may involve replacing amino acids of the I- or V-set domain with amino acids derived from the solvent exposed face of an IgNAR variable domain. Grafting of the solvent exposed face onto the I- or V-set domain preferably occurs after removal of all or a portion of the CDR2 loop. Preferably, the modification introduces charged or polar amino acids at these positions. Preferably, this modification improves the solubility of the I- or V-set domain.
  • the V-set domain is a TCRV ⁇ or V ⁇ domain and the equivalent amino acids to the solvent exposed surface of am IgNAR variable domain are Gly30, Ser31, Phe32, Phe33, Phe62, Thr63, Ala64 and Gln65.
  • the modification involves the introduction of polar or charged amino acids in these positions.
  • the method involves modifying one or more residues of a TCR V ⁇ or V ⁇ domain, wherein the one or more residues is located at the interface between the V ⁇ and V ⁇ domains.
  • the one or more amino acid residue is selected from the group consisting of Ser31, Pro43, Leu89 and Phel06 and combinations thereof.
  • the modification involves the introduction of one or more charged amino acids in these positions.
  • the method involves modifying one or more residues of an antibody VH or VL domain, wherein the one or more residues is located at the interface between the VH and V domains.
  • the one or more amino acid residue is equivalent to an amino acid of the TCR V ⁇ or V ⁇ domain selected from the group consisting of Ser31, Pro43, Leu89 and Phe 106 and combinations thereof.
  • the modification involves the introduction of one or more charged amino acids in these positions.
  • the modification improves the solubility of the I- or V-set domain.
  • the present invention provides a method of modifying an I- or V-set domain, said method comprising introducing a modification into a region of the I- or V-set domain equivalent to loop region 4 and/or loop region 8 of an IgNAR variable domain as defined by Figure 2.
  • the present invention provides a modified V-set domain produced by a method of the present invention.
  • the present invention also provides a binding moiety comprising a multimer comprising:
  • IgNAR domains which may be the same or different, and at least one of which is a IgNAR variable domain
  • I-set domains which may be the same or different, and at least one of which is a I-set domain according to the present invention
  • V-set domains at least two V-set domains, wliich may be the same or different, and at least one of which is a V-set domain according to the present invention.
  • the two domains may be derived from the same or different sources. The following description is directed to IgNAR domain multimers.
  • the multimer comprises two IgNAR variable domains.
  • the one or the at least two of the IgNAR domains is/are variable IgNAR domains(s) comprising eight ⁇ -strand regions, designated A, A', B, C, D, E, F and G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2.
  • at least one IgNAR variable domains is modified by substitution, deletion or addition of at least one amino acid within in at least one of the ⁇ -strand or loop regions as described hereinabove.
  • the multimer comprises at least two IgNAR variable domains
  • the two domains preferably form stable homodimers, preferably at least partially through salt bridges.
  • a preferred modification is one in which at least one of the IgNAR variable domains has been modified such that the propensity to form a stable homodimer is increased.
  • the least one IgNAR variable domain has been modified so as to increase the dissociation constant of the homodimer formed compared to the homodimer formed by the unmodified IgNAR variable domain.
  • both IgNAR variable domains have been modified such that the propensity to form a stable homodimer is increased.
  • this is achieved by replacing the following residues of one or both of the unmodified monomers (as defined in Table 1) with cysteine residues: residues 57 and/or 61; residues 51 and
  • the multimer comprises at least one IgNAR variable domain and at least one IgNAR constant domain.
  • the constant domain is the Cl constant domain of an IgNAR, i.e. the constant domain closest to the IgNAR variable domain in nature.
  • connecting an IgNAR variable domain to an IgNAR constant domain has no effect on the level of binding affinity (see Example 16). This means it is possible to add mass to the binding moieties without facilitating multimerisation or loss of binding affinity. Therefore, such multimer constructs have potential as commercial biosensor reagents. Multimers are one preferred design for therapeutic reagents since they have the potential to provide increased avidity and slower blood clearance rates which may provide favourable pharmacokinetic and biodistribution properties.
  • the IgNAR domains may be connected either through covalent linkage or non-covalent linkage or a combination of linkages, including the use of chemical or genetically-encoded linkers.
  • Linkers used to link protein domains are well-known and well understood in the art, in particular in relation to proteins in the immunoglobulin superfamilies (e.g. Casey JL et al, 2002 Br J Cancer., 86(9):1401-10; Pl ⁇ ckthun, A., and Pack, P 1997. Immunotechnology, 3, 83-105). Therefore, the skilled person will appreciate that any suitable hinge or means of connection may be used to connect the two at least IgNAR domains.
  • suitable chemical linkage examples include linking the two domains using a suitable cross-linker such as dimaleimide.
  • the two domains may be linked by providing cysteine residues at the respective C- and N- terminals and forming a disulphide bond.
  • they could be linked using single chain Gly Ser linkers such as GlyGlyGlyGlySer.
  • the domains may also be linked genetically using techniques well-know in the art. The resulting multimers from any of these linker strategies described may possess the same, or different target specificities thus providing multivalent or multispecific reagents.
  • two IgNAR variable domains may be joined to form a heterodimer through either covalent linkage or non-covalent linkage or a combination of linkages thereby providing two target binding affinities. If two or more IgNAR variable domains in the multimer have the same target specificity, the multimer will be multivalent and have increased avidity (functional affinity) for binding to two or more target molecules. In the case of multimers, it will be appreciated by the skilled person that the IgNAR domains must be suitably orientated with respect to each other. The first IgNAR domain should be suitably hinged or connected to the second IgNAR domain. Where the multimer comprises an IgNAR variable domain and an IgNAR constant domain, the domains are preferably orientated with respect to each other as they would be in the respective native protein(s) from which they are derived.
  • binding moieties of the present invention comprising IgNAR variable domains
  • such binding moieties comprise an IgNAR variable domain which has been modified such that at least one property of the IgNAR variable domain is altered. It will be understood that such binding moieties do not encompass and do not relate to the full-length, wild-type proteins from which suitable IgNAR variable domains may be derived. Rather, they encompass and relate to portions of IgNARs comprising the variable domain, which have been removed or isolated from their natural environments.
  • the IgNAR variable domain of the binding moiety accounts for at least 25%, preferably at least 40%, more preferably at least 50%, yet more preferably at least 10%, even more preferably at least 80%, yet more preferably at least 90% and most preferably at least 95% by weight of the total molecular weight of and/or number of amino acid residues in the binding moiety.
  • the binding moiety consists essentially of the CBD.
  • the only binding domains present in the binding moieties of the present invention are the modified IgNAR variable domain, the I-set domain or the V- set domain.
  • the binding moieties of the invention may be in a substantially isolated form.
  • binding moieties of the invention may also be in a substantially purified form, in which case they will generally comprise the protein in a preparation in which more than 90%, e.g. 95%, 98% or 99% of the protein in the preparation is a binding moiety of the invention.
  • the binding moieties of the invention may also be linked to other molecules, for example by covalent or non-covalent means.
  • the binding moieties of the invention may be linked (without restriction) to molecules such as enzymes, drugs, lipids, sugars, nucleic acids and viruses.
  • the present invention provides a binding moiety of the present invention linked to a diagnostic reagent.
  • the diagnostic reagent is selected from the group consisting of streptavidin, biotin , a radioisotope, dye marker, other imaging reagent and combinations thereof.
  • the present invention provides a binding moiety of the present invention immobilised on a solid support or coupled to a biosensor surface.
  • the binding moiety may contain solvent exposed cysteine residues for the site-specific attachment of other entities.
  • Binding moieties of the invention can be linked to other molecules, typically by covalent or non-covalent means. For example, binding moieties may be produced as fusion proteins, linked to other polypeptide sequences.
  • Fusion partners can include enzymes, detectable labels and/or affinity tags for numerous diagnostic applications or to aid in purification. Fusion partners, without restriction, may be GFP (green fluorescent protein), GST (glutathione S-transferase), thioredoxin or hexahistidine. Other fusion partners include targeting sequences that direct binding moieties to particular sub-cellular locations or direct binding moieties to extracellular locations e.g. secretion signals. In a preferred embodiment, binding moieties of the invention do not comprise other regions of the protein from which they are derived i.e. any fusion partners are heterologous to the IgNAR or protein from which I-set or V-set domains are derived.
  • the heterologous sequence may be any sequence which allows the resulting fusion protein to retain the activity of the modified IgNAR variable domain, modified I-set domain or modified V-set domain.
  • the heterologous sequences include for example, immunoglobulin fusions, such as Fc fusions, or fusions to other cellular ligands which may increase stability or aid in purification of the protein.
  • Diagnostic or therapeutic agents that can be linked to the binding moieties of the invention include pharmacologically active substances such as toxins or prodrugs, immunomodulatory agents, nucleic acids, such as inhibitory nucleic acids or nucleic acids encoding polypeptides, molecules that enhance the in vivo stability or lipophilic behaviour of the binding moieties such as PEG, and detectable labels such as radioactive compounds, dyes, chromophores, fluorophores or other imaging reagents.
  • Binding moieties may also be immobilised to a solid phase, such as a substantially planar surface (e.g. a chip or a microtitre plate) or beads. Techniques for immobilising polypeptides to a solid phase are known in the art.
  • binding moieties of the invention function as a protein scaffold with other polypeptide sequences being inserted into solvent-exposed regions of the binding moiety for display on the surface of the scaffold.
  • Such scaffolds may, for example, serve as a convenient means to present peptides in a conformationally constrained manner.
  • the scaffolds may be used to produce IgNAR variable domains, I-set domains or V-set domains with altered binding specificities and also to produce and/or screen for binding moieties having specificity for any target molecule of interest.
  • Heterologous polypeptide sequences may be inserted into one or more solvent exposed regions such as, for example, one or more loops of the IgNAR variable domains, I-set domains or V-set domains.
  • the IgNAR variable domain, I-set domain or V-set domain of the binding moiety functions as a protein scaffold for the inserted heterologous sequences, displaying the heterologous sequences on the surface of the binding moiety.
  • the heterologous sequences may replace all or part of the loop of the IgNAR variable domain, I-set domain or V-set domain into wliich they are inserted, or may simply form additional sequence.
  • a plurality of heterologous sequences are inserted into a plurality of loops.
  • the heterologous sequences may be derived from solvent exposed regions such as, for example, loops of another IgNAR variable domain, I-set domains or V-set domains. They may also be derived from other molecules or be partially of fully randomised.
  • Polynucleotides, vectors and hosts The present invention provides a polynucleotide encoding a IgNAR variable domain or multimeric reagent according to the present invention.
  • the present invention also provides a vector comprising a polynucleotide of the present invention.
  • the present invention further provides a host cell comprising the vector of the invention.
  • the present invention also provides a method of producing a binding moiety according to the present invention which comprises culturing a host cell of the present invention under conditions enabling expression of the binding moiety and optionally recovering the IgNAR variable domain.
  • the method of producing a binding moiety according to the present invention which comprises culturing a host cell of the present invention under conditions enabling expression of the binding moiety and optionally recovering the IgNAR variable domain.
  • Polynucleotides of the invention may comprise DNA or RNA. They may be single-stranded or double-stranded. They may also be polynucleotides which include within them synthetic or modified nucleotides. A number of different types of modifications to oligonucleotides are known in the art. These include methylphosphonate and phosphorothioate backbones, addition of acridine or polylysine chains at the 3' and/or 5' ends of the molecule. For the purposes of the present invention, it is to be understood that the polynucleotides described herein may be modified by any method available in the art.
  • Polynucleotides of the invention can be incorporated into a recombinant replicable vector.
  • the vector may be used to replicate the nucleic acid in a compatible host cell.
  • a polynucleotide of the invention in a vector is operably linked to a control sequence that is capable of providing for the expression of the coding sequence by a host cell or using an in vitro transcription/translation system, i.e. the vector is an expression vector.
  • the term "operably linked" means that the components described are in a relationship permitting them to function in their intended manner.
  • a regulatory sequence "operably linked" to a coding sequence is ligated in such a way that expression of the coding sequence is achieved under condition compatible with the control sequences.
  • the control sequences may be modified, for example by the addition of further transcriptional regulatory elements to make the level of transcription directed by the control sequences more responsive to transcriptional modulators.
  • Vectors of the invention may be transformed or transfected into a suitable host cell to provide for expression of a binding moiety according to the invention. This process may comprise culturing a host cell transformed with an expression vector under conditions to provide for expression by the vector of a coding sequence encoding the binding moiety, and optionally recovering the expressed binding moiety.
  • the vectors may be, for example, plasmid, phagemid or virus vectors provided with an origin of replication, optionally a promoter for the expression of the said polynucleotide and optionally a regulator of the promoter.
  • the vectors may contain one or more selectable marker genes, for example an ampicillin resistance gene in the case of a bacterial plasmid or a neomycin resistance gene for a mammalian vector.
  • Vectors may be used, for example, to transfect or transform a host cell.
  • Control sequences operably linked to sequences encoding the protein of the invention include promoters/enhancers and other expression regulation signals. These control sequences may be selected to be compatible with the host cell for which the expression vector is designed to be used in.
  • promoter is well-known in the art and encompasses nucleic acid regions ranging in size and complexity from minimal promoters to promoters including upstream elements and enhancers.
  • the promoter is typically selected from promoters which are functional in prokaryotic or eukaryotic cells. With respect to eukaryotic promoters, they may be promoters that function in a ubiquitous manner or, alternatively, a tissue-specific manner. They may also be promoters that respond to specific stimuli.
  • Viral promoters may also be used, for example the Moloney murine leukaemia virus long terminal repeat (MMLV LTR) promoter, the rous sarcoma virus (RSV) LTR promoter or the human cytomegalovirus (CMV) IE promoter. It may also be advantageous for the promoters to be inducible so that the levels of expression of the binding moiety can be regulated during the life-time of the cell. Inducible means that the levels of expression obtained using the promoter can be regulated. In a number of embodiments of the present invention, heterologous sequences are inserted into the various domains (including IgNAR variable domains, I-set domains and V-set domains) of the present invention.
  • MMLV LTR Moloney murine leukaemia virus long terminal repeat
  • RSV rous sarcoma virus
  • CMV human cytomegalovirus
  • Such modifications are generally made by manipulating polynucleotides of the invention encoding the respective domain.
  • This may conveniently be achieved by providing cloning vectors that comprise a sequence encoding a domain which sequence comprises one or more unique insertion sites to allow for easy insertion of nucleotide sequences encoding heterologous sequences into the appropriate region of the domain.
  • Each "unique" insertion site typically contains a nucleotide sequence that is recognised and cleaved by a type II restriction endonuclease, the nucleotide sequence not being present elsewhere in the cloning vector such that the cloning vector is cleaved by the restriction endonuclease only at the "unique" insertion site.
  • Vectors and polynucleotides of the invention may be introduced into host cells for the purpose of replicating the vectors/polynucleotides and/or expressing the binding moiety according to the invention encoded by the polynucleotides.
  • Any suitable host cell may be used, including prokaryotic host cells (such as Escherichia coli, Streptomyces spp.
  • eukaryotic host cells include insect cells (e.g. using the baculovirus expression system), mammalian cells, fungal (e.g. yeast) cells and plant cells.
  • eukaryotic host cells include insect cells (e.g. using the baculovirus expression system), mammalian cells, fungal (e.g. yeast) cells and plant cells.
  • Preferred mammalian cells are animal cells such as CHO, COS, C 127, 3T3, HeLa, HEK 293, NIH 3T3, BHK and Bowes melanoma (particularly preferred being CHO-K1, COS7, YI adrenal and carcinoma cells).
  • Vectors/polynucleotides of the invention may introduced into suitable host cells using any of a large number of techniques known in the art such as, for example, transfection (for example calcium phosphate transfection or DEAE-Dextran mediated transfection), transformation and electroporation.
  • transfection for example calcium phosphate transfection or DEAE-Dextran mediated transfection
  • transformation for example calcium phosphate transfection or DEAE-Dextran mediated transfection
  • electroporation for example calcium phosphate transfection or DEAE-Dextran mediated transfection
  • vectors/polynucleotides of the invention are to be administered to animals, several techniques are known in the art, for example infection with recombinant viral vectors such as retroviruses, herpes simplex viruses and adenoviruses, direct injection of nucleic acids and biolistic transformation.
  • Host cells comprising polynucleotides of the invention may be used to express proteins of the invention.
  • binding moieties are cultured under suitable conditions wliich allow for expression of the binding moieties according to the invention.
  • Expression of the binding moieties may be constitutive such that they are continually produced, or inducible, requiring a stimulus to initiate expression.
  • protein production can be initiated when required by, for example, addition of an inducer substance to the culture medium, for example dexamethasone or IPTG, or inducible expression may achieved through heat-induction, thereby denaturing the repressor and initiating protein synthesis.
  • Binding moieties according to the invention can be extracted from host cells by a variety of techniques known in the art, including enzymatic, chemical and/or osmotic lysis and physical disruption. Cell-free translation systems can also be used to produce the peptides of the invention. Appropriate cloning and expression vectors for use with prokaryotic and eukaryotic hosts are described in Sambrook (1989).
  • Binding moieties according to the invention may be provided as libraries comprising a plurality of binding moieties which have different sequences in the IgNAR variable domains, I-set domains or V-set domains. Preferably, the variations reside in one or more loops. These libraries can typically be used in screening methods to identify a binding reagent with an activity of interest, such as affinity for a specific target molecule of interest. Libraries of binding moieties are conveniently provided as libraries of polynucleotides encoding the binding moieties. The polynucleotides are generally mutagenised or randomised to produce a large number of different sequences which differ at one or more positions within at least one ⁇ strand or loop region.
  • Mutations can be introduced using a variety of techniques known in the art, such as site-directed mutagenesis.
  • a number of methods for site-directed mutagenesis are known in the art, from methods employing single-stranded phage such as Ml 3 to PCR-based techniques (see “PCR Protocols: A guide to methods and applications", M.A. Innis, D.H. Gelfand, J.J. Sninsky, TJ. White (eds.). Academic Press, New York, 1990).
  • Another technique is to use the commercially available "Altered Sites II in vitro Mutagenesis System” (Promega - U.S. Patent N° 5,955,363). Techniques for site- directed mutagenesis are described above.
  • Pluralities of randomly mutated sequences can be made by introducing mutations into a nucleotide sequence or pool of nucleotide sequences 'randomly' by a variety of techniques in vivo, including; using 'mutator strains', of bacteria such as E. coli mutD5 (Low et al, 1996, J Mol Biol 60: 9-68); and using the antibody hypermutation system of B-lymphocytes (Yelamos et al, 1995, Nature 376: 225-9). Random mutations can also be introduced both in vivo and in vitro by chemical mutagens, and ionising or UV irradiation (Friedberg et al, 1995, DNA repair and mutagenesis.
  • mutagemc base analogues Zaccolo et al, 1996 J Mol Biol 255: 589-603
  • 'Random' mutations can also be introduced into genes in vitro during polymerisation for example by using error- prone polymerases (Leung et al, 1989, Technique 1: 11-15). It is generally preferred to use mutagenesis techniques that vary the sequences present in the loop regions of the IgNAR variable domains, although framework changes (e.g. changes in the ⁇ stands) may also occur which may or may not be desirable.
  • One method for targeting the loop regions is to provide a plurality of relatively short nucleotide sequences that are partially or fully mutagenised/randomised and clone these sequences into specific insertion sites in the IgNAR variable domains.
  • Another approach is to synthesise a plurality of random synthetic oligonucleotides and then insert the oligonucleotides into a sequence encoding the IgNAR variable domain, I-set domain or V-set domain and/or replace a sequence encoding the IgNAR variable domains, I-set domain or V-set domain with the random synthetic oligonucleotides.
  • oligonucleotide synthesis is performed using techniques that are well known in the art (see Eckstein, Oligonucleotides and Analogues: A Practical Approach, IRL Press at Oxford University Press 1991). Libraries can also be specified and purchased commercially.
  • the synthetic process can be performed to allow the generation of all or most possible combinations over the length of the nucleic acid, thus generating a library of randomised nucleic acids.
  • These randomised sequences are synthesised such that they allow in frame expression of the randomised peptide with any fusion partner.
  • the library is fully randomised, with no sequence preferences or constants at any position.
  • the library is biased, i.e. partially randomised in which some positions within the sequence are either held constant, or are selected from a limited number of possible variations. Thus some nucleic acid or amino acid positions are kept constant with a view to maintaining certain structural or chemical characteristics.
  • the randomised oligonucleotides can then be inserted into a suitable site and/or replace a suitable sequence encoding a IgNAR variable domains, I-set domain or V-set domain.
  • the library of sequences will be large enough such that a structurally diverse population of random sequences is presented. This ensures that a large subset of shapes and structures is represented and maximises the probability of a functional interaction.
  • the library comprises at least 1000 different nucleotide sequences, more preferably at least 10 4 , 10 5 or 10 6 different sequences.
  • the library comprises from 10 4 to 10 10 different sequences.
  • the present invention provides a method of selecting a binding moiety of the present invention with an affinity for a target molecule which comprises screening a library of polynucleotides of the present invention for expression of a binding moiety with an affinity for the target molecule.
  • the libraries of polynucleotides encoding binding moieties can be screened using any suitable technique to identify a binding moiety having an activity of interest.
  • the library of polynucleotides is incubated under conditions that allow for expression of the binding moiety polypeptides encoded by the polynucleotides and binding of the polypeptides to the target molecule assessed. Binding is typically assessed in vitro or using whole cell assays. Suitable techniques for screening the library for binding moieties having an activity of interest include phage display and ribosome display as well as the use of viral vectors, such as retroviral vectors and in vivo compartmentalisation screening by protein bioarray.
  • this method involves displaying the IgNAR variable domain or multimeric reagent of the present invention as gene III protein fusions on the surface of bacteriophage particles.
  • the method involves displaying the IgNAR variable domain or multimeric reagent of the present invention in a ribosomal display selection system.
  • the sequence of binding moieties identified in the screen can conveniently be determined using standard DNA sequencing techniques.
  • Binding moieties of the invention may be used in methods of diagnosis/therapy by virtue of their specific binding to a target molecule of interest. Such uses will be analogous to the plethora of diagnostic/therapeutic applications already known in relation to antibodies and fragments thereof.
  • binding moieties of the invention may be used to detect the presence or absence of molecules of interest in a biological sample.
  • it may be convenient to immobilise the binding reagent to a solid phase, such as a dipstick, microtitre plate or chip.
  • binding moieties of the invention when used diagnostically will typically be linked to a diagnostic reagent such as a detectable label to allow easy detection of binding events in vitro or in vivo.
  • Suitable labels include radioisotopes, dye markers or other imaging reagents for in vivo detection and/or localisation of target molecules.
  • Binding moieties may also be used therapeutically. For example, binding moieties may be used to target ligands that bind to extracellular receptors.
  • binding moieties of the invention may be used, in a similar manner to antibodies, to target pharmacologically active substances to a cell of interest, such as a tumour cell, by virtue of binding to a cell surface molecule present specifically on the tumour cell to which the binding moiety binds specifically.
  • the present invention provides a pharmaceutical composition comprising an IgNAR variable domain or multimeric reagent according to the present invention and a pharmaceutically acceptable carrier or diluent.
  • the present invention provides a method of treating a pathological condition in a subject, which method comprises administering to the subject a pharmaceutical composition according to the present invention.
  • Binding moieties of the invention including binding moieties identified by the screening methods of the invention may preferably be combined with various components to produce compositions of the invention.
  • the compositions are combined with a pharmaceutically acceptable carrier, adjuvant or diluent to produce a pharmaceutical composition (which may be for human or animal use).
  • Suitable carriers and diluents include isotonic saline solutions, for example phosphate-buffered saline.
  • the composition of the invention may be administered by direct injection.
  • the composition may be formulated for parenteral, intramuscular, intravenous, subcutaneous, intraocular, oral or transdermal administration.
  • each protein may be administered at a dose of from 0.01 to 30 mg/kg body weight, preferably from 0.1 to 10 mg/kg, more preferably from 0.1 to 1 mg/kg body weight.
  • Polynucleotides/vectors encoding binding moieties may be administered directly as a naked nucleic acid construct.
  • the amount of nucleic acid administered may typically be in the range of from 1 ⁇ g to 10 mg, preferably from 100 ⁇ g to 1 mg.
  • Uptake of naked nucleic acid constructs by mammalian cells is enhanced by several known transfection techniques for example those including the use of transfection agents.
  • these agents include cationic agents (for example calcium phosphate and DEAE-dextran) and lipofectants (for example lipofectamTM and transfectamTM).
  • nucleic acid constructs are mixed with the transfection agent to produce a composition.
  • the polynucleotide or vector of the invention is combined with a pharmaceutically acceptable carrier or diluent to produce a pharmaceutical composition.
  • suitable carriers and diluents include isotonic saline solutions, for example phosphate-buffered saline.
  • the composition may be formulated for parenteral, intramuscular, intravenous, subcutaneous, oral, intraocular or transdermal administration.
  • the routes of administration and dosages described are intended only as a guide since a skilled practitioner will be able to determine readily the optimum route of administration and dosage for any particular patient and condition.
  • the various features and embodiments of the present invention, referred to in individual sections above apply, as appropriate, to other sections, mutatis mutandis. Consequently features specified in one section may be combined with features specified in other sections, as appropriate.
  • the present invention will now be further described in the following non- limiting Examples.
  • EXAMPLE 1 Expression of V NAR 12Y-1 and 12Y-2 proteins Recombinant proteins 12Y-1 (SEQ ID NOs: 1 & 2) and 12Y-2 (SEQ ID NOs: 3
  • Eluted proteins were dialysed against two changes of 0.02M Tris pH7.5, concentrated by ultrafiltration over a 3000 Da cutoff membrane (YM3, Diaflo), and analysed for purity and activity by size exclusion chromatography, SDS- polyacrylamide gel electrophoresis, and biosensor.
  • EXAMPLE la Expression of VNA R 1A-7 and 12A-9 proteins Recombinant proteins 1 A-7 (SEQ ID NOs: 5 & 6) and 12A-9 (SEQ ID NOs: 9 & 10) were expressed into the E. coli periplasm, purified and analysed exactly as described in Example 1 above.
  • EXAMPLE 2 Crystallization of V NAR 12Y-1 and 12Y-2 proteins Recombinant protein 12Y-2 (14mg/ml) was set up in 2 ⁇ l hanging drops using the Hampton Research sparse matrix crystallization screening kit. Plates were incubated at 25°C. Final crystallization conditions were 0.1M Sodium citrate pH4.6/20% v/v iso-Propanol/20% PEG4000. Diffraction quality crystals were obtained after 48h. Recombinant protein 12Y-1 (6mg/ml) was set up as 0.2 ⁇ l sitting drops using a
  • EXAMPLE 2a Crystallization of V NAR 12A-9 and 1A-7 proteins Recombinant protein 12A-9 (7mg/ml) was set up as 0.2 ⁇ l sitting drops using a
  • EXAMPLE 3 Data collection and structure determination for 12Y-1 and 12Y-2 X-ray diffraction data collections from all crystals were conducted in-house using Rigaku RAXIS IV (Rigaku-MSC) and Mar 180 (MarResearch) image plate detectors mounted on a Rigaku HR3 HB X-ray generator equipped with monocapillary focusing optics (AXCO). Data were collected at -160°C; the crystals required no added cryoprotectant. All data processing was carried out using the DENZO/SCALEPACK suite (Otwinoski 1997). Diffraction data statistics are summarized in Table 2.
  • the residual and anomalous difference Fourier maps produced by SHARP were examined in order to locate further heavy atom peaks, which were included in subsequent cycles of phase refinement and calculation using SHARP. Several iterations of this cycle located additional positions and improved phases to 2.82A. This result was achieved using the phasing power of both Lu and Re.
  • the model was manually built using XtalView (McRee 1999) into the electron- density map (centroid map) produced by SHARP. The model was then refined against the native 12Y-1 data using CNS (Brunger 1998) and CCP4 (CCP) packages. Difference electron density maps 2m
  • the libration tensor showed significant anisotropy.
  • the final R and Rf ⁇ ee values were 0.166 and 0.254, respectively for a 6-2.82A range of refined data.
  • the final 12Y-1 model contains 100 amino acids (residues 1-87 and 99-111) and 97 water molecules. Of the residues in the 12Y-1 model, 84.5% fall in the most favourable regions of a Ramachandran plot generated by CCP4 PROCHECK (Laskowski 1993) with no residues in the generously allowed or disallowed regions. Further details are given in Table 2.
  • the structure of 12Y-2 was determined by molecular replacement using CCP4
  • the search model was the 12Y-1 structure (above) without the CDR3 analogous loop.
  • Two 12Y-2 monomers (A and B) were identified in the asymmetric unit of the I2 ⁇ 2 ⁇ 2 ⁇ space group.
  • Iterative model building using XtalView and refinement using REFMAC5 allowed a complete trace of A and B monomers including extended CDR3 analogous loops.
  • the electron density was well defined in the CDR3 analogous loop region.
  • Progress of the refinement was monitored using the R ⁇ statistic based on a set encompassing 5% of the observed diffraction amplitudes. Water molecules were added automatically with the program ARP as described for 12Y-1.
  • the final refinement included the TLS parameters for each molecule individually as a TLS group in the asymmetric unit and converged to R and -g- ee values of 0.176 and 0.247 , respectively, for the 18.12-2.18A range of experimental data.
  • 12Y-1 only the libration tensor was significant, though less anisotropic.
  • the final model comprises residues 1 to 113 of the 12Y-2 A and B chains, and 358 water molecules. In total, 93.4% of residues are in the most favoured regions of the Ramachandran plot, with no residues in the generously allowed or disallowed regions. This indicates that the 12Y-2 model is consistent with a highly refined protein structure. Further details are in Table 2.
  • EXAMPLE 3a Data collection and structure determination for 12A-9 and 1A-7 X-ray diffraction data collection for 1 A-7 crystal was conducted in-house using Mar 180 (MarResearch) image plate detectors mounted on a Rigaku HR3 HB X-ray generator equipped with monocapillary focusing optics (AXCO). X-ray diffraction data for 12A-9 crystal was collected at the Photon Factory synchrotron BL5 beamline in Japan. Data for both crystals were collected at -160°C; the crystals required no added cryoprotectant. All data processing was carried out using the DENZO/SCALEPACK suite (Otwinoski 1997). Diffraction data statistics are summarized in Table 2.
  • the structures of 1A-7 and 12A-9 were determined by molecular replacement using CCP4 MOLREP.
  • the search model for 1A-7 was the 12Y-1 two-fold dimer without the CDR3 analogous loops.
  • 1A-7 monomers A, B, C and D
  • Iterative model building using XtalView and refinement using REFMAC5 allowed a complete trace of A and C monomers including CDR3 analogous loops.
  • the electron density was not well defined in the CDR3 analogous loop region (89-98) for monomers B and D.
  • the A & B and C & D chains form two approximately 2-fold dimers (see Figure 15) similar to those observed in 12Y-1 and 12Y-2 structures.
  • the final refinement included the TLS parameters for each molecule individually as a TLS group in the asymmetric unit and converged to R and ?& e e values of 0.176 and 0.265, respectively, for the full 21.6-2.7 A range of experimental data.
  • the final model comprises residues 1 to 111 of the 1A-7 A and C chains, and residues 1-88 and 99-111 for B and D chains, and 489 water molecules. In total, 90.9% of residues are in the most favoured regions of the Ramachandran plot, with 2 residues for chain C in the generously allowed or disallowed regions.
  • EXAMPLE 4 Structure of the crystallographic dimer The inter-dimer relative disposition of monomers can be described as rotation by
  • EXAMPLE 5a Coordinates for 12A-9 and 1A-7 The coordinates for 12A-9 and 1A-7 are attached as Appendices 1(c) and 1(d) respectively.
  • EXAMPLE 6 Modifications to loop regions of 12Y-2 Loop region 8 of 12Y-2 adopts a ⁇ -hai ⁇ in configuration with ⁇ -strands extending for a significant portion of its length, stabilized by main-chain hydrogen bonds. This ⁇ -hai ⁇ in configuration is conserved by main-chain hydrogen bonds, for example, between: Tyr87 (O) - PhelOO (N); Leu89 (N) - Leu98 (O); Leu89 (O) - Leu98 (N).
  • the elongated loop extends outward and upward from the immunoglobulin framework and creates a structure ideal for penetrating buried clefts and cavities in, for example, enzyme active sites, parasite coat proteins, or viral canyons.
  • the following table is a comparison of the length of loop region 8 of 12Y-2 with long CDR3 loops from cleft binding antibodies such as bl2 Ig (targeting HIV gpl20; Saphire 2001); camelid VHH IMEL (targeting lysozyme, Desmyter 1994); and T cell receptor IQRN.
  • the sequence RVGPYSWDDSPQDNYYM may be grafted onto the 12Y-2 scaffold in the vicinity of loop region 8 to form an extended loop corresponding to the anti-HIV antibody bl2 (IHZH) and thereby provide novel binding moiety with an IgNAR scaffold capable of binding HIV gpl20.
  • the grafting may involve, for example, replacement of amino acid residues 86 to 103 of 12Y-2 (or a portion of these residues) with RVGPYSWDDSPQDNYYM.
  • sequence CSKPSDSNC representing a protruding loop of the major surface antigen (HBsAg) from hepatitis B virus (HBV) may be grafted onto the VNAR scaffold 24G-3 (SEQ ID NO: 101), in place of the CDR3 loop.
  • the resulting IgNAR could then be used to assess the interaction of the HBsAg loop with other HBV proteins.
  • the sequence GYRFSNFVI of the anti-HIV antibody bl2 may be grafted onto the 12Y-2 scaffold in the vicinity of loop region 4 and, when combined with the CDR3 loop graft of the anti-HIV antibody bl2 described in (1) above, will enhance the binding affinity to gpl20.
  • the grafting may involve, for example, replacement of amino acid residues 28 to 33 of 12Y-2 (or a portion of these residues) with the sequence GYRFSNFVI.
  • IgNAR protein present varied among the clones (only 4 of 88 produced no detectable protein). This indicates that the CDRl sequence and conformation are also vital to IgNAR expression levels and protein production.
  • Sequence differences map predominantly to the CDRl loop region, with some contribution from framework residues, and have a marked affect on both affinity and protein expression levels.
  • VN AR library was expanded by designing new degenerate oligonucleotide primers for CDR3 (loop region 8) with loop lengths of either 12 or 13 residues and framework residue combination of either: Gly84 + Glul03, or Gln84 + Gly 102. These and other CDR3 combinations were used to construct a further V NAR library of > 2x 10 members.
  • the following new primer oligonucleotides were used: A0295 (SEQ ID NO: 64), A0296 (SEQ ID NO: 62), A0297 (SEQ ID NO: 63) and A0298 (SEQ ID NO: 61).
  • the IgNAR domain was completed using combinations of the primers disclosed in SEQ ID Nos: 47-60.
  • Randomisation of the residues at the tip of loop region 8 for example, from residues Pro90-Ser97, or other such variations, and expansion or contraction of this loop by incorporation or removal of residues, and differing number and strategy of randomised residues.
  • loop region 8 residues Leu98, Leu99 may be made in a similar manner. For example:
  • Leu89 to Ser97 replaced by 7 randomised residues; Leu98 constrained modification according to the nucleic acid encoding formula: (NNK)7 + (SNK)1.
  • a library based on 12Y-2 of size -1x10 s independent clones was constructed using equal representations of these 6 oligonucleotide primers.
  • the library was screened against different strains of Plasmodium falciparum AMAl, i.e. W2MEF and HB3 (not recognised by the parent 12Y-2), and original antigen AMA-1 3D7 (positive control).
  • Figure 18 shows the KH (12Y-2 loop) library panned against different malarial strains.
  • EXAMPLE 7 Proposed modifications to expand the binding face of the VNAR Results presented herein show that the V NAR "CDR2" loop is non-existent, replaced by a short ⁇ -turn at the bottom of the molecule. This is graphically illustrated in Figure 12, where the V NAR "CDR2" is aligned with that of a typical human antibody. The "bottom” position of this loop, combined with the low sequence variability, strongly suggests that this region has little impact on the interaction with antigen. However, the loss of the conventional C" and D strands suggests a possible alternative model for antigen binding, where the extended 12Y-2 loop region 8 combines with the large concave pocket opened in the absence of the conventional CDR2. This concave pocket is a potential antigen binding face.
  • the pocket comprises residues loop region 8, loop region 5 and C & D ⁇ -strands.
  • residues for 12Y-2
  • residues include: Asp33, Tyr37, Glu46, Ser48, Ser50, Ile51, Val59, Lys61, Phe86, Tyr94, Asn95, Tyr96, Leu98, Leu99 & ArglOl.
  • This antigen binding surface is unlike any antibody paratope (the antigen-binding surface of an antibody), since the loop regions are distant from each other (are not in contact) and the antigen contact residues may include framework residues between the loop regions.
  • Ig-like reagent This will form a human binding domain Ig-like reagent with only the variable loop regions derived from non-human sources. These may be particularly useful as cleft-binding "human-Ig-like" reagents, since they possess antigen-binding surfaces different from any known naturally occurring antibody.
  • I-set framework molecules such as NCAM, ICAM or Telokin:
  • NCAM Neural Cell Adhesion Molecule 1
  • CD56 The Neural Cell Adhesion Molecule 1
  • the extracellular domain consists of 5 Ig superfamily domains followed by 2 fibronectin Type 3 domains (see Figure 23(a)).
  • Domain 1 of NCAM is classified within the I-set of the Ig superfamily and is unmodified by glycosylation or other post-translational modification. Coding sequences for the wild-type human NCAM domain 1 (SEQ ID NO: 37) and wild-type human NCAM domains 1+2 (SEQ ID NO: 39) were amplified from a human cDNA library and cloned in-frame into the E.
  • A0657 (SEQ ID No: 77) was used as the forward 5' primer for domain 1.
  • A0658 (SEQ ID No: 78) was used as the reverse 3' primer for domain 1.
  • A0659 (SEQ ID NO: 79) was used as the reverse primer for domain 2.
  • A0979 (SEQ ID NO: 80) was used as the NCAM secondary extension primer. Clones were verified by DNA sequencing. Both the wild-type domain 1 (clone 21H-5: SEQ ID NO: 36) and wild-type domains 1+2 (clone 21G-1: SEQ ID NO: 38) were successfully expressed as soluble protein into the E.
  • Myosin Light Chain Kinase consists of 3 N-terminal Ig-like domains, a calmodulin-binding catalytic domain, and one C-terminal Ig-like domain (see Figure 24(a)). Activation of MLCK following binding by calcium-calmodulin results in phosphorylation of a specific serine in the N-terminus of a myosin light chain, leading to the formation of calmodulin/MLCK signal transduction complexes which allow selective transduction of calcium signals, ultimately causing muscle contraction.
  • FPLC Fast Protein Liquid Chromatography
  • the Ig-like domains flanking the catalytic domain enable binding of MLCK to myosin.
  • Independent transcription of the C-terminal Ig-like domain of MLCK from an internal promoter gives rise to the production of the mature protein, Telokin.
  • Telokin is an I-set Ig domain and has phosphorylation sites at Ser-12 and Ser-18. It appears to modulate MLCK activity by binding to unphosphorylated myosin thus preventing phosphorylation by MLCK.
  • the coding sequence for the human Telokin domain 1 was amplified from a human cDNA library and cloned in-frame into the E. coli cloning/expression vector pGC. A0678 (SEQ ID No: 88) was used as the forward 5' primer.
  • A0677 (SEQ ID NO: 89) was used as the reverse 3 'primer.
  • A0999 (SEQ ID NO: 96) was used as the Telokin N-terminus secondary extension primer.
  • Clone 21 J-4 was correct as verified by DNA sequencing (SEQ ID NO: 42).
  • Telokin domain was successfully expressed as soluble protein (SEQ ID NO: 41) into the E. coli periplasmic space as measured by FPLC (see Figure 24(c)) and SDS-PAGE.
  • VN AR CDR3 structures by visual inspection and for potential stability (energy) according to the modeller objective scores.
  • the best scoring models were for NCAM model 5, and for Telokin model 3 and model 5.
  • NCAM - 1A-7 loop grafts The best NCAM/shark 1A-7 CDR3 loop graft (model 5) was constructed by overlap PCR using oligonucleotide primer A0989 (SEQ ID NO: 81). The resulting clone designated 23B-2 was verified by DNA sequencing (SEQ ID NO: 40). Protein expression and purification showed that the resulting recombinant protein appeared more stable than the wild type, for example there appeared little degradation by SDS-PAGE (see Figure 25(c)), and a single peak by FPLC (see Figure 25(b)). This protein when placed in crystallisation trials gave several strong crystal leads, indicating that it was folded into a stable and ordered structure.
  • Recombinant protein 23B-2 specifically interacted with the target antigen (monoclonal antibody 5G- 8) but not to a negative control antigen (lysozyme) in an ELISA (see Figure 25(d)). Specific binding of the 23B-2 but not wild type NCAM domain 1 was confirmed by Biosensor (see Figure 25(e)).
  • Telokin 1A-7 loop grafts The best Telokin/shark 1 A-7 CDR3 loop grafts (models 3 & 5) were constructed by overlap PCR using oligonucleotide primers A1022 (primary extension primer) (SEQ ID NO: 90) and A1023 (secondary extension primer) (SEQ ID NO: 91) (Model 3), and primers A1024 (primary extension primer) (SEQ ID NO: 92) and A1025 (secondary extension primer) (SEQ ID NO: 93) (Model 5).
  • the resulting clones were designated 24F-4 (SEQ ID NOs: 43 & 44) (model 3) and 23C-7 (SEQ ID NOs: 45 & 46) (model 5), and were verified by DNA sequencing. Protein expression and purification showed that the resulting recombinant proteins were expressed into the E. coli periplasmic space. FPLC traces and SDS- PAGE profiles of the recombinant proteins are shown in Figure 26(b) & (c). Both loop graft model recombinant protein (23C-7, 24F-4) specifically interacted with the target antigen (monoclonal antibody 5G-8) but not a negative control antigen (lysozyme) (see Figure 26(d)). Specific binding of the 24F-4, but not wild type Telokin, was confirmed by Biosensor (see Figure 26(e)).
  • EXAMPLE 9 Generation of therapeutics or diagnostics by loop grafting from human domains to shark V N A R S.
  • the structures of IgNARs human Immunoglobulin superfamily I-set domains are homologous enough to allow prediction of framework/loop region junctions, take- off angles of strands, and loop orientations.
  • I-set domains such as ICAM-1 have been implicated as receptors for viruses such a rhinovirus. Binding loops on ICAM-1 specific for rhinovirus binding can be grafted to VNA R frameworks, giving rise to novel binding moieties. This can be further expanded to other viral diagnostics based on I-set domains. For example, the following modifications may be made to shark NARs:
  • VLRs are the variable loop regions of V-set and I-set domains, these being the loop regions which typically extend between ⁇ -strand conformations and which demonstrate natural amino acid variation without compromising the framework structure of the domain.
  • VLRs include those regions typically referred to as CDRs.
  • EXAMPLE 10 Generation of soluble human variable domains by "sharkisation”: CDR2 region CDR2 loops generated by the C and C" strands of the V-set immunoglobulin superfamily proteins are important in antigen binding and maintenance of the solvent solubility of the immunoglobulin.
  • shark domain CDR2 loop equivalent in “bottom” position there is now a solvent-exposed patch of residues at the C-terminus of loop region 4 and in the C and D ⁇ -strands, which in other immunoglobulin domains is shielded by the CDR2 loop.
  • This solvent-exposed face consists mainly of the 12Y-2 residues Lys32, Asp33, Thr34, Gly35, Tyr55, Glu57, Thr58.
  • residues Asp33-Thr34-Glu57 appears to be particularly significant.
  • these residues may be "transferred” to I-set variable domains, for example neural cell adhesion molecules (NCAMs), to render these proteins more soluble when expressed in a single domain format.
  • NCAMs neural cell adhesion molecules
  • these residues may be "transferred” to V-set domains such as TCRs and antibodies, where the CDR2 loop has been removed to avoid superantigen stimulation. See, for example, the following table:
  • Residue Ser31 in the TCR interface is almost always a serine or tyrosine: thus a polar residue. In VNARS it can be a charged (Asp) residue, or a serine in -50% of cases. Mutation of residue 31 of a TCR domain to Asp may therefore enhance solubility. 2. Significant residues in the TCR domain interface are Pro43/Leu89/Phel06 (and equivalents). This is an extensive hydrophobic patch in TCR V ⁇ and V ⁇ domains. Mutation of these residues to form a charged pocket, similar to that formed by residues Glu46, Lys82, Lys 104 of 12Y-2 may therefore enhance solubility.
  • EXAMPLE 12 Generation of soluble antibody variable domains by "sharkisation”: VH/VL interface Attempts in the past to produce single antibody variable domains have encountered solubility and expression problems. Comparison of the 12Y-1 and 12Y-2
  • VNARS to antibody VH and VL domains shows a number of aspects where these individual domains could be modified by reference to the shark structure, to improve solubility and expression levels. For example:
  • EXAMPLE 13 Modification of V NA R dimers
  • the 12Y-1 & 12 Y-2 dimer forms are a continuous 8-stranded ⁇ -sheet underneath the loop regions (buried surface area at interface -1760 A2).
  • the interactions between the 2-fold monomers involve main-chain ⁇ sheet interactions between D strands and between loop region 8 as well as side-chain interactions and water mediated contacts. This suggests a significant propensity for dimer interactions with non-standard involvement of loop regions in complex formation.
  • the dimer form may act as a single binding entity with the loop region 8 residues and framework residues of the dimer available for mutation and library selection. This suggests that the following modifications may be made to generate binding moieties with potential diagnostic or therapeutic applications: 1.
  • Stabilisation of a recombinant dimer by introduction of cysteine residues at positions Lys61 and Glu57 in the D strand of a VN AR -
  • stabilisation may be achieved by the introduction of cysteine residues at positions Ile51 and either Lys61 or Gly62 in the D strand.
  • EXAMPLE 14 Design, Construction, and Screening of Human I-set domains based on shark IgNAR principles.
  • Shark IgNAR antibodies are structurally close to I-set domain immunoglobulins such as Telokin and domain 1 of NCAM. Specifically, what would otherwise be a CDR2 loop is at the "bottom" of the molecule.
  • the foregoing structural, protein engineering, and library selection experiments suggest that the principles learnt from shark IgNAR antibody structures can be successfully applied to the generation of binding repertoires of human I-set immunoglobulins. Such libraries are anticipated to primarily contain variability in the CDRl and CDR3 analogous regions.
  • the human CDR3 framework was extended by analogy with the successful human/shark model 5 loop grafts, to provide a CDR3 loop extending several residues above the NCAM or Telokin scaffold (NCAM/A0988 library; Telokin/A1017 library).
  • oligonucleotide primers were designed to build human-scaffold-based libraries, based on both NCAM domain 1 and Telokin domain.
  • NCAM library oligonucleotide primers A0980 NCAM CDRl randomisation 6-loop (SEQ ID NO: 82); A0981 NCAM CDRl randomisation 7-loop (SEQ ID NO: 83); A0982 NCAM CDR3 randomisation: rev compl; 8 loop (SEQ ID NO: 84); A0987 NCAM CDR3 randomisation: rev compl; 11 loop (SEQ ID NO: 85); A1018 NCAM CDR3 randomisation: rev compl; 14 loop (SEQ ID NO: 86); A0988 NCAM CDR3 randomisation: rev compl; 8 loop based on Model 5 (SEQ ID NO: 87).
  • Telokin library oligonucleotide primers AlOOl Telokin CDRl randomisation; 7 loop (SEQ ID NO: 94); A1002 Telokin CDRl randomisation; 9 loop (SEQ ID NO: 95); A1000 Telokin CDR3 randomisation: rev compl; 6 loop (SEQ ID NO: 97); A 1003 Telokin CDR3 randomisation: rev compl; 9 loop (SEQ ID NO: 98); A 1004 Telokin CDR3 randomisation: rev compl; 12 loop (SEQ ID NO: 99); A1017 Telokin CDR3 randomisation: rev compl; 9 loop based on Model 5 (SEQ ID NO: 100).
  • Figure 30 shows the results of the panning against amyloid a ⁇ (1-42) peptide (panels and A and B) and CEA (panels and C and D). In particular, binding to antigens (panels A & C) and comparative expression levels of individual clones (panels B & D) are shown.
  • Figure 31 shows the titres of eluted phage from the NCAM library panned against monoclonal antibody 5G8 (- ⁇ -), AMAl (- ⁇ -), Hepatitis B virus E antigen (- A-), ab 1-42 peptide (-x-), Carcino Embryonic Antigen (*); and, the Telokin library panned against monoclonal antibody 5G8 (•).
  • EXAMPLE 15 12Y-2 IgNAR protein stability. Shark blood is rich in urea. Thus IgNAR domains may be hypothesised to have evolved to be unusually resistant to treatment with such harsh chemical agents. Recombinant IgNAR 14M-15 (12Y-2 Pro90Leu variant) (SEQ ID NO: 11) was tested for its ability to refold after denaturation in 8M urea. Regeneration was measured by intrinsic fluorescent intensity (see Figure 32). The IgNAR domain re-folded to its native conformation following removal of the urea. EXAMPLE 16: Full IgNAR Coding Sequence and the production of variable and constant domain reagents for biosensor analysis.
  • the full wobbegong shark (Orectolobus maculatus) IgNAR coding sequence was cloned from shark cDNA (clone designated 18H-2 (SEQ ID NOs: 31 & 32)).
  • the full DNA and amino acid sequences are given in Figure 33.
  • the DNA sequence encodes a single polypeptide chain encompassing one IgNAR I-set domain and 5 C- domains (see Figure 34(a)).
  • these chains form a dimer mediated by half-cystine residues at positions Cys430 and Cys660.
  • the resulting two disulphide bridges are located (1) C-terminal to constant domain 3 and N-terminal to constant domain 4 and (2) C-terminal to constant domain 5.
  • each constant domain is -12 kDa in molecular weight.
  • Sequential addition of constant domains 1, 2, and 3 to an IgNAR variable domain produce a set of single chain monovalent proteins with identical affinity for antigen, but varying in their molecular weight (see table below).
  • addition of the 12 Y-2 variable domain to varying numbers of constant domains produces a set of molecules with identical affinities for the target antigen AMAl, but with varying molecular weights.
  • biosensors many rely on mass differences. These reagents provide an ideal test system of measuring the effect of mass differences for a single affinity.
  • Type 3 IgNAR is similar in CDR3 length and disulphide-bond position to Type 3 IgNARs, which are found in embryonic sharks. See Genbank AAM77190 (SEQ ID NO: 29) and AAM77191 (SEQ ID NO: 30) (Nurse shark Type 3 IgNARs).
  • the Type 3 IgNAR variable domains are characterized by constant length loop regions analogous to CDR3s, disulphide bonds connecting the CDRl and CDR3 analogous loops (wliich happens to be in the same position as in 12 A- 9), and a conserved tryptophan residue at position 31.
  • Figure 35 shows the modeling of Type 3 V NAR AAM77191 based on the 12A-9 crystal structure. The results of four modelling runs are shown compared with the template 12A-9.
  • Figure 36 shows a model of a VNAR Type 3 CDRl and CDR3 analogous regions based on the 12A-9 structure. The isotype has limited diversity with the hypervariable residues (by sequence alignment) depicted in dark grey. The modeling suggests that the conserved Phe96 can adopt a number of structural conformations, dramatically enhancing the antigen-binding range of this antibody, despite the low sequence variability It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.
  • Navaza, J. AMoRe an automated package for molecular replacement. Acta Cryst., A50, 157-163 (1994). Nieba, L., Honegger, A., Krebber, C. & Pluckthun, A. Disrupting the hydrophobic patches at the antibody variable/constant domain interface: improved in vivo folding and physical characterization of an engineered scFv fragment. Protein Eng. 4, 435-444 (1997).
  • the CCP4 Suite Programs for Protein Crystallography, Acta Cryst., D50, 760-763 (1994). Xu, D., Xu, Y. & Uberbacher, E.C. Computational tools for protein modeling, Curr. Protein Pept. Sci., 1(1), 1-21 (2000).
  • Var Variant amino acids : These columns show the variation in amino acid residues found in the corresponding positions in the twelve other Type 2 V NAR s sequences in Figure 1 and in other Type 2 V NARs reported in Nuttall 2002 and 2003.
  • Con Consensus sequence Table 2 : Diffraction data and refinement statist
  • REMARK Bll A**2) 3.53000 REMARK B22 (A**2) 3.53000 REMARK B33 (A**2) -7.06000 REMARK B12 (A**2) 0.00000 REMARK B13 (A**2) 0.00000 REMARK B23 (A**2) 0.00000 REMARK REMARK ESTIMATED OVERALL COORDINATE ERROR.
  • REMARK 300 WHICH CONSISTS OF 1 CHAIN(S). SEE REMARK 350 FOR REMARK 300 INFORMATION ON GENERATING THE BIOLOGICAL MOLECULE (S). REMARK 350 REMARK 350 GENERATING THE BIOMOLECULE REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS REMARK 350 GIVEN BELOW. BOTH NON-CRYSTALLOGRAPHIC AND REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.
  • ATOM 52 CA PRO A 7 39, .187 42, .740 10, ,490 1, ,00 42, .90 C
  • ATOM 78 C ALA A 10 36. ,711 44. ,153 17. ,968 1. ,00 46. ,02 c
  • ATOM 220 CD1 TYR A 29 57, .416 33, ,832 -2, .066 1, ,00 46, .98 c
  • ATOM 227 CA GLY A 30 53, .046 29, .169 -1, ,518 1, .00 46, .80 c
  • ATOM 228 C GLY A 30 53, .063 29, ,488 -0, .029 1, .00 47, .05 c
  • ATOM 244 CD GLU A 32 55, .433 25, ,258 2, .727 1, .00 52, .14 c
  • ATOM 254 CA THR A 34 52, .243 30, .289 10, .107 1. ,00 45, .56 C
  • ATOM 258 OG1 THR A 34 50, .659 28, .479 10, .376 1. .00 47, ,83 O
  • ATOM 261 CA GLY A 35 52, .193 32, .203 13, .362 1. ,00 43, .84 C

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Abstract

The present invention relates to immunoglobulin new antigen receptors (IgNARs) from fish and uses thereof. In particular, the present invention relates to modified IgNAR variable domains and to domains from members of the immunoglobulin superfamily that have been modified to include structural features derived from IgNAR variable domains.

Description

BINDING MOIETIES BASED ON SHARK IgNAR DOMAINS
Field of the Invention The present invention relates to immunoglobulin new antigen receptors (IgNARs) from fish and uses thereof. In particular, the present invention relates to modified IgNAR variable domains and to domains from members of the immunoglobulin superfamily that have been modified to include structural features derived from IgNAR variable domains.
Background of the Invention The immunoglobulin superfamily (IgSF) includes immunoglobulins and numerous other cell surface and soluble molecules that mediate recognition, adhesion or binding functions in the immune system. They share partial amino acid sequence homology and tertiary structural features that were originally identified in immunoglobulin (Ig) heavy and light chains. Molecules of the IgSF are identified by a characteristic IgSF fold structure, a β- sandwich structure formed by two β-sheets, packed face-to-face and linked by a disulphide bond between the B and F strands (Bork 1994; Chothia 1998). IgSF frameworks are further classified into 3-4 major categories, the Variable (V)-, Constant (C)-, I- and I2-sets, based on β-strand number, configuration and hydrogen bond patterns (Bork 1994; Cassasnovas 1998). Conventional immunoglobulins have two heavy polypeptide chains linked by disulphide bonds at a hinge portion, and two light polypeptide chains, each of which is linked to a respective heavy chain by disulphide bonding. Each heavy chain comprises a variable (VH) domain at the N-terminal end and a number of constant (CH) domains. Each light chain has a variable (VL) domain at the N-terminal end and a constant (CL) domain at the C-terminal end, the VL and CL domains aligning with the VH domain and the first CH domain, respectively. Unlike immunoglobulins, T-cell receptors (TCRs) are heterodimers having α and β chains of equal size, each chain consisting of an N-terminal variable domain (Vα or Vβ) and a constant domain. Typically, the variable domains on different polypeptide chains interact across hydrophobic interfaces to form binding sites designed to receive a particular target molecule. In the case of immunoglobulins, each pair of VH/VL domains form an antigen binding site, the CH and CL domains not being directly involved in binding the antibody to the antigen. Similarly, in the case of TCRs, the Vα and Vβ domains form the binding site for target molecules, namely peptides presented by a histocompatibility antigen. The amino acid sequences of variable domains vary particularly from one molecule to another. This variation in sequence enables the molecules to recognise an extremely wide variety of target molecules. Variable domains are often viewed as comprising four framework regions, whose sequences are relatively conserved, connected by three hypervariable or complementarity determining loop regions (CDRs) (Kabat 1983 & 1987; Bork 1994). The CDRs are held in close proximity by the framework regions and, with the CDRs from the other variable domain, contribute to the formation of the binding site. With the development of new molecular biology and recombinant DNA techniques, research interest in the IgSF field has increased. Among the main reasons for this increased interest is the desire to develop novel therapeutics and diagnostics based on immunoglobulins or other IgSF molecules. Using the hybridoma technique developed by Kohler and Milstein, the production of monoclonal antibodies (MAbs) of almost any specificity is now well known. However, the production of human antibodies remains difficult, with the vast majority of MAbs produced being of rodent, in particular mouse, origin. Such antibodies are often antigenic in humans. Researchers have therefore investigated producing modified immunoglobulins which are as "human" as possible, but which still retain the appropriate specificity. For example, "chimeric" antibodies have been constructed in which an animal antigen- binding variable domain is coupled to a human constant domain. The isotype of the human constant domain may be selected to tailor the chimeric antibody for participation in antibody-dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity. However, chimeric antibodies typically may contain about one third rodent (or other non-human species) sequence and consequently are often still capable of eliciting a significant antigenic response in humans. In a further effort to resolve the antigen binding functions of antibodies and to minimize the use of heterologous sequences in human antibodies, others have modified the specific domains by, for example, substituting rodent CDRs for CDR sequences from the corresponding segments of a human antibody. In some cases, substituting CDRs from rodent antibodies for the human CDRs in human frameworks is sufficient to transfer high antigen binding affinity as described in EP 239400. An alternative approach has been to use fragments of immunoglobulins or other molecules of the IgSF. For example, specific binding reagents can be formed by association of only the VH and VL domains into a Fv module. Bacterial expression is then enhanced by joining the variable domains with a linker polypeptide into a single- chain scFv molecule. Methods to improve the expression and folding characteristics of single-chain Fv molecules have been described by Nieba (1997). The properties of single V- domains, derived from natural mammalian antibodies, have been described in WO 90/05144, EP 368684 and WO 91/08482. Single camelid V-domains have been described by WO/96/34103 and in WO/94/25591. A method for reducing the hydrophobicity of the surface of a human VH domain by replacing human amino acid sequences with camelid amino acid sequences was described by Davies and Riechmann (1994). Methods to exchange other regions of human VH sequences with camel sequences to further enhance protein stability, including the insertion of cysteine residues in CDR loops, were described by Davies and Riechmann (1996). Several attempts to engineer high-affinity single domain binding reagents using either the VH or VL domains alone, have been unsuccessful, due to lack of binding specificity and the inherent insolubility of single domains exposing unpaired hydrophobic VH/VL binding faces (Kortt 1995). The TCR has two variable domains that combine into a structure similar to the
Fv module of an antibody that results from combination of the VH and VL domains. Novotny (1991) described how the Vα and Vβ domains of the TCR can be fused and expressed as a single chain polypeptide and, further, how to alter surface residues to reduce the hydrophobicity directly analogous to an antibody scFv. Other publications describe the expression characteristics of single-chain TCRs comprising two Vα and Vβ domains (Wulfing 1994; Ward 1991). The three-dimensional crystal structures have been published for intact immunoglobulins, a variety of immunoglobulin fragments, antibody-antigen complexes and for other IgSF molecules such as the TCR. It is known that the function of IgSF molecules is dependent on their three dimensional structure, and that amino acid substitutions can change the three-dimensional structure of, for example, an antibody (Snow and Amzel 1986). Based upon molecular modelling, it has been shown that the antigen binding affinity of a humanized antibody can be increased by mutagenesis (Riechmann 1988; Queen 1989). The Immunoglobulin New Antigen Receptors (IgNARs) are an unconventional subset of antibodies recently identified in fish. In domain structure, IgNAR proteins are reportedly similar to other immune effector molecules, being disulphide-bonded homodimers of two polypeptide chains having five constant domains (CNARS) and one variable domain (VNAR) (Greenberg 1995). However, unlike conventional antibodies, there are no associated light chains and the individual variable domains are independent in solution and do not appear to associate across a hydrophobic interface (as seen for conventional VH/VL type antibodies) (Roux 1998). IgNARs have been identified in all shark species studied to date. In particular,
IgNARs have been identified in the serum of nurse sharks Ginglymostoma cirratum (Greenberg 1995) and wobbegong sharks Orectolobus maculatus (Nuttall 2001). The cell-surface expression of IgNARs has also been reported (Rumfelt 2002). Research has implicated IgNARs as true molecules of the immune armoury, and as the most probable agents of the shark antigen-driven affinity-maturation antibody response (Diaz 1999; Nuttall 2002; Dooley 2003). IgNARs identified to date have been placed into three categories based on their time of appearance during the shark development and on their postulated disulphide bonding pattern within the variable domains (Diaz 2002; Nuttall 2003). Type 1 VNAR topology is characterised by an extra framework disulphide linkage and, usually, cysteines in the extended loop region analogous to a conventional CDR3 loop, which it has been suggested may form intra-loop disulphide bonds. Type 2 VNAR topology is characterised by cysteines in the loop regions analogous to conventional CDRl and CDR3 loops in approximately two thirds of cases, which it has been postulated may form inter-loop disulphide bonds. Type 3 VNAR topology is characterised by a relatively constant sized loop region analogous to a conventional CDR3 loop of limited diversity and a characteristic conserved tryptophan residue within the loop region analogous to a CDRl loop. Regardless of type, all IgNARs identified to date are reported as having minimally variable loop regions analogous to conventional CDRl and CDR2 loops, with diversity being concentrated in an elongated loop region analogous to a conventional CDR3 loop (Greenberg 1995; Nuttall 2001; Diaz 2002). The elongated loop region can reportedly vary in length from 5 to 23 residues in length, though the modal classes are more in the order of 15 to 17 residues (Nuttall 2003). This is significantly larger than for conventional murine and human antibodies, but approximate to the extended CDR3 loops found in camelid single VH antibodies (Wu 1993; Muyldermans 1994). Large bacteriophage libraries have been generated based upon the Type 2 VNAR repertoire from wobbegong sharks and used to isolate a number of Type 2 VNARS proteins encapsulating significant variability within the framework and the loop region analogous to a conventional CDRl loop. However, the most significant diversity was within the extended loop region analogous to a conventional CDR3 loop, the extended loop region varying in both length and amino acid composition (Nuttall 2001; Nuttall 2003). Various computer-modelled structures for Type 2 V A S have been reported in the literature (Roux 1998; Nuttall 2001; Diaz 2002; Nuttall 2004). Although such computer modelling can offer key insights into structure, the definitive structure remains to be determined from crystallographic analysis. In the case of VNARS, the elucidation of the crystal structure is particularly important.
Summary of the Invention In a first aspect, the present invention provides a crystal of a variable domain of a Type 2 IgNAR that effectively diffracts X-rays for the determination of the atomic coordinates of the variable domain of the IgNAR to a resolution of better than 4.0A, wherein the variable domain of the Type 2 IgNAR consists of 105 to 125 amino acid residues and comprises an amino acid sequence according to Table 1 and/or Figure 1. In another aspect, the present invention provides a crystal of a variable domain of a Type 2 IgNAR comprising a structure defined by all or a portion of the coordinates of Appendix 1(a), (b), (c) or (d) + a root mean square deviation from the Cα atoms of less than 0.5 A. In another aspect, the present invention provides a method of homology modelling comprising the steps of: (a) aligning a representation of an amino acid sequence of an IgSF domain with the amino acid sequence of 12Y-1, 12Y-2, 12A-9 or 1A-7 as shown in Figure 1 to match homologous regions of the amino acid sequences; (b) modelling the structure of the matched homologous regions of said IgSF domain on the corresponding regions of the 12Y-1, 12Y-2, 12A-9 or 1A-7 structure as defined by Appendix 1(a), (b), (c) or (d); and (c) determining a conformation (e.g. so that favourable interactions are formed within the IgSF domain and/or so that a low energy conformation is formed) for said IgSF domain which substantially preserves the structure of said matched homologous regions. In another aspect, the present invention provides a method for determining the structure of a protein, which method comprises; providing the co-ordinates of Appendix 1(a), (b), (c) or (d), and either (a) positioning the co-ordinates in the crystal unit cell of said protein so as to provide a structure for said protein or (b) assigning NMR spectra Peaks of said protein by manipulating the coordinates of Appendix 1(a), (b), (c) or (d). In another aspect, the present invention provides systems, particularly a computer system, the systems containing at least one of the following: (a) atomic coordinate data according to Appendix I, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7 or at least selected coordinates thereof; (b) structure factor data (where a structure factor comprises the amplitude and phase of the diffracted wave) for 12Y-1, 12Y-2, 12A-9 or 1A-7, said structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of an IgSF domain generated by homology modelling of the IgSF domain based on the data of Appendix I; (d) atomic coordinate data of the IgSF domain generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Appendix I; and (e) structure factor data derivable from the atomic coordinate data of (c) or (d). In another aspect, the present invention provides a computer-readable storage medium, comprising a data storage material encoded with computer readable data, wherein the data are defined by all or a portion (e.g. selected coordinates as defined herein) of the structure coordinates of 12Y-1, 12Y-2, 12A-9 or 1A-7, or a variant of 12Y-1, 12Y-2, 12A-9 or 1A-7, wherein said variant comprises backbone atoms that have a root mean square deviation from the Cα or backbone atoms (nitrogen-carbonα- carbon) of Appendix I of less than 2 A, such as not more than 1.5 A, preferably less than 1.5 A, more preferably less than 1.0 A, even more preferably less than 0.74 A, even more preferably less than 0.72 A and most preferably less than 0.5 A. In another aspect, the present invention provides a computer-readable data storage medium comprising a data storage material encoded with a first set of computer-readable data comprising a Fourier transform of at least a portion (e.g. selected coordinates as defined herein) of the structural coordinates for 12Y-1, 12Y-2, 12A-9 or 1A-7 according to Appendix I; which, when combined with a second set of machine readable data comprising an X-ray diffraction pattern of a molecule or molecular complex of unknown structure, using a machine programmed with the instructions for using said first set of data and said second set of data, can determine at least a portion of the structure coordinates corresponding to the second set of machine readable data. In another aspect, the present invention provides computer readable media with at least one of: (a) atomic coordinate data according to Appendix I recorded thereon, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, or at least selected coordinates thereof; (b) structure factor data for 12Y-1, 12Y-2, 12A-9 or 1A-7 recorded thereon, the structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of a target IgSF domain generated by homology modelling of the IgSF domain based on the data of Appendix 1; (d) atomic coordinate data of a modified IgSF domain generated by interpreting X- ray crystallographic data or NMR data by reference to the data of Appendix I; and (e) structure factor data derivable from the atomic coordinate data of (c) or (d). In another aspect, the present invention provides a method of providing data for generating structures and/or performing rational drug design for IgSF domains, the method comprising: (i) establishing communication with a remote device containing computer-readable data comprising at least one of: (a) atomic coordinate data according to Appendix I, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, at least one sub-domain of the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, or the coordinates of a plurality of atoms of 12Y-1, 12Y-2, 12A-9 or 1A-7; (b) structure factor data for 12Y-1, 12Y-2, 12A-9 or 1A-7, said structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of a modified IgSF domain generated by homology modelling of the domain based on the data of Appendix I; (d) atomic coordinate data of a protein generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Appendix I; and (e) structure factor data derivable from the atomic coordinate data of (c) or (d); and (ii) receiving said computer-readable data from said remote device. In another aspect, the present invention provides a method of altering a property of an IgNAR variable domain comprising eight β-strand regions, designated A, A', B, C, D, E, F and G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2, said method comprising modifying the IgNAR variable domain within at least one of the β-strand regions or loop regions. In another aspect, the present invention provides a binding moiety comprising a modified IgNAR variable domain produced by a method according to any one of claims 1 to 5. In another aspect, the present invention provides a binding moiety comprising an IgNAR variable domain comprising eight β-strand regions, designated A, A', B, C, D, E, F and G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2, wherein the IgNAR variable domain has been modified within at least one of the β-strand regions or loop regions. In a further aspect, the present invention provides a method of modifying an I- set domain, said method comprising inserting and/or substituting one or more structural features from an IgNAR variable domain into the I-set domain. In another aspect, the present invention provides a binding moiety comprising a
I-set domain, wherein the I-set domain has been modified by insertion and/or substitution of one or more structural features from an IgNAR variable domain into the
I-set domain and/or by introducing a modification into a region equivalent to loop region 4 or loop region 8 of an IgNAR variable domain In a further aspect, the present invention provides a method of modifying a V- set domain, said method comprising inserting and/or substituting one or more structural features from an IgNAR variable domain into the V-set domain. In another aspect, the present invention provides a binding moiety comprising a V-set domain, wherein the V-set domain has been modified by insertion and/or substitution of one or more structural features from an IgNAR variable domain into the
V-set domain and/or by introducing a modification into a region equivalent to loop region 4 or loop region 8 of an IgNAR variable domain. In another aspect, the present invention provides a binding moiety comprising a multimer comprising:
(i) at least two IgNAR domains, which may be the same or different, and at least one of which is a IgNAR variable domain; (ii) at least two I-set domains, which may be the same or different, and at least one of which is a I-set domain according to the present invention; or (iii) at least two V-set domains, which may be the same or different, and at least one of which is a V-set domain according to the present invention. In another aspect, the present invention provides a binding moiety according to the invention linked to a diagnostic reagent. In another aspect, the present invention provides a binding moiety according to the invention immobilised on a solid support or coupled to a biosensor surface. In another aspect, the present invention provides a polynucleotide encoding a binding moiety according to the invention. In another aspect, the present invention provides a vector comprising a polynucleotide according to the present invention. In another aspect, the present invention contemplates a host cell comprising a vector according to the invention. In another aspect, the present invention provides a method of producing a binding moiety according to the invention which comprises culturing a host cell of the present invention under conditions enabling expression of the binding moiety according to the invention and optionally recovering the a binding moiety. In another aspect, the present invention provides a pharmaceutical composition comprising a binding moiety according to the invention and a pharmaceutically acceptable carrier or diluent. In another aspect, the present invention provides a method of treating a pathological condition in a subject, which method comprises administering to the subject a binding moiety according to the invention. In another aspect, the present invention provides a method of selecting a binding moiety according to the invention with an affinity for a target molecule which comprises screening a library of polynucleotides of the present invention for expression of a binding moiety according to the invention with an affinity for the target molecule. In a further aspect, the present invention provides a polynucleotide library comprising a plurality of polynucleotides encoding binding moieties according to the invention, which polynucleotides comprise one or more modifications in the IgNAR variable domain, I-set domain or V-set domain.
Brief Description of the Figures
Figure 1. Amino acid sequence alignment of VNARS 12Y-1, 12Y-2, 12A-9 and 1A-7 with 12 naturally occurring Type 2 IgNAR variable domain sequences. Figure 2. 2D topology diagram of the 12Y-1, 12Y-2, 12A-9 and 1A-7 folds showing the loop regions and β-strand regions. The labelled 8 strands form a sandwich of 2 sheets: front and back sheets are shown with thick and thin arrows, respectively. The switch of N-terminal strand A to A', adjacent to the bulge in the C-terminal strand G, is shown as a kink between the A and A' strands.
Figure 3. Detailed 2D topology diagram of the 12Y-1, 12Y-2, 12A-9 and 1A-7 folds showing the loop regions and β-strand regions. The labelled 10 strands form a sandwich of 2 sheets: front and back sheets are shown with thick and thin arrows, respectively. The disulfide bond is indicated as a horizontal line connecting the B and
F strands. The switch of N-terminal strand A to A', adjacent to the bulge in the C- terminal strand G, is shown as a kink between the A and A' strands.
Figure 4. H-bond pattern of the 12Y-2 β-sheets. β-sheets are presented as filled circles, and broken lines represent H-bonds between main-chain atoms.
Figure 5. Stereo images of superimposed IgSF domains in ribbon representation of the
12Y-2 A chain, the 12Y-2 B chain and the 12Y-1 chain. Figures were produced using
VMD. The CDRl analogous region (loop region 4) and CDR3 analogous region (loop region 8) are labelled. Figure 5a. Stereo images of superimposed 1A-7 A chain, 1A-7 C chain and 12Y-2 A chain. Figures were produced using VMD. The CDRl analogous region (loop region
4) and CDR3 analogous region (loop region 8) are labeled.
Figure 6. Stereo images of superimposed IgSF domains in ribbon representation of the
12Y-2 A chain, Telokin(lFHG) and the NCAM domain 1 (1QZ1). Figures were produced using VMD.
Figure 7. Stereo images of superimposed IgSF domains in ribbon representation of the
12Y-2 A chain, human TCR Vα (1A07), human VH and VL (1IGM), and camel VHH
(1MEL). Figures were produced using VMD.
Figure 8. CDR analogous regions in VNAR 12Y-2. The 12Y-2 chain A structure in ribbon representation is overlayed with transparent molecular surface. The positions of the CDRl, "CDR2" and CDR3 analogous regions are indicated.
Figure 9. CDR analogous regions in VNAR 12Y-2. Overlay of the CDRl analogous region (loop region 4) of the 12Y-2 chain A and the CDRl of human VL (1HZH)
(r.m.s.d. 1.22A2) in liquorice representation. Figure 10. CDR analogous regions in VNAR 12Y-2. Positioning of the CDRl analogous region (loop region 4) and the CDR3 analogous region (loop region 8) in the 12Y-2 chain A in ribbon representation. Residues Phe29 and Lys32 (possible half- cystine positions) are oriented toward the CDR3 analogous region (loop region 8), ideally placed to make inter-loop contacts.
Figure 11. CDR analogous regions in VNAR 12Y-2. Backbone of CDR3 analogous region (loop region 8) in the 12Y-2 chain A (86-103). β-hairpin main-chain hydrogen bonds are shown by dashed lines. Residues at the mutation positions (Pro90Leu and PhelOOLeu) and residues at the tip of the loop (Tyr94 and Tyr96) are shown with side- chains. Figure 12. CDR analogous regions in VNAR 12Y-2. Overlay of the backbone "CDR2" region (loop region 5) of the 12Y-2 chain A in liquorice representation and CDR2 of human VH (lhzh) in ribbon semitransparent representation. This figure was produced using VMD.
Figure 13. Structures of the VNAR 12Y-2 2-fold symmetry dimer. (a) View from the top of the CDR3 analogous region (loop region 8) and (b) side view. Each chain is shown in ribbon representation. The N and C termini, and the CDRl analogous region (loop region 4) and CDR3 analogous region (loop region 8) of each chain are labelled. Figure 14. MOLSCRIPT/RASTERED3D diagram of the 12A-9 chain. The chain is shown in ribbon representation. Cysteine residues are shown as ball-and-sticks. Figure 15. MOLSCRIPT/RASTERED3D diagrams of (a) 1A-7 chain A, (b) 1A-7 chain A and B dimer, and (c) 1A-7 chains A, B, C and D in the asymmetric unit of crystal structure. Each chain is shown as a ribbon representation. The N- and C- termini and the CDR analogous regions are labeled.
Figure 16. ELISA analysis of 12 14M-15 variants (12Y-2 with Pro90Leu) for binding to AMA1 and a control negative antigen. Comparative expression levels are also shown. The CDRl analogous region (loop region 4) has been shuffled in the variants. Figure 17. Amino acid sequence alignment of 14M-15 variant IgNAR clones in which the CDRl analogous region (loop region 4) has been shuffled. Five clones with affinity for the AMA-1 antigen (24A-82, 24A-72, 24A-58, 24A-75, 24A-46) and five with no affinity (24A-24, 24A-28, 24A-33, 24A-10, 24A-19) are shown. Sequence differences map predominantly to the CDRl analogous region (loop region 4), with some contribution from framework residues. Figure 18. Titres of total eluted phage from 12Y-2 loop library panned against different malarial strains: W2MEF (-♦-), W2MEF (-■-), W2/HB/W2/3D7 (- A-), HB3 (-X-), HB3 (-*-), HB/W2/HB/3D7 (-•-). The initial titre of phage added for reading 1 pan is taken as the zero reading. Figure 19. Schematic diagram of loop region 8 (analogous to CDR3) variability for IgNAR libraries. Loop region 8 varies in length and in coding sequence and randomization strategy. Generations 1 to 3 are based on the existing shark libraries. Generation 4 libraries were designed with reference to the structures of 12Y-1 and 12Y-2. Oligonucleotides A0298, A0296, A0297, A0295, 8477, 8476, 7210, 7211, 6980 and 6981 correspond to SEQ ID Nos: 61-70, respectively.
Figure 20. Schematic diagram of loop region 8 (analogous to CDR3) variability for IgNAR libraries based on the 12Y-2 structure. The tip of the 12Y02 loop region 8 is modified by 6 different strategies, varying in amino acid randomisation, loop length and amino acid variation pattern. Oligonucleotides KH0001RC, KH0002RC, KH0003RC, KH0004RC, KH0005RC and KH0006RC correspond to SEQ ID Nos: 71- 76, respectively.
Figure 21. (a) Modelled liquorice representation of CDR3 analogous loop (loop region 8) of the 12Y-2 structure showing the position of the Leu89 and Ser97 residues, (b) Portion of the 12Y-2 nucleotide/amino acid sequences showing the CDR3 analogous region (light shade), (c) Schematic diagram of loop region 8 (analogous to CDR3) libraries based on the 12Y-2 structure, where the tip of the 12Y-2 loop region 8 has been modified by 6 different strategies, varying in amino acid randomisation, loop length, and amino acid variation pattern. Figure 22: (a) ELISA analysis of 40 12Y-2 variants binding to AMA-1 and a control negative antigen, (b) Alignment of 12Y-2 variants 22A-2 (Thr39Ser; Pro90Leu) and 14M-15 (Pro90Leu). (c) Three-dimensional structure of 12Y-2 illustrating affinity- enhancing CDRl and CDR3 mutation and the framework affinity-enhancing mutation Thr39Ser. (d) FPLC traces of 12Y-2 variants 14M-15 and 22A-2. Both show identical expression and folding characteristics, (e) Biosensor traces of purified 12Y-2 variant proteins 14M-15 and 22A-2. 22A-2 shows 2-fold enhanced affinity over 14M-15 (20- fold better affinity than 12Y-2). Figure 23: (a) Schematic figure of NCAM (CD56) ectodomain showing Ig superfamily and fibronectin domains, (b) Amino acid sequences of NCAM domain 1 (21H-5) and domain 1+2 (21G-1) recombinant proteins. Dual C-terminal FLAG affinity tags are not shown, (c) FPLC traces of NCAM domain 1 (21H-5) and domain 1 +2 (21 G- 1 ) recombinant proteins .
Figure 24: (a) Schematic figure of Myosin Light Chain Kinase showing Ig, catalytic, and Telokin domains, (b) Protein sequences of human wild type Telokin (21J-4). Dual C-terminal FLAG affinity tags are not shown, (c) FPLC trace of Telokin (21J-4) recombinant protein. Figure 25: (a) Alignment of NCAM domain 1 (21H-5) and loop-graft variant 23B-2. Dual C-terminal FLAG affinity tags are not shown, (b) FPLC traces of NCAM domain 1 (21H-5) and loop-graft variant 23B-2 recombinant proteins. Protein 23B-2 shows a "cleaner" profile, (c) SDS-PAGE profiles of NCAM domain 1 (21H-5) and domain 1 loop-graft variant 23B-2. NCAM domain 1+2 (21G-1) is shown for comparison, (d) ELISA analysis showing binding of NCAM domain 1 loop-graft variant 23B-2 to the target antigen (monoclonal antibody 5G-8) but not to negative control antigens. The parental anti-5G-8 IgNAR (1 A-7) similarly binds, but not the wild type NCAM domain 1 or domain 1+2. (e) Biosensor traces of NCAM domain 1 (21H-5) and loop-graft variant 23B-2 recombinant proteins. The loop graft protein binds. The wild type does not.
Figure 26: (a) Alignment of Telokin (21J-4) and loop-graft variants 23C-7 and 23F-4. Dual C-terminal FLAG affinity tags are not shown, (b) FPLC traces of recombinant proteins 21J-4, 23C-7, and 23F-4. (c) SDS-PAGE profiles of recombinant proteins 21J-4, 23C-7, and 23F-4. (d) ELISA analysis showing binding of Telokin loop-graft variants 23C-7 and 23F-4 to the target antigen (monoclonal antibody 5G-8) but not to negative control antigens. The parental anti-5G-8 IgNAR (1A-7) similarly binds, but not the wild type Telokin (21 J-4). (e) Biosensor traces of Telokin (21J-4) and loop- graft variant 23F-4 recombinant proteins. The loop graft protein binds. The wild type does not. Figure 27: (a) Alignment of 12Y-2 variants 14M-15 and 21B-5. (b) Affinity purified proteins 21B-5 and 14M-15 binding to the target antigen AMA1 and a negative control antigen, (c) FPLC traces of 12Y-2 variants 14M-15 and 21B-5, the disulphide-bonded dimer runs as a dimer. (d) Biosensor traces of purified 21B-5 monomeric and dimeric forms. The disulphide-bonded dimer does not bind the target antigen, demonstrating both the importance of the CDR3 and that the novel dimer form presents a different interface to antigen than the monomeric protein, (e) SDS-PAGE and western blot analysis 12Y-2 variants 14M-15 and 21B-5. The disulphide-bonded dimer runs as a dimeric form in the absence of reducing agent (β-mercaptoethanol). Incorporation of Leu99Cys drives the dominant protein form to dimer. Figure 28: Schematic diagram of CDRl and CDR3 variability for NCAM domain 1 libraries. CDRl and CDR3 both vary in length and in coding sequence and randomization strategy. The NCAM wild type sequence is given for comparison. Framework residues N- and C-terminal to the CDR loop regions are also shown. Figure 29: Schematic diagram of CDRl and CDR3 variability for Telokin libraries. CDRl and CDR3 both vary in length and in coding sequence and randomization strategy. The Telokin wild type sequence is given for comparison. Framework residues N- and C-terminal to the CDR loop regions are also shown. Figure 30. Immunopanning of NCAM domain 1 library by bacteriophage display against amyloid aβ (1-42) peptide (panels A & B) and the Carcino Embryonic Antigen (CEA) (panels C & D). Binding to antigens (panels A & C) and comparative expression levels of individual clones (panels B & D) are shown.
Figure 31. Figure 30a: Titres of eluted phage/ml from NCAM library panned against monoclonal antibody 5G8 (-♦-), AMA1 (-■-), Hepatitis B virus E antigen (- A-), ab 1- 42 peptide (-x-), Carcino Embryonic Antigen (*); and, the Telokin library panned against monoclonal antibody 5G8 (•). Figure 32: Fluorescent intensity graph following regeneration of VNAR 14M-15 (12Y-
2 Pro90Leu variant) after denaturation in 8M urea.
Figure 33: The full wobbegong shark (Orectolobus maculatus) IgNAR coding sequence.
Figure 34: (a) Cartoon of 17T-6 protein, with 12Y-2 variable and constant domain.1. (b) Comparative FPLC traces of IgNARs 12Y-2 and 17T-6. (c) SDS PAGE of IgNARs 12Y-2 and 17T-6. (d) Biosensor traces of equal masses of IgNARs 12Y-2 and 17T-6 binding to immobilized AMAl .
Figure 35. Modelling of Type 3 IgNAR AAM77191 based on the 12A-9 crystal structure. The results of four modelling runs are shown compared with the template 12A-9. Run 1 = Loopref; run 2 = Loopref_cis; run 3 = Nolloopref; run 4 =
Noloopref_cis. Two solutions were selected from the top ten of each with buried Trp 31 residues and illustrating the variability of the Phe 96 in the modelling solutions. Figure 36. Model of IgNAR Type 3 CDRl and CDR3 analogous regions (and some framework residues) based on the 12A-9 structure. This isotype has limited diversity. Hypervariable residues (by sequence alignment) are shown in dark grey.
Detailed Description of the invention All publications discussed above are incorporated herein in their entirety. Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is solely for the purpose of providing a context for the present invention. It is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present invention as it existed before the priority date of each claim of this application. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art (e.g., in molecular biology and biochemistry). Standard techniques are used for molecular and biochemical methods (see generally, Sambrook et al, Molecular Cloning: A Laboratory Manual, 3rd ed. (2001) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. and Ausubel et al, Short Protocols in Molecular Biology (1999) 4th Ed, John Wiley & Sons, Inc. - and the full version entitled Current Protocols in Molecular Biology, which are incorporated herein by reference) and chemical methods. Throughout the specification the word "comprise", or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps. By "hydrophobic residues" or "nonpolar residues" as used herein is meant valine, leucine, isoleucine, methionine, phenylalanine, tyrosine, and tryptophan. By "polar residues" herein is meant serine, threonine, histidine, aspartic acid, asparagine, glutamic acid, glutamine, arginine, and lysine. We have previously identified two closely related IgNAR variable domains
(VNARS) targeting the apical membrane antigen- 1 (AMA1) of Plasmodium falciparum malarial parasites (Nuttall 2004). These proteins, designated 12Y-1 (SEQ ID NOs: 1 & 2) and 12Y-2 (SEQ ID NOs: 3 & 4), were isolated from a library containing a broad mixture of Type 2 VNAR framework scaffolds derived from the native wobbegong shark repertoire, combined with both naturally occurring and synthetic loop regions analogous to CDR3 sequences (Nuttall 2003). We have now isolated two further IgNAR variable domains designated 12A-9 and 1A-7. VNAR 12A-9 (SEQ ID NOs: 9 & 10) was isolated from a library containing a broad mixture of naturally occurring Type 2 VNAR framework scaffolds derived from the wobbegong shark by biopanning against the Gingipain K protease from Porphyromonas gingivalis (Nuttall et al. 2002). This IgNAR is completely natural, including the CDR3 analogous loop region (loop region 8). In common with many IgNAR variable domains, a disulphide bridge links and stabilises the CDRl and CDR3 analogous loop regions, in this case connecting residues Cys29 and Cys89. VNAR 1A-7 (SEQ ID NOs: 5 & 6) is specific for the anti-AMA-1 mouse IgG
5G8 and was isolated using the same procedure as described for the isolation of 12Y-1 and 12Y-2, i.e. biopanning of the phage displayed IgNAR library. Binding is through an "SYP" motif found in the 1 A-7 "synthetic" CDR3 analogous loop region (i.e. loop region 8). While the 12Y-1, 12Y-2 and 1A-7 loop regions analogous to conventional
CDR3 loops fit into the synthetic category, their lengths (16, 18 and 16 residues, respectively) and amino acid composition are typical of naturally occurring IgNAR antibodies. 12A-9 is a naturally occurring shark IgNAR and has a loop region of length 13 residues analogous to a conventional CDR3 loop. Figure 1 presents the sequence alignments of 12Y-1, 12Y-2, 12A-9, 1A-7 and twelve naturally occurring Type 2 VNARS: 7E-22 (SEQ ID NO: 17), 7E-23 (SEQ ID NO: 18), 7E-51 (SEQ ID NO: 19), 7E-54 (SEQ ID NO: 20), 7E-56 (SEQ ID NO: 21), 7E-58 (SEQ ID NO: 22), 7E-68 (SEQ ID NO: 23), 7E-77 (SEQ ID NO: 24), 7E-80 (SEQ ID NO: 25), 7E-87 (SEQ ID NO: 26), 7E-91 (SEQ ID NO: 27), 7E-93 (SEQ ID NO: 28). Half cysteine residues occur in ~2/3rds of cases in loop regions 4 and 8 (as defined herein), forming a disulphide bridge between the loops analogous to conventional CDRl and CDR3 loops. 12A-9 has cysteine residues is both loop region 4 and loop region 8. 12Y-1, 12Y2 and 1A-7 contain no cysteine residues in loop regions 4 and 8. Table 1 shows the amino acid variation across the sixteen Type 2 VNARS sequences in Figure 1 and the Type 2 VNARS sequences reported by Nuttall (2002 & 2003). It is evident from Figure 1 and Table 1 that there is a large degree of conservation of sequence outside of the loop regions analogous to conventional CDRl and CDR3 loops. We have now successfully generated crystals of 12Y-1, 12Y-2, 12A-9 and 1A-7 and have determined the structures of these proteins. Furthermore, we have compared these structures with a range of known immune molecules, i.e. members of the immunoglobulin superfamily. 12Y-1 and 12Y-2 VNARS were expressed in Escherichia coli and placed into crystallization trials in the presence or absence of AMA1 antigen. No crystal leads were observed in the presence of antigen, possibly due to the intrinsically flexible domain structure of the AMA1 protein (Hodder 1996). In contrast, good quality crystals were obtained for both 12Y-1 (space group 14^2) and 12Y-2 (space group I2ι2ι2ι) in the absence of antigen. 12A-9 and 1A-7 VNARS were expressed in Escherichia coli and placed into crystallization trials. Successful conditions were scaled up and diffraction quality crystals obtained for both 12A-9 (space group P21212) and 1 A-7 (space group I2ι212ι). Data sets generated for 12Y-1 and 12Y-2 crystal forms resisted solution by standard molecular replacement techniques, using a broad range of immunoglobulin superfamily proteins as template. We believed this was indicative of the unique nature of these proteins, thus the 12Y-1 structure was solved ah initio by phasing with two isomoφhous heavy atom derivatives (Lutetium (III) Acetate Hydrate: LAH, and Potassium Hexachloro Rhenium: PHR). However, this structure was incomplete, lacking residues Phe88 to Pro98, most likely due to inherent flexibility of the loop region analogous to a conventional CDR3 loop within this crystal form. The complete 12Y-2 structure was then solved by molecular replacement using the 2.8 A 12Y-1 structure as a model. Whereas the 12Y-1 asymmetric unit contains one molecule, the 12Y-2 crystal asymmetric units contain two molecules (Chains A; B); the relative disposition of these two 12Y-2 monomers requires rotation by 176.2° and screw translation by -l.lA to overlay the Cα atoms. The final 12Y-2 structure was refined to 2.18A resolution, with 93.4% of residues in the most favoured regions of the Ramachandran plot with no residues in the generously allowed or disallowed regions. Details of the diffraction data and refinement statistics are presented in Table 2. The coordinates for 12Y-1 and 12Y-2 are attached as Appendix 1(a) and (b) respectively. The structures of 12A-9 and 1A-7 were determined by molecular replacement. The search model for 12A-9 was the 12Y-1 structure (above) without the CDR3 loop. The search model for 1A-7 was the 12Y-1 two-fold dimer structure without the CDR3 loops. In the final 12A-9 structure, 88.4% of the residues are in the most favoured regions of the Ramachandran plot, with one residue in the generously allowed or disallowed regions. In the final 1A-7 structure, 90.9%) of the residues are in the most favoured regions of the Ramachandran plot, with two residues for chain C in the generously allowed or disallowed regions. Details of the diffraction data and refinement statistics are presented in Table 2. The coordinates for 12A-9 and 1 A-7 are attached as Appendix 1(c) and (d), respectively. Thus, is a first aspect, the present invention provides a crystal of a variable domain of a Type 2 IgNAR that effectively diffracts X-rays for the determination of the atomic coordinates of the variable domain of the IgNAR to a resolution of better than 4.θA, wherein the variable domain of the Type 2 IgNAR consists of 105 to 125 amino acid residues and comprises an amino acid sequence according to Table 1 and/or Figure 1. It will be understood that reference herein to comprising an amino acid sequence according to Table 1 includes amino acid sequences having a high degree of sequence homology with the consensus sequence given in Table 1. Preferably, amino acid sequences will have at least 80%, more preferably at least 85% and yet more preferably at least 90% sequence identity with the consensus sequence in Table 1. Preferably, amino acid sequences will have at least 90%, more preferably at least 95% sequence identity with those residues in the consensus sequence in Table 1 that are totally conserved. It will be understood that reference herein to comprising an amino acid sequence according to Figure 1 includes amino acid sequences having at least at least 80%, more preferably at least 85% and yet more preferably at least 90% sequence identity with a sequence shown in Figure 1. For the avoidance of doubt, the sequence identity figures given above in respect of Table 1 and Figure 1 exclude the variable regions in Table 1 and corresponding variable regions in Figure 1. In one embodiment, the crystal has a space group 14^2 with unit cell dimensions of a= 97.26 A, b= 97.26 A and c= 65.23 A, and a unit cell variability of 5% in all dimensions. In another embodiment, the crystal has a space group \2 2{2\ with unit cell dimensions of a= 65.28 A, b= 92.05 A and c= 98.22 A, and a unit cell variability of 5% in all dimensions. In another embodiment, the crystal has a space group P21212 with unit cell dimensions of a= 38.27 A, b= 68.32 A and c= 39.51 A, and a unit cell variability of 5% in all dimensions. In another embodiment, the crystal has a space group \2{2\2\ with unit cell dimensions of a= 80.50 A, b= 88.66 A and c= 101.75 A, and a unit cell variability of 5% in all dimensions. Preferably, the crystals effectively diffract X-rays to a resolution of better than 3.θA, more preferably better than 2.5 A. In a further aspect, the present invention provides a crystal of a variable domain of a Type 2 IgNAR comprising a structure defined by all or a portion of the coordinates of Appendix 1(a), (b), (c) or (d) + a root mean square deviation from the Cα atoms of less than 0.5 A. The IgNAR domain structures set out in Appendices 1(a), (b), (c) and (d) are monomer structures. This is the first time that a monomer has been observed crystallographically for an IgNAR variable domain. In Appendices 1(a), (b), (c) and (d), the third column denotes the atom type, the fourth column the residue type, the fifth column the chain identification, the sixth column the residue number (the atom numbering as described in Hong (2000)), the seventh, eighth and ninth columns the X, Y, Z coordinates, respectively, of the atom in question, the tenth column the occupancy of the atom, the eleventh column the temperature factor of the atom, and the last the atom type. Each of the Appendices is presented in an internally consistent format. For example, the coordinates of the atoms of each amino acid residue are listed such that the backbone nitrogen atom is first, followed by the C-α backbone carbon atom, designated CA, followed by the carbon and oxygen of the protein backbone and finally side chain residues (designated according to one standard convention). Alternative file formats (e.g. such as a format consistent with that of the EBI Macromolecular Structure Database (Hinxton, UK)) which may include a different ordering of these atoms, or a different designation of the side-chain residues, may be used or preferred by others of skill in the art. However it will be apparent that the use of a different file format to present or manipulate the coordinates of the Appendices is within the scope of the present invention. As discussed herein, we have identified structural features in 12Y-1, 12Y-2, 12A-9 and 1A-7 IgNAR variable domains that are important for antigen binding or solubility/stability of these domains. These features can be introduced into domains of other members of the IgSF (for example, I-set or V-set domains) in order to alter binding properties or to improve solubility and/or stability. The information presented in Appendix I can be used, for example, to compare structures of IgSF domains that have been modified so as to more closely resemble the structure of IgNAR variable domains. Protein structure similarity is routinely expressed and measured by the root mean square deviation (r.m.s.d.), which measures the difference in positioning in space between two sets of atoms. By "root mean square deviation" we mean the square root of the arithmetic mean of the squares of the deviations from the mean. The r.m.s.d. measures distance between equivalent atoms after their optimal superposition. The r.m.s.d. can be calculated over all atoms, over residue backbone atoms (i.e. the nitrogen-carbon-carbon backbone atoms of the protein amino acid residues), main chain atoms only (i.e. the nitrogen-carbon-oxygen-carbon backbone atoms of the protein amino acid residues), side chain atoms only or more usually over C-α atoms only. For the purposes of this invention, the r.m.s.d. can be calculated over any of these, using any of the methods outlined below. Methods of comparing protein structures are discussed in Methods of Enzymology, vol 115, pg 397-420. The necessary least-squares algebra to calculate r.m.s.d.. has been given by Rossman (1975) although faster methods have been described by Kabsch (1976 & 1978), Hendrickson (1979) and McLachan (1979). Some algorithms use an iterative procedure in which the one molecule is moved relative to the other, such as that described by Ferro (1977). Other methods e.g. Kabsch's algorithm locate the best fit directly. It is usual to consider C-α atoms and the r.m.s.d. can then be calculated using programs such as LSQKAB (Collaborative Computational Project 4. (CCP4 1994)), MNYFIT (part of a collection of programs called COMPOSER) (Sutcliffe (1987)), MAPS (Lu 1998), QUANTA (Jones 1991 and commercially available from Accelerys, San Diego, Calif), Insight (commercially available from Accelerys, San Diego, Calif), Sybyl.RTM. (commercially available from Tripos, Inc., St Louis), O (Jones 1991) and other coordinate fitting programs. In, for example, the programs LSQKAB and O, the user can define the residues in the two proteins that are to be paired for the purpose of the calculation. Alternatively, the pairing of residues can be determined by generating a sequence alignment of the two proteins. The atomic coordinates can then be superimposed according to this alignment and an r.m.s.d.. value calculated. The program Sequoia (Bruns 1999) performs the alignment of homologous protein sequences, and the superposition of homologous protein atomic coordinates. Once aligned, the r.m.s.d.. can be calculated using programs detailed above. For sequence identical, or highly identical, the structural alignment of proteins can be done manually or automatically as outlined above. Another approach would be to generate a superposition of protein atomic coordinates without considering the sequence. It is more normal when comparing significantly different sets of coordinates to calculate the r.m.s.d. value over C-α atoms only. It is particularly useful when analysing side chain movement to calculate the r.m.s.d. over all atoms and this can be done using LSQKAB and other programs. Varying the atomic positions of the atoms of the structure by up to about 0.5 A in a concerted way, preferably up to about 0.3 A in any direction will result in a structure which is substantially the same as the structure of Appendix 1(a) or (b) in terms of both its structural characteristics and utility e.g. for molecular structure-based analysis. Those of skill in the art will appreciate that in many applications of the invention, it is not necessary to utilise all the coordinates of Appendix 1(a), (b), (c) or (d), but merely a portion of them. The term portion is intended to define a sub-set of the coordinates, which may or may not represent contiguous amino acid residues in the 12Y-1, 12Y-2, 12A-9 or 1A-7 structure. The invention also provides a means for homology modelling of other IgSF domains. By "homology modelling", it is meant the prediction of related IgSF domain structures based either on X-ray crystallographic data or computer-assisted de novo prediction of structure, based upon manipulation of the coordinate data of Appendix I. The term "homologous regions" describes amino acid residues in two sequences that are identical or have similar (e.g. aliphatic, aromatic, polar, negatively charged, or positively charged) side-chain chemical groups. Identical and similar residues in homologous regions are sometimes described as being respectively "invariant" and "conserved" by those skilled in the art. In general, the method involves comparing the amino acid sequences of the IgNAR domain of Appendix 1(a), (b), (c) or (d) with a modified IgSF domain by aligning the amino acid sequences (Dunbrack (1997)). Amino acids in the sequences are then compared and groups of amino acids that are homologous (conveniently referred to as "corresponding regions") are grouped together. This method detects conserved regions of the polypeptides and accounts for amino acid insertions or deletions. Homology between amino acid sequences can be determined using commercially available algorithms. The programs BLAST, gapped BLAST, BLASTN, PSI-BLAST and BLAST 2 sequences (provided by the National Center for Biotechnology Information) are widely used in the art for this purpose, and can align homologous regions of two amino acid sequences. These may be used with default parameters to determine the degree of homology between the amino acid sequence of the 12Y-1, 12Y-2, 12A-9 or 1A-7 protein and other IgSF domains, which are to be modelled. Homology modelling as such is a technique that is well known to those skilled in the art (see e.g. Greer 1985 and Blundell 1988). The techniques described in these references, as well as other homology modelling techniques, generally available in the art, may be used in performing the present invention Thus the invention provides a method of homology modelling comprising the steps of: (a) aligning a representation of an amino acid sequence of an IgSF domain with the amino acid sequence of 12Y-1, 12Y-2, 12A-9 or 1A-9 as shown in Figure 1 to match homologous regions of the amino acid sequences; (b) modelling the structure of the matched homologous regions of said IgSF domain on the corresponding regions of the 12Y-1, 12Y-2, 12A-9 or 1A-7 structure as defined by Appendix 1(a), (b), (c) or (d); and (c) determining a conformation (e.g. so that favourable interactions are formed within the IgSF domain and/or so that a low energy conformation is formed) for said IgSF domain which substantially preserves the structure of said matched homologous regions. Preferably one or all of steps (a) to (c) are performed by computer modelling. The aspects of the invention described herein which utilise the 12Y-1, 12Y-2, 12A-9 or 1A-7 structure in silico may be equally applied to models of modified IgSF domains obtained by methods of the present invention, and this application forms a further aspect of the present invention. Thus having determined the conformation of 12Y-1, 12Y-2, 12A-9 or 1A-7, such conformation may be used in a computer-based method of rational design of modified domains for diagnostic or therapeutic applications as described herein. The structure of 12Y-1, 12Y-2, 12A-9 or 1A-7 can also be used to solve the crystal structure of other IgNAR domains, where X-ray diffraction data or NMR specfroscopic data of these other domains has been generated and requires interpretation in order to provide a structure. One method that may be employed for these purposes is molecular replacement. In this method, the unknown IgNAR domain crystal structure, may be determined using the 12Y-1, 12Y-2, 12A-9 or 1A-7 structure coordinates as provided herein. This method will provide an accurate structural form for the unknown crystal more quickly and efficiently than attempting to determine such information ab initio. Examples of computer programs known in the art for performing molecular replacement are CNX (Brunger 1998a (also commercially available from Accelerys San Diego, Calif.)) or AMORE (Navaza 1994). Thus, in a further aspect, the invention provides a method for determining the structure of a protein, which method comprises; providing the co-ordinates of Appendix 1(a), (b), (c) or (d), and either (a) positioning the co-ordinates in the crystal unit cell of said protein so as to provide a structure for said protein or (b) assigning NMR spectra Peaks of said protein by manipulating the coordinates of Appendix 1(a), (b), (c) or (d). In another aspect, the present invention provides systems, particularly a computer system, the systems containing at least one of the following: (a) atomic coordinate data according to Appendix I, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7 or at least selected coordinates thereof; (b) structure factor data (where a structure factor comprises the amplitude and phase of the diffracted wave) for 12Y-1, 12Y-2, 12A-9 or 1A-7, said structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of an IgSF domain generated by homology modelling of the IgSF domain based on the data of Appendix I; (d) atomic coordinate data of the IgSF domain generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Appendix I; and (e) structure factor data derivable from the atomic coordinate data of (c) or (d). For example the computer system may comprise: (i) a computer-readable data storage medium comprising data storage material encoded with the computer-readable data; (ii) a working memory for storing instructions for processing said computer- readable data; and (iii) a central-processing unit coupled to said working memory and to said computer-readable data storage medium for processing said computer-readable data and thereby generating structures and/or performing rational drug design. The computer system may further comprise a display coupled to said central-processing unit for displaying said structures. The invention also provides such systems containing atomic coordinate data of modified IgSF domains wherein such data has been generated according to the methods of the invention described herein based on the starting data provided by Appendix I. Such data is useful for a number of purposes, including the generation of structures to analyze the mechanisms of action of IgSF domains and/or to perform rational design of IgSF domains for diagnostic or therapeutic purposes. In another aspect, the invention provides a computer-readable storage medium, comprising a data storage material encoded with computer readable data, wherein the data are defined by all or a portion (e.g. selected coordinates as defined herein) of the structure coordinates of 12Y-1, 12Y-2, 12A-9 or 1A-7, or a variant of 12Y-1, 12Y-2, 12A-9 or 1 A-7, wherein said variant comprises backbone atoms that have a root mean square deviation from the Cα or backbone atoms (nitrogen-carbonα-carbon) of Appendix I of less than 2 A, such as not more than 1.5 A, preferably less than 1.5 A, more preferably less than 1.0 A, even more preferably less than 0.74 A, even more preferably less than 0.72 A and most preferably less than 0.5 A. The invention also provides a computer-readable data storage medium comprising a data storage material encoded with a first set of computer-readable data comprising a Fourier transformation of at least a portion (e.g. selected coordinates as defined herein) of the structural coordinates for 12Y-1, 12Y-2, 12A-9 or 1A-7 according to Appendix I; which, when combined with a second set of machine readable data comprising an X-ray diffraction pattern of a molecule or molecular complex of unknown structure, using a machine programmed with the instructions for using said first set of data and said second set of data, can determine at least a portion of the structure coordinates corresponding to the second set of machine readable data. In a further aspect, the present invention provides computer readable media with at least one of: (a) atomic coordinate data according to Appendix I recorded thereon, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, or at least selected coordinates thereof; (b) structure factor data for 12Y-1, 12Y-2, 12A-9 or 1A-7 recorded thereon, the structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of a target IgSF domain generated by homology modelling of the IgSF domain based on the data of Appendix 1 ; (d) atomic coordinate data of a modified IgSF domain generated by interpreting X- ray crystallographic data or NMR data by reference to the data of Appendix I; and (e) structure factor data derivable from the atomic coordinate data of (c) or (d). By providing such computer readable media, the atomic coordinate data can be routinely accessed to model IgSF domains or selected coordinates thereof. For example, RASMOL (Sayle 1995) is a publicly available computer software package which allows access and analysis of atomic coordinate data for structure determination and/or rational drug design. On the other hand, structure factor data, which are derivable from atomic coordinate data (see e.g. Blundell 1976), are particularly useful for calculating e.g. difference Fourier electron density maps. A further aspect of the invention provides a method of providing data for generating structures and/or performing rational drug design for IgSF domains, the method comprising: (i) establishing communication with a remote device containing computer-readable data comprising at least one of: (a) atomic coordinate data according to Appendix I, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, at least one sub-domain of the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, or the coordinates of a plurality of atoms of 12Y-1, 12Y-2, 12A-9 or 1A-7; (b) structure factor data for 12Y-1, 12Y-2, 12A-9 or 1A-7, said structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of a modified IgSF domain generated by homology modelling of the domain based on the data of Appendix I; (d) atomic coordinate data of a protein generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Appendix I; and (e) structure factor data derivable from the atomic coordinate data of (c) or (d); and (ii) receiving said computer-readable data from said remote device. A further aspect of the invention provides a method of providing data for generating structures and/or performing rational drug design for IgSF domains, the method comprising: (i) establishing communication with a remote device containing computer-readable data comprising at least one of: (a) atomic coordinate data according to Appendix I, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, at least one sub-domain of the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, or the coordinates of a plurality of atoms of 12Y-1, 12Y-2, 12A-9 or 1A-7; (b) structure factor data for 12Y-1, 12Y-2, 12A-9 or 1A-7, said structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of a modified IgSF domain generated by homology modelling of the domain based on the data of Appendix I; (d) atomic coordinate data of a protein generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Appendix I; and (e) structure factor data derivable from the atomic coordinate data of (c) or (d); and (ii) receiving said computer-readable data from said remote device. Thus the remote device may comprise, for example, a computer system or computer readable media of one of the previous aspects of the invention. The device may be in a different country or jurisdiction from where the computer-readable data is received. The communication may be via the internet, intranet, email etc. Typically the communication will be electronic in nature, but some or all of the communication pathway may be optical, for example, over optical fibres. Additionally, the communication may be through radio signals or satellite transmissions. The folding topologies of the 12Y-1, 12Y-2, 12A-9 and 1A-7 structures show the characteristic immunoglobulin superfamily (IgSF) fold, identified by a β-sandwich structure formed by two β-sheets, packed face-to-face and linked by a disulfide bond between strands B and F (Bork 1994, Chothia 1998). The inner-strand features are turns, coils and loops including two loop regions analogous to CDRl and CDR3 loops. The structures comprise eight β-strand regions, designated A, A', B, C, D, E, F and G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2. As used herein, a "loop region" is a portion of peptide sequence that extends either from or between a β-strand conformation or β-strand conformations. As used herein, a "β-strand region" contains an extended β-strand conformation, i.e. β-strands comprising at least 4, preferably at least 5 amino acids. Loop regions are typically free of extended β-strand conformations but may include shortened β-strand conformations, i.e. β-strands comprising less than 4 amino acids. Apart from N- and C-terminal loop regions, the loop regions connect β-strands running in opposite directions. Preferably, loop region 5 contains shortened β-strand conformations. We have also found that loop region 8 may contain β-strand conformations, which may be either shortened or extended, and these are discussed in more detail below. Preferably, no other loop regions contain β-strand conformations. Detailed analysis of the 12Y-1, 12Y-2, 12A-9 and 1A-7 frameworks indicates a novel folding topology which resembles the intermediate (I-set) fold in a number of important characteristics, but also with distinct structural features found in variable (V- set) domains. More particularly, the structures comprise 8 β-strand regions, designated A, A', B, C, D, E, F and G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2, in which loop region 5 comprises 2 shortened β-strand regions, designated D' and C, and 3 loop regions, designated 5a, 5b and 5c, according to Figure 3. From the data assimilated, Table 3 presents a breakdown of the number of amino acid residues present in the various loop and β-strand regions of Type 2 VNARS. Loop region 4 is analogous to a conventional CDRl loop. Loop region 8 is analogous to a conventional CDR3 loop. As loop region 8 can contain a variable number of amino acids ranging from about 5 to 30, a default value of 18 is used on which to base the residue numbering for subsequent regions. Consequently, the residue numbering does not necessarily correlate with the total number of amino acid residues present in the sequence. It is based on loop region 8 having a default value of 18 amino acid residues. Table 3 A presents a breakdown of the number of amino acid residues present in the loop region 5 of Type 2 VNARS. Loop region 5 comprises 2 shortened β-strand regions, designated D' and C, and 3 loop regions, designated 5a, 5b and 5c. Both V-set and I-set proteins have a typical kink in the first strand (A'), which allows the first part of the strand (A) to hydrogen bond to one part of the β-sandwich sheet and the second part (A') to the extended G strand of the other β-sheet. This first- strand kink is found in the VNAR proteins as depicted in Figure 4. It starts with the highly conserved cw-proline (Pro7), the most typical residue in first-strand kinks of variable domains (Spada 1998). Like V-set proteins, 12Y-1, 12Y-2, 12A-9 and 1A-7 also have bulges in the C terminal G strand (conserved Gly-Ala-Gly motif) and in the C strand. Most significantly, 12Y-1, 12Y-2, 12A-9 and 1A-7 resemble I-set proteins in having a short C strand (three H-bonds) and a very short C" strand (labelled as D' in Figure 3) which atypically switches from one β-sheet to the other, such that a single hydrogen bond links it to the D strand rather than the C strand as in V-set domains. The 12Y-2 chain A and B (r.m.s.d. of 0.53 A for Cα of 113 residues), and the 12Y-1 framework (r.m.s.d. of 0.72 A for Cα of 100 residues) are closely related (see Figure 5). Further structural comparison (see Figures 6 and 7) of the 12Y-2 chain A to diverse variable and intermediate set proteins for which structural information is available, shows VNARS to be most closely related to I-set molecules such as the Neural Cell Adhesion Molecules (NCAMs) ( Harpaz 1994; Chothia 1997; Soroka 2003,) and Telokin (Chothia 1997; Holden 1992). This similarity is heavily biased by the absence of extended C and C" strands, connected by a CDR2 loop, that in conventional antibodies extends up to the top of the molecule and participates in immune recognition. In contrast, comparison of the 12Y-2 chain A to conventional T cell receptor (TCR) Vα, and VH, VL, and single-domain VHH antibodies, shows little consistent structural identity beyond a core of residues based around the major strands, minus the C, C" and CDR regions. The single VHH domains found in the Camelidae may be expected to be similar to the VNAR structure, however, these single domain antibodies clearly arose from a mammalian IgG-like progenitor, successively acquiring solubilizing, stabilizing, and extensive CDR3 mutations (Nguyen 2002). The low structural homology between VHH and VNARS is consistent with their very low sequence homology, and reflects convergent evolutionary solutions to the problem of achieving solvent solubility and binding affinity. In Figure 8, the relative positions of the three classically defined antibody CDR or hypervariable loop regions are shown. Sequence alignments show IgNAR antibody variability confined to the loop regions 4 and 8 corresponding to conventional CDRl and CDR-3 regions, and this is confirmed by our structural analysis where a loop region analogous to a typical "CDR2 loop" is missing and its bottom turn appears to be well separated from the antigen-binding face (or paratope). Sequence analysis also suggests that loop region 4 is the minor loop component, invariant in length and limited in diversity. This region is confined to residues 28-33 (12Y-1: NSYGLESC; 12Y-2: NSFELKDC), with a topology close to that of canonical structure 2 observed in antibody light chain variable domains (see Figure 9; Cα r.m.s.d. of 1.22A with lhzh VL) (Chothia 1989). Where a half cysteine is present in the VNAR loop region 4, it is exclusively found at positions 29 or 32. The side chains of these two residues extend outward and upward towards the extended loop region 8, and are ideally positioned to make contact with the concomitant half cysteine in this region (see Figure 10). Given the enormous topological latitude inherent in the highly diverse loop regions 8, a wide variety of conformations can clearly be adopted by loop region 8, despite the restraints of these stabilizing disulphide linkages. Such extreme diversity has also been observed for the
CDR3 loop of VHH single domain antibodies, with a single antigen eliciting a highly varied immune response with significantly different loop topologies (Desmyter 2002). The 12Y-2 CDR3 loop is present in two crystal forms, corresponding to chains A and B, and extends from residues Phe86 to Glul03. Unusually, the chain A loop region 8 adopts a clear β-hairpin configuration with β-strands from Phe86-Leu89, and Leu98-Glul03, separated by a flexible loop (Pro90-Ser97). For chain B, the β-hairpin extends even further into loop region 8 with residues Phe86-Asp93 and Tyr96-Glul03 involved in β-strand formation (see Figure 11). Structurally, the β-hairpins are formed by the main chain hydrogen bonds (< 3 A): Tyr87 (O) - PhelOO (N); Tyr87 (N) - PhelOO (O); Leu89 (N) - Leu98 (O); Leu89 (O) - Leu98 (N), and, Asp93(O) - Tyr96(O) (Figure 11). Additional H-bonds for loop region 8 of chain B are: Asp93 (N) - Tyr96 (O); Asp93 (O) - Tyr96 (N); and, Leu91 (O) - Tyr96 (O). Thus, the 12Y-2 loop region 8 extends outward and upward from the immunoglobulin framework, at the furthest point extending ~2θA above the conserved β-sheet framework, and tipped by the bulky side-chains of tyrosine residues at positions 94 and 96 (see Figures 8 and 11). Such extended antigen binding paratopes have been observed in but a limited number of antibodies, for example the camel anti-lysozyme VHH cAb-Lys3 (Desmyter 1996), and the H3 loop of human antibody bl2, which penetrates deeply into the HIV gpl20 binding cleft (Sapphire 2001). A comparison of the extended loop lengths of the 12Y-2 region 8 with these antibodies reveals that the 12Y-2 loop region 8 is of greater length and may bind antigen in a similar manner. Thus, it is apparent that structures based on the 12Y-2 loop region 8 with its extended β-hairpin structure may prove ideal for penetrating buried clefts and cavities in for example enzyme active sites, parasite coat proteins, or viral canyons. .We previously identified two mutations in the 12Y-2 loop region 8 which independently enhanced AMA1 antigen binding affinity ~10-fold (Nuttall 2004). Without being limited by theory, it is believed that these mutations (Pro90Leu and PhelOOLeu) probably act to increase the flexibility of the β-hairpin around hinge regions relative to the rest of the framework (see Figure 11). For example, the three aromatic residues: Phe29 of CDRl, and Tyr87 and PhelOO of loop region 8 have side chains involved in stabilizing C-H-π-interactions (dc-x <4.8A, where X is the centre-of- mass of the π-system (Brandl 2001)). Additional stability comes from hydrogen bond Tyr87 (OH) - Glul03(Oε). Thus, binding of 12Y-2 to the AMA1 target is probably mediated by the rigid β-hairpin, with increased access to the antigen mediated by flexibility at the bottom of the loop structure. In contrast, the 12Y-1 loop region 8 is unresolved in the crystal structure and is probably highly flexible in solution around similar hinge-like residues. The aromatic loop region 8 residues of 12Y-2 are replaced with Arg87 and Pro98 in 12Y-1, reducing the stability of the loop region, i.e. the Phe29 of loop region 4 is now hydrogen bonded to GlulOl (Glul03 in 12Y-2) (Tyr29(OH) - Glu 101 (Oε)) leaving the hinges of the loop region 8 unsupported. We turn now to the impact of the unusual VNAR C'C'D strand topology on antigen recognition. The VNAR "CDR2" loop is non-existent, replaced by a short β-turn at the bottom of the molecule. This is graphically illustrated in Figure 12, where the VNAR "CDR2" is aligned with that of a typical human antibody. The "bottom" position of this loop, combined with the low sequence variability, strongly suggests that this region has little impact on the interaction with antigen. However, the loss of the conventional C" and D strands suggests a possible alternative model for antigen binding, where the extended 12Y-2 loop region 8 combines with the large concave pocket opened in the absence of the conventional CDR2 (Figure 8). Additional structural variability is also observed in the 12Y-1 and 12Y-2 structures for the C strand loop ranging from residues Lys40 to Glu46, just prior to the "CDR2" (Figure 12). Comparison of V ARS from different shark species shows significant sequence heterogeneity in this region, which most likely reflects an area under less intensive selection pressure than the rest of the molecule, and susceptible to some degree of structural plasticity. Lack of an extended CDR2 loop also has a significant impact on the interaction between isolated VNARS. Both 12Y-1 and 12Y-2 form crystallographic 2-fold symmetry dimers, which form a continuous 8-stranded β-sheet underneath the loop regions 4 and 8, which correspond to conventional CDRl and CDR3 loops respectively (see Figure 13). Contact areas are highly conserved between the 12Y-1 and 12Y-2 proteins, despite different crystal forms (12Y-1 tetragonal; 12Y-2 orthorhombic). A comparison of the 12Y-2 and 12Y-1 dimeric forms shows that the interaction surface between the 2-fold monomers is not continuous and can be subdivide into three areas: (i) the main-chain β-sheet interactions between D strands; (ii) the interaction between loop regions 4; and (iii) the interactions between loop regions 8 (see Figure 13 and Table 4). While the contact between loop regions 8 in 12Y-2 is extensive, the dimeric arrangement is preserved in 12Y-1 crystals notwithstanding the more flexible and significantly distorted loop region 8, indicating that the conformation of loop region 8 is not absolutely required. Thus, the most significant dimer contacts are probably mediated by the loop regions 4 and especially by the D strands, where the main-chain interactions are independent of side-chain variation. With a buried surface area of -1760 A2, the 12Y-2 dimer appears to be a true protein-protein interaction site, as the statistical probability of finding a non-specific interface of such dimensions in a crystal is <1% (Lo Conte 1999). We suggest that this configuration is a general phenomenon for independent IgNAR variable domains (i.e. not tethered to constant domains), as we have also observed such dimeric species in other recombinant VNARS (Nuttall 2002). In heterodimeric immune receptors such as VH/VL antibodies and Vα/Vβ TCRs, the paired domains interact across a broad hydrophobic interface. This non-solvent exposed region is formed by a conserved patch of residues on the AGFCC β-strands, with additional CDR3 interactions. In contrast, many IgSF-based cell surface receptors are single domains in solution and this face of the β-sandwich takes on a more charged/polar character. We have compared this region on the 12Y-2 VNAR, a camel VHH, a TCR Vα, an antibody VH, and NCAM and Telokin domains. The hydrophobic region of inter-domain contact is immediately apparent for the TCR and antibody domains, centred around aromatic residues at the centre of the interface. The surface character is altered for VHH domains, for example by mutations Leu45Arg and Gly44Glu, to give a more charged character. However, the relatively short evolutionary time since the development of these single domain antibodies in the Camelidae mean that other solutions have also been adopted, for example the illustrated antibody where part of the loop region 8 (analogous to a conventional CDR3 loop) descends to partly cover the former VL interface, for example residues Aspl21 and Tyrl20. Although these camelid adaptations can be directly transplanted to murine and human antibody variable domains, the resulting proteins often achieve increased solubility by non-predictable conformational changes (Riechmann 1996). Isolation of soluble human single variable domains can also depend on conformational perturbations, for example the side chain of conserved residue Trp47 flipping into a cavity on the VL interface (Jespers 2004). In contrast, for the VNARS this face is dominated by the charged and polar residues Tyr37, Glu46, Lys82, Gln84, ArglOl, and Lysl04. Residues Glu46, Lys82, and Lys 104 especially are well conserved across type 2 V ARS, and in this instance form a charged pocket with a pattern of hydrogen bonds between side-chains (i.e. Glu46Oεl-Lysl04 Nζ) and to adjacent water molecules (i.e. Glu46Oε2 - H20 - Lys82 Nζ). The central Tyr37 is well-conserved as an aromatic species across the immunoglobulin superfamily, and it and residues Gln84 and ArglOl also participate in forming a framework-CDR3 hydrogen bond network (Argl01(NH2) - Gln84(Nζ2); Tyr87(OH) - Argl01(NH2). The combined effect of these residues is to form a conserved charged pocket, which displays a high degree of solvent solubility such that it is ringed by water molecules in the crystal forms. The conservation of the Glu46, Lys82, and Lys 104 trio suggests a stable and well-established face. A similar situation is observed in NCAM, where this face is dominated by the charged residues Lys76 and Glu88, and for Telokin, where a charged and polar interface is maintained by a combination of hydrogen bonds.
Modifications to the IgNAR variable domain Analysis of the crystal structures has revealed the potential of VNAR proteins as, for example, therapeutic, diagnostic and bioarray reagents. For example, VNAR proteins have potential to act as cleft-binding antibodies in which the β-hairpin structures are extended to form paratopes capable of penetrating otherwise cryptic antigenic sites. Furthermore, these proteins have a high degree of stability which offers significant advantages in terms of their manipulation and practical application. Thus, the present invention provides a method of altering a property of an IgNAR variable domain comprising eight β-strand regions, designated A, A', B, C, D, E, F and G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2, said method comprising modifying the IgNAR variable domain within at least one of the β-strand regions or loop regions. The IgNAR variable domain is modified such that a property of the IgNAR variable domains is altered. A property of an' IgNAR variable domain, I-set domain or V-set domain is altered if any characteristic or attribute of the domain differs from the corresponding property of the unmodified domain. These properties include, but are not limited to, substrate specificity, substrate affinity, binding affinity, binding selectivity, catalytic activity, thermal stability, alkaline stability, pH activity profile, resistance to proteolytic degradation, kinetic association, kinetic dissociation, immunogenicity, ability to be secreted, ability to activate receptors, ability to treat disease, solubility, cytotoxic activity and oxidative stability. Unless otherwise specified, a property of an IgNAR variable domain, I-set domain or V-set domain is considered to be altered when the property exhibits at least a 5%, preferably at least 10%, more preferably at least a 20%, yet more preferably at least a 50%, and most preferably at least a 2-fold increase or decrease relative to the corresponding property in the unmodified domain. In a preferred embodiment, the solubility of the modified IgNAR variable domain, and concomitantly the binding moiety, is altered, preferably improved, relative to the corresponding unmodified IgNAR variable domain. In another preferred embodiment, the stability of the IgNAR variable domain, and concomitantly the binding moiety, is altered, preferably improved, relative to the corresponding unmodified IgNAR variable domain. Examples of altering the stability include changing one of the following properties:- thermal stability, alkaline stability, pH activity profile and resistance to proteolytic degradation. In a particularly preferred embodiment, the binding characteristics of the IgNAR variable domain are altered relative to the corresponding unmodified IgNAR variable domain. Examples of altering the binding characteristics include changing one of the following properties: substrate specificity, substrate affinity, catalytic activity, kinetic association, kinetic dissociation, binding affinity and binding selectivity. In another preferred embodiment, the modification increases or decreases the propensity for IgNAR variable domain to form homodimers compared to the unmodified IgNAR variable domains. The present invention also provides a binding moiety comprising a modified IgNAR variable domain produced by a method according to the invention. The present invention also provides a binding moiety comprising an IgNAR variable domain comprising eight β-strand regions, designated A, A', B, C, D, E, F and
G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2, wherein the IgNAR variable domain has been modified within at least one of the β- strand regions or loop regions. Preferably, the unmodified β-strand regions and loop regions have the amino acid residue numbering according to Table 3. Preferably, the unmodified loop region 5 comprises two β-strand regions designated C and D' and three loop regions designated 5a, 5b and 5c, all according to Figure 3. Thus, in a preferred embodiment, an IgNAR variable comprises 10 β-strand regions, designated A, A', B, C, C, D', D, E, F and G according to Figure 3, and eleven loop regions, designated 1, 2, 3, 4, 5a, 5b, 5c, 6, 7, 8 and 9 according to Figure 3. Preferably, the loop regions 5a, 5b and 5c, and β-strand regions C, C and D' have the amino acid residue numbering according to Table 3 A. In a preferred embodiment, where an IgNAR variable domain is to be modified, prior to the modification, the Cα trace of loop region 5b extends no more than 5 A above the plane formed by the Cα trace of residues 22, 83 and 36 as defined in Table 1. In a preferred embodiment, the amino acid sequence of the unmodified β-strand regions A, A', B, C, D, E, F and G and loop regions 1, 2, 3, 6, 7 and 9 comprises an amino acid sequence according to Figure 1 and/or Table 1. In a preferred embodiment, the IgNAR is a Type 2 or Type 3 IgNAR, preferably Type 2. Preferably, the IgNAR is derived from a shark, preferably a wobbegong shark. In a further preferred embodiment, the unmodified IgNAR variable domain has a sequence as shown in Figure 1. More preferably, the unmodified IgNAR is 12Y-1, 12Y-2, 12A-9 or 1A-7. Suitable modifications include substitutions, insertions and deletions within at least one at least one of the β-strand regions or loop regions. A combination of deletion, insertion and substitution can be made to generate the IgNAR modified variable domain. Modifications can be prepared by introducing appropriate nucleotide changes into a nucleic acid of the present invention, or by in vitro synthesis of the desired polypeptide. Such mutants include, for example, deletions, insertions or substitutions of residues within the amino acid sequence. In designing amino acid sequence mutants, the location of the mutation site and the nature of the mutation will depend on characteristic(s) to be modified. The sites for mutation can be modified individually or in series, for example by (1) substituting first with conservative amino acid choices and then with more radical selections depending upon the results achieved, (2) deleting the target residue, or (3) inserting other residues adjacent to the located site. Encompassed within the scope of the invention are modifications which are tantamount to conservative substitutions but which alter a property of the IgNAR variable domain. Examples of conservative substitutions are given in as follows:
Figure imgf000039_0001
Furthermore, if desired, unnatural amino acids or chemical amino acid analogues can be introduced as a substitution or addition into the polypeptides of the present invention. Such amino acids include, but are not limited to, the D-isomers of the common amino acids, 2,4-diaminobutyric acid, α-amino isobutyric acid, 4- aminobutyric acid, 2-aminobutyric acid, 6-amino hexanoic acid, 2-amino isobutyric acid, 3 -amino propionic acid, ornithine, norleucine, norvaline, hydroxyproline, sarcosine, citrulline, homocitrulline, cysteic acid, t-butylglycine, t-butylalanine, phenylglycine, cyclohexylalanine, β-alanine, fluoro-amino acids, designer amino acids such as β-methyl amino acids, Cα-methyl amino acids, Nα-methyl amino acids, and amino acid analogues in general. Also included within the scope of the invention are chemically modified derivates of IgNAR variable domains which may provide advantages such as increasing stability and circulating time of the polypeptide, or decreasing immunogenicity (see U.S. Patent No. 4,179,337). The chemical moieties for derivatization may be selected from water-soluble polymers such as polyethylene glycol, ethylene glycol/propylene glycol copolymers. carboxymethylcellulose, dextran, polyvinyl alcohol and the like. Also included within the scope of the invention are variable domains of the present invention that are differentially modified during or after synthesis, for example, by biotinylation, benzylation, glycosylation, acetylation, phosphorylation, amidation, derivatization by known protecting/blocking groups, proteolytic cleavage, linkage to an antibody molecule or other cellular ligand, etc. The IgNAR variable domain may be modified at random positions within the molecule or at predetermined positions within the molecule and may include one, two, three or more attached chemical moieties. These modifications may, for example, serve to increase the stability and/or bioactivity of the modified domains of the invention. The IgNAR variable domains may also be modified by having C- or N-terminal truncations. However, the scope for such modifications is limited and it is preferred that no more than 8, preferably no more than 6 and more preferably no more than 4 residues be removed. Preferably there is no truncation at the N-terminal and more preferably there is no truncation at either the N- or C-terminals. Modified domains of the present invention can be produced in a variety of ways, including production and recovery of natural proteins, production and recovery of recombinant proteins, and chemical synthesis of the proteins. In one embodiment, an isolated polypeptide of the present invention is produced by culturing a cell capable of expressing the polypeptide under conditions effective to produce the polypeptide, and recovering the polypeptide. In a preferred embodiment the modification comprises insertion of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,19, 20 or more amino acids. In another preferred embodiment the modification comprises deletion of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acids. In a further preferred embodiment, the modification involves more than mere substitution of a cysteine residue in one loop region, the cysteine residue being involved in disulphide formation with another cysteine residue in another loop region. In a further preferred embodiment, the modification is not substitution of residue 43 as shown in Table 1 or involves more than mere substitution of the residue 43. In another preferred embodiment, the modification is made to one or more amino acid residues within the patch defined by residues 33, 37, 46, 48, 50, 51, 59, 61, 86, 94, 95, 96, 98, 99 and 101 as shown in Table 1. In a preferred embodiment, when loop region 4 or loop region 8 of the IgNAR is modified, at least one of the β-strand regions or loop regions 1-3, 5-7 or 9 is also modified. In a further preferred embodiment, at least one of β-strand regions C, D, E or F or loop regions 5, 6 or 7 has been modified. In a further preferred embodiment, at least one of β-strand regions C or D or loop region 5 has been modified. In a further preferred embodiment, loop region 5 has been modified. In one preferred embodiment, the modification involves point mutations within loop region 8. For example, residues Pro90 and/or PhelOO may be replaced in order to enhance flexibility of loop region 8. In another embodiment of the invention, the modification involves randomisation of loop region 8. In yet another embodiment, the modification involves insertion of amino acids into loop region 8. In yet another embodiment the modification involves grafting a CDR loop or portion thereof from a V-set or an I-set domain onto the IgNAR variable domain. For example, the CDR3 loop of an antibody may be grafted onto the IgNAR variable domain in the vicinity of loop region 8. The grafting may involve, for example, replacing amino acids from loop region 8 (for example amino acids 86 to 103 as defined in Table 1 or a portion thereof) with amino acids that constitute an antibody CDR 3 loop or portion thereof. The modification may further involve replacing amino acids from loop region 4 (for example amino acids 28 to 33 as defined in Table 1 or a portion thereof) with amino acids that constitute an antibody CDR 1 loop or portion thereof. In a further preferred embodiment, when the amino acid residues at the N- terminal and C-terminal ends of loop region 8 are each capable of adopting a β-strand configuration, loop region 8 is modified by substitution, deletion or addition, preferably by addition, of at least one amino acid within that part of the loop not capable of adopting the β-strand configuration. In a further preferred embodiment from 2 to 10, preferably from the 3 to 8, amino acid residues at the N-terminal and C-terminal ends of loop region 8 are capable of adopting β-strand configurations. In a further preferred embodiment, loop region 8 is modified by substitution, deletion or addition, preferably by addition or substitution, of one or more amino acid residues at the C- and/or N-terminal ends of the loop region to facilitate the adoption of β-strand configurations at the C- and/or N-terminal ends. In a further preferred embodiment, loop region 8 is modified so as to facilitate the adoption of β-strand configurations at the C- and/or N-terminal ends of 2 to 10, preferably from 3 to 8, amino acid residues in length. It will be appreciated by those skilled in the art that it is possible to predict whether or not any given sequence is capable of forming a β-strand configuration by in silico modelling. Many computer programs are available and are know to the skilled person (see, for example, Wolfson et al. 2005 and Xu et al. 2000). Examples of suitable programs can also be found on the secondary structure prediction server at http://www.predictprotein.org. In one embodiment, the modification increases or decreases the binding characteristics, e.g. the affinity, of the modified IgNAR variable domain for a predetermined target molecule compared to the unmodified IgNAR variable domain. That part of the IgNAR variable domain which normally contacts a ligand (e.g. an antigen) or which appear, from the studies we have undertaken, to be available for interacting with a ligand (e.g. a receptor, enzyme etc.) are typically the solvent exposed regions of the IgNAR variable domain. In particular, they are generally made up of the surface exposed loops, and in particular loop regions 8 and 4 of the IgNAR variable domain. Preferably, the unmodified IgNAR variable domain has had one or more loop regions modified. In particular, this can be achieved by replacing one or more solvent exposed loops of the IgNAR variable domain with one or more loops from the variable domains of other members of the IgSF. Preferably, loop regions 4 and/or 8, or part thereof, is modified, preferably replaced, by a corresponding loop structure (e.g. a CDRl or CDR3 loop structure, respectively) from another molecule. Modifications can also be made to regions of the IgNAR variable domain that are not solvent exposed and/or which do not form part of a binding loop, e.g. the β strand regions. In another preferred embodiment, the modification increases or decreases the propensity for the IgNAR variable domain to form homodimers compared to the unmodified IgNAR variable domains. In another preferred embodiment, the modification increases the solubility of the IgNAR variable domain compared to the unmodified IgNAR variable domain. In a preferred embodiment, one or more solvent exposed loops is/are modified to improve solubility. Solubility may be improved by, for example, either removing disulphide bond-forming cysteines and/or replacing disulphide bond-forming cysteines from within the solvent exposed loops with amino acids such as alanine or serine. Modifications to improve solubility may be desirable where the IgNAR variable domains are being designed to function in an intracellular context and/or their method of production favours expression in a soluble form. It will also be evident to the skilled person that it may be necessary to modify the solubility characteristics of the IgNAR variable domains at the same time or even prior to making other modifications, such as, changing the binding characteristics. The physicochemical properties, such as stability and solubility, of the IgNAR variable domains may be qualitatively and/or quantitatively determined using a wide range of methods known in the art. Methods which may find use in the present invention for characterizing the biophysical/physicochemical properties of the binding moieties include gel electrophoresis, chromatography such as size exclusion chromatography, reversed-phase high performance liquid chromatography, mass spectrometry, ultraviolet absorbance spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy, isothermal titration calorimetry, differential scanning calorimetry, analytical ultra-centrifugation, dynamic light scattering, proteolysis, cross- linking, turbidity measurement, filter retardation assays, immunological assays, fluorescent dye binding assays, protein-staining assays, microscopy, and detection of aggregates via ELISA or other binding assay. Structural analysis employing X-ray crystallographic techniques and NMR spectroscopy may also find use. Protein stability (e.g. structural integrity) may, for example, be determined by measuring the thermodynamic equilibrium between folded and unfolded states. In one embodiment, stability and/or solubility may be measured by determining the amount of soluble protein after some defined period of time. In such an assay, the protein may or may not be exposed to some extreme condition, for example elevated temperature, low pH, or the presence of denaturant. Because unfolded and aggregated protein is not expected to maintain its function, e.g. be capable of binding to a predetermined target molecule, the amount of activity remaining provides a measure of the binding moieties stability and solubility. Thus, one method of assessing solubility and/or stability is to assay a solution comprising a binding moiety for its ability to bind a target molecule, then expose the solution to elevated temperature for one or more defined periods of time, then assay for antigen binding again. Alternatively, the modified IgNAR binding domains could be expressed in prokaryotic expression systems and the protein isolated from the cell lysate by a series of biochemical purification steps including differential centrifugation, affinity isolation chromatography using attached tags such as poly histidine, ion-exchange chromatography and gel filtration chromatography. A measure of the improvement in the solubility of the modified polypeptide can be obtained by making a comparison of the amount of soluble protein obtained at the end of the purification procedure to that obtained using the unmodified polypeptide, when starting with a similar amount of expressed unfractionated product. Levels of expression of product in culture can be normalised by a comparison of product band densities after polyacrylamide gel electrophoresis of equivalent aliquots of SDS detergent-solubilised cell lysate. In addition, IgNAR variable domains can be unfolded using chemical denaturant, heat, or pH, and this transition be monitored using methods including, but not limited to, circular dichroism spectroscopy, fluorescence spectroscopy, absorbance spectroscopy, NMR spectroscopy, calorimetry, and proteolysis. As will be appreciated by those skilled in the art, the kinetic parameters of the folding and unfolding transitions may also be monitored using these and other techniques. The solubility of the IgNAR variable domains of the present invention preferably correlates with the production of correctly folded, monomeric polypeptide. The solubility of the modified IgNAR variable domains may therefore also be assessed by HPLC or FPLC. For example, soluble (non-aggregated) domains will give rise to a single peak on a HPLC or FPLC chromatograph, whereas insoluble (aggregated) domains will give rise to a plurality of peaks. Furthermore, the ability to be able to correctly fold and form ordered crystal leads and structures is also often indicative of good solubility. As an example of an accelerated stability trial, aliquots of the IgNAR variable domain can be stored at different temperatures, such as -20°C, 4°C, 20°C and 37°C and an activity of the IgNAR variable domain assayed at different time intervals. For example, successful maintenance of activity during storage at 37°C for 12 weeks is roughly equivalent to storage stability for 12 months at 4°C. The trial can also be conducted to compare the effect of different protecting additives in the storage buffer on the stability of the protein. Such additives can include compounds such as glycerol, sorbitol, non-specific protein such as bovine serum albumin, or other protectants that might be used to increase the shelf life of the protein.
Modifications of members of the IgSF based on the IgNAR variable domain The results presented herein also identify structural features in IgNAR variable domains that are important for antigen binding or solubility/stability of these domains. These features can be introduced into domains of other members of the IgSF (for example, I-set or V-set domains) in order to alter binding properties or to improve solubility and/or stability. Accordingly, in a further aspect the present invention provides a method of modifying an I- or V-set domain, said method comprising inserting and/or substituting one or more structural features from an IgNAR variable domain into the I- or V-set domain. In a further aspect, the present invention provides a binding moiety comprising an I- or V-set domain, wherein the I- or V-set domain has been modified by substitution or insertion of one or more structural features from an IgNAR variable domain into the I- or V-set domain. By "I-set domain" is meant a domain comprising nine β-strand regions, designated A, A', B, C, C, D, E, F and G, as set out and according to Chothia (1997). Examples of representative I-set domain molecules include NCAM, VCAM, ICAM, Telokin, MADCAM-1, Twitchin and Titin. By "V-set domain" is meant a domain comprising ten β-strand regions, designated A, A', B, C, C, C", D, E, F and G, as , as set out and according to Chothia (1997). Examples of representative V-set domain molecules include antibodies, T cell receptors (TCRs), CTLA-4, CD28, ICOS, CD2, CD4, Cd7, CD22, CD33, CD80, CD86, CD48 and CD58. Preferably, the I-set or V-set domain is modified such that a property of the domain is altered. In one embodiment, the structural feature is a loop region from an IgNAR variable domain. For example, loop region 8 and/or loop region 4 from an IgNAR variable domain may be grafted onto the I- or V-set domain. The grafting may involve, for example, replacing suitable (e.g. predeteremined) amino acids of the I- or V-set domain with amino acids 86 to 103 as defined in Table 1 or a portion thereof. In another embodiment, the method comprises removing all or a portion of the CDR2 loop of the I- or V-set domain. In another embodiment the structural feature is the solvent exposed face of an
IgNAR variable domain at the C-terminus of loop region 4 and in the C and D β- strands (for example comprising residues 32, 33, 34, 35, 55, 57 and 58 as defined in Table 1). The method may involve modifying amino acids of the I- or V-set domain equivalent to amino acids 32, 33, 34, 35, 55, 57 and 58 as defined in Table 1 or a portion thereof. The method may involve grafting the solvent exposed face of an IgNAR variable domain (for example comprising residues 32, 33, 34, 35, 55, 57 and 58 as defined in Table 1) or a portion thereof onto the I- or V-set domain. Grafting may involve replacing amino acids of the I- or V-set domain with amino acids derived from the solvent exposed face of an IgNAR variable domain. Grafting of the solvent exposed face onto the I- or V-set domain preferably occurs after removal of all or a portion of the CDR2 loop. Preferably, the modification introduces charged or polar amino acids at these positions. Preferably, this modification improves the solubility of the I- or V-set domain. In one preferred embodiment, the V-set domain is a TCRVα or Vβ domain and the equivalent amino acids to the solvent exposed surface of am IgNAR variable domain are Gly30, Ser31, Phe32, Phe33, Phe62, Thr63, Ala64 and Gln65. Preferably, the modification involves the introduction of polar or charged amino acids in these positions. In another embodiment, the method involves modifying one or more residues of a TCR Vα or Vβ domain, wherein the one or more residues is located at the interface between the Vα and Vβ domains. In a preferred embodiment, the one or more amino acid residue is selected from the group consisting of Ser31, Pro43, Leu89 and Phel06 and combinations thereof. Preferably, the modification involves the introduction of one or more charged amino acids in these positions. In another embodiment, the method involves modifying one or more residues of an antibody VH or VL domain, wherein the one or more residues is located at the interface between the VH and V domains. In a preferred embodiment, the one or more amino acid residue is equivalent to an amino acid of the TCR Vα or Vβ domain selected from the group consisting of Ser31, Pro43, Leu89 and Phe 106 and combinations thereof. Preferably, the modification involves the introduction of one or more charged amino acids in these positions. In a preferred embodiment, the modification improves the solubility of the I- or V-set domain. In a further aspect, the present invention provides a method of modifying an I- or V-set domain, said method comprising introducing a modification into a region of the I- or V-set domain equivalent to loop region 4 and/or loop region 8 of an IgNAR variable domain as defined by Figure 2. In another aspect, the present invention provides a modified V-set domain produced by a method of the present invention.
Multimers The present invention also provides a binding moiety comprising a multimer comprising:
(i) at least two IgNAR domains, which may be the same or different, and at least one of which is a IgNAR variable domain; (ii) at least two I-set domains, which may be the same or different, and at least one of which is a I-set domain according to the present invention; or (iii) at least two V-set domains, wliich may be the same or different, and at least one of which is a V-set domain according to the present invention. The two domains may be derived from the same or different sources. The following description is directed to IgNAR domain multimers. It will, however, be apparent to the skilled person that many of the embodiments described with respect to IgNAR domain multimers can equally be applied to I-set and V-set domain multimers. Furthermore, it will be apparent to the skilled person that the various embodiments of the invention described herein in relation to IgNAR variable domains, I-set domains and V-set domains equally apply to IgNAR variable domains, I-set domains and V-set domains, respectively, present in the multimer embodiments of the invention. Preferably, the multimer comprises two IgNAR variable domains. In a preferred embodiment, the one or the at least two of the IgNAR domains is/are variable IgNAR domains(s) comprising eight β-strand regions, designated A, A', B, C, D, E, F and G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2. In a preferred embodiment, at least one IgNAR variable domains is modified by substitution, deletion or addition of at least one amino acid within in at least one of the β-strand or loop regions as described hereinabove. Where the multimer comprises at least two IgNAR variable domains, the two domains preferably form stable homodimers, preferably at least partially through salt bridges. Thus, a preferred modification is one in which at least one of the IgNAR variable domains has been modified such that the propensity to form a stable homodimer is increased. In a further preferred embodiment, the least one IgNAR variable domain has been modified so as to increase the dissociation constant of the homodimer formed compared to the homodimer formed by the unmodified IgNAR variable domain. Preferably both IgNAR variable domains have been modified such that the propensity to form a stable homodimer is increased. Preferably, this is achieved by replacing the following residues of one or both of the unmodified monomers (as defined in Table 1) with cysteine residues: residues 57 and/or 61; residues 51 and
' either 61 or 62; residues 32 and/or 33; residue 99; or residue 59. We have now cloned the full wobbegong shark (Orectolobus maculatus) IgNAR coding sequence (see Figure 33). The coding sequence encodes a single polypeptide chain encompassing one IgNAR I-set domain and 5 C-domains. In the mature IgNAR antibody, these chains form a dimer mediated by half-cystine residues at positions Cys430 and Cys660. The resulting two disulphide bridges are located (1) C-terminal to constant domain 3 and N-terminal to constant domain 4 and (2) C-terminal to constant domain 5. Thus in a further embodiment, the multimer comprises at least one IgNAR variable domain and at least one IgNAR constant domain. Preferably the constant domain is the Cl constant domain of an IgNAR, i.e. the constant domain closest to the IgNAR variable domain in nature. We have found that connecting an IgNAR variable domain to an IgNAR constant domain has no effect on the level of binding affinity (see Example 16). This means it is possible to add mass to the binding moieties without facilitating multimerisation or loss of binding affinity. Therefore, such multimer constructs have potential as commercial biosensor reagents. Multimers are one preferred design for therapeutic reagents since they have the potential to provide increased avidity and slower blood clearance rates which may provide favourable pharmacokinetic and biodistribution properties. The IgNAR domains may be connected either through covalent linkage or non-covalent linkage or a combination of linkages, including the use of chemical or genetically-encoded linkers. Linkers used to link protein domains are well-known and well understood in the art, in particular in relation to proteins in the immunoglobulin superfamilies (e.g. Casey JL et al, 2002 Br J Cancer., 86(9):1401-10; Plϋckthun, A., and Pack, P 1997. Immunotechnology, 3, 83-105). Therefore, the skilled person will appreciate that any suitable hinge or means of connection may be used to connect the two at least IgNAR domains. Examples of suitable chemical linkage include linking the two domains using a suitable cross-linker such as dimaleimide. Alternatively, the two domains may be linked by providing cysteine residues at the respective C- and N- terminals and forming a disulphide bond. In addition, they could be linked using single chain Gly Ser linkers such as GlyGlyGlyGlySer. The domains may also be linked genetically using techniques well-know in the art. The resulting multimers from any of these linker strategies described may possess the same, or different target specificities thus providing multivalent or multispecific reagents. In a preferred embodiment, two IgNAR variable domains may be joined to form a heterodimer through either covalent linkage or non-covalent linkage or a combination of linkages thereby providing two target binding affinities. If two or more IgNAR variable domains in the multimer have the same target specificity, the multimer will be multivalent and have increased avidity (functional affinity) for binding to two or more target molecules. In the case of multimers, it will be appreciated by the skilled person that the IgNAR domains must be suitably orientated with respect to each other. The first IgNAR domain should be suitably hinged or connected to the second IgNAR domain. Where the multimer comprises an IgNAR variable domain and an IgNAR constant domain, the domains are preferably orientated with respect to each other as they would be in the respective native protein(s) from which they are derived.
Binding moieties With regards to binding moieties of the present invention comprising IgNAR variable domains, such binding moieties comprise an IgNAR variable domain which has been modified such that at least one property of the IgNAR variable domain is altered. It will be understood that such binding moieties do not encompass and do not relate to the full-length, wild-type proteins from which suitable IgNAR variable domains may be derived. Rather, they encompass and relate to portions of IgNARs comprising the variable domain, which have been removed or isolated from their natural environments. In a preferred embodiment, the IgNAR variable domain of the binding moiety accounts for at least 25%, preferably at least 40%, more preferably at least 50%, yet more preferably at least 10%, even more preferably at least 80%, yet more preferably at least 90% and most preferably at least 95% by weight of the total molecular weight of and/or number of amino acid residues in the binding moiety. In a particularly preferred embodiment, the binding moiety consists essentially of the CBD. Preferably, the only binding domains present in the binding moieties of the present invention are the modified IgNAR variable domain, the I-set domain or the V- set domain. The binding moieties of the invention may be in a substantially isolated form. It will be understood that the protein may be mixed with carriers or diluents which will not interfere with the intended purpose of the protein and still be regarded as substantially isolated. Binding moieties of the invention may also be in a substantially purified form, in which case they will generally comprise the protein in a preparation in which more than 90%, e.g. 95%, 98% or 99% of the protein in the preparation is a binding moiety of the invention. The binding moieties of the invention may also be linked to other molecules, for example by covalent or non-covalent means. In preferred embodiments, the binding moieties of the invention may be linked (without restriction) to molecules such as enzymes, drugs, lipids, sugars, nucleic acids and viruses. In one aspect, the present invention provides a binding moiety of the present invention linked to a diagnostic reagent. In a preferred embodiment of this aspect, the diagnostic reagent is selected from the group consisting of streptavidin, biotin , a radioisotope, dye marker, other imaging reagent and combinations thereof. In another aspect, the present invention provides a binding moiety of the present invention immobilised on a solid support or coupled to a biosensor surface. In one embodiment, the binding moiety may contain solvent exposed cysteine residues for the site-specific attachment of other entities. Binding moieties of the invention can be linked to other molecules, typically by covalent or non-covalent means. For example, binding moieties may be produced as fusion proteins, linked to other polypeptide sequences. Fusion partners can include enzymes, detectable labels and/or affinity tags for numerous diagnostic applications or to aid in purification. Fusion partners, without restriction, may be GFP (green fluorescent protein), GST (glutathione S-transferase), thioredoxin or hexahistidine. Other fusion partners include targeting sequences that direct binding moieties to particular sub-cellular locations or direct binding moieties to extracellular locations e.g. secretion signals. In a preferred embodiment, binding moieties of the invention do not comprise other regions of the protein from which they are derived i.e. any fusion partners are heterologous to the IgNAR or protein from which I-set or V-set domains are derived. The heterologous sequence may be any sequence which allows the resulting fusion protein to retain the activity of the modified IgNAR variable domain, modified I-set domain or modified V-set domain. The heterologous sequences include for example, immunoglobulin fusions, such as Fc fusions, or fusions to other cellular ligands which may increase stability or aid in purification of the protein. Diagnostic or therapeutic agents that can be linked to the binding moieties of the invention include pharmacologically active substances such as toxins or prodrugs, immunomodulatory agents, nucleic acids, such as inhibitory nucleic acids or nucleic acids encoding polypeptides, molecules that enhance the in vivo stability or lipophilic behaviour of the binding moieties such as PEG, and detectable labels such as radioactive compounds, dyes, chromophores, fluorophores or other imaging reagents. Binding moieties may also be immobilised to a solid phase, such as a substantially planar surface (e.g. a chip or a microtitre plate) or beads. Techniques for immobilising polypeptides to a solid phase are known in the art. In addition, where libraries of binding moieties are used (e.g. in screening methods), arrays of binding moieties immobilised to a solid phase can be produced (Lee YS and Mrksich, M, 2002 Trends Biotechnol. 20(12 Suppl):S14-8. and references contained therein). In another embodiment of the invention, the binding moieties of the invention function as a protein scaffold with other polypeptide sequences being inserted into solvent-exposed regions of the binding moiety for display on the surface of the scaffold. Such scaffolds may, for example, serve as a convenient means to present peptides in a conformationally constrained manner. The scaffolds may be used to produce IgNAR variable domains, I-set domains or V-set domains with altered binding specificities and also to produce and/or screen for binding moieties having specificity for any target molecule of interest. Heterologous polypeptide sequences may be inserted into one or more solvent exposed regions such as, for example, one or more loops of the IgNAR variable domains, I-set domains or V-set domains. The IgNAR variable domain, I-set domain or V-set domain of the binding moiety functions as a protein scaffold for the inserted heterologous sequences, displaying the heterologous sequences on the surface of the binding moiety. The heterologous sequences may replace all or part of the loop of the IgNAR variable domain, I-set domain or V-set domain into wliich they are inserted, or may simply form additional sequence. Preferably, a plurality of heterologous sequences are inserted into a plurality of loops. The heterologous sequences may be derived from solvent exposed regions such as, for example, loops of another IgNAR variable domain, I-set domains or V-set domains. They may also be derived from other molecules or be partially of fully randomised. Polynucleotides, vectors and hosts The present invention provides a polynucleotide encoding a IgNAR variable domain or multimeric reagent according to the present invention. The present invention also provides a vector comprising a polynucleotide of the present invention. The present invention further provides a host cell comprising the vector of the invention. The present invention also provides a method of producing a binding moiety according to the present invention which comprises culturing a host cell of the present invention under conditions enabling expression of the binding moiety and optionally recovering the IgNAR variable domain. In a preferred embodiment of this aspect the
IgNAR variable domain or multimeric reagent is unglycosylated. Polynucleotides of the invention may comprise DNA or RNA. They may be single-stranded or double-stranded. They may also be polynucleotides which include within them synthetic or modified nucleotides. A number of different types of modifications to oligonucleotides are known in the art. These include methylphosphonate and phosphorothioate backbones, addition of acridine or polylysine chains at the 3' and/or 5' ends of the molecule. For the purposes of the present invention, it is to be understood that the polynucleotides described herein may be modified by any method available in the art. Such modifications may be carried out in order to enhance the in vivo activity or life span of polynucleotides of the invention. Polynucleotides of the invention can be incorporated into a recombinant replicable vector. The vector may be used to replicate the nucleic acid in a compatible host cell. Preferably, a polynucleotide of the invention in a vector is operably linked to a control sequence that is capable of providing for the expression of the coding sequence by a host cell or using an in vitro transcription/translation system, i.e. the vector is an expression vector. The term "operably linked" means that the components described are in a relationship permitting them to function in their intended manner. A regulatory sequence "operably linked" to a coding sequence is ligated in such a way that expression of the coding sequence is achieved under condition compatible with the control sequences. The control sequences may be modified, for example by the addition of further transcriptional regulatory elements to make the level of transcription directed by the control sequences more responsive to transcriptional modulators. Vectors of the invention may be transformed or transfected into a suitable host cell to provide for expression of a binding moiety according to the invention. This process may comprise culturing a host cell transformed with an expression vector under conditions to provide for expression by the vector of a coding sequence encoding the binding moiety, and optionally recovering the expressed binding moiety.. The vectors may be, for example, plasmid, phagemid or virus vectors provided with an origin of replication, optionally a promoter for the expression of the said polynucleotide and optionally a regulator of the promoter. The vectors may contain one or more selectable marker genes, for example an ampicillin resistance gene in the case of a bacterial plasmid or a neomycin resistance gene for a mammalian vector. Vectors may be used, for example, to transfect or transform a host cell. Control sequences operably linked to sequences encoding the protein of the invention include promoters/enhancers and other expression regulation signals. These control sequences may be selected to be compatible with the host cell for which the expression vector is designed to be used in. The term "promoter" is well-known in the art and encompasses nucleic acid regions ranging in size and complexity from minimal promoters to promoters including upstream elements and enhancers. The promoter is typically selected from promoters which are functional in prokaryotic or eukaryotic cells. With respect to eukaryotic promoters, they may be promoters that function in a ubiquitous manner or, alternatively, a tissue-specific manner. They may also be promoters that respond to specific stimuli. Viral promoters may also be used, for example the Moloney murine leukaemia virus long terminal repeat (MMLV LTR) promoter, the rous sarcoma virus (RSV) LTR promoter or the human cytomegalovirus (CMV) IE promoter. It may also be advantageous for the promoters to be inducible so that the levels of expression of the binding moiety can be regulated during the life-time of the cell. Inducible means that the levels of expression obtained using the promoter can be regulated. In a number of embodiments of the present invention, heterologous sequences are inserted into the various domains (including IgNAR variable domains, I-set domains and V-set domains) of the present invention. Such modifications are generally made by manipulating polynucleotides of the invention encoding the respective domain. This may conveniently be achieved by providing cloning vectors that comprise a sequence encoding a domain which sequence comprises one or more unique insertion sites to allow for easy insertion of nucleotide sequences encoding heterologous sequences into the appropriate region of the domain. Each "unique" insertion site typically contains a nucleotide sequence that is recognised and cleaved by a type II restriction endonuclease, the nucleotide sequence not being present elsewhere in the cloning vector such that the cloning vector is cleaved by the restriction endonuclease only at the "unique" insertion site. This allows for easy insertion of nucleotide sequences having the appropriate ends by ligation with cut vector using standard techniques well know by persons skilled in the art. Preferably the insertion site is engineered - i.e. where the domain is derived from a naturally occurring sequence, the insertion site does not naturally occur in the natural sequence. Vectors and polynucleotides of the invention may be introduced into host cells for the purpose of replicating the vectors/polynucleotides and/or expressing the binding moiety according to the invention encoded by the polynucleotides. Any suitable host cell may be used, including prokaryotic host cells (such as Escherichia coli, Streptomyces spp. and Bacillus subtilis) and eukaryotic host cells. Suitable eukaryotic host cells include insect cells (e.g. using the baculovirus expression system), mammalian cells, fungal (e.g. yeast) cells and plant cells. Preferred mammalian cells are animal cells such as CHO, COS, C 127, 3T3, HeLa, HEK 293, NIH 3T3, BHK and Bowes melanoma (particularly preferred being CHO-K1, COS7, YI adrenal and carcinoma cells). Vectors/polynucleotides of the invention may introduced into suitable host cells using any of a large number of techniques known in the art such as, for example, transfection (for example calcium phosphate transfection or DEAE-Dextran mediated transfection), transformation and electroporation. Where vectors/polynucleotides of the invention are to be administered to animals, several techniques are known in the art, for example infection with recombinant viral vectors such as retroviruses, herpes simplex viruses and adenoviruses, direct injection of nucleic acids and biolistic transformation. Host cells comprising polynucleotides of the invention may be used to express proteins of the invention. Host cells are cultured under suitable conditions wliich allow for expression of the binding moieties according to the invention. Expression of the binding moieties may be constitutive such that they are continually produced, or inducible, requiring a stimulus to initiate expression. In the case of inducible expression, protein production can be initiated when required by, for example, addition of an inducer substance to the culture medium, for example dexamethasone or IPTG, or inducible expression may achieved through heat-induction, thereby denaturing the repressor and initiating protein synthesis. Binding moieties according to the invention can be extracted from host cells by a variety of techniques known in the art, including enzymatic, chemical and/or osmotic lysis and physical disruption. Cell-free translation systems can also be used to produce the peptides of the invention. Appropriate cloning and expression vectors for use with prokaryotic and eukaryotic hosts are described in Sambrook (1989).
Libraries of binding moieties Binding moieties according to the invention may be provided as libraries comprising a plurality of binding moieties which have different sequences in the IgNAR variable domains, I-set domains or V-set domains. Preferably, the variations reside in one or more loops. These libraries can typically be used in screening methods to identify a binding reagent with an activity of interest, such as affinity for a specific target molecule of interest. Libraries of binding moieties are conveniently provided as libraries of polynucleotides encoding the binding moieties. The polynucleotides are generally mutagenised or randomised to produce a large number of different sequences which differ at one or more positions within at least one β strand or loop region. Mutations can be introduced using a variety of techniques known in the art, such as site-directed mutagenesis. A number of methods for site-directed mutagenesis are known in the art, from methods employing single-stranded phage such as Ml 3 to PCR-based techniques (see "PCR Protocols: A guide to methods and applications", M.A. Innis, D.H. Gelfand, J.J. Sninsky, TJ. White (eds.). Academic Press, New York, 1990). Another technique is to use the commercially available "Altered Sites II in vitro Mutagenesis System" (Promega - U.S. Patent N° 5,955,363). Techniques for site- directed mutagenesis are described above. Pluralities of randomly mutated sequences can be made by introducing mutations into a nucleotide sequence or pool of nucleotide sequences 'randomly' by a variety of techniques in vivo, including; using 'mutator strains', of bacteria such as E. coli mutD5 (Low et al, 1996, J Mol Biol 60: 9-68); and using the antibody hypermutation system of B-lymphocytes (Yelamos et al, 1995, Nature 376: 225-9). Random mutations can also be introduced both in vivo and in vitro by chemical mutagens, and ionising or UV irradiation (Friedberg et al, 1995, DNA repair and mutagenesis. SM Press, Washington D.C.), or incorporation of mutagemc base analogues (Zaccolo et al, 1996 J Mol Biol 255: 589-603). 'Random' mutations can also be introduced into genes in vitro during polymerisation for example by using error- prone polymerases (Leung et al, 1989, Technique 1: 11-15). It is generally preferred to use mutagenesis techniques that vary the sequences present in the loop regions of the IgNAR variable domains, although framework changes (e.g. changes in the β stands) may also occur which may or may not be desirable. One method for targeting the loop regions is to provide a plurality of relatively short nucleotide sequences that are partially or fully mutagenised/randomised and clone these sequences into specific insertion sites in the IgNAR variable domains. Another approach is to synthesise a plurality of random synthetic oligonucleotides and then insert the oligonucleotides into a sequence encoding the IgNAR variable domain, I-set domain or V-set domain and/or replace a sequence encoding the IgNAR variable domains, I-set domain or V-set domain with the random synthetic oligonucleotides. A suitable method is described in WO 97/27213 where degenerate oligonucleotides are produced by adding more than one nucleotide precursor to the reaction at each step. The advantage of this method is that there is complete control over the extent to which each nucleotide position is held constant or randomised. Furthermore, if only C, G or T are allowed at the third base of each codon, the likelihood of producing premature stop codons is significantly reduced since two of the three stop codons have an A at this position (TAA and TGA). Oligonucleotide synthesis is performed using techniques that are well known in the art (see Eckstein, Oligonucleotides and Analogues: A Practical Approach, IRL Press at Oxford University Press 1991). Libraries can also be specified and purchased commercially. The synthetic process can be performed to allow the generation of all or most possible combinations over the length of the nucleic acid, thus generating a library of randomised nucleic acids. These randomised sequences are synthesised such that they allow in frame expression of the randomised peptide with any fusion partner. In one embodiment, the library is fully randomised, with no sequence preferences or constants at any position. In another embodiment, the library is biased, i.e. partially randomised in which some positions within the sequence are either held constant, or are selected from a limited number of possible variations. Thus some nucleic acid or amino acid positions are kept constant with a view to maintaining certain structural or chemical characteristics. The randomised oligonucleotides can then be inserted into a suitable site and/or replace a suitable sequence encoding a IgNAR variable domains, I-set domain or V-set domain. Generally the library of sequences will be large enough such that a structurally diverse population of random sequences is presented. This ensures that a large subset of shapes and structures is represented and maximises the probability of a functional interaction. It is preferred that the library comprises at least 1000 different nucleotide sequences, more preferably at least 104, 105 or 106 different sequences. Preferably, the library comprises from 104 to 1010 different sequences. Preferably at least 5, 10, 15 or 20 amino acid residues of the peptides encoded by the nucleotide sequences are randomised. Typically, the inserted peptides encoded by the randomised nucleotide sequences comprise at least 5, 8, 10 or 20 amino acids. Preferably, they also comprise fewer than 50, 30 or 25 amino acids. In another aspect, the present invention provides a method of selecting a binding moiety of the present invention with an affinity for a target molecule which comprises screening a library of polynucleotides of the present invention for expression of a binding moiety with an affinity for the target molecule. The libraries of polynucleotides encoding binding moieties can be screened using any suitable technique to identify a binding moiety having an activity of interest. For example, to identify a binding moiety that binds to a target molecule of interest, the library of polynucleotides is incubated under conditions that allow for expression of the binding moiety polypeptides encoded by the polynucleotides and binding of the polypeptides to the target molecule assessed. Binding is typically assessed in vitro or using whole cell assays. Suitable techniques for screening the library for binding moieties having an activity of interest include phage display and ribosome display as well as the use of viral vectors, such as retroviral vectors and in vivo compartmentalisation screening by protein bioarray. In a preferred embodiment this method involves displaying the IgNAR variable domain or multimeric reagent of the present invention as gene III protein fusions on the surface of bacteriophage particles. In another preferred embodiment the method involves displaying the IgNAR variable domain or multimeric reagent of the present invention in a ribosomal display selection system. The sequence of binding moieties identified in the screen can conveniently be determined using standard DNA sequencing techniques.
Diagnostic/Therapeutic Uses of Binding Moieties Binding moieties of the invention, including those identified in the screening methods of the invention, may be used in methods of diagnosis/therapy by virtue of their specific binding to a target molecule of interest. Such uses will be analogous to the plethora of diagnostic/therapeutic applications already known in relation to antibodies and fragments thereof. For example, binding moieties of the invention may be used to detect the presence or absence of molecules of interest in a biological sample. For diagnostic purposes, it may be convenient to immobilise the binding reagent to a solid phase, such as a dipstick, microtitre plate or chip. As discussed above, binding moieties of the invention when used diagnostically will typically be linked to a diagnostic reagent such as a detectable label to allow easy detection of binding events in vitro or in vivo. Suitable labels include radioisotopes, dye markers or other imaging reagents for in vivo detection and/or localisation of target molecules. Binding moieties may also be used therapeutically. For example, binding moieties may be used to target ligands that bind to extracellular receptors. In addition, binding moieties of the invention may be used, in a similar manner to antibodies, to target pharmacologically active substances to a cell of interest, such as a tumour cell, by virtue of binding to a cell surface molecule present specifically on the tumour cell to which the binding moiety binds specifically.
Administration In another aspect the present invention provides a pharmaceutical composition comprising an IgNAR variable domain or multimeric reagent according to the present invention and a pharmaceutically acceptable carrier or diluent. In another aspect the present invention provides a method of treating a pathological condition in a subject, which method comprises administering to the subject a pharmaceutical composition according to the present invention. Binding moieties of the invention including binding moieties identified by the screening methods of the invention may preferably be combined with various components to produce compositions of the invention. Preferably the compositions are combined with a pharmaceutically acceptable carrier, adjuvant or diluent to produce a pharmaceutical composition (which may be for human or animal use). Suitable carriers and diluents include isotonic saline solutions, for example phosphate-buffered saline. The composition of the invention may be administered by direct injection. The composition may be formulated for parenteral, intramuscular, intravenous, subcutaneous, intraocular, oral or transdermal administration. Typically, each protein may be administered at a dose of from 0.01 to 30 mg/kg body weight, preferably from 0.1 to 10 mg/kg, more preferably from 0.1 to 1 mg/kg body weight. Polynucleotides/vectors encoding binding moieties may be administered directly as a naked nucleic acid construct. When the polynucleotides/vectors are administered as a naked nucleic acid, the amount of nucleic acid administered may typically be in the range of from 1 μg to 10 mg, preferably from 100 μg to 1 mg. Uptake of naked nucleic acid constructs by mammalian cells is enhanced by several known transfection techniques for example those including the use of transfection agents. Example of these agents include cationic agents (for example calcium phosphate and DEAE-dextran) and lipofectants (for example lipofectam™ and transfectam™). Typically, nucleic acid constructs are mixed with the transfection agent to produce a composition. Preferably the polynucleotide or vector of the invention is combined with a pharmaceutically acceptable carrier or diluent to produce a pharmaceutical composition. Suitable carriers and diluents include isotonic saline solutions, for example phosphate-buffered saline. The composition may be formulated for parenteral, intramuscular, intravenous, subcutaneous, oral, intraocular or transdermal administration. The routes of administration and dosages described are intended only as a guide since a skilled practitioner will be able to determine readily the optimum route of administration and dosage for any particular patient and condition. The various features and embodiments of the present invention, referred to in individual sections above apply, as appropriate, to other sections, mutatis mutandis. Consequently features specified in one section may be combined with features specified in other sections, as appropriate. The present invention will now be further described in the following non- limiting Examples. EXAMPLES
EXAMPLE 1: Expression of VNAR 12Y-1 and 12Y-2 proteins Recombinant proteins 12Y-1 (SEQ ID NOs: 1 & 2) and 12Y-2 (SEQ ID NOs: 3
& 4) were expressed into the E. coli periplasm in frame with 21 residue C-terminal dual octapeptide FLAG epitopes and linker regions (N"AAADYKDDDDKAADYKDDDDK" ) as described (Nuttall 2004). Briefly, E. coli TGI starter cultures were grown overnight in 2YT medium/ ampicillin (100 μg/mL)/ glucose (2.0% w/v.), diluted 1/100 into fresh 2 YT/ 100 μg/mL ampicillin/ glucose (0.1 % w/v) and then grown at 37°C/200 m until OD55onm = 0.2-0.4. Cultures were then induced with IPTG (lmM final), grown for a further 16 hours at 28°C and harvested by centrifugation (Beckman JA- 14/6K/10min/4°C). Periplasmic fractions were isolated by the method of Minsky (Minsky 1994) and recombinant protein purified by affinity chromatography through an anti-FLAG antibody-Sepharose column (10 x 1cm). The affinity column was equilibrated in TBS, pH 7.4 and bound protein eluted with ImmunoPure™ gentle elution buffer (Pierce). Eluted proteins were dialysed against two changes of 0.02M Tris pH7.5, concentrated by ultrafiltration over a 3000 Da cutoff membrane (YM3, Diaflo), and analysed for purity and activity by size exclusion chromatography, SDS- polyacrylamide gel electrophoresis, and biosensor.
EXAMPLE la: Expression of VNAR 1A-7 and 12A-9 proteins Recombinant proteins 1 A-7 (SEQ ID NOs: 5 & 6) and 12A-9 (SEQ ID NOs: 9 & 10) were expressed into the E. coli periplasm, purified and analysed exactly as described in Example 1 above.
EXAMPLE 2: Crystallization of VNAR 12Y-1 and 12Y-2 proteins Recombinant protein 12Y-2 (14mg/ml) was set up in 2μl hanging drops using the Hampton Research sparse matrix crystallization screening kit. Plates were incubated at 25°C. Final crystallization conditions were 0.1M Sodium citrate pH4.6/20% v/v iso-Propanol/20% PEG4000. Diffraction quality crystals were obtained after 48h. Recombinant protein 12Y-1 (6mg/ml) was set up as 0.2μl sitting drops using a
Cartesian Honey Bee robot. Plates were incubated at 25°C. Successful conditions were scaled up to 2μl hanging drops, using 12Y-1 protein at 13mg/ml. Final crystallization conditions were 0.1M bis-tris Propane pH6.5/45% PPG P400. Diffraction quality crystals were obtained after 7 days.
EXAMPLE 2a: Crystallization of VNAR 12A-9 and 1A-7 proteins Recombinant protein 12A-9 (7mg/ml) was set up as 0.2 μl sitting drops using a
Cartesian Honey Bee robot. Plates were incubated at 25°C. Successful conditions were scaled up to 2 μl hanging drops. Final crystallization conditions were 0.1M CHES pH 9.5/50% PEG200. Diffraction quality crystals (space group P2i2]2) were obtained after 40 days. Recombinant protein 1A-7 (6mg/ml) was set up as 0.2μl sitting drops using a
Cartesian Honey Bee robot. Plates were incubated at 25°C. Successful conditions were scaled up to 2μl hanging drops. Final crystallization conditions were 0.1M acetate pH 4.6/20% PEP (17/8 PO/OH). Diffraction quality crystals (space group I2ι2ι2ι) were obtained after 10 days.
EXAMPLE 3: Data collection and structure determination for 12Y-1 and 12Y-2 X-ray diffraction data collections from all crystals were conducted in-house using Rigaku RAXIS IV (Rigaku-MSC) and Mar 180 (MarResearch) image plate detectors mounted on a Rigaku HR3 HB X-ray generator equipped with monocapillary focusing optics (AXCO). Data were collected at -160°C; the crystals required no added cryoprotectant. All data processing was carried out using the DENZO/SCALEPACK suite (Otwinoski 1997). Diffraction data statistics are summarized in Table 2. Initial heavy atom screening for 12Y-1 protein was performed by native polyacrylamide gel electrophoresis using the Heavy Atom Screen M2 kit (Hampton Research. Band shifts were observed for Lutetium (III) Acetate Hydrate (LAH; Lu(O C2H3)2) and Potassium Hexachloro Rhenium (PHR; K2ReCl6). Isomoφhous heavy atom derivatives were obtained by soaking 12Y-1 crystals for -30 min in 0.8 1 of 50mM of LAH or PHR. Heavy atom sites were identified and refined with the statistical phasing program SHARP (La fortell 1997), and solvent-fattening procedures DM and SOLOMON used to resolve the phase ambiguity. The residual and anomalous difference Fourier maps produced by SHARP were examined in order to locate further heavy atom peaks, which were included in subsequent cycles of phase refinement and calculation using SHARP. Several iterations of this cycle located additional positions and improved phases to 2.82A. This result was achieved using the phasing power of both Lu and Re. The model was manually built using XtalView (McRee 1999) into the electron- density map (centroid map) produced by SHARP. The model was then refined against the native 12Y-1 data using CNS (Brunger 1998) and CCP4 (CCP) packages. Difference electron density maps 2m|i? 0|-D| c| and m| 0|-| c| were used to improve the model in the XtalView program. During the model building and refinement, 5% of the data was flagged for cross-validation to monitor the progress of refinement. The electron density map allowed unambiguous tracing of all residues except the CDR3 analogous loop residues (88-98), which disordered. Water molecules were located automatically with the program ARP (Lamzin 1997) for >2σ peaks in the m|E0|- | C| map and retained if they satisfied H-bond criteria and returned 2m| 0|-D| 0| density after refinement. Following the convergence in standard refinement, a further improvement of more than 2% in R factors was achieved by refining all protein atoms as one anisotropic domain with the TLS procedure in CCP4 REFMAC5 (Wins 2001). The libration tensor showed significant anisotropy. The final R and Rfιee values were 0.166 and 0.254, respectively for a 6-2.82A range of refined data. The final 12Y-1 model contains 100 amino acids (residues 1-87 and 99-111) and 97 water molecules. Of the residues in the 12Y-1 model, 84.5% fall in the most favourable regions of a Ramachandran plot generated by CCP4 PROCHECK (Laskowski 1993) with no residues in the generously allowed or disallowed regions. Further details are given in Table 2. The structure of 12Y-2 was determined by molecular replacement using CCP4
MOLREP. The search model was the 12Y-1 structure (above) without the CDR3 analogous loop. Two 12Y-2 monomers (A and B) were identified in the asymmetric unit of the I2χ2\2\ space group. Iterative model building using XtalView and refinement using REFMAC5 allowed a complete trace of A and B monomers including extended CDR3 analogous loops. The electron density was well defined in the CDR3 analogous loop region. Progress of the refinement was monitored using the R^ statistic based on a set encompassing 5% of the observed diffraction amplitudes. Water molecules were added automatically with the program ARP as described for 12Y-1. The final refinement included the TLS parameters for each molecule individually as a TLS group in the asymmetric unit and converged to R and -g-ee values of 0.176 and 0.247 , respectively, for the 18.12-2.18A range of experimental data. As for 12Y-1, only the libration tensor was significant, though less anisotropic. The final model comprises residues 1 to 113 of the 12Y-2 A and B chains, and 358 water molecules. In total, 93.4% of residues are in the most favoured regions of the Ramachandran plot, with no residues in the generously allowed or disallowed regions. This indicates that the 12Y-2 model is consistent with a highly refined protein structure. Further details are in Table 2.
EXAMPLE 3a: Data collection and structure determination for 12A-9 and 1A-7 X-ray diffraction data collection for 1 A-7 crystal was conducted in-house using Mar 180 (MarResearch) image plate detectors mounted on a Rigaku HR3 HB X-ray generator equipped with monocapillary focusing optics (AXCO). X-ray diffraction data for 12A-9 crystal was collected at the Photon Factory synchrotron BL5 beamline in Japan. Data for both crystals were collected at -160°C; the crystals required no added cryoprotectant. All data processing was carried out using the DENZO/SCALEPACK suite (Otwinoski 1997). Diffraction data statistics are summarized in Table 2. The structures of 1A-7 and 12A-9 were determined by molecular replacement using CCP4 MOLREP. The search model for 1A-7 was the 12Y-1 two-fold dimer without the CDR3 analogous loops. Four 1A-7 monomers (A, B, C and D) were identified in the asymmetric unit of the \2 2\2\ space group. Iterative model building using XtalView and refinement using REFMAC5 allowed a complete trace of A and C monomers including CDR3 analogous loops. The electron density was not well defined in the CDR3 analogous loop region (89-98) for monomers B and D. The A & B and C & D chains form two approximately 2-fold dimers (see Figure 15) similar to those observed in 12Y-1 and 12Y-2 structures. Water molecules were added and progress of the refinement was monitored as described for 12Y-1 and 12Y-2. The final refinement included the TLS parameters for each molecule individually as a TLS group in the asymmetric unit and converged to R and ?&ee values of 0.176 and 0.265, respectively, for the full 21.6-2.7 A range of experimental data. The final model comprises residues 1 to 111 of the 1A-7 A and C chains, and residues 1-88 and 99-111 for B and D chains, and 489 water molecules. In total, 90.9% of residues are in the most favoured regions of the Ramachandran plot, with 2 residues for chain C in the generously allowed or disallowed regions. Overlay of 1A-7 full chains A and C, and 12Y-2 chain A is shown in Figure 5a. Further details are given in Table 2. The search model for 12A-9 was the 12Y-1 structure (above) without the CDR3 analogous loop. One molecule of 12A-9 was identified in the asymmetric unit of the P2A2 space group. The electron density was traceable in the CDR3 analogous loop, however with somewhat diffuse 92-95 region. The final refinement included the TLS parameters for whole molecule and converged to R and Rft∞ values of 0.217 and 0.280, respectively, for the full 39.5-2.1 A range of experimental data. The final model comprises residues 1 to 108 of the 12A-9 (see Figure 14) and 140 water molecules. In total, 88.4% of residues are in the most favoured regions of the Ramachandran plot, with 1 residue in the generously allowed regions. Further details are in Table 2.
EXAMPLE 4: Structure of the crystallographic dimer The inter-dimer relative disposition of monomers can be described as rotation by
6.9° and screw translation by -0.43A. This was calculated as follows. The 12Y-1 dimer was overlaid onto that of the 12Y-2 dimer using a least-squares supeφosition of corresponding Cα atoms selected from a single monomer only, then the magnitude of the rotation (about the centre of mass) and translation then required to superimpose the remaining monomer from the first crystal form onto that from the second crystal form was calculated. EXAMPLE 5: Coordinates for 12Y-1 and 12Y-2 The coordinates for 12Y-1 and 12Y-2 are attached as Appendices 1(a) and 1(b) respectively.
EXAMPLE 5a: Coordinates for 12A-9 and 1A-7 The coordinates for 12A-9 and 1A-7 are attached as Appendices 1(c) and 1(d) respectively. EXAMPLE 6: Modifications to loop regions of 12Y-2 Loop region 8 of 12Y-2 adopts a β-haiφin configuration with β-strands extending for a significant portion of its length, stabilized by main-chain hydrogen bonds. This β-haiφin configuration is conserved by main-chain hydrogen bonds, for example, between: Tyr87 (O) - PhelOO (N); Leu89 (N) - Leu98 (O); Leu89 (O) - Leu98 (N). The elongated loop extends outward and upward from the immunoglobulin framework and creates a structure ideal for penetrating buried clefts and cavities in, for example, enzyme active sites, parasite coat proteins, or viral canyons. The following table is a comparison of the length of loop region 8 of 12Y-2 with long CDR3 loops from cleft binding antibodies such as bl2 Ig (targeting HIV gpl20; Saphire 2001); camelid VHH IMEL (targeting lysozyme, Desmyter 1994); and T cell receptor IQRN.
Figure imgf000068_0001
These figures show that the 12Y-2 loop region 8 is relatively long, suggesting that the VNAR scaffold is ideal for displaying such long CDR3-like loops. This analysis indicates that modifications to loop region 8 may lead to the generation of novel diagnostic or therapeutic binding moieties. Additionally, modifications to other regions of the VNAR scaffold, and in particular the 12Y-2 scaffold, may also lead to the generation of novel diagnostic or therapeutic binding moieties. Examples of modifications include:
1. Grafting of extended CDR3 loops with specifically designed amino acid sequences onto the VNAR scaffold in the vicinity of loop region 8. For example, the sequence RVGPYSWDDSPQDNYYM may be grafted onto the 12Y-2 scaffold in the vicinity of loop region 8 to form an extended loop corresponding to the anti-HIV antibody bl2 (IHZH) and thereby provide novel binding moiety with an IgNAR scaffold capable of binding HIV gpl20. The grafting may involve, for example, replacement of amino acid residues 86 to 103 of 12Y-2 (or a portion of these residues) with RVGPYSWDDSPQDNYYM. In another example, the sequence CSKPSDSNC, representing a protruding loop of the major surface antigen (HBsAg) from hepatitis B virus (HBV) may be grafted onto the VNAR scaffold 24G-3 (SEQ ID NO: 101), in place of the CDR3 loop. The resulting IgNAR could then be used to assess the interaction of the HBsAg loop with other HBV proteins.
2. Grafting of CDRl loops with specifically designed amino acid sequences onto the VNAR scaffold in the vicinity of loop region 4. For example, the sequence GYRFSNFVI of the anti-HIV antibody bl2 (IHZH) may be grafted onto the 12Y-2 scaffold in the vicinity of loop region 4 and, when combined with the CDR3 loop graft of the anti-HIV antibody bl2 described in (1) above, will enhance the binding affinity to gpl20. The grafting may involve, for example, replacement of amino acid residues 28 to 33 of 12Y-2 (or a portion of these residues) with the sequence GYRFSNFVI. To determine if CDRl loop grafting would change the affinity and expression qualities of the 12Y-2 VNAR, the N-terminal half of the 14M-15 clone (SEQ ID NOs: 11 & 12) of 12Y-2 was replaced with a library of sequences. This effectively produced a library of CDRl/N-terminus framework variants combined with a fixed CDR3. 88 CDRl shuffled VNAR clones were analysed by ELISA for binding to AMAl antigen.
Nineteen clones had affinity for AM-1, whilst the remaining 69 showed no binding.
No clones had detectable affinity for a negative control antigen (bovine serum albumin). This indicates that the CDRl sequence and conformation is vital to IgNAR binding. Figure 16 presents the results of ELISA analysis of five clones with high affinity and 5 clones with no detectable affinity. Comparative expression levels are also given. Figure 17 presents the amino acid sequence alignment of the clones from
Figure 16. Of the clones with highest affinity, three had similar CDRl sequences (24A-58, 24A-75, 24A-46) but the remaining two were significantly different (24A-82 and 24A-
72). The similar clones shared the common CDRl sequence "RDTSCAFSSTG" and had 1-3 residues differing in the framework region near the N-terminus. The sequences for 5 clones with no detectable antigen affinity also had significant variability.
Additionally, the amount of IgNAR protein present varied among the clones (only 4 of 88 produced no detectable protein). This indicates that the CDRl sequence and conformation are also vital to IgNAR expression levels and protein production.
Sequence differences map predominantly to the CDRl loop region, with some contribution from framework residues, and have a marked affect on both affinity and protein expression levels.
3. Mutation or insertion of specific residues in loop region 8. For example, mutating residues Pro90 and/or PhelOO may enhance the flexibility of loop region 8 thereby resulting in improved antigen binding. A randomly generated library of 12Y-2 variant containing on average one amino acid change per 100 residues was screened against AMAl antigen. Two high affinity clones were isolated each separately showing 10-fold enhanced affinity over the wild type 12Y-2. These were designated 14M-15 (Pro90Leu) (SEQ ID NOs: 11 & 12) and
14M-8 (PhelOOLeu) (Nuttall et al. 2004).
4. Randomisation of the entire loop region 8, varying in length and amino acid composition. This is in effect the creation of new shark libraries which are described in various Examples below.
5. Randomisation of the entire loop region 8, varying in length and amino acid composition together with improvement of the loop region-framework junctions by incorporation of the combinations of paired junction residues: Gly84 + Glul03, or Gln84 + Gly 102. The VNAR library was expanded by designing new degenerate oligonucleotide primers for CDR3 (loop region 8) with loop lengths of either 12 or 13 residues and framework residue combination of either: Gly84 + Glul03, or Gln84 + Gly 102. These and other CDR3 combinations were used to construct a further VNAR library of > 2x 10 members.
The following new primer oligonucleotides were used: A0295 (SEQ ID NO: 64), A0296 (SEQ ID NO: 62), A0297 (SEQ ID NO: 63) and A0298 (SEQ ID NO: 61). The IgNAR domain was completed using combinations of the primers disclosed in SEQ ID Nos: 47-60.
6. Randomisation of the residues at the tip of loop region 8, for example, from residues Pro90-Ser97, or other such variations, and expansion or contraction of this loop by incorporation or removal of residues, and differing number and strategy of randomised residues.
Modification of loop region 8 residues Leu98, Leu99 may be made in a similar manner. For example:
Set 1 (Short loop 8 residues)
Leu89 to Ser97 replaced by 7 randomised residues; Leu98 constrained modification according to the nucleic acid encoding formula: (NNK)7 + (SNK)1.
Set 2 (Randomised loop 10 residues) Leu89 to Ser97 replaced by 9 randomised residues; Leu98 constrained modification according to the nucleic acid encoding formula: (NNK)9 + (SNK)1.
Set 3 (Long Loop Leu98-99) Leu89 to Ser97 replaced by 8 randomised residues with a tyrosine/ring amino acid bias and Leu99 constrained modifications according to the nucleic acid encoding formula: (NNK)1 (YMC)l (NNK)1 (YMC)l (NNK)2 (YMC)l (NNK)1 (SNK)1 (SNK)1.
Set 4 (Long Loop 11 residues) Leu89 to Ser97 replaced by 10 randomised residues with a central tyrosine/ring amino acid bias and Leu98 constrained modification according to the nucleic acid encoding formula: (NNK)3 (YMC)4 (NNK)3 (SNK)1.
Set 5 (Long Loop 12 residues) Leu89 to Ser97 replaced by 12 randomised residues with an aromatic bias and no Leu98 constraints according to the nucleic acid encoding formula: (NNK)3 (WDB)1 (NNB)2 (WD )i (NNK)2 (WDS)1 (NNB)2
Set 6 (Long Loop 12 residues) Leu89 to Ser97 replaced by 12 randomised residues with an aromatic bias and no Leu98 constraints according to the nucleic acid encoding formula: (WDB)! (NNK) (WDS)j (NNB)2 (WDB)i (NNK)2 (WDB)X (NNB)2
A library based on 12Y-2 of size -1x10s independent clones was constructed using equal representations of these 6 oligonucleotide primers. The library was screened against different strains of Plasmodium falciparum AMAl, i.e. W2MEF and HB3 (not recognised by the parent 12Y-2), and original antigen AMA-1 3D7 (positive control).
Figure 18 shows the KH (12Y-2 loop) library panned against different malarial strains.
EXAMPLE 7: Proposed modifications to expand the binding face of the VNAR Results presented herein show that the VNAR "CDR2" loop is non-existent, replaced by a short β-turn at the bottom of the molecule. This is graphically illustrated in Figure 12, where the VNAR "CDR2" is aligned with that of a typical human antibody. The "bottom" position of this loop, combined with the low sequence variability, strongly suggests that this region has little impact on the interaction with antigen. However, the loss of the conventional C" and D strands suggests a possible alternative model for antigen binding, where the extended 12Y-2 loop region 8 combines with the large concave pocket opened in the absence of the conventional CDR2. This concave pocket is a potential antigen binding face. The pocket comprises residues loop region 8, loop region 5 and C & D β-strands. These residues (for 12Y-2) include: Asp33, Tyr37, Glu46, Ser48, Ser50, Ile51, Val59, Lys61, Phe86, Tyr94, Asn95, Tyr96, Leu98, Leu99 & ArglOl. This antigen binding surface is unlike any antibody paratope (the antigen-binding surface of an antibody), since the loop regions are distant from each other (are not in contact) and the antigen contact residues may include framework residues between the loop regions. This analysis suggests that the randomisation of selected residues within the C, C\ D strands, and the loop regions 5 and 8, can be used to construct "pincerbody" molecular libraries, which will bind antigen by a combination of loop and framework residues. Suitable target residues (for the 12Y-2 structure) are, singly and in combination:
Figure imgf000073_0001
Figure imgf000074_0001
A randomly generated library of 12Y-2 variants containing on average one amino acid change per 100 residues was screened against AMAl antigen. A high affinity clone was isolated incoφorating the mutations Pro90Leu (identical to 14M-15) and the additional mutation Thr39Ser. This protein (22A-2: SEQ ID NO: 15) had twofold better affinity than 14M-15, by ELISA (see Figure 22(a)), biosensor (see Figure 22(e)), and protein bioarray (KD 2.6nM VS KD 6.5nM). Protein expression characteristics were unchanged (see Figure 22(d)). This mutation is at position 39 in the framework just N-terminal to β-strand region C (see Figures 22(b) and (c)). This indicates that framework region mutations can have a significant effect upon affinity, especially in the vicinity of "CDR2". Without being limited by theory, it is believed that this may affect the torsions of the strands which alter the CDR conformations sufficiently to enhance binding. EXAMPLE 8: Generation of therapeutics or diagnostics by loop grafting from shark to human domains The structures of IgNARs and human Immunoglobulin superfamily I-set domains are homologous enough to allow prediction of framework/loop region junctions, take-off angles of strands, and loop orientations. Binding loops discovered for VNARS can be grafted to human I-set frameworks such as but not limited to NCAM, ICAM, and Telokin. This will form a human binding domain Ig-like reagent with only the variable loop regions derived from non-human sources. These may be particularly useful as cleft-binding "human-Ig-like" reagents, since they possess antigen-binding surfaces different from any known naturally occurring antibody. The following modifications may, for example, be made to I-set framework molecules such as NCAM, ICAM or Telokin:
1. Grafting of anti- AMAl loop region 8 from 12Y-2 onto I-set framework. 2. Grafting of anti- AMAl loop region 4 and 8 from 12Y-2 onto I-set framework.
3. Grafting of anti-AMAl loop region 8 from 12Y-1 onto I-set framework.
4. Grafting of anti-AMAl loop region 4 and 8 from 12Y-1 onto I-set framework.
5. Grafting other VNAR loop region 8 onto I-set framework.
6. Grafting other VNAR loop region 4 onto I-set framework. 7. Grafting of loop regions 4 and 8 from VNA S onto I-set framework, where these loops are linked by a disulphide bridge.
8. Incoφoration of loop region 4-8 disulphide bridges into loops grafted onto I-set framework.
9. Generation of a library of I-set frameworks by randomising equivalent loops the loop regions 4 and 8.
10. Generation of a library of I-set frameworks by randomising equivalent loops to loop regions 4 and 8, and use as a set of variable "virus traps" for identifying viruses targeting the cell adhesion molecules.
Cloning of NCAM and Telokin. The Neural Cell Adhesion Molecule 1 (NCAM; CD56) is a mammalian cell- surface glycoprotein which mediates neuronal cell adhesion. The extracellular domain consists of 5 Ig superfamily domains followed by 2 fibronectin Type 3 domains (see Figure 23(a)). Domain 1 of NCAM is classified within the I-set of the Ig superfamily and is unmodified by glycosylation or other post-translational modification. Coding sequences for the wild-type human NCAM domain 1 (SEQ ID NO: 37) and wild-type human NCAM domains 1+2 (SEQ ID NO: 39) were amplified from a human cDNA library and cloned in-frame into the E. coli cloning/expression vector pGC. A0657 (SEQ ID No: 77) was used as the forward 5' primer for domain 1. A0658 (SEQ ID No: 78) was used as the reverse 3' primer for domain 1. A0659 (SEQ ID NO: 79) was used as the reverse primer for domain 2. A0979 (SEQ ID NO: 80) was used as the NCAM secondary extension primer. Clones were verified by DNA sequencing. Both the wild-type domain 1 (clone 21H-5: SEQ ID NO: 36) and wild-type domains 1+2 (clone 21G-1: SEQ ID NO: 38) were successfully expressed as soluble protein into the E. coli periplasmic space as measured by Fast Protein Liquid Chromatography (FPLC) (see Figure 23(c)) and SDS- PAGE. Crystal leads were obtained for providing evidence for folding into an ordered conformation. Myosin Light Chain Kinase (MLCK) consists of 3 N-terminal Ig-like domains, a calmodulin-binding catalytic domain, and one C-terminal Ig-like domain (see Figure 24(a)). Activation of MLCK following binding by calcium-calmodulin results in phosphorylation of a specific serine in the N-terminus of a myosin light chain, leading to the formation of calmodulin/MLCK signal transduction complexes which allow selective transduction of calcium signals, ultimately causing muscle contraction. The Ig-like domains flanking the catalytic domain enable binding of MLCK to myosin. Independent transcription of the C-terminal Ig-like domain of MLCK from an internal promoter gives rise to the production of the mature protein, Telokin. Telokin is an I-set Ig domain and has phosphorylation sites at Ser-12 and Ser-18. It appears to modulate MLCK activity by binding to unphosphorylated myosin thus preventing phosphorylation by MLCK. The coding sequence for the human Telokin domain 1 was amplified from a human cDNA library and cloned in-frame into the E. coli cloning/expression vector pGC. A0678 (SEQ ID No: 88) was used as the forward 5' primer. A0677 (SEQ ID NO: 89) was used as the reverse 3 'primer. A0999 (SEQ ID NO: 96) was used as the Telokin N-terminus secondary extension primer. Clone 21 J-4 was correct as verified by DNA sequencing (SEQ ID NO: 42). Telokin domain was successfully expressed as soluble protein (SEQ ID NO: 41) into the E. coli periplasmic space as measured by FPLC (see Figure 24(c)) and SDS-PAGE.
Modeling and loop grafts In order to produce human binding domain Ig-like reagent with only the variable loop regions derived from non-human sources, i.e. shark IgNAR antibodies, the CDR3 loop from VNAR 1A-7 was modeled for loop-grafting to NCAM domain 1 and Telokin I-set domains. Shark VNARS, NCAM domain 1 and Telokin were least squares aligned to determine where framework structural homology was greatest to assess grafting points for variable "VNAR CDR3" loops. These loops varied in both length and sequence and were modelled as chimeras onto NCAM domain 1 and Telokin frameworks to produce human binding domain Ig-like reagents. A variety of chimeras were then designed and constructed using Modeller6v2 with variation of the VNAR CDR3 (i.e. loop region 8) length and sequence according to
Table 5. Each model was then assessed for deviation from the human framework and
VNAR CDR3 structures by visual inspection and for potential stability (energy) according to the modeller objective scores. The best scoring models were for NCAM model 5, and for Telokin model 3 and model 5.
NCAM - 1A-7 loop grafts: The best NCAM/shark 1A-7 CDR3 loop graft (model 5) was constructed by overlap PCR using oligonucleotide primer A0989 (SEQ ID NO: 81). The resulting clone designated 23B-2 was verified by DNA sequencing (SEQ ID NO: 40). Protein expression and purification showed that the resulting recombinant protein appeared more stable than the wild type, for example there appeared little degradation by SDS-PAGE (see Figure 25(c)), and a single peak by FPLC (see Figure 25(b)). This protein when placed in crystallisation trials gave several strong crystal leads, indicating that it was folded into a stable and ordered structure. Recombinant protein 23B-2 specifically interacted with the target antigen (monoclonal antibody 5G- 8) but not to a negative control antigen (lysozyme) in an ELISA (see Figure 25(d)). Specific binding of the 23B-2 but not wild type NCAM domain 1 was confirmed by Biosensor (see Figure 25(e)).
Telokin 1A-7 loop grafts The best Telokin/shark 1 A-7 CDR3 loop grafts (models 3 & 5) were constructed by overlap PCR using oligonucleotide primers A1022 (primary extension primer) (SEQ ID NO: 90) and A1023 (secondary extension primer) (SEQ ID NO: 91) (Model 3), and primers A1024 (primary extension primer) (SEQ ID NO: 92) and A1025 (secondary extension primer) (SEQ ID NO: 93) (Model 5). The resulting clones were designated 24F-4 (SEQ ID NOs: 43 & 44) (model 3) and 23C-7 (SEQ ID NOs: 45 & 46) (model 5), and were verified by DNA sequencing. Protein expression and purification showed that the resulting recombinant proteins were expressed into the E. coli periplasmic space. FPLC traces and SDS- PAGE profiles of the recombinant proteins are shown in Figure 26(b) & (c). Both loop graft model recombinant protein (23C-7, 24F-4) specifically interacted with the target antigen (monoclonal antibody 5G-8) but not a negative control antigen (lysozyme) (see Figure 26(d)). Specific binding of the 24F-4, but not wild type Telokin, was confirmed by Biosensor (see Figure 26(e)).
EXAMPLE 9: Generation of therapeutics or diagnostics by loop grafting from human domains to shark VNARS. The structures of IgNARs human Immunoglobulin superfamily I-set domains are homologous enough to allow prediction of framework/loop region junctions, take- off angles of strands, and loop orientations. I-set domains such as ICAM-1 have been implicated as receptors for viruses such a rhinovirus. Binding loops on ICAM-1 specific for rhinovirus binding can be grafted to VNAR frameworks, giving rise to novel binding moieties. This can be further expanded to other viral diagnostics based on I-set domains. For example, the following modifications may be made to shark NARs:
1. Grafting of rhinovirus-binding ICAM-1 VLR loops onto the 12Y-2 framework.
2. Grafting of rhinovirus-binding ICAM-1 VLR loops onto the 12Y-1 framework.
3. Grafting of rhinovirus-binding ICAM- 1 VLR loops onto a VNAR framework. 4. Grafting of rhinovirus-binding ICAM-1 VLR loops onto a dimeric or multimeric VNAR framework. 5. Grafting of rabies virus-binding NCAM VLR loops onto the 12Y-2 framework.
6. Grafting of rabies virus-binding NCAM VLR loops onto the 12Y-1 framework.
7. Grafting of rabies virus-binding NCAM VLR loops onto a VNAR framework.
8. Grafting of rabies virus-binding NCAM VLR loops onto a dimeric or multimeric VNAR framework.
9. Grafting of virus-binding I-set VLR loops onto a VNAR framework.
10. Grafting of virus-binding I-set VLR loops onto a dimeric or multimeric VNAR framework. VLRs are the variable loop regions of V-set and I-set domains, these being the loop regions which typically extend between β-strand conformations and which demonstrate natural amino acid variation without compromising the framework structure of the domain. VLRs include those regions typically referred to as CDRs.
EXAMPLE 10: Generation of soluble human variable domains by "sharkisation": CDR2 region CDR2 loops generated by the C and C" strands of the V-set immunoglobulin superfamily proteins are important in antigen binding and maintenance of the solvent solubility of the immunoglobulin. With the shark domain CDR2 loop equivalent in "bottom" position, there is now a solvent-exposed patch of residues at the C-terminus of loop region 4 and in the C and D β-strands, which in other immunoglobulin domains is shielded by the CDR2 loop. This solvent-exposed face consists mainly of the 12Y-2 residues Lys32, Asp33, Thr34, Gly35, Tyr55, Glu57, Thr58. The charged and polar patch formed by residues Asp33-Thr34-Glu57 appears to be particularly significant. In one example, these residues may be "transferred" to I-set variable domains, for example neural cell adhesion molecules (NCAMs), to render these proteins more soluble when expressed in a single domain format. In another example, these residues may be "transferred" to V-set domains such as TCRs and antibodies, where the CDR2 loop has been removed to avoid superantigen stimulation. See, for example, the following table:
Figure imgf000080_0001
§ For TCR α of lao7. If In Nurse shark Typel, this position occupied by half-cysteine. * Across Wobbegong, Nurse, and Bamboo sharks, Types 1, 2, & 3 IgNARs. EXAMPLE 11: Generation of soluble human TCRs by "sharkisation": VH/VL interface Attempts in the past to produce single human TCR domains have been problematic at best, due to low solubility and difficulty in expression. Comparison of the 12Y-1 and 12Y-2 VNARS to the TCR α (and β) domains show a number of aspects where the human TCR could be modified by reference to the shark structure. "Sharkisation" gives us the opportunity to separately produce the TCR Vα or Vβ domain and enhance its solubility by directed mutation. Table 6 presents a comparison of TCR interfaces with the 12Y-2 and camelid variable domains. This analysis suggests that the following modifications may be made to enhance solubility of TCR domains:
1. Residue Ser31 in the TCR interface is almost always a serine or tyrosine: thus a polar residue. In VNARS it can be a charged (Asp) residue, or a serine in -50% of cases. Mutation of residue 31 of a TCR domain to Asp may therefore enhance solubility. 2. Significant residues in the TCR domain interface are Pro43/Leu89/Phel06 (and equivalents). This is an extensive hydrophobic patch in TCR Vα and Vβ domains. Mutation of these residues to form a charged pocket, similar to that formed by residues Glu46, Lys82, Lys 104 of 12Y-2 may therefore enhance solubility.
EXAMPLE 12: Generation of soluble antibody variable domains by "sharkisation": VH/VL interface Attempts in the past to produce single antibody variable domains have encountered solubility and expression problems. Comparison of the 12Y-1 and 12Y-2
VNARS to antibody VH and VL domains shows a number of aspects where these individual domains could be modified by reference to the shark structure, to improve solubility and expression levels. For example:
1. Modification of the VH or VL interface to enhance solubility of the isolated single domain, using residues described in Example 11 above. Mutation of these residues to form a charged pocket, similar to that formed by residues Glu46, Lys82, Lys 104 of 12 Y-2 may therefore enhance solubility.
EXAMPLE 13: Modification of VNAR dimers The 12Y-1 & 12 Y-2 dimer forms are a continuous 8-stranded β-sheet underneath the loop regions (buried surface area at interface -1760 A2). The interactions between the 2-fold monomers involve main-chain β sheet interactions between D strands and between loop region 8 as well as side-chain interactions and water mediated contacts. This suggests a significant propensity for dimer interactions with non-standard involvement of loop regions in complex formation. The dimer form may act as a single binding entity with the loop region 8 residues and framework residues of the dimer available for mutation and library selection. This suggests that the following modifications may be made to generate binding moieties with potential diagnostic or therapeutic applications: 1. Stabilisation of a recombinant dimer by introduction of cysteine residues at positions Lys61 and Glu57 in the D strand of a VNAR- Alternatively, stabilisation may be achieved by the introduction of cysteine residues at positions Ile51 and either Lys61 or Gly62 in the D strand.
2. Stabilisation of the recombinant dimer by introduction of cysteine residues at positions Lys32 and Asp33 in loop region 4 of the VNAR-
3. Stabilisation of the recombinant dimer by introduction of cysteine residues at position Val 59.
4. Stabilisation of a recombinant dimer by introduction of cysteine residues at positions Leu98 and/or Leu99 in loop region 8 of the VNAR region.
5. Randomisation of loop region 8 of 12 Y-2 and β sheet residues to form a binding surface. For eg 12 Y-2 residues Asp26 - Glu30 inclusive (27 should be hydrophobic); Tyr87- Glul03, though buried residues should be hydrophobic. In this case residues Asp93-Tyr96 are from the symmetry related molecules.
6. Randomisation of the loop regions 4 and 8 of the VNAR and β sheet residues to form a binding surface. It will be appreciated that the loop region sequences will be different for each example.
7. Multimerisation by using the dimer to present two copies of the same binding specificity.
8. Multimerisation by using the dimer to present two different binding specificities.
Modification of the VNAR dimer If the crystallographic dimer is a natural form, and the continuous 8-stranded β- sheet is formed under physiological conditions, then various residues are paired across the dimer interface. Thus, in the crystallographic structure the side chains of Leu99 residue are adjacent, in the correct orientation, and of appropriate distance (-3 A) to from a disulphide bridge. To test this hypothesis, the double 12 Y-2 mutant Pro90Leu and Leu99Cys was created. These mutations enhance the natural affinity for the target antigen (Pro90Leu), making binding easier to detect, and are in the correct position to moderate dimerisation (Leu99Cys). Overlap PCR using oligonucleotide primers was used to construct DNA clone 21B-5 (SEQ ID NO: 13 & 14). This was confirmed as correct by DNA sequencing. The resultant clone 21B-5 was clearly visible as a dimer form by FPLC and by
SDS-PAGE in the absence of reducing agent (see Figure 27(c) & (e)), compared to the wild type (14M-15, Pro90Leu only). Purified monomer bound immobilised AMAl by ELISA and by biosensor (See Figure 27(b) & (d)). The purified disulphide-linked dimer did not bind the target antigen, demonstrating both the importance of the CDR3 and that the novel dimer form appears to present a different interface to antigen than the monomeric protein. The dimer species could be crystallised, is stable, and may form the basis of a binding interface different from that of monomeric IgNAR forms.
EXAMPLE 14: Design, Construction, and Screening of Human I-set domains based on shark IgNAR principles. Shark IgNAR antibodies are structurally close to I-set domain immunoglobulins such as Telokin and domain 1 of NCAM. Specifically, what would otherwise be a CDR2 loop is at the "bottom" of the molecule. The foregoing structural, protein engineering, and library selection experiments suggest that the principles learnt from shark IgNAR antibody structures can be successfully applied to the generation of binding repertoires of human I-set immunoglobulins. Such libraries are anticipated to primarily contain variability in the CDRl and CDR3 analogous regions. The foregoing experiments also indicated that downstream affinity maturation strategies targeting framework regions (as well as the loop regions) of the NCAM and Telokin domains may result in altered and enhanced binding affinities and specificities. Shark IgNAR antibodies and NCAM domain 1 and Telokin were modelled to determine the best CDR-framework junction residues for mutation and incoφoration of library randomisation. This allowed incoφoration of randomised "CDR" loops which varied in both length and sequence. Additionally, in at least one variant for each of NCAM and Telokin, the human CDR3 framework was extended by analogy with the successful human/shark model 5 loop grafts, to provide a CDR3 loop extending several residues above the NCAM or Telokin scaffold (NCAM/A0988 library; Telokin/A1017 library). Following identification of framework junctions, oligonucleotide primers were designed to build human-scaffold-based libraries, based on both NCAM domain 1 and Telokin domain.
NCAM library oligonucleotide primers: A0980 NCAM CDRl randomisation 6-loop (SEQ ID NO: 82); A0981 NCAM CDRl randomisation 7-loop (SEQ ID NO: 83); A0982 NCAM CDR3 randomisation: rev compl; 8 loop (SEQ ID NO: 84); A0987 NCAM CDR3 randomisation: rev compl; 11 loop (SEQ ID NO: 85); A1018 NCAM CDR3 randomisation: rev compl; 14 loop (SEQ ID NO: 86); A0988 NCAM CDR3 randomisation: rev compl; 8 loop based on Model 5 (SEQ ID NO: 87). Telokin library oligonucleotide primers: AlOOl Telokin CDRl randomisation; 7 loop (SEQ ID NO: 94); A1002 Telokin CDRl randomisation; 9 loop (SEQ ID NO: 95); A1000 Telokin CDR3 randomisation: rev compl; 6 loop (SEQ ID NO: 97); A 1003 Telokin CDR3 randomisation: rev compl; 9 loop (SEQ ID NO: 98); A 1004 Telokin CDR3 randomisation: rev compl; 12 loop (SEQ ID NO: 99); A1017 Telokin CDR3 randomisation: rev compl; 9 loop based on Model 5 (SEQ ID NO: 100).
Three molecular libraries were constructed as follows:
Figure imgf000084_0001
Figure imgf000085_0001
Library numbers 1 and 2 from the above table were pooled and immunopanned by bacteriophage display against amyloid aβ (1-42) peptide and the Carcino Embryonic Antigen (CEA). Figure 30 shows the results of the panning against amyloid aβ (1-42) peptide (panels and A and B) and CEA (panels and C and D). In particular, binding to antigens (panels A & C) and comparative expression levels of individual clones (panels B & D) are shown. Figure 31 shows the titres of eluted phage from the NCAM library panned against monoclonal antibody 5G8 (-♦-), AMAl (-■-), Hepatitis B virus E antigen (- A-), ab 1-42 peptide (-x-), Carcino Embryonic Antigen (*); and, the Telokin library panned against monoclonal antibody 5G8 (•).
EXAMPLE 15: 12Y-2 IgNAR protein stability. Shark blood is rich in urea. Thus IgNAR domains may be hypothesised to have evolved to be unusually resistant to treatment with such harsh chemical agents. Recombinant IgNAR 14M-15 (12Y-2 Pro90Leu variant) (SEQ ID NO: 11) was tested for its ability to refold after denaturation in 8M urea. Regeneration was measured by intrinsic fluorescent intensity (see Figure 32). The IgNAR domain re-folded to its native conformation following removal of the urea. EXAMPLE 16: Full IgNAR Coding Sequence and the production of variable and constant domain reagents for biosensor analysis. The full wobbegong shark (Orectolobus maculatus) IgNAR coding sequence was cloned from shark cDNA (clone designated 18H-2 (SEQ ID NOs: 31 & 32)). The full DNA and amino acid sequences are given in Figure 33. The DNA sequence encodes a single polypeptide chain encompassing one IgNAR I-set domain and 5 C- domains (see Figure 34(a)). In the mature IgNAR antibody, these chains form a dimer mediated by half-cystine residues at positions Cys430 and Cys660. The resulting two disulphide bridges are located (1) C-terminal to constant domain 3 and N-terminal to constant domain 4 and (2) C-terminal to constant domain 5. The numbering adopted is for protein 18H-2; residues numbers will be different in each IgNAR due to the size differences in the variable domains. Each constant domain is -12 kDa in molecular weight. Sequential addition of constant domains 1, 2, and 3 to an IgNAR variable domain produce a set of single chain monovalent proteins with identical affinity for antigen, but varying in their molecular weight (see table below). For example, addition of the 12 Y-2 variable domain to varying numbers of constant domains produces a set of molecules with identical affinities for the target antigen AMAl, but with varying molecular weights. Of the variety of biosensors available, many rely on mass differences. These reagents provide an ideal test system of measuring the effect of mass differences for a single affinity.
Figure imgf000086_0001
12 Y-2 and 17T-6 proteins were compared by protein chemistry and biosensor (see Figure 34(b)-(d)). Results indicate that 17T-6 (i.e. 12 Y-2 + constant domain 1) is produced as a soluble monomeric protein of the correct molecular weight. It has identical binding affinity for the target AMAl as does the parent 12Y-2, when adjusted for mass. EXAMPLE 17: Modelling of Type 3 IgNAR. One of the Type 2 IgNAR variable domains solved structures is 12A-9. This structure has a disulphide linkage between loops regions 4 and 8 (i.e. between the CDRl - CDR3 analogous regions). This particular IgNAR is similar in CDR3 length and disulphide-bond position to Type 3 IgNARs, which are found in embryonic sharks. See Genbank AAM77190 (SEQ ID NO: 29) and AAM77191 (SEQ ID NO: 30) (Nurse shark Type 3 IgNARs). As a class, the Type 3 IgNAR variable domains are characterized by constant length loop regions analogous to CDR3s, disulphide bonds connecting the CDRl and CDR3 analogous loops (wliich happens to be in the same position as in 12 A- 9), and a conserved tryptophan residue at position 31.
Alignment of 12A-9 with two Type 3 IgNARs
CLUSTAL W (1.74) multiple sequence alignment
12A-9 ARVDQTPRIATKETGESLTINCVLRDTACALDSTN YRTKLGSTKEQTISIGGRYSETVD
AAM77190 ARVDQTPKTITKETGESLTINCVLSDTSCAWDSTYWYRKKLDSTNEESTSKGGRYVETVN AAM77191 ARVDQTPKTITKETGESLTINCVLSDTSCAWDSTYWYRKKLDSTNEESTSKGGRYVETVN
12A-9 EGSNSASLTIRDLRVEDSGTYKCKAYRRCAFNTGVGYKEGAGTVLTVK AAM77190 SESTSFSLRINDLTVEDSGTYRCRAYLYCGSQLDSFDEYGGGTIVTVS AAM77191 SESTSFSLRINDLTVEDSGTYRCRAYLYCGAELDSFDEYGGGTIVTVN
12A-9 ARVDQTPRIATKETGESLTINCVLRDTACALDSTNWYRTKLGSTKEQTISIGGRYSETVD AAM77191 ARVDQTPKTITKETGESLTINCVLSDTSCAWDSTYWYRKKLDSTNEESTSKGGRYVETVN *******. ************** **.** *** ***_**_**.*.. * **** ***.
12A-9 EGSNSASLTIRDLRVEDSGTYKCKAYRRCAFNTGVGYKEGAGTVLTVK AAM77191 SESTSFSLRINDLTVEDSGTYRCRAYLYCGAELDSFDEYGGGTIVTVN
Figure 35 shows the modeling of Type 3 VNAR AAM77191 based on the 12A-9 crystal structure. The results of four modelling runs are shown compared with the template 12A-9. Figure 36 shows a model of a VNAR Type 3 CDRl and CDR3 analogous regions based on the 12A-9 structure. The isotype has limited diversity with the hypervariable residues (by sequence alignment) depicted in dark grey. The modeling suggests that the conserved Phe96 can adopt a number of structural conformations, dramatically enhancing the antigen-binding range of this antibody, despite the low sequence variability It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention as shown in the specific embodiments without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.
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Table 1 : Amino acid variation across the 14 Type 2 VN RS sequences in Figure 1
Figure imgf000098_0001
Var : Variant amino acids : These columns show the variation in amino acid residues found in the corresponding positions in the twelve other Type 2 VNARs sequences in Figure 1 and in other Type 2 VNARs reported in Nuttall 2002 and 2003. Con: Consensus sequence Table 2 : Diffraction data and refinement statist
Figure imgf000099_0001
Table 3 : Number and numbering of amino acid residues in each region
Figure imgf000100_0001
Table 3A : Number and numbering of amino acid residues in loop region 5
Figure imgf000101_0001
Table 4. Dimer interactions
Figure imgf000102_0001
Subscript "s" is for a symmetry (2-fold) related molecule. Table 5 : Amino acid sequences of NCAM/IgNAR and Telokin/TgNAR chimeras
NCAM FRAMEWORK
NCAM LQVDIVPSQGEISVGESKFFLCQVAGDAKDKDISWFSPNGEKLTPNQQRISW NDDSSS TLTIYNANIDDAGIYKCWTGED GSESEA-TVNVKIFQ
NCAM IgNAR CDR3 grafted NCAM
N1A7_1 N1A7_2 TLTIYNANIDDAGIYKC GAYFSDAMSNYSYPIPGEK A-TVNVKIFQ N1A7_3 TLTIYNANIDDAGIYKCV AYFSDAMSNYSYPIPGE- SA-TVNVKIFQ N1A7_4 TLTIYNANIDDAGIYKCW YFSDAMSNYSYPIPG-- SEA-TVNVKIFQ N1A7 5 TLTIYNANIDDAGIYKCWT FSDAMSNYSYPIP ESEA-TVNVKIFQ TLTIYNANIDDAGIYKCWTG SDAMSNYSYPI SESEA-TVNVKIFQ
TELOKIN FRAMEWORK
TELOKIN PYFSKTIRDLEWEGSAARFDCKIEGYPDPEWWFKDDQSIRESRHFQIDYDEDGN CSLTISEVCGDDDAKYTCKAVNS LGEATC-TAELIVE
TELOKIN IgNAR CDR3 grafted TELOKIN
T1A7_1 CSLIISDVCGDDDAKYTC GAYFSDAMSNYSYPIPGEK— -C-TAELIVE- T1A7_2 CSLIISDVCGDDDAKYTCK AYFSDAMSNYSYPIPGE TC-TAELIVE- T1A7_3 CSLIISDVCGDDDAKYTCKA YFSDAMSNYSYPIPG TC-TAELIVE- T1A7_4 CSLIISDVCGDDDAKYTCKAV FSDAMSNYSYPIP EATC-TAELIVE- T1A7 5 CSLIISDVCGDDDAKYTCKAVN SDAMSNYSYPI GEATC-TAELIVE-
Table 6 : Comparison of TCR interfaces:
Figure imgf000104_0001
* Residues is TCR CDR2 loop, no equivalent position in IgNAR variable domains. ¥ Deviation between Cα traces of shark and TCR structures. £ Camelisation of human domains, difficult to correlate.
NB: This does not include interface residues incorporated within the highly variable VLR3 loop regions. For example 12Y-2 residue ArglOl would also contribute to covering the hydrophobic interface if modelled onto the TCR domain. APPENDIX I (a)
HEADER IMMUNE SYSTEM 05-APR-04 1VER
TITLE STRUCTURE OF NEW ANTIGEN RECEPTOR VARIABLE DOMAIN FROM SHARKS
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: NEW ANTIGEN RECEPTOR;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: VARIABLE DOMAIN;
COMPND 5 SYNONYM: VNAR;
COMPND 6 ENGINEERED: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: ORECTOLOBUS MACULATUS;
SOURCE 3 ORGANISM_COMMON: SPOTTED WOBBEGONG;
SOURCE 4 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 5 EXPRESSION_SYSTEM_COMMON: BACTERIA
KEYWDS IG VNAR, NATIVE, 12Y-1
EXPDTA X-RAY DIFFRACTION
AUTHOR V.A.STRELTSOV
JRNL AUTH V.A.STRELTSOV, J. . VARGHESE, P. .HUDSON, R.A. IRVING,
JRNL AUTH J.A. CARMICHAEL, S.D. NUTTALL
JRNL TITL CRYSTAL STRUCTURE OF A SHARK NEW ANTIGEN RECEPTOR
JRNL TITL (IGNAR) VARIABLE DOMAIN
JRNL REF TO BE PUBLISHED
JRNL REFN
REMARK 1
REMARK 2
REMARK 2 RESOLUTION. 2.82 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT .
REMARK 3 PROGRAM REFMAC 5.1.24
REMARK 3 AUTHORS MURSHUDOV, VAGIN, DODSON
REMARK 3
REMARK 3 REFINEMENT TARGET : MAXIMUM LIKELIHOOD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) 2.82
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) 6.00
REMARK 3 DATA CUTOFF (SIGMA(F)) NULL
REMARK 3 COMPLETENESS FOR RANGE (%) 99.3
REMARK 3 NUMBER OF REFLECTIONS 3353
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 CROSS-VALIDATION METHOD THROUGHOUT
REMARK 3 FREE R VALUE TEST SET SELECTION RANDOM
REMARK 3 R VALUE (WORKING + TEST SET) 0.170
REMARK 3 R VALUE (WORKING SET) 0.166
REMARK 3 FREE R VALUE 0.254
REMARK 3 FREE R VALUE TEST SET SIZE (%) 4.400
REMARK 3 FREE R VALUE TEST SET COUNT 153
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED 20
REMARK 3 BIN RESOLUTION RANGE HIGH 2.82
REMARK 3 BIN RESOLUTION RANGE LOW 2.88
REMARK 3 REFLECTION IN BIN (WORKING SET) 195
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) NULL
REMARK 3 BIN R VALUE (WORKING SET) 0.3390
REMARK 3 BIN FREE R VALUE SET COUNT 11
REMARK 3 BIN FREE R VALUE 0.5430
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 ALL ATOMS : 867
REMARK 3
REMARK 3 B VALUES. REMARK FROM WILSON PLOT (A**2) NULL REMARK MEAN B VALUE (OVERALL, A**2) 40.21 REMARK OVERALL ANISOTROPIC B VALUE. REMARK Bll (A**2) 3.53000 REMARK B22 (A**2) 3.53000 REMARK B33 (A**2) -7.06000 REMARK B12 (A**2) 0.00000 REMARK B13 (A**2) 0.00000 REMARK B23 (A**2) 0.00000 REMARK REMARK ESTIMATED OVERALL COORDINATE ERROR. REMARK ESU BASED ON R VALUE (A) NULL REMARK ESU BASED ON FREE R VALUE (A) 0.370 REMARK ESU BASED ON MAXIMUM LIKELIHOOD (A) 0.288 REMARK ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2) 16.179 REMARK REMARK CORRELATION COEFFICIENTS. REMARK CORRELATION COEFFICIENT FO-FC .965 REMARK CORRELATION COEFFICIENT FO-FC FREE .911 REMARK REMARK RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT REMARK BOND LENGTHS REFINED ATOMS (A) 780 0.012 0.021 REMARK BOND LENGTHS OTHERS (A) 710 0.002 0.020 REMARK BOND ANGLES REFINED ATOMS (DEGREES) 1050 1.552 1.955 REMARK BOND ANGLES OTHERS (DEGREES) 1648 0.838 3.000 REMARK TORSION ANGLES, PERIOD 1 (DEGREES) 98 8.873 5.000 REMARK TORSION ANGLES, PERIOD 2 (DEGREES) NULL NULL NULL REMARK TORSION ANGLES, PERIOD 3 (DEGREES) NULL NULL NULL REMARK TORSION ANGLES, PERIOD 4 (DEGREES) NULL NULL NULL REMARK CHIRAL-CENTER RESTRAINTS (A**3) 121 0.085 0.200 REMARK GENERAL PLANES REFINED ATOMS (A) 857 0.005 0.020 REMARK GENERAL PLANES OTHERS (A) 165 0.001 0.020 REMARK NON-BONDED CONTACTS REFINED ATOMS (A) 147 0.220 0.200 REMARK NON-BONDED CONTACTS OTHERS (A) 841 0.224 0.200 REMARK NON-BONDED TORSION REFINED ATOMS (A) NULL NULL NULL REMARK NON-BONDED TORSION OTHERS (A) 558 0.089 0.200 REMARK H-BOND (X...Y) REFINED ATOMS (A) 32 0.220 0.200 REMARK H-BOND (X...Y) OTHERS (A) NULL NULL NULL REMARK POTENTIAL METAL-ION REFINED ATOMS (A) NULL NULL NULL REMARK POTENTIAL METAL-ION OTHERS (A) NULL NULL NULL REMARK SYMMETRY VDW REFINED ATOMS (A) 11 0.370 0.200 REMARK SYMMETRY VDW OTHERS (A) 26 0.364 0.200 REMARK SYMMETRY H-BOND REFINED ATOMS (A) 11 0.160 0.200 REMARK SYMMETRY H-BOND OTHERS (A) NULL NULL NULL REMARK REMARK ISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT REMARK MAIN-CHAIN BOND REFINED ATOMS (A**2 488 0.363 1.500 REMARK MAIN-CHAIN BOND OTHER ATOMS (A**2) NULL NULL NULL REMARK MAIN-CHAIN ANGLE REFINED ATOMS (A**2) 783 0.690 2.000 REMARK SIDE-CHAIN BOND REFINED ATOMS (A**2) 292 1.038 3.000 REMARK SIDE-CHAIN ANGLE REFINED ATOMS (A**2) 267 1.864 4.500 REMARK REMARK ANISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT REMARK RIGID-BOND RESTRAINTS (A**2) NULL NULL NULL REMARK SPHERICITY; FREE ATOMS (A**2) NULL NULL NULL REMARK SPHERICITY; BONDED ATOMS (A**2) NULL NULL NULL REMARK REMARK NCS RESTRAINTS STATISTICS REMARK NUMBER OF DIFFERENT NCS GROUPS REMARK REMARK TLS DETAILS REMARK NUMBER OF TLS GROUPS : 1 REMARK REMARK TLS GROUP : 1 REMARK 3 NUMBER OF COMPONENTS GROUP : 1
REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI
REMARK 3 RESIDUE RANGE : A 1 A 111
REMARK 3 ORIGIN FOR THE GROUP (A): 45. 6110 36 4110 14.2350
REMARK 3 T TENSOR
REMARK 3 Til: 0.0948 T22 0.2124
REMARK 3 T33: 0.2758 T12 -0.1415
REMARK 3 T13: -0.1115 T23 0.1801
REMARK 3 L TENSOR
REMARK 3 Lll: 3.5582 L22 7.2854
REMARK 3 L33: 17.6513 L12 0.4045
REMARK 3 L13: -0.8273 L23 -0.9129
REMARK 3 S TENSOR
REMARK 3 Sll: 0.1545 S12 -0.6840 S13: -0 0196
REMARK 3 S21: 0.7097 S22 -0.6861 S23: -0 3902
REMARK 3 S31: -0.4080 S32 0.6079 S33: 0 5316
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : BABINET MODEL WITH MASK
REMARK 3 PARAMETERS FOR MASK CALCULATION
REMARK 3 VDW PROBE RADIUS 1.40
REMARK 3 ION PROBE RADIUS 0.80
REMARK 3 SHRINKAGE RADIUS 0.80
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 IVER COMPLIES WITH FORMAT V. 2.3, 09-JULY- -1998
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBJ ON 07-APR-2004.
REMARK 100 THE RCSB ID CODE IS RCSB006537.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION OCT-03
REMARK 200 TEMPERATURE (KELVIN) 113.0
REMARK 200 PH 6.50
REMARK 200 NUMBER OF CRYSTALS USED 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) N
REMARK 200 RADIATION SOURCE ROTATING ANODE
REMARK 200 BEAMLINE NULL
REMARK 200 X-RAY GENERATOR MODEL RIGAKU HR3 HB
REMARK 200 MONOCHROMATIC OR LAUE (M/L) M
REMARK 200 WAVELENGTH OR RANGE (A) 1.5418
REMARK 200 MONOCHROMATOR NI FILTER
REMARK 200 OPTICS AXCO MICROCAPILLARY FOCUSING
REMARK 200 C 5PTICS
REMARK 200
REMARK 200 DETECTOR TYPE IMAGE PLATE
REMARK 200 DETECTOR MANUFACTURER MAR 180
REMARK 200 INTENSITY-INTEGRATION SOFTWARE DENZO
REMARK 200 DATA SCALING SOFTWARE SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS 3975
REMARK 200 RESOLUTION RANGE HIGH (A) 2.820
REMARK 200 RESOLUTION RANGE LOW (A) 69.010
REMARK 200 REJECTION CRITERIA (SIGMA(I)) 0.000
REMARK 200
REMARK 200 OVERALL .
REMARK 200 COMPLETENESS FOR RANGE (%) 99.0
REMARK 200 DATA REDUNDANCY 15.100
REMARK 200 R MERGE (I) 0.04500
REMARK 200 R SYM (I) 0.04500
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET 18.1000 REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.82
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.90
REMARK 200 COMPLETENESS FOR SHELL (%) 94.3
REMARK 200 DATA REDUNDANCY IN SHELL 4.30
REMARK 200 R MERGE FOR SHELL (I) NULL
REMARK 200 R SYM FOR SHELL (I) NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL 1.800
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MIR
REMARK 200 SOFTWARE USED: SHARP
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%) : NULL
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA) NULL
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0. IM BIS-TRIS PROPANE, 45% PPG
REMARK 280 P400, PH 6.50, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 298K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: I 41 2 2
REMARK 290
REMARK 290 SYMOP SYMMETRY REMARK 290 NNNMMM ( OPERATOR REMARK 290 1555 ] X,Y,Z REMARK 290 2555 l/2-X,l/2-Y,l/2+Z REMARK 290 3555 -Y,l/2+X,l/4+Z REMARK 290 4555 l/2+Y,-X,3/4+Z REMARK 290 5555 l/2-X,Y,3/4-Z REMARK 290 6555 ; X,l/2-Y,l/4-Z REMARK 290 7555 l/2+Y,l/2+X,l/2-Z REMARK 290 8555 -Y,-X,-Z REMARK 290 9555 l/2+X,l/2+Y,l/2+Z REMARK 290 10555 1/1-X,1/1-Y,1/1+Z REMARK 290 11555 l/2-Y,l/l+X,3/4+Z REMARK 290 12555 l/l+Y,l/2-X,5/4+Z REMARK 290 13555 l/l-X,l/2+Y,5/4-Z REMARK 290 14555 l/2+X,l/l-Y,3/4-Z REMARK 290 15555 1/1+Y,1/1+X, 1/1-Z REMARK 290 16555 l/2-Y,l/2-X, 1/2-Z REMARK 290 REMARK 290 WHERE NNN -> OPERATOR NUMBER REMARK 290 MMM -> TRANSLATION VECTOR
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY TRANSFORMATIONS
REMARK 290 THE FOLLOWING TRANSFORMATIONS OPERATE ON THE ATOM/HETATM
REMARK 290 RECORDS IN THIS ENTRY TO PRODUCE CRYSTALLOGRAPHICALLY
REMARK 290 RELATED MOLECULES.
REMARK 290 SMTRY1 1 1 000000 0 000000 0 000000 0 00000
REMARK 290 SMTRY2 1 0 000000 1 000000 0 000000 0 00000
REMARK 290 SMTRY3 1 0 000000 0 000000 1 000000 0 00000
REMARK 290 SMTRY1 2 -1 000000 0 000000 0 000000 48 62950
REMARK 290 SMTRY2 2 0 000000 -1 000000 0 000000 48 62950
REMARK 290 SMTRY3 2 0 000000 0 000000 1 000000 32 61400
REMARK 290 SMTRY1 3 0 000000 -1 000000 0 000000 0 00000
REMARK 290 SMTRY2 3 1 000000 0 000000 0 000000 48 62950
REMARK 290 SMTRY3 3 0 000000 0 000000 1 000000 16 30700
REMARK 290 SMTRY1 4 0 000000 1 000000 0 000000 48 62950
REMARK 290 SMTRY2 4 -1 000000 0 000000 0 000000 0 00000 REMARK 290 SMTRY3 4 0.,000000 0.,000000 1..000000 48,,92100
REMARK 290 SMTRY1 5 -1. ,000000 0. .000000 0. .000000 48. ,62950
REMARK 290 SMTRY2 5 0. ,000000 1. ,000000 0. .000000 0, ,00000
REMARK 290 SMTRY3 5 0. .000000 0, .000000 -1. .000000 48. .92100
REMARK 290 SMTRY1 6 1. .000000 0, .000000 0. .000000 0. .00000
REMARK 290 SMTRY2 6 0. .000000 -1, .000000 0. .000000 48, ,62950
REMARK 290 SMTRY3 6 0. .000000 0. .000000 -1. .000000 16. .30700
REMARK 290 SMTRY1 7 0, .000000 1. .000000 0. .000000 48, .62950
REMARK 290 SMTRY2 7 1. .000000 0. ,000000 0. .000000 48, .62950
REMARK 290 SMTRY3 7 0, .000000 0. ,000000 -1. ,000000 32, .61400
REMARK 290 SMTRY1 8 0. .000000 -1. .000000 0. .000000 0, ,00000
REMARK 290 SMTRY2 8 -1. .000000 0. .000000 0. .000000 0, ,00000
REMARK 290 SMTRY3 8 0. .000000 0. .000000 -1. .000000 0, ,00000
REMARK 290 SMTRY1 9 1. .000000 0. .000000 0. .000000 48, ,62950
REMARK 290 SMTRY2 9 0. .000000 1. .000000 0. .000000 48, ,62950
REMARK 290 SMTRY3 9 0. .000000 0, .000000 1. .000000 32, ,61400
REMARK 290 SMTRY1 10 -1. .000000 0. .000000 0. .000000 97, .25900
REMARK 290 SMTRY2 10 0. ,000000 -1. .000000 0. .000000 97. .25900
REMARK 290 SMTRY3 10 0. .000000 0. .000000 1. .000000 65, .22800
REMARK 290 SMTRY1 11 0. .000000 -1. .000000 0, .000000 48, ,62950
REMARK 290 SMTRY2 11 1. .000000 0. .000000 0, ,000000 97, .25900
REMARK 290 SMTRY3 11 0. .000000 0. .000000 1. .000000 48, ,92100
REMARK 290 SMTRY1 12 0. ,000000 1. .000000 0. .000000 97, .25900
REMARK 290 SMTRY2 12 -1. .000000 0. .000000 0. .000000 48. .62950
REMARK 290 SMTRY3 12 0. .000000 0. .000000 1. .000000 81, .53500
REMARK 290 SMTRY1 13 -1. .000000 0. .000000 0, ,000000 97, .25900
REMARK 290 SMTRY2 13 0. .000000 1. .000000 0, .000000 48, .62950
REMARK 290 SMTRY3 13 0. .000000 0. .000000 -1, .000000 81, ,53500
REMARK 290 SMTRY1 14 1, .000000 0. .000000 0, .000000 48, .62950
REMARK 290 SMTRY2 14 0, .000000 -1, .000000 0, .000000 97, .25900
REMARK 290 SMTRY3 14 0, .000000 0, .000000 -1, .000000 48, ,92100
REMARK 290 SMTRY1 15 0. .000000 1. .000000 0. .000000 97, ,25900
REMARK 290 SMTRY2 15 1. ,000000 0. ,000000 0. ,000000 97, ,25900
REMARK 290 SMTRY3 15 0. ,000000 0. .000000 -1. .000000 65, .22800
REMARK 290 SMTRY1 16 0. .000000 -1. .000000 0, ,000000 48, .62950
REMARK 290 SMTRY2 16 -1, .000000 0. .000000 0, .000000 48, .62950
REMARK 290 SMTRY3 16 0. .000000 0. .000000 -1, .000000 32, .61400
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1
REMARK 300 THIS ENTRY CONTAINS THE CRYSTALLOGRAPHIC ASYMMETRIC UNIT
REMARK 300 WHICH CONSISTS OF 1 CHAIN(S). SEE REMARK 350 FOR REMARK 300 INFORMATION ON GENERATING THE BIOLOGICAL MOLECULE (S). REMARK 350 REMARK 350 GENERATING THE BIOMOLECULE REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS REMARK 350 GIVEN BELOW. BOTH NON-CRYSTALLOGRAPHIC AND REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN. REMARK 350 REMARK 350 BIOMOLECULE: 1 REMARK 350 APPLY THE FOLLOWING TO CHAINS: A REMARK 350 1 1, ,000000 0, .000000 0, ,000000 0, .00000 REMARK 350 1 0. ,000000 1, .000000 0, ,000000 0, .00000 REMARK 350 1 0, ,000000 0, ,000000 1, ,000000 0, ,00000 REMARK 465 REMARK 465 MISSING RESIDUES REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE
REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.) REMARK 465 REMARK 465 M RES C SSSEQI REMARK 465 PHE A
REMARK 465 TRP A 89
REMARK 465 LEU A 90
REMARK 465 PRO A 91
REMARK 465 TYR A 92
REMARK 465 GLY A 93
REMARK 465 TYR A 94
REMARK 465 GLY A 95
REMARK 465 SER A 96
REMARK 465 LEU A 97
REMARK 465 PRO A 98
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CLOSE CONTACTS IN SAME ASYMMETRIC UNIT
REMARK 500
REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT.
REMARK 500
REMARK 500 ATM1 RES C SSEQI ATM2 RES SSEQI
REMARK 500 N ALA A 1 O HOH 54 1.94
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CLOSE CONTACTS
REMARK 500
REMARK 500 THE FOLLOWING ATOMS THAT ARE RELATED BY CRYSTALLOGRAPHIC
REMARK 500 SYMMETRY ARE IN CLOSE CONTACT. AN ATOM LOCATED WITHIN 0.15
REMARK 500 ANGSTROMS OF A SYMMETRY RELATED ATOM IS ASSUMED TO BE ON A
REMARK 500 SPECIAL POSITION AND IS, THEREFORE, LISTED IN REMARK 375
REMARK 500 INSTEAD OF REMARK 500. ATOMS WITH NON-BLANK ALTERNATE
REMARK 500 LOCATION INDICATORS ARE NOT INCLUDED IN THE CALCULATIONS.
REMARK 500
REMARK 500 DISTANCE CUTOFF:
REMARK 500 2.2 ANGSTROMS FOR CONTACTS NOT INVOLVING HYDROGEN ATOMS
REMARK 500 1.6 ANGSTROMS FOR CONTACTS INVOLVING HYDROGEN ATOMS
REMARK 500
REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI SSYMOP DISTANCE
REMARK 500 O ALA A 1 O ALA A 1 8665 2.07
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: NON-CIS, NON-TRANS
REMARK 500
REMARK 500 THE FOLLOWING PEPTIDE BONDS DEVIATE SIGNIFICANTLY FROM BOTH
REMARK 500 CIS AND TRANS CONFORMATION. CIS BONDS, IF ANY, ARE LISTED
REMARK 500 ON CISPEP RECORDS. TRANS IS DEFINED AS 180 +/- 30 AND
REMARK 500 CIS IS DEFINED AS 0 +/- 30 DEGREES.
REMARK 500 MODEL OMEGA
REMARK 500 SER A 100 GLU A 101 144.45
REMARK 525
REMARK 525 SOLVENT
REMARK 525 THE FOLLOWING SOLVENT MOLECULES LIE FARTHER THAN EXPECTED
REMARK 525 FROM THE PROTEIN OR NUCLEIC ACID MOLECULE AND MAY BE
REMARK 525 ASSOCIATED WITH A SYMMETRY RELATED MOLECULE (M=MODEL
REMARK 525 NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE REMARK 525 NUMBER; I=INSERTION CODE) REMARK 525
REMARK 525 M RES CSSEQI REMARK 525 HOH 28 DISTANCE = 5, ,01 ANGSTROMS REMARK 525 HOH 60 DISTANCE = 9, ,08 ANGSTROMS REMARK 525 HOH 75 DISTANCE = 5, ,80 ANGSTROMS REMARK 525 HOH 86 DISTANCE = 9, .33 ANGSTROMS REMARK 525 HOH 90 DISTANCE = 5, .58 ANGSTROMS REMARK 525 HOH 92 DISTANCE = 7, ,18 ANGSTROMS REMARK 525 HOH DISTANCE = 11, .83 ANGSTROMS REMARK 900 REMARK 900 RELATED ENTRIES REMARK 900 RELATED ID : 1VES RELATED DB : PDB
REMARK 900 THE SAME PROTEIN ( 12Y-2 )
REMARK 999
REMARK 999 SEQUENCE
REMARK 999 A SEQUENCE DATABASE REFERENCE FOR THIS PROTEIN DOES
REMARK 999 NOT CURRENTLY EXIST.
SEQRES 1 A 111 ALA TRP VAL . ASP GLN' THR PRO ARG THR ALA THR LYS GLU
SEQRES 2 A 111 THR GLY GLU SER LEU THR ILE ASN CYS VAL LEU ARG ASP
SEQRES 3 A 111 ALA SER TYR GLY LEU GLU SER THR GLY TRP TYR ARG THR
SEQRES 4 A 111 LYS LEU GLY SER THR ASN GLU GLN THR ILE SER ILE GLY
SEQRES 5 A 111 GLY ARG TYR ' VAL GLU THR VAL ASN LYS GLY SER LYS SER
SEQRES 6 A 111 PHE SER LEU . ARG ILE ARG ASP LEU ARG VAL GLU ASP SER
SEQRES 7 A 111 GLY THR TYR LYS CYS GLY ALA PHE ARG PHE TRP LEU PRO
SEQRES 8 A 111 TYR GLY TYR GLY SER LEU PRO LEU SER GLU LYS GLY ALA
SEQRES 9 A 111 GLY THR VAL LEU THR VAL LYS
FORMUL 2 HOH *97 (H2 01)
HELIX 1 1 ARG A 74 SER . A 78 5 5
SHEET 1 A 4 TRP A 2 THR A 6 0
SHEET 2 A 4 LEU A 18 ARG A 25 -1 O ARG A 25 N TRP A 2
SHEET 3 A 4 SER A 65 ILE A 70 -1 O ILE A 70 N LEU A 18
SHEET 4 A 4 TYR A 55 ASN A 60 -1 N ASN A 60 O SER A 65
SHEET 1 B 5 THR A 9 ALA A 10 0
SHEET 2 B 5 THR A 106 LEU A 108 1 O VAL A 107 N ALA A 10
SHEET 3 B 5 GLY A 79 ALA A 85 -1 N GLY A 79 O LEU A 108
SHEET 4 B 5 THR A 34 ARG A 38 -1 N TYR A 37 O LYS A 82
SHEET 5 B 5 GLN A 47 THR A 48 -1 O GLN A 47 N ARG A 38
SHEET 1 C 4 THR A 9 ALA A 10 0
SHEET 2 C 4 THR A 106 LEU A 108 1 O VAL A 107 N ALA A 10
SHEET 3 C 4 GLY A 79 ALA A 85 -1 N GLY A 79 O LEU A 108
SHEET 4 C 4 GLU A 101 LYS A 102 -1 O GLU A 101 N ALA A 85
SSBOND 1 CYS A 22 CYS A 83
CISPEP 1 THR A 6 PRO A 7 0 ■3.12
CRYST1 97. 259 97.259 65.228 90.00 90.0C ) 90.00 I 41 2 2 16
ORIGX1 1.000000 Ci.OOOOOO 0.000000 O.OOOOC 1
ORIGX2 0.000000 1 .000000 0.000000 0.00000 1
ORIGX3 0.000000 0i.OOOOOO 1.000000 0.00000 1
SCALE1 0.010282 0i.OOOOOO 0.000000 0.00000 1
SCALE2 0.000000 0 1.010282 0.000000 0.00000 1
SCALE3 0.000000 0i.OOOOOO 0.015331 0.00000 1
ATOM 1 N ALA A 1 55.513 40.915 -1. .352 1.00 39.81 N
ATOM 2 CA ALA A 1 54.244 40.231 -0. .986 1.00 39.92 C
ATOM 3 C ALA A 1 53.526 40.997 0. .141 1.00 40.10 C
ATOM 4 O ALA A 1 53.961 42.071 0, .568 1.00 ,39.99 O
ATOM 5 CB ALA A 1 54.548 38.792 -0. .565 1.00 '39.81 C
ATOM 6 N TRP A 2 52.424 40.457 0. .635 1.00 40.03 N
ATOM 7 CA TRP A 2 51.839 41.010 1. ,842 1.00 40.13 C
ATOM 8 C TRP A 2 50.807 40.092 2. ,398 1.00 40.02 C
ATOM 9 O TRP A 2 50.312 39.214 1. ,691 1.00 39.96 O
ATOM 10 CB TRP A 2 51.215 42.378 1. .578 1.00 40.30 C
ATOM 11 CG TRP A 2 50.173 42.417 0. ,480 1.00 41.25 C
ATOM 12 CD1 TRP A 2 50.368 42.203 -0. ,853 1.00 41.78 C
ATOM 13 CD2 TRP A 2 48.787 42.751 0. ,629 1.00 41.72 C
ATOM 14 NE1 TRP A 2 49.188 42.376 -1. ,533 1.00 41.43 N
ATOM 15 CE2 TRP A 2 48.206 42.712 -0. ,641 1.00 41.13 C
ATOM 16 CE3 TRP A 2 47.977 43.089 1. ,723 1.00 43.91 C
ATOM 17 CZ2 TRP A 2 46.867 42.980 -0. ,851 1.00 42.60 C
ATOM 18 CZ3 TRP A 2 46.637 43.363 1. ,506 1.00 43.85 C
ATOM 19 CH2 TRP A 2 46.100 43.300 0. 233 1.00 43.32 C
ATOM 20 N VAL A 3 50.489 40.299 3. 675 1.00 39.97 N
ATOM 21 CA VAL A 3 49.447 39.528 4. 356 1.00 39.89 C
ATOM 22 C VAL A 3 48.257 40.456 4. 600 1.00 40.16 C
ATOM 23 O VAL A 3 48.404 41.631 4. 929 1.00 40.00 O
ATOM 24 CB VAL A 3 49.958 38.817 5. 658 1.00 39.49 C Ill
ATOM 25 CGI VAL A 3 48 .829 38 .221 6 .441 1 .00 39 .82 c
ATOM 26 CG2 VAL A 3 50 .923 37 .704 5 .310 1 .00 38 .65 c
ATOM 27 N ASP A 4 47 .075 39 .886 4 .397 1 .00 40 .79 N
ATOM 28 CA ASP A 4 45 .818 40 .616 4 .341 1 .00 40 .59 C
ATOM 29 C ASP A 4 45 .024 40 .126 5 .538 1 .00 40 .13 C
ATOM 30 O ASP A 4 44 .435 39 .061 5 .532 1 .00 38 .36 O
ATOM 31 CB ASP A 4 45 .110 40 .349 2 .990 1 .00 40 .76 C
ATOM 32 CG ASP A 4 44 .054 41 .400 2 .640 1 .00 40 .56 c
ATOM 33 OD1 ASP A 4 43, .544 41 .358 1 .487 1 .00 37 .98 0
ATOM 34 OD2 ASP A 4 43 .664 42 .283 3 .449 1 .00 39 .55 0
ATOM 35 N GLN A 5 45 .083 40 .921' 6 .591 1 .00 40 .81 N
ATOM 36 CA GLN A 5 44, .451 40, .587 7 .845 1, .00 41 .30 C
ATOM 37 C GLN A 5 43, .186 41 .395 8. .027 1, .00 41 .46 C
ATOM 38 O GLN A 5 43 .123 42 .577 7 .702 1 .00 41 .23 O
ATOM 39 CB GLN A 5 45 .400 40 .847 9 .003 1 .00 41 .37 C
ATOM 40 CG GLN A 5 44, .887 40, .277 10, .299 1, .00 42, .10 C
ATOM 41 CD GLN A 5 45, .861 40, .424 11 .402 1, .00 42 .51 C
ATOM 42 OEl GLN A 5 47, .069 40 .451 11 .166 1, .00 44 .78 O
ATOM 43 NE2 GLN A 5 45, .352 40 .534 12 .624 1 .00 41 .68 N
ATOM 44 N THR A 6 42, .214 40, ,738 8, .641 1, .00 42, .08 N
ATOM 45 CA THR A 6 40, ,819 41, .137 8, .591 1, .00 42, .22 C
ATOM 46 C THR A 6 40, .083 40, .525 9, .824 1, .00 42, .57 C
ATOM 47 O THR A 6 40, .242 39 .345 10 .099 1, .00 43, .00 O
ATOM 48 CB THR A 6 40, ,290 40, .612 7, .239 1, ,00 41, ,88 C
ATOM 49 OG1 THR A 6 39, .946 41, .711 6, .391 1, .00 41, .95 O
ATOM 50 CG2 THR A 6 39, .025 39, .834 7, .380 1, .00 42, .09 C
ATOM 51 N PRO A 7 39, .344 41, .292 10 .619 1, .00 42, .73 N
ATOM 52 CA PRO A 7 39, .187 42, .740 10, ,490 1, ,00 42, .90 C
ATOM 53 C PRO A 7 40, .330 43, ,531 11, .124 1, .00 42, .96 C
ATOM 54 O PRO A 7 41, .152 42, .995 11, .849 1, .00 42, .51 O
ATOM 55 CB PRO A 7 37, .880 43, .001 11, .256 1, .00 42, .96 C
ATOM 56 CG PRO A 7 37, .869 41. .963 12, .343 1. .00 42, .75 C
ATOM 57 CD PRO A 7 38, .595 40. ,759 11, .773 1. .00 42. .62 C
ATOM 58 N ARG A 8 40, .342 44, ,827 10, ,863 1, .00 43, ,73 N
ATOM 59 CA ARG A 8 41, .356 45, .709 11, .405 1. .00 44, .66 C
ATOM 60 C ARG A 8 40, .985 46. ,138 12, .829 1, .00 44, ,54 C
ATOM 61 O ARG A 8 41, .804 46. ,687 13, .565 1, .00 44, .09 0
ATOM 62 CB ARG A 8 41, .542 46. .920 10, .471 1, .00 45, .24 c
ATOM 63 CG ARG A 8 42. .962 47, .049 9, .838 1, .00 47, .41 c
ATOM 64 CD ARG A 8 43. .159 46, .295 8, .519 1, .00 49, .70 c
ATOM 65 NE ARG A 8 43, .473 47, .198 7, .407 1. .'00 52, .43 N
ATOM 66 CZ ARG A 8 43, .429 46, ,856 6, .105 1. .00 54, .91 C
ATOM 67 NH1 ARG A 8 43. ,082 45. .621 5, ,715 1. ,00 54. ,18 N
ATOM 68 NH2 ARG A 8 43, ,739 47, .765 5, ,175 1. ,00 55, ,49 N
ATOM 69 N THR A 9 39, ,736 45. .876 13. .195 1. .00 45, .02 N
ATOM 70 CA THR A 9 39, .191 46. ,199 14, .512 1. .00 45. .42 C
ATOM 71 C THR A 9 38. ,029 45. ,259 14. ,826 1. ,00 45. ,80 C
ATOM 72 O THR A 9 37. ,109 45. ,112 14. ,013 1. ,00 46. ,14 0
ATOM 73 CB THR A 9 38. ,648 47, ,646 14. ,554 1. ,00 45. ,22 c
ATOM 74 OG1 THR A 9 38. ,000 47. ,954 13. ,311 1. ,00 45. ,04 0
ATOM 75 CG2 THR A 9 39. ,777 48. 670 14. ,677 1. ,00 45. ,18 c
ATOM 76 N ALA A 10 38. ,057 44. ,646 16. ,007 1. ,00 45. ,93 N
ATOM 77 CA ALA A 10 36. ,911 43. ,887 16. ,487 1. ,00 45. ,99 c
ATOM 78 C ALA A 10 36. ,711 44. ,153 17. ,968 1. ,00 46. ,02 c
ATOM 79 O ALA A 10 37. 496 43. 675 18. 785 1. 00 46. 26 0
ATOM 80 CB ALA A 10 37. 100 42. ,385 16. 221 1. ,00 45. 95 c
ATOM 81 N THR A 11 35. ,679 44. ,937 18. 302 1. 00 45. 89 N
ATOM 82 CA THR A 11 35. ,211 45. ,069 19. ,687 1. 00 45. ,55 C
ATOM 83 C THR A 11 34. 095 44. 051 19. 970 1. 00 45. 47 C
ATOM 84 O THR A 11 32. 901 44. 352 19. 936 1. 00 45. 09 O
ATOM 85 CB THR A 11 34. 806 46. 535 20. 052 1. 00 45. 51 c
ATOM 86 OG1 THR A 11 34. 375 46. 597 21. 420 1. 00 44. 83 0
ATOM 87 CG2 THR A 11 33. 601 47. 035 19. 257 1. 00 45. 59 c
ATOM 88 N LYS A 12 34. 536 42. 821 20. 219 1. 00 45. 62 N ATOM 89 CA LYS A 12 33.681 41.730 20.660 1.00 45.76 C
ATOM 90 C LYS A 12 33 .400 41 .907 22 .149 1 .00 45 .70 C
ATOM 91 O LYS A 12 33 .885 42 .864 22 .765 1 .00 45 .63 O
ATOM 92 CB LYS A 12 34 .386 40 .390 20 .416 1 .00 45 .92 C
ATOM 93 CG LYS A 12 34 .484 39 .985 18 .949 1 .00 46 .82 c
ATOM 94 CD LYS A 12 33 .149 39 .399 18 .453 1 .00 47 .89 c
ATOM 95 CE LYS A 12 33 .151 39 .145 16 .934 1 .00 48 .84 c
ATOM 96 NZ LYS A 12 31 .796 39 .348 16 .320 1 .00 48 .93 N
ATOM 97 N GLU A 13 32 .612 41 .002 22 .731 1 .00 45 .55 N
ATOM 98 CA GLU A 13 32 .409 41, .008 24 .181 1 .00 45 .41 C
ATOM 99 C GLU A 13 32 .642 39 .635 24 .805 1 .00 45 .16 C
ATOM 100 O GLU A 13 32 .848 38 .657 24 .088 1 .00 45 .05 O
ATOM 101 CB GLU A 13 31 .046 41, .606 24 .567 1 .00 45 .43 C
ATOM 102 CG GLU A 13 29 .861 41, .148 23 .742 1 ,00 45 .72 C
ATOM 103 CD GLU A 13 28 .564 41 .822 24 .170 1 .00 46 .47 C
ATOM 104 OEl GLU A 13 28 .600 42, .702 25 .066 1, .00 46 .24 o
ATOM 105 OE2 GLU A 13 27 .500 41, .468 23 .610 1 .00 46 .90 0
ATOM 106 N THR A 14 32 .644 39, .593 26 .140 1 .00 44 .90 N
ATOM 107 CA THR A 14 33, .083 38, .428 26, .911 1, .00 44, .71 C
ATOM 108 C THR A 14 32, .125 37, .269 26, .709 1, .00 44 .50 C
ATOM 109 O THR A 14 30, .911 37, .449 26, .735 1 .00 44 .21 O
ATOM 110 CB THR A 14 33 .238 38, .792 28 .435 1 .00 44 .82 C
ATOM 111 OG1 THR A 14 34, .553 39. .314 28, .685 1, .00 44, .93 O
ATOM 112 CG2 THR A 14 33, .164 37, .561 29, .361 1, .00 44, .75 C
ATOM 113 N GLY A 15 32 .694 36, .085 26, .496 1. .00 44, .50 N
ATOM 114 CA GLY A 15 31, .931 34. .889 26, .197 1, .00 44, .65 C
ATOM 115 C GLY A 15 31, .896 34. .603 24, ,710 1, .00 44, .80 C
ATOM 116 O GLY A 15 31, .830 33, .436 24, .318 1, .00 44, .91 O
ATOM 117 N GLU A 16 31. .938 35. ,667 23. .896 1. .00 44, .95 N
ATOM 118 CA GLU A 16 31, .877 35. ,577 22. .428 1, .00 44, .98 C
ATOM 119 C GLU A 16 33, .187 35. .043 21, .885 1. .00 44, .72 C
ATOM 120 O GLU A 16 34, .108 34. .803 22, ,648 1, .00 44, .90 O
ATOM 121 CB GLU A 16 31, .594 36. .948 21. ,789 1, .00 45. .01 C
ATOM 122 CG GLU A 16 30, .329 37. ,640 22. ,280 1, .00 45. .66 C
ATOM 123 CD GLU A 16 29, .871 38, .772 21. .368 1, .'00 46. .88 C
ATOM 124 OEl GLU A 16 28, .712 39, .223 21. .498 1. .00 47. .16 O
ATOM 125 OE2 GLU A 16 30, .668 39, .221 20. .518 1, .00 48. .78 O
ATOM 126 N SER A 17 33. .267 34. .847 20. .572 1, ,00 44. .36 N
ATOM 127 CA SER A 17 34. .525 34. ,452 19. ,945 1, ,00 44. .22 C
ATOM 128 C SER A 17 34. .950 35. ,435 18. ,848 1, ,00 43. .95 C
ATOM 129 O SER A 17 34, .197 36. ,323 18. ,477 1. ,00 43, ,90 o
ATOM 130 CB SER A 17 34. ,430 33. ,018 19. ,417 1. ,00 44. ,27 c
ATOM 131 OG SER A 17 33. ,581 32. ,935 18. ,296 1. ,00 44. ,57 0
ATOM 132 N LEU A 18 36. .173 35. ,281 18. ,361 1. ,00 43. ,92 N
ATOM 133 CA LEU A 18 36, .724 36. ,130 17. ,302 1. ,00 44. ,02 C
ATOM 134 C LEU A 18 37. ,370 35. 255 16. 226 1. ,00 43. ,55 C
ATOM 135 O LEU A 18 38. ,128 34. 358 16. 549 1. ,00 43. ,25 O
ATOM 136 CB LEU A 18 37, ,782 37. ,064 17. 905 1. ,00 44. ,33 C
ATOM 137 CG LEU A 18 38. ,245 38. 374 17. 238 1. 00 45. 16 C
ATOM 138 CD1 LEU A 18 39. ,734 38. 631 17. 509 1. 00 45. ,46 C
ATOM 139 CD2 LEU A 18 37. ,995 38. 410 15. 752 1. 00 46. ,71 C
ATOM 140 N THR A 19 37. 068 35. 503 14. 961 1. 00 43. 45 N
ATOM 141 CA THR A 19 37. 811 34. 883 13. 873 1. 00 43. 78 C
ATOM 142 C THR A 19 38. ,532 35. 969 13. 100 1. 00 44. 14 C
ATOM 143 O THR A 19 37. 898 36. 792 12. 447 1. 00 43. 91 O
ATOM 144 CB THR A 19 36. 883 34. 098 12. 919 1. 00 44. 21 C
ATOM 145 OG1 THR A 19 36. 260 32. 974 13. 596 1. 00 43. 80 O
ATOM 146 CG2 THR A 19 37. 701 33. 482 11. 751 1. 00 43. 99 C
ATOM 147 N ILE A 20 39. 855 35. 995 13. 228 1. 00 44. 85 N
ATOM 148 CA ILE A 20 40. 724 36. 824 12. 400 1. 00 45. 39 C
ATOM 149 C ILE A 20 41. 108 36. 004 11. 155 1. 00 45. 61 C
ATOM 150 O ILE A 20 41. 388 34. 805 11. 253 1. 00 45. 68 O
ATOM 151 CB ILE A 20 42. 012 37. 231 13. 181 1. 00 45. 75 C
ATOM 152 CGI ILE A 20 41. 681 37. 954 14. 485 1. 00 45. 74 C ATOM 153 CG2 ILE A 20 42.932 38.125 12 . 340 1.00 46.03 c
ATOM 154 CD1 ILE A 20 42.736 37.725 15 . 527 1 .00 45 .77 c
ATOM 155 N ASN A 21 41.139 36.664 9 . 997 1 .00 45 .69 N
ATOM 156 CA ASN A 21 41.425 36.011 8 . 731 1 .00 45 .87 c
ATOM 157 C ASN A 21 42.566 36.673 8 . 007 1, .00 45, .77 c
ATOM 158 O ASN A 21 42.517 37.865 7 . 702 1 .00 45 .99 0
ATOM 159 CB ASN A 21 40.197 36.006 7 . 832 1 .00 45 .95 c
ATOM 160 CG ASN A 21 39.197 34.957 8 . 240 1, .00 46, .88 c
ATOM 161 OD1 ASN A 21 38.008 35.241 8 . 394 1 .00 45, .42 0
ATOM 162 ND2 ASN A 21 39.678 33.729 8 . 444 1 .00 49 .22 N
ATOM 163 N CYS A 22 43.589 35.867 7 . 733 1, ..00 45, .61 N
ATOM 164 CA CYS A 22 44.744 36.274 6 . 942 1, .00 45, .36 C
ATOM 165 C CYS A 22 44.808 35.587 5 . 576 1, .00 44, ,39 C
ATOM 166 O CYS A 22 44.397 34.437 5 . 442 1, .00 44, .02 0
ATOM 167 CB CYS A 22 46.018 36.007 7 . 733 1, .00 45, .38 c
ATOM 168 SG CYS A 22 46.155 37.120 9 . 136 1, .00 47, ,07 s
ATOM 169 N VAL A 23 45.299 36.314 4. 564 1, .00 43, ,69 N
ATOM 170 CA VAL A 23 45.610 35.707 3.. 272 1, .00 42, .87 C
ATOM 171 C VAL A 23 46.930 36.260 2 , 699 1. .00 42, .09 C
ATOM 172 O VAL A 23 47.175 37.458 2. 743 1, .00 41, .16 O
ATOM 173 CB VAL A 23 44.411 35.789 2. 289 1, .00 42, .69 C
ATOM 174 CGI VAL A 23 44.004 37.187 2. 072 1. .00 42. .87 c
ATOM 175 CG2 VAL A 23 44.734 35.101 0 . 943 1, .00 43, .10 c
ATOM 176 N LEU A 24 47.789 35.346 2 . 229 1, .00 41, .64 N
ATOM 177 CA LEU A 24 49.057 35.682 1 . 605 1. .00 41, .41 C
ATOM 178 C LEU A 24 48.809 36.129 0 . 181 1, .00 41, ,77 C
ATOM 179 O LEU A 24 48.420 35.330 -0 . 689 1, .00 41, .43 O
ATOM 180 CB LEU A 24 50.032 34.502 614 1. ,00 41. .29 C
ATOM 181 CG LEU A 24 51.469 34.832 175 1, .00 41. .13 C
ATOM 182 CD1 LEU A 24 52.229 35.654 232 1, ,00 41. .67 C
ATOM 183 CD2 LEU A 24 52.248 33.586 0.829 1, .00 40, ,60 C
ATOM 184 N ARG A 25 49.090 37.411 -0.055 1, .00 41, .98 N
ATOM 185 CA ARG A 25 48.726 38.075 -1.287 1, .00 42, .00 C
ATOM 186 C ARG A 25 49.889 38.325 -2.241 1, .00 42, .03 C
ATOM 187 O ARG A 25 51.012 38.537 -1.824 1, .00 41, .90 O
ATOM 188 CB ARG A 25 48.032 39.373 -0.938 1, .00 42, .03 C
ATOM 189 CG ARG A 25 46.623 39.140 -0.474 1, ,00 42, .99 c
ATOM 190 CD ARG A 25 45.621 39.047 -1.599 1, .00 44, .97 c
ATOM 191 NE ARG A 25 44.560 40.014 -1.353 1. ,00 47, .71 N
ATOM 192 CZ ARG A 25 44.099 40.915 -2.219 1, .00 47, .44 C
ATOM 193 NH1 ARG A 25 43.147 41.739 -1.836 1, .00 46, .78 N
ATOM 194 NH2 ARG A 25 44.563 41.001 -3.456 1, .00 48, .53 N
ATOM 195 N ASP A 26 49.588 38.295 -3.536 1. .00 42. ,42 N
ATOM 196 CA ASP A 26 50.527 38.682 -4.575 1. ,00 42. .66 C
ATOM 197 C ASP A 26 51.931 38.119 -4.330 1, ,00 43. .02 C
ATOM 198 O ASP A 26 52.910 38.831 -4.519 1, .00 43. .38 0
ATOM 199 CB ASP A 26 50.554 40.217 -4.690 1, .00 42. .63 c
ATOM 200 CG ASP A 26 49.267 40.784 -5.308 1, .00 42. .95 c
ATOM 201 OD1 ASP A 26 48.444 41.361 -4.570 1, .00 41. .75 o
ATOM 202 OD2 ASP A 26 48.985 40.699 -6.526 1. .00 43. .93 0
ATOM 203 N ALA A 27 52.019 36.849 -3.918 1, .00 43. .15 N
ATOM 204 CA ALA A 27 53.298 36.200 -3.589 1, .00 43. .42 C
ATOM 205 C ALA A 27 53.539 34.998 -4.486 1. .00 43. .84 C
ATOM 206 O ALA A 27 52.683 34.130 -4.576 1, .00 44. .30 O
ATOM 207 CB ALA A 27 53.320 35.760 -2.119 1. .00 43. .12 C
ATOM 208 N SER A 28 54.707 34.934 -5.118 1, ,00 44. ,23 N
ATOM 209 CA SER A 28 55.060 33.830 -6.031 l: .00 45. ,06 C
ATOM 210 C SER A 28 55.236 32.425 -5.371 1. .00 45, .41 C
ATOM 211 O SER A 28 55.084 31.382 -6.024 1. ,00 45. ,34 0
ATOM 212 CB SER A 28 56.347 34.192 -6.792 1. ,00 45. ,26 c
ATOM 213 OG SER A 28 57.380 34.588 -5.892 1. .00 45. .67 o
ATOM 214 N TYR A 29 55.569 32.417 -4.087 1. ,00 45. ,63 N
ATOM 215 CA TYR A 29 55.743 31.191 -3.322 1. ,00 46. ,00 C
ATOM 216 C TYR A 29 54.418 30.837 -2.637 1. ,00 46. 01 C ATOM 217 O TYR A 29 53.559 31,.681 -2,.501 1,.00 45.94 0
ATOM 218 CB TYR A 29 56 .864 31, .377 -2, .283 1, .00 46 .23 c
ATOM 219 CG TYR A 29 56 .797 32 .700 -1, .550 1, .00 46 .49 c
ATOM 220 CD1 TYR A 29 57, .416 33, ,832 -2, .066 1, ,00 46, .98 c
ATOM 221 CD2 TYR A 29 56, .085 32, .824 -0, .361 1, .00 48 .01 c
ATOM 222 CE1 TYR A 29 57 .343 35, .050 -1, .415 1, ,00 47 .91 c
ATOM 223 CE2 TYR A 29 55, .998 34, .044 0, .307 1, .00 49 .09 c
ATOM 224 CZ TYR A 29 56, .635 35, .156 -0, .229 1, .00 49, .16 c
ATOM 225 OH TYR A 29 56, .559 36, .376 0, ,412 1, .00 49, .69 0
ATOM 226 N GLY A 30 54, .259 29, .594 -2, ,202 1, .00 46, .34 N
ATOM 227 CA GLY A 30 53, .046 29, .169 -1, ,518 1, .00 46, .80 c
ATOM 228 C GLY A 30 53, .063 29, ,488 -0, .029 1, .00 47, .05 c
ATOM 229 O GLY A 30 53, .892 30, .277 0, .419 1, .00 47, .34 0
ATOM 230 N LEU A 31 52, .168 28, .870 0, .741 1. .00 47, .02 N
ATOM 231 CA LEU A 31 52, .073 29, .121 2, ,180 1, .00 47, .04 C
ATOM 232 C LEU A 31 52, .846 28, ,046 2. ,918 1, .00 47, .34 C
ATOM 233 O LEU A 31 52, .657 26, .854 2, .672 1, ,00 47, .29 0
ATOM 234 CB LEU A 31 50, .620 29. ,072 2, .653 1, ,00 46. .88 C
ATOM 235 CG LEU A 31 50, ,129 30, ,133 3, .642 1, ,00 46, .91 c
ATOM 236 CD1 LEU A 31 48, .959 29, ,592 4, .454 1, ,00 47, .38 c
ATOM 237 CD2 LEU A 31 51, ,222 30, .614 4, .558 1, .00 47, .01 c
ATOM 238 N GLU A 32 53. .712 28, ,452 3, ,832 1, .00 47. .44 N
ATOM 239 CA GLU A 32 54. .431 27, .474 4, .604 1, .00 47, .70 C
ATOM 240 C GLU A 32 54, .182 27, .729 6, .092 1, .00 47, .35 C
ATOM 241 O GLU A 32 53. .023 27, .704 6. .485 1. .00 47. .96 O
ATOM 242 CB GLU A 32 55, .882 27, .401 4, .135 1. .00 48. .20 C
ATOM 243 CG GLU A 32 56, ,334 25, .976 3, .750 1, .00 50. .58 c
ATOM 244 CD GLU A 32 55, .433 25, ,258 2, .727 1, .00 52, .14 c
ATOM 245 OEl GLU A 32 54, ,939 25, .923 1, .779 1, ,00 52. .31 0
ATOM 246 OE2 GLU A 32 55, ,240 24, .015 2, ,871 1. .00 52. .34 0
ATOM 247 N SER A 33 55, .178 27, .958 6, ,940 1, ,00 46, ,79 N
ATOM 248 CA SER A 33 54, .873 28, .132 8, ,367 1. .00 46, .45 C
ATOM 249 C SER A 33 53. .863 29. .273 8, ,593 1. .00 46, .08 C
ATOM 250 O SER A 33 53, ,672 30. .135 7, ,739 1, .00 46, ,14 O
ATOM 251 CB SER A 33 56, .152 28, .351 9, ,188 1, ,00 46, .57 C
ATOM 252 OG SER A 33 55. .888 28, .890 10, .475 1, ,00 46, .71 0
ATOM 253 N THR A 34 53. ,188 29, .239 9, .730 1. .00 45, .62 N
ATOM 254 CA THR A 34 52, .243 30, .289 10, .107 1. ,00 45, .56 C
ATOM 255 C THR A 34 52. .425 30, .607 11. ,569 1. .00 44, ,81 C
ATOM 256 O THR A 34 52. .995 29, .815 12, ,293 1. .00 45, .14 O
ATOM 257 CB THR A 34 50, .802 29, .825 9, .885 1. .00 45, .92 C
ATOM 258 OG1 THR A 34 50, .659 28, .479 10, .376 1. .00 47, ,83 O
ATOM 259 CG2 THR A 34 50, .459 29, .745 8. ,384 1. ,00 45, ,65 C
ATOM 260 N GLY A 35 51, .910 31, .742 12. ,016 1. ,00 44, ,17 N
ATOM 261 CA GLY A 35 52, .193 32, .203 13, .362 1. ,00 43, .84 C
ATOM 262 C GLY A 35 51. ,335 33. .355 13. ,829 1. ,00 43. ,55 C
ATOM 263 O GLY A 35 51. ,044 34, .257 13. ,065 1. ,00 43, .37 O
ATOM 264 N TRP A 36 50. ,951 33. .333 15. ,098 1. ,00 43, ,43 N
ATOM 265 CA TRP A 36 50. .125 34. .387 15. ,662 1, ,00 43, ,65 C
ATOM 266 C TRP A 36 50. .808 35. .017 16. ,862 1. ,00 43. ,76 C
ATOM 267 O TRP A 36 51, .562 34, ,348 17. ,536 1. ,00 44. ,10 O
ATOM 268 CB TRP A 36 48. .736 33, .832 16. ,015 1. ,00 43, ,66 C
ATOM 269 CG TRP A 36 48. ,035 33. ,281 14. ,791 1. ,'00 43. ,52 C
ATOM 270 CD1 TRP A 36 48. ,228 32. ,056 14. 203 1. ,00 43. ,11 C
ATOM 271 CD2 TRP A 36 47. .066 33. ,955 13. 989 1. ,00 43. ,23 C
ATOM 272 NE1 TRP A 36 47. .429 31. ,932 13. ,091 1. ,00 42. ,76 N
ATOM 273 CE2 TRP A 36 46. ,708 33. ,079 12. 933 1. 00 42. ,13 C
ATOM 274 CE3 TRP A 36 46. ,465 35. ,212 14. 052 1. 00 42. ,31 C
ATOM 275 CZ2 TRP A 36 45, ,786 33. ,412 11. ,970 1. 00 42. ,17 C
ATOM 276 CZ3 TRP A 36 45, .545 35. ,541 13. ,101 1. ,00 42. ,77 C
ATOM 277 CH2 TRP A 36 45. ,213 34. ,645 12. 060 1. 00 43. 22 C
ATOM 278 N TYR A 37 50. ,547 36. ,306 17. 100 1. 00 44. ,26 N
ATOM 279 CA TYR A 37 51. ,155 37. ,090 18. 178 1. 00 44. ,69 C
ATOM 280 C TYR A 37 50. 145 38. 050 18. 793 1. 00 45. 68 C ATOM 281 O TYR A 37 49.574 38.884 18.132 1.00 45.58 0
ATOM 282 CB TYR A 37 52, .357 37, .862 17, .660 1, .00 44 .51 c
ATOM 283 CG TYR A 37 53, .257 36, .964 16 .865 1, .00 44 .82 c
ATOM 284 GDI TYR A 37 54, .326 36, .311 17 .461 1 .00 45 .09 c
ATOM 285 CD2 TYR A 37 52, ,993 36, .705 15, .529 1, .00 45 .84 c
ATOM 286 CE1 TYR A 37 55, .114 35, .452 16, .740 1, .00 45 .33 c
ATOM 287 CE2 TYR A 37 53, .776 35 .854 14 .802 1, .00 45 .95 c
ATOM 288 CZ TYR A 37 54. .826 35, .232 15, .411 1, .00 45 .91 c
ATOM 289 OH TYR A 37 55, .589 34, .380 14, .672 1, .00 49 .07 o
ATOM 290 N ARG A 38 49, .900 37, .872 20, .079 1, .00 47 .31 N
ATOM 291 CA ARG A 38 49, .134 38, ,801 20, .909 1, .00 48, .10 c
ATOM 292 C ARG A 38 50, ,091 39, .931 21, .209 1, .00 47 .87 c
ATOM 293 O ARG A 38 51. .303 39, .726 21. .173 1, .00 47, .88 0
ATOM 294 CB ARG A 38 48. .759 38. .111 22, .249 1. ,00 48, .62 c
ATOM 295 CG ARG A 38 47, .377 38, .432 22, .831 1, .00 50, .71 c
ATOM 296 CD ARG A 38 46, .603 37, .207 23. .407 1, .00 53, ,44 c
ATOM 297 NE ARG A 38 46, .786 37, .089 24, .850 1, .00 55, .90 N
ATOM 298 CZ ARG A 38 47, ,813 36, .479 25, ,449 1. .00 58, .69 C
ATOM 299 NH1 ARG A 38 47, ,882 36, .457 26, .782 1, .00 59, .57 N
ATOM 300 NH2 ARG A 38 48, .779 35. .889 24, .738 1, .00 59, .59 N
ATOM 301 N THR A 39 49, .567 41, .114 21, .489 1, .00 47, .47 N
ATOM 302 CA THR A 39 50, .306 42. .060 22, .309 1, .00 47. .36 C
ATOM 303 C THR A 39 49, .306 42, ,440 23. .385 1. .00 47, .23 C
ATOM 304 O THR A 39 48, ,311 43, .116 23, .131 1, .00 47, .09 O
ATOM 305 CB THR A 39 50, ,927 43. .249 21, .480- 1, .00 47, .47 C
ATOM 306 OG1 THR A 39 52. ,344 43, .323 21. .720 1, .00 47. .03 O
ATOM 307 CG2 THR A 39 50. .436 44, .627 21, .920 1. .00 47, .35 C
ATOM 308 N LYS A 40 49. .535 41. .920 24. .582 1, .00 47, .19 N
ATOM 309 CA LYS A 40 48. .558 42. .086 25. .633 1. .00 47. ,13 C
ATOM 310 C LYS A 40 48. ,444 43. ,571 25. ,866 1. ,00 47, ,19 C
ATOM 311 O LYS A 40 49, .445 44, ,248 26, ,082 1, .00 47, .17 O
ATOM 312 CB LYS A 40 48, .928 41, .324 26, .921 1, .00 47, ,02 C
ATOM 313 CG LYS A 40 47, .688 40, .729 27, ,623 1, .00 46, .82 C
ATOM 314 CD LYS A 40 48, .015 39. ,740 28, ,748 1, .00 46, .47 C
ATOM 315 CE LYS A 40 47. .890 40, .377 30, .145 1. .00 46, .50 C
ATOM 316 NZ LYS A 40 46. ,755 41. .347 30, .294 1. .00 45, ,86 N
ATOM 317 N LEU A 41 47. ,225 44. .076 25, ,723 1, .00 47, ,30 N
ATOM 318 CA LEU A 41 46. ,871 45. .412 26, .180 1, .00 47, .33 C
ATOM 319 C LEU A 41 47, ,530 45. .674 27, .555 1. .00 47, .66 C
ATOM 320 O LEU A 41 47, ,133 45. .093 28, .587 1, .00 47, .69 0
ATOM 321 CB LEU A 41 45, ,346 45. .509 26, .247 1, .00 47, .14 C
ATOM 322 CG LEU A 41 44, .683 46. .802 26, .698 1. .00 46, .34 c
ATOM 323 CD1 LEU A 41 43. ,722 47. .282 25, ,653 1, .'oo 45. .95 c
ATOM 324 CD2 LEU A 41 43. ,951 46. .576 28, ,014 1, .00 46. .62 c
ATOM 325 N GLY A 42 48. ,559 46. .526 27. .547 1. .00 47, ,83 N
ATOM 326 CA GLY A 42 49. ,360 46, .802 28. .732 1. ,00 47. .73 C
ATOM 327 C GLY A 42 50. ,836 46. ,954 28. ,413 1. ,00 47. ,74 C
ATOM 328 O GLY A 42 51. ,489 47, ,872 28. ,901 1. ,00 47. ,48 O
ATOM 329 N SER A 43 51. .351 ' 46. .050 27. ,583 1. ,00 48. ,04 N
ATOM 330 CA SER A 43 52. ,779 45. ,973 27. ,275 1. ,00 48. ,28 C
ATOM 331 C SER A 43 53. ,132 46. ,240 25. ,793 1. ,00 48. ,76 C
ATOM 332 O SER A 43 52, ,263 46. ,291 24. ,909 1'. ,00 48. ,44 O
ATOM 333 CB SER A 43 53. ,307 44. ,595 27. 691 1. 00 48. 30 C
ATOM 334 OG SER A 43 52. ,660 43. ,559 26. 975 1. 00 47. ,07 O
ATOM 335 N THR A 44 54. ,429 46. ,431 25. ,548 1. ,00 49. ,30 N
ATOM 336 CA THR A 44 54. 965 46. 557 24. 185 1. 00 49. ,61 C
ATOM 337 C THR A 44 55. ,542 45. ,219 23. 671 1. 00 49. ,81 C
ATOM 338 O THR A 44 55. ,581 44. ,967 22. ,450 1. ,00 49. ,86 O
ATOM 339 CB THR A 44 56. 019 47. 712 24. 113 1. 00 49. 63 C
ATOM 340 OG1 THR A 44 56. 404 47. 937 22. 748 1. 00 49. 78 O
ATOM 341 CG2 THR A 44 57. 330 47. ,364 24. 847 1. 00 49. 19 C
ATOM 342 N ASN A 45 55. 995 44. 395 24. 627 1. 00 49. 77 N
ATOM 343 CA ASN A 45 56. 406 43. 001 24. 416 1. 00 49. 48 C
ATOM 344 C ASN A 45 55. 386 42. 201 23. 612 1. 00 49. 23 C ATOM 345 O ASN A 45 54.319 41.857 24.120 1,.00 49.15 O
ATOM 346 CB ASN A 45 56, .617 42, .324 25, .786 1, .00 49, .49 c
ATOM 347 CG ASN A 45 57, .451 41 .059 25, .705 1 .00 49, .18 c
ATOM 348 OD1 ASN A 45 56, .931 39, .971 25, .446 1, .00 47, .89 0
ATOM 349 ND2 ASN A 45 58, .755 41, .195 25, .957 1, .00 48, .90 N
ATOM 350 N GLU A 46 55, .703 41 .923 22, .352 1 .00 49, .07 N
ATOM 351 CA GLU A 46 54, ,849 41, .064 21, .544 1, .00 49, .04 C
ATOM 352 C GLU A 46 55, .201 39, .618 21, .828 1, .00 48, .82 C
ATOM 353 O GLU A 46 56, .369 39 .233 21, .815 1 .00 48, .78 O
ATOM 354 CB GLU A 46 54, .967 41, .353 20, ,047 1, .00 49, ,09 C
ATOM 355 CG GLU A 46 53, .704 40, .968 19, .284 1, .00 49, .83 c
ATOM 356 CD GLU A 46 53. .952 40, .570 17, .838 1, .00 51, .36 c
ATOM 357 OEl GLU A 46 53, .070 40, .860 16, ,976 1, .00 51, ,15 0
ATOM 358 OE2 GLU A 46 55, .014 39, .951 17, .570 1, .00 51, .52 0
ATOM 359 N GLN A 47 54. .166 38, ,828 22. .082 1. .00 48. .68 N
ATOM 360 CA GLN A 47 54, .310 37, .447 22. .519 1, .00 48, .37 C
ATOM 361 C GLN A 47 53, .572 36, .493 21, .577 1, .00 47, .51 C
ATOM 362 O GLN A 47 52. .394 36, .706 21. .249 1, .00 47, .38 O
ATOM 363 CB GLN A 47 53, .787 37, .293 23, ,954 1, .00 48, ,68 C
ATOM 364 CG GLN A 47 52, .342 37. .807 24. ,195 1. .00 49, ,39 C
ATOM 365 CD GLN A 47 51. .875 37, .558 25. ,625 1. .00 50, .87 C
ATOM 366 OEl GLN A 47 50, .669 37, .523 25. .893 1, .00 51. .36 0
ATOM 367 NE2 GLN A 47 52. .832 37, .379 26. .546 1. .00 50. .64 N
ATOM 368 N THR A 48 54. ,288 35, .448 21. .159 1. .00 46. .35 N
ATOM 369 CA THR A 48 53, .721 34, .349 20, .381 1, .00 45. .37 C
ATOM 370 C THR A 48 52. ,475 33, ,751 21. .058 1. .00 44, ,66 C
ATOM 371 O THR A 48 52, .422 33, .619 22. .271 1, .00 44, .42 O
ATOM 372 CB THR A 48 54. .795 33, ,240 20. ,174 1. .00 45, .26 C
ATOM 373 OG1 THR A 48 56, .010 33, .809 19. .668 ι: ,00 43, ,92 O
ATOM 374 CG2 THR A 48 54, .372 32, .261 19, .087 1, .00 45, .53 C
ATOM 375 N ILE A 49 51. .470 33. .420 20. .262 1. .00 43, .99 N
ATOM 376 CA ILE A 49 50, .325 32, .645 20. .724 1. .00 43, .43 C
ATOM 377 C ILE A 49 50, .598 31. .154 20. ,458 1. .00 43, ,66 C
ATOM 378 O ILE A 49 51, .019 30, .794 19. ,352 1, .00 44, ,12 0
ATOM 379 CB ILE A 49 49, .060 33, .106 19, .994 I; .00 42, .82 c
ATOM 380 CGI ILE A 49 48, .633 34. .473 20, ,529 1, ,00 41, .60 c
ATOM 381 CG2 ILE A 49 47, .949 32, .065 20, ,138 1, .00 42, ,75 c
ATOM 382 GDI ILE A 49 47, .627 35, .211 19. .649 1. .00 40, .71 c
ATOM 383 N SER A 50 50, .357 30, ,302 21. ,457 1, .00 43. .62 N
ATOM 384 CA SER A 50 50, ,546 28, ,846 21. ,321 1, .00 43. .72 C
ATOM 385 C SER A 50 49, ,252 28, .069 21. ,024 1. ,00 43, ,40 C
ATOM 386 O SER A 50 48, .505 27. .736 21. ,944 1, ,00 43. .31 O
ATOM 387 CB SER A 50 51. .169 28, ,288 22. ,586 1, .00 43. .69 C
ATOM 388 OG SER A 50 52. ,525 28, ,670 22, ,645 1. .00 45. ,22 O
ATOM 389 N ILE A 51 49. .051 27, ,741 19, ,744 1, .00 43. ,11 N
ATOM 390 CA ILE A 51 47. .804 27, ,170 19, ,211 1, .00 42. ,81 C
ATOM 391 C ILE A 51 47. .340 25, ,902 19. .933 1, .00 42. ,89 C
ATOM 392 O ILE A 51 48. .044 24, ,893 19. .973 1. ,00 43. ,22 0
ATOM 393 CB ILE A 51 47, .928 26, ,862 17. ,691 1. ,00 42. 60 c
ATOM 394 CGI ILE A 51 48, ,287 28, ,126 16. ,869 1, ,00 42. ,42 c
ATOM 395 CG2 ILE A 51 46, .646 26, ,231 17. .177 1. ,00 42. ,42 c
ATOM 396 CD1 ILE A 51 47, ,368 29, ,346 17. ,030 1. ,00 41. 97 c
ATOM 397 N GLY A 52 46, .125 25. ,975 20. ,464 1. ,00 42. 68 N
ATOM 398 CA GLY A 52 45. .517 24, ,912 21. ,226 1. ,00 42. ,57 C
ATOM 399 C GLY A 52 44. ,403 25. ,490 22. 076 1. ,00 42. 68 C
ATOM 400 O GLY A 52 44, ,396 26. ,683 22. ,359 1. ,00 42. 51 0
ATOM 401 N GLY A 53 43. ,467 24. ,636 22. 488 1. ,00 42. 80 N
ATOM 402 CA GLY A 53 42, ,378 25, ,025 23. ,372 1. ,00 42. 58 c
ATOM 403 C GLY A 53 41. .385 26. ,025 22. ,801 1. ,00 42. 38 c
ATOM 404 O GLY A 53 40. ,644 25. ,714 21. 855 1. 00 42. 63 0
ATOM 405 N ARG A 54 41. ,353 27. ,211 23. ,410 1. ,00 41. 93 N
ATOM 406 CA ARG A 54 40. .476 28. ,301 22. ,981 1. ,00 41. 82 c
ATOM 407 C ARG A 54 40. ,875 28. ,889 21. 641 1. 00 41. 60 c
ATOM 408 O ARG A 54 40. ,031 29. ,296 20. 881 1. 00 41. 77 0 ATOM 409 CB ARG A 54 40.,516 29.,441 23..985 1.,00 41.,91 c
ATOM 410 CG ARG A 54 39. ,826 29. ,154 25, .263 1. .00 42, .28 c
ATOM 411 CD ARG A 54 40. ,540 29. ,674 26, ,510 1, .00 43, .07 c
ATOM 412 NE ARG A 54 41, ,425 30. ,833 26. .339 1, .00 42. .41 N
ATOM 413 CZ ARG A 54 41. ,047 32. .056 25, .963 1. .00 42. .94 C
ATOM 414 NH1 ARG A 54 39. ,789 32. .339 25, .636 1, .00 42. .52 N
ATOM 415 NH2 ARG A 54 41. ,957 33. .008 25, .885 1, .00 43. .60 N
ATOM 416 N TYR A 55 42. .166 28. .988 21, .378 1, ,00 41, .61 N
ATOM 417 CA TYR A 55 42. .650 29. .497 20, .103 1, ,00 41. .70 C
ATOM 418 C TYR A 55 42. .726 28. .309 19, .159 1. .00 41. .39 C
ATOM 419 O TYR A 55 43, .364 27. .317 19. .490 1, .00 41. ,66 0
ATOM 420 CB TYR A 55 44, .045 30. .071 20. .256 1, .00 41, .78 c
ATOM 421 CG TYR A 55 44. .264 31, .058 21. ,374 1, .00 43, .01 c
ATOM 422 GDI TYR A 55 44. .114 32. .412 21. ,151 1, .00 45. .49 c
ATOM 423 CD2 TYR A 55 44. .698 30. .648 22. ,625 1, .00 44, ,41 c
ATOM 424 CE1 TYR A 55 44. .364 33. .356 22, ,149 1, .00 46. ,84 c
ATOM 425 CE2 TYR A 55 44. ,951 ' ' 31. .580 23, ,642 1, .00 46, .64 c
ATOM 426 CZ TYR A 55 44. .783 32, .942 23, .394 1, ,00 47, .72 c
ATOM 427 OH TYR A 55 45. ,036 33. .905 24, .366 1, .00 49. .23 0
ATOM 428 N VAL A 56 42. .074 28, .395 18, .004 1, ,00 41, .05 N
ATOM 429 CA VAL A 56 42. .029 27. .272 17. .070 1. .00 41. .07 c
ATOM 430 C VAL A 56 42. .311 27. .777 15. .674 1, .00 41. .10 c
ATOM 431 O VAL A 56 41, .569 28, ,596 15. ,132 1, .00 41, .64 0
ATOM 432 CB VAL A 56 40. .694 26. .430 17. ,153 1, .00 41. .25 c
ATOM 433 CGI VAL A 56 39. .609 27. .137 17. ,971 1. .00 41. .73 c
ATOM 434 CG2 VAL A 56 40. .172 26. .028 15. ,763 1, .00 40. ,97 c
ATOM 435 N GLU A 57 43. .409 27. ,292 15. ,105 1, ,00 40. .96 N
ATOM 436 CA GLU A 57 43, .907 27, .802 13. .840 1, .00 40, .50 C
ATOM 437 C GLU A 57 43. .551 26, ,841 12. .720 1, ,00 40. .33 C
ATOM 438 O GLU A 57 43. ,610 25, .629 12. ,889 1, .00 39. .83 O
ATOM 439 CB GLU A 57 45. .415 27, .998 13. ,907 1, .00 40. ,54 c
ATOM 440 CG GLU A 57 46. ,000 28, .762 12. ,727 1, ,00 39. .88 c
ATOM 441 CD GLU A 57 47, .473 28, .469 12. ,482 1, .00 38, ,40 c
ATOM 442 OEl GLU A 57 48. .114 29, ,301 11, ,801 1, ,00 38. ,52 0
ATOM 443 OE2 GLU A 57 47, .983 27, .414 12, ,932 1, .00 36. .20 0
ATOM 444 N THR A 58 43. .186 27, .423 11, ,578 1, .00 40. .58 N
ATOM 445 CA THR A 58 42, ,790 26, .704 10, .378 1, .00 40. ,61 c
ATOM 446 C THR A 58 43, .598 27, .214 9, .204 1, .00 40, .52 c
ATOM 447 O THR A 58 43, .541 28, .376 8, .894 1, ,00 40. ,83 0
ATOM 448 CB THR A 58 41, .319 26, .947 10, .131 1, .00 40, .51 c
ATOM 449 OG1 THR A 58 40, ,594 26, ,653 11, ,332 1, .00 40. .91 0
ATOM 450 CG2 THR A 58 40, ,770 25, .955 9, ,126 1, ,00 40. .94 c
ATOM 451 N VAL A 59 44, ,354 26, .342 8, .559 1, .00 40, .88 N
ATOM 452 CA VAL A 59 45, .209 26, .761 7, ,469 1, .00 41. .62 C
ATOM 453 C VAL A 59 44, .781 26, .118 6, ,177 1. .00 41. .67 C
ATOM 454 O VAL A 59 44, .760 24, .902 6. ,034 1, ,00 40. .44 O
ATOM 455 CB VAL A 59 46, .709 26. .454 7, ,729 1, .00 42. .11 C
ATOM 456 CGI VAL A 59 47, .562 26, .709 6, ,467 1, ,00 42. .52 C
ATOM 457 CG2 VAL A 59 47, .238 27. .304 8. ,895 1, .00 42. .97 c
ATOM 458 N ASN A 60 44. .438 26. ,981 5. ,234 1, .00 42, .73 N
ATOM 459 CA ASN A 60 44. ,254 26. ,580 3. .848 1. .00 43. .69 C
ATOM 460 C ASN A 60 45, ,350 27. .108 2, .904 1, .00 44, .08 C
ATOM 461 O ASN A 60 45, .186 28. .134 2. ,225 I; .00 44, ,00 O
ATOM 462 CB ASN A 60 42, .850 26. .963 3. ,411 1, .00 43. ,92 C
ATOM 463 CG ASN A 60 41, .801 26. .329 4. ,299 1, .00 44, ,18 C
ATOM 464 OD1 ASN A 60 41. .512 25, .128 4. ,195 1, .00 43. .39 O
ATOM 465 ND2 ASN A 60 41. .270 27, .117 5. ,219 1, .00 44, ,84 N
ATOM 466 N LYS A 61 46. .487 26, .399 2, ,909 1, .00 44. ,37 N
ATOM 467 CA LYS A 61 47. .524 26, .609 1. ,918 l: .00 44. ,47 C
ATOM 468 C LYS A 61 46. .898 26, .038 0. ,671 1, .00 44, ,64 C
ATOM 469 O LYS A 61 46. .173 25. .035 0. ,742 1. ,00 44. ,99 0
ATOM 470 CB LYS A 61 48. .856 25. .930 2. ,313 1. .00 44. ,51 c
ATOM 471 CG LYS A 61 48, .903 24. .387 2. ,322 1, .00 44. ,75 c
ATOM 472 CD LYS A 61 50. ,173 23, .793 1. ,630 1. ,00 45. ,19 c ATOM 473 CE LYS A 61 51.015 22,.846 2.575 1.00 46.53 c
ATOM 474 NZ LYS A 61 50, .959 21, .330 2, .328 1 .00 45 .04 N
ATOM 475 N GLY A 62 47, .119 26, .692 -0, .457 1 .00 44 .60 N
ATOM 476 CA GLY A 62 46, .387 26, .359 -1 .667 1 .00 44 .89 C
ATOM 477 C GLY A 62 45, .563 27. ,560 -2, .050 1 .00 45 .08 C
ATOM 478 O GLY A 62 45, .623 28, .028 -3, .199 1 .00 45 .76 O
ATOM 479 N SER A 63 44, .806 28, .073 -1, .079 1. .00 44 .83 N
ATOM 480 CA SER A 63 44, .249 29. ,417 -1, ,186 1, .00 44 .31 C
ATOM 481 C SER A 63 45, .076 30. .389 -0, .342 1 .00 44 .40 C
ATOM 482 O SER A 63 44, .659 31, .524 -0, .106 1, .00 45 .19 O
ATOM 483 CB SER A 63 42, ,765 29. .447 -0, ,796 1, .00 43 .91 C
ATOM 484 OG SER A 63 42, .566 29. .106 0, .552 1 .00 42 .61 O
ATOM '485 N LYS A 64 46, ,252 29. .969 0. .114 1, .00 44, .25 N
ATOM 486 CA LYS A 64 47. ,113 30. .860 0. .890 1, .00 44 .38 C
ATOM 487 C LYS A 64 46. .362 31. .577 2, .063 1, .00 44 .90 C
ATOM 488 O LYS A 64 46. .748 32. .662 2. .520 1, .00 44, .39 O
ATOM 489 CB LYS A 64 47. .771 31. .866 -0. .063 1, .00 43, .88 C
ATOM 490 CG LYS A 64 49, ,066 31. .391 -0, .649 1, .00 43 .04 C
ATOM 491 CD LYS A 64 49, ,237 31. ,859 -2. .077 1, ,00 43, .15 C
ATOM 492 CE LYS A 64 50. .702 31. .983 -2. .440 1, .00 43, .42 C
ATOM 493 NZ LYS A 64 51, .009 31. ,656 -3, ,874 1, .00 43, .88 N
ATOM 494 N SER A 65 45, .296 30, ,938 2. ,545 1, .00 45, .34 N
ATOM 495 CA SER A 65 44, .506 31, .436 3. .657 1, .00 45, .55 C
ATOM 496 C SER A 65 44, .859 30. .722 4. .949 1, .00 45, .70 C
ATOM 497 O SER A 65 45, .151 29. .524 4. ,968 1, ,00 45, .65 0
ATOM 498 CB SER A 65 43, .043 31. .218 3. .368 1, .00 45, .66 c
ATOM 499 OG SER A 65 42, .746 31, .666 2. .060 1, .00 47, .51 0
ATOM 500 N PHE A 66 44, .879 31. ,496 6, .022 1, .00 46, .04 N
ATOM 501 CA PHE A 66 44, .975 30. .970 7, ,373 1, .00 46, .46 C
ATOM 502 C PHE A 66 44, .180 31. .868 8. ,289 1, .00 46, .96 C
ATOM 503 O PHE A 66 43, .821 32. ,983 7, ,917 1, .00 47. .34 O
ATOM 504 CB PHE A 66 46, .418 30, ,795 7. ,864 1, .00 46, .58 c
ATOM 505 CG PHE A 66 47, .295 32, ,024 7, ,739 1, .00 46. .03 c
ATOM 506 GDI PHE A 66 47, .894 32. ,562 8, ,850 1. .00 45. .98 c
ATOM 507 CD2 PHE A 66 47. .593 32. .571 6, ,502 1, .00 45, .65 c
ATOM 508 CE1 PHE A 66 48. .736 33. .644 8, .736 1, .00 -46. .45 c
ATOM 509 CE2 PHE A 66 48. ,420 33, .648 6, .387 1, .00 46. .28 c
ATOM 510 CZ PHE A 66 48. .998 34, .190 7, .507 1, ,00 46, .93 c
ATOM 511 N SER A 67 43. .887 31. ,362 9. ,483 1, ,00 47, .40 N
ATOM 512 CA SER A 67 42. .797 31. ,900 10. ,301 1, ,00 47, .25 C
ATOM 513 C SER A 67 42. .861 31, .390 11. ,738 1, .00 47, .20 C
ATOM 514 O SER A 67 43. .245 30. ,241 12. ,007 1. .00 46, .85 0
ATOM 515 CB SER A 67 41. .445 31. .534 9. ,663 1, .00 47, ,08 C
ATOM 516 OG SER A 67 40. ,452 31. .232 10. ,624 1. ,00 46, ,69 0
ATOM 517 N LEU A 68 42. .476 32. ,272 12. ,649 1. ,00 47. .00 N
ATOM 518 CA LEU A 68 42. .493 31. ,990 14. ,065 1, ,00 47, ,00 c
ATOM 519 C LEU A 68 41. ,130 32. ,354 14. 616 1. ,00 47. ,52 c
ATOM 520 O LEU A 68 40. ,742 33. ,530 14. ,551 1. ,00 47. ,90 0
ATOM 521 CB LEU A 68 43. .587 32. ,842 14. ,724 1. ,00 46. ,58 c
ATOM 522 CG LEU A 68 43. ,663 32. 936 16. 246 1. ,00 45. ,67 c
ATOM 523 CD1 LEU A 68 44. ,187 31. 659 16. 863 1. .00 44. ,93 c
ATOM 524 CD2 LEU A 68 44. .549 34. ,085 16. ,631 1. ,00 46. ,07 c
ATOM 525 N ARG A 69 40. ,394 31. 355 15. 124 1. ,00 47. 58 N
ATOM 526 CA ARG A 69 39. ,227 31. 612 15. 975 1. ,00 47. ,49 C
ATOM 527 C ARG A 69 39. ,629 31. 518 17. 432 1. ,00 47. ,38 C
ATOM 528 O ARG A 69 40. ,130 30. 483 17. 850 1. 00 46. 69 0
ATOM 529 CB ARG A 69 38. ,084 30. 631 15. 698 1. ,00 47. 74 c
ATOM 530 CG ARG A 69 36. ,735 31. 107 16. 207 1. ,00 48. ,05 c
ATOM 531 CD ARG A 69 35. 559 30. 284 15. 720 1. 00 50. 06 c
ATOM 532 NE ARG A 69 34. ,814 29. 685 16. 848 1. 00 52. 61 N
ATOM 533 CZ ARG A 69 33. 507 29. 870 17. 130 1. ,00 52. 39 c
ATOM 534 NH1 ARG A 69 32. 724 30. 653 16. 378 1. 00 52. 14 N
ATOM 535 NH2 ARG A 69 32. 982 29. 261 18. 189 1. 00. 51. 54 N
ATOM 536 N ILE A 70 39. 427 32. 603 18. 187 1. 00 47. 73 N ATOM 537 CA ILE A 70 39,.636 32..606 19,.643 1..00 48,.12 c
ATOM 538 C ILE A 70 38. .291 32. .469 20. .350 1. .00 48, .27 c
ATOM 539 O ILE A 70 37, .476 33. .380 20, .289 1. .00 48, .45 0
ATOM 540 CB ILE A 70 40, .311 33. .899 20, .149 1, .00 48. .01 c
ATOM 541 CGI ILE A 70 41, .379 34. .400 19, .189 1. .00 48, .22 c
ATOM 542 CG2 ILE A 70 40, .912 33. .652 21, .524 1. .00 47, .97 c
ATOM 543 GDI ILE A 70 41, .707 35. .866 19. .402 1. .00 49, .26 c
ATOM 544 N ARG A 71 38, .091 31. .353 21, .048 1. .00 48, .47 N
ATOM 545 CA ARG A 71 36, .793 30. .972 21. .600 1. .00 48, .71 C
ATOM 546 C ARG A 71 36, .670 31. ,511 22, .987 1. .00 48, .26 C
ATOM 547 O ARG A 71 37, .671 31. ,684 23. .675 1. .00 48. .07 0
ATOM 548 CB ARG A 71 36, .661 29. ,448 21, ,702 1. .00 49, .15 c
ATOM 549 CG ARG A 71 36, .940 28. ,673 20. .415 1. .00 51. .24 c
ATOM 550 CD ARG A 71 37, .414 27. ,240 20, .664 1. .00 53, .73 c
ATOM 551 NE ARG A 71 36, .868 26. .293 19. .682 1, .00 56. .03 N
ATOM "552 CZ ARG A 71 36. .941 24. ,966 19, .790 1, .00 56, .30 C
ATOM 553 NH1 ARG A 71 36, ,417 24. ,190 18, .841 1. .00 56, .29 N
ATOM 554 NH2 ARG A 71 37, .542 24, ,412 20, ,838 1, ,00 56, .89 N
ATOM 555 N ASP A 72 35, .435 31. ,734 23, ,416 1. ,00 48, .12 N
ATOM 556 CA ASP A 72 35, .173 32. ,117 24, .795 1, ,00 48, .04 C
ATOM 557 C ASP A 72 36, ,106 33. ,276 25, ,179 1. .00 47, ,53 C
ATOM 558 O ASP A 72 37, .067 33, .104 25, .928 1, .00 47, .76 O
ATOM 559 CB ASP A 72 35, .350 30, .890 25, .705 1, .00 48, .14 C
ATOM 560 CG ASP A 72 35, .188 31, .210 27, .176 1, .00 49, .09 C
ATOM 561 OD1 ASP A 72 34, .318 32, .035 27, .531 1, .00 51, ,07 O
ATOM 562 OD2 ASP A 72 35, .891 30. .667 28. .051 1, .00 49, .87 O
ATOM 563 N LEU A 73 35. .810 34. .456 24, .646 1, .00 46. .77 N
ATOM 564 CA LEU A 73 36, .660 35, .618 24, .835 1, .00 46. .24 C
ATOM 565 C LEU A 73 36, .615 36, .074 26, .282 1, .00 45. .94 C
ATOM 566 O LEU A 73 35, .542 36. .191 26, .874 1, ,00 45. ,87 O
ATOM 567 CB LEU A 73 36, .222 36. .772 23. .939 1, .00 46. .11 c
ATOM 568 CG LEU A 73 36. .560 36, ,698 22. .459 1. .00 45. ,54 c
ATOM 569 GDI LEU A 73 35, .845 37, .825 21. .761 1, .00 45. .64 c
ATOM 570 CD2 LEU A 73 38. .049 36. .783 22. .216 1, .00 45. .68 c
ATOM 571 N ARG A 74 37, .794 36. .314 26. .843 1, .00 45. .60 N
ATOM 572 CA ARG A 74 37. .927 36. ,893 28. .175 1, .00 45. .37 C
ATOM 573 C ARG A 74 38, .273 38. ,376 28, .000 1, .00 45, .01 C
ATOM 574 O ARG A 74 38. ,583 38. ,817 26. ,891 1, .00 44, ,82 O
ATOM 575 CB ARG A 74 39, .010 36, ,146 28, .980 1, .00 45, .33 C
ATOM 576 CG ARG A 74 38, .584 34, ,734 29, ,475 1. .00 45, .30 C
ATOM 577 CD ARG A 74 39. .360 33. ,541 28, ,851 1, ,00 44, .76 c
ATOM 578 NE ARG A 74 38, .631 32. .259 28. ,955 1, .00 43. .64 N
ATOM 579 CZ ARG A 74 39. .075 31. .144 29, ,556 1, .00 42. .68 C
ATOM 580 NH1 ARG A 74 38. .322 30. .052 29. .576 1, .00 42. .05 N
ATOM 581 NH2 ARG A 74 40. .266 31, .094 30. .134 1, .00 42, .74 N
ATOM 582 N VAL A 75 38, ,209 39, .146 29, .079 1, .00 44, .67 N
ATOM 583 CA VAL A 75 38. .682 40. .533 29. .036 1, .00 44, ,47 C
ATOM 584 C VAL A 75 40. ,205 40. .543 28, ,869 1. ,00 44, .30 C
ATOM 585 O VAL A 75 40. ,744 41. .405 28, ,175 1. .00 44. ,10 O
ATOM 586 CB VAL A 75 38. .319 41, .335 30. ,307 1. .00 44, .42 C
ATOM 587 CGI VAL A 75 38. .693 42. ,808 30, .125 1'. ,00 44. ,06 C
ATOM 588 CG2 VAL A 75 36. .833 41, .170 30. .660 1. .00 44. .41 C
ATOM 589 N GLU A 76 40, .873 39. ,573 29. ,514 1. ,00 44. ,03 N
ATOM 590 CA GLU A 76 42, .327 39. .344 29. .397 1. ,00 43. ,64 C
ATOM 591 C GLU A 76 42. .840 39. ,312 27. ,962 1. ,00 43. .24 C
ATOM 592 O GLU A 76 44. .036 39. .503 27. ,733 1. ,00 42. ,95 O
ATOM 593 CB GLU A 76 42. .726 38. .014 30. .062 r. .00 43. ,51 C
ATOM 594 CG GLU A 76 43, .101 38. ,123 31. ,531 1. ,00 43. ,72 C
ATOM 595 CD GLU A 76 44, .528 38. .599 31. ,769 1. ,00 43. ,87 C
ATOM 596 OEl GLU A 76 45, .099 38. ,292 32. ,839 1. ,00 43. 97 O
ATOM 597 OE2 GLU A 76 45. .085 39. ,296 30. ,904 1. ,00 44. ,56 O
ATOM 598 N ASP A 77 41. ,934 39. ,055 27. ,018 1. 00 42. 97 N
ATOM 599 CA ASP A 77 42. .277 38. ,875 25. ,609 1. ,00 42. 98 C
ATOM 600 C ASP A 77 42. ,373 40. 157 24. ,790 1. 00 42. 77 C ATOM 601 O ASP A 77 42.913 40,.136 23,.703 1.00 42.39 0
ATOM 602 CB ASP A 77 41, .279 37, .912 24, .954 1, .00 43 .02 c
ATOM 603 CG ASP A 77 41 .334 36, .537 25, .560 1 .00 43 .11 c
ATOM 604 OD1 ASP A 77 42, .385 36, .208 26, .154 1, .00 43, .48 0
ATOM 605 OD2 ASP A 77 40 .386 35, .725 25, .510 1 .00 43 .48 o
ATOM 606 N SER A 78 41, .859 41, .263 25. .304 1, .00 43, .07 N
ATOM 607 CA SER A 78 41 .994 42, .532 24, .613 1, .00 43, .54 C
ATOM 608 C SER A 78 43, .462 42, .791 24. .304 1, .00 44, .00 C
ATOM 609 O SER A 78 44, .327 42, .631 25, .167 1, .00 43, .80 O
ATOM 610 CB SER A 78 41, .445 43. .691 25. .441 1, .00 43, .62 C
ATOM 611 OG SER A 78 40, .216 43, .356 26. .048 1, .00 44, .60 o
ATOM 612 N GLY A 79 43, .715 43. .187 23. .058 1, ,00 44, .73 N
ATOM 613 CA GLY A 79 45, .050 43, .480 22, .558 1, .00 45, .12 C
ATOM 614 C GLY A 79 45, .102 43. .517 21. .037 1, .00 45, .35 C
ATOM 615 O GLY A 79 44, .062 43. .549 20. .369 1, .00 45, .53 O
ATOM 616 N THR A 80 46. .317 43. .496 20. .492 1, .00 45, .41 N
ATOM 617 CA THR A 80 46, .524 43. .585 19, .054 1, .00 45, .52 C
ATOM 618 C THR A 80 47, .169 42. .327 18, ,490 1, ,00 45, .73 C
ATOM 619 O THR A 80 48, .314 42. .017 18, ,796 1, .00 45, .71 O
ATOM 620 CB THR A 80 47. ,366 44. .798 18, ,741 1, .00 45. .47 C
ATOM 621 OG1 THR A 80 46, ,544 45. .965 18, .844 1, .00 45, .71 O
ATOM 622 CG2 THR A 80 47. ,818 44. .794 17, .300 1, .00 45. ,82 C
ATOM 623 N TYR A 81 46, .416 41. .641 17, .632 1, .00 46. ,25 N
ATOM 624 CA TYR A 81 46, .764 40. .329 17, .103 1, .00 46. ,37 C
ATOM 625 C TYR A 81 47, ,323 40. .466 15, .717 1. .00 46. .94 C
ATOM 626 O TYR A 81 46, .771 41. .180 14, .900 1, .00 46. .88 O
ATOM 627 CB TYR A 81 45, .528 39. .444 17, .046 1, .00 46. .07 C
ATOM 628 CG TYR A 81 44, .964 39. .157 18, .407 1, .00 45. .69 C
ATOM 629 GDI TYR A 81 45, ,211 37. .938 19, .033 1. .00 45. .97 c
ATOM 630 CD2 TYR A 81 44. ,203 40. ,109 19, .089 1, .00 45. .33 c
ATOM 631 CE1 TYR A 81 44, ,705 37. .660 20, .297 1. .00 45. .78 c
ATOM 632 CE2 TYR A 81 43. .700 39. ,843 20. ,354 1, .00 45. .41 c
ATOM 633 CZ TYR A 81 43. .955 38, .618 20, .947 1, .00 45, ,24 c
ATOM 634 OH TYR -A 81 43. ,477 38, ,341 22, ,195 1, .00 45, .03 O
ATOM 635 N LYS A 82 48, ,429 39. .779 15, ,464 1, .00 47, ,75 N
ATOM 636 CA LYS A 82 49, .024 39, .725 14, ,140 1, .00 48, .32 c
ATOM 637 C LYS A 82 49, .286 38. .281 13, ,752 1. ,00 48, ,72 c
ATOM 638 O LYS A 82 49, .633 37, .451 14, ,579 1, .00 48, .30 O
ATOM 639 CB LYS A 82 50, ,311 40, ,541 14, ,073 1, ,00 48, .32 c
ATOM 640 CG LYS A 82 50, .043 42, .030 13, ,997 1, .00 48, .91 c
ATOM 641 CD LYS A 82 51. .254 42, .821 14, ,378 1. .00 50, .39 c
ATOM 642 CE LYS A 82 50, .900 44, .278 14, .589 1, .00 52, .20 c
ATOM 643 NZ LYS A 82 51. .775 44, .922 15, ,629 1, .00 53, .56 N
ATOM 644 N CYS A 83 49. ,074 37, .995 12, ,475 1, .00 49, .15 N
ATOM 645 CA CYS A 83 49. .442 36, .717 11. ,920 1, .00 49, .17 C
ATOM 646 C CYS A 83 50. .727 36, .864 11, ,140 1, .00 49, .28 C
ATOM 647 O CYS A 83 51. .136 37, ,983 10. .811 1, .00 49, .33 0
ATOM 648 CB CYS A 83 48, .351 36, .228 11. .017 1, .00 49, .00 c
ATOM 649 SG CYS A 83 48, .139 37. .232 9. ,569 1, .00 49, .18 s
ATOM 650 N GLY A 84 51, .341 35. .724 10, ,836 1, .00 49, .33 N
ATOM 651 CA GLY A 84 52. .629 35. .673 10. ,166 1, ,00 49. .19 c
ATOM 652 C GLY A 84 52, .664 34, .559 9. ,141 1, .00 49. .12 c
ATOM 653 O GLY A 84 52. .266 33. ,442 9. 430 1, ,00 49. ,28 0
ATOM 654 N ALA A 85 53. .114 34, .862 7. ,935 1, .00 49, .01 N
ATOM 655 CA ALA A 85 53. .339 33. ,844 6. 937 1. ,00 49. ,26 C
ATOM 656 C ALA A 85 54. .841 33, .726 6. ,775 1. ,00 49, ,76 c
ATOM 657 O ALA A 85 55. ,508 34. ,740 6. 569 1. ,00 49. ,89 0
ATOM 658 CB ALA A 85 52. .687 34, ,240 5. ,632 1. .00 49. ,16 c
ATOM 659 N PHE A 86 55. ,369 32. ,504 6. 901 1. ,00 50. ,29 N
ATOM 660 CA PHE A 86 56. ,787 32. ,209 6. ,632 1. ,00 50. ,83 C
ATOM 661 C PHE A 86 56. ,962 31. ,172 5. 505 1. ,00 51. 30 C
ATOM 662 O PHE A 86 56. ,044 30. ,388 5. 203 1. ,00 51. ,47 0
ATOM 663 CB PHE A 86 57. ,500 31. ,686 7. 874 1. ,00 50. 78 c
ATOM 664 CG PHE A 86 57. ,296 32. ,520 9. 099 1. ,00 51. ,53 c ATOM 665 GDI PHE A 86 58..337 33,.299 9.603 1,.00 52.02 c
ATOM 666 CD2 PHE A 86 56, ,073 32, .502 9 .777 1 .00 52 .06 c
ATOM 667 CE1 PHE A 86 58, .158 34 .064 10 .757 1 .00 52 .26 c
ATOM 668 CE2 PHE A 86 55. .876 33, .270 10, .928 1, .00 52 .10 c
ATOM 669 CZ PHE A 86 56. .920 34, .056 11 .417 1 .00 52 .60 c
ATOM 670 N ARG A 87 58. .163 31, .168 4, .915 1, .00 51, .82 N
ATOM 671 CA ARG A 87 58. .515 30, .298 3, .781 1, .00 51 .91 C
ATOM 672 C ARG A 87 59, .001 28, .925 4 .242 1 .00 51 .90 C
ATOM 673 O ARG A 87 58. ,918 27, ,952 3, .493 1, .00 51, .72 0
ATOM 674 CB ARG A 87 59. .609 30, .946 2, .925 1, .00 51 .90 c
ATOM 675 CG ARG A 87 59. .285 31, .033 1, .440 1, ,00 52, .27 c
ATOM 676 CD ARG A 87 59. .985 32, .196 0, .751 1, .00 52 .53 c
ATOM 677 NE ARG A 87 59. .902 32, .136 -0 .707 1, .00 53 .38 N
ATOM 678 CZ ARG A 87 60. ,590 31, ,293 -1, .486 1, .00 54, .43 C
ATOM 679 NH1 ARG A 87 60. .423 31, .344 -2, .809 1, .00 54 .34 N
ATOM 680 NH2 ARG A 87 61. .453 30. .411 -0, .969 1, ,00 54, .98 N
ATOM 681 N LEU A 99 62. .366 34, ,803 7, .148 1, .00 48, .13 N
ATOM 682 CA LEU A 99 61. .580 35, .970 6, .729 1, .00 48 .11 C
ATOM 683 C LEU A 99 60. .051 35. .873 6, .978 1, ,00 47, .80 C
ATOM 684 O LEU A 99 59, .295 35, .253 6, .215 1, .00 47, .42 O
ATOM 685 CB LEU A 99 61, .848 36. .317 5, .256 1, ,00 48, .34 C
ATOM 686 CG LEU A 99 61. .841 35. ,196 4, .211 1, .00 48, .54 C
ATOM 687 CD1 LEU A 99 60, .746 35, .451 3, .132 1, .00 48, .20 C
ATOM 688 CD2 LEU A 99 63, .255 35. .054 3, .600 1, .00 47, .97 C
ATOM 689 N SER A 100 59, .641 36, .505 8, .076 1, .00 47, .37 N
ATOM 690 CA SER A 100 58, .263 36. .875 8. .346 1, .00 47. .04 C
ATOM 691 C SER A 100 57, .684 37. .768 7, .233 1, .00 46, ,75 C
ATOM 692 O SER A 100 58, .413 38, .487 6, .570 1, .00 46, .99 o
ATOM 693 CB SER A 100 58, .229 37. .667 9, .673 1, ,00 46, .92 c
ATOM 694 OG SER A 100 57, .110 37. .317 10, .475 1, .00 47, .46 0
ATOM 695 N GLU A 101 56. .376 37, .721 7. .023 1, .00 46. .31 N
ATOM 696 CA GLU A 101 55. .660 38, .937 6, .639 1, .00 46, .11 C
ATOM 697 C GLU A 101 54. .328 38, .924 7, .349 1, .00 44, .85 C
ATOM 698 O GLU A 101 53. .675 37, .918 7, .372 1. ,00 44. ,33 O
ATOM 699 CB GLU A 101 55. .524 39. .113 5, .132 1, .00 46, .54 C
ATOM 700 CG GLU A 101 54. .675 38. .081 4. .410 1, ,00 49. .34 c
ATOM 701 CD GLU A 101 55. .438 37, .372 3. .300 1, .00 52. ,97 c
ATOM 702 OEl GLU A 101 55. .890 38, .064 2, .356 1, .00 55, .23 0
ATOM 703 OE2 GLU A 101 55, .598 36, .123 3. ,376 1. ,00 55. .84 0
ATOM 704 N LYS A 102 53. .950 40, .050 7. ,939 1, .00 44. .25 N
ATOM 705 CA LYS A 102 52. ,908 40. ,088 8. ,953 1. ,00 43. .97 C
ATOM 706 C LYS A 102 51. .747 41, ,024 8. ,619 1, ,00 43, .73 C
ATOM 707 O LYS A 102 51. .950 42. ,118 8. .109 1, ,00 43, .86 O
ATOM 708 CB LYS A 102 53. ,548 40. ,502 10. .279 1, ,00 44. .02 C
ATOM 709 CG LYS A 102 54, .611 39. .507 10. .770 1, ,00 44. .31 C
ATOM 710 CD LYS A 102 54. ,571 39. .285 12, .286 1. .00 44. .93 c
ATOM 711 CE LYS A 102 54. .919 40. .565 13, ,066 1, .00 45. .78 c
ATOM 712 NZ LYS A 102 55. .844 40. .345 14, ,224 1, .00 45. .77 N
ATOM 713 N GLY A 103 50. ,523 40. ,600 8. ,923 I: .00 43, ,50 N
ATOM 714 CA GLY A 103 49. .358 41. ,453 8, ,754 1. .00 43. .47 c
ATOM 715 C GLY A 103 49. ,452 42, ,664 9. ,652 1. ,00 43. ,24 c
ATOM 716 O GLY A 103 50. ,251 42, .663 10. ,554 1. ,00 44. ,06 0
ATOM 717 N ALA A 104 48. ,665 43. .705 9. ,422 1. .00 43. .06 N
ATOM 718 CA ALA A 104 48. ,750 44. .902 10, ,262 1. ,00 42. ,99 c
ATOM 719 C ALA A 104 47. ,958 44. .776 11, .576 ι: ,00 42. ,96 c
ATOM 720 O ALA A 104 47. 924 45. ,701 12. ,406 1. ,00 42. ,63 0
ATOM 721 CB ALA A 104 48. ,295 46. ,085 9, ,505 1. ,00 43. ,28 c
ATOM 722 N GLY A 105 47. ,306 43. .637 11, ,767 1. ,00 42. ,51 N
ATOM 723 CA GLY A 105 46. 757 43. ,346 13. ,067 1. ,00 42. ,31 C
ATOM 724 C GLY A 105 45. ,302 43. ,726 13. ,257 1. ,00 41. ,97 C
ATOM 725 O GLY A 105 44. 699 44. ,464 12. 477 1. 00 41. 85 O
ATOM 726 N THR A 106 44. 753 43. ,187 14. ,334 1. 00 41. 36 N
ATOM 727 CA THR A 106 43. ,365 43. ,308 14. ,680 1. ,00 40. ,73 C
ATOM 728 C THR A 106 43. 414 43. ,897 16. 077 1. 00 40. 07 C ATOM 729 O THR A 106 43,.987 43,.294 16.972 1,.00 40.05 o
ATOM 730 CB THR A 106 42, .723 41, .874 14. .678 1, .00 41 .01 c
ATOM 731 OG1 THR A 106 42, .896 41, .244 13, .393 1, .00 41 .37 0
ATOM 732 CG2 THR A 106 41, .192 41 .909 14 .880 1, .00 40 .73 c
ATOM 733 N VAL A 107 42, .850 45, .078 16, .280 1, .00 39 .30 N
ATOM 734 CA VAL A 107 42, .791 45, .629 17 .628 1, .00 38 .84 C
ATOM 735 C VAL A 107 41, .513 45, .153 18, .341 1, .00 38, .25 C
ATOM 736 O VAL A 107 40, .449 45, .765 18 .230 1, .00 37 .76 O
ATOM 737 CB VAL A 107 42, .903 47, ,153 17, ,609 1. ,00 38, .89 C
ATOM 738 CGI VAL A 107 42, .771 47, .696 19, .003 1, .00 39, .50 c
ATOM 739 CG2 VAL A 107 44, .250 47. .583 17, .018 1. .00 38, .81 c
ATOM 740 N LEU A 108 41, .628 44, .033 19, .047 1. .00 37, .85 N
ATOM 741 CA LEU A 108 40. ,480 43. .435 19. .720 1. .00 37, .95 C
ATOM 742 C LEU A 108 40, .263 44, .075 21, .076 1. .00 37, .90 C
ATOM 743 O LEU A 108 41. ,218 44. .325 21, .827 1. .00 37, .90 O
ATOM 744 CB LEU A 108 40, .641 41, .921 19, .875 1. .00 38, .13 C
ATOM 745 CG LEU A 108 39. .674 41. .188 20, .817 1. .00 38, ,58 C
ATOM 746 CD1 LEU A 108 38, .324 40, ,947 20, .132 1. .00 39, .30 C
ATOM 747 CD2 LEU A 108 40. ,275 39. ,883 21. .355 1, ,00 37, .97 ■ C
ATOM 748 N THR A 109 38, .988 44. .328 21, ,376 1. .00 37, .62 N
ATOM 749 CA THR A 109 38, .567 45, .006 22, .592 1, .00 37, .27 C
ATOM 750 C THR A 109 37. .389 44. .227 23. .139 1. .00 36, .65 C
ATOM 751 O THR A 109 36, .394 44, .059 22, .454 1, .00 36, .27 o
ATOM 752 CB THR A 109 38, .171 46. .458 22. .265 1. .00 37, ,47 c
ATOM 753 OG1 THR A 109 39, .347 47, .266 22, .112 1. .00 37, .69 0
ATOM 754 CG2 THR A 109 37. .446 47. .111 23. .426 1, .00 38. .07 c
ATOM 755 N VAL A 110 37, .510 43, .763 24, .378 1, .00 36, .34 N
ATOM 756 CA VAL A 110 36, .562 42. .815 24. ,957 1. .00 36. .14 C
ATOM 757 C VAL A 110 35, .880 43, .403 26, .157 1, .00 35, .82 c
ATOM 758 O VAL A 110 36, .546 43. .920 27. .035 1. .00 35. .99 0
ATOM 759 CB VAL A 110 37, .267 41, .549 25. ,429 1. ,00 36, .16 c
ATOM 760 CGI VAL A 110 36, ,267 40. .606 26. .101 1. ,00 36. .38 c
ATOM 761 CG2 VAL A 110 37, ,976 40, .871 24. .252 1. .00 36. .41 c
ATOM 762 N LYS A 111 34, .556 43, .280 26, ,196 1, .00 35, .74 N
ATOM 763 CA LYS A 111 33, .712 43, .808 27, .277 1, ,00 35. .65 c
ATOM 764 C LYS A 111 33, .882 45, .319 27, .426 1, ,00 35. .69 c
ATOM 765 O LYS A 111 33, ,593 46, .069 26. ,493 1, ,00 35, .75 0
ATOM 766 CB LYS A 111 33, .971 43, ,086 28. .607 1, .00 35, .42 c
ATOM 767 CG LYS A 111 33, ,345 43, .774 29, .823 1, .00 35, .29 c
ATOM 768 CD LYS A 111 33, .221 42, ,838 31. .025 1, .00 34, ,49 c
ATOM 769 CE LYS A 111 31, ,800 42, ,353 31. .211 1. ,00 33, ,74 c
ATOM 770 NZ LYS A 111 31, .760 41, .205 32. .135 1, .00 33, ,10 N
TER 771 LYS A 111
HETATM 772 O HOH 1 49, .245 46, .328 5. .022 1, .00 62, ,33 0
HETATM 773 O HOH 2 51. .667 42, .393 5, ,253 1. ,00 64. ,26 o
HETATM 774 O HOH 3 45. .146 47, .489 13, .258 1. ,00 72, ,01 o
HETATM 775 O HOH 4 34. ,352 33. .440 15. ,578 1. ,00 45, ,87 0
HETATM 776 O HOH 5 45. ,505 44. .955 4, ,778 1. .00 64. ,32 0
HETATM 777 O HOH 6 52, .352 45. .006 8. ,090 1. ,00 59. ,13 o
HETATM 778 O HOH 7 47. .204 46. ,514 3. ,486 1. ,00 68. ,76 0
HETATM 779 O HOH 8 52. ,395 44. ,051 10. ,998 1. 00 71. ,90 0
HETATM 780 O HOH 9 52, .999 37. ,102 -8. ,462 1. ,00 86. ,85 0
HETATM 781 O HOH 10 41. ,419 38. ,464 5. 175 1. 00 59. ,45 0
HETATM 782 0 HOH 11 49. .959 34. ,680 -3. ,470 1. 00 67. ,87 0
HETATM 783 0 HOH 12 53. .994 41. ,486 -5. ,678 I: 00 65. ,92 0
HETATM 784 0 HOH 13 51. ,536 27. ,053 17. ,915 1. 00 74. ,52 0
HETATM 785 0 HOH 14 47. .163 43. ,295 6. ,450 0. 50 37. ,28 0
HETATM 786 0 HOH 15 40. ,047 28. ,796 12. 708 1. 00 49. 93 0
HETATM 787 0 HOH 16 40. ,421 33. ,389 3. ,038 1. 00 72. ,11 o
HETATM 788 0 HOH 17 55. ,257 43. ,445 8. 358 1. 00 69. 83 0
HETATM 789 0 HOH 18 46. ,613 34. ,179 -2. ,484 1. 00 75. 26 0
HETATM 790 0 HOH 19 41. 926 30. ,672 -4. 416 1. 00 69. 47 0
HETATM 791 0 HOH 20 38. ,111 45. ,323 8. 830 1. 00 71. 05 0
HETATM 792 0 HOH 21 33. 282 42. 452 35. 017 1. 00 56. 31 0 HETATM 793 0 HOH 22 38..097 28..022 27,.567 1.,00 82.,82 O
HETATM 794 0 HOH 23 36. .861 38..358 7..741 1..00 59..93 0
HETATM 795 0 HOH 24 35. .632 41. .106 33, .951 1. .00 64. .85 o
HETATM 796 0 HOH 25 39. .694 51. .545 17. .552 1. .00 88. .01 0
HETATM 797 0 HOH 26 38..301 46..295 27..232 1..00 79..40 0
HETATM 798 0 HOH 27 46. ,017 40. .012 -5. .952 1. .00 71. .49 o
HETATM 799 0 HOH 28 33. .459 47. .017 11. ,159 1. .00 91. .29 0
HETATM 800 0 HOH 29 54. .056 48. .074 21. ,658 1. .00 87. .62 o
HETATM 801 0 HOH 30 42, .698 30. .957 -9. ,926 1. .00 85. .37 0
HETATM 802 0 HOH 31 49, ,053 46. ,541 23. ,570 0. ,50 40. ,58 0
HETATM 803 0 HOH 32 36, ,644 26. ,866 16. .515 1. ,00 63. .49 o
HETATM 804 0 HOH 33 35,.842 41.,211 8..228 1..00 61..91 0
HETATM 805 0 HOH 34 45, .847 31, ,003 -4. .217 1. .00 60, .17 0
HETATM 806 0 HOH 35 36, .559 42, ,530 6. .037 1. .00 80, .60 o
HETATM 807 0 HOH 36 41. .738 38. .583 -0. .756 1. .00 78. .58 0
HETATM 808 0 HOH 37 41, ,721 37. ,198 -2. .911 1. ,00 70. .53 o
HETATM 809 0 HOH 38 55,.564 31,.245 15,.877 1,.00 66..47 0
HETATM 810 0 HOH 39 48,,594 26,.834 -5..493 1,.00 71.,61 0
HETATM 811 0 HOH 40 57, .648 37, .697 17. .683 1, ,00 76, .43 o
HETATM 812 0 HOH 41 54,,466 30..209 22..435 1,,00 82..25 0
HETATM 813 0 HOH 42 46, .207 40. .360 32. ,941 1, .00 74. .06 0
HETATM 814 0 HOH 43 29, .341 42. .492 20. ,689 1, .00 80. ,60 0
HETATM 815 0 HOH 44 50, .735 47. .197 19. ,342 1, .00 88. ,78 o
HETATM 816 0 HOH 45 39, .469 48, .751 19, .274 1. .00 64. ,53 0
HETATM 817 0 HOH 46 54, .578 43, .702 3. .150 1, .00 53. ,90 0
HETATM 818 0 HOH 47 51. .878 45, ,740 1, .436 0, .50 43. ,20 0
HETATM 819 0 HOH 48 26. .610 38, .072 22. .759 1, .00 73. ,32 0
HETATM 820 0 HOH 49 33. .027 41, .919 15. .357 1, .00 89. ,15 0
HETATM" 821 0 HOH 50 49. ,309 31, .953 24. .818 1. ,00 75, ,95 0
HETATM 822 0 HOH 51 44, .607 44, .158 29. .925 0, .50 38, ,52 o
HETATM 823 0 HOH 52 42, .536 26, .524 0, .006 1, ,00 74, ,15 0
HETATM 824 0 HOH 53 51. ,130 19. .337 0, .472 1, ,00 89, ,67 o
HETATM 825 0 HOH 54 56,.592 41,.377 -2,.899 1,,00 52,,63 o
HETATM 826 0 HOH 55 30. ,159 45. .430 25. .057 1, ,00 75. ,58 0
HETATM 827 0 HOH 56 59. ,017 28. ,005 8, .578 1, ,00 83. ,63 o
HETATM 828 0 HOH 57 50. ,030 33. ,674 -8. .476 1, ,00 76, ,97 0
HETATM 829 0 HOH 58 41. ,264 29, .369 5. .970 1, ,00 70, ,36 0
HETATM 830 0 HOH 59 35, .397 35, .904 9, ,882 1. .00 66, .45 0
HETATM 831 0 HOH 60 29. .699 24, .263 29. ,792 1, .00 77, .96 o
HETATM 832 0 HOH 61 41. .632 39. .734 2, .099 1, .00 49, .35 o
HETATM 833 0 HOH 62 26. .312 40. .818 31. .981 1, ,00 87, .48 0
HETATM 834 0 HOH 63 43..409 32..875 -2..653 1,.00 97,.68 o
HETATM 835 0 HOH 64 39,,233 30.,631 0.,994 1,,00 60,,94 0
HETATM 836 0 HOH 65 50, .583 48. ,025 0. .811 0, .50 55, .46 o
HETATM 837 0 HOH 66 59, .008 24. .532 6, .787 0, .50 41, .79 o
HETATM 838 0 HOH 67 57, .610 30. .961 12, .027 1. .00 68, .40 0
HETATM 839 0 HOH 68 54,,850 26..829 -1,.181 1,.00 81..14 0
HETATM 840 0 HOH 69 34,,060 39..827 6.,446 1,.00 72..84 o
HETATM 841 0 HOH 70 27, .701 35. ,938 20, ,953 1. .00 71. .47 o
HETATM 842 0 HOH 71 47,,661 26,,712 24,.623 1,.00 78..24 0
HETATM 843 0 HOH 72 43, ,403 49. ,234 14, ,571 1. .00 81. .06 o
HETATM 844 0 HOH 73 40, .989 30. .459 -7, ,252 I; .00 75. .18 o
HETATM 845 0 HOH 74 50,,187 28,,078 -0,,705 1..00 88.,41 0
HETATM 846 0 HOH 75 52,,501 22..888 23,,124 1,.00 72..12 o
HETATM 847 0 HOH 76 51,,937 26..536 26,,291 1.,00 76.,44 o
HETATM 848 0 HOH 77 57,,772 29,.623 -5,,664 1,,00 67.,63 o
HETATM 849 0 HOH 78 50,,926 25,.600 5,,056 1.,00 80.,32 o
HETATM 850 0 HOH 79 61,,922 29,.045 9,,305 1.,00 77.,07 0
HETATM 851 0 HOH 80 54,,189 23,.727 5..680 1,,00 76.,46 0
HETATM 852 0 HOH 81 38, ,768 24, .307 10. .848 1. ,00 69. 70 0
HETATM 853 0 HOH 82 36. ,445 22, ,153 24. .035 1. ,00 78. ,79 0
HETATM 854 0 HOH 83 47. ,196 46, ,033 21. .492 1. ,00 74. 35 0
HETATM 855 0 HOH 84 35. ,057 43, ,461 13. ,870 1. ,00 69. ,66 0
HETATM 856 0 HOH 85 51.,118 42,,221 17..798 1.,00 84. ,91 0 HETATM 857 0 HOH 86 50..992 23..568 30..307 1..00 85,,90 0
HETATM 858 0 HOH 87 24. ,118 39. .727 34, .347 1. .00 68, .74 0
HETATM 859 0 HOH 88 38. ,823 28. .953 8. .669 1. .00 85. .42 0
HETATM 860 0 HOH 89 49. .288 26. .659 27, .113 1. .00 85. .90 o
HETATM 861 0 HOH 90 37. .335 18. .846 21, ,135 1. .00 92. .05 0
HETATM 862 0 HOH 91 57. .599 27. .914 1, .058 1. .00 76, .63 0
HETATM 863 0 HOH 92 60. .682 24. .384 -4, .788 1. .00 91, .50 o
HETATM 864 0 HOH 93 34. .218 35. .108 7, .727 1. .00 61, .57 0
HETATM 865 0 HOH 94 62, .389 21, .875 -9, .626 1. .00 83, .23 o
HETATM 866 0 HOH 95 44. .801 42. .200 27, .630 1. .00 93, .68 0
HETATM 867 0 HOH 96 56, .200 28, .893 20, .739 1. ,00 76, .88 o
HETATM 868 0 HOH 97 57, .817 39. .521 1, .149 0. ,50 33, .39 0
CONECT 168 649
CONECT 649 168
MASTER 365 0 0 13 867
END
APPENDIX 1(b)
HEADER IMMUNE SYSTEM 05-APR-04 1VES
TITLE STRUCTURE OF NEW ANTIGEN RECEPTOR VARIABLE DOMAIN FROM
TITLE 2 SHARKS
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: NEW ANTIGEN RECEPTOR;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: VARIABLE DOMAIN;
COMPND 5 SYNONYM: VNAR;
COMPND 6 ENGINEERED: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: ORECTOLOBUS MACULATUS;
SOURCE 3 ORGANISM_COMMON: SPOTTED WOBBEGONG;
SOURCE 4 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 5 EXPRESSION_SYSTEM_COMMON: BACTERIA
KEYWDS IG VNAR, 12Y-2
EXPDTA X-RAY DIFFRACTION
AUTHOR V.A.STRELTSOV
JRNL AUTH V.A.STRELTSOV, J.N. VARGHESE, P.J.HUDSON, R.A. IRVING,
JRNL AUTH J.A. CARMICHAEL, S . D . NUTTALL
JRNL TITL CRYSTAL STRUCTURE OF A SHARK NEW ANTIGEN RECEPTOR
JRNL TITL (IGNAR) VARIABLE DOMAIN
JRNL REF TO BE PUBLISHED
JRNL REFN
REMARK
REMARK
REMARK RESOLUTION. 2.18 ANGSTROMS.
REMARK
REMARK REFINEMENT.
REMARK PROGRAM REFMAC 5.1.24
REMARK AUTHORS MURSHUDOV, VAGIN, DODSON
REMARK
REMARK REFINEMENT TARGET : MAXIMUM LIKELIHOOD
REMARK
REMARK DATA USED IN REFINEMENT.
REMARK RESOLUTION RANGE HIGH (ANGSTROMS) 2.18
REMARK RESOLUTION RANGE LOW (ANGSTROMS) 18.12
REMARK DATA CUTOFF (SIGMA (F)) NULL
REMARK COMPLETENESS FOR RANGE (%) 99.9
REMARK NUMBER OF REFLECTIONS 14981
REMARK
REMARK FIT TO DATA USED IN REFINEMENT.
REMARK CROSS-VALIDATION METHOD THROUGHOUT
REMARK FREE R VALUE TEST SET SELECTION RANDOM
REMARK R VALUE (WORKING + TEST SET) 0.179
REMARK R VALUE (WORKING SET) 0.176
REMARK FREE R VALUE 0.247
REMARK FREE R VALUE TEST SET SIZE (%) 5.000
REMARK FREE R VALUE TEST SET COUNT 783
REMARK
REMARK FIT IN THE HIGHEST RESOLUTION BIN.
REMARK TOTAL NUMBER OF BINS USED 20
REMARK BIN RESOLUTION RANGE HIGH 2.18
REMARK BIN RESOLUTION RANGE LOW 2.23
REMARK REFLECTION IN BIN (WORKING SET) 1057
REMARK BIN COMPLETENESS (WORKING+TEST) (%) NULL
REMARK BIN R VALUE (WORKING SET) 0.2250
REMARK BIN FREE R VALUE SET COUNT 46
REMARK BIN FREE R VALUE 0.3110
REMARK
REMARK NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK ALL ATOMS : 2120
REMARK REMARK B VALUES. REMARK FROM WILSON PLOT (A**2) NULL REMARK MEAN B VALUE (OVERALL, A**2) 21.29 REMARK OVERALL ANISOTROPIC B VALUE. REMARK Bll (A**2) -1.07000 REMARK B22 (A**2) 0.07000 REMARK B33 (A**2) 00000 REMARK B12 (A**2) 00000 REMARK B13 (A**2) 00000 REMARK B23 (A**2) 00000 REMARK REMARK ESTIMATED OVERALL COORDINATE ERROR. REMARK ESU BASED ON R VALUE (A) 0 . 223 REMARK ESU BASED ON FREE R VALUE (A) 0 . 206 REMARK ESU BASED ON MAXIMUM LIKELIHOOD (A) 0. 140 REMARK ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2 ) 5 . 392 REMARK REMARK CORRELATION COEFFICIENTS. REMARK CORRELATION COEFFICIENT FO-FC ,961 REMARK CORRELATION COEFFICIENT FO-FC FREE ,922 REMARK REMARK RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT REMARK BOND LENGTHS REFINED ATOMS (A) 1794 0.012 0.021 REMARK BOND LENGTHS OTHERS (A) 1596 0.002 0.020 REMARK BOND ANGLES REFINED ATOMS (DEGREES) 2422 1.484 1.958 REMARK BOND ANGLES OTHERS (DEGREES) 3716 0.868 3.000 REMARK TORSION ANGLES, PERIOD 1 (DEGREES) 224 6.648 5.000 REMARK TORSION ANGLES, PERIOD 2 (DEGREES) NULL NULL NULL REMARK TORSION ANGLES, PERIOD 3 (DEGREES) NULL NULL NULL REMARK TORSION ANGLES, PERIOD 4 (DEGREES) NULL NULL NULL REMARK CHIRAL-CENTER RESTRAINTS (A**3) 270 0.101 0.200 REMARK GENERAL PLANES REFINED ATOMS (A) 1994 0.005 0.020 REMARK GENERAL PLANES OTHERS (A) 384 0.002 0.020 REMARK NON-BONDED CONTACTS REFINED ATOMS (A) 303- 0.193 0.200 REMARK NON-BONDED CONTACTS OTHERS (A) 1944 0.251 0.200 REMARK NON-BONDED TORSION REFINED ATOMS (A) NULL NULL NULL REMARK NON-BONDED TORSION OTHERS (A) 1227 0.086 0.200 REMARK H-BOND (X...Y) REFINED ATOMS (A) 216 0.188 0.200 REMARK H-BOND (X...Y) OTHERS (A) NULL NULL NULL REMARK POTENTIAL METAL-ION REFINED ATOMS (A) NULL NULL NULL REMARK POTENTIAL METAL-ION OTHERS (A) NULL NULL NULL REMARK SYMMETRY VDW REFINED ATOMS (A) 29 0.208 0.200 REMARK SYMMETRY VDW OTHERS (A) 115 0.251 0.200 REMARK SYMMETRY H-BOND REFINED ATOMS (A) 43 0.199 0.200 REMARK SYMMETRY H-BOND OTHERS (A) NULL NULL NULL REMARK REMARK ISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT REMARK MAIN-CHAIN BOND REFINED ATOMS (A**2) 1110 0.591 1.500 REMARK MAIN-CHAIN BOND OTHER ATOMS (A**2) NULL NULL NULL REMARK MAIN-CHAIN ANGLE REFINED ATOMS (A**2) 1780 1.140 2.000 REMARK SIDE-CHAIN BOND REFINED ATOMS (A**2) 684 1.826 3.000 REMARK SIDE-CHAIN ANGLE REFINED ATOMS (A**2) 642 3.050 4.500 REMARK REMARK ANISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT REMARK RIGID-BOND RESTRAINTS (A**2) NULL ; NULL NULL REMARK SPHERICITY; FREE ATOMS (A**2) NULL ; NULL NULL REMARK SPHERICITY; BONDED ATOMS (A**2) NULL ; NULL NULL REMARK REMARK NCS RESTRAINTS STATISTICS REMARK NUMBER OF DIFFERENT NCS GROUPS REMARK REMARK TLS DETAILS REMARK NUMBER OF TLS GROUPS : 2 REMARK REMARK 3 TLS GROUP : 1
REMARK 3 NUMBER OF COMPONENTS GROUP : 1
REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI
REMARK 3 RESIDUE RANGE : A 1 A 113
REMARK 3 ORIGIN FOR THE GROUP (A): 5.3834 33.1578 25. 0745
REMARK 3 T TENSOR
REMARK 3 Til: 0.1096 T22 0.0299
REMARK 3 T33: 0.1185 T12 0.0303
REMARK 3 T13: -0.0055 T23 -0.0341
REMARK 3 L TENSOR
REMARK 3 Lll: 3.3390 L22 4.7309
REMARK 3 L33: 3.2713 L12 -0.1654
REMARK 3 L13: 0.6888 L23 -0.6154
REMARK 3 S TENSOR
REMARK 3 Sll: 0.1195 S12 0.0442 S13: -0.2338
REMARK 3 S21: -0.2682 S22 0.0273 S23: -0.3948
REMARK 3 S31: 0.1461 S32 0.1933 S33: -0.1468
REMARK 3
REMARK 3 TLS GROUP : 2
REMARK 3 NUMBER OF COMPONENTS GROUP : 1
REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI
REMARK 3 RESIDUE RANGE : B 1 B 113
REMARK 3 ORIGIN FOR THE GROUP (A): -20.7040 46.2053 38 . 5402
REMARK 3 T TENSOR
REMARK 3 Til: 0.1451 T22 0.2403
REMARK 3 T33: 0.1040 T12 -0.0402
REMARK 3 T13: 0.0700 T23 -0.0394
REMARK 3 L TENSOR
REMARK 3 Lll: 3.2727 L22 4.0810
REMARK 3 L33: 5.0389 L12 0.5719
REMARK 3 L13: 0.1006 L23 0.6479
REMARK 3 S TENSOR
REMARK 3 Sll: 0.1393 S12 -0.0589 S13: -0.0029
REMARK 3 S21: 0.1389 S22 -0.3008 S23: 0.2593
REMARK 3 S31: -0.0779 S32 : -0.5470 S33: 0.1615
REMARK 3
REMARK 3 BULK SOLVENT MODELLINC
REMARK 3 METHOD USED : BABINErϋ MODEL WITH MASK
REMARK 3 PARAMETERS FOR MASK ( [CALCULATION
REMARK 3 VDW PROBE RADIUS 1.40
REMARK 3 ION PROBE RADIUS 0.80
REMARK 3 SHRINKAGE RADIUS 0.80
REMARK 3
REMARK 3 OTHER REFINEMENT REMAI =IKS : HYDROGENS HAVE BEEN
REMARK 3 RIDING POSITIONS
REMARK 4
REMARK 4 IVES COMPLIES WITH FOR! 4AT V. 2.3, 09- JULY-1998
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBJ ON 07-APR-2004 ,
REMARK 100 THE RCSB ID CODE IS RCSB006538 .
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE X-RAY DIFFRACTION
REMARK 200 DATE OF' DATA COLLECTION NULL
REMARK 200 TEMPERATURE (KELVIN) 113.0
REMARK 200 PH 4.60
REMARK 200 NUMBER OF CRYSTALS USED 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) N
REMARK 200 RADIATION SOURCE ROTATING ANODE
REMARK 200 BEAMLINE NULL
REMARK 200 X-RAY GENERATOR MODEL RIGAKU HR3 HB
REMARK 200 MONOCHROMATIC OR LAUE (M/L) M
REMARK 200 WAVELENGTH OR RANGE (A) 1.5418 REMARK 200 MONOCHROMATOR : NI FILTER
REMARK 200 OPTICS : AXCO MICROCAPILLARY FOCUSING
REMARK 200 OPTICS
REMARK 200
REMARK 200 DETECTOR TYPE IMAGE PLATE
REMARK 200 DETECTOR MANUFACTURER MAR 1 0
REMARK 200 INTENSITY-INTEGRATION SOFTWARE DENZO
REMARK 200 DATA SCALING SOFTWARE SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS 14981
REMARK 200 RESOLUTION RANGE HIGH (A) 2.180
REMARK 200 RESOLUTION RANGE LOW (A) 18.120
REMARK 200 REJECTION CRITERIA (SIGMA(I)) 0.000
REMARK 200
REMARK 200 OVERALL .
REMARK 200 COMPLETENESS FOR RANGE (%) 100.0
REMARK 200 DATA REDUNDANCY 6.600
REMARK 200 R MERGE (I) 0.05400
REMARK 200 R SYM (I) 0.05400
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET 32.5000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) 2.18
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) 2.24
REMARK 200 COMPLETENESS FOR SHELL (%) 99.4
REMARK 200 DATA REDUNDANCY IN SHELL 6.30
REMARK 200 R MERGE FOR SHELL (I) NULL
REMARK 200 R SYM FOR SHELL (I) NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL 4.000
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: MOLREP
REMARK 200 STARTING MODEL: 12Y-1 VNAR PDB ENTRY IVER
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS : NULL
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA) NULL
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1M SODIUM CITRATE, 20% V/V ISO-
REMARK 280 PROPANOL, 20% PEG4000, PH 41,.6, VAPOR DIFFUSION, HANGING DROP,
REMARK 280 TEMPERATURE 298K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: I 21 21 21
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 l/2-X,-Y,l/2+Z
REMARK 290 3555 -X,l/2+Y,l/2-Z
REMARK 290 4555 l/2+X,l/2-Y,-Z
REMARK 290 5555 l/2+X,l/2+Y,l/2+Z
REMARK 290 6555 -X,l/2-Y,Z
REMARK 290 7555 l/2-X,Y,-Z
REMARK 290 8555 X,-Y,l/2-Z
REMARK 290
REMARK 290 WHERE NNN -> OPERATOR NUMBER
REMARK 290 MMM -> TRANSLATION VECTOR
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY TRANSFORMATIONS
REMARK 290 THE FOLLOWING TRANSFORMATIONS OPERATE ON THE ATOM/HETATM REMARK 290 RECORDS IN THIS ENTRY TO PRODUCE CRYSTALLOGRAPHICALLY REMARK 290 RELATED MOLECULES.
REMARK 290 SMTRY1 1 1. ,000000 0. ,000000 0, ,000000 0, ,00000
REMARK 290 SMTRY2 1 0. ,000000 1. ,000000 0. ,000000 0. ,00000
REMARK 290 SMTRY3 1 0, .000000 0. ,000000 1. ,000000 0, ,00000
REMARK 290 SMTRY1 2 -1, ,000000 0. ,000000 0. .000000 32. .64150
REMARK 290 SMTRY2 2 0, .000000 -1. ,000000 0. .000000 0. .00000
REMARK 290 SMTRY3 2 0, .000000 0. .000000 1. .000000 49, .11200
REMARK 290 SMTRY1 3 -1, .000000 0. .000000 0. .000000 0, .00000
REMARK 290 SMTRY2 3 0. .000000 1, .000000 0, .000000 46. .02300
REMARK 290 SMTRY3 3 0, ,000000 0, .000000 -1, .000000 49, .11200
REMARK 290 SMTRY1 4 1. .000000 0. .000000 0. ,000000 32, ,64150
REMARK 290 SMTRY2 4 0. .000000 -1, .000000 0. ,000000 46. .02300
REMARK 290 SMTRY3 4 0. .000000 0, .000000 -1, ,000000 0. ,00000
REMARK 290 SMTRY1 5 1, .000000 0, .000000 0, ,000000 32, .64150
REMARK 290 SMTRY2 5 0, .000000 1. .000000 0. ,000000 46, .02300
REMARK 290 SMTRY3 5 0, .000000 0, .000000 1, ,000000 49. .11200
REMARK 290 SMTRY1 6 -1. .000000 0. ,000000 0. ,000000 0, .00000
REMARK 290 SMTRY2 6 0, .000000 -1, .000000 0, ,000000 46, .02300
REMARK 290 SMTRY3 6 0, .000000 0, .000000 1, .000000 0. .00000
REMARK 290 SMTRY1 7 -1, .000000 0. .000000 0, ,000000 32, .64150
REMARK 290 SMTRY2 7 0, .000000 1, .000000 0, ,000000 0, .00000
REMARK 290 SMTRY3 7 0, .000000 0, .000000 -1, ,000000 0, .00000
REMARK 290 SMTRY1 8 1, ,000000 0. .000000 0. ,000000 0. .00000
REMARK 290 SMTRY2 8 0, .000000 -1, .000000 0, ,000000 0, .00000
REMARK 290 SMTRY3 8 0, .000000 0, .000000 -1, ,000000 49, .11200
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1, 2
REMARK 300 THIS ENTRY CONTAINS THE CRYSTALLOGRAPHIC ASYMMETRIC UNIT REMARK 300 WHICH CONSISTS OF 2 CHAIN(S). SEE REMARK 350 FOR REMARK 300 INFORMATION ON GENERATING THE BIOLOGICAL MOLECULE (S). REMARK 350
'REMARK 350 GENERATING THE BIOMOLECULE
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS REMARK 350 GIVEN BELOW. BOTH NON-CRYSTALLOGRAPHIC AND REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN. REMARK 350
REMARK 350 BIOMOLECULE: 1
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A REMARK 350 BIOMT1 1 1.000000 0.000000 0.000000 00000 REMARK 350 BIOMT2 1 0.000000 1.000000 0.000000 0.00000 REMARK 350 BIOMT3 1 0.000000 0.000000 1.000000 0.00000 REMARK 350 BIOMOLECULE: 2
REMARK 350 APPLY THE FOLLOWING TO CHAINS: B REMARK 350 BIOMT1 2 1.000000 0.000000 0.000000 0.00000
REMARK 350 BIOMT2 2 0.000000 1.000000 0.000000 0.00000
REMARK 350 BIOMT3 2 0.000000 0.000000 1.000000 0.00000
REMARK 375
REMARK 375 SPECIAL POSITION
REMARK 375 THE FOLLOWING ATOMS ARE FOUND TO BE WITHIN 0.15 ANGSTROMS
REMARK 375 OF A SYMMETRY RELATED ATOM AND ARE ASSUMED TO BE ON SPECIAL
REMARK 375 POSITIONS.
REMARK 375
REMARK 375 ATOM RES CSSEQI
REMARK 375 HOH 60 LIES ON A SPECIAL POSITION.
REMARK 375 HOH 167 LIES ON A SPECIAL POSITION.
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CLOSE CONTACTS IN SAME ASYMMETRIC UNIT
REMARK 500 REMARK 500 'HE FOLLOWING ATOMS ARE IN CLOSE CONTACT REMARK 500 REMARK 500 ATM1 RES C SSEQI ATM2 RES C SSEQI REMARK 500 0O HHOOHH 113322 0O HHOOHH 332244 2.11 REMARK 500 OOEEll GGLLUU AA 7766 0O HHOOHH 331199 2.14 REMARK 500 0O HHOOHH 5555 0O HHOOHH 116622 2.14 REMARK 500 0O HHOOHH 226622 00 HHOOHH 332266 2.14 REMARK 500 0O HHOOHH 4477 00 HHOOHH 226688 2.15 REMARK 500 REMARK 500 GEOMETRY AND STEREOCHEMISTRY REMARK 500 SUBTOPIC: COVALENT BOND LENGTHS REMARK 500 REMARK 500 TTHHEE SSTTEERREEOOCCHHEEMMIICCAALL PPAARRAAMMEETTEERRSS OOFF TTHHEE FFOOLLLLOOWWIINNGG RESIDUES REMARK 500 HHAAVVEE VVAALLUUEESS WWHHIICCHH DDEEVVIIAATTEE FFRROOMM EEXXPPEECCTTEEDD VVAALLUUEESS BY MORE REMARK 500 TTHHAANN 66**RRMMSSDD ((MM==MMOODDEELL NNUUMMBBEERR;; RREESS==RREESSIIDDUUEE NNAAMMEE;; C=CHAIN REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE) . REMARK 500 REMARK 500 STANDARD TABLE: REMARK 500 FORMAT: (10X,I3,1X,2 (A3, IX, Al, 14 , Al, IX, A4 , 3X) ,F6.3) REMARK 500 REMARK 500 EXPECTED VALUES: ENGH AND HUBER, 1991 REMARK 500 REMARK 500 M RES CSSEQI ATM1 RES CSSEQI ATM2 DEVIATION REMARK 500 LYS A 61 CG LYS A 61 CD 0.080 REMARK 500 ARG B 25 CG ARG B 25 CD -0.072 REMARK 500 REMARK 500 GEOMETRY AND STEREOCHEMISTRY REMARK 500 SUBTOPIC: COVALENT BOND ANGLES REMARK 500 REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE) . REMARK 500 REMARK 500 STANDARD TABLE: REMARK 500 FORMAT : (10X, 13, IX,A3, IX,Al, 14 , l, 3 ( IX,A4 , 2X) , 12X, F5.1) REMARK 500 REMARK 500 EXPECTED VALUES: ENGH AND HUBER, 1991 REMARK 500 REMARK 500 M RES CSSEQI ATM1 ATM2 ATM3 REMARK 500 TYR A 94 CA ■ - C - N ANGL. DEV. = 10.7 DEGREES REMARK 500 ASN A 95 C - N - CA ANGL . DEV. = 10.8 DEGREES REMARK 500 REMARK 500 GEOMETRY AND STEREOCHEMISTRY REMARK 500 SUBTOPIC: NON-CIS, NON-TRANS REMARK 500 REMARK 500 THE FOLLOWING PEPTIDE BONDS DEVIATE SIGNIFICANTLY FROM BOTH REMARK 500 CIS AND TRANS CONFORMATION. CIS BONDS, IF ANY, ARE LISTED REMARK 500 ON CISPEP RECORDS. TRANS IS DEFINED AS 180 +/- 30 AND REMARK 500 CIS IS DEFINED AS 0 +/- 30 DEGREES. REMARK 500 MODEL OMEGA REMARK 500 VAL A 112 LYS A 113 149.69 REMARK 525 REMARK 525 SOLVENT REMARK 525 THE FOLLOWING SOLVENT MOLECULES LIE FARTHER THAN EXPECTED REMARK 525 FROM THE PROTEIN OR NUCLEIC ACID MOLECULE AND MAY BE REMARK 525 ASSOCIATED WITH A SYMMETRY RELATED MOLECULE (M=MODEL REMARK 525 NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE
REMARK 525 NUMBER; I=INSERTION CODE) :
REMARK 525
REMARK 525 M RES CSSEQI
REMARK 525 HOH 298 DISTANCE = 8. .93 ANGSTROMS
REMARK 525 HOH 311 DISTANCE = 5. .86 ANGSTROMS
REMARK 525 HOH 312 DISTANCE = 7. .03 ANGSTROMS REMARK 525 HOH 313 DISTANCE = 7.02! ANGSTROMS
REMARK 525 HOH 341 DISTANCE = 5.38 ! ANGSTROMS
REMARK 525 HOH 342 DISTANCE = 5.1C 1 ANGSTROMS
REMARK 525 HOH 35C ) DISTANCE = 8.5C ) ANGSTROMS
REMARK 525 HOH 351 DISTANCE = 8.05i ANGSTROMS
REMARK 525 HOH 353 DISTANCE = 6.37 1 ANGSTROMS
REMARK 525 HOH 354 DISTANCE = 6.8C 1 ANGSTROMS
REMARK 525 HOH 355 DISTANCE = 12.75i ANGSTROMS
REMARK 525 HOH 356 DISTANCE = 6.5S ) ANGSTROMS
REMARK 525 HOH 357 DISTANCE = 5.98 ! ANGSTROMS
REMARK 525 HOH 358 DISTANCE = 13.58 ! ANGSTROMS
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: IVER RELATED DB : PDB
REMARK 900 THE SAME PROTEIN (12Y-1] )
REMARK 999
REMARK 999 SEQUENCE
REMARK 999 A SEQUENCE DATABASE REFERENCE FOR THIS PROTEIN DOES
REMARK 999 NOT CURRENTLY EXIST
SEQRES 1 A 113 ALA TRP VAL ASP GLN THR PRO ARG THR ALA THR LYS GLU
SEQRES 2 A 113 THR GLY GLU SER LEU THFl ILE ASN CYS VAL LEU ARG ASP
SEQRES 3 A 113 ALA SER PHE GLU LEU LYS ! ASP THR GLY TRP TYR ARG THR
SEQRES 4 A 113 LYS LEU GLY SER THR ASK [ GLU GLN SER ILE SER ILE GLY
SEQRES 5 A 113 GLY ARG TYR VAL GLU THR VAL ASN LYS GLY SER LYS SER
SEQRES 6 A 113 PHE SER LEU ARG ILE SER ASP LEU ARG VAL GLU ASP SER
SEQRES 7 A 113 GLY THR TYR LYS CYS GLK I ALA PHE TYR SER LEU PRO LEU
SEQRES 8 A 113 GLY ASP TYR ASN TYR SEF I LEU LEU PHE ARG GLY GLU LYS
SEQRES 9 A 113 GLY ALA GLY THR ALA LEU I THR VAL LYS
SEQRES 1 B 113 ALA TRP VAL ASP GLN THR PRO ARG THR ALA THR LYS GLU
SEQRES 2 B 113 THR GLY GLU SER LEU THR ILE ASN CYS VAL LEU ARG ASP
SEQRES 3 B 113 ALA SER PHE GLU LEU LYΞ ! ASP THR GLY TRP TYR ARG THR
SEQRES 4 B 113 LYS LEU GLY SER THR ASK I GLU GLN SER ILE SER ILE GLY
SEQRES 5 B 113 GLY ARG TYR VAL GLU THR VAL ASN LYS GLY SER LYS SER
SEQRES 6 B 113 PHE SER LEU ARG ILE SER ASP LEU ARG VAL GLU ASP SER
SEQRES 7 B 113 GLY THR TYR LYS CYS GLK I ALA PHE TYR SER LEU PRO LEU
SEQRES 8 B 113 GLY ASP TYR ASN TYR SER LEU LEU PHE ARG GLY GLU LYS
SEQRES 9 B 113 GLY ALA GLY THR ALA LEU I THR VAL LYS
FORMUL 3 HOH *358(H2 01)
HELIX 1 1 ARG A 74 ASP A 77 5
HELIX 2 2 ARG B 74 ASP B 77 5
SHEET 1 A 4 TRP A 2 THF I A 6 0
SHEET 2 A 4 LEU A 18 ARG ; A 25 - -1 O ARG A 25 N TRP A 2
SHEET 3 A 4 SER A 65 ILE ; A 70 - -1 O LEU A 68 N ILE A 20
SHEET 4 A 4 TYR A 55 ASK I A 60 - -1 N ASN A 60 O SER A 65
SHEET 1 B 5 THR A 9 GLU 1 A 13 0
SHEET 2 B 5 THR A 108 LYSi A : L13 1 O THR A 111 N LYS A 12
SHEET 3 B 5 GLY A 79 LEU I A 89 - -1 N GLY A 79 O LEU A : L10
SHEET 4 B 5 . ASP A 33 LYS : A 40 - -1 N TYR A 37 Q LYS A 82
SHEET 5 B 5 GLN A 47 SER A 48 - -1 O GLN A 47 N ARG A 38
SHEET 1 C 4 ' THR A 9 GLUf A 13 0
SHEET 2 C 4 THR A 108 LYS : A : L13 1 O THR A 111 N LYS A 12
SHEET 3 C 4 i GLY A 79 LEU 1 A 89 - -1 N GLY A 79 O LEU A : L10
SHEET 4 c 4 : LEU A 98 LYS : A : L04 - -1 O PHE A 100 N TYR A 87
SHEET 1 D 4 l TRP B 2 THB '„ B 6 0
SHEET 2 D 4 : LEU B 18 ARG ; B 25 - -1 O ARG B 25 N TRP B 2
SHEET 3 D 4 , SER B 65 ILE ; B 70 - -1 O ILE B 70 N LEU B 18
SHEET 4 D 4 ' TYR B 55 ASK 1 B 60 - -1 N ASN B 60 O SER B 65
SHEET 1 E 5 THR B 9 GLU [ B 13 0
SHEET 2 E 5 ' THR B 108 LYS ; B : L13 1 O THR B 111 N LYS B 12
SHEET 3 E 5 ' GLY B 79 LEU 1 B 89 - -1 N GLY B 79 O LEU B 110
SHEET 4 E 5 i ΆSP B 33 LYS I B 40 - -1 N TYR B 37 O LYS B 82
SHEET 5 E 5 i GLN B 47 SER B 48 - -1 O GLN B 47 N ARG B 38
SHEET 1 F 4 ' THR B 9 GLU I B 13 0
SHEET 2 F 4 ' THR B 108 LYS ; B : L13 1 O THR B 111 N LYS B 12 SHEET 3 F 4 GLY B 79 LEU B 89 -■1 N GLY B 79 O LEU B 110
SHEET 4 F 4 LEU B 98 LYS B 104 - •1 O PHE B 100 N TYR B 87
SSBOND 1 CYS A 22 CYS A- 83
SSBOND 2 CYS B 22 CYS B 83
CISPEP 1 THR A 6 PRO A 7 0 - 8.21
CISPEP 2 TYR A 94 ASN A 95 0 - 6.39
CISPEP 3 THR B 6 PRO B 7 0 - 3.51
CISPEP 4 PRO B 90 LEU B 91 0 3.64
CRYST1 65. ,283 92.046 98.224 90.00 90.00 90.00 I 21 ; 21 21 16
ORIGX1 1.000000 0. .000000 0.000000 0.00000
ORIGX2 0.000000 1. ,000000 0.000000 0.00000
ORIGX3 0.000000 0. .000000 1.000000 0.00000
SCALE1 0.015318 0. ,000000 0.000000 0.00000
SCALE2 0.000000 0. ,010864 0.000000 0.00000
SCALE3 0.000000 0. .000000 0.010181 0.00000
ATOM 1 N ALA A 1 -9.545 39.140 18.378 1.00 15, .32 N
ATOM 2 CA ALA A 1 -8.794 38.432 19.437 1.00 16, .13 C
ATOM 3 C ALA A 1 -7.548 39.217 19.826 1.00 16, .68 C
ATOM 4 O ALA A 1 -7.010 39.977 19.012 1.00 16, .60 O
ATOM 5 CB ALA A 1 -8.408 37.046 18.960 1.00 16, ,79 C
ATOM 6 N TRP A 2 -7.111 39.048 21.078 1.00 16, .98 N
ATOM 7 CA TRP A 2 -5.862 39.620 21.552 1.00 17, .64 C
ATOM 8 C TRP A 2 -5.260 38.787 22.680 1.00 18, .87 C
ATOM 9 O TRP A 2 -5.963 38.059 23.370 1.00 19, .72 0
ATOM 10 CB TRP A 2 -6.069 41.092 21.974 1.00 18, .44 C
ATOM 11 CG TRP A 2 -6.976 41.289 23.105 1.00 18. .44 c
ATOM 12 GDI TRP A 2 -8.346 41.195 23.092 1.00 21, .94 c
ATOM 13 CD2 TRP A 2 -6.613 41.616 24.447 1.00 19. .52 c
ATOM 14 NE1 TRP A 2 -8.849 41.469 24.338 1.00 22, .38 N
ATOM 15 CE2 TRP A 2 -7.811 41.725 25.193 1.00 20, .62 c
ATOM 16 CE3 TRP A 2 -5.399 41.870 25.095 1.00 18, .50 c
ATOM 17 CZ2 TRP A 2 " -7.825 42.048 26.558 1.00 19. .76 c
ATOM 18 CZ3 TRP A 2 -5.422 42.212 26.453 1.00 20, .59 c
ATOM 19 CH2 TRP A 2 -6.625 42.294 27.161 1.00 18. .64 c
ATOM 20 N VAL A 3 -3.943 38.845 22.809 1.00 19, .14 N
ATOM 21 CA VAL A 3 -3.232 38.167 23.869 1.00 19'. .37 c
ATOM 22 C VAL A 3 -2.927 39.147 24.993 1.00 18. ,82 C
ATOM 23 O VAL A 3 -2.330 40.236 24.792 1.00 17, ,99 O
ATOM 24 CB VAL A 3 -1.929 37.489 23.381 1.00 19. ,52 C
ATOM 25 CGI VAL A 3 -1.186 36.857 24.535 1.00 20. ,40 c
ATOM 26 CG2 VAL A 3 -2.251 36.437 22.333 1.00 18. ,97 c
ATOM 27 N ASP A 4 -3.365 38.725 26.175 l'.OO 17. ,88 N
ATOM 28 CA ASP A 4 -3.223 39.473 27.406 1.00 18. ,63 c
ATOM 29 C ASP A 4 -1.983 38.946 28.134 1.00 18. ,37 c
ATOM 30 O ASP' A 4 -2.035 37.909 28.778 1.00 18. .22 O
ATOM 31 CB ASP A 4 -4.489 39.238 28.221 1.00 19. ,11 c
ATOM 32 ' CG ASP A 4 -4.542 40.031 29.474 1.00 19. ,12 c
ATOM 33 OD1 ASP A 4 -3.571 40.746 29.799 1.00 18. ,98 0
ATOM 34 OD2 ASP A 4 -5.553 40.002 30.189 l'.OO 19. ,61 0
ATOM 35 N GLN A 5 -0.872 39.673 28.022 1.00 18. .58 N
ATOM 36 CA GLN A 5 0.425 39.258 28.554 1.00 19. ,07 c
ATOM 37 C GLN A 5 0.820 40.096 29.787 1.00 19. ,50 C
ATOM 38 O GLN A 5 0.930 41.331 29.694 1.00 19. ,48 O
ATOM 39 CB GLN A 5 1.522 39.386 27.498 1.00 19. ,16 C
ATOM 40 CG GLN A 5 2.892 38.959 28.076 1.00 18. 91 C
ATOM 41 CD GLN A 5 4.025 38.930 27.080 1.00 20. ,12 C
ATOM 42 OEl GLN A 5 3.808 38.996 25.860 1.00 19. 01 O
ATOM 43 NE2 GLN A 5 5.257 38.774 27.601 1.00 21. 06 N
ATOM 44 N THR A 6 1.012 39.408 30.922 1.00 19. 09 N
ATOM 45 CA THR A 6 1.455 39.999 32.185 1.00 19. 10 C
ATOM 46 C THR A 6 2.649 39.241 32.756 1.00 18. 83 C
ATOM 47 O THR A 6 2.811 38.051 32.503 1.00 18. 32 O
ATOM 48 CB THR A 6 0.336 39.996 33.272 1.00 19. 25 C ATOM 49 OG1 THR A 6 -0,.242 38,.695 33,.415 1,.00 20.21 0
ATOM 50 CG2 THR A 6 -0, .839 40 .879 32, .862 1 .00 20 .66 c
ATOM 51 N PRO A 7 3, .490 39, .909 33, ,536 1, .00 18 .47 N
ATOM 52 CA PRO A 7 3, .446 41, .358 33. .746 1, .00 18 .39 c
ATOM 53 C PRO A 7 4, .101 42, .136 32, .581 1, .00 18 .90 c
ATOM 54 O PRO A 7 4, .863 41, .586 31, .800 1, .00 19 .06 0
ATOM 55 CB PRO A 7 4. .249 41, .535 35, .035 1, .00 18 .51 c
ATOM 56 CG PRO A 7 5, .270 40, .458 34, .979 1, .00 18 .08 c
ATOM 57 CD PRO A 7 4. .567 39. .269 34. .305 1. ,00 18, .29 c
ATOM 58 N ARG A 8 3, .824 43, .428 32, .481 1, .00 19 .39 N
ATOM 59 CA ARG A 8 4. .423 44. ,236 31. .427 1. .00 20, .40 C
ATOM 60 C ARG A 8 5, .901 44, .520 31, ,671 1, .00 20 .17 C
ATOM 61 O ARG A 8 6. .677 44. .614 30, .731 1. .00 20, .60 O
ATOM 62 CB ARG A 8 3. .729 45. .562 31. ,330 1, ,00 21, .36 C
ATOM 63 CG ARG A 8 2, .267 45. .512 31. .058 1. ,00 26, .32 c
ATOM 64 CD ARG A 8 1. ,723 46. .911 30. .612 1. ,00 32, .78 c
ATOM 65 NE ARG A 8 0, ,712 46, .823 29. ,555 1, ,00 39, .53 N
ATOM 66 CZ ARG A 8 0, .909 46. ,247 28. ,363 1. .00 41, .67 C
ATOM 67 NH1 ARG A 8 2, ,081 45, .690 28, .054 1, .00 41, .52 N
ATOM 68 NH2 ARG A 8 -0. .081 46. .223 27. ,483 1. ,00 44, .76 N
ATOM 69 N THR A 9 6, .257 44. .755 32. ,922 1. ,00 19, .16 N
ATOM 70 CA THR A 9 7. .650 44, .901 33. .306 1. .00 19, .79 C
ATOM 71 C THR A 9 7, .915 44, .061 34, .546 1. .00 19, .40 C
ATOM 72 O THR A 9 7, .002 43, .753 35, .316 1, .00 19, .52 O
ATOM 73 CB THR A 9 8, .035 46, .376 33, .619 1. .00 19, .33 C
ATOM 74 OG1 THR A 9 7, .222 46. .871 34, .684 1. .00 20, .29 O
ATOM 75 CG2 THR A 9 7, ,730 47, .333 32. .449 1. ,00 20, .56 C
ATOM 76 N ALA A 10 9, .181 43. .716 34. .731 1. .00 19, .17 N
ATOM 77 CA ALA A 10 9. ,621 43, .034 35. .927 1, ,00 18, .67 C
ATOM 78 C ALA A 10 11, ,091 43. .315 36. ,193 1. ,00 18, .87 C
ATOM 79 O ALA A 10 11, ,874 43. .475 35. ,265 1. ,00 18, .47 0
ATOM 80 CB ALA A 10 9. .388 41, .559 35, .780 1. .00 18, .21 c
ATOM 81 N THR A 11 11, ,434 43, .391 37, ,479 1. .00 19, .55 N
ATOM 82 CA THR A 11 12, ,804 43. .457 37, .960 1. ,00 20, .22 c
ATOM 83 C THR A 11 13, .033 42. .289 38, .912 1. ,00 20, .63 c
ATOM 84 O THR A 11 12, ,264 42. .070 39. ,845 1, ,00 20, ,97 0
ATOM 85 CB THR A 11 13, .033 44. ,787 38, ,690 1. ,00 20, .37 c
ATOM 86 OG1 THR A 11 12. .846 45. .867 37. ,770 1, ,00 20, .04 0
ATOM 87 CG2 THR A 11 14. .489 44. ,931 39. ,151 1, ,00 20. .37 c
ATOM 88 N LYS A 12 14. .082 41. .530 38. ,655 1, ,00 21. .26 N
ATOM 89 CA LYS A 12 14. .424 40, .372 39. ,459 1, ,00 21. .82 C
ATOM 90 C LYS A 12 15. .893 40. .438 39, ,791 1, ,00 22. .04 C
ATOM 91 0 LYS A 12 16. .651 41. .144 39. ,126 1. ,00 22. .38 O
ATOM 92 CB LYS A 12 14, ,105 39. .091 38, ,683 1. ,00 21. .97 C
ATOM 93 CG LYS A 12 12, .634 38, .936 38. ,327 1. ,00 22, .31 c
ATOM 94 CD LYS A 12 11, .764 38, .741 39. .565 1, ,00 24, .83 c
ATOM 95 CE LYS A 12 10, .287 38. .577 39. ,202 1, ,00 26. .64 c
ATOM 96 NZ LYS A 12 9. ,480 37. .955 40. ,305 1. ,00 29. ,33 N
ATOM 97 N GLU A 13 16. .284 39, .750 40. ,857 1. ,00 22. .55 N
ATOM 98 CA GLU A 13 17. ,689 39. .566 41. ,190 1. ,00 22. ,57 C
ATOM 99 C GLU A 13 18. ,116 38, .280 40. ,506 1. ,00 22, .01 C
ATOM 100 O GLU A 13 17. ,271 37. .462 40. ,150 1. ,00 21. ,38 O
ATOM 101 CB GLU A 13 17. ,881 39. .456 42. ,710 1. ,00 23. .24 C
ATOM 102 CG GLU A 13 17. ,221 40. .587 43. ,496 1. ,00 25. ,57 C
ATOM 103 CD GLU A 13 17. ,761 40. ,775 44. 916 1. 00 29. ,95 C
ATOM 104 OEl GLU A 13 18. ,899 40. ,333 45. ,239 1. ,00 31. ,64 O
ATOM 105 OE2 GLU A 13 17. 032 41. ,393 45. 733 1. 00 33. ,30 O
ATOM 106 N THR A 14 19. ,419 38. ,098 40. ,314 1. 00 21. ,84 N
ATOM 107 CA THR A 14 19. 942 36. ,855 39. 760 1. 00 21. 60 C
ATOM 108 C THR A 14 19. 574 35. 713 40. 711 1. 00 21. 52 C
ATOM 109 O THR A 14 19. 536 35. ,898 41. 932 1. 00 20. 88 O
ATOM 110 CB THR A 14 21. 494 36. 916 39. 555 1. 00 21. 62 C
ATOM 111 OG1 THR A 14 22. ,147 37. ,283 40. 775 1. 00 21. 67 O
ATOM 112 CG2 THR A 14 21. 894 38. 012 38. 574 1. 00 21. 13 C ATOM 113 N GLY A 15 19.249 34.549 40.150 1.00 21.90 N
ATOM 114 CA GLY A 15 18, .859 33, .401 40, .955 1, .00 22, .03 C
ATOM 115 C GLY A 15 17 .361 33 .283 41 .186 1 .00 22 .17 C
ATOM 116 O GLY A 15 16, .888 32, .210 41, .554 1, .00 21, .94 O
ATOM 117 N GLU A 16 16 .610 34 .369 40 .982 1, .00 22 .35 N
ATOM 118 CA GLU A 16 15, .150 34, .339 41, .162 1, .00 22, .54 C
ATOM 119 C GLU A 16 14 .486 33, .740 39 .927 1, .00 22, .68 C
ATOM 120 O GLU A 16 15, .175 33, .386 38, .962 1, .00 22, .39 o
ATOM 121 CB GLU A 16 14, .602 35, .749 41, .433 1, .00 22, .57 c
ATOM 122 CG GLU A 16 15, .079 36, .337 42, .746 1, .00 23, .97 c
ATOM 123 CD GLU A 16 14, .377 37, .629 43, .137 1, .00 24, ,41 c
ATOM 124 OEl GLU A 16 14, .028 38. .434 42. ,262 1, .00 22, .72 0
ATOM 125 OE2 GLU A 16 14, .205 37, .853 44, .354 1, ,00 28, .36 0
ATOM 126 N SER A 17 13, ,152 33, .630 39. .971 1, .00 22. .69 N
ATOM 127 CA SER A 17 12, .336 33, .179 38, .838 1, .00 22, ,73 C
ATOM 128 C SER A 17 11. .374 34. .262 38. .378 1, .00 21. ,71 C
ATOM 129 O SER A 17 10, .951 35, .079 39, .167 1, .00 21. .49 O
ATOM 130 CB SER A 17 11. .486 31. .970 39. .228 1, .00 22. .48 c
ATOM 131 OG SER A 17 12, .316 30, .895 39, .591 1, .00 26. ,64 0
ATOM 132 N LEU A 18 11. .030 34. .234 37. .092 1, .00 21. ,08 N
ATOM 133 CA LEU A 18 9, .965 35, .047 36, .536 1, .00 20. ,89 C
ATOM 134 C LEU A 18 8. .886 34. .144 35. .952 1, .00 20. ,71 c
ATOM 135 O LEU A 18 9, .189 33, .225 35. .204 1, .00 21, ,21 0
ATOM 136 CB LEU A 18 10. .519 35. .882 35. .402 1. .00 21, ,29 c
ATOM 137 CG LEU A 18 9, ,809 37, ,138 34. .870 1, .00 21, ,60 c
ATOM 138 CD1 LEU A 18 9. .814 37. .122 33. .381 1, .00 21, ,64 c
ATOM 139 CD2 LEU A 18 8. .433 37, .400 35. .427 1, .00 23, ,34 c
ATOM 140 N THR A 19 7. .630 34. .423 36. .251 1, .00 20. ,13 N
ATOM 141 CA THR A 19 6. ,526 33. ,784 35. .550 1, .00 19, ,98 C
ATOM 142 C THR A 19 5. .861 34. ,824 34. .686 1, .00 19. ,47 c
ATOM 143 O THR A 19 5. .528 35. .897 35. .160 1, .00 20. ,11 o
ATOM 144 CB THR A 19 5. .553 33. .199 36. .573 1. .00 20, ,46 c
ATOM 145 OG1 THR A 19 6. .197 32. .115 37. .255 1. ,00 17. .99 0
ATOM 146 CG2 THR A 19 4. .325 32. .538 35, .876 1. ,00 19. .65 c
ATOM 147 N ILE A 20 5. ,710 34. .538 33, .403 1, ,00 19, .31 N
ATOM 148 CA ILE A 20 4. ,965 35. .398 32, .489 1. .00 18. .89 C
ATOM 149 C ILE A 20 3. .702 34. .640 32, .137 1, .00 18. .68 C
ATOM 150 O ILE A 20 3, ,780 33. ,481 31, ,737 1, .00 18. ,03 O
ATOM 151 CB ILE A 20 5, ,765 35, .676 31, .218 1, .00 18. .83 C
ATOM 152 CGI ILE A 20 7. ,142 36, ,265 31, ,574 1. ,00 21. .66 C
ATOM 153 CG2 ILE A 20 4, ,935 36, .550 30, .252 1, ,00 19. .66 C
ATOM 154 CD1 ILE A 20 8. ,099 36, ,433 30. ,374 1. .00 23. ,01 c
ATOM 155 N ASN A 21 2. ,549 35, ,293 32, ,277 1. ,00 18. ,35 N
ATOM 156 CA ASN A 21 1, ,260 34. .685 31. ,989 1. .00 19. .67 C
ATOM 157 C ASN A 21 0. ,644 35, .318 30. ,746 1. ,00 20. ,00 C
ATOM 158 O ASN A 21 0, .570 36, .546 30, ,640 1. ,00 20. ,11 O
ATOM 159 CB ASN A 21 0. .310 34, .883 33, ,179 1. ,00 20. ,34 C
ATOM 160 CG ASN A 21 0, .743 34, .107 34, ,414 1. ,00 23. ,88 C
ATOM 161 OD1 ASN A 21 0, ,884 32. .884 34, ,364 1. ,00 27. ,13 o
ATOM 162 ND2 ASN A 21 0, .943 34, .807 35, ,531 1. ,00 22. ,89 N
ATOM 163 N CYS A 22 0, .155 34. ,472 29. ,841 1. ,00 19. ,78 N
ATOM 164 CA CYS A 22 -0, .550 34, ,913 28, ,653 1. ,00 18. ,87 C
ATOM 165 C CYS A 22 -1, .932 34. ,294 28. ,600 1. ,00 18. ,28 C
ATOM 166 O CYS A 22 -2, .099 33, ,099 28. ,874 1. ,00 18. ,57 O
ATOM 167 CB CYS A 22 0. .251 34. ,591 27. ,375 1. ,00 18. ,23 C
ATOM 168 SG CYS A 22 1, .687 35, ,685 27. ,122 1. ,00 22. ,18 S
ATOM 169 N VAL A 23 -2. .930 35, ,099 28. ,241 1. 00 17. 04 N
ATOM 170 CA VAL A 23 -4. .289 34, ,573 28. ,085 1. ,00 17. ,69 C
ATOM 171 C VAL A 23 -4. ,780 35. ,074 26. ,736 1. 00 17. 84 C
ATOM 172 O VAL A 23 -4, .752 36, ,272 26. ,452 1. ,00 17. ,82 O
ATOM 173 CB VAL A 23 -5. ,257 35. ,034 29. ,209 1. 00 16. 92 C
ATOM 174 CGI VAL A 23 -6. ,628 34. ,402 29. ,040 1. 00 16. 56 C
ATOM 175 CG2 VAL A 23 -4. ,682 34. ,676 30. ,574 1. 00 18. 84 C
ATOM 176 N LEU A 24 -5. ,205 34. ,150 25. ,896 1. 00 18. 50 N ATOM 177 CA LEU A 24 -5 848 34 505 24 625 1 00 18 68 C
ATOM 178 C LEU A 24 -7 287 34 970 24 888 1 00 18 .14 c
ATOM 179 O LEU A 24 -8 116 34 183 25 284 1 00 18 93 0
ATOM 180 CB LEU A 24 -5 870 33 273 23 754 1 00 19 49 c
ATOM 181 CG LEU A 24 -5 907 33 369 22 218 1 00 21 72 c
ATOM 182 CD1 LEU A 24 -6 724 32 226 21 629 1 00 21 29 c
ATOM 183 CD2 LEU A 24 -6 311 34 697 21 692 1 00 20 69 c
ATOM 184 N ARG A 25 -7 569 36 242 24 642 1 00 .17 64 N
ATOM 185 CA ARG A 25 -8 868 36 862 24 894 1 00 17 04 C
ATOM 186 C ARG A 25 -9 727 37 050 23 621 1 00 17 73 C
ATOM 187 O ARG A 25 -9 215 37 396 22 549 1 00 16 17 o
ATOM 188 CB ARG A 25 -8 647 38 248 25 479 1 00 17 56 c
ATOM 189 CG ARG A 25 -7 649 38 332 26 652 1 00 17 53 c
ATOM 190 CD ARG A 25 -8 169 37 706 27 893 1 00 15 71 c
ATOM 191 NE ARG A 25 -9 439 38 300 28 305 1 00 15 64 N
ATOM 192 CZ ARG A 25 -9 622 39 154 29 313 1 00 14 07 c
ATOM 193 NH1 ARG A 25 -8 604 39 617 30 029 1 00 15 08 N
ATOM 194 NH2 ARG A 25 10 841 39 592 29 562 1 00 13 06 N
ATOM 195 N ASP A 26 11 036 36 867 23 764 1 00 18 00 N
ATOM 196 CA ASP A 26 11 988 37 148 22 696 1 00 19 25 C
ATOM 197 C ASP A 26 11 575 36 398 21 429 1 00 19 75 C
ATOM 198 O ASP A 26 11 446 36 979 20 340 1 00 20 42 O
ATOM 199 CB ASP A 26 12 075 38 658 22 424 1 00 19 21 C
ATOM 200 CG ASP A 26 13 200 39 012 21 457 1 00 21 12 C
ATOM 201 OD1 ASP A 26 13 038 39 948 20 634 1 00 23 28 O
ATOM 202 OD2 ASP A 26 14 288 38 390 21 446 1 00 22 43 O
ATOM 203 N ALA A 27 11 367 35 101 21 596 1 00 19 84 N
ATOM 204 CA ALA A 27 10 842 34 247 20 552 1 00 20 65 C
ATOM 205 C ALA A 27 11 891 33 953 19 486 1 00 21 01 C
ATOM 206 O ALA A 27 13 064 33 807 19 789 1 00 21 53 O
ATOM 207 CB ALA A 27 10 311 32 928 21 173 1 00 20 13 C
ATOM 208 N SER A 28 11 453 33 887 18 233 1 00 21 92 N
ATOM 209 CA SER A 28 12 274 33 408 17 128 1 00 22 37 C
ATOM 210 C SER A 28 11 935 31 949 16 842 1 00 22 77 C
ATOM 211 O SER A 28 12 830 31 137 16 616 1 00 23 65 O
ATOM 212 CB SER A 28 12 036 34 237 15 853 1 00 22 37 C
ATOM 213 OG SER A 28 12 317 35 605 16 069 1 00 22 84 O
ATOM 214 N PHE A 29 10 641 31 638 16 835 1 00 22 53 N
ATOM 215 CA PHE A 29 10 137 30 321 16 469 1 00 22 25 C
ATOM 216 C PHE A 29 -9 596 29 606 17 697 1 00 22 55 C
ATOM 217 O PHE A 29 -9 297 30 236 18 716 1 00 21 65 O
ATOM 218 CB PHE A 29 -9 050 30 465 15 410 1 00 21 99 c
ATOM 219 •CG PHE A 29 -9 491 31 247 14 202 1 00 22 87 c
ATOM 220 GDI PHE A 29 10 415 30 715 13 324 1 00 22 45 c
ATOM 221 CD2 PHE A 29 -8 999 32 528 13 959 1 00 22 23 c
ATOM 222 CE1 PHE A 29 10 841 31 441 12 224 1 00 23 02 c
ATOM 223 CE2 PHE A 29 -9 409 33 249 12 861 1 00 22 01 c
ATOM 224 CZ PHE A 29 10 333 32 715 11 992 1 00 23 18 c
ATOM 225 N GLU A 30 -9 487 28 285 17 594 1 00 23 28 N
ATOM 226 CA GLU A 30 -9 087 27 435 18 716 1 00 24 16 c
ATOM 227 C GLU A 30 -7 578 27 456 18 866 1 00 23 70 c
ATOM 228 O GLU A 30 -6 846 27 260 17 901 1 00 22 38 o
ATOM 229 CB GLU A 30 -9 509 25 975 18 500 1 00 24 28 c
ATOM 230 CG GLU A 30 10 965 25 743 18 147 1 00 27 72 c
ATOM 231 CD GLU A 30 11 183 24 367 17 543 1 00 30 78 c
ATOM 232 OEl GLU A 30 11 872 24 247 16 501 1 00 33 08 0
ATOM 233 OE2 GLU A 30 10 648 23 395 18 122 1 00 34 13 0
ATOM 234 N LEU A 31 -7 110 27 670 20 083 1 00 25 10 N
ATOM 235 CA LEU A 31 -5 674 27 654 20 347 1 00 25 75 C
ATOM 236 C LEU A 31 -5 098 26 262 20. 072 1. 00 26. 30 C
ATOM 237 O LEU A 31 -5 584 25 272 20 610 1 00 27 18 0
ATOM 238 CB LEU A 31 -5 412 28 059 21. 791 1. 00 26 27 c
ATOM 239 CG LEU A 31 -3 944 28 189 22 199 1 00 26 18 c
ATOM 240 CD1 LEU A 31 -3 256 29 266 21. 376 1. 00 27 21 c ATOM 241 CD2 LEU A 31 -3..871 28..497 23,.665 1..00 24,.85 c
ATOM 242 N LYS A 32 -4. .093 26. .191 19. .204 1. .00 26, .63 N
ATOM 243 CA LYS A 32 -3. .472 24. .920 18. .830 1. .00 27, ,19 C
ATOM 244 C LYS A 32 -2. .050 24, .735 19, ,399 1. .00 27, .32 C
ATOM 245 O LYS A 32 -1. .738 23, .676 19. .959 1. .00 29. .44 O
ATOM 246 CB LYS A 32 -3. .465 24, .784 17. .311 1. .00 27. .22 c
ATOM 247 CG LYS A 32 -4. .868 24, .598 16. .683 1. .00 28. .87 c
ATOM 248 CD LYS A 32 -5, .729 23, .562 17. .425 1. .00 30. ,06 c
ATOM 249 CE LYS A 32 -7, .067 23. .300 16. .738 1. .00 31. ,53 c
ATOM 250 NZ LYS A 32 -8, .044 22. .702 17. .719 1, .00 32, ,23 N
ATOM 251 N ASP A 33 -1, .205 25. .745 19. ,235 1. .00 25, ,91 N
ATOM 252 CA ASP A 33 0. .173 25, .738 19. ,692 1. .00 25, ,17 C
ATOM 253 C ASP A 33 0, .501 27, .137 20. .232 1. .00 24. ,01 C
ATOM 254 O ASP A 33 -0, .299 28, .066 20. .103 1. .00 22. ,47 O
ATOM 255 CB ASP A 33 1, .128 25, .388 18. .555 1. .00 25. ,62 C
ATOM 256 CG ASP A 33 2, .537 24, .989 19. .043 1. .00 28. .98 C
ATOM 257 OD1 ASP A 33 2, .698 24, ,558 20. .216 1. .00 32. .36 O
ATOM 258 OD2 ASP A 33 3, ,560 25, ,093 18. .322 1. .00 32. .29 O
ATOM 259 N THR A 34 1, .662 27. ,243 20, .872 1. .00 22. ,48 N
ATOM 260 CA THR A 34 2, .151 28. .470 21, .460 1, .00 22, ,17 C
ATOM 261 C THR A 34 3. ,646 28. ,602 21, ,244 1. ,00 21, ,74 C
ATOM 262 O THR A 34 4, .358 27, .618 21. .122 1. .00 21, .43 O
ATOM 263 CB THR A 34 1, .888 28, .485 22. .961 1. .00 21, .97 C
ATOM 264 OG1 THR A 34 2, ,412 27, .294 23. ,557 1. ,00 23, ,15 O
ATOM 265 CG2 THR A 34 0, .409 28, .455 23. .278 1. .00 22. .95 C
ATOM 266 N GLY A 35 4, .121 29. .838 21. .250 1. .00 21. ,66 N
ATOM 267 CA GLY A 35 5, .534 30, .118 21. .096 1. .00 21. .46 C
ATOM 268 C GLY A 35 5, ,966 31, ,234 22. ,008 1, ,00 20. .74 C
ATOM 269 O GLY A 35 5, ,136 32. ,033 22. ,416 1, .00 21. .18 O
ATOM 270 N TRP A 36 7, .261 31, .259 22, ,322 1, ,00 20. .14 N
ATOM 271 CA TRP A 36 7, .865 32, .251 23. .196 1, .00 19. .89 C
ATOM 272 C TRP A 36 9, .108 32. .819 22. .516 1, .00 20. ,02 c
ATOM 273 O TRP A 36 9, .907 32, .078 21, .925 1, .00 19. .67 0
ATOM 274 CB TRP A 36 8, .209 31. .632 24. .541 1. .00 19. .58 c
ATOM 275 CG TRP A 36 6, .975 31. .292 25. .283 1, .00 20. .08 c
ATOM 276 GDI TRP A 36 6, .239 30, .125 25. .181 1, ,00 17. .81 c
ATOM 277 CD2 TRP A 36 6, ,255 32, .141 26. .182 1. .00 19. .53 c
ATOM 278 NE1 TRP A 36 5, .123 30. .216 25. ,975 1, .00 17. .93 N
ATOM 279 CE2 TRP A 36 5, .116 31, .426 26. .619 1. .00 20. .01 C
ATOM 280 CE3 TRP A 36 6, .462 33, .427 26. .678 1, .00 20. .31 C
ATOM 281 CZ2 TRP A 36 4, .208 31. .954 27. .537 1, .00 17. .18 C
ATOM 282 CZ3 TRP A 36 5, ,576 33, .940 27, .584 1, .00 18, ,90 c
ATOM 283 CH2 TRP A 36 4, .447 33, .216 27. .997 1, .00 20, .01 c
ATOM 284 N TYR A 37 9, .237 34, .132 22. .568 1, ,00 19, .65 N
ATOM 285 CA TYR A 37 10, .324 34, .829 21. .888 1, ,00 20, .62 C
ATOM 286 C TYR A 37 10, .939 35. .874 22. .815 1, ,00 20. .41 C
ATOM 287 O TYR A 37 10, .273 36. .379 23. .721 1, ,00 20, .08 O
ATOM 288 CB TYR A 37 9. .811 35. .508 20, ,613 1, ,00 20. .67 C
ATOM 289 CG TYR A 37 9, .135 34, .556 19. ,685 1, ,00 22, .11 C
ATOM 290 CD1 TYR A 37 9, .860 33, .886 18. ,710 1. .00 21. ,85 C
ATOM 291 CD2 TYR A 37 7, .775 34, .281 19, .815 1. ,00 22. .28 c
ATOM 292 CE1 TYR A 37 9, .244 33, .001 17. .853 1. ,00 23. .13 c
ATOM 293 CE2 TYR A 37 7. .146 33, .390 18. .974 1. ,00 24. ,22 c
ATOM 294 CZ TYR A 37 7, .887 32, .746 17. .999 1. ,00 25, .26 c
ATOM 295 OH TYR A 37 7. .279 31, .839 17, ;172 1. ,00 28. ,45 0
ATOM 296 N ARG A 38 12. .213 36. .178 22. .589 1. ,00 20. ,59 N
ATOM 297 CA ARG A 38 12, .916 37, .187 23. .372 1. ,00 21, ,53 C
ATOM 298 C ARG A 38 13. .924 37, ,949 22, .522 1. ,00 20. ,82 C
ATOM 299 O ARG A 38 14. ,625 37, ,360 21. .684 1. ,00 20. ,22 0
ATOM 300 CB ARG A 38 13. .675 36, ,540 24, .541 1. ,00 22. ,61 c
ATOM 301 CG ARG A 38 14. .457 35, ,317 24. .149 1. ,00 25. ,21 c
ATOM 302 CD ARG A 38 15. ,896 35. ,288 24. ,635 1. 00 30. 36 c
ATOM 303 NE ARG A 38 15. .951 35, ,051 26. .073 1. ,00 32. ,29 N
ATOM 304 CZ ARG A 38 16. .900 34, ,374 26. .707 1. ,00 33. ,39 C ATOM 305 NH1 ARG A 38 17,.920 33,.843 26.048 1,.00 35.30 N
ATOM 306 NH2 ARG A 38 16, .828 34, .232 28 .028 1 .00 33 .42 N
ATOM 307 N THR A 39 13, .986 39, ,259 22, .742 1, .00 20 .17 N
ATOM 308 CA THR A 39 15, .114 40, .050 22 .319 1, .00 19 .76 C
ATOM 309 C THR A 39 15, .921 40, .363 23 .569 1 .00 19 .85 C
ATOM 310 O THR A 39 15, .501 41, ,152 24, .420 1, .00 19 .60 O
ATOM 311 CB THR A 39 14, .645 41, .323 21 .624 1, .00 19 .79 C
ATOM 312 OG1 THR A 39 13, ,894 40. ,983 20, .455 1, ,00 19, .66 O
ATOM 313 CG2 THR A 39 15, .814 42, .101 21 .084 1, .00 18 .73 C
ATOM 314 N LYS A 40 17. .092 39. .752 23, .676 1, .00 19, .48 N
ATOM 315 CA LYS A 40 17, .911 39. .924 24, .867 1, .00 19 .94 C
ATOM 316 C LYS A 40 18, .632 41, ,250 24 .878 1, .00 18 .92 C
ATOM 317 O LYS A 40 18. .852 41. .865 23, .831 1, ,00 18, .69 O
ATOM 318 CB LYS A 40 18, .892 38. ,759 25, .026 1, .00 20 .70 C
ATOM 319 CG LYS A 40 19. .989 38. ,670 24, .006 1, .00 23, .62 C
ATOM 320 CD LYS A 40 20. .384 37. ,199 23, .759 1, .00 29, .14 C
ATOM 321 CE LYS' A 40 20. .713 36. ,432 25, ,055 1. ,00 31, .07 C
ATOM 322 NZ LYS A 40 19. .484 35. .955 25, .759 1, ,00 31, .81 N
ATOM 323 N LEU A 41 18, .963 41. .696 26, .084 1, .00 18, .33 N
ATOM 324 CA LEU A 41 19. .757 42. ,899 26, .296 1, .00 18, .50 C
ATOM 325 C LEU A 41 20. .999 42. .826 25, .425 1, .00 18, .22 C
ATOM 326 O LEU A 41 21. .609 41. .761 25. .309 1, .00 17. .78 O
ATOM 327 CB LEU A 41 20. .141 42. .998 27, .781 1, .00 18, .70 C
ATOM 328 CG LEU A 41 21, ,006 44. .117 28, .359 1, .00 18, .56 C
ATOM 329 GDI LEU A 41 22. .449 43. .720 28, ,319 1, .00 20, .25 C
ATOM 330 CD2 LEU A 41 20. .799 45. .471 27, .673 1, .00 18, .34 C
ATOM 331 N GLY A 42 21, .348 43. .954 24, .804 1, .00 18. .35 N
ATOM 332 CA GLY A 42 22, ,512 44. ,066 23, .938 1, .00 18, .25 C
ATOM 333 C GLY A 42 22, ,285 43. ,684 22. .478 1, .00 18. .60 C
ATOM 334 O GLY A 42 23, .143 43. ,927 21, .632 1, .00 18, .22 o
ATOM 335 N SER A 43 21, .130 43. .103 22, .176 1, .00 19, .23 N
ATOM 336 CA SER A 43 20, .856 42. .563 20. .852 1, .00 19, ,97 C
ATOM 337 C SER A 43 19, .564 43. .140 20, .264 1, .00 20, .80 C
ATOM 338 O SER A 43 18, .597 43. .416 20, .987 1, .00 19. .75 O
ATOM 339 CB SER A 43 20, .752 41, .031 20, .944 1, .00 20, .21 C
ATOM 340 OG SER A 43 19, .979 40, .482 19. .895 1, .00 20. .83 O
ATOM 341 N THR A 44 19, .564 43, .282 18. .941 1, ,00 21. .88 N
ATOM 342 CA THR A 44 18, ,399 43, .715 18, .172 1, .00 23, .21 C
ATOM 343 C THR A 44 17, ,589 42, .547 17. ,573 1, .00 24. ,06 c
ATOM 344 O THR A 44 16, .511 42, .760 17, ,035 1, .00 24, .67 o
ATOM 345 CB THR A 44 18. .869 44, .658 17, ,033 1, .00 23, .62 c
ATOM 346 OG1 THR A 44 19. .802 45, .624 17, ,536 1, .00 23, .82 0
ATOM 347 CG2 THR A 44 17. .752 45. ,508 16, ,559 1. ,00 24, ,67 c
ATOM 348 N ASN A 45 18, ,097 41, ,320 17. ,681 1. ,00 24. .92 N
ATOM 349 CA ASN A 45 17, .466 40. .137 17, ,080 1, .00 25. .63 C
ATOM 350 C ASN A 45 16. .523 39. .406 18, ,032 1. ,00 25, .35 C
ATOM 351 O ASN A 45 16, ,956 38. .938 19, ,087 1. ,00 25. .12 O
ATOM 352 CB ASN A 45 18. ,566 39. ,159 16. ,607 1. ,00 26. ,48 c
ATOM 353 CG ASN A 45 18, ,127 38. .290 15. ,422 1. ,00 28. .96 c
ATOM 354 OD1 ASN A 45 17. ,167 37. ,517 15. ,520 1. ,00 34. .50 o
ATOM 355 ND2 ASN A 45 18. ,834 38. ,420 14. ,295 1. ,00 33. .05 N
ATOM 356 N GLU A 46 15. ,243 39. ,310 17. ,656 1. ,00 25. .20 N
ATOM 357 CA GLU A 46 14. ,277 38. ,489 18. ,385 1. ,00 25. ,43 C
ATOM 358 C GLU A 46 14. ,524 37. ,037 18, ,050 1. ,00 25. ,11 C
ATOM 359 O GLU A 46 14. ,639 36. 680 16. ,882 1. 00 25. ,36 O
ATOM 360 CB ' GLU A 46 12. ,818 38. ,836 18. ,045 1. 00 25. ,34 C
ATOM 361 CG GLU A 46 11. ,826 38. ,236 19. .042 1. ,00 27. ,16 C
ATOM 362 CD GLU A 46 10. ,364 38. 576 18. ,756 1. 00 29. ,67 C
ATOM 363 OEl GLU A 46 9. ,873 38. ,238 17. ,667 1. 00 32. ,34 O
ATOM 364 OE2 GLU A 46 9. 686 39. 166 19. 619 1. 00 30. 61 O
ATOM 365 N GLN A 47 14. ,614 36. 202 19. ,070 1. 00 24. 89 N
ATOM 366 CA GLN A 47 14. 818 34. 783 18. 845 1. 00 25. 04 C
ATOM 367 C GLN A 47 13. ,840 33. 922 19. 634 1. 00 24. 11 C
ATOM 368 O GLN A 47 13. ,292 34. 332 20. ,649 1. 00 23. 89 O ATOM 369 CB GLN A 47 16..266 34,.404 19.128 1,.00 25,.75 c
ATOM 370 CG GLN A 47 16, .667 34, .505 20 .582 1, .00 28 .80 c
ATOM 371 CD GLN A 47 18. .162 34. .706 20, .766 1, .00 31, .99 c
ATOM 372 OEl GLN A 47 18, ,579 35, .306 21 .755 1, .00 35, .39 O
ATOM 373 NE2 GLN A 47 18. .968 34. .198 19, .830 1, .00 33, .93 N
ATOM 374 N SER A 48 13, .580 32, ,743 19 .098 1, .00 23, .33 N
ATOM 375 CA SER A 48 12, .753 31. ,745 19, .742 1, .00 23, .09 C
ATOM 376 C SER A 48 13, .408 31, ,195 21 .015 1, .00 22, .17 C
ATOM 377 O SER A 48 14, .630 31. .025 21, .088 1, .00 22, .12 O
ATOM 378 CB SER A 48 12, .523 30, .588 18 .758 1, .00 23, .69 C
ATOM 379 OG SER A 48 11, .687 29. .601 19, .332 1, .00 25, .84 O
ATOM 380 N ILE A 49 12. ,577 30, .889 21, .998 1, .00 21, .60 N
ATOM 381 CA ILE A 49 13. .000 30. .234 23, .233 1. .00 21, ,35 C
ATOM 382 C ILE A 49 12. .617 28. ,772 23, .125 1. .00 21, .11 C
ATOM 383 O ILE A 49 11. .453 28. ,458 22, .908 1. .00 20, .72 O
ATOM 384 CB ILE A 49 12. .262 30. .865 24, .434 1. .00 21. .53 C
ATOM 385 CGI ILE A 49 12. .625 32. .331 24, .552 1, .00 22, .11 c
ATOM 386 CG2 ILE A 49 12'. .620 30. .170 25, .733 1. .00 21. .54 c
ATOM 387 GDI ILE A 49 11. .854 33, .061 25, .590 1, .00 22, .85 c
ATOM 388 N SER A 50 13. .582 27, ,875 23, .268 1. .00 21. .72 N
ATOM 389 CA SER A 50 13. .290 26, .445 23, .322 1, .00 22, .28 c
ATOM 390 C SER A 50 12. .803 26, .065 24, .704 1. .00 22. .38 c
ATOM 391 O SER A 50 13. .495 26, ,313 25, .680 1. .00 22, .36 0
ATOM 392 CB SER A 50 14. .540 25, .641 23, .014 1. .00 22. .55 c
ATOM 393 OG SER A 50 15. .092 26, .052 21. .776 1. .00 25. .68 0
ATOM 394 N ILE A 51 11. .609 25, .477 24, .791 1. .00 22. ,85 N
ATOM 395 CA ILE A 51 11. ,048 25, .047 26. .074 1. .00 22. ,89 C
ATOM 396 C ILE A 51 11. .789 23, .819 26, ,591 1. ,00 22, .70 c
ATOM 397 O ILE A 51 11. .923 22, .838 25. .879 1. ,00 22, .61 0
ATOM 398 CB ILE A 51 9. .531 24. .744 25, .960 1. .00 22, .93 c
ATOM 399 CGI ILE A 51 8. .776 25. ,963 25, .434 1. .00 22, .33 c
ATOM 400 CG2 ILE A 51 8. .960 24. ,349 27, .321 1. .00 22. .98 c
ATOM 401 GDI ILE A 51 9. .133 27. ,260 26, .103 1. ,00 22. .64 c
ATOM 402 N GLY A 52 12. .264 23. .912 27, .838 1. .00 22. .98 N
ATOM 403 CA GLY A 52 13. ,061 22. .887 28, .488 1. .00 22. .87 c
ATOM 404 C GLY A 52 14, ,047 23, ,530 29. .461 1. ,00 23, ,19 c
ATOM 405 O GLY A 52 14, ,408 24, .718 29, .301 1, ,00 22. ,95 0
ATOM 406 N GLY A 53 14, ,453 22. .760 30. .477 1. ,00 22, ,92 N
ATOM 407 CA GLY A 53 15, ,429 23. .194 31. .470 1. ,00 23, ,02 c
ATOM 408 C GLY A 53 14, .970 24. .311 32. .405 1, ,00 23. ,04 c
ATOM 409 O GLY A 53 14, .065 24, .133 33. .226 1, ,00 22. ,84 o
ATOM 410 N ARG A 54 15. ,626 25. ,463 32. .294 1. ,00 23, .35 N
ATOM 411 CA ARG A 54 15, .251 26. .664 33. ,053 1. ,00 23. .76 C
ATOM 412 C ARG A 54 13. .909 27. ,234 32. ,576 1, ,00 23. ,14 C
ATOM 413 O ARG A 54 13. ,253 27, .954 33. ,310 1. ,00 23, ,45 O
ATOM 414 CB ARG A 54 16. .336 27. .749 32. ,923 1. .00 23. ,80 C
ATOM 415 CG ARG A 54 17. .649 27, .414 33. ,591 1, ,00 25. ,73 C
ATOM 416 CD ARG A 54 18. .552 28. .632 33. ,876 1. ,00 27. ,25 C
ATOM 417 NE ARG A 54 18. ,898 29. ,355 32. .648 1. ,00 28. ,42 N
ATOM 418 CZ ARG A 54 18, ,492 30. ,588 32, .323 1. ,00 29. ,63 C
ATOM 419 NH1 ARG A 54 17. ,700 31. ,296 33. ,130 1. ,00 30. 29 N
ATOM 420 NH2 ARG A 54 18. ,888 31. ,118 31. .169 1. ,00 29. ,15 N
ATOM 421 N TYR A 55 13. ,524 26. ,908 31. ,341 1. ,00 22. 88 N
ATOM 422 CA TYR A 55 12. ,314 27. ,425 30. .687 1. ,00 22. ,07 C
ATOM 423 C TYR A 55 11. ,188 26. ,385 30. ,719 1. ,00 21. 17 C
ATOM 424 O TYR A 55 11. ,243 25. ,395 30, ,009 1. ,00 22. 31 O
ATOM 425 CB TYR A 55 12. ,623 27. ,784 29. ,234 1. ,00 21. 88 C
ATOM 426 CG TYR A 55 13. ,801 28. ,715 29, .070 1. ,00 23. 92 C
ATOM 427 GDI TYR A 55 15. ,055 28. ,228 28. ,712 1. 00 26. 80 C
ATOM 428 CD2 TYR A 55 13. ,667 30. ,090 29. ,282 1. ,00 26. 62 C
ATOM 429 CE1 TYR A 55 16. ,154 29. ,090 28. ,557 1. 00 28. 70 C
ATOM 430 CE2 TYR A 55 14. 745 30. 954 29. ,134 1. 00 28. 10 C
ATOM 431 CZ TYR A 55 15. ,989 30. ,448 28. ,769 1. 00 29. 67 C
ATOM 432 OH TYR A 55 17. 071 31. 294 28. ,629 1. 00 33. 06 O ATOM 433 N VAL A 56 10..185 26,.610 31.559 1,.00 20,.05 N
ATOM 434 CA VAL A 56 9, .087 25, .671 31 .779 1 .00 19 .16 C
ATOM 435 C VAL A 56 7, .774 26, .317 31, .360 1, .00 18, .52 C
ATOM 436 O VAL A 56 7. .357 27. .357 31, .901 1, ,00 18. .12 O
ATOM 437 CB VAL A 56 9, .010 25, ,219 33, .252 1, .00 19, .07 C
ATOM 438 CGI VAL A 56 7. .790 24. .279 33, .487 1, .00 19, .53 C
ATOM 439 CG2 VAL A 56 10, .320 24. .501 33, .664 1, .00 19, ,48 C
ATOM 440 N GLU A 57 7. .147 25. .747 30, .344 1, .00 18. ,03 N
ATOM 441 CA GLU A 57 5, ,850 26. ,236 29, .904 1. .00 17. ,33 C
ATOM 442 C GLU A 57 4, .703 25. ,360 30, .398 1, .00 17, .50 C
ATOM 443 O GLU A 57 4, ,778 24. ,125 30, .351 1. ,00 18, .48 0
ATOM 444 CB GLU A 57 5, ,820 26. .327 28, .381 1, .00 17, .47 c
ATOM 445 CG GLU A 57 4. ,663 27. .191 27, .861 1. .00 15, .92 c
ATOM 446 CD GLU A 57 4. ,299 26, ,942 26, .395 1, .00 16, ,52 c
ATOM 447 OEl GLU A 57 4, .605 25. .850 25, .893 1, .00 14, .24 0
ATOM 448 OE2 GLU A 57 3, .678 27. .830 25, .749 1, .00 14, .65 0
ATOM 449 N THR A 58 3. .633 26. ,008 30, .835 1, .00 17. .44 N
ATOM 450 CA THR A 58 2, .374 25. ,364 31, .168 1. .00 17, .09 c
ATOM 451 C THR A 58 1, .245 25. .931 30, .325 1, .00 17, .31 c
ATOM 452 O THR A 58 1. .010 27. .153 30, .328 1, ,00 17, .84 0
ATOM 453 CB THR A 58 2, .063 25. .622 32. .638 1. .00 17, ,50 c
ATOM 454 OG1 THR A 58 3, .208 25. .265 33, .412 1, .00 17, .51 0
ATOM 455 CG2 THR A 58 0, .965 24. .689 33, .140 1. .00 18, .00 c
ATOM 456 N VAL A 59 0. .545 25. .045 29, .625 1, .00 16, .46 N
ATOM 457 CA VAL A 59 -0, .542 25. .426 28, .736 1, .00 16, .43 c
ATOM 458 C VAL A 59 -1, .832 24. .740 29. ,183 1, ,00 15, .86 c
ATOM 459 O VAL A 59 -1, .883 23. .513 29, ,342 1, .00 14, .34 0
ATOM 460 CB VAL A 59 -0, ,251 25. .040 27, .252 1, .00 16, .37 c
ATOM 461 CGI VAL A 59 -1, .433 25. .440 26, .343 1, .00 16, ,25 c
ATOM 462 CG2 VAL A 59 1, .054 25. .676 26, .743 1, .00 16, .91 c
ATOM 463 N ASN A 60 -2, ,863 25. .554 29, .391 1, .00 16. ,01 N
ATOM 464 CA ASN A 60 -4. .224 25. .100 29, .657 1. .00 16. ,49 C
ATOM 465 C ASN A 60 -5, .142 25. .565 28. ,542 1, .00 16. ,38 C
ATOM 466 O ASN A 60 -5. .575 26. ,728 28, .538 1, .00 15. .18 O
ATOM 467 CB ASN A 60 -4, .673 25. .660 30, .994 1, .00 17. .22 c
ATOM 468 CG ASN A 60 -3, .700 25, .309 32, .116 1, .00 21. .86 c
ATOM 469 OD1 ASN A 60 -2, .920 26. .170 32, .564 1, .00 31. .74 o
ATOM 470 ND2 ASN A 60 -3, .708 24. .035 32. .552 1, .00 22. .53 N
ATOM 471 N LYS A 61 -5, .435 24. .678 27, .592 1, .00 16. .48 N
ATOM 472 CA LYS A 61 -6, .109 25. .081 26. .351 1, .00 18. .49 C
ATOM 473 C LYS A 61 -7, .533 25. .551 26, .650 1. .00 19. .11 C
ATOM 474 O LYS A 61 -8, .031 26. .453 26. .006 1, .00 19, ,85 O
ATOM 475 CB LYS A 61 -6, .143 23. .937 25. .319 1. .00 19, ,58 C
ATOM 476 CG LYS A 61 -5, .129 24. ,036 24. .136 1, .00 21. ,70 C
ATOM 477 CD LYS A 61 -5, .345 22. ,853 23. .081 1, .00 23, ,52 C
ATOM 478 CE LYS A 61 -4, .572 21. ,530 23. .383 1, .00 23, ,96 C
ATOM 479 NZ LYS A 61 -5, .373 20. ,217 23. .361 1, .00 22. ,11 N
ATOM 480 N GLY A 62 -8. ,165 24. ,952 27, ,657 1. .00 19. ,79 N
ATOM 481 CA GLY A 62 -9, ,545 25. ,256 28, .002 1. .00 20. ,12 C
ATOM 482 C GLY A 62 -9, ,743 26. ,668 28, .515 1. ,00 20. ,10 C
ATOM 483 O GLY A 62 10. ,726 27, ,305 28, .206 1, .00 20, ,62 O
ATOM 484 N SER A 63 -8. ,790 27. ,159 29. .286 1, .00 20. ,78 N
ATOM 485 CA SER A 63 -8. .812 28. ,532 29, .772 1, .00 21, ,23 C
ATOM 486 C SER A 63 -8. .030 29. ,506 28. .874 1. ,00 21. ,06 C
ATOM 487 O SER A 63 -7. ,870 30. ,670 29. ,206 1. ,00 21. ,02 O
ATOM 488 CB SER A 63 -8. ,252 28. ,543 31, .171 1. ,00 21. ,10 C
ATOM 489 OG SER A 63 -6. ,856 28. ,412 31. ,117 1. ,00 23. ,25 O
ATOM 490 N LYS A 64 -7. ,545 29. ,008 27. ,742 1. ,00 21. ,07 N
ATOM 491 CA LYS A 64 -6. ,786 29. ,774 26. ,765 1. ,00 21. 34 C
ATOM 492 C LYS A 64 -5. 552 30. 450 27. ,383 1. 00 20. 91 C
ATOM 493 O LYS A 64 -5. ,128 31. ,527 26. ,953 1. ,00 19. 71 O
ATOM 494 CB LYS A 64 -7. 716 30. 743 26. ,029 1. 00 22. 29 C
ATOM 495 CG LYS A 64 -8. ,976 30. ,047 25. ,476 1. ,00 25. 28 C
ATOM 496 CD LYS A 64 10. ,033 31. ,046 25. ,074 1. 00 30. 88 C ATOM 497 CE LYS A 64 •11,.210 30,.411 24,.334 1,.00 32.43 c
ATOM 498 NZ LYS A 64 ■11, .472 28 .992 24 .760 1, .00 35 .69 N
ATOM 499 N SER A 65 -4, .962 29, .765 28, .363 1, .00 19, .94 N
ATOM 500 CA SER A 65 -3, .825 30, .267 29, .102 1 .00 20 .67 C
ATOM 501 C SER A 65 -2. .559 29, .472 28, .830 1, .00 19, .83 C
ATOM 502 O SER A 65 -2, .584 28, .250 28, .720 1, .00 18 .60 O
ATOM 503 CB SER A 65 -4, .121 30, .218 30, .600 1, .00 20, .77 C
ATOM 504 OG SER A 65 -5, .350 30, .878 30, .850 1, .00 25, .20 o
ATOM 505 N PHE A 66 -1, .460 30 .205 28 .769 1, .00 19 .55 N
ATOM 506 CA PHE A 66 -0, .136 29, .672 28, .581 1, .00 19, .48 C
ATOM 507 C PHE A 66 0, .856 30, .619 29, .278 1, .00 20 .09 C
ATOM 508 O PHE A 66 0. .790 31, .851 29. .113 1, .00 20, .75 O
ATOM 509 CB PHE A 66 0, .208 29, .430 27, .091 1, .00 18, .76 C
ATOM 510 CG PHE A 66 -0, .156 30, .556 26, .151 1, .00 20, .98 C
ATOM 511 CD1 PHE A 66 -1, .490 30, .838 25, .849 1, .00 21, .10 C
ATOM 512 CD2 PHE A 66 0, .838 31, .279 25, ,494 1, ,00 22, .63 C
ATOM 513 CE1 PHE A 66 -1. .827 31, .847 24, .961 1, .00 21, .88 C
ATOM 514 CE2 PHE A 66 0, .506 32, .282 24, .577 1, .00 22, .52 C
ATOM 515 CZ PHE A 66 -0, .837 32, .573 24, ,329 1, .00 23, .43 c
ATOM 516 N SER A 67 1, .743 30, .001 30, .062 1, .00 20, .70 N
ATOM 517 CA SER A 67 2, .698 30. .632 30. .961 1, .00 21, .27 C
ATOM 518 C SER A 67 4, .087 30, .068 30, .777 1, .00 20, .65 C
ATOM 519 O SER A 67 4, ,261 28, ,874 30, .548 1, ,00 21. .14 O
ATOM 520 CB SER A 67 2, .356 30, .312 32, .415 1, .00 21, .31 C
ATOM 521 OG SER A 67 1. .311 31. .136 32. .822 1, .00 27. .23 O
ATOM 522 N LEU A 68 5. .074 30, .929 30, .947 1, .00 20, .50 N
ATOM 523 CA LEU A 68 6, .469 30. .538 30. .937 1. .00 20. .82 C
ATOM 524 C LEU A 68 7, ,013 30, .914 32, .298 1, ,00 20. .84 C
ATOM 525 O LEU A 68 6, .866 32, .052 32, .706 1, .00 19, .92 O
ATOM 526 CB LEU A 68 7, .181 31, .344 29. ,878 1. .00 20. .70 C
ATOM 527 CG LEU A 68 8, .317 30, .832 29, .005 1, .00 23, ,40 c
ATOM 528 CD1 LEU A 68 9, ,303 31. .968 28. .773 1, .00 22. .63 c
ATOM 529 CD2 LEU A 68 8, .988 29, .587 29. ,503 1, ,00 23. .71 c
ATOM 530 N ARG A 69 7, ,647 29. .974 32. .980 1. .00 20. .92 N
ATOM 531 CA ARG A 69 8, .411 30, .263 34. .187 1, .00 21. .67 C
ATOM 532 C ARG A 69 9, .892 30. .041 33. .895 1. .00 21. .75 C
ATOM 533 O ARG A 69 10. ,296 28, .963 33, ,478 1. ,00 21. .02 O
ATOM 534 CB ARG A 69 7, .980 29, .371 35, .335 1, .00 21, .50 C
ATOM 535 CG ARG A 69 8. .705 29, ,694 36, ,648 1. .00 23. .03 C
ATOM 536 CD ARG A 69 8. .145 28, .935 37, .842 1, .00 23, .71 C
ATOM 537 NE ARG A 69 8. .827 29. .247 39. .101 1. .00 26, .51 N
ATOM 538 CZ ARG A 69 9. .899 28, .610 39. ,592 1, ,00 29. ,47 C
ATOM 539 NH1 ARG A 69 10. .481 27. .609 38. .932 1, ,00 31. ,37 N
ATOM 540 NH2 ARG A 69 10. .411 28. ,986 40. ,762 1, .00 30. .68 N
ATOM 541 N ILE A 70 10. .680 31. ,082 34. ,107 1. .00 22. .33 N
ATOM 542 CA ILE A 70 12. .120 31. ,054 33. ,892 1, .00 22, .69 C
ATOM 543 C ILE A 70 12. .770 31. ,073 35. ,263 1, .00 22, .58 C
ATOM 544 O ILE A 70 12. .595 32, ,017 36. ,011 1. .00 22. ,40 O
ATOM 545 CB ILE A 70 12. .552 32, ,275 33, ,064 1, .00 22. .65 C
ATOM 546 CGI ILE A 70 11. .665 32. ,389 31. ,835 1. ,00 23. ,48 C
ATOM 547 CG2 ILE A 70 14. .039 32, ,178 32. ,641 1. ,00 22. ,68 C
ATOM 548 CD1 ILE A 70 11. ,910 33. ,600 31. ,053 1. ,00 26. ,54 C
ATOM 549 N SER A 71 13. .495 30. .006 35. ,585 1. ,00 23. ,04 N
ATOM 550 CA SER A 71 14. ,143 29. ,844 36. ,878 1. ,00 23. ,02 C
ATOM 551 C SER A 71 15. ,597 30. ,286 36. ,806 1. ,00 22. ,90 C
ATOM 552 O SER A 71 16. .154 30. ,394 35. .719 1. ,00 22. ,88 O
ATOM 553 CB SER A 71 14. ,080 28. ,367 37. ,301 1. ,00 23. ,74 C
ATOM 554 OG SER A 71 14, ,571 27, ,509 36. ,275 1. ,00 23. ,76 O
ATOM 555 N ASP A 72 16. ,199 30. ,550 37. ,968 1. 00 22. 96 N
ATOM 556 CA ASP A 72 17. ,634 30. ,801 38. ,076 1. ,00 23. ,04 C
ATOM 557 C ASP A 72 18. ,076 31. 853 37. 083 1. 00 22. 39 C
ATOM 558 O ASP A 72 18. ,929 31. ,604 36. 236 1. 00 22. 72 O
ATOM 559 CB ASP A 72 18. 431 29. 498 37. 862 1. 00 23. 38 C
ATOM 560 CG ASP A 72 19. ,932 29. 668 38. 126 1. 00 24. 56 C ATOM 561 OD1 ASP A 72 20.,305 30.,618 38,,854 1..00 24,.85 0
ATOM 562 OD2 ASP A 72 20. ,800 28. .892 37. ,649 1. .00 25, ,90 0
ATOM 563 N LEU A 73 17. ,494 33. .038 37. .200 1, .00 22, .00 N
ATOM 564 CA LEU A 73 17. ,729 34. .078 36. .216 1. .00 21, .94 c
ATOM 565 C LEU A 73 19. .143 34. .619 36. .349 1. .00 21, .62 c
ATOM 566 O LEU A 73 19. .704 34, .654 37, ,434 1. .00 20, .95 0
ATOM 567 CB LEU A 73 16. .724 35. .217 36. ,361 1, .00 21, .83 c
ATOM 568 CG LEU A 73 15. .270 34. .871 36. ,009 1. ,00 21, .51 c
ATOM 569 GDI LEU A 73 14. .329 35. .768 36. ,771 1. .00 20, .80 c
ATOM 570 CD2 LEU A 73 14. .991 34. .947 34. .493 1, .00 22, .55 c
ATOM 571 N ARG A 74 19. .709 35. .011 35. .217 1. .00 21. .85 N
ATOM 572 CA ARG A 74 20. .977 35. .727 35. .179 1. .00 22. .48 c
ATOM 573 C ARG A 74 20. .777 37, .032 34. .419 1, ,00 21, ,94 c
ATOM 574 O ARG A 74 19. .741 37. .232 33. .786 1. ,00 21. .58 0
ATOM 575 CB ARG A 74 22. .103 34. .885 34, .564 1. .00 23. .01 c
ATOM 576 CG ARG A 74 21. .719 33, .699 33, .687 1. ,00 25. .24 c
ATOM 577 CD ARG A 74 21. .299 32. ,418 34, .444 1. ,00 28. .74 c
ATOM 578 NE ARG A 74 21. ,739 31. ,104 33, ,907 1. ,00 31. ,12 N
ATOM 579 CZ ARG A 74 21. ,911 30. ,754 32. ,613 1, ,00 33. .00 C
ATOM 580 NH1 ARG A 74 21. .730 31, .606 31. ,607 1, .00 35, ,30 N
ATOM 581 NH2 ARG A 74 22. .299 29. .513 32. ,319 1. .00 33. .69 N
ATOM 582 N VAL A 75 21, ,752 37. .932 34. .489 1. .00 21. .59 N
ATOM 583 CA VAL A 75 21, .531 39. .275 33. .970 1, .00 21. .69 C
ATOM 584 C VAL A 75 21, .395 39. .261 32. .443 1. .00 21. .72 C
ATOM 585 O VAL A 75 20. .763 40, .147 31. .881 1, .00 21. .66 O
ATOM 586 CB VAL A 75 22. .578 40, .354 34. .481 1, .00 21. ,62 C
ATOM 587 CGI VAL A 75 23, .363 39, .870 35. .698 1, .00 20, .91 C
ATOM 588 CG2 VAL A 75 23. ,488 40, .839 33. ,373 1, .00 21, ,89 C
ATOM 589 N GLU A 76 21, .975 38. .263 31. ,778 1, .00 21, ,76 N
ATOM 590 CA GLU A 76 21. .853 38, .163 30, ,319 1, .00 21, .87 C
ATOM 591 C GLU A 76 20. .441 37. .747 29. ,866 1, .00 21, ,85 c
ATOM 592 O GLU A 76 20, .088 37, .963 28. ,709 1, .00 22, .39 0
ATOM 593 CB GLU A 76 22. .916 37, .233 29. ,714 1. .00 21, .99 c
ATOM 594 CG GLU A 76 22, .876 35, .791 30. .199 1, .00 22, .56 c
ATOM 595 CD GLU A 76 24, .002 35, .449 31. .160 1, .00 24, .12 c
ATOM 596 OEl GLU A 76 24, .518 36, .377 31, .853 1. .00 22, .56 0
ATOM 597 OE2 GLU A 76 24, .360 34, .245 31, .225 1, .00 24, .41 0
ATOM 598 N ASP A 77 19, .654 37, .159 30, .773 1, .00 21, ,45 N
ATOM 599 CA ASP A 77 18, .227 36, .896 30, .540 1, .00 21. .34 C
ATOM 600 C ASP A 77 17, ,391 38, .163 30, .461 1, ,00 21. .15 c
ATOM 601 O ASP A 77 16, .243 38, .119 30, .018 1, ,00 21. .28 0
ATOM 602 CB ASP A 77 17, ,626 36, .043 31. .662 1. ,00 21. ,32 c
ATOM 603 CG ASP A 77 18, .151 34, .641 31. .670 1, .00 21. .44 c
ATOM 604 OD1 ASP A 77 18, .584 34, .160 30. ,603 1, .00 22. .02 0
ATOM 605 OD2 ASP A 77 18, .164 33. .948 32, ,698 1. .00 21, ,47 0
ATOM 606 N SER A 78 17, ,929 39, .278 30, .934 1. .00 20, .42 N
ATOM 607 CA SER A 78 17. .203 40. .533 30, .829 1, .00 20, .88 C
ATOM 608 C SER A 78 16, .915 40, .804 29, ,334 1, .00 20, .27 C
ATOM 609 O SER A 78 17. .656 40, ,373 28. ,469 1, .00 20. .38 O
ATOM 610 CB SER A 78 17, .976 41, ,658 31. ,542 1, .00 21, ,09 C
ATOM 611 OG SER A 78 18. .806 42. .351 30, ,650 1. .00 23, ,22 0
ATOM 612 N GLY A 79 15. ,793 41. ,444 29, ,039 1. ,00 20. ,44 N
ATOM 613 CA GLY A 79 15, .346 41. .653 27, ,669 1, ,00 20. ,21 C
ATOM 614 C GLY A 79 13. .831 41. .698 27. ,595 1. ,00 20. ,09 C
ATOM 615 O GLY A 79 13. .160 41, .737 28. ,627 1. ,00 20. ,37 O
ATOM 616 N THR A 80 13. .287 41, .710 26. ,381 1. ,00 19. ,79 N
ATOM 617 CA THR A 80 11. .837 41, .728 26. ,191 1. .00 20. ,31 C
ATOM 618 C THR A 80 11. .367 40, .356 25. ,727 1. .00 19. ,48 C
ATOM 619 O THR A 80 11. .904 39, .818 24, ,781 1, .00 20. ,27 O
ATOM 620 CB THR A 80 11. ,436 42, ,804 25. ,173 1. .00 20. ,39 C
ATOM 621 OG1 THR A 80 11. ,688 44, ,111 25. ,721 1. ,00 23. 13 0
ATOM 622 CG2 THR A 80 9. ,906 42, ,787 24. ,943 1. ,00 22. ,27 c
ATOM 623 N TYR A 81 10, ,379 39. ,809 26. ,415 1. ,00 19. 45 N
ATOM 624 CA TYR A 81 9, .814 38, ,487 26. ,146 1. ,00 18. ,67 C ATOM 625 C TYR A 81 393 38.662 25.599 1..00 19,.26 C
ATOM 626 O TYR A 81 ,633 39.512 26.075 1, .00 18, .23 O
ATOM 627 CB TYR A 81 761 37.660 27.429 1. .00 18, .65 C
ATOM 628 CG TYR A 81 11.112 37.287 27.977 1, .00 15, .74 c
ATOM 629 CD1 TYR A 81 11.549 35.980 27.944 1, .00 18, .49 c
ATOM 630 CD2 TYR A 81 11.952 38.238 28.529 1. .00 17. .22 c
ATOM 631 CEl TYR A 81 12.817 35.616 28.425 1.00 18, .28 c
ATOM 632 CE2 TYR A 81 13.225 37.889 29.020 1.00 16. ,72 c
ATOM 633 CZ TYR A 81 13.644 36.577 28.963 1.00 17, .27 c
ATOM 634 OH TYR A 81 14.878 36.206 29.433 1.00 15. .49 O
ATOM 635 N LYS A 82 8.051 37.877 24.586 1.00 19, .68 N
ATOM 636 CA LYS A 82 6.726 37.899 23.982 1.00 19. .85 c
ATOM 637 C LYS A 82 6.238 36.470 23.773 1.00 19, .88 c
ATOM 638 O LYS A 82 7.005 35.613 23.348 1.00 20. .39 O
ATOM 639 CB LYS A 82 6.802 38.639 22.652 1.00 20. .14 c
ATOM 640 CG LYS A 82 6.918 40.185 22.820 1.00 21. .90 c
ATOM 641 CD LYS A 82 ,840 40.903 21.446 1.00 23. .26 c
ATOM 642 CE LYS A 82 .806 42.409 21.625 1.00 24, .18 c
ATOM 643 NZ LYS A 82 .979 43.197 20.363 1.00 24, .03 N
ATOM 644 N CYS A 83 .966 36.214 24.064 11..00 19, .38 N
ATOM 645 CA CYS A 83 .326 34.925 23.758 11.,00 19, ,54 C
ATOM 646 C CYS A 83 .495 35.063 22.498 11.,00 19, ,13 C
ATOM 647 O CYS A 83 .115 36.166 22.140 11.,00 20, ,12 O
ATOM 648 CB CYS A 83 .383 34.516 24.881 11.,00 18, .81 C
ATOM 649 SG CYS A 83 .064 35.745 25.124 11..00 19, ,61 S
ATOM 650 N GLN A 84 .155 33.940 21.873 11.,00 19, ,01 N
ATOM 651 CA GLN A 84 .386 33.949 20.620 11.,00 18, ,39 C
ATOM 652 C GLN A 84 .471 32.748 20.533 11.,00 17, ,66 C
ATOM 653 O GLN A 84 .878 31.646 20.855 11..00 17. .08 0
ATOM 654 CB GLN A 84 .302 33.945 19.400 11.,00 18, ,68 c
ATOM 655 CG GLN A 84 .520 34.082 18.069 11.,00 20, ,36 c
ATOM 656 CD GLN A 84 .286 34.805 16.985 11.,00 22, ,07 c
ATOM 657 OEl GLN A 84 .702 35.549 16.177 11.,00 25, ,82 0
ATOM 658 NE2 GLN A 84 4.580 34.620 16.970 11.,00 22, ,45 N
ATOM 659 N ALA A 85 0.227 32.986 20.120 11.,00 17. ,06 N
ATOM 660 CA ALA A 85 -0.752 31.946 19.883 11.,00 17, ,04 C
ATOM 661 C ALA A 85 -0.578 31.510 18.439 11.,00 17. ,40 C
ATOM 662 O ALA A 85 -0.174 32.300 17.593 11.,00 17. ,89 0
ATOM 663 CB ALA A 85 -2.189 32.477 20.111 11.00 16, ,15 c
ATOM 664 N PHE A 86 -0.882 30.249 18.186 11.,00 17, ,84 N
ATOM 665 CA PHE A 86 -0.926 29.674 16.839 11.,00 18, ,83 C
ATOM 666 C PHE A 86 -2.239 28.934 16.677 11.,00 18, ,76 C
ATOM 667 O PHE A 86 -2.756 28.351 17.623 11.00 19. ,07 O
ATOM 668 CB PHE A 86 0.206 28.670 16.608 11.,00 19, ,07 C
ATOM 669 CG PHE A 86 1.557 29.293 16.556 11.,00 20. ,07 C
ATOM 670 GDI PHE A 86 .196 29.652 17.710 11.,00 21. ,17 C
ATOM 671 CD2 PHE A 86 .192 29.507 15.341 1, .00 22. .69 C
ATOM 672 CEl PHE A 86 .454 30.230 17.671 1, .00 24. ,31 C
ATOM 673 CE2 PHE A 86 .446 30.106 15.289 1, .00 24. .05 c
ATOM 674 CZ PHE A 86 .086 30.451 16.456 1, .00 23. .58 c
ATOM 675 N TYR A 87 -2.747 28.949 15.455 1, .00 19. .72 N
ATOM 676 CA TYR A 87 -4.017 28.334 15.122 1, .00 19. ,98 C
ATOM 677 C TYR A 87 -3.833 27.437 13.920 1, ,00 20. ,47 C
ATOM 678 O TYR A 87 -2.759 27.389 13.340 1, .00 20. ,29 O
ATOM 679 CB TYR A 87 -5.023 29.428 14.726 1, .00 19, .55 C
ATOM 680 CG TYR A 87 -5.267 30.538 15.730 1, .00 18. .80 C
ATOM 681 GDI TYR A 87 -5.009 31.865 15.394 1, .00 17, .12 C
ATOM 682 CD2 TYR A 87 -5.834 30.275 16.967 1, .00 19. .29 C
ATOM 683 CEl TYR A 87 -5.264 32.881 16.260 1, .00 18, .87 c
ATOM 684 CE2 TYR A 87 -6.096 31.298 17.859 1, ,00 19. .95 c
ATOM 685 CZ TYR A 87 -5.817 32.608 17.489 1, ,00 19. ,14 c
ATOM 686 OH TYR A 87 -6.068 33.645 18.340 1, .00 20. .15 0
ATOM 687 N SER A 88 -4.898 26.764 13.512 1. .00 21. ,28 N
ATOM 688 CA SER A 88 -4.836 25.962 12.295 1, .00 23. .13 C ATOM 689 C SER A 88 -6,.079 26,.121 11,.419 1,.00 23.96 c
ATOM 690 O SER A 88 -7, .179 26, .346 11, .918 1 .00 23 .81 0
ATOM 691 CB SER A 88 -4, .625 24, .475 12, .629 1, .00 22 .85 c
ATOM 692 OG SER A 88 -5, .821 23, .903 13, ,115 1, .00 22, .43 0
ATOM 693 N LEU A 89 -5, .880 26, .008 10, .110 1, .00 25 .98 N
ATOM 694 CA LEU A 89 -6, .990 25, .886 9, .165 1, .00 27 .25 C
ATOM 695 C LEU A 89 -7, .002 24. .483 8. .576 1, ,00 28, .06 c
ATOM 696 O LEU A 89 -5, .951 23, .950 8, .222 1, .00 27 .98 0
ATOM 697 CB LEU A 89 -6, .866 26, .932 8. .058 1, .00 27, .52 c
ATOM 698 CG LEU A 89 -7. .803 28. .155 8. .114 1, ,00 29, .73 c
ATOM 699 CD1 LEU A 89 -8, .235 28, .564 9, .533 1, .00 30 .33 c
ATOM 700 CD2 LEU A 89 -7, .145 29, .358 7, .411 1, .00 31, .16 c
ATOM 701 N PRO A 90 -8, .187 23. .883 8, .443 1, .00 29, .63 N
ATOM 702 CA PRO A 90 -8, .283 22, .530 7, ,881 1, .00 30 .44 c
ATOM 703 C PRO A 90 -7, .902 22, .525 6. .417 1, .00 31, .06 c
ATOM 704 O PRO A 90 -7, .949 23, .559 5, .752 1, .00 31, .55 0
ATOM 705 CB PRO A 90 -9, .768 22, .177 8, ,033 1, .00 30 .50 c
ATOM 706 CG PRO A 90 ■10, .464 23, .490 8. .063 1, .00 30, .55 c
ATOM 707 CD PRO A 90 -9, .519 24. .431 8, .766 1. .00 29, .62 c
ATOM 708 N LEU A 91 -7, .497 21, .360 5, .944 1, .00 31 .85 N
ATOM 709 CA LEU A 91 -7, .196 21, .143 4. .538 1. .00 32, .49 C
ATOM 710 C LEU A 91 -7, .932 19, .896 4, .069 1. .00 32, ,76 C
ATOM 711 O LEU A 91 -8. .475 19, .142 4, ,882 1, .00 32, .71 O
ATOM 712 CB LEU A 91 -5, .689 20, .983 4. .341 1, .00 32, .58 c
ATOM 713 CG LEU A 91 -4, .854 22, .143 4, .890 1, ,00 32, .68 c
ATOM 714 GDI LEU A 91 -3, .396 21, .736 5, .042 1, .00 32. ,35 c
ATOM 715 CD2 LEU A 91 -5, .001 23, .362 3, ,984 1, .00 33, .25 c
ATOM 716 N GLY A 92 -7, .967 19, .694 2, ,756 1, .00 33, ,35 N
ATOM 717 CA GLY A 92 -8, .603 18. .519 2, ,186 1, .00 33, .87 C
ATOM 718 C GLY A 92 -7, .625 17, .370 2, .018 1. .00 34, ,24 C
ATOM 719 O GLY A 92 -7, .469 16, .853 0, .909 1, .00 34, .70 O
ATOM 720 N ASP A 93 -6. .982 16. .962 3, .114 1, .00 34, .68 N
ATOM 721 CA ASP A 93 -5, .910 15, .961 3, .084 1, ,00 34, .86 C
ATOM 722 C ASP A 93 -5. .524 15, .542 4, .505 1, .00 34, .75 C
ATOM 723 O ASP A 93 -5. .313 16. .404 5, .367 1, .00 34, ,57 0
ATOM 724 CB ASP A 93 -4, .674 16, .526 2, .365 1, .00 35, ,11 c
ATOM 725 CG ASP A 93 -3, .673 15, ,447 1, .968 1, .00 35, ,84 c
ATOM 726 OD1 ASP A 93 -2. ,481 15, ,594 2, .311 1, .00 37, ,57 0
ATOM 727 OD2 ASP A 93 -3, .972 14, .429 1, .305 1, .00 36, .48 0
ATOM 728 N TYR A 94 -5, .444 14, .227 4, .736 1, .00 34, .54 N
ATOM 729 CA TYR A 94 -4, .999 13. ,649 6. .018 1. .00 34, ,59 c
ATOM 730 C TYR A 94 -5, ,877 14, ,239 7. ,177 1, ,00 34, ,53 c
ATOM 731 O TYR A 94 -7, .063 14, ,418 6, ,898 1, ,00 34, ,76 0
ATOM 732 CB TYR A 94 -3, .469 13, .756 6. .099 1, ,00 34. ,48 c
ATOM 733 CG TYR A 94 -2, .755 12, .615 5. ,379 1. ,00 35. ,44 c
ATOM 734 CD1 TYR A 94 -2, .816 12, .498 3. .990 1, ,00 35. .43 c
ATOM 735 CD2 TYR A 94 -2, .027 11, .650 6. ,084 1. ,00 35, ,46 c
ATOM 736 CEl TYR A 94 -2. .168 11. .471 3. ,326 1, ,00 35. ,92 c
ATOM 737 CE2 TYR A 94 -1, .372 10. .614 5. ,424 1, ,00 35. ,24 c
ATOM 738 CZ TYR A 94 -1, .447 10. .526 4. ,044 1, ,00 36. ,16 c
ATOM 739 OH TYR A 94 -0. ,812 9, ,494 3. ,371 1. ,00 35. ,86 0
ATOM 740 N ASN A 95 -5, .475 14, .527 8. ,433 1. ,00 34. ,45 N
ATOM 741 CA ASN A 95 -4. ,201 14. ,291 9. ,157 1. ,00 34. ,25 c
ATOM 742 C ASN A 95 -3. ,022 15. ,236 8. 862 1. 00 33. ,88 c
ATOM 743 O ASN A 95 -2. ,011 15. ,209 9. ,573 1. ,00 33. ,88 0
ATOM 744 CB ASN A 95 -3. ,787 12. ,810 9. ,182 1. ,00 34. 55 c
ATOM 745 CG ASN A 95 -4. ,911 11. ,887 9. 652 1. 00 35. 37 c
ATOM 746 OD1 ASN A 95 -5. ,961 12. ,340 10. ,123 1. ,00 36. 86 0
ATOM 747 ND2 ASN A 95 -4. ,684 10. ,586 9. 535 1. 00 34. 95 N
ATOM 748 N TYR A 96 -3. ,181 16. 096 7. 854 1. 00 33. 16 N
ATOM 749 CA TYR A 96 -2. ,272 17. ,219 7. 616 1. 00 32. 52 C
ATOM 750 C TYR A 96 -3. ,106 18. ,492 7. 595 1. 00 31. 59 C
ATOM 751 O TYR A 96 -3. 950 18. 681 6. 719 1. 00 31. 58 O
ATOM 752 CB TYR A 96 -1. 505 17. 067 6. 293 1. 00 32. 50 C ATOM 753 CG TYR A 96 0 684 15 793 6 168 1 00 32.98 C
ATOM 754 GDI TYR A 96 0 589 15 124 4 953 1 00 32 .82 c
ATOM 755 CD2 TYR A 96 0 004 15 261 7 257 1 00 33 .53 c
ATOM 756 CEl TYR A 96 0 163 13 958 4 829 1 00 33 77 c
ATOM 757 CE2 TYR A 96 0 754 14 078 7 145 1 00 33 .88 c
ATOM 758 CZ TYR A 96 0 833 13 438 5 928 1 00 34 01 c
ATOM 759 OH TYR A 96 1 573 12 273 5 796 1 00 36 25 0
ATOM 760 N SER A 97 2 880 19 346 8 581 1 00 30 72 N
ATOM 761 CA SER A 97 3 553 20 627 8 672 1 00 30 02 C
ATOM 762 C SER A 97 2 541 21 733 8 385 1 00 29 28 C
ATOM 763 O SER A 97 1 330 21 466 8 090 1 00 29 .12 0
ATOM 764 CB SER A 97 4 171 20 793 10 073 1 00 30 20 c
ATOM 765 OG SER A 97 5 560 21 058 9 980 1 00 30 59 0
ATOM 766 N LEU A 98 3 053 22 970 8 500 1 00 28 61 N
ATOM 767 CA LEU A 98 2 294 24 187 8 237 1 00 28 32 C
ATOM 768 C LEU A 98 2 146 25 042 9 499 1 00 27 54 C
ATOM 769 O LEU A 98 3 081 25 719 9 893 1 00 27 36 O
ATOM 770 CB LEU A 98 3 022 24 990 7 154 1 00 28 70 C
ATOM 771 CG LEU A 98 2 230 26 112 6 484 1 00 29 45 C
ATOM 772 GDI LEU A 98 2 319 25 982 4 986 1 00 30 13 C
ATOM 773 CD2 LEU A 98 2 737 27 483 6 936 1 00 30 42 c
ATOM 774 N LEU A 99 0 966 24 999 10 113 1 00 27 09 N
ATOM 775 CA LEU A 99 0 634 25 803 11 291 1 00 26 86 C
ATOM 776 C LEU A 99 0 334 27 232 10 848 1 00 26 50 C
ATOM 777 O LEU A 99 0 386 27 430 9 882 1 00 26 79 O
ATOM 778 CB LEU A 99 0 620 25 241 11 987 1 00 27 12 C
ATOM 779 CG LEU A 99 0 716 24 913 13 491 1 00 27 84 c
ATOM 780 CD1 LEU A 99 2 068 25 380 14 026 1 00 28 72 c
ATOM 781 CD2 LEU A 99 0 407 25 463 14 359 1 00 27 90 c
ATOM 782 N PHE A 100 0 873 28 225 11 539 1 00 25 62 N
ATOM 783 CA PHE A 100 0 539 29 617 11 225 1 00 25 27 C
ATOM 784 C PHE A 100 0 417 30 504 12 463 1 00 24 37 C
ATOM 785 O PHE A 100 1 028 30 246 13 492 1 00 23 75 O
ATOM 786 CB PHE A 100 1 508 30 206 10 188 1 00 25 37 C
ATOM 787 CG PHE A 100 2 881 30 528 10 719 1 00 25 83 C
ATOM 788 CD1 PHE A 100 3 156 31 790 11 251 1 00 25 42 c
ATOM 789 CD2 PHE A 100 3 911 29 597 10 632 1 00 25 10 c
ATOM 790 CEl PHE A 100 4 427 32 096 11 733 1 00 25 81 c
ATOM 791 CE2 PHE A 100 5 193 29 899 11 100 1 00 25 01 c
ATOM 792 CZ PHE A 100 5 458 31 150 11 643 1 00 25 23 c
ATOM 793 N ARG A 101 0 432 31 518 12 337 1 00 24 07 N
ATOM 794 CA ARG A 101 0 744 32 458 13 403 1 00 24 11 C
ATOM 795 C ARG A 101 0 453 33 293 13 822 1 00 22 64 C
ATOM 796 O ARG A 101 1 103 33 900 12 999 1 00 21 90 O
ATOM 797 CB ARG A 101 1 836 33 417 12 943 1 00 25 10 C
ATOM 798 CG ARG A 101 3 199 33 076 13 483 1 00 28 74 c
ATOM 799 CD ARG A 101 4 328 33 811 12 806 1 00 31 82 c
ATOM 800 NE ARG A 101 5 487 32 933 12 696 1 00 36 92 N
ATOM 801 CZ ARG A 101 6 334 32 670 13 693 1 00 40 20 C
ATOM 802 NH1 ARG A 101 7 359 31 849 13 489 1 00 42 57 N
ATOM 803 NH2 ARG A 101 6 172 33 215 14 891 1 00 40 80 N
ATOM 804 N GLY A 102 0 713 33 331 15 121 1 00 21 51 N
ATOM 805 CA GLY A 102 1 791 34 111 15 670 1 00 20 54 C
ATOM 806 C GLY A 102 1 254 35 330 16 398 1 00 20 64 C
ATOM 807 O GLY A 102 0 148 35 845 16 108 1 00 20 15 O
ATOM 808 N GLU A 103 2 040 35 777 17 366 1 00 20 11 N
ATOM 809 CA GLU A 103 1 764 37 023 18 082 1 00 20 21 C
ATOM 810 C GLU A 103 0 595 36 863 19 039 1 00 19 74 C
ATOM 811 O GLU A 103 0 319 35 778 19 539 1 00 19 27 O
ATOM 812 CB GLU A 103 3 005 37 520 18 834 1 00 20 37 C
ATOM 813 CG GLU A 103 4 122 38 017 17 910 1 00 19 56 C
ATOM 814 CD GLU A 103 4 997 36 877 17 407 1 00 20 62 C
ATOM 815 OEl GLU A 103 5 788 37 120 16 497 1 00 18 31 O
ATOM 816 OE2 GLU A 103 4 887 35 735 17 938 1 00 19 67 O ATOM 817 N LYS A 104 0,.105 37..962 19..236 1..00 19,.97 N
ATOM 818 CA LYS A 104 1. .308 38. .022 20. .041 1. .00 21, .39 C
ATOM 819 C LYS A 104 1. .005 38. .882 21. .252 1. .00 21, .45 C
ATOM 820 O LYS A 104 0. .296 39. .882 21. .145 1. .00 21, .44 O
ATOM 821 CB LYS A 104 2. .446 38. .656 19. ,216 1. .00 22, .22 C
ATOM 822 CG LYS A 104 3. .791 37. .935 19. ,294 1. .00 23, .77 C
ATOM 823 CD LYS A 104 4. .795 38. .501 18. .284 1. .00 25, .29 C
ATOM 824 CE LYS A 104 6. .247 38. .271 18. .753 1. .00 25, .29 C
ATOM 825 NZ LYS A 104 7, ,244 38. ,247 17. ,638 1. .00 24. .86 N
ATOM 826 N GLY A 105 1, ,549 38. ,506 22. ,406 1, .00 21, .96 N
ATOM 827 CA GLY A 105 1, ,483 39, .357 23. ,578 1, .00 21, .61 C
ATOM 828 C GLY A 105 2, ,263 40. ,654 23. ,371 1, .00 21. .52 C
ATOM 829 0 GLY A 105 3, .169 40. .740 22, ,540 1. .00 20. .89 O
ATOM 830 N ALA A 106 1, .939 41. .650 24, .176 1, .00 21, ,15 N
ATOM 831 CA ALA A 106 2. .552 42, .977 24, .030 1, .00 21. .77 C
ATOM 832 C ALA A 106 3. .948 43, .018 24, .648 1, ,00 21, .64 C
ATOM 833 O ALA A 106 4, .659 43, .974 24, .461 1. ,00 22. .09 O
ATOM 834 CB ALA A 106 1, .664 44, .046 24, .659 1, .00 21, ,61 C
ATOM 835 N GLY A 107 4. .325 41. .984 25, .395 1, .00 21. ,27 N
ATOM 836 CA GLY A 107 5, .678 41. .876 25, .896 1, .00 20, .82 C
ATOM 837 C GLY A 107 5. .816 42. .112 27, ,392 1, .00 20. .64 C
ATOM 838 O GLY A 107 4, .971 42. .748 28, ,029 1, .00 20, .50 O
ATOM 839 N THR A 108 6. .896 41. .549 27, ,927 1, .00 19, .91 N
ATOM 840 CA THR A 108 7. .362 41. .715 29, .291 1, ,00 19, .05 C
ATOM 841 C THR A 108 8, .815 42, .207 29, .235 1. ,00 18. .80 C
ATOM 842 O THR A 108 9, .673 41, .495 28. .703 1, ,00 18, .74 O
ATOM 843 CB THR A 108 7, ,367 40, .355 30. .019 1, ,00 18. .67 C
ATOM 844 OG1 THR A 108 6. .026 39, .840 30. .183 1, .00 19, .42 O
ATOM 845 CG2 THR A 108 7, .954 40. .510 31. .435 1. .00 18. .69 C
ATOM 846 N ALA A 109 9. .096 43, .390 29. .783 1, .00 18, .07 N
ATOM 847 CA ALA A 109 10, .460 43. .927 29. .825 1. .00 17, .50 C
ATOM 848 C ALA A 109 11, .078 43. .528 31. .144 1, .00 17, .58 C
ATOM 849 O ALA A 109 10, .755 44. .091 32. .198 1, .00 17. ,14 O
ATOM 850 CB ALA A 109 10, ,461 45, .464 29, ,673 1, .00 17, .07 C
ATOM 851 N LEU A 110 11, ,951 42. .536 31, .080 1, .00 17, ,82 N
ATOM 852 CA LEU A 110 12. ,601 42. ,003 32, .265 1, ,00 17, .96 C
ATOM 853 C LEU A 110 13. .973 42, .624 32, .467 1, ,00 18, ,14 C
ATOM 854 0 LEU A 110 14. .762 42. .710 31. ,550 1, ,00 17, .77 O
ATOM 855 CB LEU A 110 12. ,714 40. .481 32. .146 1, ,00 17, .52 C
ATOM 856 CG LEU A 110 13. .640 39. .772 33. .158 1. ,00 17, ,20 C
ATOM 857 CD1 LEU A 110 13. .102 39. .836 34, .603 1, ,00 16, .63 C
ATOM 858 CD2 LEU A 110 13. .878 38. ,331 32, ,704 1, ,00 16, .47 C
ATOM 859 N THR A 111 14. .245 43. .003 33, .709 1, .00 18, ,82 N
ATOM 860 CA THR A 111 15. ,523 43. ,520 34, .138 1. .00 19, ,38 C
ATOM 861 C THR A 111 16. .042 42, .609 35, .241 1, .00 19, .63 C
ATOM 862 O THR A 111 15. .412 42, .494 36. .289 1. .00 19, .13 O
ATOM 863 CB THR A 111 15. .319 44, .941 34. .690 1. .00 19, .40 C
ATOM 864 OG1 THR A 111 15. ,061 45, .835 33, .604 1. .00 19. .72 O
ATOM 865 CG2 THR A 111 16. .575 45, .478 35, .381 1, .00 19. .59 C
ATOM 866 N VAL A 112 17. .194 41. .977 35. .006 1. ,00 20, .01 N
ATOM 867 CA VAL A 112 17. .834 41, .153 36. .012 1. .00 20, .08 C
ATOM 868 C VAL A 112 19, .158 41, .763 36, .479 1. ,00 21. .01 C
ATOM 869 O VAL A 112 20, .018 42, .101 35. .663 1. ,00 20. .26 O
ATOM 870 CB VAL A 112 18, .107 39. .732 35. .497 1. ,00 20, .00 C
ATOM 871 CGI VAL A 112 18, ,756 38. .892 36, .586 1. ,00 19, .88 C
ATOM 872 CG2 VAL A 112 16. ,812 39. ,060 34, ,991 1. ,00 20. .28 C
ATOM 873 N LYS A 113 19, ,268 41. .953 37, ,792 1. ,00 21. .94 N
ATOM 874 CA LYS A 113 20, ,551 41. .895 38. ,508 1. ,00 23. .25 C
ATOM 875 C LYS A 113 20, .351 41. .882 40. ,024 1. ,00 23. .33 C
ATOM 876 O LYS A 113 20. .719 40. .909 40. ,703 1. ,00 23. .34 O
ATOM 877 CB LYS A 113 21. ,503 43. .027 38. .130 1. ,00 23. .42 C
ATOM 878 CG LYS A 113 22, ,819 43. ,037 38. .937 1. ,00 25, ,55 C
ATOM 879 CD LYS A 113 23. ,597 41. ,700 38. ,876 1. ,00 27. ,66 C
ATOM 880 CE LYS A 113 24. ,257 41. .325 40. ,233 1. ,00 27. ,87 C ATOM 881 NZ LYS A 113 23 252 40.985 41 318 1.00 27.98 N
TER 882 LYS A 113
ATOM 883 N ALA B 1 -5 294 52 .838 33 861 1 .00 15 59 N
ATOM 884 CA ALA B 1 -6 196 51 900 34 558 1 00 14 51 C
ATOM 885 C ALA B 1 -7 435 51 573 33 721 1 00 14 54 C
ATOM 886 O ALA B 1 -8 023 52 453 33 056 1 00 13 96 O
ATOM 887 CB ALA B 1 -6 596 52 455 35 882 1 00 15 29 C
ATOM 888 N TRP B 2 -7 792 50 292 33 747 1 00 13 89 N
ATOM 889 CA TRP B 2 -8 997 49 798 33 142 1 00 14 26 C
ATOM 890 C TRP B 2 -9 652 48 680 33 968 1 00 15 11 C
ATOM 891 O TRP B 2 -9 016 48 015 34 809 1 00 16 01 O
ATOM 892 CB TRP B 2 -8 729 49 330 31 723 1 00 14 66 C
ATOM 893 CG TRP B 2 -7 843 48 087 31 565 1 00 14 26 C
ATOM 894 CD1 TRP B 2 -6 506 47 993 31 797 1 00 14 52 C
ATOM 895 CD2 TRP B 2 -8 254 46 803 31 086 1 00 13 13 C
ATOM 896 NE1 TRP B 2 -6 056 46 727 31 499 1 00 15 51 N
ATOM 897 CE2 TRP B 2 -7 106 45 978 31 045 1 00 13 67 C
ATOM 898 CE3 TRP B 2 -9 473 46 271 30 660 1 00 12 74 C
ATOM 899 CZ2 TRP B 2 -7 144 44 653 30 609 1 00 14 07 C
ATOM 900 CZ3 TRP B 2 -9 515 44 948 30 232 1 00 14 11 C
ATOM 901 CH2 TRP B 2 -8 361 44 152 30 218 1 00 14 28 C
ATOM 902 N VAL B 3 10 946 48 523 33 743 1 00 14 74 N
ATOM 903 CA VAL B 3 11 725 47 514 34 399 1 00 14 76 C
ATOM 904 C VAL B 3 11 983 46 417 33 410 1 00 14 88 C
ATOM 905 O VAL B 3 12 581 46 644 32 364 1 00 14 62 0
ATOM 906 CB VAL B 3 13 048 48 039 34 946 1 00 14 64 c
ATOM 907 CGI VAL B 3 13 891 46 849 35 486 1 00 15 90 c
ATOM 908 CG2 VAL B 3 12 788 49 051 36 036 1 00 12 79 c
ATOM 909 N ASP B 4 11 493 45 224 33 765 1 00 14 91 N
ATOM 910 CA ASP B 4 11 605 44 027 32 955 1 00 15 16 c
ATOM 911 C ASP B 4 12 829 43 217 33 403 1 00 15 05 c
ATOM 912 O ASP B 4 12 789 42 529 34 422 1 00 15 65 0
ATOM 913 CB ASP B 4 10 314 43 231 33 119 1 00 14 69 c
ATOM 914 CG ASP B 4 10 240 42 019 32 220 1 00 15 63 c
ATOM 915 OD1 ASP B 4 11 195 41 730 31 457 1 00 13 74 0
ATOM 916 OD2 ASP B 4 -9 226 41 299 32 226 1 00 14 48 0
ATOM 917 N GLN B 5 13 917 43 340 32 650 1 00 15 33 N
ATOM 918 CA GLN B 5 15 213 42 752 33 000 1 00 15 77 C
ATOM 919 C GLN B 5 15 519 41 512 32 150 1 00 15 63 C
ATOM 920 O GLN B 5 15 503 41 581 30 946 1 00 15 80 O
ATOM 921 CB GLN B 5 16 339 43 795 32 845 1 00 15 67 C
ATOM 922 CG GLN B 5 17 760 43 235 33 121 1 00 16 80 c
ATOM 923 CD GLN B 5 18 885 44 261 32 983 1 00 17 15 c
ATOM 924 OEl GLN B 5 18 630 45 443 32 871 1 00 18 07 O
ATOM 925 NE2 GLN B 5 20 132 43 794 33 006 1 00 16 71 N
ATOM 926 N THR B 6 15 813 40 391 32 802 1 00 15 97 N
ATOM 927 CA THR B 6 16 163 39 147 32 127 1 00 15 83 C
ATOM 928 C THR B 6 17 374 38 489 32 805 1 00 16 25 C
ATOM 929 O THR B 6 17 561 38 649 34 004 1 00 15 50 O
ATOM 930 CB THR B 6 14 995 38 146 32 194 1 00 16 30 C
ATOM 931 OG1 THR B 6 14 547 38 023 33 550 1 00 15 78 O
ATOM 932 CG2 THR B 6 13 767 38 649 31 413 1 00 16 41 C
ATOM 933 N PRO B 7 18 176 37 721 32 068 1 00 16 95 N
ATOM 934 CA PRO B 7 18 021 37 519 30 628 1 00 17 42 C
ATOM 935 C PRO B 7 18 597 38 687 29 856 1 00 17. 85 C
ATOM 936 O PRO B 7 19 411 39 454 30 375 1 00 17 30 O
ATOM 937 CB PRO B 7 18 861 36 265 30 365 1 00 17. 52 C
ATOM 938 CG PRO B 7 19 937 36 316 31 380 1 00 17 28 C
ATOM 939 CD PRO B 7 19 324 36 967 32. 593 1 00 17. 21 C
ATOM 940 N ARG B 8 18 184 38 802 28 605 1 00 19 10 N
ATOM 941 CA ARG B 8 18 717 39 826 27. 719 1. 00 20. 43 C
ATOM 942 C ARG B 8 20 149 39 521 27 296 1 00 19. 68 C
ATOM 943 O ARG B 8 20 933 40 434 27. 059 1. 00 19. 82 O
ATOM 944 CB ARG B 8 17 823 39 985 26. 483 1 00 21. 79 C ATOM 945 CG ARG B 8 16.418 40.439 26.812 1.00 25.91 c
ATOM 946 CD ARG B 8 16 335 41 .781 27 546 1 00 31 .75 c
ATOM 947 NE ARG B 8 15 643 42 783 26 732 1 00 37 11 N
ATOM 948 CZ ARG B 8 16 233 43 675 25 925 1 00 40 95 C
ATOM 949 NH1 ARG B 8 17 563 43 759 25 817 1 00 42 20 N
ATOM 950 NH2 ARG B 8 15 475 44 500 25 209 1 00 42 21 N
ATOM 951 N THR B 9 20 468 38 243 27 163 1 00 19 30 N
ATOM 952 CA THR B 9 21 836 37 810 26 904 1 00 19 45 C
ATOM 953 C THR B 9 22 125 36 529 27 644 1 00 18 89 C
ATOM 954 O THR B 9 21 230 35 774 28 021 1 00 18 82 o
ATOM 955 CB THR B 9 22 125 37 537 25 389 1 00 19 83 c
ATOM 956 OG1 THR B 9 21 516 36 311 25 004 1 00 21 08 0
ATOM 957 CG2 THR B 9 21 487 38 550 24 454 1 00 20 14 c
ATOM 958 N ALA B 10 23 410 36 271 27 810 1 00 18 26 N
ATOM 959 CA ALA B 10 23 861 35 097 28 512 1 00 17 32 c
ATOM 960 C ALA B 10 25 289 34 832 28 117 1 00 17 20 c
ATOM 961 O ALA B 10 26 077 35 749 27 930 1 00 15 99 0
ATOM 962 CB ALA B 10 23 759 35 304 30 010 1 00 17 04 c
ATOM 963 N THR B 11 25 595 33 555 27 968 1 00 17 78 N
ATOM 964 CA THR B 11 26 949 33 102 27 803 1 00 18 49 C
ATOM 965 C THR B 11 27 249 32 171 28 946 1 00 19 15 C
ATOM 966 O THR B 11 26 481 31 250 29 230 1 00 19 45 O
ATOM 967 CB THR B 11 27 096 32 385 26 474 1 00 18 37 C
ATOM 968 OG1 THR B 11 27 013 33 355 25 429 1 00 19 62 0
ATOM 969 CG2 THR B 11 28 487 31 786 26 316 1 00 18 50 C
ATOM 970 N LYS B 12 28 381 32 425 29 587 1 00 19 79 N
ATOM 971 CA LYS B 12 28 833 31 655 30 718 1 00 20 44 C
ATOM 972 C LYS B 12 30 323 31 299 30 553 1 00 20 18 C
ATOM 973 O LYS B 12 31 035 31 916 29 776 1 00 19 79 O
ATOM 974 CB LYS B 12 28 588 32 465 31 998 1 00 20 72 C
ATOM 975 CG LYS B 12 27 432 31 942 32 858 1 00 22 57 C
ATOM 976 CD LYS B 12 26 102 32 568 32 529 1 00 24 40 C
ATOM 977 CE LYS B 12 24 953 31 573 32 674 1 00 25 84 C
ATOM 978 NZ LYS B 12 24 586 31 287 34 076 1 00 26 38 N
ATOM 979 N GLU B 13 30 763 30 282 31 275 1 00 20 44 N
ATOM 980 CA GLU B 13 32 173 29 910 31 332 1 00 20 98 C
ATOM 981 C GLU B 13 32 757 30 643 32 525 1 00 20 99 C
ATOM 982 O GLU B 13 32 003 31 058 33 409 1 00 20 59 O
ATOM 983 CB GLU B 13 32 321 28 404 31 536 1 00 21 11 C
ATOM 984 CG GLU B 13 31 536 27 530 30 561 1 00 22 38 C
ATOM 985 CD GLU B 13 32 114 27 528 29 159 1 00 22 84 C
ATOM 986 OEl GLU B 13 33 252 27 051 28 965 1 00 22 94 0
ATOM 987 OE2 GLU B 13 31 422 28 010 28 244 1 00 25 76 0
ATOM 988 N THR B 14 34 078 30 811 32 582 1 00 21 09 N
ATOM 989 CA THR B 14 34 654 31 436 33 772 1 00 21 59 C
ATOM 990 C THR B 14 34 457 30 448 34 910 1 00 22 01 C
ATOM 991 O THR B 14 34 570 29 236 34 713 1 00 21 49 O
ATOM 992 CB THR B 14 36 161 31 873 33 652 1 00 21 37 C
ATOM 993 OG1 THR B 14 37 020 30 818 34 079 1 00 21 82 O
ATOM 994 CG2 THR B 14 36 592 32 178 32 225 1 00 21 18 C
ATOM 995 N GLY B 15 34 098 30 970 36 082 1 00 22 66 N
ATOM 996 CA GLY B 15 33 883 30 142 37 256 1 00 23 26 C
ATOM 997 C GLY B 15 32 410 29 995 37 566 1 00 23 45 C
ATOM 998 O GLY B 15 32 033 29 909 38 729 1 00 23 59 0
ATOM 999 N GLU B 16 31 582 29 967 36 524 1 00 24. 06 N
ATOM 1000 CA GLU B 16 30 133 29 924 36 681 1 00 24 32 C
ATOM 1001 C GLU B 16 29 621 31 250 37 214 1 00 24. 70 C
ATOM 1002 O GLU B 16 30 382 32 215 37 327 1. 00 25. 07 O
ATOM 1003 CB GLU B 16 29 458 29 604 35 348 1 00 24. 49 C
ATOM 1004 CG GLU B 16 29. 883 28 252 34. 783 1. 00 24. 62 C
ATOM 1005 CD GLU B 16 28 994 27 748 33 659 1 00 25. 18 C
ATOM 1006 OEl GLU B 16 28. 404 28 574 32. 920 1. 00 23. 51 0
ATOM 1007 OE2 GLU B 16 28 906 26 505 33 503 1 00 27. 51 0
ATOM 1008 N SER B 17 28. 330 31 286 37. 538 1. 00 24. 45 N ATOM 1009 CA SER B 17 27 680 32 487 38 013 1 00 24 38 c
ATOM 1010 C SER B 17 26 524 32 917 37 097 1 00 23 43 c
ATOM 1011 O SER B 17 26 074 32 161 36 229 1 00 23 02 o
ATOM 1012 CB SER B 17 27 181 32 267 39 441 1 00 24 82 c
ATOM 1013 OG SER B 17 26 182 31 263 39 474 1 00 27 20 o
ATOM 1014 N LEU B 18 26 079 34 153 37 296 1 00 22 87 N
ATOM 1015 CA LEU B 18 24 952 34 742 36 565 1 00 22 89 C
ATOM 1016 C LEU B 18 23 964 35 355 37 532 1 00 22 41 C
ATOM 1017 O LEU B 18 24 365 36 105 38 414 1 00 22 16 O
ATOM 1018 CB LEU B 18 25 455 35 873 35 654 1 00 22 72 C
ATOM 1019 CG LEU B 18 24 729 36 314 34 379 1 00 23 50 c
ATOM 1020 CD1 LEU B 18 24 683 37 821 34 299 1 00 22 99 c
ATOM 1021 CD2 LEU B 18 23 348 35 686 34 150 1 00 24 23 c
ATOM 1022 N THR B 19 22 678 35 065 37 339 1 00 21 68 N
ATOM 1023 CA THR B 19 21 605 35 809 37 980 1 00 21 02 C
ATOM 1024 C THR B 19 20 890 36 641 36 923 1 00 19 99 C
ATOM 1025 O THR B 19 20 510 36 120 35 877 1 00 20 15 O
ATOM 1026 CB THR B 19 20 597 34 864 38 665 1 00 21 31 C
ATOM 1027 OG1 THR B 19 21 255 34 102 39 683 1 00 20 95 O
ATOM 1028 CG2 THR B 19 19 544 35 654 39 448 1 00 20 49 C
ATOM 1029 N ILE B 20 20 777 37 941 37 188 1 00 18 82 N
ATOM 1030 CA ILE B 20 19 940 38 853 36 425 1 00 18 18 C
ATOM 1031 C ILE B 20 18 750 39 217 37 289 1 00 17 93 C
ATOM 1032 O ILE B 20 18 909 39 593 38 456 1 00 16 31 O
ATOM 1033 CB ILE B 20 20 697 40 134 36 059 1 00 18 01 C
ATOM 1034 CGI ILE B 20 22 010 39 806 35 333 1 00 19 21 C
ATOM 1035 CG2 ILE B 20 19 791 41 077 35 275 1 00 17 59 C
ATOM 1036 CD1 ILE B 20 22 927 41 015 35 129 1 00 18 61 C
ATOM 1037 N ASN B 21 17 555 39 079 36 717 1 00 18 25 N
ATOM 1038 CA ASN B 21 16 320 39 372 37 423 1 00 18 53 C
ATOM 1039 C ASN B 21 15 681 40 625 36 827 1 00 17 94 C
ATOM 1040 O ASN B 21 15 519 40 729 35 600 1 00 17 76 O
ATOM 1041 CB ASN B 21 15 371 38 171 37 294 1 00 19 21 C
ATOM 1042 CG ASN B 21 15 909 36 916 37 998 1 00 20 45 C
ATOM 1043 OD1 ASN B 21 16 162 36 930 39 210 1 00 22 21 O
ATOM 1044 ND2 ASN B 21 16 098 35 841 37 241 1 00 20 12 N
ATOM 1045 N CYS B 22 15 288 41 537 37 707 1 00 17 20 N
ATOM 1046 CA CYS B 22 14 600 42 758 37 346 1 00 17 12 C
ATOM 1047 C CYS B 22 13 282 42 865 38 076 1 00 16 44 C
ATOM 1048 O CYS B 22 13 205 42 692 39 299 1 00 16 37 O
ATOM 1049 CB CYS B 22 15 478 43 958 37 653 1 00 17 80 C
ATOM 1050 SG CYS B 22 16 804 44 155 36 434 1 00 20 00 S
ATOM 1051 N VAL B 23 12 226 43 149 37 330 1 00 15 88 N
ATOM 1052 CA VAL B 23 10 920 43 356 37 919 1 00 15 42 C
ATOM 1053 C VAL B 23 10 391 44 710 37 454 1 00 15 65 C
ATOM 1054 O VAL B 23 10 316 44 989 36 242 1 00 14 61 O
ATOM 1055 CB VAL B 23 -9 939 42 248 37 497 1 00 15 66 C
ATOM 1056 CGI VAL B 23 -8 606 42 369 38 272 1 00 16 38 C
ATOM 1057 CG2 VAL B 23 10 572 40 871 37 674 1 00 17 32 C
ATOM 1058 N LEU B 24 -9 981 45 525 38 413 1 00 15 75 N
ATOM 1059 CA LEU B 24 -9 359 46 813 38 126 1 00 17 10 C
ATOM 1060 C LEU B 24 -7 861 46 601 37 940 1 00 16 81 C
ATOM 1061 O LEU B 24 -7 173 46 203 38 879 1 00 16 22 O
ATOM 1062 CB LEU B 24 -9 632 47 769 39 287 1 00 17 80 C
ATOM 1063 CG LEU B 24 -9 501 49 301 39 180 1 00 21 15 C
ATOM 1064 CD1 LEU B 24 -8 606 49 843 40 273 1 00 22 01 C
ATOM 1065 CD2 LEU B 24 -9 090 49 806 37 868 1 00 20 50 C
ATOM 1066 N ARG B 25 -7 380 46 916 36 739 1 00 16 84 N
ATOM 1067 CA ARG B 25 -6 028 46 650 36 300 1 00 17. 59 C
ATOM 1068 C ARG B 25 -5 231 47 898 35 946 1 00 18 31 C
ATOM 1069 O ARG B 25 -5 787 48 885 35 476 1 00 17. 08 0
ATOM 1070 CB ARG B 25 -6 094 45 782 35 057 1 00 17 34 C
ATOM 1071 CG ARG B 25 -6. 879 44 498 35. 348 1. 00 17. 33 C
ATOM 1072 CD ARG B 25 -6 852 43 502 34 297 1 00 13 60 C ATOM 1073 NE ARG B 25 -5 497 43 263 33.810 1.00 13.84 N
ATOM 1074 CZ ARG B 25 -5 222 42 392 32 860 1 00 11 .47 C
ATOM 1075 NH1 ARG B 25 -6 199 41 653 32 .333 1 .00 10 .08 N
ATOM 1076 NH2 ARG B 25 -3 982 42 241 32 449 1 00 9 .16 N
ATOM 1077 N ASP B 26 -3 915 47 804 36 .136 1 .00 19 .61 N
ATOM 1078 CA ASP B 26 -2 985 48 906 35 901 1 00 21 22 C
ATOM 1079 C ASP B 26 -3 494 50 171 36 568 1 00 21 82 C
ATOM 1080 O ASP B 26 -3 598 51 200 35 928 1 00 21 62 O
ATOM 1081 CB ASP B 26 -2 809 49 154 34 403 1 00 21 90 C
ATOM 1082 CG ASP B 26 -2 338 47 932 33 658 1 00 24 84 C
ATOM 1083 OD1 ASP B 26 -1 885 46 971 34 333 1 00 28 20 O
ATOM 1084 OD2 ASP B 26 -2 362 47 846 32 398 1 00 27 28 O
ATOM 1085 N ALA B 27 -3 843 50 068 37 847 1 00 22 97 N
ATOM 1086 CA ALA B 27 -4 447 51 166 38 590 1 00 23 99 C
ATOM 1087 C ALA B 27 -3 441 51 917 39 438 1 00 24 59 c
ATOM 1088 O ALA B 27 -2 510 51 332 39 989 1 00 25 39 0
ATOM 1089 CB ALA B 27 -5 545 50 662 39 473 1 00 24 37 c
ATOM 1090 N SER B 28 -3 656 53 223 39 532 1 00 24 85 N
ATOM 1091 CA SER B 28 -2 864 54 109 40 385 1 00 25 14 C
ATOM 1092 C SER B 28 -3 564 54 234 41 736 1 00 25 22 C
ATOM 1093 O SER B 28 -2 930 54 167 42 789 1 00 25 75 o
ATOM 1094 CB SER B 28 -2 719 55 492 39 742 1 00 24 69 c
ATOM 1095 OG SER B 28 -3 158 55 481 38 395 1 00 23 71 0
ATOM 1096 N PHE B 29 -4 881 54 398 41 687 1 00 25 03 N
ATOM 1097 CA PHE B 29 -5 667 54 683 42 872 1 00 24 87 c
ATOM 1098 C PHE B 29 -6 194 53 393 43 483 1 00 25 13 c
ATOM 1099 O PHE B 29 -6 483 52 430 42 776 1 00 25 12 0
ATOM 1100 CB PHE B 29 -6 813 55 629 42 510 1 00 24 68 c
ATOM 1101 CG PHE B 29 -6 347 56 966 41 964 1 00 24 08 c
ATOM 1102 CD1 PHE B 29 -5 477 57 755 42 688 1 00 23 02 c
ATOM 1103 CD2 PHE B 29 -6 780 57 423 40 732 1 00 22 29 c
ATOM 1104 CEl PHE B 29 -5 045 58 957 42 188 1 00 22 75 c
ATOM 1105 CE2 PHE B 29 -6 349 58 641 40 235 1 00 21 38 c
ATOM 1106 CZ PHE B 29 -5 492 59 402 40 960 1 00 21 68 c
ATOM 1107 N GLU B 30 -6 303 53 397 44 806 1 00 25 15 N
ATOM 1108 CA GLU B 30 -6 873 52 294 45 554 1 00 25 25 c
ATOM 1109 C GLU B 30 -8 365 52 275 45 326 1 00 24 28 c
ATOM 1110 O GLU B 30 -9 011 53 315 45 373 1 00 23 91 0
ATOM llll CB GLU B 30 -6 626 52 465 47 062 1 00 25 56 c
ATOM 1112 CG GLU B 30 -5 300 51 916 47 562 1 00 28 36 c
ATOM 1113 CD GLU B 30 -5 210 51 924 49 090 1 00 31 12 c
ATOM 1114 OEl GLU B 30 -4 192 52 404 49 626 1 00 33 68 o
ATOM 1115 OE2 GLU B 30 -6 167 51 464 49 765 1 00 33 34 0
ATOM 1116 N LEU B 31 -8 902 51 083 45 105 1 00 23 64 N
ATOM 1117 CA LEU B 31 10 335 50 901 44 925 1 00 23 41 C
ATOM 1118 C LEU B 31 11 025 51 255 46 232 1 00 23 46 c
ATOM 1119 O LEU B 31 10 698 50 690 47 260 1 00 22 93 0
ATOM 1120 CB LEU B 31 10 628 49 446 44 530 1 00 23 08 c
ATOM 1121 CG LEU B 31 12 086 49 084 44 216 1 00 22 85 c
ATOM 1122 CD1 LEU B 31 12 580 49 784 42 952 1 00 22 62 c
ATOM 1123 CD2 LEU B 31 12 209 47 591 44 057 1 00 21 60 c
ATOM 1124 N LYS B 32 11 931 52 229 46 195 1 00 23 73 N
ATOM 1125 CA LYS B 32 12 700 52 604 47 367 1 00 23 85 c
ATOM 1126 C LYS B 32 14 096 51 978 47 350 1 00 24 25 c
ATOM 1127 O LYS B 32 14 432 51 229 48 255 1 00 26 21 0
ATOM 1128 CB LYS B 32 12 803 54 124 47 507 1 00 24 04 c
ATOM 1129 CG LYS B 32 11 473 54 841 47 853 1 00 24 78 c
ATOM 1130 CD LYS B 32 10 603 54 086 48 865 1 00 25 77 c
ATOM 1131 CE LYS B 32 -9 387 54 910 49 284 1 00 27 06 c
ATOM 1132 NZ LYS B 32 -9 419 55 331 50 735 1 00 29 57 N
ATOM 1133 N ASP B 33 14 904 52 294 46 345 1 00 23 49 N
ATOM 1134 CA ASP B 33 16 296 51 860 46 288 1 00 22 67 C
ATOM 1135 C ASP B 33 16 550 51 276 44 893 1 00 21 88 C
ATOM 1136 O ASP B 33 15 689 51 354 44 023 1 00 21. 30 O ATOM 1137 CB ASP B 33 17 205 53 064 46 591 1 00 22 52 c
ATOM 1138 CG ASP B 33 18 693 52 694 46 790 1 00 23 90 c
ATOM 1139 OD1 ASP B 33 19 082 51 493 46 850 1 00 20 86 o
ATOM 1140 OD2 ASP B 33 19 560 53 589 46 897 1 00 26 09 0
ATOM 1141 N THR B 34 17 693 50 631 44 712 1 00 20 74 N
ATOM 1142 CA THR B 34 18 077 50 071 43 436 1 00 20 55 c
ATOM 1143 C THR B 34 19 533 50 336 43 181 1 00 20 18 c
ATOM 1144 O THR B 34 20 303 50 579 44 099 1 00 19 74 o
ATOM 1145 CB THR B 34 17 904 48 557 43 451 1 00 20 76 c
ATOM 1146 OG1 THR B 34 18 595 48 017 44 592 1 00 19 54 0
ATOM 1147 CG2 THR B 34 16 445 48 157 43 635 1 00 20 79 c
ATOM 1148 N GLY B 35 19 911 50 250 41 914 1 00 19 65 N
ATOM 1149 CA GLY B 35 21 296 50 368 41 521 1 00 19 23 c
ATOM 1150 C GLY B 35 21 562 49 486 40 318 1 00 18 79 c
ATOM 1151 O GLY B 35 20 674 49 157 39 555 1 00 18 14 0
ATOM 1152 N TRP B 36 22 815 49 103 40 182 1 00 18 24 N
ATOM 1153 CA TRP B 36 23 269 48 213 39 155 1 00 18 12 c
ATOM 1154 C TRP B 36 24 497 48 867 38 514 1 00 18 61 c
ATOM 1155 O TRP B 36 25 295 49 496 39 202 1 00 17 92 0
ATOM 1156 CB TRP B 36 23 589 46 867 39 787 1 00 17 76 c
ATOM 1157 CG TRP B 36 22 365 46 120 40 219 1 00 16 23 c
ATOM 1158 GDI TRP B 36 21 729 46 213 41 421 1 00 15 56 c
ATOM 1159 CD2 TRP B 36 21 621 45 167 39 445 1 00 16 02 c
ATOM 1160 NE1 TRP B 36 20 642 45 372 41 451 1 00 15 36 N
ATOM 1161 CE2 TRP B 36 20 540 44 728 40 247 1 00 16 32 C
ATOM 1162 CE3 TRP B 36 21 749 44 644 38 148 1 00 15 74 c
ATOM 1163 CZ2 TRP B 36 19 612 43 786 39 808 1 00 14 00 c
ATOM 1164 CZ3 TRP B 36 20 836 43 705 37 711 1 00 15 81 c
ATOM 1165 CH2 TRP B 36 19 770 43 290 38 537 1 00 15 63 c
ATOM 1166 N TYR B 37 24 595 48 738 37 190 1 00 19 18 N
ATOM 1167 CA TYR B 37 25 576 49 446 36 347 1 00 '19 61 C
ATOM 1168 C TYR B 37 26 075 48 525 35 243 1 00 19 35 C
ATOM 1169 O TYR B 37 25 336 47 676 34 777 1 00 18 84 O
ATOM 1170 CB TYR B 37 24 921 50 647 35 653 1 00 19 72 C
ATOM 1171 CG TYR B 37 24 347 51 638 36 617 1 00 21 51 C
ATOM 1172 CD1 TYR B 37 25 145 52 640 37 160 1 00 24 75 c
ATOM 1173 CD2 TYR B 37 23 021 51 554 37 023 1 00 22 63 c
ATOM 1174 CEl TYR B 37 24 633 53 547 38 079 1 00 25 58 c
ATOM 1175 CE2 TYR B 37 22 503 52 444 37 945 1 00 24 41 c
ATOM 1176 CZ TYR B 37 23 312 53 443 38 460 1 00 26 84 c
ATOM 1177 OH TYR B 37 22 810 54 333 39 372 1 00 30 18 0
ATOM 1178 N ARG B 38 27 312 48 713 34 802 1 00 19 09 N
ATOM 1179 CA ARG B 38 27 809 47 989 33 639 1 00 19 55 C
ATOM 1180 C ARG B 38 28 798 48 765 32 791 1 00 18 49 C
ATOM 1181 O ARG B 38 29 565 49 591 33 287 1 00 18 38 0
ATOM 1182 CB ARG B 38 28 469 46 674 34 044 1 00 19 81 c
ATOM 1183 CG ARG B 38 29 525 46 843 35 070 1 00 22 46 c
ATOM 1184 CD ARG B 38 30 798 46 162 34 774 1 00 25 60 c
ATOM 1185 NE ARG B 38 30 898 44 895 35 479 1 00 27 28 N
ATOM 1186 CZ ARG B 38 32 035 44 353 35 887 1 00 27 55 C
ATOM 1187 NH1 ARG B 38 33 193 44 976 35 690 1 00 29 81 N
ATOM 1188 NH2 ARG B 38 32 016 43 184 36 506 1 00 26 89 N
ATOM 1189 N THR B 39 28 749 48 467 31 501 1 00 17 65 N
ATOM 1190 CA THR B 39 29 814 48 769 30 572 1 00 17 38 C
ATOM 1191 C THR B 39 30 609 47 483 30 339 1 00 16 90 C
ATOM 1192 O THR B 39 30 148 46 579 29 661 1 00 16 35 O
ATOM 1193 CB THR B 39 29 211 49 268 29 255 1 00 17 27 C
ATOM 1194 OG1 THR B 39 28 274 50 310 29 534 1 00 17 58 O
ATOM 1195 CG2 THR B 39 30 287 49 925 28 355 1 00 17 17 C
ATOM 1196 N LYS B 40 31 803 47 394 30 906 1 00 16 71 N
ATOM 1197 CA LYS B 40 32 592 46 182 30 757 1 00 16 42 C
ATOM 1198 C LYS B 40 33 348 46 177 29 428 1 00 16 17 C
ATOM 1199 O LYS B 40 33 530 47 215 28 787 1 00 15 22 O
ATOM 1200 CB LYS B 40 33 525 45 964 31 949 1 00 16 51 C ATOM 1201 CG LYS B 40 34 574 47.016 32 136 1 00 18.21 c
ATOM 1202 CD LYS B 40 35 .245 46 .898 33 .506 1 .00 19 .27 c
ATOM 1203 CE LYS B 40 36 626 47 526 33 477 1 00 20 .69 c
ATOM 1204 NZ LYS B 40 37 .393 47 .282 34 .746 1 .00 22 .98 N
ATOM 1205 N LEU B 41 33 754 44 978 29 023 1 00 16 .05 N
ATOM 1206 CA LEU B 41 34 419 44 .741 27 .754 1 00 16 .04 C
ATOM 1207 C LEU B 41 35 694 45 576 27 639 1 00 16 .59 C
ATOM 1208 O LEU B 41 36 414 45 .783 28 .619 1 00 16 .92 O
ATOM 1209 CB LEU B 41 34 746 43 248 27 628 1 00 15 .95 c
ATOM 1210 CG LEU B 41 35 555 42 752 26 427 1 00 16 05 c
ATOM 1211 GDI LEU B 41 34 641 42 434 25 239 1 00 15 .75 c
ATOM 1212 CD2 LEU B 41 36 408 41 535 26 800 1 00 15 80 c
ATOM 1213 N GLY B 42 35 967 46 055 26 430 1 00 16 .75 N
ATOM 1214 CA GLY B 42 37 081 46 951 26 185 1 00 16 88 C
ATOM 1215 C GLY B 42 36 866 48 376 26 664 1 00 17 .13 C
ATOM 1216 O GLY B 42 37 767 49 201 26 530 1 00 17 20 O
ATOM 1217 N SER B 43 35 685 48 681 27 192 1 00 17 18 N
ATOM 1218 CA SER B 43 35 417 50 000 27 745 1 00 17 77 C
ATOM 1219 C SER B 43 34 087 50 586 27 256 1 00 18 27 C
ATOM 1220 O SER B 43 33 140 49 870 26 945 1 00 17 60 0
ATOM 1221 CB SER B 43 35 466 49 951 29 284 1 00 17 81 C
ATOM 1222 OG SER B 43 34 746 51 026 29 864 1 00 18 04 0
ATOM 1223 N THR B 44 34 042 51 910 27 217 1 00 19 66 N
ATOM 1224 CA THR B 44 32 907 52 670 26 711 1 00 21 11 c
ATOM 1225 C THR B 44 32 100 53 352 27 846 1 00 21 91 c
ATOM 1226 O THR B 44 31 000 53 871 27 624 1 00 22 34 0
ATOM 1227 CB THR B 44 33 454 53 681 25 660 1 00 21 50 c
ATOM 1228 OG1 THR B 44 32 669 53 614 24 459 1 00 23 73 0
ATOM 1229 CG2 THR B 44 33 377 55 141 26 129 1 00 21 82 c
ATOM 1230 N ASN B 45 32 628 53 319 29 066 1 00 22 83 N
ATOM 1231 CA ASN B 45 32 014 54 024 30 205 1 00 23 46 C
ATOM 1232 C ASN B 45 31 136 53 131 31 066 1 00 23 26 c
ATOM 1233 O ASN B 45 31 591 52 099 31 558 1 00 23 12 0
ATOM 1234 CB ASN B 45 33 106 54 667 31 077 1 00 23 67 c
ATOM 1235 CG ASN B 45 33 466 56 067 30 609 1 00 25 41 c
ATOM 1236 OD1 ASN B 45 34 592 56 322 30 178 1 00 26 74 0
ATOM 1237 ND2 ASN B 45 32 498 56 987 30 688 1 00 27 93 N
ATOM 1238 N GLU B 46 29 881 53 532 31 252 1 00 23 42 N
ATOM 1239 CA GLU B 46 28 997 52 825 32 171 1 00 23 74 C
ATOM 1240 C GLU B 46 29 372 53 162 33 610 1 00 23 50 C
ATOM 1241 O GLU B 46 29 600 54 324 33 967 1 00 23 84 O
ATOM 1242 CB GLU B 46 27 509 53 116 31 908 1 00 24 34 C
ATOM 1243 CG GLU B 46 26 610 52 000 32 432 1 00 25 93 C
ATOM 1244 CD GLU B 46 25 140 52 365 32 520 1 00 28 62 C
ATOM 1245 OEl GLU B 46 24 813 53 403 33 137 1 00 32 72 0
ATOM 1246 OE2 GLU B 46 24 306 51 589 32 008 1 00 28 07 0
ATOM 1247 N GLN B 47 29 421 52 125 34 431 1 00 23 10 N
ATOM 1248 CA GLN B 47 30 050 52 178 35 744 1 00 22 80 C
ATOM 1249 C GLN B 47 29 087 51 583 36 767 1 00 22 28 C
ATOM 1250 O GLN B 47 28 519 50 516 36 546 1 00 21 53 O
ATOM 1251 CB GLN B 47 31 325 51 328 35 716 1 00 23 05 C
ATOM 1252 CG GLN B 47 32 607 52 035 36 047 1 00 25 12 C
ATOM 1253 CD GLN B 47 33 784 51 074 36 091 1 00 27 20 C
ATOM 1254 OEl GLN B 47 33 945 50 234 35 192 1 00 28 88 O
ATOM 1255 NE2 GLN B 47 34 602 51 184 37 135 1 00 27 84 N
ATOM 1256 N SER B 48 28 922 52 265 37 890 1 00 21 60 N
ATOM 1257 CA SER B 48 28 186 51 721 39 010 1 00 21 63 C
ATOM 1258 C SER B 48 28 843 50 437 39 546 1 00 21 29 C
ATOM 1259 O SER B 48 30 048 50 361 39. 660 1. 00 20. 52 O
ATOM 1260 CB SER B 48 28 131 52 766 40 124 1. 00 22 04 C
ATOM 1261 OG SER B 48 27 498 52 228 41. 261 1. 00 23. 32 O
ATOM 1262 N ILE B 49 28 031 49 440 39 875 1. 00 21 21 N
ATOM 1263 CA ILE B 49 28. 505 48 225 40. 529 1. 00 21. 20 C
ATOM 1264 C ILE B 49 28 340 48 370 42 049 1. 00 21 46 C ATOM 1265 O ILE B 49 27 271 48 725 42 553 1 00 21 11 O
ATOM 1266 CB ILE B 49 27 713 46 980 40 005 1 00 21 53 C
ATOM 1267 CGI ILE B 49 27 996 46 756 38 511 1 00 20 53 c
ATOM 1268 CG2 ILE B 49 28 080 45 740 40 843 1 00 21 49 c
ATOM 1269 CD1 ILE B 49 27 027 45 830 37 797 1 00 '22 53 c
ATOM 1270 N SER B 50 29 409 48 078 42 774 1 00 22 04 N
ATOM 1271 CA SER B 50 29 406 48 084 44 233 1 00 22 35 C
ATOM 1272 C SER B 50 28 888 46 745 44 755 1 00 22 25 C
ATOM 1273 O SER B 50 29 509 45 708 44 539 1 00 22 62 O
ATOM 1274 CB SER B 50 30 823 48 335 44 765 1 00 22 21 c
ATOM 1275 OG SER B 50 30 800 49 354 45 746 1 00 23 43 0
ATOM 1276 N ILE B 51 27 744 46 771 45 428 1 00 22 47 N
ATOM 1277 CA ILE B 51 27 136 45 539 45 918 1 00 22 78 C
ATOM 1278 C ILE B 51 27 933 45 009 47 098 1 00 22 80 C
ATOM 1279 O ILE B 51 28 062 45 677 48 127 1 00 22 88 O
ATOM 1280 CB ILE B 51 25 635 45 742 46 289 1 00 22 82 C
ATOM 1281 CGI ILE B 51 24 833 46 198 45 059 1 00 22 79 C
ATOM 1282 CG2 ILE B 51 25 041 44 451 46 872 1 00 22 51 c
ATOM 1283 CD1 ILE B 51 25 034 45 335 43 799 1 00 23 44 c
ATOM 1284 N GLY B 52 28 470 43 808 46 922 1 00 23 07 N
ATOM 1285 CA GLY B 52 29 354 43 185 47 899 1 00 23 46 C
ATOM 1286 C GLY B 52 30 214 42 108 47 244 1 00 23 47 C
ATOM 1287 O GLY B 52 30 438 42 136 46 027 1 00 23 12 O
ATOM 1288 N GLY B 53 30 673 41 149 48 043 1 00 23 65 N
ATOM 1289 CA GLY B 53 31 579 40 111 47 571 1 00 24 06 C
ATOM 1290 C GLY B 53 30 945 39 186 46 542 1 00 24 34 C
ATOM 1291 O GLY B 53 29 968 38 492 46 838 1 00 24 13 O
ATOM 1292 N ARG B 54 31 513 39 178 45 334 1 00 24 75 N
ATOM 1293 CA ARG B 54 31 014 38 374 44 210 1 00 24 67 C
ATOM 1294 C ARG B 54 29 618 38 827 43 735 1 00 23 81 C
ATOM 1295 O ARG B 54 28 868 38 043 43 158 1 00 23 10 O
ATOM 1296 CB ARG B 54 32 004 38 433 43 027 1 00 24 89 C
ATOM 1297 CG ARG B 54 33 349 37 771 43 297 1 00 27 65 c
ATOM 1298 CD ARG B 54 34 212 37 530 42 032 1 00 30 21 c
ATOM 1299 NE ARG B 54 34 407 38 753 41 234 1 00 31 75 N
ATOM 1300 CZ ARG B 54 33 979 38 962 39 977 1 00 32 55 C
ATOM 1301 NH1 ARG B 54 33 278 38 042 39 305 1 00 33 03 N
ATOM 1302 NH2 ARG B 54 34 248 40 126 39 390 1 00 31 95 N
ATOM 1303 N TYR B 55 29 293 40 089 43 991 1 00 23 32 N
ATOM 1304 CA TYR B 55 28 022 40 699 43 607 1 00 23 27 C
ATOM 1305 C TYR B 55 26 985 40 714 44 741 1 00 22 65 C
ATOM 1306 O TYR B 55 27 022 41 627 45 569 1 00 23 40 O
ATOM 1307 CB TYR B 55 28 280 42 156 43 200 1 00 23 51 C
ATOM 1308 CG TYR B 55 29 332 42 366 42 128 1 00 25 16 C
ATOM 1309 GDI TYR B 55 30 554 42 974 42 433 1 00 27 40 C
ATOM 1310 CD2 TYR B 55 29 098 41 990 40 809 1 00 25 31 C
ATOM 1311 CEl TYR B 55 31 526 43 176 41 448 1 00 28 63 C
ATOM 1312 CE2 TYR B 55 30 052 42 193 39 814 1 00 27 21 C
ATOM 1313 CZ TYR B 55 31 262 42 784 40 136 1 00 29 16 C
ATOM 1314 OH TYR B 55 32 216 42 985 39 165 1 00 30 31 O
ATOM 1315 N VAL B 56 26 068 39 741 44 814 1 00 21 32 N
ATOM 1316 CA VAL B 56 25 013 39 817 45 831 1 00 20 28 C
ATOM 1317 C VAL B 56 23 637 40 141 45 224 1 00 19 36 C
ATOM 1318 O VAL B 56 23 141 39 458 44 307 1 00 18 27 O
ATOM 1319 CB VAL B 56 24 976 38 592 46 817 1 00 20 58 C
ATOM 1320 CGI VAL B 56 26 399 38 065 47 118 1 00 20 96 C
ATOM 1321 CG2 VAL B 56 24 080 37 497 46 328 1 00 21 01 C
ATOM 1322 N GLU B 57 23 075 41 249 45 707 1 00 18 11 N
ATOM 1323 CA GLU B 57 21 745 41 689 45 348 1 00 17 19 C
ATOM 1324 C GLU B 57 20 708 41 168 46 343 1 00 16 51 C
ATOM 1325 O GLU B 57 20 935 41 148 47 548 1 00 17 87 O
ATOM 1326 CB GLU B 57 21 689 43 211 45 299 1 00 17 51 C
ATOM 1327 CG GLU B 57 20 379 43 725 44 737 1 00 16 73 C
ATOM 1328 CD GLU B 57 20 183 45 223 44 875 1 00 17 23 C ATOM 1329 OEl GLU B 57 20 587 45 808 45 907 1 00 18 09 O
ATOM 1330 OE2 GLU B 57 19 597 45 818 43 938 1 00 13 96 0
ATOM 1331 N THR B 58 19 571 40 742 45 826 1 00 15 66 N
ATOM 1332 CA THR B 58 18 425 40 374 46 630 1 00 15 37 C
ATOM 1333 C THR B 58 17 281 41 269 46 156 1 00 15 05 C
ATOM 1334 O THR B 58 16 978 41 276 44 986 1 00 14 93 O
ATOM 1335 CB THR B 58 18 058 38 900 46 381 1 00 15 38 C
ATOM 1336 OG1 THR B 58 19 184 38 058 46 659 1 00 14 54 O
ATOM 1337 CG2 THR B 58 16 981 38 447 47 346 1 00 16 33 C
ATOM 1338 N VAL B 59 16 665 42 012 47 064 1 00 14 77 N
ATOM 1339 CA VAL B 59 15 529 42 862 46 748 1 00 15 29 C
ATOM 1340 C VAL B 59 14 298 42 387 47 510 1 00 15 36 C
ATOM 1341 O VAL B 59 14 342 42 194 48 728 1 00 14 34 0
ATOM 1342 CB VAL B 59 15 814 44 337 47 101 1 00 14 87 C
ATOM 1343 CGI VAL B 59 14 650 45 211 46 733 1 00 15 38 c
ATOM 1344 CG2 VAL B 59 17 081 44 826 46 388 1 00 16 71 c
ATOM 1345 N ASN B 60 13 209 42 205 46 767 1 00 16 17 N
ATOM 1346 CA ASN B 60 11 895 41 886 47 303 1 00 17 20 C
ATOM 1347 C ASN B 60 10 940 43 002 46 931 1 00 17 56 C
ATOM 1348 O ASN B 60 10 420 43 048 45 813 1 00 16 19 O
ATOM 1349 CB ASN B 60 11 397 40 536 46 770 1 00 17 33 C
ATOM 1350 CG ASN B 60 12 368 39 418 47 033 1 00 20 49 C
ATOM 1351 OD1 ASN B 60 12 978 38 869 46 103 1 00 27 00 O
ATOM 1352 ND2 ASN B 60 12 538 39 068 48 309 1 00 24 14 N
ATOM 1353 N LYS B 61 10 725 43 930 47 860 1 00 18 73 N
ATOM 1354 CA LYS B 61 -9 984 45 152 47 523 1 00 20 20 C
ATOM 1355 C LYS B 61 -8 524 44 868 47 247 1 00 20 68 C
ATOM 1356 O LYS B 61 -7 929 45 496 46 389 1 00 20 73 O
ATOM 1357 CB LYS B 61 10 056 46 190 48 628 1 00 20 55 C
ATOM 1358 CG LYS B 61 11 155 47 169 48 436 1 00 22 89 C
ATOM 1359 CD LYS B 61 11 078 48 286 49 467 1 00 26 16 c
ATOM 1360 CE LYS B 61 12 306 49 166 49 399 1 00 27 62 c
ATOM 1361 NZ LYS B 61 13 300 48 623 48 388 1 00 29 13 N
ATOM 1362 N GLY B 62 -7 961 43 930 47 994 1 00 21 46 N
ATOM 1363 CA GLY B 62 -6 559 43 575 47 852 1 00 22 44 C
ATOM 1364 C GLY B 62 -6 243 43 175 46 423 1 00 22 90 C
ATOM 1365 O GLY B 62 -5 297 43 708 45 842 1 00 24 02 O
ATOM 1366 N SER B 63 -7 067 42 279 45 874 1 00 22 81 N
ATOM 1367 CA SER B 63 -6 944 41 770 44 511 1 00 23 15 C
ATOM 1368 C SER B 63 -7 628 42 667 43 487 1 00 23 09 C
ATOM 1369 O SER B 63 -7 706 42 330 42 312 1 00 23 32 O
ATOM 1370 CB SER B 63 -7 550 40 373 44 429 1 00 23 09 C
ATOM 1371 OG SER B 63 -8 972 40 441 44 436 1 00 23 15 O
ATOM 1372 N LYS B 64 -8 154 ■ 43 793 43 960 1 00 22 85 N
ATOM 1373 CA LYS B 64 -8 785 44 801 43 138 1 00 22 19 C
ATOM 1374 C LYS B 64 -9 942 44 238 42 309 1 00 21 21 C
ATOM 1375 O LYS B 64 10 214 44 712 41 204 1 00 19 51 O
ATOM 1376 CB LYS B 64 -7 737 45 482 42 255 1 00 23 45 C
ATOM 1377 CG LYS B 64 -6 574 46 121 43 043 1 00 25 37 C
ATOM 1378 CD LYS B 64 -6 368 47 592 42 640 1 00 28 91 C
ATOM 1379 CE LYS B 64 -4 962 48 125 42 973 1 00 30 56 C
ATOM 1380 NZ LYS B 64 -4 919 49 645 42 954 1 00 31 78 N
ATOM 1381 N SER B 65 10 630 43 234 42 850 1 00 19 74 N
ATOM 1382 CA SER B 65 11 720 42 615 42 118 1 00 19 85 C
ATOM 1383 C SER B 65 13 073 42 732 42 831 1 00 18 80 C
ATOM 1384 O SER B 65 13 165 42 809 44 057 1 00 17 00 o
ATOM 1385 CB SER B 65 11 398 41 177 41 757 1 00 20 53 c
ATOM 1386 OG SER B 65 10 882 40 462 42 843 1 00 23 59 o
ATOM 1387 N PHE B 66 14 104 42 817 42. 010 1 00 18 42 N
ATOM 1388 CA PHE B 66 15 463 42 953 42 454 1 00 19 37 C
ATOM 1389 C PHE B 66 16 404 42 203 41. 511 1 00 19 75 C
ATOM 1390 O PHE B 66 16 303 '42 317 40 285 1 00 20 89 O
ATOM 1391 CB PHE B 66 15 867 44 435 42. 664 1 00 19 52 C
ATOM 1392 CG PHE B 66 15 477 45 392 41. 550 1 00 19. 35 C ATOM 1393 CD1 PHE B 66 14.162 45.594 41.201 1.00 19.89 c
ATOM 1394 CD2 PHE B 66 16 .447 46 173 40 942 1 00 22 .22 c
ATOM 1395 CEl PHE B 66 13 817 46 489 40 211 1 00 23 .28 c
ATOM 1396 CE2 PHE B 66 16 .121 47 079 39 .942 1 .00 22 .06 c
ATOM 1397 CZ PHE B 66 14 804 47 239 39 577 1 00 24 .56 c
ATOM 1398 N SER B 67 17 301 41 407 42 089 1 00 19 90 N
ATOM 1399 CA SER B 67 18 226 40 596 41 307 1 00 20 .00 C
ATOM 1400 C SER B 67 19 671 40 698 41 776 1 00 19 50 C
ATOM 1401 O SER B 67 19 .951 41 023 42 915 1 00 19 .54 O
ATOM 1402 CB SER B 67 17 786 39 139 41 278 1 00 19 89 C
ATOM 1403 OG SER B 67 17 691 38 597 42 569 1 00 23 57 0
ATOM 1404 N LEU B 68 20 580 40 428 40 848 1 00 18 79 N
ATOM 1405 CA LEU B 68 21 998 40 461 41 082 1 00 18 33 C
ATOM 1406 C LEU B 68 22 553 39 108 40 665 1 00 18 42 C
ATOM 1407 O LEU B 68 22 380 38 712 39 524 1 00 18 10 O
ATOM 1408 CB LEU B 68 22 615 41 528 40 194 1 00 18 09 C
ATOM 1409 CG LEU B 68 23 841 42 366 40 571 1 00 18 46 C
ATOM 1410 GDI LEU B 68 24 726 42 505 39 396 1 00 18 36 C
ATOM 1411 CD2 LEU B 68 24 609 41 922 41 814 1 00 17 75 C
ATOM 1412 N ARG B 69 23 194 38 406 41 587 1 00 18 74 N
ATOM 1413 CA ARG B 69 23 923 37 179 41 278 1 00 19 25 C
ATOM 1414 C ARG B 69 25 429 37 453 41 352 1 00 19 35 C
ATOM 1415 O ARG B 69 25 948 37 865 42 402 1 00 18 55 0
ATOM 1416 CB ARG B 69 23 547 36 057 42 238 1 00 19 56 c
ATOM 1417 CG ARG B 69 24 193 34 712 41 888 1 00 21 15 c
ATOM 1418 CD ARG B 69 23 508 33 525 42 544 1 00 23 00 c
ATOM 1419 NE ARG B 69 23 997 32 225 42 077 1 00 23 21 N
ATOM 1420 CZ ARG B 69 24 973 31 514 42 651 1 00 26 91 c
ATOM 1421 NH1 ARG B 69 25 607 31 945 43 746 1 00 27 11 N
ATOM 1422 NH2 ARG B 69 25 322 30 340 42 124 1 00 27 81 N
ATOM 1423 N ILE B 70 26 108 37 270 40 222 1 00 19 75 N
ATOM 1424 CA ILE B 70 27 553 37 452 40 117 1 00 20 46 C
ATOM 1425 C ILE B 70 28 187 36 081 40 074 1 00 20 76 C
ATOM 1426 O ILE B 70 27 852 35 304 39 201 1 00 19 79 O
ATOM 1427 CB ILE B 70 27 914 38 220 38 829 1 00 20 68 C
ATOM 1428 CGI ILE B 70 27 058 39 472 38 680 1 00 21 64 C
ATOM 1429 CG2 ILE B 70 29 385 38 622 38 815 1 00 20 79 C
ATOM 1430 CD1 ILE B 70 27 131 40 061 37 288 1 00 23 84 C
ATOM 1431 N SER B 71 29 106 35 794 41 013 1 00 21 41 N
ATOM 1432 CA SER B 71 29 778 34 489 41 114 1 00 22 13 C
ATOM 1433 C SER B 71 31 295 34 535 40 702 1 00 22 62 C
ATOM 1434 O SER B 71 31 913 35 609 40 661 1 00 22 56 O
ATOM 1435 CB SER B 71 29 633 33 953 42 548 1 00 22 67 C
ATOM 1436 OG SER B 71 30 156 34 874 43 500 1 00 22 85 O
ATOM 1437 N ASP B 72 31 867 33 370 40 373 1 00 23 13 N
ATOM 1438 CA ASP B 72 33 302 33 248 39 942 1 00 23 77 C
ATOM 1439 C ASP B 72 33 660 34 144 38 730 1 00 23 69 C
ATOM 1440 O ASP B 72 34 691 34 924 38 744 1 00 24 26 O
ATOM 1441 CB ASP B 72 34 234 33 567 41 120 1 00 23 85 C
ATOM 1442 CG ASP B 72 35 733 33 299 40 809 1 00 26 52 C
ATOM 1443 OD1 ASP B 72 36 086 32 403 39 975 1. 00 28 52 O
ATOM 1444 OD2 ASP B 72 36 650 33 939 41 381 1 00 27 73 O
ATOM 1445 N LEU B 73 32 763 34 051 37 704 1. 00 23 03 N
ATOM 1446 CA LEU B 73 32 827 34 936 36 552 1 00 22 50 C
ATOM 1447 C LEU B 73 34 185 34 813 35 870 1. 00 22 48 C
ATOM 1448 O LEU B 73 34 819 33 754 35. 886 1. 00 22. 20 O
ATOM 1449 CB LEU B 73 31 678 34 664 35 562 1. 00 22 31 C
ATOM 1450 CG LEU B 73 30 259 35 096 35. 998 1. 00 20. 96 C
ATOM 1451 GDI LEU B 73 29 192 34 406 35. 158 1. 00 21. 05 C
ATOM 1452 CD2 LEU B 73 30 062 36 598 35. 937 1. 00 20. 29 C
ATOM 1453 N ARG B 74 34 630 35. 917 35. 285 1. 00 22. 48 N
ATOM 1454 CA ARG B 74 35. 889 35. 960 34. 554 1. 00 22. 53 C
ATOM 1455 C ARG B 74 35 647 36. 673 33. 230 1. 00 21. 88 C
ATOM 1456 O ARG B 74 34. 612 37. 320 33. 046 1. 00 20. 92 0 ATOM 1457 CB ARG B 74 36 939 36.677 35.391 1.00 23.31 c
ATOM 1458 CG ARG B 74 36 941 36 233 36 866 1 .00 26 .36 c
ATOM 1459 CD ARG B 74 38 018 36 857 37 719 1 00 30 47 c
ATOM 1460 NE ARG B 74 37 625 38 189 38 197 1 00 33 .76 N
ATOM 1461 CZ ARG B 74 38 058 39 348 37 687 1 00 35 80 C
ATOM 1462 NH1 ARG B 74 37 633 40 495 38 218 1 00 36 67 N
ATOM 1463 NH2 ARG B 74 38 905 39 378 36 654 1 00 35 80 N
ATOM 1464 N VAL B 75 36 584 36 542 32 298 1 00 21 12 N
ATOM 1465 CA VAL B 75 36 404 37 117 30 966 1 00 20 73 C
ATOM 1466 C VAL B 75 36 158 38 627 31 034 1 00 20 51 C
ATOM 1467 0 VAL B 75 35 397 39 177 30 221 1 00 19 93 O
ATOM 1468 CB VAL B 75 37 606 36 808 30 050 1 00 20 73 C
ATOM 1469 CGI VAL B 75 37 525 37 604 28 740 1 00 20 89 C
ATOM 1470 CG2 VAL B 75 37 661 35 314 29 753 1 00 20 79 C
ATOM 1471 N GLU B 76 36 781 39 270 32 024 1 00 20 02 N
ATOM 1472 CA GLU B 76 36 723 40 717 32 209 1 00 20 19 C
ATOM 1473 C GLU B 76 35 321 41 208 32 623 1 00 19 74 C
ATOM 1474 O GLU B 76 35 004 42 382 32 440 1 00 20 00 O
ATOM 1475 CB GLU B 76 37 790 41 154 33 244 1 00 20 38 C
ATOM 1476 CG GLU B 76 37 555 42 511 33 904 1 00 22 07 C
ATOM 1477 CD GLU B 76 38 751 43 040 34 673 1 00 24 50 C
ATOM 1478 OEl GLU B 76 38 901 42 686 35 863 1 00 26 47 O
ATOM 1479 OE2 GLU B 76 39 544 43 817 34 087 1 00 26 87 0
ATOM 1480 N ASP B 77 34 504 40 314 33 185 1 00 19 27 N
ATOM 1481 CA ASP B 77 33 105 40 609 33 542 1 00 18 84 c
ATOM 1482 C ASP B 77 32 144 40 679 32 358 1 00 18 39 c
ATOM 1483 O ASP B 77 30 973 41 095 32 520 1 00 18 03 0
ATOM 1484 CB ASP B 77 32 572 39 564 34 531 1 00 19 00 c
ATOM 1485 CG ASP B 77 33 338 39 553 35 836 1 00 19 95 c
ATOM 1486 OD1 ASP B 77 33 747 40 645 36 287 1 00 20 99 0
ATOM 1487 OD2 ASP B 77 33 586 38 504 36 470 1 00 20 23 o
ATOM 1488 N SER B 78 32 603 40 255 31 183 1 00 17 22 N
ATOM 1489 CA SER B 78 31 825 40 445 29 973 1 00 17 27 C
ATOM 1490 C SER B 78 31 410 41 909 29 880 1 00 16 95 C
ATOM 1491 O SER B 78 32 182 42 808 30 218 1 00 17 21 0
ATOM 1492 CB SER B 78 32 623 40 060 28 714 1 00 17 26 c
ATOM 1493 OG SER B 78 33 040 38 701 28 749 1 00 17 63 0
ATOM 1494 N GLY B 79 30 195 42 147 29 405 1 00 16 58 N
ATOM 1495 CA GLY B 79 29 696 43 501 29 261 1 00 16 32 C
ATOM 1496 C GLY B 79 28 197 43 570 29 333 1 00 15 94 C
ATOM 1497 O GLY B 79 27 520 42 550 29 407 1 00 15 54 O
ATOM 1498 N THR B 80 27 679 44 788 29 314 1 00 15 66 N
ATOM 1499 CA THR B 80 26 253 45 004 29 385 1 00 15 73 C
ATOM 1500 C THR B 80 25 903 45 522 30 770 1 00 15 82 C
ATOM 1501 O THR B 80 26 410 46 558 31 193 1 00 16 07 0
ATOM 1502 CB THR B 80 25 830 45 984 28 287 1 00 15 80 C
ATOM 1503 OG1 THR B 80 26 002 45 369 27 000 1 00 15 74 0
ATOM 1504 CG2 THR B 80 24 334 46 296 28 374 1 00 15 85 C
ATOM 1505 N TYR B 81 25 045 44 774 31 461 1 00 15 97 N
ATOM 1506 CA TYR B 81 24 585 45 082 32 807 1 00 16 35 C
ATOM 1507 C TYR B 81 23 181 45 663 32 775 1 00 16 12 C
ATOM 1508 O TYR B 81 22 326 45 216 31 999 1 00 16 10 O
ATOM 1509 CB TYR B 81 24 590 43 808 33 669 1 00 16 87 C
ATOM 1510 CG TYR B 81 25 986 43 276 33 931 1 00 17 11 c
ATOM 1511 CD1 TYR B 81 26 565 43 384 35 186 1 00 16 85 c
ATOM 1512 CD2 TYR B 81 26 739 42 686 32 916 1 00 16 44 c
ATOM 1513 CEl TYR B 81 27 856 42 911 35 443 1 00 15 57 c
ATOM 1514 CE2 TYR B 81 28 051 42 219 33. 163 1 00 15 21 c
ATOM 1515 CZ TYR B 81 28 596 42 326 34 431 1 00 14 59 c
ATOM 1516 OH TYR B 81 29 886 41. 875 34. 722 1. 00 12. 32 0
ATOM 1517 N LYS B 82 22 943 46 662 33 611 1 00 16 11 N
ATOM 1518 CA LYS B 82 21 618 47 268 33. 736 1. 00 16. 55 C
ATOM 1519 C LYS B 82 21 290 47 528 35. 202 1 00 16 62 C
ATOM 1520 O LYS B 82 22 154 47. 904 35. 987 1. 00 17. 10 0 ATOM 1521 CB LYS B 82 -21.543 48.567 32.938 00 16.71 C
ATOM 1522 CG LYS B 82 -21.334 48.337 31.463 00 17.46 C
ATOM 1523 CD LYS B 82 -21.201 49.623 30.709 00 18.30 C
ATOM 1524 CE LYS B 82 -21.401 49.380 29.236 00 19.09 C
ATOM 1525 NZ LYS B 82 -21.113 50.617 28.492 00 21.44 N
ATOM 1526 N CYS B 83 -20.036 47.301 35.550 00 16.49 N
ATOM 1527 CA CYS B 83 -19.504 47.644 36.852 1.00 17.38 C
ATOM 1528 C CYS B 83 -18.682 48.929 36.761 00 17.36 C
ATOM 1529 O CYS B 83 -18.203 49.275 35.699 00 18.22 O
ATOM 1530 CB CYS B 83 -18.606 46.514 37.328 00 18.04 C
ATOM 1531 SG CYS B 83 -17.223 46.143 36.230 00 19.55 S
ATOM 1532 N GLN B 84 -18.522 49.647 37.862 00 17.20 N
ATOM 1533 CA GLN B 84 -17.693 50.849 37.870 00 17.02 C
ATOM 1534 C GLN B 84 -16.913 50.936 39.156 00 16.97 C
ATOM 1535 O GLN B 84 -17.444 50.623 40.223 00 16.56 O
ATOM 1536 CB GLN B 84 -18.525 52.109 37.748 00 17.35 C
ATOM 1537 CG GLN B 84 -17.666 53.383 37.630 00 18.26 C
ATOM 1538 CD GLN B 84 -18.275 54.425 36.724 00 20.08 C
ATOM 1539 OEl GLN B 84 -17.572 55.069 35.941 00 23.24 O
ATOM 1540 NE2 GLN B 84 -19.570 54.603 36.828 00 18.52 N
ATOM 1541 N ALA B 85 -15.653 51.358 39.031 00 16.63 N
ATOM 1542 CA ALA B 85 -14.775 51.612 40.166 00 16.67 C
ATOM 1543 C ALA B 85 -14.937 53.058 40.599 00 16.25 C
ATOM 1544 O ALA B 85 -15.165 53.933 39.767 00 16.09 O
ATOM 1545 CB ALA B 85 -13.288 51.341 39.783 1.00 16.01 C
ATOM 1546 N PHE B 86 -14.767 53.283 41.897 00 16.14 N
ATOM 1547 CA PHE B 86 -14.710 54.606 42.488 00 16.71 C
ATOM 1548 C PHE B 86 -13.449 54.774 43.339 00 16.53 C
ATOM 1549 O PHE B 86 -12.977 53.828 43.967 00 15.05 o
ATOM 1550 CB PHE B 86 -15.910 54.831 43.403 00 17.17 c
ATOM 1551 CG PHE B 86 -17.195 54.931 42.676 00 ,63 c
ATOM 1552 CD1 PHE B 86 -17.871 53.797 42.296 00 73 c
ATOM 1553 CD2 PHE B 86 -17.730 56.170 42.371 00 21.86 c
ATOM 1554 CEl PHE B 86 -19.047 53.881 41.600 00 20.98 c
ATOM 1555 CE2 PHE B 86 -18.916 56.265 41.679 00 23.65 c
ATOM 1556 CZ PHE B 86 -19.578 55.103 41.290 00 22.79 c
ATOM 1557 N TYR B 87 -12.961 56.014 43.379 00 17.00 N
ATOM 1558 CA TYR B 87 -11.781 56.396 44.122 00 17.28 C
ATOM 1559 C TYR B 87 -12.120 57.517 45.070 00 18.27 C
ATOM 1560 O TYR B 87 -13.229 58.030 45.038 00 17.26 0
ATOM 1561 CB TYR B 87 -10.746 56.915 43.139 00 17.73 c
ATOM 1562 CG TYR B 87 -10.346 55.916 42.097 00 16.88 c
ATOM 1563 CD1 TYR B 87 -10.367 56.245 40.752 00 17.20 c
ATOM 1564 CD2 TYR B 87 -9.946 54.629 42.459 00 17.73 c
ATOM 1565 CEl TYR B 87 -9.982 55.327 39.782 00 17.23 c
ATOM 1566 CE2 TYR B 87 -9.553 53.697 41.496 00 18.63 c
ATOM 1567 CZ TYR B 87 -9.577 54.054 40.154 00 18.65 c
ATOM 1568 OH TYR B 87 -9.190 53.137 39.183 00 19.23 0
ATOM 1569 N SER B 88 -11.152 57.919 45.891 00 19.12 N
ATOM 1570 CA SER B 88 -11.294 59.134 46.674 00 20.75 c
ATOM 1571 C SER B 88 -9.993 59.942 46.761 00 22.29 c
ATOM 1572 O SER B 88 -8.890 59.421 46.612 00 22.12 o
ATOM 1573 CB SER B 88 -11.789 58.819 48.096 00 20.72 c
ATOM 1574 OG SER B 88 -10.788 58.145 48.827 00 20.04 0
ATOM 1575 N LEU B 89 -10.139 61.227 47.018 00 24.28 N
ATOM 1576 CA LEU B 89 -8.987 62.040 47.362 00 26.19 C
ATOM 1577 C LEU B 89 -9.266 62.856 48.625 00 27.08 C
ATOM 1578 O LEU B 89 -10.419 63.118 48.968 00 26.58 O
ATOM 1579 CB LEU B 89 -8.557 62.907 46.171 00 26.68 C
ATOM 1580 CG LEU B 89 -9.445 64.001 45.544 00 28.47 C
ATOM 1581 CD1 LEU B 89 -9.280 63.988 44.028 00 28.80 C
ATOM 1582 CD2 LEU B 89 -10.922 63.909 45.883 00 29.53 C
ATOM 1583 N PRO B . 90 -8.223 63.187 49.372 00 28.97 N
ATOM 1584 CA PRO B 90 -8.336 64.275 50.351 1.00 29.81 C ATOM 1585 C PRO B 90 -8 264 65 614 49 611 1 00 30 96 c
ATOM 1586 O PRO B 90 -7 366 65 718 48 772 1 00 31 41 0
ATOM 1587 CB PRO B 90 -7 118 64 072 51 260 1 00 29 62 c
ATOM 1588 CG PRO B 90 -6 516 62 752 50 856 1 00 29 50 c
ATOM 1589 CD PRO B 90 -6 899 62 539 49 417 1 00 29 26 c
ATOM 1590 N LEU B 91 -9 127 66 610 49 864 1 00 32 14 N
ATOM 1591 CA LEU B 91 10 181 66 619 50 890 1 00 32 64 c
ATOM 1592 C LEU B 91 -9 654 66 206 52 261 1 00 32 94 c
ATOM 1593 O LEU B 91 -9 912 65 096 52 744 1 00 33 37 o
ATOM 1594 CB LEU B 91 11 402 65 789 50 453 1 00 33 03 c
ATOM 1595 CG LEU B 91 12 780 66 333 50 876 1 00 33 50 c
ATOM 1596 CD1 LEU B 91 12 873 66 545 52 382 1 00 33 54 c
ATOM 1597 CD2 LEU B 91 13 093 67 641 50 143 1 00 33 79 c
ATOM 1598 N GLY B 92 -8 924 67 132 52 874 1 00 32 78 N
ATOM 1599 CA GLY B 92 -8 174 66 865 54 078 1 00 32 66 C
ATOM 1600 C GLY B 92 -8 970 67 126 55 336 1 00 32 67 C
ATOM 1601 O GLY B 92 -8 948 68 230 55 894 1 00 31 99 0
ATOM 1602 N ASP B 93 -9 696 66 098 55 765 1 00 32 42 N
ATOM 1603 CA ASP B 93 10 223 66 050 57 131 1 00 32 02 C
ATOM 1604 C ASP B 93 10 482 64 577 57 505 1 00 31 47 C
ATOM 1605 O ASP B 93 10 682 63 721 56 621 1 00 30 74 O
ATOM 1606 CB ASP B 93 11 468 66 936 57 272 1 00 32 07 C
ATOM 1607 CG ASP B 93 12 260 66 640 58 522 1 00 32 22 C
ATOM 1608 OD1 ASP B 93 13 295 65 950 58 415 1 00 32 43 O
ATOM 1609 OD2 ASP B 93 11 915 67 035 59 657 1 00 33 64 0
ATOM 1610 N TYR B 94 10 421 64 287 58 808 1 00 30 71 N
ATOM 1611 CA TYR B 94 10 430 62 905 59 294 1 00 30 32 C
ATOM 1612 C TYR B 94 11 721 62 175 58 944 1 00 29 29 C
ATOM 1613 O TYR B 94 11 677 61 040 58 486 1 00 29 11 O
ATOM 1614 CB TYR B 94 10 162 62 821 60 811 1 00 30 66 C
ATOM 1615 CG TYR B 94 10 018 61 390 61 314 1 00 32 23 C
ATOM 1616 CD1 TYR B 94 -9 185 60 479 60 655 1 00 33 94 C
ATOM 1617 CD2 TYR B 94 10 733 60 939 62 426 1 00 33 45 c
ATOM 1618 CEl TYR B 94 -9 055 59 166 61 099 1 00 34 92 c
ATOM 1619 CE2 TYR B 94 10 611 59 618 62 878 1 00 34 33 c
ATOM 1620 CZ TYR B 94 -9 769 58 736 62 208 1 00 35 76 c
ATOM 1621 OH TYR B 94 -9 635 57 423 62 629 1 00 37 28 0
ATOM 1622 N ASN B 95 12 862 62 829 59 137 1 00 28 16 N
ATOM 1623 CA ASN B 95 14 144 62 221 58 784 1 00 27 21 C
ATOM 1624 C ASN B 95 14 461 62 276 57 279 1 00 26 08 C
ATOM 1625 O ASN B 95 15 162 61 393 56 787 1 00 26 22 O
ATOM 1626 CB ASN B 95 15 296 62 844 59 58'9 1 00 27 50 c
ATOM 1627 CG ASN B 95 15 025 62 868 61 093 1 00 28 06 c
ATOM 1628 OD1 ASN B 95 15 185 61 861 61 784 1 00 29 15 0
ATOM 1629 ND2 ASN B 95 14 616 64 025 61 600 1 00 28 91 N
ATOM 1630 N TYR B 96 13 931 63 265 56 545 1 00 24 35 N
ATOM 1631 CA TYR B 96 14 346 63 501 55 145 1 00 23 11 c
ATOM 1632 C TYR B 96 13 270 63 343 54 042 1 00 21 64 c
ATOM 1633 O TYR B 96 12 145 63 812 54 171 1 00 21 25 0
ATOM 1634 CB TYR B 96 15 001 64 882 55 013 1 00 23 06 c
ATOM 1635 CG TYR B 96 16 167 65 107 55 963 1 00 24 50 c
ATOM 1636 GDI TYR B 96 16 118 66 099 56 952 1 00 25 24 c
ATOM 1637 CD2 TYR B 96 17 317 64 335 '55 879 1 00 24 87 c
ATOM 1638 CEl TYR B 96 17 191 66 306 57 827 1 00 25. 86 c
ATOM 1639 CE2 TYR B 96 18 398 64 535 56 754 1 00 25 97 c
ATOM 1640 CZ TYR B 96 18 330 65 520 57 722 1 00 26 29 c
ATOM 1641 OH TYR B 96 19 395 65 713 58 586 1 00 26. 82 0
ATOM 1642 N SER B 97 13 655 62 674 52 960 1 00 20 03 N
ATOM 1643 CA SER B 97 12 905 62 653 51 699 1 00 19. 27 c
ATOM 1644 C SER B 97 13 869 62 771 50 523 1 00 18. 44 c
ATOM 1645 O SER B 97 15 080 62 683 50 680 1 00 17 65 0
ATOM 1646 CB SER B 97 12 097 61 357 51 533 1 00 19. 13 c
ATOM 1647 OG SER B 97 10 972 61 327 52 399 1 00 19. 63 0
ATOM 1648 N LEU B 98 13 328 62 982 49. 336 1. 00 18. 23 N ATOM 1649 CA LEU B 98 14 162 63 093 48 161 1 00 18.60 C
ATOM 1650 C LEU B 98 14 082 61 839 47 355 1 00 17 81 c
ATOM 1651 O LEU B 98 13 018 61 400 46 967 1 .00 17 .98 o
ATOM 1652 CB LEU B 98 13 761 64 271 47 287 1 00 19 46 c
ATOM 1653 CG LEU B 98 14 959 65 100 46 824 1 00 20 85 c
ATOM 1654 CD1 LEU B 98 15 248 66 226 47 810 1 00 20 64 c
ATOM 1655 CD2 LEU B 98 14 699 65 623 45 416 1 00 22 29 c
ATOM 1656 N LEU B 99 15 243 61 265 47 125 1 00 17 .25 N
ATOM 1657 CA LEU B 99 15 387 60 098 46 297 1 00 17 01 c
ATOM 1658 C LEU B 99 15 487 60 578 44 854 1 00 16 38 c
ATOM 1659 O LEU B 99 16 166 61 556 44 576 1 00 15 68 0
ATOM 1660 CB LEU B 99 16 682 59 387 46 654 1 00 17 31 c
ATOM 1661 CG LEU B 99 16 740 57 946 47 140 1 00 19 55 c
ATOM 1662 CD1 LEU B 99 18 108 57 398 46 718 1 00 21 25 c
ATOM 1663 CD2 LEU B 99 15 627 57 043 46 660 1 00 18 90 c
ATOM 1664 N PHE B 100 14 822 59 892 43 941 1 00 15 94 N
ATOM 1665 CA PHE B 100 14 995 60 202 42 535 1 00 16 65 c
ATOM 1666 C PHE B 100 15 046 58 977 41 629 1 00 16 49 c
ATOM 1667 O PHE B 100 14 625 57 896 41 988 1 00 16 43 0
ATOM 1668 CB PHE B 100 13 986 61 265 42 045 1 00 16 45 c
ATOM 1669 CG PHE B 100 12 550 60 818 42 013 1 00 16 97 c
ATOM 1670 GDI PHE B 100 11 938 60 466 40 810 1 00 18 14 c
ATOM 1671 CD2 PHE B 100 11 788 60 798 43 176 1 00 16 86 c
ATOM 1672 CEl PHE B 100 10 582 60 077 40 771 1 00 17 07 c
ATOM 1673 CE2 PHE B 100 10 445 60 405 43 145 1 00 18 19 c
ATOM 1674 CZ PHE B 100 -9 840 60 053 41 930 1 00 17 19 c
ATOM 1675 N ARG B 101 15 608 59 200 40 450 1 00 17 08 N
ATOM 1676 CA ARG B 101 15 884 58 172 39 477 1 00 17 76 c
ATOM 1677 C ARG B 101 14 597 57 728 38 822 1 00 17 11 c
ATOM 1678 O ARG B 101 13 847 58 555 38 310 1 00 16 40 0
ATOM 1679 CB ARG B 101 16 824 58 737 38 395 1 00 18 57 c
ATOM 1680 CG ARG B 101 18 056 57 886 38 135 1 00 21 82 c
ATOM 1681 CD ARG B 101 19 196 58 631 37 439 1 00 24 74 c
ATOM 1682 NE ARG B 101 20 327 58 826 38 341 1 00 27 71 N
ATOM 1683 CZ ARG B 101 21 194 57 878 38 692 1 00 28 04 ■C
ATOM 1684 NH1 ARG B 101 21 081 56 639 38 235 1 00 29 97 N
ATOM 1685 NH2 ARG B 101 22 187 58 174 39 515 1 00 30 47 N
ATOM 1686 N GLY B 102 14 378 56 415 38 808 1 00 16 71 N
ATOM 1687 CA GLY B 102 13 265 55 820 38 094 1 00 16 36 C
ATOM 1688 C GLY B 102 13 731 55 107 36 836 1 00 16 19 C
ATOM 1689 O GLY B 102 14 804 55 376 36 305 1 00 15 43 O
ATOM 1690 N GLU B 103 12 947 54 131 36 411 1 00 15 92 N
ATOM 1691 CA GLU B 103 13 155 53 459 35 126 1 00 16 00 C
ATOM 1692 C GLU B 103 14 294 52 456 35 219 1 00 16 23 C
ATOM 1693 O GLU B 103 14 661 52 007 36 297 1 00 14 93 O
ATOM 1694 CB GLU B 103 11 882 52 731 34 703 1 00 15 57 C
ATOM 1695 CG GLU B 103 10 726 53 669 34 411 1 00 16 30 C
ATOM 1696 CD GLU B 103 -9 986 54 115 35 652 1 00 16 19 c
ATOM 1697 OEl GLU B 103 -9 137 54 998 35 508 1 00 16 39 0
ATOM 1698 OE2 GLU B 103 10 260 53 592 36 777 1 00 15 82 0
ATOM 1699 N LYS B 104 14 828 52 096 34 063 1 00 17 04 N
ATOM 1700 CA LYS B 104 16 031 51 299 33 978 1 00 17 92 C
ATOM 1701 C LYS B 104 15 728 50 063 33 124 1 00 17 90 C
ATOM 1702 O LYS B 104 14 934 50 121 32 169 1 00 16 60 O
ATOM 1703 CB LYS B 104 17 150 52 159 33. 363 1 00 18 66 C
ATOM 1704 CG LYS B 104 18 552 51 885 33 857 1 00 21 78 C
ATOM 1705 CD LYS B 104 19 605 52 757 33 118 1 00 24 78 c
ATOM 1706 CE LYS B 104 21 036 52 466 33 580 1 00 25 87 c
ATOM 1707 NZ LYS B 104 22 126 53 297 32. 887 1 00 28 01 N
ATOM 1708 N GLY B 105 16 362 48 942 33. 484 1. 00 17. 73 N
ATOM 1709 CA GLY B 105 16 316 47 745 32. 677 1 00 17 68 C
ATOM 1710 C GLY B 105 16 960 47 943 31. 323 1. 00 17. 40 C
ATOM 1711 O GLY B 105 17. 822 48. 799 31. 162 1. 00 17. 93 0
ATOM 1712 N ALA B 106 16 523 47 159 30. 343 1. 00 16. 99 N ATOM 1713 CA ALA B 106 17 004 47 300 28 969 1 00 17 63 c
ATOM 1714 C ALA B 106 18 384 46 692 28 753 1 00 17 50 c
ATOM 1715 O ALA B 106 18 974 46 949 27 732 1 00 17 21 0
ATOM 1716 CB ALA B 106 16 013 46 688 27 977 1 00 17 39 c
ATOM 1717 N GLY B 107 18 860 45 882 29 704 1 00 17 48 N
ATOM 1718 CA GLY B 107 20 216 45 352 29 709 1 00 17 63 c
ATOM 1719 C GLY B 107 20 338 43 833 29 604 1 00 17 28 c
ATOM 1720 O GLY B 107 19 452 43 160 29 110 1 00 17 81 0
ATOM 1721 N THR B 108 21 478 43 316 30 052 1 00 17 48 N
ATOM 1722 CA THR B 108 21 879 41 917 29 908 1 00 16 91 c
ATOM 1723 C THR B 108 23 251 41 948 29 289 1 00 16 96 c
ATOM 1724 O THR B 108 24 159 42 543 29 874 1 00 16 69 0
ATOM 1725 CB THR B 108 22 010 41 208 31 293 1 00 16 78 c
ATOM 1726 OG1 THR B 108 20 720 41 021 31 894 1 00 15 50 0
ATOM 1727 CG2 THR B 108 22 588 39 765 31 132 1 00 17 18 c
ATOM 1728 N ALA B 109 23 420 41 306 28 131 1 00 16 67 N
ATOM 1729 CA ALA B 109 24 706 41 262 27 448 1 00 16 55 c
ATOM 1730 C ALA B 109 25 353 39 961 27 846 1 00 16 99 c
ATOM 1731 O ALA B 109 24 939 38 896 27 394 1 00 17 11 0
ATOM 1732 CB ALA B 109 24 540 41 324 25 893 1 00 16 53 c
ATOM 1733 N LEU B 110 26 363 40 047 28 699 1 00 17 44 N
ATOM 1734 CA LEU B 110 27 059 38 870 29 180 1 00 17 82 C
ATOM 1735 C LEU B 110 28 334 38 654 28 402 1 00 18 45 C
ATOM 1736 O LEU B 110 29 121 39 585 28 200 1 00 18 97 O
ATOM 1737 CB LEU B 110 27 410 39 018 30 660 1 00 17 67 C
ATOM 1738 CG LEU B 110 28 233 37 905 31 297 1 00 16 52 c
ATOM 1739 CD1 LEU B 110 27 559 36 562 31 143 1 00 15 11 c
ATOM 1740 CD2 LEU B 110 28 502 38 236 32 784 1 00 17 55 c
ATOM 1741 N THR B 111 28 529 37 408 27 989 1 00 18 42 N
ATOM 1742 CA THR B 111 29 781 36 945 27 444 1 00 18 62 C
ATOM 1743 C THR B 111 30 320 35 854 28 342 1 00 18 54 C
ATOM 1744 O THR B 111 29 648 34 855 28 574 1 00 18 20 O
ATOM 1745 CB THR B 111 29 557 36 395 26 049 1 00 18 49 C
ATOM 1746 OG1 THR B 111 29 304 37 485 25 159 1 00 19 06 O
ATOM 1747 CG2 THR B 111 30 821 35 724 25 509 1 00 18 48 C
ATOM 1748 N VAL B 112 31 529 36 063 28 854 1 00 18 62 N
ATOM 1749 CA VAL B 112 32 203 35 061 29 650 1 00 18 98 C
ATOM 1750 C VAL B 112 33 437 34 563 28 897 1 00 19 41 C
ATOM 1751 O VAL B 112 34 285 35 347 28 455 1 00 19 07 0
ATOM 1752 CB VAL B 112 32 666 35 600 31 023 1 00 18 78 C
ATOM 1753 CGI VAL B 112 33 204 34 452 31 902 1 00 18 38 C
ATOM 1754 CG2 VAL B 112 31 540 36 356 31 735 1 00 19 56 c
ATOM 1755 N LYS B 113 33 518 33 255 28 732 1 00 20 11 N
ATOM 1756 CA LYS B 113 34 805 32 612 28 521 1 00 20 80 c
ATOM 1757 C LYS B 113 34 736 31 166 28 964 1 00 20 93 c
ATOM 1758 O LYS B 113 35 505 30 751 29 825 1 00 21 05 o
ATOM 1759 CB LYS B 113 35 265 32 714 27 070 1 00 21 14 c
ATOM 1760 CG LYS B 113 36 797 32 926 26 932 1 00 21 95 c
ATOM 1761 CD LYS B 113 37 613 31 644 27 254 1 00 23 53 c
ATOM 1762 CE LYS B 113 38 619 31 803 28 420 1 00 23 96 c
ATOM 1763 NZ LYS B 113 38 373 30 833 29 560 1 00 24 62 N
TER 1764 LYS B 113
HETATM 1765 O HOH 1 -3 603 22 565 27 326 1 00 32 62 O
HETATM 1766 O HOH 2 -2 025 37 576 31 649 1 00 28 80 O
HETATM 1767 O HOH 3 11 564 37 382 17 647 1 00 29 79 O
HETATM 1768 O HOH 4 12 147 50 601 31 887 1 00 29 72 O
HETATM 1769 O HOH 5 14 153 45 214 30 485 1 00 27 66 0
HETATM 1770 O HOH 6 -8 057 56 130 33 388 1 00 37 02 o
HETATM 1771 O HOH 7 17 902 51 226 29 662 1 00 34 89 0
HETATM 1772 O HOH 8 12 752 39 758 34 757 1 00 28 89 0
HETATM 1773 O HOH 9 -8 631 55 669 45 707 1 00 41 15 o
HETATM 1774 O HOH 10 13 151 25 246 35 468 1. 00 53 94 0
HETATM 1775 O HOH 11 20 020 44 397 48 086 1 00 34 26 o
HETATM 1776 O HOH 12 -2 478 40 620 21 138 1. 00 31 91 0 HETATM 1777 0 HOH 13 6,.817 45..918 20,,781 1.00 34.15 o
HETATM 1778 0 HOH 14 ■10, .720 41. .048 19. ,742 1, .00 29 .28 0
HETATM 1779 0 HOH 15 5, .136 27. .001 33, .682 1, .00 34 .01 o
HETATM 1780 0 HOH 16 -8, .752 34. .083 17, .394 1, .00 32 .30 0
HETATM 1781 0 HOH 17 6, .370 25. .987 36, .062 1, .00 46 .53 0
HETATM 1782 0 HOH 18 -2. .835 44. .271 34. .848 1, .00 46 .44 o
HETATM 1783 0 HOH 19 12, .329 46. .062 32. .976 1, .00 41 .31 o
HETATM 1784 0 HOH 20 7. .260 23. .068 29. .837 1, .00 38, .09 0
HETATM 1785 0 HOH 21 9, ,196 26. ,047 36, .490 1, .00 47, .12 0
HETATM 1786 0 HOH 22 15. ,395 35. ,722 34. .664 1, ,00 41, .20 0
HETATM 1787 0 HOH 23 -0. ,653 40. .172 17. .501 1, ,00 37, .13 o
HETATM 1788 0 HOH 24 -5. ,694 32. ,125 32, ,899 1, .00 44, .72 0
HETATM 1789 0 HOH 25 12. ,701 48. ,162 29. .678 1. .00 45, .56 o
HETATM 1790 0 HOH 26 -2. ,261 42, ,933 22. .850 1, ,00 45, .39 0
HETATM 1791 0 HOH 27 -1. ,180 27. .915 31. .872 1, .00 44, .10 o
HETATM 1792 0 HOH 28 11. .917 36. .985 27. ,031 1, .00 46, .78 0
HETATM 1793 0 HOH 29 22. .053 53. .082 44, ,383 1, .00 57, .53 o
HETATM 1794 0 HOH 30 8. .896 28. .691 22, .223 1. .00 36, .55 0
HETATM 1795 0 HOH 31 11. .139 27. .149 35, .370 1, .00 40, .73 o
HETATM 1796 0 HOH 32 16. .384 43. .712 24, .651 1, .00 35, .03 0
HETATM 1797 0 HOH 33 -1. ,673 32. .550 31, .734 1. .00 53, .95 o
HETATM 1798 0 HOH 34 -0. .534 41. .750 25, .977 1, .00 26, .15 0
HETATM 1799 0 HOH 35 25. .707 49. .370 30. .021 1, ,00 55, .33 o
HETATM 1800 0 HOH 36 7. .758 32. .565 39, .383 1. .00 44, .45 0
HETATM 1801 0 HOH 37 -9. .122 42. .014 49. .736 1, .00 40, .33 0
HETATM 1802 0 HOH 38 -7, .490 26. .790 15. .325 1, .00 45, .84 o
HETATM 1803 0 HOH 39 15. .093 35. .774 21. .413 1, .00 58, ,89 o
HETATM 1804 0 HOH 40 13, .787 53, .303 31. .695 1, .00 48, .06 o
HETATM 1805 0 HOH 41 26, ,881 36, .152 44. .074 1. .00 45, .18 0
HETATM 1806 0 HOH 42 •31, .999 47, .971 25. .667 1, .00 45, .30 0
HETATM 1807 0 HOH 43 -2, .869 45, .128 37. .465 1, .00 51, .46 0
HETATM 1808 0 HOH 44 •11, .522 33. .793 24, .204 1, .00 48, .27 o
HETATM 1809 0 HOH 45 0, .741 49. .839 30, .801 1. .00 64, .89 0
HETATM 1810 0 HOH 46 3, .995 28, ,946 34. .996 1, .00 46, .15 0
HETATM 1811 0 HOH 47 1, .716 24, ,921 22. .872 1, ,00 50, .97 0
HETATM 1812 0 HOH 48 14. .528 49. ,967 29, .489 1, .00 32. .12 0
HETATM 1813 0 HOH 49 -3, ,397 54. ,514 35, .732 1, ,00 75, .25 0
HETATM 1814 0 HOH 50 7. ,350 36. ,188 38, .637 1, ,00 44. .58 0
HETATM 1815 0 HOH 51 11, .258 36. .392 32, .460 1, .00 64, .14 0
HETATM 1816 0 HOH 52 -5. .919 28. .213 33, ,670 1, .00 53. .43 0
HETATM 1817 0 HOH 53 29. ,035 35, .826 45, .961 1, .00 52, .26 0
HETATM 1818 0 HOH 54 0, .619 37, .563 35, .722 1. .00 36. .13 0
HETATM 1819 0 HOH 55 17, .630 44, .800 22, .683 0, .50 19. .47 0
HETATM 1820 0 HOH 56 10. .658 48. .432 27, .654 1, .00 57. .06 0
HETATM 1821 0 HOH 57 12, .883 47, .166 27, .270 1, .00 47. .82 0
HETATM 1822 0 HOH 58 10. .204 43, .420 20, .875 1. .00 54. .59 0
HETATM 1823 0 HOH 59 •17, ,821 36, .045 26, .779 1, .00 48. .73 o
HETATM 1824 0 HOH 60 33, .575 46. ,023 24. .555 0, .50 57. .14 0
HETATM 1825 0 HOH 61 -9, .513 32. .401 30. .497 1, .00 49. .08 0
HETATM 1826 0 HOH 62 22, .035 32. ,931 35. .329 1, .00 53. .74 o
HETATM 1827 0 HOH 63 26, .276 37. .813 25, .169 1, ,00 43, .04 0
HETATM 1828 0 HOH 64 6, .554 36. ,026 15. .888 1, ,00 49. .25 0
HETATM 1829 0 HOH 65 14, .945 36. .915 28. .030 1, ,00 55, .95 0
HETATM 1830 0 HOH 66 11. ,110 41. ,062 21, ,523 1. ,00 47. .74 0
HETATM 1831 0 HOH 67 3. .797 45. .196 35. .142 1, ,00 49. .98 0
HETATM 1832 0 HOH 68 -7. .103 48. ,353 46, ,125 1. .00 63. .67 0
HETATM 1833 0 HOH 69 26. .227 28. .904 36. ,563 1, ,00 67, .40 0
HETATM 1834 0 HOH 70 21. .008 37. .879 44, ,773 1, ,00 38, .83 0
HETATM 1835 0 HOH 71 -8. .401 39, .932 48. ,004 1. ,00 59. .32 0
HETATM 1836 0 HOH 72 -7. .060 55. ,805 37, ,587 1, ,00 36, .59 0
HETATM 1837 0 HOH 73 2, ,254 43. .055 28. ,212 1. .00 37. .43 0
HETATM 1838 0 HOH 74 15. ,957 41. ,782 22. ,346 1, ,00 52. ,21 0
HETATM 1839 0 HOH 75 30. .836 46. ,157 27. ,026 1. .00 41. ,75 o
HETATM 1840 0 HOH 76 0, ,243 30. ,979 36. ,033 1. ,00 54. ,97 0 HETATM 1841 0 HOH 77 0,.247 38..128 13..711 1,.00 71,,28 0
HETATM 1842 0 HOH 78 5, .404 42, .527 18, .589 1 .00 45, .84 0
HETATM 1843 0 HOH 79 10, .308 34. .296 26, .893 1, .00 53, .88 0
HETATM 1844 0 HOH 80 -6, .664 53, .994 39, .217 1, .00 42, .65 0
HETATM 1845 0 HOH 81 -5, .087 41, ,168 17. .628 1, .00 50, ,54 0
HETATM 1846 0 HOH 82 ■22. .020 51, .083 47, .018 1, .00 63, .47 0
HETATM 1847 0 HOH 83 -5, .142 35. .512 13. .750 1, .00 49, .89 0
HETATM 1848 0 HOH 84 10, .297 24, .970 22, .199 1, .00 54, .97 0
HETATM 1849 0 HOH 85 -3, .029 49. .876 30. ,159 1, .00 67. .18 0
HETATM 1850 0 HOH 86 ■15, .585 36, .101 16, .657 1, .00 62, .06 0
HETATM 1851 0 HOH 87 ■31, .964 47. ,184 41. .589 1, .00 51. ,59 0
HETATM 1852 0 HOH 88 ■32, .818 49. .890 32. .367 1, .00 49, ,76 0
HETATM 1853 0 HOH 89 15, .015 43. .317 14. .283 1, .00 57. .75 0
HETATM 1854 0 HOH 90 ■21, ,719 31. .012 37, .760 1, .00 72, .98 o
HETATM 1855 0 HOH 91 •32, .335 46, .485 39. .125 1, ,00 68. .68 0
HETATM 1856 0 HOH 92 0, .069 40. .947 11. .925 1. ,00 58. .64 0
HETATM 1857 0 HOH 93 15, .333 44. .973 29. .047 1, .00 •58. .06 0
HETATM 1858 0 HOH 94 4, .602 29. .902 37. .670 1. .00 58. .96 0
HETATM 1859 0 HOH 95 8, .321 46, .401 37. .041 1, .00 79. .54 0
HETATM 1860 0 HOH 96 16, .844 44. .827 27. .035 1, .00 53. .07 0
HETATM 1861 0 HOH 97 8, .643 34, .976 14. .645 1, .00 61, .34 0
HETATM 1862 0 HOH 98 15, .081 30. .053 40. ,624 1, ,00 58, .50 0
HETATM 1863 0 HOH 99 ■29, .173 38, .671 49, ,216 1, .00 77, .24 0
HETATM 1864 0 HOH 100 •34, .367 30. .230 40, ,676 1, ,00 87. .45 0
HETATM 1865 0 HOH 101 13, .024 40. ,796 42, .706 1, ,00 66. .67 o
HETATM 1866 0 HOH 102 24, .986 34. .816 45, .384 1, .00 54. .92 o
HETATM 1867 0 HOH 103 3, .596 42. ,385 20, .233 1, .00 37. .71 0
HETATM 1868 0 HOH 104 •23, .493 49, .334 44, .992 1, .00 44. .76 o
HETATM 1869 0 HOH 105 •22, .358 44, .809 26, .526 1, .00 68. .31 0
HETATM 1870 0 HOH 106 ■17, .446 32, .842 37, .601 1, .00 65. .30 0
HETATM 1871 0 HOH 107 22, .821 52. .720 29, .818 1. .00 71. .05 0
HETATM 1872 0 HOH 108 -8, .572 26, .810 23. .048 1, .00 81. ,52 o
HETATM 1873 0 HOH 109 4, .419 46, .453 27, ,301 1, .00 63. ,98 0
HETATM 1874 0 HOH 110 23, .410 26, .310 29, ,884 1, .00 72. .88 0
HETATM 1875 0 HOH 111 9, .649 42, .598 19, ,288 1, .00 58. .11 0
HETATM 1876 0 HOH 112 ■15. .692 35. .133 41, ,149 1, .00 63. ,89 0
HETATM 1877 0 HOH 113 ■26, .983 54, .986 35, .486 1, .00 87. ,73 0
HETATM 1878 0 HOH 114 24. .223 45. ,040 24, .854 0, .50 34. ,45 0
HETATM 1879 0 HOH 115 -5, .537 55, .893 46, .218 1, .00 46, .13 0
HETATM 1880 0 HOH 116 22. .125 35. .353 45, .825 1, ,00 54. .11 0
HETATM 1881 0 HOH 117 -4, .303 38, .534 32, .607 1, ,00 65. .18 0
HETATM 1882 0 HOH 118 24. .701 49. .655 42. .592 1, ,00 44. ,09 0
HETATM 1883 0 HOH 119 -6, .344 37, .080 33. .536 1, .00 56, ,70 0
HETATM 1884 0 HOH 120 16. .010 39. ,018 19. .540 1. .00 47, ,12 0
HETATM 1885 0 HOH 121 27. .762 40. ,565 50, .157 1, .00 65, ,48 0
HETATM 1886 0 HOH 122 38. ,022 50. .782 33. ,568 1, .00 73. ,64 0
HETATM 1887 0 HOH 123 -1, .625 52. .480 34. .057 1, .00 74, ,28 0
HETATM 1888 0 HOH 124 21, ,663 35. .323 48. ,955 1, .00 65. ,30 0
HETATM 1889 0 HOH 125 -6, ,821 48. .170 48. ,922 1. .00 73. ,82 0
HETATM 1890 0 HOH 126 13, ,845 39. .478 40. ,011 1, .00 60. ,84 0
HETATM 1891 0 HOH 127 6, ,927 41, .038 17. ,007 1. .00 68. ,49 0
HETATM 1892 0 HOH 128 -1, ,966 52, ,839 44. ,944 1. .00 87. ,28 0
HETATM 1893 0 HOH 129 -7, ,847 23. ,965 22. ,241 1. .00 58. ,88 0
HETATM 1894 0 HOH 130 -3, ,206 50, .463 45. ,678 1. .00 81. ,46 0
HETATM 1895 0 HOH 131 20, ,734 33, .268 29. ,612 1. .00 65. ,97 0
HETATM 1896 0 HOH 132 -3, ,239 43, .318 28. ,931 1, ,00 60. ,99 0
HETATM 1897 0 HOH 133 40. ,181 49, .870 32. ,489 1. ,00 76. 03 0
HETATM 1898 0 HOH 134 ■13. ,701 39, .202 25. .401 1. .00 64. ,57 0
HETATM 1899 0 HOH 135 28, ,332 46. .062 26. ,011 1, ,00 50. 13 0
HETATM 1900 0 HOH 136 ■14. ,074 29, .707 23. ,160 1. .00 83. 09 o
HETATM 1901 0 HOH 137 -4, ,377 47. .534 39. ,617 1. ,00 61. 39 0
HETATM 1902 0 HOH 138 14. ,674 39. .434 43. ,947 1. ,00 61. 24 0
HETATM 1903 0 HOH 139 28. ,314 52. .582 28. ,145 1. .00 60. 30 0
HETATM 1904 0 HOH 140 18. ,687 49. .110 26. 208 1. ,00 54. 09 0 HETATM 1905 0 HOH 141 •15..685 39,,305 23,.521 1.,00 65,.29 0
HETATM 1906 0 HOH 142 ■33, .598 49, .435 41, .980 1. .00 83, .02 0
HETATM 1907 0 HOH 143 ■38, .646 26, .243 29 .939 1. ,00 92, .35 0
HETATM 1908 0 HOH 144 ■20. .693 42, .535 25, .536 1. .00 61, .60 0
HETATM 1909 0 HOH 145 ■21, .614 55, .217 35, .058 1. .00 54, .35 0
HETATM 1910 0 HOH 146 20. .340 33. .477 28, .720 1. .00 57. .13 0
HETATM 1911 0 HOH 147 ■14, .937 35, .262 30, .134 1. .00 80, .62 0
HETATM 1912 0 HOH 148 ■30, .357 41, .475 51, .126 1. .00 55, .90 0
HETATM 1913 0 HOH 149 -7. ,343 19, .838 22, .057 1. .00 58, ,33 0
HETATM 1914 0 HOH 150 10, .363 41, .633 41, .955 1. .00 80, .85 0
HETATM 1915 0 HOH 151 ■28. .516 56. .353 29, .977 1. .00 67. ,64 0
HETATM 1916 0 HOH 152 0. .289 49, .396 28, .161 1. .00 82, ,96 0
HETATM 1917 0 HOH 153 -5, .197 44, .204 39, .334 1. .00 57, .87 0
HETATM 1918 0 HOH 154 -1. .892 29. .898 33, .032 1. ,00 81. ,31 0
HETATM 1919 0 HOH 155 -6, .354 40, .306 40, .369 1. ,00 64, .96 0
HETATM 1920 0 HOH 156 ■35. .505 42, .575 36, ,471 1. ,00 61. .68 0
HETATM 1921 0 HOH 157 11. .766 41, .049 25, .763 1. ,00 67. .31 0
HETATM 1922 0 HOH 158 24, .549 41, .790 44, .796 1. .00 94, .46 0
HETATM 1923 0 HOH 159 21. .990 42. .199 17. .194 1. .00 71. .97 0
HETATM 1924 0 HOH 160 ■21, .524 48, .235 45, .392 1, .00 38, .60 0
HETATM 1925 0 HOH 161 -8. .232 11. .927 11. .548 1, .00 77. .25 0
HETATM 1926 0 HOH 162 18, .993 45, .611 24, .121 0, .50 48, ,25 0
HETATM 1927 0 HOH 163 -3, .423 33, .004 33, .502 1, .00 46, .87 0
HETATM 1928 0 HOH 164 ■12. .067 38, .301 39. .035 1. .00 66. ,32 0
HETATM 1929 0 HOH 165 ■19, .240 57, .453 34, .326 1, .00 62, .19 0
HETATM 1930 0 HOH 166 •15. .369 57. .421 34, .820 1. .00 56. .53 0
HETATM 1931 0 HOH 167 •12. .383 46, .024 24, .556 0, .50107. .60 0
HETATM 1932 0 HOH 168 9, .582 23, .067 37, .226 1. .00 68, .06 0
HETATM 1933 0 HOH 169 13. ,979 44, .653 23, .993 1, .00 59. .28 0
HETATM 1934 0 HOH 170 7, .020 20, .778 33, .662 1, .00 55, .70 0
HETATM 1935 0 HOH 171 -6. .632 18. .659 6. .953 1. .00 57. .16 0
HETATM 1936 0 HOH 172 ■40. .140 40, .092 30. .271 1. ,00 83. .42 0
HETATM 1937 0 HOH 173 •25, .859 49, .080 46, .581 1, .00 72, .05 0
HETATM 1938 0 HOH 174 11. .903 33. .915 42. .794 1, .00 62. .47 0
HETATM 1939 0 HOH 175 4, .443 37, .316 14, .253 1. .00 54. .63 0
HETATM 1940 0 HOH 176 23. .109 32. .164 39. .230 1. .00 58. .67 0
HETATM 1941 0 HOH 177 16. .134 23, .618 36. .264 1. .00 72. .38 0
HETATM 1942 0 HOH 178 6, ,026 27, .145 18, .930 1. .00 77. .90 0
HETATM 1943 0 HOH 179 -9. ,688 38. .334 40. .737 1. .00 61. .53 0
HETATM 1944 0 HOH 180 22. .696 49, .211 25. .803 1. .00 65. .15 0
HETATM 1945 0 HOH 181 30. .846 54. .695 38. .649 1. ,00 60. .05 0
HETATM 1946 0 HOH 182 19. .785 63. .595 61. ,341 1. .00 89. .42 0
HETATM 1947 0 HOH 183 13. .553 19, .460 30. ,403 1. .00 79. .86 0
HETATM 1948 0 HOH 184 4. .577 49. .300 32. ,750 1. ,00 64, ,93 0
HETATM 1949 0 HOH 185 1. .307 28, .028 35, .709 1. .00 65. ,55 0
HETATM 1950 0 HOH 186 -4. .209 8, ,016 10, .568 1. ,00 76. ,31 0
HETATM 1951 0 HOH 187 -7. ,990 57, ,550 66, .176 1. .00 84. ,96 0
HETATM 1952 0 HOH 188 ■11. ,759 70, ,211 53, .014 1. .00 68, ,57 0
HETATM 1953 0 HOH 189 15. ,093 31, ,958 14. .184 1. ,00 77. ,18 0
HETATM 1954 0 HOH 190 23. ,127 28, ,574 35, .811 1. ,00 84. .33 0
HETATM 1955 0 HOH 191 ■12. ,687 42, ,314 29. .442 1. ,00 56. ,81 0
HETATM 1956 0 HOH 192 -3. ,637 39, ,435 35. .154 1. ,00 57. ,23 0
HETATM 1957 0 HOH 193 13. ,948 40, ,445 14. .939 1. .00 74. .56 0
HETATM 1958 0 HOH 194 24. ,452 59. ,655 41. .252 1. ,00 95. ,39 0
HETATM 1959 0 HOH 195 35. ,101 41. .960 42. .068 1. ,00 74. .52 0
HETATM 1960 0 HOH 196 21. ,224 54, .576 30, .539 1. ,00 93. ,57 0
HETATM 1961 0 HOH 197 -6. ,699 59. ,049 64, .130 1. ,00 90. ,32 0
HETATM 1962 0 HOH 198 12. ,852 44. .654 28, .015 1. ,00 65. .04 0
HETATM 1963 0 HOH 199 35. ,270 35. .608 25. .394 1. ,00 91. ,63 0
HETATM 1964 0 HOH 200 27, ,591 55. ,725 41, .984 1. ,00 78. ,78 0
HETATM 1965 0 HOH 201 -2. ,304 42. ,014 35. ,867 1. 00 60. 76 0
HETATM 1966 0 HOH 202 -7. ,873 38. ,784 35, ,085 1. ,00 60. 96 0
HETATM 1967 0 HOH 203 1. ,437 49, ,049 33, .215 1. ,00 91. ,38 0
HETATM 1968 0 HOH 204 9. ,087 29. ,635 19, ,856 1. 00 44. 92 0 HETATM 1969 0 HOH 205 4 632 27 259 38 041 1 00 73 19 0
HETATM 1970 0 HOH 206 -6 312 40 374 36 109 1 00 54 83 o
HETATM 1971 0 HOH 207 16 399 32 078 23 121 1 00 87 24 0
HETATM 1972 0 HOH 208 15 627 25 767 26 517 1 00 68 61 o
HETATM 1973 0 HOH 209 22 940 40 400 23 162 1 00 66 19 o
HETATM 1974 0 HOH 210 9 044 42 885 39 388 1 00 52 86 0
HETATM 1975 0 HOH 211 2 686 10 774 3 076 1 00 86 36 o
HETATM 1976 0 HOH 212 21 576 32 568 32 413 1 00 63 08 0
HETATM 1977 0 HOH 213 12 714 21 953 33 512 1 00 69 19 o
HETATM 1978 0 HOH 214 18 333 25 494 30 728 1 00 59 02 0
HETATM 1979 0 HOH 215 10 477 70 874 59 283 1 00 90 02 0
HETATM 1980 0 HOH 216 24 719 51 729 41 022 1 00 46 48 0
HETATM 1981 0 HOH 217 14 511 48 063 37 259 1 00 60 62 o
HETATM 1982 0 HOH 218 10 655 26 875 15 002 1 00 83 41 o
HETATM 1983 0 HOH 219 11 207 48 612 31 720 1 00 62 53 0
HETATM 1984 0 HOH 220 12 020 30 028 27 373 1 00 74 67 o
HETATM 1985 0 HOH 221 37 489 47 701 29 803 1 00 68 54 0
HETATM 1986 0 HOH 222 6 582 42 620 37 908 1 00 52 68 o
HETATM 1987 0 HOH 223 -5 169 54 977 49 059 1 00 81 54 o
HETATM 1988 0 HOH 224 11 648 73 225 58 749 1 00 71 11 0
HETATM 1989 0 HOH 225 1 769 39 751 36 817 1 00 83 19 o
HETATM 1990 0 HOH 226 12 017 35 767 45 531 1 00 87 64 0
HETATM 1991 0 HOH 227 21 914 39 637 26 810 1 00 61 56 o
HETATM 1992 0 HOH 228 13 853 42 384 18 211 1 00 47 88 0
HETATM 1993 0 HOH 229 -2 593 54 747 48 184 1 00 85 82 o
HETATM 1994 0 HOH 230 16 494 26 070 37 419 1 00 66 70 0
HETATM 1995 0 HOH 231 -9 482 37 452 37 786 1 00 78 29 o
HETATM 1996 0 HOH 232 13 412 29 804 19 190 1 00 95 07 0
HETATM 1997 0 HOH 233 11 326 24 573 13 894 1 00 85 94 o
HETATM 1998 0 HOH 234 18 269 38 041 21 145 1 00 51 57 0
HETATM 1999 0 HOH 235 11 946 37 393 36 577 1 00 61 47 0
HETATM 2000 0 HOH 236 29 656 56 618 26 887 1 00 77 90 o
HETATM 2001 0 HOH 237 12 732 32 774 38 409 1 00 74 56 o
HETATM 2002 0 HOH 238 17 956 23 840 34 384 1 00 63 80 0
HETATM 2003 0 HOH 239 -9 416 37 923 44 514 1 00 90 86 0
HETATM 2004 0 HOH 240 14 456 60 996 37 550 1 00 80 66 o
HETATM 2005 0 HOH 241 -1 720 44 079 26 371 1 00 64 22 0
HETATM 2006 0 HOH 242 10 339 38 706 33 728 1 00 67 90 o
HETATM 2007 0 HOH 243 24 244 36 669 35 828 1 00 53 46 0
HETATM 2008 0 HOH 244 -7 769 23 449 11 359 1 00 84 35 0
HETATM 2009 0 HOH 245 11 242 21 377 31 295 1 00 59 50 0
HETATM 2010 0 HOH 246 29 651 41 449 25 764 1 00 55 60 0
HETATM 2011 0 HOH 247 13 689 59 872 55 361 1 00 57 65 0
HETATM 2012 0 HOH 248 4 670 26 514 16 406 1 00 78 28 o
HETATM 2013 0 HOH 249 38 061 52 151 30 188 1 00 74 73 0
HETATM 2014 0 HOH 250 13 040 26 819 19 529 1 00 73 16 o
HETATM 2015 0 HOH 251 17 381 34 165 33 393 1 00 64 24 0
HETATM 2016 0 HOH 252 -2 223 34 352 37 730 1 00 83 71 0
HETATM 2017 0 HOH 253 16 079 31 443 19 478 1 00 84 26 o
HETATM 2018 0 HOH 254 -8 067 30 366 34 807 1 00 75 21 0
HETATM 2019 0 HOH 255 16 052 32 626 17 086 1 00111 60 o
HETATM 2020 0 HOH 256 -3 151 32 317 36 134 1 00 76 07 0
HETATM 2021 0 HOH 257 28 340 43 292 26 140 1 00 84 47 0
HETATM 2022 0 HOH 258 13 201 34 779 40 218 1 00 78 14 0
HETATM 2023 0 HOH 259 28 742 28 673 28 253 1 00 65 42 o
HETATM 2024 0 HOH 260 20 148 45 068 25 903 0 50 74 24 0
HETATM 2025 0 HOH 261 11 073 36 391 42 363 1 00 95 30 o
HETATM 2026 0 HOH 262 15 738 48 828 48 039 1 00 55 95 0
HETATM 2027 0 HOH 263 19 088 33 527 26 503 1 00 87 58 0
HETATM 2028 0 HOH 264 -0 687 47 729 38 514 1 00 82 39 o
HETATM 2029 0 HOH 265 13 291 35 265 47 736 1 00 85 03 0
HETATM 2030 0 HOH 266 -2 672 19 489 1 571 1 00 72 65 0
HETATM 2031 0 HOH 267 39 451 43 535 26 005 0 50 61 33 o
HETATM 2032 0 HOH 268 -0 307 24 319 23 263 1 00 61 23 0 HETATM 2033 0 HOH 269 18.114 42,,357 14.347 00 74.03 O
HETATM 2034 0 HOH 270 -1.953 37, ,146 36.068 00 98.52 O
HETATM 2035 0 HOH 271 -37.503 39. ,278 41.064 00 73.24 O
HETATM 2036 0 HOH 272 -40.189 28, ,850 28.128 00 87.08 O
HETATM 2037 0 HOH 273 24.328 34. ,368 36.983 00 75.80 O
HETATM 2038 0 HOH 274 -37.020 37. ,405 24.990 00 71.53 O
HETATM 2039 0 HOH 275 -19.465 36, ,641 43.076 00 67.93 O
HETATM 2040 0 HOH 276 -7.655 24. ,826 31.230 00 49.77 O
HETATM 2041 0 HOH 277 -2.621 23. ,763 22.594 00 88.43 O
HETATM 2042 0 HOH 278 -2.830 35. .434 33.849 00 88.49 O
HETATM 2043 0 HOH 279 -32.334 34. .377 45.004 00 93.57 O
HETATM 2044 0 HOH 280 1.641 44. .356 34.318 00 50.87 O
HETATM 2045 0 HOH 281 -36.662 44. .555 31.032 00 55.72 O
HETATM 2046 0 HOH 282 -0.094 34. ,840 10.372 00 66.27 O
HETATM 2047 0 HOH 283 -13.878 31. .752 27.095 00 69.99 O
HETATM 2048 0 HOH 284 23.476 43. .421 42.279 00105.55 O
HETATM 2049 0 HOH 285 -23.343 31. .731 28.830 00 70.21 O
HETATM 2050 0 HOH 286 5.253 45. ,138 37.445 00 94.42 O
HETATM 2051 0 HOH 287 10.412 31. .220 14.882 00 87.46 O
HETATM 2052 0 HOH 288 14.940 31. ,880 16.303 00 66.56 O
HETATM 2053 0 HOH 289 17.168 36. .449 45.600 0.50 54.04 O
HETATM 2054 0 HOH 290 2.003 41. ,955 38.222 00 69.37 O
HETATM 2055 0 HOH 291 6.621 39. .950 38.526 00 58.61 O
HETATM 2056 0 HOH 292 -22.166 32, .743 25.751 00 79.54 O
HETATM 2057 0 HOH 293 -21.155 47. ,190 26.170 0.50 53.13 O
HETATM 2058 0 HOH 294 21.374 37. .864 20.799 00 77.05 0
HETATM 2059 0 HOH 295 -13.520 70, .582 51.050 00 88.38 0
HETATM 2060 0 HOH 296 25.541 38, ,807 32.374 00 52.13 0
HETATM 2061 0 HOH 297 -20.150 33. ,543 42.049 00 69.15 0
HETATM 2062 0 HOH 298 -16.241 69. .662 40.827 00 75.97 0
HETATM 2063 0 HOH 299 -15.650 66. .556 60.490 00 96.19 0
HETATM 2064 0 HOH 300 -4.674 46. .553 26.268 00 89.63 0
HETATM 2065 0 HOH 301 -18.802 36. .355 49.179 00 77.59 0
HETATM 2066 0 HOH 302 -25.774 35. .475 24.450 00 61.75 0
HETATM 2067 0 HOH 303 -4.490 16. .888 11.049 00 90.74 0
HETATM 2068 0 HOH 304 -26.802 27. ,808 30.640 00 77.04 0
HETATM 2069 0 HOH 305 5.669 22. .533 35.676 00 73.26 o
HETATM 2070 0 HOH 306 -31.095 43. .543 25.917 00 67.07 0
HETATM 2071 0 HOH 307 -10.776 20. .519 3.866 00 88.13 o
HETATM 2072 0 HOH 308 -24.474 29. .167 30.418 00 83.44 0
HETATM 2073 0 HOH 309 4.054 47. ,866 34.653 00 67.34 o
HETATM 2074 0 HOH 310 -40.069 32. ,480 34.827 00 87.72 0
HETATM 2075 0 HOH 311 -13.867 22. .452 8.366 00 81.23 o
HETATM 2076 0 HOH 312 -6.729 34. .615 36.646 00 91.79 0
HETATM 2077 0 HOH 313 -13.851 67. .948 42.822 00104.93 o
HETATM 2078 0 HOH 314 -9.942 22. .490 2.278 00 76.63 0
HETATM 2079 0 HOH 315 -12.535 69. .113 55.555 00 84.39 0
HETATM 2080 0 HOH 316 -35.917 50. .015 39.350 00102.90 0
HETATM 2081 0 HOH 317 6.860 27. .799 16.464 00 94.15 0
HETATM 2082 0 HOH 318 -6.624 47, .121 27.551 00 55.25 0
HETATM 2083 0 HOH 319 25.633 36. .301 33.674 00 90.78 0
HETATM 2084 0 HOH 320 -40.011 28. .195 30.647 00 72.48 o
HETATM 2085 0 HOH 321 -0.548 21. .349 5.340 00 76.60 0
HETATM 2086 0 HOH 322 -19.675 66, .803 60.854 00 94.58 o
HETATM 2087 0 HOH 323 -2.728 51. .206 32.260 00 77.64 0
HETATM 2088 0 HOH 324 -1.247 43, ,110 29.580 00 56.25 o
HETATM 2089 0 HOH 325 -34.343 37, ,661 47.184 00 73.61 0
HETATM 2090 0 HOH 326 -17.710 48. ,503 47.282 00 51.09 o
HETATM 2091 0 HOH 327 19.728 28. ,197 29.672 00 71.53 0
HETATM 2092 0 HOH 328 -16.815 43. ,464 29.032 00 38.64 0
HETATM 2093 0 HOH 329 -8.769 46. ,895 26.815 00 63.95 0
HETATM 2094 0 HOH 330 19.385 30. ,108 27.998 00 84.78 0
HETATM 2095 0 HOH 331 20.296 46. ,890 36.277 00 69.10 o
HETATM 2096 0 HOH 332 10.011 39. ,138 22.129 00 73.04 0 HETATM 2097 O HOH 333 34,.667 43..573 39..921 1.,00 94,.23 0
HETATM 2098 O HOH 334 25. .038 44. .754 44. .084 1. .00 62. .57 0
HETATM 2099 O HOH 335 18..836 44..474 39..123 1..00 79,.24 0
HETATM 2100 O HOH 336 5. .728 24. .703 20. .348 1. .00 91. .70 0
HETATM 2101 O HOH 337 37..708 28..757 29..261 1,.00 89,.30 0
HETATM 2102 O HOH 338 24. .041 44. .585 36. .443 1. .00 87. .02 0
HETATM 2103 O HOH 339 16. .021 34. .803 49. .305 0, .50 57, .78 0
HETATM 2104 O HOH 340 23. .445 54. .520 27, .866 1. .00 97, .08 0
HETATM 2105 O HOH 341 12. .151 43. ,628 46. .109 1. .00 87, .45 0
HETATM 2106 O HOH 342 21.,420 30..507 17..302 1,.00 70,.53 0
HETATM 2107 O HOH 343 34.,255 41..798 50.,132 1,.00 81..37 0
HETATM 2108 O HOH 344 18. .390 20. .362 32. .308 1, .00 83, ,10 0
HETATM 2109 O HOH 345 25,.000 56..746 38,.927 1,.00 94,.33 0
HETATM 2110 O HOH 346 -8. .804 60. .068 50. .157 1, .00 79, ,38 0
HETATM 2111 O HOH 347 20, .488 55. .011 45, .150 1. .00 91, .93 0
HETATM 2112 O HOH 348 -0. .212 46. .908 32. .365 1, ,00 84, .10 o
HETATM 2113 O HOH 349 -7..494 7..448 7,,764 1..00 76,.18 0
HETATM 2114 O HOH 350 17,.446 73,.178 55,.029 1..00 76,.88 0
HETATM 2115 O HOH 351 -7. ,818 4. .607 5. .147 1, .00 67, .95 0
HETATM 2116 O HOH 352 18,.532 34,.688 16,.174 1,.00 80,.19 0
HETATM 2117 O HOH 353 38. .919 53. .773 41. .038 1, .00 77, .53 0
HETATM 2118 0 HOH 354 4,,686 42..380 42,.213 1,.00 66,.79 0
HETATM 2119 0 HOH 355 ■43, .020 57, ,512 44, .325 1. .00 74, .66 0
HETATM 2120 0 HOH 356 36, .610 51. .515 43. .519 1. .00 80, .73 0
HETATM 2121 0 HOH 357 ■40,.125 38,.357 26,.648 1..00 83,.64 0
HETATM 2122 0 HOH 358 ■42, .612 55. .808 47. .578 1. ,00 69, .35 0
CONECT 168 649
CONECT 649 168
CONECT 1050 1531
CONECT 1531 1050
MASTER 377 0 0 26 6 2120
END
APPENDIX I (c)
HEADER 12A-9 COMPND 12A-9 REMARK 3 REMARK REFINEMENT . REMARK PROGRAM REFMAC 5.2.0005 REMARK AUTHORS MURSHUDOV, VAGIN, DODSON REMARK REMARK REFINEMENT TARGET : MAXIMUM LIKELIHOOD REMARK REMARK DATA USED IN REFINEMENT. REMARK RESOLUTION RANGE HIGH (ANGSTROMS) 2.10 REMARK RESOLUTION RANGE LOW (ANGSTROMS) 34.20 REMARK DATA CUTOFF (SIGMA(F)) NONE REMARK COMPLETENESS FOR RANGE (%) 98.55 REMARK NUMBER OF REFLECTIONS 6040 REMARK REMARK FIT TO DATA USED IN REFINEMENT. REMARK CROSS-VALIDATION METHOD THROUGHOUT REMARK FREE R VALUE TEST SET SELECTION RANDOM REMARK R VALUE (WORKING + TEST SET) 0.22276 REMARK R VALUE (WORKING SET) 0.21668 REMARK FREE R VALUE 0.34914 REMARK FREE R VALUE TEST SET SIZE (%) 4.7 REMARK FREE R VALUE TEST SET COUNT 297 REMARK REMARK FIT IN THE HIGHEST RESOLUTION BIN. REMARK TOTAL NUMBER OF BINS USED 20 REMARK BIN RESOLUTION RANGE HIGH 2.100 REMARK BIN RESOLUTION RANGE LOW 2.154 REMARK REFLECTION IN BIN (WORKING SET) 432 REMARK BIN COMPLETENESS (WORKING+TEST) (%) 100.00 REMARK BIN R VALUE (WORKING SET) 0.261 REMARK BIN FREE R VALUE SET COUNT 19 REMARK BIN FREE R VALUE 0.397 REMARK REMARK NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT. REMARK ALL ATOMS : 963 REMARK REMARK B VALUES. REMARK FROM WILSON PLOT A**2) NULL REMARK MEAN B VALUE (OVERALL, A**2) 46.514 REMARK OVERALL ANISOTROPIC B VALUE. REMARK Bll (A**2) 38 REMARK B22 (A**2) 21 REMARK B33 (A**2) 17 REMARK B12 (A**2) 00 REMARK B13 (A**2) 00 REMARK B23 (A**2) 00 REMARK REMARK ESTIMATED OVERALL COORDINATE ERROR. REMARK ESU BASED ON R VALUE (A) 0.308 REMARK ESU BASED ON FREE R VALUE (A) 0.299 REMARK ESU BASED ON MAXIMUM LIKELIHOOD (A) 0.266 REMARK ESU FOR B VALUES BASED ON MAXIMUM LIKELIIHHOOOODD (A**2) 18.684 REMARK REMARK CORRELATION COEFFICIENTS . REMARK CORRELATION COEFFICIENT FO-FC 0.938 REMARK CORRELATION COEFFICIENT FO-FC FREE 0.852 REMARK REMARK RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT REMARK BOND LENGTHS REFINED ATOMS (A) 833 ; o.oi; i ; 0.022 REMARK BOND ANGLES REFINED ATOMS (DEGREES) 1125 ; 1.58! 3 ; 1.959 REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES) 107 7.310 5 000 REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES) 35 31.640 22 857 REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES) 149 17.871 15 000 REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES) 9 15.120 15 000 REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3) 132 098 0 200 REMARK 3 GENERAL PLANES REFINED ATOMS (A) 610 006 0 020 REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A) 328 262 0.200 REMARK 3 NON-BONDED TORSION REFINED ATOMS (A) 540 307 0.200 REMARK 3 H-BOND (X...Y) REFINED ATOMS (A) 88 234 0.200 REMARK 3 SYMMETRY VDW REFINED ATOMS (A) 40 230 0.200 REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A) 34 251 0.200 REMARK 3 REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT REMARK 3 MAIN-CHAIN BOND REFINED ATOMS (A**2) 542 684 1.500 REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2) 853 129 2.000 REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2) 327 950 3.000 REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2) 272 921 4.500 REMARK 3 REMARK 3 NCS RESTRAINTS STATISTICS REMARK 3 NUMBER OF NCS GROUPS : NULL REMARK 3 REMARK 3 REMARK 3 TLS DETAILS REMARK 3 NUMBER OF TLS GROUPS : 1 REMARK 3 ATOM RECORD CONTAINS RESIDUAL B FACTORS ONLY REMARK 3 REMARK 3 TLS GROUP : 1 REMARK 3 NUMBER OF COMPONENTS GROUP 1 REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI REMARK 3 RESIDUE RANGE : A 1 A 108 REMARK 3 ORIGIN FOR THE GROUP (A) : 9430 24.5360 17.1020 REMARK 3 T TENSOR REMARK 3 Til 1693 T22 1046 REMARK 3 T33 2013 T12 0063 REMARK 3 T13 0567 T23 0059 REMARK 3 TENSOR REMARK 3 Lll 2257 L22 2213 REMARK 3 L33 2779 L12 8504 REMARK 3 L13 5143 L23 1677 REMARK 3 TENSOR REMARK 3 Sll 0246 S12 4407 S13 0.2852 REMARK 3 S21 1471 S22 0358 S23 -0.0174 REMARK 3 S31 1461 S32 0338 S33 -0.0604 REMARK 3 REMARK 3 REMARK 3 BULK SOLVENT MODELLING. REMARK 3 METHOD USED : MASK REMARK 3 PARAMETERS FOR MASK CALCULATION REMARK 3 VDW PROBE RADIUS 1.20 REMARK 3 ION PROBE RADIUS 0.80 REMARK 3 SHRINKAGE RADIUS 0.80 REMARK 3 REMARK 3 OTHER REFINEMENT REMARKS: REMARK 3 HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS REMARK 3 SSBOND 1 CYS A 22 CYS A 83 SSBOND 2 CYS A 29 CYS A CISPEP 1 THR A 6 PRO A 7 ,00 CRYST1 38.268 68.324 39.511 90.00 90.00 90.00 21 21 SCALE1 0.026131 0.000000 0 .000000 0.00000 SCALE2 0.000000 0.014636 0 .000000 0.00000 SCALE3 0.000000 0.000000 0 .025309 0.00000
ATOM ALA A 4.330 25.995 2.005 1.00 43.85 ATOM 2 CA ALA A 1 4.728 27.133 1.107 1.00 43.77 C
ATOM 3 CB ALA A 1 3 .593 27 .517 0 .176 1.00 43 .63 C
ATOM 4 C ALA A 1 5 .151 28 .332 1 .936 1.00 43 .39 C
ATOM 5 O ALA A 1 5 .918 29 .172 1 .470 1.00 43 .85 O
ATOM 6 N ARG A 2 4 .579 28 .432 3 .132 1.00 42 .78 N
ATOM 7 CA ARG A 2 5 .102 29 .264 4 .216 1.00 42 .72 C
ATOM 8 CB ARG A 2 4 .780 30 .749 4 .023 1.00 42 .82 C
ATOM 9 CG ARG A 2 5 .657 31 .676 4 .877 1.00 44 .95 c
ATOM 10 CD ARG A 2 5, .472 33 .132 4 .480 1.00 47 .25 c
ATOM 11 NE ARG A 2 6 .437 34 .012 5 .135 1.00 49 .81 N
ATOM 12 CZ ARG A 2 6 .603 35 .304 4 .828 1.00 51 .50 C
ATOM 13 NH1 ARG A 2 5, .863 35 .873 3 .885 1.00 51, .25 N
ATOM 14 NH2 ARG A 2 7 .507 36 .040 5, .465 1.00 51 .63 N
ATOM 15 C ARG A 2 4, .476 28 .768 5 .506 1.00 42 .13 C
ATOM 16 O ARG A 2 3, .283 28, .457 5, .534 1.00 41, .66 O
ATOM 17 N VAL A 3 5, .280 28 .675 6 .567 1.00 41, .68 N
ATOM 18 CA VAL A 3 4 .755 28 .407 7 .899 1.00 41 .27 C
ATOM 19 CB VAL A 3 5, .585 27, .367 8, .690 1.00 41, .29 C
ATOM 20 CGI VAL A 3 5, .631 26 .054 7, .981 1.00 41, .79 C
ATOM 21 CG2 VAL A 3 4, .962 27, .123 10, .045 1.00 42, .69 C
ATOM 22 C VAL A 3 4, ,695 29, .732 8, .678 1.00 41. .43 c
ATOM 23 O VAL A 3 5, .675 30, .493 8, .728 1.00 41. .02 0
ATOM 24 N ASP A 4 3, .534 30, .006 9, .274 1.00 41. .22 N
ATOM 25 CA ASP A 4 3. ,393 31, ,135 10. .171 1.00 40. .99 C
ATOM 26 CB ASP A 4 2, .059 31, .870 9, .961 1.00 40. .51 C
ATOM 27 CG ASP A 4 1, .862 32, .377 8, .537 1.00 43, ,34 C
ATOM 28 OD1 ASP A 4 0. .693 32, .684 8. .183 1.00 44, ,24 0
ATOM 29 OD2 ASP -A 4 2. .854 32, .502 7, .779 1.00 45, .58 0
ATOM 30 C ASP A 4 3, .469 30, .569 11, .581 1.00 40, .39 c
ATOM 31 O ASP A 4 2. .629 29. .730 11, .968 1.00 40, .91 0
ATOM 32 N GLN A 5 4. .470 31, .000 12, .342 1.00 39, .37 N
ATOM 33 CA GLN A 5 4, .613 30, .557 13, .755 1.00 39, .62 C
ATOM 34 CB GLN A 5 6, .033 30. .097 14, .056 1.00 39. .21 C
ATOM 35 CG GLN A 5 6. .143 29. .286 15, .330 1.00 39. .71 C
ATOM 36 CD GLN A 5 7. .566 28, ,809 15, .616 1.00 40. ,20 C
ATOM 37 OEl GLN A 5 8. .281 28, .355 14. .720 1.00 38. .99 0
ATOM 38 NE2 GLN A 5 7. ,995 28, .953 16. .871 1.00 39. .67 N
ATOM 39 C GLN A 5 4. ,305 31, .695 14. .702 1.00 39, .74 C
ATOM 40 O GLN A 5 4. ,878 32. .804 14. .545 1.00 39. ,27 0
ATOM 41 N THR A 6 3, ,436 31. .431 15, .683 1.00 39. ,68 N
ATOM 42 CA THR A 6 3. ,127 32, .446 16, .692 1.00 39. ,83 C
ATOM 43 CB THR A 6 1. ,908 33. ,215 16. ,266 1.00 39. ,82 C
ATOM 44 OG1 THR A 6 1. ,666 34. ,263 17. ,204 1.00 43. ,51 O
ATOM 45 CG2 THR A 6 0, ,689 32. .306 16. .156 1.00 37. ,32 c
ATOM 46 C THR A 6 3. ,048 31. ,917 18. ,149 1.00 40. 58 c
ATOM 47 O THR A 6 2, ,734 30. ,743 18. ,359 1.00 39. 70 0
ATOM 48 N PRO A 7 3. .405 32. .748 19. ,163 1.00 41. 05 N
ATOM 49 CA PRO A 7 3. ,870 34. ,153 19. 132 1.00 41. 58 c
ATOM 50 CB PRO A 7 3. ,722 34. ,616 20. 587 1.00 41. 21 c
ATOM 51 CG PRO A 7 3. ,829 33. ,371 21. ,381 1.00 42. 26 C
ATOM 52 CD PRO A 7 3. 378 32. 213 20. 535 1.00 40. 83 C
ATOM 53 C PRO A 7 5. ,323 34. ,205 18. 715 1.00 41. 50 C
ATOM 54 O PRO A 7 5. ,996 33. ,179 18. 810 1.00 40. 92 O
ATOM 55 N ARG A 8 5. 782 35. 367 18. 252 1.00 41. 56 N
ATOM 56 CA ARG A 8 7. 166 35. 551 17. 879 1.00 42. 59 C
ATOM 57 CB ARG A 8 7. 324 36. ,786 16. 982 1.00 43. 86 C
ATOM 58 CG ARG A 8 8. 768 37. 127 16. 567 1.00 47. 00 c
ATOM 59 CD ARG A 8 9. 356 36. 117 15. 546 1.00 52. 83 c
ATOM 60 NE ARG A 8 10. 695 35. 623 15. 908 1.00 54. 23 N
ATOM 61 CZ ARG A 8 11. 824 36. 329 15. 838 1.00 55. 74 c
ATOM 62 NH1 ARG A 8 12. 973 35. 762 16. 189 1.00 55. 74 N
ATOM 63 NH2 ARG A 8 11. 817 37. 602 15. 438 1.00 55. 73 N
ATOM 64 C ARG A 8 8. 025 35. 667 19. 144 1.00 42. 90 C
ATOM 65 O ARG A 8 9. 165 35. 198 19. 172 1.00 42. 04 O ATOM 66 N ILE A 9 7.469 36.281 20.193 1.00 42.94 N
ATOM 67 CA ILE A 9 8.171 36.410 21.483 1 .00 43 .38 C
ATOM 68 CB ILE A 9 8.863 37.808 21.679 1 .00 43 .29 C
ATOM 69 CGI ILE A 9 7.854 38.897 22.063 1. .00 42 .77 C
ATOM 70 GDI ILE A 9 7.657 40.025 21.036 1, .00 44 .86 C
ATOM 71 CG2 ILE A 9 9.665 38.186 20.442 1 .00 44 .36 C
ATOM 72 C ILE A 9 7.211 36.153 22.641 1 .00 43 .85 C
ATOM 73 O ILE A 9 6.005 36.392 22.529 1, .00 43, .69 O
ATOM 74 N ALA A 10 7.754 35.682 23.758 1 .00 44 .25 N
ATOM 75 CA ALA A 10 6.946 35.359 24.930 1 .00 44 .42 C
ATOM 76 CB ALA A 10 6.407 33.930 24.805 1, .00 44, .54 C
ATOM 77 C ALA A 10 7.777 35.528 26.215 1, .00 44, .54 C
ATOM 78 O ALA A 10 8.956 35.154 26.271 1, .00 44 .06 O
ATOM 79 N THR A 11 7.180 36.136 27.231 1, .00 44, .75 N
ATOM 80 CA THR A 11 7.803 36.159 28.539 1, .00 45, .12 C
ATOM 81 CB THR A 11 8.201 37.568 28.982 1. .00 45, .29 C
ATOM 82 OG1 THR A 11 7.042 38.405 28.976 1, .00 46, .91 O
ATOM 83 CG2 THR A 11 9.283 38.154 28.075 1, .00 46, .06 C
ATOM 84 C THR A 11 6.833 35.565 29.545 1. .00 45. .16 C
ATOM 85 O THR A 11 5.795 36.146 29.848 1. .00 45. .26 O
ATOM 86 N LYS A 12 7.203 34.397 30.048 1, ,00 45, .15 N
ATOM 87 CA LYS A 12 6..446 33.666 31.037 1. ,00 45. .46 C
ATOM 88 CB LYS A 12 6..323 32.221 30.584 1. .00 45, .35 C
ATOM 89 CG LYS A 12 5.099 31.914 29.756 1. .00 47. .76 C
ATOM 90 CD LYS A 12 4, .697 33.007 28.777 1. .00 49, .69 C
ATOM 91 CE LYS A 12 3, .521 32.560 27.920 1. .00 49, .05 C
ATOM 92 NZ LYS A 12 2.306 32.457 28.739 1, .00 49, ,64 N
ATOM 93 C LYS A 12 7, .102 33.718 32.424 1. .00 45, ,30 C
ATOM 94 O LYS A 12 8.283 34.053 32.569 1. .00 45, ,21 O
ATOM 95 N GLU A 13 6.302 33.416 33.442 1, .00 45. .31 N
ATOM 96 CA GLU A 13 .776 33.188 34.807 1. .00 45. .37 C
ATOM 97 CB GLU A 13 .857 33.935 35.759 1. .00 45, .85 C
ATOM 98 CG GLU A 13 .752 35.414 35.367 1. .00 48, ,54 C
ATOM 99 CD GLU A 13 .509 36.109 35.878 1, .00 51. .63 C
ATOM 100 OEl GLU A 13 .402 37.334 35.645 1, ,00 53. .17 O
ATOM 101 OE2 GLU A 13 ,646 35.448 36.511 1. ,00 54, ,08 O
ATOM 102 C GLU A 13 .797 31.674 35.096 1. ,00 44, ,83 C
ATOM 103 O GLU A 13 .029 30.902 34.496 1. .00 43. ,74 O
ATOM 104 N THR A 14 7.675 31.229 35.986 1. ,00 44. ,58 N
ATOM 105 CA THR A 14 7.792 29.794 36.199 1. ,00 45. ,00 C
ATOM 106 CB THR A 14 8.810 29.381 37.292 1. ,00 45. .21 C
ATOM 107 OG1 THR A 14 8.341 29.745 38.606 1. ,00 44. ,01 O
ATOM 108 CG2 THR A 14 10.190 29.968 37.006 1. ,00 45. ,34 C
ATOM 109 C THR A 14 6..419 29.253 36.532 1. ,00 45. ,37 C
ATOM 110 O THR A 14 5..614 29.949 37.138 1. ,00 45. 15 O
ATOM 111 N GLY A 15 6..141 28.031 36.099 1. ,00 45. ,55 N
ATOM 112 CA GLY A 15 4..838 27.446 36.328 1. ,00 45. .89 C
ATOM 113 C GLY A 15 3, .778 27.733 35.276 .00 46.24 C
ATOM 114 O GLY A 15 2..773 27.020 35.217 .00 47.04 O
ATOM 115 N GLU A 16 3, .978 28.754 34.439 .00 46.01 N
ATOM 116 CA GLU A 16 3, .004 29.052 33.376 ,00 45.58 C
ATOM 117 CB GLU A 16 3, .171 30.483 32.865 1.00 45.77 C
ATOM 118 CG GLU A 16 2, .684 31.561 33.810 1.00 45.94 C
ATOM 119 CD GLU A 16 2, .551 32.924 33.137 .00 46.28 C
ATOM 120 OEl GLU A 16 1, .414 33.434 33.026 .00 48.01 O
ATOM 121 OE2 GLU A 16 3, .577 33.492 32.719 ,00 46.37 O
ATOM 122 C GLU A 16 3, .100 28.042 32.214 .00 44.90 C
ATOM 123 O GLU A 16 3, .937 27.152 32.242 .00 44.86 O
ATOM 124 N SER A 17 2..217 28.187 31.224 .00 44.50 N
ATOM 125 CA SER A 17 2..222 27.396 29.989 ,00 44.60 C
ATOM 126 CB SER A 17 0.842 26.775 29.738 ,00 44.45 C
ATOM 127 OG SER A 17 0.453 25.965 30.811 ,00 44.72 O
ATOM 128 C SER A 17 2.523 28.302 28.823 ,00 44.08 C
ATOM 129 O SER A 17 2.185 29.476 28.861 1.00 44.27 0 ATOM 130 N LEU A 18 3,.128 27,.748 27,.783 1,.00 44.07 N
ATOM 131 CA LEU A 18 3, ,221 28, .413 26. .500 1. .00 44, .43 C
ATOM 132 CB LEU A 18 4, .676 28, .794 26. .169 1, .00 44, .33 C
ATOM 133 CG LEU A 18 4. .894 29. .325 24. .724 1, .00 45, .37 C
ATOM 134 CD1 LEU A 18 4, .372 30, .754 24. .566 1. .00 46, .79 C
ATOM 135 CD2 LEU A 18 6, .337 29, .238 24. .266 1, .00 44, .61 C
ATOM 136 C LEU A 18 2. .643 27. .515 25. .389 1. .00 44, .31 C
ATOM 137 O LEU A 18 2. .907 26. .316 25. .342 1. .00 45, .00 O
ATOM 138 N THR A 19 1, ,845 28, .108 24. .511 1, .00 43, .57 N
ATOM 139 CA THR A 19 1, ,392 27. .424 23. .329 1, .00 42. .81 C
ATOM 140 CB THR A 19 0. ,133 27, ,292 23. .333 1, .00 43, .09 C
ATOM 141 OG1 THR A 19 0, ,529 26. .408 24. .397 1. .00 41, .89 O
ATOM 142 CG2 THR A 19 0, .661 26. .725 22. .038 1. .00 42, .37 C
ATOM 143 C THR A 19 1, .956 28, .171 22. .123 1, .00 42, .99 C
ATOM 144 O THR A 19 1, .816 29. ,395 21. .994 1. .00 43, ,18 O
ATOM 145 N ILE A 20 2, .676 27, .437 21. .289 1, .00 42, .98 N
ATOM 146 CA ILE A 20 3, .236 27, .974 20. .038 1, .00 42, .80 C
ATOM 147 CB ILE A 20 4, .705 27, .584 19. .883 1. .00 43, .04 C
ATOM 148 CGI ILE A 20 5, ,526 28, .107 21. .081 1, .00 43, .37 C
ATOM 149 GDI ILE A 20 6, .953 27. .570 21. ,100 1. .00 44. .96 c
ATOM 150 CG2 ILE A 20 5. .277 28. .026 18. ,480 1. .00 43, .19 c
ATOM 151 C ILE A 20 2, .446 27, .323 18. .917 1, .00 42, .22 c
ATOM 152 O ILE A 20 2, ,329 26. .084 18. .880 1. .00 41, ,41 o
ATOM 153 N ASN A 21 1, .875 28, .159 18. .052 1, .00 41, .71 N
ATOM 154 CA ASN A 21 1, .036 27, .726 16, .926 1. .00 42, .93 C
ATOM 155 CB ASN A 21 0, .183 28, ,639 16, .820 1, .00 42, ,54 C
ATOM 156 CG ASN A 21 ■0, .976 28, .682 18, .083 1, .00 44, .72 C
ATOM 157 OD1 ASN A 21 1, ,349 29. .757 18, .551 1. .00 45, .71 O
ATOM 158 ND2 ASN A 21 ■1, .219 27, .513 18, .674 1, ,00 42, .93 N
ATOM 159 C ASN A 21 1, .770 27, .795 15, .592 1, .00 43, .02 C
ATOM 160 O ASN A 21 2, .331 28, .828 15, .282 1, ,00 43. .10 O
ATOM 161 N CYS A 22 1, .766 26, .706 14, .818 1, .00 43, .57 N
ATOM 162 CA CYS A 22 2, .380 26, .727 13, .466 1, .00 44, .69 C
ATOM 163 CB CYS A 22 3, .504 25, .707 13, .321 1, ,00 44, .60 C
ATOM 164 SG CYS A 22 4, .986 26, .277 14, .143 1, ,00 50, .05 s
ATOM 165 C CYS A 22 1, ,353 26, .444 12, .415 1, ,00 43, .98 c
ATOM 166 O CYS A 22 0, .883 25, .306 12, ,305 1, ,00 44, .31 0
ATOM 167 N VAL A 23 0, .991 27, .470 11, ,656 1, ,00 42, .86 N
ATOM 168 CA VAL A 23 0, .041 27, .309 10. .574 1, ,00 42, .98 C
ATOM 169 CB VAL A 23 1, .009 28, .482 10. .517 1, .00 42, .82 C
ATOM 170 CGI VAL A 23 ■1, .749 28, .606 11. ,828 1, ,00 42, .81 C
ATOM 171 CG2 VAL A 23 0, ,349 29, ,798 10. ,236 1, .00 43, .32 C
ATOM 172 C VAL A 23 0, .776 27, .117 9. .224 1, .00 42, .77 C
ATOM 173 O VAL A 23 1, .634 27. .906 8. ,863 1, .00 42. .18 0
ATOM 174 N LEU A 24 0, .440 26. .055 8. ,498 1, .00 43, ,14 N
ATOM 175 CA LEU A 24 1, .036 25, .814 7. ,191 1, .00 43, .73 C
ATOM 176 CB LEU A 24 1, .249 24. .329 6. ,928 1. .00 43, ,14 C
ATOM 177 CG LEU A 24 1. .546 23. .903 5. ,485 1, .00 43, ,95 C
ATOM 178 GDI LEU A 24 1, .681 22, ,390 5, ,387 1. ,00 43, ,88 C
ATOM 179 CD2 LEU A 24 2, .799 24, .576 4. ,951 1. .00 41, ,94 C
ATOM 180 C LEU A 24 0, .134 26, .444 6, ,139 1, .00 4'4, ,52 C
ATOM 181 O LEU A 24 0, ,906 25, ,887 5. ,749 1. ,00 44. ,87 O
ATOM 182 N ARG A 25 0, ,528 27, ,626 5. ,692 1. ,00 44. .92 N
ATOM 183 CA ARG A 25 0, .296 28, .383 4. ,783 1. ,00 45. .81 C
ATOM 184 CB ARG A 25 0. .088 29. .882 5. ,010 1. ,00 45, ,82 C
ATOM 185 CG ARG A 25 0, .384 30. ,338 6. ,442 1. ,00 47. ,76 C
ATOM 186 CD ARG A 25 1, .877 30, ,620 6. ,729 1. 00 50. ,07 C
ATOM 187 NE ARG A 25 2. .337 31. .949 6. ,312 1. ,00 53. ,50 N
ATOM 188 CZ ARG A 25 1, .548 32, .969 5, ,958 1. ,00 55, ,85 C
ATOM 189 NH1 ARG A 25 0. ,231 32. .824 5. 983 1. 00 56. ,20 N
ATOM 190 NH2 ARG A 25 2. .074 34, .141 5. ,571 1. ,00 55. ,64 N
ATOM 191 C ARG A 25 0. .043 27, .961 3. ,361 1. ,00 46. ,02 C
ATOM 192 O ARG A 25 1. ,085 28. .348 2. 822 1. 00 45. 99 O
ATOM 193 N ASP A 26 0. ,843 27, .155 2. 777 1. ,00 46. ,53 N ATOM 194 CA ASP A 26 -0,.624 26.523 1.488 1.00 47.22 C
ATOM 195 CB ASP A 26 0, .407 25 .390 1, .604 1. .00 47 .06 c
ATOM 196 CG ASP A 26 0, .809 24, .833 0, .248 1, .00 46 .67 c
ATOM 197 OD1 ASP A 26 0, .263 25, .302 -0, .772 1 .00 46 .55 0
ATOM 198 OD2 ASP A 26 1, .676 23 .946 0, .195 1 .00 46 .05 0
ATOM 199 C ASP A 26 -1 .901 25 .928 0 .953 1. .00 47 .74 c
ATOM 200 O ASP A 26 -2, ,360 24, .914 1, .462 1 .00 49 .08 0
ATOM 201 N THR A 27 -2, .452 26 .524 -0 .096 1 .00 48 .30 N
ATOM 202 CA THR A 27 -3, .694 26 .029 -0 .712 1 .00 48 .55 C
ATOM 203 CB THR A 27 -4. .261 27, .048 -1, .707 1, .00 48, .30 C
ATOM 204 OG1 THR A 27 -3, .194 27, .563 -2, .505 1, .00 48, .97 0
ATOM 205 CG2 THR A 27 -4, .952 28, .201 -0, .984 1 .00 48 .44 c
ATOM 206 C THR A 27 -3. .548 24, ,685 -1, .447 1, .00 48, .44 c
ATOM 207 O THR A 27 -4, ,559 24, .048 -1, .785 1, .00 48, .34 0
ATOM 208 N ALA A 28 -2, .300 24, .264 -1, .679 1, .00 47, .65 N
ATOM 209 CA ALA A 28 -2. .003 23. .004 -2, .379 1, .00 46, .66 C
ATOM 210 CB ALA A 28 -0, .974 23, .244 -3, .482 1, .00 46, .92 C
ATOM 211 C ALA A 28 -1, .610 21, .758 -1, .522 1, .00 46, .70 C
ATOM 212 O ALA A 28 -1, .761 20, .627 -2 .016 1 .00 46, .77 o
ATOM 213 N CYS A 29 -1. .129 21. .935 -0, .279 1, .00 45, .33 N
ATOM 214 CA CYS A 29 -0. .631 20, .784 0, .521 1, .00 44, .73 C
ATOM 215 CB CYS A 29 0, .909 20, .674 0, .491 1, .00 44, .19 C
ATOM 216 SG CYS A 29 1. ,740 20. .865 -1. .109 1. .00 44, .32 S
ATOM 217 C CYS A 29 -1. .074 20. .722 1, .983 1, .00 43, .81 C
ATOM 218 O CYS A 29 -1. .289 21, .754 2, .630 1, .00 43, ,43 O
ATOM 219 N ALA A 30 -1. .164 19. .495 2, .495 1, ,00 42. ,66 N
ATOM 220 CA ALA A 30 -1. .505 19. ,233 3, .886 1, .00 42, .28 C
ATOM 221 CB ALA A 30 -2. .285 17, ,930 3, .997 1, .00 42, .02 C
ATOM 222 C ALA A 30 -0. .269 19. ,154 4. .771 1. .00 41, .62 c
ATOM 223 O ALA A 30 0. ,712 18, .511 4, .429 1, .00 41, .53 0
ATOM 224 N LEU A 31 -0, .325 19, .794 5, ,923 1, .00 41. .91 N
ATOM 225 CA LEU A 31 0, .662 19, .561 6, .967 1, .00 42. .25 C
ATOM 226 CB LEU A 31 0. .404 20, .523 8, .124 1. .00 42. .32 C
ATOM 227 CG LEU A 31 1. .190 20, ,318 9. .432 1, .00 43. .10 C
ATOM 228 CD1 LEU A 31 0. .828 21, .343 10, .499 1, .00 44. .14 C
ATOM 229 CD2 LEU A 31 2. ,648 20, ,360 9, .184 1. .00 41. ,11 c
ATOM 230 C LEU A 31 0. .556 18, ,104 7, .445 1. .00 42, ,95 c
ATOM 231 O LEU A 31 -0. .355 17, .764 8. .187 1. ,00 42, ,73 0
ATOM 232 N ASP A 32 1, .461 17. ,234 7, .017 1. ,00 44, ,01 N
ATOM 233 CA ASP A 32 1, .352 15. ,832 7, .416 1. .00 45, .57 c
ATOM 234 CB ASP A 32 1, .979 14. ,882 6, .399 1. .00 45, .87 c
ATOM 235 CG ASP A 32 1. ,289 13, ,517 6, ,377 1. ,00 48. ,45 c
ATOM 236 OD1 ASP A 32 1. ,974 12. .499 6. ,104 1. ,00 51. ,52 0
ATOM 237 OD2 ASP A 32 0, .056 13. .451 6, .625 1. .00 51. ,42 0
ATOM 238 C ASP A 32 1. .928 15. ,561 8, .799 1. .00 46. ,12 c
ATOM 239 O ASP A 32 1. ,336 14, ,820 9. ,586 1, ,00 48. ,01 0
ATOM 240 N SER A 33 3. ,060 16. ,168 9. ,112 1. ,00 45. ,67 N
ATOM 241 CA SER A 33 3. .754 15. ,910 10. .367 1, ,00 45. ,25 C
ATOM 242 CB SER A 33 4. ,803 14. ,811 10. ,179 1. ,00 45. 41 C
ATOM 243 OG SER A 33 4. ,209 13. ,522 10. ,260 1. .00 47. 47 0
ATOM 244 C SER A 33 4. ,436 17. ,192 10. ,801 1, .00 44. ,88 c
ATOM 245 O SER A 33 4. ,494 18. ,142 10. 048 1. ,00 44. 07 o
ATOM 246 N THR A 34 4. ,924 17. ,211 12. 037 1. ,00 44. 87 N
ATOM 247 CA THR A 34 5. ,688 18. ,333 12. ,566 1. ,00 44. 62 C
ATOM 248 CB THR A 34 4. ,807 19. ,303 13. ,360 1. ,00 44. 16 C
ATOM 249 OG1 THR A 34 3. 591 19. 534 12. 654 1. ,00 45. 91 O
ATOM 250 CG2 THR A 34 5. 499 20. 667 13. 570 1. ,00 44. 99 C
ATOM 251 C THR A 34 6. ,725 17. ,760 13. 515 1. ,00 44. 44 C
ATOM 252 O THR A 34 6. 480 16. 725 14. 145 1. 00 44. 41 O
ATOM 253 N ASN A 35 7. 886 18. 407 13. 577 1. ,00 43. 58 N
ATOM 254 CA ASN A 35 8. 814 18. ,241 14. 693 1. ,00 42. 87 C
ATOM 255 CB ASN A 35 10. 126 17. 582 14. 245 1. 00 45. 18 C
ATOM 256 CG ASN A 35 9. 995 16. 083 13. 991 1. 00 47. 53 C
ATOM 257 OD1 ASN A 35 9. 134 15. 403 14. 564 1. 00 54. 08 O ATOM 258 ND2 ASN A 35 10,.873 15..555 13,.136 1,.00 49,.76 N
ATOM 259 C ASN A 35 9, .074 19. .624 15. .301 1. .00 41, .97 C
ATOM 260 O ASN A 35 8, .830 20. .677 14. .667 1, .00 40, .57 O
ATOM 261 N TRP A 36 9. .528 19, .609 16, ,542 1, .00 40, .82 N
ATOM 262 CA TRP A 36 9, .709 20, .808 17. ,311 1, .00 40, .85 C
ATOM 263 CB TRP A 36 8, .676 20. .850 18, .471 1, .00 41, .37 C
ATOM 264 CG TRP A 36 7, .177 20. .913 17. .976 1, .00 40, .86 C
ATOM 265 GDI TRP A 36 6, .334 19. .850 17. .742 1. .00 40, .28 C
ATOM 266 NE1 TRP A 36 5, .096 20. .302 17. .342 1, .00 40, .69 N
ATOM 267 CE2 TRP A 36 5, .132 21. .676 17. .280 1, .00 40, .81 C
ATOM 268 CD2 TRP A 36 6. .426 22. .091 17. ,646 1, .00 39. .78 C
ATOM 269 CE3 TRP A 36 6, .709 23. .467 17. .680 1, .00 42, ,09 C
ATOM 270 CZ3 TRP A 36 5. .707 24. .367 17. .335 1, .00 39. ,48 c
ATOM 271 CH2 TRP A 36 4, .455 23. .918 16. .931 1. .00 41, .78 c
ATOM 272 CZ2 TRP A 36 4. .136 22. .578 16. .914 1, .00 40. ,38 c
ATOM 273 C TRP A 36 11, ,133 20. .823 17. .820 1, ,00 40. .66 c
ATOM 274 O TRP A 36 11, .659 19. .781 18. ,190 1. ,00 38. .51 o
ATOM 275 N TYR A 37 11, .749 22. .013 17. .804 1. .00 40, .65 N
ATOM 276 CA TYR A 37 13, .153 22. ,209 18. .092 1, .00 41, .40 C
ATOM 277 CB TYR A 37 13, .942 22. .596 16, .813 1, ,00 42, .81 C
ATOM 278 CG TYR A 37 13. .855 21. .544 15. ,747 1, ,00 44. .19 C
ATOM 279 CD1 TYR A 37 12, ,811 21. .548 14. ,841 1, .00 46. .04 C
ATOM 280 CEl TYR A 37 12, .690 20. .563 13. ,899 1, .00 47, .40 c
ATOM 281 CZ TYR A 37 13, .604 19. .559 13. ,838 1, .00 47. .21 c
ATOM 282 OH TYR A 37 13, .457 18. .596 12. .859 1, .00 47, .93 0
ATOM 283 CE2 TYR A 37 14, .669 19. .518 14. ,740 1. .00 46. .59 c
ATOM 284 CD2 TYR A 37 14, .769 20, .499 15. .698 1, .00 44, .56 c
ATOM 285 C TYR A 37 13, .333 23. .320 19. .098 1, .00 42. ,34 c
ATOM 286 O TYR A 37 12, .664 24, .359 19. .009 1, .00 42, .93 0
ATOM 287 N ARG A 38 14, .264 23. .110 20. .015 1. .00 42. .19 N
ATOM 288 CA ARG A 38 14, .595 24, .070 21. ,025 1, .00 42. .96 C
ATOM 289 CB ARG A 38 14, .270 23. .477 22. .397 1, .00 42. .92 C
ATOM 290 CG ARG A 38 14, .763 24. .313 23. .558 1. .00 44. .39 c
ATOM 291 CD ARG A 38 14, .561 23. .598 24. ,854 1, ,00 44. .38 c
ATOM 292 NE ARG A 38 15, .527 22. .532 25. .049 1, .00 45. ,25 N
ATOM 293 CZ ARG A 38 15, .442 21. .627 26. .008 1, .00 45. ,72 C
ATOM 294 NH1 ARG A 38 14, .428 21. .656 26. .880 1, ,00 47. ,04 N
ATOM 295 NH2 ARG A 38 16, ,370 20. .697 26. ,090 1, ,00 46. ,29 N
ATOM 296 C ARG A 38 16, .066 24. .380 20, ,947 1, .OC 42. ,48 C
ATOM 297 0 ARG A 38 16, .886 23. .480 20, .836 1, .00 41, .77 O
ATOM 298 N THR A 39 16, .385 25. .665 20. ,950 1, .00 42, .48 N
ATOM 299 CA THR A 39 17, .734 26. .114 21. ,184 1. .00 42, ,41 C
ATOM 300 CB THR A 39 18, ,241 27. .037 20. ,048 1, .00 42, ,54 C
ATOM 301 OG1 THR A 39 18, .228 26. .312 18, ,820 1, .00 42, .53 0
ATOM 302 CG2 THR A 39 19, .673 27. ,527 20. ,311 1. ,00 41, .06 c
ATOM 303 C THR A 39 17. .676 26. .873 22. ,510 1, .00 42, ,92 c
ATOM 304 O THR A 39 17. .003 27. ,900 22. ,564 1. .00 42. ,88 o
ATOM 305 N LYS A 40 18. ,365 26, .371 23, ,548 1, .00 42, ,04 N
ATOM 306 CA LYS A 40 18. ,419 27. .030 24. ,866 1. .00 43. .09 C
ATOM 307 CB LYS A 40 19. .207 26. .194 25. .881 1, .00 42. .59 C
ATOM 308 CG LYS A 40 18. .404 24, .966 26. ,364 1. .00 44. ,24 c
ATOM 309 CD LYS A 40 19. .096 24, ,238 27. ,544 1, .00 44. ,63 c
ATOM 310 CE LYS A 40 18, .461 22, ,852 27. ,732 1. ,00 48. ,13 c
ATOM 311 NZ LYS A 40 19. .384 21. ,866 28. ,429 1. ,00 50. ,65 N
ATOM 312 C LYS A 40 19, .035 28. ,410 24. ,737 1. ,00 42. ,81 C
ATOM 313 O LYS A 40 19, .920 28. ,594 23. ,919 1. ,00 42. ,34 O
ATOM 314 N LEU A 41 18, ,546 29. ,379 25. ,510 1. .00 43. ,09 N
ATOM 315 CA LEU A 41 19. ,033 30. ,752 25. ,382 1. ,00 44. ,01 C
ATOM 316 CB LEU A 41 18. ,276 31. ,698 26. ,311 1. ,00 44. ,25 C
ATOM 317 CG LEU A 41 17. ,782 33. ,024 25. ,744 1. ,00 43. 95 C
ATOM 318 CD1 LEU A 41 16. ,729 32. ,793 24. ,645 1. ,00 46. ,04 C
ATOM 319 CD2 LEU A 41 17. ,186 33. ,805 26. 889 1. 00 42. 63 C
ATOM 320 C LEU A 41 20. .491 30. ,797 25. ,743 1. ,00 44. 32 C
ATOM 321 O LEU A 41 20. ,875 30. ,255 26. 776 1. 00 44. 32 O ATOM 322 N GLY A 42 21.276 31.465 24.894 1..00 44.48 N
ATOM 323 CA GLY A 42 22 .724 31 .559 25 .032 1 .00 45 .33 C
ATOM 324 C GLY A 42 23 .534 30 .447 24 .379 1 .00 45 .16 C
ATOM 325 O GLY A 42 24 .750 30 .546 24 .253 1 .00 46 .05 O
ATOM 326 N SER A 43 22 .866 29 .382 23 .979 1 .00 45 .58 N
ATOM 327 CA SER A 43 23 .513 28 .241 23 .342 1 .00 45 .64 C
ATOM 328 CB SER A 43 22 .919 26 .938 23 .886 1 .00 45 .67 C
ATOM 329 OG SER A 43 23 .459 25 .792 23 .251 1 .00 46 .70 O
ATOM 330 C SER A 43 23 .289 28 .358 21 .832 1, .00 46 .16 C
ATOM 331 O SER A 43 22 .467 29 .164 21 .372 1, .00 45 .71 O
ATOM 332 N THR A 44 24 .043 27 .569 21 .077 1 .00 46 .22 N
ATOM 333 CA THR A 44 23, .942 27 .526 19 .633 1, .00 46, .87 C
ATOM 334 CB THR A 44 25 .270 27 .986 18 .993 1, .00 47 .20 C
ATOM 335 OG1 THR A 44 25 .567 29 .313 19 .456 1, .00 50 .26 O
ATOM 336 CG2 THR A 44 25, .165 28, .027 17, .487 1, .00. 49, .30 C
ATOM 337 C THR A 44 23 .531 26 .104 19 .198 1, .00 46, .11 C
ATOM 338 O THR A 44 23 .339 25 .840 18 .003 1, .00 46 .05 O
ATOM 339 N LYS A 45 23, .348 25, .220 20, .187 1, .00 45, .02 N
ATOM 340 CA LYS A 45 22, .925 23 .823 19, .974 1, .00 43, .74 C
ATOM 341 CB LYS A 45 23 .431 22 .949 21 .138 1, .00 44 .10 C
ATOM 342 CG LYS A 45 23, .218 21, .441 20, .990 1, ,00 41, .77 C
ATOM 343 CD LYS A 45 23, .748 20, .699 22, .202 1, .00 41, .15 C
ATOM 344 CE LYS A 45 23, .276 19 .255 22, .208 1, .00 40, .36 C
ATOM 345 NZ LYS A 45 24, .119 18, ,427 23, .140 1. .00 35, .82 N
ATOM 346 C LYS A 45 21, .406 23, .683 19, .838 1. .00 44, .15 C
ATOM 347 O LYS A 45 20, .662 23, .948 20, .788 1, .00 43, .67 O
ATOM 348 N GLU A 46 20, ,948 23, .234 18, ,669 1. .00 44, .10 N
ATOM 349 CA GLU A 46 19, .534 22, .901 18, .453 1. .00 44. .73 C
ATOM 350 CB GLU A 46 19, .187 23, .050 16, .961 1, .00 44, .68 C
ATOM 351 CG GLU A 46 17. .697 22. .939 16, .568 1. .00 46. , 31 C
ATOM 352 CD GLU A 46 17. .489 23, .212 15, .065 1. .00 46. .94 C
ATOM 353 OEl GLU A 46 16, .943 24, .286 14, .702 1. .00 51, .63 O
ATOM 354 OE2 GLU A 46 17, .922 22. .371 14. .253 1. .00 48. ,82 O
ATOM 355 C GLU A 46 19. .248 21. ,467 18. .895 1. .00 44, ,02 C
ATOM 356 O GLU A 46 20, .008 20, ,526 18. .582 1. .00 43, .31 O
ATOM 357 N GLN A 47 18. .155 21. ,298 19. .629 1. .00 44, .37 N
ATOM 358 CA GLN A 47 17. .669 19. ,946 19. .923 1. .00 45, .03 C
ATOM 359 CB GLN A 47 17. .925 19. .522 21. .378 1, .00 45, .59 C
ATOM 360 CG GLN A 47 17, .466 20. .462 22, .441 1. ,00 47. ,40 C
ATOM 361 CD GLN A 47 18, .514 20. .692 23, .534 1, .00 48. .12 C
ATOM 362 OEl GLN A 47 18, .640 21. .814 24, .024 1. .00 50, .42 O
ATOM 363 NE2 GLN A 47 19, ,275 19. .650 23. ,905 1. ,00 44, ,87 N
ATOM 364 C GLN A 47 16. .232 19. .743 19. ,520 1. ,00 44. .93 C
ATOM 365 O GLN A 47 15, .397 20. .664 19. ,618 1, .00 43. .86 O
ATOM 366 N THR A 48 15. ,966 18. ,539 19. ,018 1. ,00 43. ,69 N
ATOM 367 CA THR A 48 14. ,612 18, .113 18, .772 1. ,00 43. ,60 C
ATOM 368 CB THR A 48 14, .572 16. .904 17. .840 1. ,00 43. ,49 C
ATOM 369 OG1 THR A 48 15. .501 17. ,082 16. ,774 1. ,00 43. ,99 O
ATOM 370 CG2 THR A 48 13. ,191 16. ,705 17, ,254 1. ,00 44. ,57 C
ATOM 371 C THR A 48 13. ,956 17, .716 20, .100 1. ,00 43. ,88 C
ATOM 372 O THR A 48 14. ,500 16. ,890 20. .858 1. 00 43. 41 O
ATOM 373 N ILE A 49 12. ,763 18. ,250 20. ,342 1. ,00 43. 65 N
ATOM 374 CA ILE A 49 11. ,949 17. ,867 21. ,500 1. ,00 44. ,19 C
ATOM 375 CB ILE A 49 10. 965 18. ,986 21. ,860 1. 00 44. 86 C
ATOM 376 CGI ILE A 49 11. ,703 20. ,311 22. ,079 1. 00 44. 80 c
ATOM 377 GDI ILE A 49 10. ,772 21. ,515 22. ,217 1. 00 45. 75 c
ATOM 378 CG2 ILE A 49 10. 129 18. 577 23. 090 1. 00 44. 23 c
ATOM 379 C ILE A- 49 11. ,116 16. ,609 21. ,250 1. 00 43. 80 c
ATOM 380 O ILE A 49 10. ,322 16. ,569 20. ,311 1. 00 44. 87 O
ATOM 381 N SER A 50 11. 268 15. 587 22. 068 1. 00 42. 75 N
ATOM 382 CA SER A 50 10. 378 14. 439 21. 955 1. 00 44. 53 C
ATOM 383 CB SER A 50 11. 064 13. 151 22. 440 1. 00 44. 13 C
ATOM 384 OG SER A 50 10. 155 12. 054 22. 445 1. 00 49. 23 O
ATOM 385 C SER A 50 9. 055 14. 758 22. 699 1. 00 44. 49 C ATOM 386 O SER A 50 9,.050 15.069 23.883 1.00 43.95 0
ATOM 387 N ILE A 51 7, .943 14, .733 21, .953 1, .00 44 .98 N
ATOM 388 CA ILE A 51 6, .609 15, .076 22, .454 1, .00 44 .02 C
ATOM 389 CB ILE A 51 5, .605 15, .221 21, .273 1, .00 44 .92 c
ATOM 390 CGI ILE A 51 6, ,024 16, .366 20, .349 1, .00 45 .18 c
ATOM 391 CD1 ILE A 51 6, .216 17, .701 21, .070 1, .00 45 .42 c
ATOM 392 CG2 ILE A 51 4. ,160 15. .429 21, .770 1. .00 44 .94 c
ATOM 393 C ILE A 51 6, .070 14, .034 23, .421 1, .00 44 .33 c
ATOM 394 O ILE A 51 6, .006 12, .838 23, .094 1, .00 43 .52 0
ATOM 395 N GLY A 52 5. .631 14, .507 24, ,591 1, .00 43 .39 N
ATOM 396 CA GLY A 52 5, .153 13, .648 25, .669 1, .00 42 .74 c
ATOM 397 C GLY A 52 5. .393 14. .348 26. .998 1. .00 41, .31 c
ATOM 398 O GLY A 52 6. .109 15, .329 27, ,063 1. ,00 39, .55 0
ATOM 399 N GLY A 53 4. .766 13, .856 28, .052 1, .00 41 .80 N
ATOM 400 CA GLY A 53 4. .940 14, .458 29. .386 1. .00 41, .49 C
ATOM 401 C GLY A 53 4. .327 15, .852 29, ,367 1. .00 41 .82 C
ATOM 402 O GLY A 53 3, ,170 16, .016 28, .982 1, .00 41 .84 O
ATOM 403 N ARG A 54 5. ,098 16, .859 29, .739 1. .00 41, .46 N
ATOM 404 CA ARG A 54 4. .562 18, ,215 29, .779 1, .00 41 .94 C
ATOM 405 CB ARG A 54 5. .290 19, .038 30. .821 1. .00 41, .77 C
ATOM 406 CG ARG A 54 6. .712 19. .369 30, .492 1. .00 41, .91 C
ATOM 407 CD ARG A 54 7. .432 19, .944 31, .739 1, .00 43, .30 C
ATOM 408 NE ARG A 54 8. .839 20. .155 31. ,471 1. .00 42, .80 N
ATOM 409 CZ ARG A 54 9. .386 21. .335 31. ,194 1. .00 41, .93 C
ATOM 410 NH1 ARG A 54 10. .684 21, ,405 30, ,941 1. .00 39, .03 N
ATOM 411 NH2 ARG A 54 8. .645 22. .441 31. ,186 1. .00 40, .55 N
ATOM 412 C ARG A 54 4. .659 18. .932 28. .459 1, .00 42, .70 C
ATOM 413 O ARG A 54 4, ,402 20. .152 28. ,406 1. .00 42, ,87 O
ATOM 414 N TYR A 55 5. ,066 18. ,196 27. ,420 1. .00 42, .17 N
ATOM 415 CA TYR A 55 5. .079 18. .703 26, ,062 1. .00 43, .29 C
ATOM 416 CB TYR A 55 6. .420 18. .416 25. ,352 1. .00 42, .79 C
ATOM 417 CG TYR A 55 7. .624 19. .132 25. .934 1. .00 43, .35 C
ATOM 418 CD1 TYR A 55 8. ,030 20. ,364 25, ,444 1. ,00 42, .33 C
ATOM 419 CEl TYR A 55 9, ,139 21. .026 25, ,985 1. .00 44. .73 C
ATOM 420 CZ TYR A 55 9, .859 20. .423 27, .010 1. .00 45, .08 C
ATOM 421 OH TYR A 55 10, .973 21. .049 27, .536 1. .00 44. .82 O
ATOM 422 CE2 TYR A 55 9, .472 19. .194 27, ,498 1. .00 42. ,19 C
ATOM 423 CD2 TYR A 55 8, .369 18. ,559 26, ,963 1. .00 44, ,00 C
ATOM 424 C TYR A 55 3. .975 18. ,027 25. .289 1, .00 43. ,41 C
ATOM 425 O TYR A 55 3, .931 16. ,785 25. .178 1. .00 43. ,01 O
ATOM 426 N SER A 56 3. ,073 18. .826 24. ,742 1. .00 43. ,44 N
ATOM 427 CA SER A 56 2. .012 18. .211 23. .977 1. .00 44. ,15 C
ATOM 428 CB SER A 56 0. .701 18, .153 24. .797 1, .00 44. .77 C
ATOM 429 OG SER A 56 0. ,143 19. .440 25. .022 1. .00 46. .86 o
ATOM 430 C SER A 56 1, ,840 18. .923 22, .660 1, .00 44. .00 c
ATOM 431 O SER A 56 2, ,180 20. .104 22. .539 1, .00 44. .53 0
ATOM 432 N GLU A 57 1. ,343 18. .188 21. ,669 1. .00 43. .36 N
ATOM 433 CA GLU A 57 1, .042 18. .751 20. .356 1, .00 42, .94 c
ATOM 434 CB GLU A 57 1. ,886 18, .064 19. ,275 1. ,00 42, .52 c
ATOM '435 CG GLU A 57 1, ,674 18, .580 17. ,860 1. .00 43, ,65 c
ATOM 436 CD GLU A 57 2. .473 17, .808 16. ,828 1. .00 43, ,95 c
ATOM 437 OEl GLU A 57 1. ,857 17. .099 16. ,011 1. ,00 48. ,95 0
ATOM 438 OE2 GLU A 57 3. ,718 17. .895 16. ,815 1. .00 45. ,70 0
ATOM 439 C GLU A 57 -0. ,426 18, .594 20. ,058 1. .00 42, ,25 c
ATOM 440 O GLU A 57 -0. ,988 17, .502 20. ,203 1. .00 43. ,26 0
ATOM 441 N THR A 58 -1, ,062 19. .692 19. ,653 1. ,00 41. ,96 N
ATOM 442 CA THR A 58 -2. ,444 19. ,661 19. ,201 1. ,00 40. ,98 C
ATOM 443 CB THR A 58 -3. ,250 20. .750 19. ,963 1. ,00 41. ,21 C
ATOM 444 OG1 THR A 58 -3. ,103 20. .492 21. ,360 1. ,00 43. ,13 o
ATOM 445 CG2 THR A 58 -4. ,746 20. ,738 19. 612 1. ,00 40. ,36 c
ATOM 446 C THR A 58 -2. ,464 19. .839 17. ,687 1. ,00 40. ,68 c
ATOM 447 O THR A 58 -1. ,796 20, .746 17. ,165 1. ,00 40. ,52 0
ATOM 448 N VAL A 59 -3. ,178 18. ,958 16. 976 1. ,00 39. ,94 N
ATOM 449 CA VAL A 59 -3. ,346 19, .089 15. ,503 1. ,00 39. ,87 C ATOM 450 CB VAL A 59 3 023 17.778 14.703 1.00 39.05 c
ATOM 451 CGI VAL A 59 1 591 17 390 14 896 1 00 41 22 c
ATOM 452 CG2 VAL A 59 3 957 16 654 15 .094 1 00 39 .56 c
ATOM 453 C VAL A 59 4 741 19 .574 15 .078 1 .00 39 .53 c
ATOM 454 O VAL A 59 5 757 19 092 15 584 1 00 39 08 0
ATOM 455 N ASP A 60 4 769 20 511 14 138 1 00 40 17 N
ATOM 456 CA ASP A 60 6 023 20 .986 13 .552 1 00 41 .52 C
ATOM 457 CB ASP A 60 6 338 22 409 14 018 1 00 41 49 C
ATOM 458 CG ASP A 60 7 695 22 896 13 549 1 00 44 26 c
ATOM 459 OD1 ASP A 60 8 177 22 474 12 490 1 00 46 98 0
ATOM 460 OD2 ASP A 60 8 294 23 739 14 230 1 00 48 31 0
ATOM 461 C ASP A 60 5 961 20 849 12 023 1 00 41 63 c
ATOM 462 O ASP A 60 5 348 21 657 11 308 1 00 41 42 0
ATOM 463 N GLU A 61 6 583 19 788 11 539 1 00 41 59 N
ATOM 464 CA GLU A 61 6 643 19 514 10 115 1 00 42 38 C
ATOM 465 CB GLU A 61 7 324 18 169 9 908 1 00 42 35 c
ATOM 466 CG GLU A 61 7 387 17 692 8 483 1 00 43 28 c
ATOM 467 CD GLU A 61 7 987 16 328 8 417 1 00 42 95 c
ATOM 468 OEl GLU A 61 9 192 16 250 8 170 1 00 40 78 0
ATOM 469 OE2 GLU A 61 7 261 15 343 8 679 1 00 46 17 0
ATOM 470 C GLU A 61 7 318 20 621 9 273 1 00 42 62 c
ATOM 471 O GLU A 61 6 886 20 941 8 155 1 00 43 01 0
ATOM 472 N GLY A 62 8 351 21 235 9 812 1 00 42 12 N
ATOM 473 CA GLY A 62 9 044 22 254 9 063 1 00 42 47 C
ATOM 474 C GLY A 62 8 255 23 509 8 831 1 00 42 28 C
ATOM 475 O GLY A 62 8 454 24 187 7 811 1 00 43 30 O
ATOM 476 N SER A 63 7 372 23 819 9 775 1 00 41 92 N
ATOM 477 CA SER A 63 6 541 25 022 9 746 1 00 41 93 C
ATOM 478 CB SER A 63 6 436 25 625 11 158 1 00 42 03 C
ATOM 479 OG SER A 63 7 720 25 762 11 737 1 00 45 80 0
ATOM 480 C SER A 63 5 128 24 761 9 245 1 00 41 03 C
ATOM 481 O SER A 63 4 339 25 696 9 181 1 00 40 56 0
ATOM 482 N ASN A 64 4 820 23 501 8 912 1 00 40 57 N
ATOM 483 CA ASN A 64 3 485 23 079 8 452 1 00 40 70 C
ATOM 484 CB ASN A 64 3 129 23 764 7 117 1 00 40 66 C
ATOM 485 CG ASN A 64 2 613 22 788 6 048 1 00 42 06 C
ATOM 486 OD1 ASN A 64 2 632 21 575 6 233 1 00 44 67 O
ATOM 487 ND2 ASN A 64 2 168 23 328 4 916 1 00 38 47 N
ATOM 488 C ASN A 64 2 456 23 441 9 524 1 00 40 57 C
ATOM 489 O ASN A 64 1 385 23 971 9 216 1 00 40 25 O
ATOM 490 N SER A 65 2 791 23 178 10 789 1 00 40 60 N
ATOM 491 CA SER A 65 1 956 23 646 11 894 1 00 40 94 C
ATOM 492 CB SER A 65 2 596 24 855 12 605 1 00 41 18 C
ATOM 493 OG SER A 65 3 789 24 507 13 278 1 00 42 58 O
ATOM 494 C SER A 65 1 543 22 593 12 895 1 00 41 28 C
ATOM 495 O SER A 65 2 160 21 526 12 983 1 00 41 22 O
ATOM 496 N ALA A 66 0 462 22 895 13 627 1 00 42 01 N
ATOM 497 CA ALA A 66 0 009 22 107 14 785 1 00 42 51 C
ATOM 498 CB ALA A 66 1 128 21 099 14 370 1 00 41 63 C
ATOM 499 C ALA A 66 0 533 23 080 15 839 1 00 43 50 C
ATOM 500 O ALA A 66 1 302 24 014 15 501 1 00 44 12 O
ATOM 501 N SER A 67 0 109 22 859 17 089 1 00 43 19 N
ATOM 502 CA SER A 67 0 496 23 663 18 237 1 00 44 12 C
ATOM 503 CB SER A 67 0 719 24 297 18 894 1 00 43 60 C
ATOM 504 OG SER A 67 1 213 25 268 17 996 1 00 47 65 O
ATOM 505 C SER A 67 1 242 22 870 19 293 1 00 43 95 C
ATOM 506 O SER A 67 0 873 21 727 19 622 1 00 44 77 O
ATOM 507 N LEU A 68 2 330 23 448 19 769 1 00 42 85 N
ATOM 508 CA LEU A 68 3 042 22 858 20 894 1. 00 43 00 C
ATOM 509 CB LEU A 68 4 564 22 921 20 678 1 00 42 58 C
ATOM 510 CG LEU A 68 5 455 22 619 21 891 1 00 42 99 C
ATOM 511 CD1 LEU A 68 5 434 21 129 22 244 1. 00 40. 58 C
ATOM 512 CD2 LEU A 68 6 910 23 118 21 663 1. 00 41 93 C
ATOM 513 C LEU A 68 2 665 23 549 22 192 1 00 42 19 C ATOM 514 O LEU A 68 2.829 24.771 22.317 1,.00 42.62 0
ATOM 515 N THR A 69 2 .163 22 .778 23 .148 1 .00 42 .05 N
ATOM 516 CA THR A 69 1 .989 23 .296 24 .507 1 .00 42 .43 C
ATOM 517 CB THR A 69 0, .577 23 .016 25 .054 1, .00 42 .69 C
ATOM 518 OG1 THR A 69 -0, .358 23 .689 24 .216 1 .00 42 .54 O
ATOM 519 CG2 THR A 69 0 .394 23 .575 26 .498 1, .00 42 .39 C
ATOM 520 C THR A 69 3, .093 22. .768 25, .430 1, .00 42 .65 c
ATOM 521 O THR A 69 3, .364 21 .550 25 .466 1, .00 42 .53 o
ATOM 522 N ILE A 70 3 .781 23 .689 26 .105 1, .00 42 .73 N
ATOM 523 CA ILE A 70 4 .745 23 .320 27 .168 1 .00 43 .57 C
ATOM 524 CB ILE A 70 6, .118 24, .002 26, .988 1, .00 43, .71 C
ATOM 525 CGI ILE A 70 6, .679 23, .746 25, .576 1, .00 44, .37 C
ATOM 526 CD1 ILE A 70 7, .838 24 .682 25, .237 1, .00 43 .90 C
ATOM 527 CG2 ILE A 70 7 .092 23 .524 28 .033 1, .00 44 .26 C
ATOM 528 C ILE A 70 4, .172 23, .754 28, .501 1, .00 43, .90 C
ATOM 529 O ILE A 70 3, .967 24, .947 28, .725 1, .00 43, .83 O
ATOM 530 N ARG A 71 3, .893 22 .799 29 .373 1, .00 44 .36 N
ATOM 531 CA ARG A 71 3, .306 23, .110 30, .676 1, .00 46, .05 C
ATOM 532 CB ARG A 71 2, .214 22, .085 31, .036 1, .00 46, .19 C
ATOM 533 CG ARG A 71 1, .045 22, .023 30, .039 1, .00 48, .10 C
ATOM 534 CD ARG A 71 0, .227 20 .724 30, .205 1, .00 49 .51 C
ATOM 535 NE ARG A 71 0, .731 19, .665 29. .316 1, .00 54, .32 N
ATOM 536 CZ ARG A 71 0, .397 18, .364 29, .365 1, .00 55, .91 C
ATOM 537 NH1 ARG A 71 0, .952 17, .520 28, .489 1, .00 53, .43 N
ATOM 538 NH2 ARG A 71 -0. .473 17, .893 30. .281 1. .00 54. .28 N
ATOM 539 C ARG A 71 4, .391 23, .175 31, .761 1, .00 45. .39 C
ATOM 540 O ARG A 71 5, .536 22, .769 31, .521 1, ,00 45, .67 O
ATOM 541 N ASP A 72 4, .026 23, .683 32, .936 1, .00 44, .59 N
ATOM 542 CA ASP A 72 4, .934 23. .834 34, .095 1. ,00 44. ,37 C
ATOM 543 CB ASP A 72 5, .092 22, .514 34. .876 1. .00 43. .81 C
ATOM 544 CG ASP A 72 5, .939 22, .686 36, .175 1. .00 46. .29 C
ATOM 545 OD1 ASP A 72 5, .735 23. .682 36. .905 1. .00 45. .23 O
ATOM 546 OD2 ASP A 72 6, ,825 21. ,839 36. .454 1. .00 47, .68 O
ATOM 547 C ASP A 72 6, .308 24, .455 33, .780 1. .00 43, .81 C
ATOM 548 O ASP A 72 7, .353 23, ,849 34, .050 1. .00 43, .52 O
ATOM 549 N LEU A 73 6, .304 25, .675 33, .239 1. .00 43, .67 N
ATOM 550 CA LEU A 73 7, .543 26, .258 32, .634 1. .00 43, .28 C
ATOM 551 CB LEU A 73 7. .266 27, .548 31, .842 1. .00 42, ,21 C
ATOM 552 CG LEU A 73 6. .698 27, .428 30, .420 1. ,00 41. .64 C
ATOM 553 CD1 LEU A 73 6. .099 28, .774 29, .995 1. ,00 40. .11 C
ATOM 554 CD2 LEU A 73 7, .740 26, .946 29, .357 1. ,00 36. .14 C
ATOM 555 C LEU A 73 8, .606 26, .517 33, .668 1, .00 43. ,26 C
ATOM 556 O LEU A 73 8, .292 26. .835 34. ,809 1. ,00 43. ,51 O
ATOM 557 N ARG A 74 9, .860 26, ,363 33. ,260 1. ,00 43. ,56 N
ATOM 558 CA ARG A 74 11, .017 26, ,486 34. .148 1. ,00 43, ,52 C
ATOM 559 CB ARG A 74 11. .654 25. ,118 34. ,295 1. ,00 43. ,58 C
ATOM 560 CG ARG A 74 10. .699 24. ,083 34. ,838 1. ,00 43. ,45 c
ATOM 561 CD ARG A 74 10. .850 22, ,733 34. ,192 1. ,00 42. ,00 c
ATOM 562 NE ARG A 74 9. .778 21, ,852 34. ,646 1. ,00 43. ,41 N
ATOM 563 CZ ARG A 74 9. ,833 20. ,523 34. ,615 1. 00 44. ,43 C
ATOM 564 NH1 ARG A 74 8. .827 19. ,802 35. ,075 1. ,00 41. ,62 N
ATOM 565 NH2 ARG A 74 10. .914 19, ,910 34. ,152 1. ,00 46. ,68 N
ATOM 566 C ARG A 74 12. .011 27. .437 33. ,489 1. ,00 43. .68 C
ATOM 567 O ARG A 74 12. ,044 27. ,522 32. 275 1. 00 43. 51 O
ATOM 568 N VAL A 75 12. ,840 28. ,117 34. ,272 1. 00 44. ,03 N
ATOM 569 CA VAL A 75 13. ,843 29. ,050 33. ,721 1. 00 44. ,68 C
ATOM 570 CB VAL A 75 14. ,721 29. ,674 34. 832 1. 00 44. 80 C
ATOM 571 CGI VAL A 75 15. ,612 30. ,776 34. 269 1. 00 45. 53 C
ATOM 572 CG2 VAL A 75 13. ,843 30. ,232 35. 978 1. 00 44. 80 C
ATOM 573 C VAL A 75 14. ,709 28. ,404 32. ,615 1. 00 44. 75 C
ATOM 574 O VAL A 75 15. ,105 29. 063 31. 660 1. 00 43. 97 O
ATOM 575 N GLU A 76 14. ,940 27. 099 32. 726 1. 00 45. 06 N
ATOM 576 CA GLU A 76 15. ,736 26. ,364 31. 737 1. 00 45. 93 C
ATOM 577 CB GLU A 76 16. 321 25. 095 32. 381 1. 00 46. 31 C ATOM 578 CG GLU A 76 15..275 24,.161 32,.999 1,.00 48.76 c
ATOM 579 CD GLU A 76 15, .109 24, .314 34 .520 1, .00 51 .57 c
ATOM 580 OEl GLU A 76 14. .648 23. .325 35, .150 1, .00 52 .40 0
ATOM 581 OE2 GLU A 76 15, .425 25, .395 35 .082 1, .00 50 .39 0
ATOM 582 C GLU A 76 14, .994 26, .043 30 .400 1, .00 45 .85 c
ATOM 583 O GLU A 76 15. .585 25, .503 29, .447 1, .00 45 .45 0
ATOM 584 N ASP A 77 13, .705 26, .374 30 .341 1, .00 45 .80 N
ATOM 585 CA ASP A 77 12. .942 26, .294 29, .082 1, .00 44, .88 C
ATOM 586 CB ASP A 77 11. .452 26, .083 29, .370 1, .00 44 .95 c
ATOM 587 CG ASP A 77 11. .160 24. ,767 30, .081 1. .00 46, .55 c
ATOM 588 OD1 ASP A 77 11. .753 23. ,722 29, .728 1. .00 46, .55 0
ATOM 589 OD2 ASP A 77 10. ,291 24, .763 30, .975 1, .00 47 .83 0
ATOM 590 C ASP A 77 13. ,162 27. .535 28, .204 1. ,00 44, .03 c
ATOM 591 O ASP A 77 12. .911 27. .494 26, .991 1. ,00 44, .02 0
ATOM 592 N SER A 78 13, ,660 28. .629 28, .789 1, ,00 43, .14 N
ATOM 593 CA SER A 78 14, ,077 29. .796 27, .985 1. .00 42, .43 C
ATOM 594 CB SER A 78 14, ,855 30. .811 28, ,812 1, ,00 42, .27 C
ATOM 595 OG SER A 78 14, .061 31. ,325 29, .855 1. .00 45, .22 O
ATOM 596 C SER A 78 14. .916 29. .363 26, .764 1, .00 41, .89 C
ATOM 597 O SER A 78 15. .849 28. .570 26, .889 1. ,00 42, .32 0
ATOM 598 N GLY A 79 14. .600 29. .892 25, .591 1. .00 41, .21 N
ATOM 599 CA GLY A 79 15. .205 29. .375 24, .348 1. .00 41, .10 C
ATOM 600 C GLY A 79 14. .457 29. .849 23, .125 1. .00 41, .37 c
ATOM 601 O GLY A 79 13. ,426 30. .528 23, .223 1, ,00 41, .44 0
ATOM 602 N THR A 80 15. .012 29, .556 21, ,961 1, ,00 41, .26 N
ATOM 603 CA THR A 80 14. ,302 29, .778 20, .702 1, ,00 41, .23 C
ATOM 604 CB THR A 80 15. ,234 30, .352 19, ,639 1, ,00 40, ,40 C
ATOM 605 OG1 THR A 80 15. .748 31. .599 20, .124 1, .00 40, .92 O
ATOM 606 CG2 THR A 80 14. .478 30. .616 18. .350 1. ,00 41, .08 C
ATOM 607 C THR A 80 13. .713 28. .441 20, .278 1, .00 41, .52 C
ATOM 608 O THR A 80 14, ,399 27, .396 20, .256 1. .00 40, .53 O
ATOM 609 N TYR A 81 12, .427 28, ,479 19, .975 1, .00 42, .20 N
ATOM 610 CA TYR A 81 11, ,701 27, .273 19, .624 1. .00 42, .88 C
ATOM 611 CB TYR A 81 10, ,517 27. .079 20. .576 1, .00 42, .50 C
ATOM 612 CG TYR A 81 10. .876 26. .675 21, .993 1, .00 43, .04 C
ATOM 613 CD1 TYR A 81 11. .258 27. .628 22. .947 1, .00 42, .08 C
ATOM 614 CEl TYR A 81 11. .591 27. .248 24. .246 1, .00 40, .82 C
ATOM 615 CZ TYR A 81 11. .540 25. ,910 24, .619 1, .00 41, .51 C
ATOM 616 OH TYR A 81 11. .888 25. .530 25, .909 1, .00 41, .77 O
ATOM 617 CE2 TYR A 81 11. .147 24. .957 23. .712 1, .00 42, ,75 C
ATOM 618 CD2 TYR A 81 10, ,807 25. .338 22. .402 1, .00 44, ,77 c
ATOM 619 C TYR A 81 11, ,244 27. .466 18. .192 1, .00 43, .89 c
ATOM 620 O TYR A 81 10. ,884 28. .587 17. .784 1. ,00 44, .08 0
ATOM 621 N LYS A 82 11. ,309 26, ,390 17. .414 1, .00 44, .31 N
ATOM 622 CA LYS A 82 10. ,903 26, .405 16. .020 1, .00 44, .69 C
ATOM 623 CB LYS A 82 12. ,116 26. ,515 15. ,090 1. .00 45, .16 C
ATOM 624 CG LYS A 82 12. ,764 27. ,870 14. .991 1, ,00 47, .79 C
ATOM 625 CD LYS A 82 14, ,103 27, ,702 14. .313 1. ,00 50, .84 C
ATOM 626 CE LYS A 82 15. ,117 28, ,697 14. .882 1. ,00 57. .07 C
ATOM 627 NZ LYS A 82 14. ,749 30. ,121 14. .595 1. ,00 58. ,51 N
ATOM 628 C LYS A 82 10, ,180 25. ,096 15. .722 1. ,00 44, .51 C
ATOM 629 0 LYS A 82 10. ,470 24. ,057 16. .367 1. ,00 43. .69 O
ATOM 630 N CYS A 83 9. ,252 25, ,164 14. ,756 1. ,00 43. ,58 N
ATOM 631 CA CYS A 83 8. ,637 23. ,975 14, .139 1. ,00 43. .92 C
ATOM 632 CB CYS A 83 7. ,118 24. ,116 14. ,069 1. 00 44. ,57 C
ATOM 633 SG CYS A 83 6. ,599 25. ,545 13. ,076 1. ,00 45. ,39 S
ATOM 634 C CYS A 83 9. ,157 23. ,755 12. ,711 1. ,00 43. ,64 C
ATOM 635 O CYS A 83 9. ,508 24. ,712 12. ,004 1. 00 41. ,71 O
ATOM 636 N LYS A 84 9. ,227 22. ,476 12. .334 1. ,00 44. ,18 N
ATOM 637 CA LYS A 84 9. ,492 22. ,022 10. ,982 1. 00 45. ,42 C
ATOM 638 CB LYS A 84 10. ,647 21. ,020 10. ,957 1. 00 46. ,76 c
ATOM 639 CG LYS A 84 12. 060 21. ,586 10. 916 1. 00 48. 51 c
ATOM 640 CD LYS A 84 12. ,977 20. ,615 10. ,171 1. 00 53. ,46 c
ATOM 641 CE LYS A 84 14. ,486 20. ,718 10. .553 1. ,00 53. ,84 c ATOM 642 NZ LYS A 84 15.072 22.085 10.793 1.00 53.72 N
ATOM 643 C LYS A 84 8 .253 21 .275 10 .551 1 .00 45 .80 C
ATOM 644 0 LYS A 84 7 .891 20 .280 11 .175 1 .00 47 .54 O
ATOM 645 N ALA A 85 7 .583 21 .781 9 .522 1 .00 45 .28 N
ATOM 646 CA ALA A 85 6 .374 21 .196 8 .991 1. .00 45 .01 C
ATOM 647 CB ALA A 85 5 .403 22, .295 8. .615 1, .00 44 .83 C
ATOM 648 C ALA A 85 6. .708 20 .343 7 .787 1 .00 45 .27 c
ATOM 649 O ALA A 85 7 .288 20 .831 6 .827 1 .00 44 .57 0
ATOM 650 N TYR A 86 6 .363 19, .058 7 .861 1, .00 45, .35 N
ATOM 651 CA TYR A 86 6 .435 18, .160 6 .717 1, .00 45, .77 C
ATOM 652 CB TYR A 86 6 .775 16 .736 7 .174 1 .00 46 .34 C
ATOM 653 CG TYR A 86 8, .056 16, .762 7 .964 1, .00 48, .76 C
ATOM 654 GDI TYR A 86 8 .038 16, .975 9 .343 1, .00 50, .37 C
ATOM 655 CEl TYR A 86 9 .214 17, .058 10 .084 1, .00 51, .40 c
ATOM 656 CZ TYR A 86 10, .427 16, .942 9, .447 1, .00 50, ,41 c
ATOM 657 OH TYR A 86 11 .579 17, .012 10 .193 1, .00 50, .04 0
ATOM 658 CE2 TYR A 86 10 .488 16, .746 8 .067 1, .00 52, .75 c
ATOM 659 CD2 TYR A 86 9, .293 16, .660 7, .327 1, .00 51, .59 c
ATOM 660 C TYR A 86 5, .110 18, .260 5 .970 1, .00 45, .44 c
ATOM 661 O TYR A 86 4 .097 18, .623 6. .568 1, .00 45, .39 0
ATOM 662 N ARG A 87 5, .113 17, .970 4, .671 1, .00 44. .88 N
ATOM 663 CA ARG A 87 3, .922 18, .186 3 .839 1, .00 45, .04 C
ATOM 664 CB ARG A 87 4, .082 19, .422 2 .940 1, .00 44, .90 c
ATOM 665 CG ARG A 87 4, .795 20. .547 3, .675 1, .00 46. .39 c
ATOM 666 CD ARG A 87 4, .537 21, .958 3, .168 1. .00 46, .94 c
ATOM 667 NE ARG A 87 4 .855 22, .168 1 .775 1, .00 44, .54 N
ATOM 668 CZ ARG A 87 6, .063 22, ,093 1, .227 1. ,00 45. .63 C
ATOM 669 NH1 ARG A 87 6, .192 22, .323 -0, .071 1. .00 41. ,09 N
ATOM 670 NH2 ARG A 87 7, .132 21, .788 1 .955 1, .00 48, .23 N
ATOM 671 C ARG A 87 3, .533 16, ,958 3, .023 1. ,00 44. .92 C
ATOM 672 O ARG A 87 4, .366 16, .103 2, .700 1. .00 45. .77 O
ATOM 673 N ARG A 88 2, .248 16, .881 2, .721 1, .00 44. ,30 N
ATOM 674 CA ARG A 88 1, ,668 15. .817 1, .928 1. .00 43. ,99 C
ATOM 675 CB ARG A 88 0, .696 15, .000 2, .807 1. .00 43. .99 C
ATOM 676 CG ARG A 88 -0, .252 14, .029 2, .076 1. .00 45. .06 c
ATOM 677 CD ARG A 88 0, ,460 12, .944 1. .277 1. .00 47, .65 c
ATOM 678 NE ARG A 88 1. .605 12, .336 1, .965 1. .00 51. ,20 N
ATOM 679 CZ ARG A 88 2, .387 11, .400 1, ,414 1. .00 52, ,98 C
ATOM 680 NH1 ARG A 88 3. .420 10, .892 2. ,085 1. .00 53. ,13 N
ATOM 681 NH2 ARG A 88 2. .132 10, .967 0. .184 1. .00 52, .26 N
ATOM 682 C ARG A 88 0. .952 16, .583 0, .837 1, .00 43, .43 C
ATOM 683 O ARG A 88 0. .038 17. .364 1. .138 1. .00 43. ,15 O
ATOM 684 N CYS A 89 1. .415 16. .420 -0. .415 1. .00 43. .21 N
ATOM 685 CA CYS A 89 0. .884 17. .212 -1. .507 1. .00 42, .95 C
ATOM 686 CB CYS A 89 2, .000 17. ,979 -2. .229 1. ,00 42. ,90 C
ATOM 687 SG CYS A 89 2, .955 19. ,217 -1. .275 1. ,00 43. ,42 s
ATOM 688 C CYS A 89 0, .128 16. .305 -2. .486 1, ,00 43. ,49 c
ATOM 689 O CYS A 89 0. .348 15. ,066 -2. ,527 1. ,00 43. ,18 0
ATOM 690 N ALA A 90 -0. .749 16. ,921 -3, ,288 1. ,00 43. 77 N
ATOM 691 CA ALA A 90 -1, .513 16. ,151 -4, ,268 1. ,00 44. 87 c
ATOM 692 CB ALA A 90 -2. ,429 17. ,069 -5. ,090 1. .00 44. 89 c
ATOM 693 C ALA A 90 -0. ,644 15. ,288 -5. ,199 1. ,00 45. 28 c
ATOM 694 O ALA A 90 -1. .169 14. ,364 -5. ,833 1. ,00 45. 43 0
ATOM 695 N PHE A 91 0. ,667 15. 576 -5. 273 1. 00 45. 99 N
ATOM 696 CA PHE A 91 1. ,545 14. 830 -6. 195 1. 00 46. 92 C
ATOM 697 CB PHE A 91 2. ,393 15. 747 -7. ,132 1. 00 46. 28 C
ATOM 698 CG PHE A 91 2. 962 16. 963 -6. 455 1. 00 44. 74 C
ATOM 699 CD1 PHE A 91 4. 151 16. 888 -5. 738 1. 00 44. 41 C
ATOM 700 CEl PHE A 91 4. ,667 18. 003 -5. 081 1. 00 44. 69 C
ATOM 701 CZ PHE A 91 3. 996 19. 211 -5. 159 1. 00 44. 49 C
ATOM 702 CE2 PHE A 91 2. 809 19. 299 -5. 898 1. 00 44. 64 c
ATOM 703 CD2 PHE A 91 2. 304 18. 182 -6. 536 1. 00 42. 85 c
ATOM 704 C PHE A 91 2. 414 13. 763 -5. 536 1. 00 48. 05 c
ATOM 705 O PHE A 91 2. 010 12. 597 -5. 460 1. 00 48. 28 0 ATOM 706 N ASN A 92 3.598 14.166 -5.067 1.00 49.62 N
ATOM 707 CA ASN A 92 4 .708 13 .232 -4 .837 1 .00 51 .06 C
ATOM 708 CB ASN A 92 5 .379 12, .890 -6. .178 1, .00 50 .88 C
ATOM 709 CG ASN A 92 .729 11 .730 -6 .890 1 .00 50 .22 C
ATOM 710 OD1 ASN A 92 4 .899 11 .570 -8 .092 1 .00 50 .52 O
ATOM 711 ND2 ASN A 92 3 .991 10 .909 -6 .156 1 .00 49 .11 N
ATOM 712 C ASN A 92 5 .801 13, .698 -3 .866 1, .00 52 .19 C
ATOM 713 O ASN A 92 5 .677 14, .734 -3 .197 1, .00 52 .40 O
ATOM 714 N THR A 93 6. .880 12 .914 -3 .824 1 .00 53 .42 N
ATOM 715 CA THR A 93 8, .083 13, .223 -3, .052 1, .00 54 .60 C
ATOM 716 CB THR A 93 8 .994 11, .972 -2, .916 1, .00 54 .62 C
ATOM 717 OG1 THR A 93 8 .874 11 .154 -4 .091 1, .00 53 .58 0
ATOM 718 CG2 THR A 93 8, .596 11, .159 -1, .685 1, .00 54, .51 C
ATOM 719 C THR A 93 8, .868 14, .414 -3, .632 1, .00 55, .41 c
ATOM 720 O THR A 93 9 .611 14, .280 -4 .620 1, .00 55 .67 0
ATOM 721 N GLY A 94 8, .692 15. ,574 -2, .998 1, .00 56, .30 N
ATOM 722 CA GLY A 94 9, .345 16. .808 -3, .421 1, .00 56, .84 C
ATOM 723 C GLY A 94 9, .800 17, .601 -2, .212 1, .00 57, .51 C
ATOM 724 O GLY A 94 9 .473 17, .239 -1 .081 1, .00 57 .17 O
ATOM 725 N VAL A 95 10, .551 18. .680 -2, .472 1. ,00 58, .10 N
ATOM 726 CA VAL A 95 11, .176 19. .569 -1, .456 1. .00 58, .30 C
ATOM 727 CB VAL A 95 11, .911 20, .790 -2, .131 1, .00 58, .41 C
ATOM 728 CGI VAL A 95 13, .412 20. .494 -2. ,326 1. .00 58, .19 C
ATOM 729 CG2 VAL A 95 11, .712 22. .104 -1, .347 1. .00 58, ,50 C
ATOM 730 C VAL A 95 10, .253 20, .029 -0, .314 1. .00 58, .52 C
ATOM 731 O VAL A 95 9, ,675 21. .124 -0. ,345 1. ,00 59, .14 O
ATOM 732 N GLY A 96 10, .150 19. .189 0. .711 1. .00 58. ,23 N
ATOM 733 CA GLY A 96 9, .231 19. .439 1, .795 1. .00 57, .55 C
ATOM 734 C GLY A 96 9. ,904 19. .629 3, .128 1. .00 57. .16 C
ATOM 735 O GLY A 96 11. .107 19. .410 3. ,291 1. .00 57. .41 0
ATOM 736 N TYR A 97 9, .080 19. .986 4, ,097 1. .00 56. .75 N
ATOM 737 CA TYR A 97 9, .536 20. .547 5, .355 1. .00 55. ,42 C
ATOM 738 CB TYR A 97 10. ,632 19. .684 6. ,021 1. .00 55. ,74 C
ATOM 739 CG TYR A 97 11. ,960 20. .312 6. .399 1, .00 56. ,10 C
ATOM 740 CD1 TYR A 97 12, .041 21. .541 7. .057 1, .00 56. ,27 c
ATOM 741 CEl TYR A 97 13. ,296 22. .095 7. ,410 1, .00 57. ,14 c
ATOM 742 CZ TYR A 97 14. ,461 21. .387 7. ,126 1. .00 56. ,83 c
ATOM 743 OH TYR A 97 15. .689 21. .887 7, ,473 1. .00 55. ,48 0
ATOM 744 CE2 TYR A 97 14. .391 20. ,154 6. ,503 1. ,00 57. .28 c
ATOM 745 CD2 TYR A 97 13. .150 19. ,623 6. .149 1. ,00 56. ,77 c
ATOM 746 C TYR A 97 9. .846 22. .013 5, ,115 1. ,00 54. ,29 c
ATOM 747 O TYR A 97 10. ,748 22. ,376 4. ,358 1. .00 54. ,07 0
ATOM 748 N LYS A 98 8. ,963 22. ,829 5. ,671 1. ,00 52. ,88 N
ATOM 749 CA LYS A 98 9. .117 24. ,254 5, ,774 1. ,00 52. ,16 c
ATOM 750 CB LYS A 98 7, .918 24, .963 5, .146 1. .00 52. ,30 c
ATOM 751 CG LYS A 98 7. .868 24. ,902 3. ,594 1. ,00 51. ,71 c
ATOM 752 CD LYS A 98 8. .873 25. ,820 2. .951 1. ,00 51. ,20 c
ATOM 753 CE LYS A 98 9, ,000 25. ,574 1. .445 1. ,00 52. ,94 c
ATOM 754 NZ LYS A 98 . 7. ,778 25. ,938 0. ,660 1. 00 53. ,22 N
ATOM 755 C LYS A 98 9. ,216 24. ,543 7. ,260 1. ,00 51. ,92 c
ATOM 756 O LYS A 98 8. ,681 23. ,804 8. ,070 1. ,00 50. ,81 0
ATOM 757 N GLU A 99 9. ,931 25. ,603 7. ,610 1. 00 52. 28 N
ATOM 758 CA GLU A 99 10. ,230 25. ,940 9. ,000 1. 00 53. 27 C
ATOM 759 CB GLU A 99 11. ,721 26. ,262 9. ,140 1. 00 53. 26 C
ATOM 760 CG GLU A 99 12. ,638 25. ,140 9. ,605 1. .00 55. 49 C
ATOM 761 CD GLU A 99 13. ,946 25. ,678 10. 221 1. 00 56. 41 C
ATOM 762 OEl GLU A 99 14. ,761 24. ,867 10. 720 1. 00 60. 13 O
ATOM 763 OE2 GLU A 99 14. ,168 26. ,916 10. ,214 1. 00 60. 48 O
ATOM 764 C GLU A 99 9. 438 27. 174 9. 456 1. 00 52. 61 C
ATOM 765 O GLU A 99 9. ,172 28. 086 8. 651 1. 00 52. 40 0
ATOM 766 N GLY A 100 9. ,078 27. ,200 10. 741 1. 00 51. 81 N
ATOM 767 CA GLY A 100 8. 580 28. 413 11. 382 1. 00 50. 72 c
ATOM 768 C GLY A 100 9. 744 29. 356 11. 618 1. 00 50. 01 c
ATOM 769 O GLY A 100 10. 886 28. 903 11. 701 1. 00 49. 52 0 ATOM 770 N ALA A 101 9,.466 30,.662 11.717 1.00 49.16 N
ATOM 771 CA ALA A 101 10. .527 31, .661 11, .904 1, .00 48 .33 C
ATOM 772 CB ALA A 101 10, .100 33, .021 11, .324 1, .00 48 .12 C
ATOM 773 C ALA A 101 11. .027 31. .803 13, ,371 1, .00 47, .76 C
ATOM 774 O ALA A 101 11, .992 32, .535 13, .634 1, .00 47, .69 O
ATOM 775 N GLY A 102 10, .355 31, .128 14, .305 1 .00 47 .20 N
ATOM 776 CA GLY A 102 10. .790 31, ,013 15. ,715 1, .00 46, .78 C
ATOM 777 C GLY A 102 9. .916 31, ,710 16, .745 1, .00 46, .63 C
ATOM 778 O GLY A 102 9, .217 32, .681 16, .417 1 .00 47 .73 o
ATOM 779 N THR A 103 9. .908 31, ,178 17. .972 1, .00 45, .85 N
ATOM 780 CA THR A 103 9. .426 31, .883 19. .169 1, .00 44, .12 C
ATOM 781 CB THR A 103 8. .331 31, .084 19. .922 1, .00 44, .44 C
ATOM 782 OG1 THR A 103 7. .235 30, ,802 19. .052 1, .00 45, .90 O
ATOM 783 CG2 THR A 103 7. .798 31, .873 21, .105 1, .00 41, .87 C
ATOM 784 C THR A 103 10. ,601 32, .067 20. .147 1, .00 43, .84 C
ATOM 785 O THR A 103 11. .257 31. .085 20. .507 1, .00 42, .90 O
ATOM 786 N VAL A 104 10. .862 33, .304 20. .589 1, .00 42, .99 N
ATOM 787 CA VAL A 104 11. .821 33. ,546 21. .693 1, .00 42, .66 C
ATOM 788 CB VAL A 104 12. .627 34. .863 21. .516 1, .00 42, .32 C
ATOM 789 CGI VAL A 104 13. .729 34. .905 22. .549 1. .00 42. ,52 C
ATOM 790 CG2 VAL A 104 13. .198 34. .982 20. .109 1, .00 42. .86 c
ATOM 791 C VAL A 104 11. .141 33. .568 23. .098 1, .00 42, .52 c
ATOM 792 O VAL A 104 10. ,465 34. .543 23. .488 1. .00 41. .37 0
ATOM 793 N LEU A 105 11. .360 32. .509 23. .866 1, .00 42. .08 N
ATOM 794 CA LEU A 105 10. .746 32, .396 25. .173 1, .00 42, .02 C
ATOM 795 CB LEU A 105 10. .134 30. .985 25. .370 1, .00 41. .41 c
ATOM 796 CG LEU A 105 9. ,750 30, ,627 26. .814 1, .00 40. .79 c
ATOM 797 GDI LEU A 105 8. ,484 31. ,377 27. .340 1. .00 37. .83 c
ATOM 798 CD2 LEU A 105 9. .593 29. ,131 26. .998 1, ,00 40. .33 c
ATOM 799 C LEU A 105 11. ,753 32, .736 26. .272 1, .00 42, .74 c
ATOM 800 O LEU A 105 12. ,894 32. .248 26. ,274 1. .00 42. .12 0
ATOM 801 N THR A 106 11. ,323 33. .587 27. ,203 1. .00 43. .70 N
ATOM 802 CA THR A 106 12. .051 33. .796 28. .459 1. .00 44, .17 C
ATOM 803 CB THR A 106 12. .621 35. .232 28, ,590 1. .00 44, ,10 C
ATOM 804 OG1 THR A 106 13. .521 35. .493 27, ,512 1. .00 43. .79 O
ATOM 805 CG2 THR A 106 13. .399 35. .362 29, ,872 1. ,00 43. .32 C
ATOM 806 C THR A 106 11. .154 33, .465 29, ,666 1, .00 45. .05 C
ATOM 807 O THR A 106 10. .015 33, .942 29. ,770 1. .00 45. .24 O
ATOM 808 N VAL A 107 11. .679 32. .648 30. ,574 1. ,00 45, ,71 N
ATOM 809 CA VAL A 107 10, .946 32. .265 31. ,780 1. ,00 46, .23 C
ATOM 810 CB VAL A 107 10. .790 30. ,730 31. ,916 1, ,00 45. ,95 c
ATOM 811 CGI VAL A 107 9, .747 30. .402 32. ,993 1. ,00 45, ,73 c
ATOM 812 CG2 VAL A 107 10, ,394 30, ,105 30. ,561 1, ,00 44. ,60 c
ATOM 813 C VAL A 107 11, ,618 32. .850 33. ,016 1. .00 47. ,10 c
ATOM 814 O VAL A 107 12. ,778 32. .556 33. ,301 1. .00 46, .92 o
ATOM 815 N LYS A 108 10. ,840 33, .668 33. ,727 1, .00 48. .46 N
ATOM 816 CA LYS A 108 11. ,258 34. .453 34. ,889 1. .00 49, ,58 C
ATOM 817 CB LYS A 108 11, ,515 33, .576 36. ,110 1, .00 49. ,94 C
ATOM 818 CG LYS A 108 10. ,246 33. ,322 36. ,937 1, ,00 49. .89 C
ATOM 819 CD LYS A 108 10. .037 34. .370 38. ,058 1. .00 48, ,87 C
ATOM 820 CE LYS A 108 11, .008 34, .151 39. ,197 1. .00 49. .35 C
ATOM 821 NZ LYS A 108 11. .300 32. ,697 39. 377 1. .00 47. ,83 N
ATOM 822 C LYS A 108 12. .435 35. ,340 34. ,583 1. .00 50. .70 C
ATOM 823 O LYS A 108 12, .374 36. .115 33. ,626 1. ,00 52, .01 O
ATOM 824 O HOH W 1 10. ,564 12. ,981 15. ,180 1. ,00 57. ,87 O
ATOM 825 O HOH W 2 4. .884 38. ,038 19. ,422 1, ,00 39. ,09 O
ATOM 826 O HOH W 3 18. ,831 30. ,006 11. 592 1. ,00 61. ,93 O
ATOM 827 O HOH W 4 1. ,789 33. ,404 36. 744 1. .00 54. ,79 O
ATOM 828 O HOH W 5 8. .978 32. ,010 7. ,686 1. .00 56. ,85 O
ATOM 829 O HOH W 6 6. ,845 33. ,982 8. 593 1. ,00 71. 15 O
ATOM 830 O HOH W 7 10. ,498 39. ,946 15. 695 1. ,00 65. ,23 0
ATOM 831 O HOH W 8 13. .932 22. ,652 30. ,685 1. ,00 42. ,16 0
ATOM 832 O HOH W 9 -3. ,165 18. ,770 8. 538 1. ,00 39. 40 0
ATOM 833 O HOH W 10 18. ,047 27. ,608 16. 064 1. ,00 55. 15 0 ATOM 834 O HOH W 11 ■11..674 22,.619 11..921 1,.00 63,,53 0
ATOM 835 O HOH w 12 12, .389 9, .964 5, .651 1, .00 63, .77 0
ATOM 836 O HOH w 13 -2, .440 23, .895 28, .901 1, .00 65, .10 0
ATOM 837 O HOH w 14 1. .615 35, .824 29, .148 1, .00 52, .11 0
ATOM 838 O HOH w 15 21. .110 27, .208 16, .490 1, .00 52, .35 0
ATOM 839 O HOH w 16 0, .817 32, .375 23, .701 1, .00 50, .69 0
ATOM 840 O HOH w 17 0, .234 31, .767 1, ,378 1, .00 58, .08 0
ATOM 841 O HOH w 18 15, .129 33, .987 33, ,625 1, .00 67, .94 0
ATOM 842 O HOH w 19 9, .080 35, .304 2, .554 1, .00 48, .79 0
ATOM 843 O HOH w 20 15, .507 38, .561 33 .060 1, .00 40, .13 0
ATOM 844 O HOH w 21 14. .043 19, .259 27, ,586 1. .00 56. ,30 0
ATOM 845 O HOH w 22 11. .011 38. .760 11, .090 1. .00 52. ,13 0
ATOM 846 O HOH w 23 19. .096 19. .513 27, .600 1. .00 45. ,11 0
ATOM 847 O HOH w 24 8. .529 10, .231 23, ,841 1. .00 54. .09 0
ATOM 848 O HOH w 25 18. .602 28, .055 41, .400 1. .00 44. .05 0
ATOM 849 O HOH w 26 -0. .858 32, .893 -3, .524 1. .00 48. .46 0
ATOM 850 O HOH w 27 6, .490 13, .377 4, .108 1. .00 66. .62 0
ATOM 851 O HOH w 28 3, .930 14, .910 13, ,874 1. .00 30. .35 0
ATOM 852 O HOH w 29 -8, .350 27, .041 7, .152 1, .00 64. .13 0
ATOM 853 O HOH w 30 19, .016 32, .914 41, .473 1, ,00 53. .57 0
ATOM 854 O HOH w 31 7, .643 36, .456 8, .441 1. .00 49, ,74 0
ATOM 855 O HOH w 32 0. .695 30. .653 25, .517 1. .00 40. ,63 o
ATOM 856 O HOH w 33 7. .361 13. .425 13, .040 1. .00 56. ,27 o
ATOM 857 O HOH w 34 16. .881 31. .557 10, .306 1. .00 60. ,57 0
ATOM 858 O HOH w 35 8. .287 13. .597 10, .547 1, ,00 57. ,02 o
ATOM 859 O HOH w 36 8. .039 13. .358 19, .018 1. ,00 34. ,10 0
ATOM 860 O HOH w 37 11. .473 14. .810 5, .085 1. .00 72. ,98 0
ATOM 861 0 HOH w 38 18. .961 23. ,256 8, .032 1. ,00 45. .71 0
ATOM 862 0 HOH w 39 7, ,350 25, .517 37, .490 1. ,00 57. .94 0
ATOM 863 0 HOH w 40 0, .871 15, .567 22, .621 1. .00 36. .05 0
ATOM 864 0 HOH w 41 9, ,259 29, .560 4, .060 1. ,00 45. .31 0
ATOM 865 0 HOH w 42 15, .495 16, .208 13, .522 1. .00 48. .14 0
ATOM 866 0 HOH w 43 -6. .942 25. .812 16, .028 1, .00 49. .25 0
ATOM 867 0 HOH w 44 8. .961 33. .009 1, ,653 1, .00 58. .96 0
ATOM 868 0 HOH w 45 8. .820 29. .722 1. ,693 1, .00 55. .31 0
ATOM 869 0 HOH w 46 0. .934 10. .101 7, ,881 1, .00 46. ,26 0
ATOM 870 0 HOH w 47 9. .394 17. .052 17, ,564 1, .00 40. ,92 0
ATOM 871 0 HOH w 48 15. .096 33. .948 15, ,334 1, .00 51. .10 0
ATOM 872 0 HOH w 49 2. .093 24. .026 37, .059 1. .00 57, .99 0
ATOM 873 0 HOH w 50 -0. ,613 16. .821 11, .553 1. ,00 40. .82 0
ATOM 874 0 HOH w 51 2. .378 35. .855 32, .307 1, ,00 57, .82 0
ATOM 875 0 HOH w 52 10. .646 16. .132 25, .937 1, ,00 28. .33 0
ATOM 876 0 HOH w 53 7. .810 15, .199 17. .107 1. ,00 35. ,66 0
ATOM 877 0 HOH w 54 7. ,946 10, .228 19. .423 1. ,00 58. ,71 0
ATOM 878 0 HOH w 55 -5. ,087 21. .855 29, .858 1. ,00 52. ,92 0
ATOM 879 0 HOH w 56 -2, ,460 30. .063 -6. .344 1. ,00 63. ,51 0
ATOM 880 0 HOH w 57 -9, ,940 27. .200 4, .714 1. ,00 62. ,80 0
ATOM 881 0 HOH w 58 7, ,680 43, .303 24, .786 1. ,00 54. ,95 0
ATOM 882 0 HOH w 59 18, ,234 20, ,029 14. .184 1. ,00 44. ,17 0
ATOM 883 0 HOH w 60 -8, ,225 25, .875 -4. .166 1. ,00 54. ,98 0
ATOM 884 0 HOH w 61 16, ,874 18, .265 12, .498 1. ,00 68. .89 0
ATOM 885 0 HOH w 62 7, ,892 14, .001 1. .905 1. ,00 65. ,53 o
ATOM 886 0 HOH w 63 -0, ,782 37, .111 37. .382 1. .00 63, .57 0
ATOM 887 0 HOH w 64 22. ,498 23. .044 16. ,311 1. ,00 36. ,02 0
ATOM 888 0 HOH w 65 12, ,976 40. .341 37. ,741 1. ,00 48. ,78 o
ATOM 889 0 HOH w 66 20. ,503 26. ,080 31. ,957 1. ,00 53. ,38 0
ATOM 890 0 HOH w 67 5. ,796 9. .451 26. ,499 1. ,00 70. ,39 0
ATOM 891 0 HOH w 68 -1. ,275 15. .214 -8. ,910 1. ,00 52. ,06 o
ATOM 892 0 HOH w 69 14. ,525 15, ,403 8. ,537 1. ,00 65. ,82 o
ATOM 893 0 HOH w 70 12. ,969 42. .361 34. ,897 1. ,00 82. ,78 o
ATOM 894 0 HOH w 71 16, ,514 20. .813 35. ,521 1. ,00 77. ,73 o
ATOM 895 0 HOH w 72 9, ,910 10. .781 13. ,915 1. ,00 58. ,26 o
ATOM 896 0 HOH w 73 12, ,437 24. .710 1. ,893 1. ,00 64. ,10 0
ATOM 897 0 HOH w 74 20. ,747 31. ,422 22. 103 1. 00 41. 64 0 ATOM 898 O HOH W 75 15.721 36.144 32.861 1.00 62.03 0
ATOM 899 O HOH W 76 0 .635 31 .352 13 .751 1 .00 31 .08 0
ATOM 900 O HOH w 77 22 .337 23 .558 24 .955 1 .00 40 .08 0
ATOM 901 O HOH w 78 7 .932 13 .265 7 .088 1 .00 67 .66 0
ATOM 902 O HOH w 79 20 .517 29 .057 29 .548 1 .00 52 .12 0
ATOM 903 O HOH w 80 15 .259 17 .514 0 .795 1 .00 60 .37 0
ATOM 904 O HOH w 81 -15 .805 25 .833 10 .294 1 .00 53 .42 0
ATOM 905 O HOH w 82 3, .946 10 .765 28 .247 1 .00 71 .57 0
ATOM 906 O HOH w 83 -5. .175 28 .237 13 .448 1 .00 54 .99 0
ATOM 907 O HOH w 84 5 .447 39 .199 25 .619 1 .00 52 .76 0
ATOM 908 O HOH w 85 16, .383 26 .315 43 .672 1 .00 52 .39 0
ATOM 909 O HOH w 86 8 .064 40 .405 25 .323 1. .00 54 .14 0
ATOM 910 O HOH w 87 13 .597 39 .136 30 .408 1 .00 59 .39 0
ATOM 911 O HOH w 88 7, .974 10 .662 16 .213 1 .00 48 .90 0
ATOM 912 O HOH w 89 3, .093 11 .244 9. .567 1 .00 53 .95 0
ATOM 913 O HOH w 90 11, .935 23, .245 26 .965 1, .00 25 .98 0
ATOM 914 O HOH w 91 15, .676 17, .694 31 .366 1 .00 49 .77 0
ATOM 915 O HOH w 92 1 .434 28 .589 -1 .853 1 .00 61 .65 0
ATOM 916 O HOH w 93 -0, .967 31, .873 18, .174 1, .00 28 .83 0
ATOM 917 O HOH w 94 3, .569 19, .724 15 .627 1, .00 69 .29 0
ATOM 918 O HOH w 95 16, .027 26, .116 17 .619 1 .00 41 .37 0
ATOM 919 O HOH w 96 -3, .179 23. .176 16, .288 1, .00 35, .67 0
ATOM 920 O HOH w 97 11. .378 36, .643 24, .903 1, .00 38, .26 0
ATOM 921 0 HOH w 98 11. .275 12, .570 12 .614 1, .00 61 .05 0
ATOM 922 0 HOH w 99 0. .392 37, ,579 30, .346 1, .00 63, .86 0
ATOM 923 0 HOH w 100 3, .615 36, .054 27, .042 1, .00 52, .83 0
ATOM 924 0 HOH w 101 19, .917 24, .030 23 .404 1, .00 33, .13 0
ATOM 925 0 HOH w 102 25, .442 22, .459 25, .169 1, .00 52, .27 0
ATOM 926 0 HOH w 103 13, .667 17, .731 8, .904 1, .00 57, .13 0
ATOM 927 0 HOH w 104 12, .838 33, .231 16, .397 1, .00 49, .03 0
ATOM 928 0 HOH w 105 -4. .419 19, .850 7, .056 1, .00 48, .59 0
ATOM 929 0 HOH w 106 2, .163 14, .571 24, .878 1, .00 58, .28 0
ATOM 930 0 HOH w 107 12. .110 41. .016 26. .077 1. .00 43. ,46 0
ATOM 931 0 HOH w 108 -6. .767 22. .389 4. ,829 1. .00 51, .02 0
ATOM 932 0 HOH w 109 -9. .391 28, .696 0, .532 1, .00 56, .17 0
ATOM 933 0 HOH w 110 12. .664 12, .157 15. .211 1. .00 69, .74 0
ATOM 934 0 HOH w 111 14. .219 30, .759 11. .453 1. ,00 54, .75 0
ATOM 935 0 HOH w 112 22. .000 34, .294 19. .285 1. .00 54, .23 0
ATOM 936 0 HOH w 113 -6. .324 17. .895 4, .472 1. .00 42, .42 o
ATOM 937 0 HOH w 114 26. .863 26. .038 22. .840 1. .00 52, .75 0
ATOM 938 0 HOH w 115 18. .802 30. ,472 41. .476 1. .00 43, .99 0
ATOM 939 0 HOH w 116 7. .804 8, .898 -3. .753 1. .00 69, ,67 0
ATOM 940 0 HOH w 117 7. .387 14, .592 -7, .052 1, .00 46, ,13 0
ATOM 941 0 HOH w 118 -0, .533 19. .834 -3, .700 1, .00 61, ,81 0
ATOM 942 0 HOH w 119 6. ,983 18. ,009 0. ,417 1. .00 58. ,96 o
ATOM 943 0 HOH w 120 7. .436 17. .165 3. .342 1, .00 61, ,89 o
ATOM 944 0 HOH w 121 20. ,944 31. .648 43. .363 1. .00 53. ,31 0
ATOM 945 0 HOH w 122 21. ,826 26. ,911 29. ,579 1. ,00 67. ,75 0
ATOM 946 0 HOH w 123 9. ,097 11. ,465 3. ,849 1, ,00 62. ,13 0
ATOM 947 0 HOH w 124 -1. ,826 21. 461 28. 064 1. 00 60. 67 o
ATOM 948 0 HOH w 125 18. ,975 22. 373 10. ,462 1. 00 47. 51 0
ATOM 949 0 HOH w 126 10. ,791 27. ,326 7. ,417 1. ,00 58. 06 o
ATOM 950 0 HOH w 127 2. 269 11. 384 25. 458 1. 00 60. 73 0
ATOM 951 0 HOH w 128 9. 714 36. 832 6. 517 1. 00 60. 04 0
ATOM 952 0 HOH w 129 17. ,055 32. 219 15. 352 1. 00 41. 93 0
ATOM 953 0 HOH w 130 1. 590 20. 061 27. 434 1. 00 37. 17 o
ATOM 954 0 HOH w 131 13. 830 21. 020 33. 287 1. 00 50. 68 o
ATOM 955 0 HOH w 132 -6. 693 16. 372 13. 047 1. 00 45. 15 0
ATOM 956 0 HOH w 133 8. 383 36. 910 33. 042 1. 00 65. 33 0
ATOM 957 0 HOH w 134 11. 374 41. 068 32. 503 1. 00 54. 93 0
ATOM 958 0 HOH w 135 6. 316 40. 823 31. 658 1. 00 68. 39 0
ATOM 959 0 HOH w 136 12. 324 14. 149 2. 727 1. 00 67. 01 0
ATOM 960 0 HOH w 137 -5. 787 27. 138 -4. 125 1. 00 65. 52 o
ATOM 961 0 HOH w 138 -9. 802 27. 322 11. 236 1. 00 60. 08 o ATOM 962 0 HOH W 139 -3.759 28, .863 -4.521 1.00 62.40 O
ATOM 963 0 HOH W 140 -2.672 19, .413 11.260 1.00 45.75 O
APPENDIX I (d)
HEADER 1A-7 COMPND 1A-7 REMARK REMARK REFINEMENT . REMARK PROGRAM REFMAC 5.2.0011 REMARK AUTHORS MURSHUDOV, VAGIN, DODSON REMARK REMARK REFINEMENT TARGET MAXIMUM LIKELIHOOD REMARK REMARK DATA USED IN REFINEMENT. REMARK RESOLUTION RANGE HIGH (ANGSTROMS) 2.71 REMARK RESOLUTION RANGE LOW (ANGSTROMS) 21.57 REMARK DATA CUTOFF (SIGMA(F)) NONE REMARK COMPLETENESS FOR RANGE (%) 95.14 REMARK NUMBER OF REFLECTIONS 18372 REMARK REMARK FIT TO DATA USED IN REFINEMENT. REMARK CROSS-VALIDATION METHOD THROUGHOUT REMARK FREE R VALUE TEST SET SELECTION RANDOM REMARK R VALUE (WORKING + TEST SET) 0.18041 REMARK R VALUE (WORKING SET) 0.17586 REMARK FREE R VALUE 0.26495 REMARK FREE R VALUE TEST SET SIZE (%) 5.1 REMARK FREE R VALUE TEST SET COUNT 982 REMARK REMARK FIT IN THE HIGHEST RESOLUTION BIN. REMARK TOTAL NUMBER OF BINS USED 20 REMARK BIN RESOLUTION RANGE HIGH 709 REMARK BIN RESOLUTION RANGE LOW 778 REMARK REFLECTION IN BIN (WORKING SET) 1089 REMARK BIN COMPLETENESS (WORKING+TEST) (%) 3.87 REMARK BIN R VALUE (WORKING SET) ,327 REMARK BIN FREE R VALUE SET COUNT 46 REMARK BIN FREE R VALUE 328 REMARK REMARK NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT. REMARK ALL ATOMS : 3765 REMARK REMARK B VALUES. REMARK FROM WILSON PLOT (A**2) NULL REMARK MEAN B VALUE (OVERALL, A**2) 43.346 REMARK OVERALL ANISOTROPIC B VALUE. REMARK Bll (A**2) 4 16 REMARK B22 (A**2) -2 46 REMARK B33 (A**2) -1 70 REMARK B12 (A**2) 0 00 REMARK B13 (A**2) 0 00 REMARK B23 (A**2) 0 00 REMARK REMARK ESTIMATED OVERALL COORDINATE ERROR. REMARK ESU BASED ON R VALUE (A) 0 . 525 REMARK ESU BASED ON FREE R VALUE (A) 0 . 336 REMARK ESU BASED ON MAXIMUM LIKELIHOOD (A) 0 . 258 REMARK ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2) 22. 695 REMARK REMARK CORRELATION COEFFICIENTS. REMARK CORRELATION COEFFICIENT FO-FC 0.950 REMARK CORRELATION COEFFICIENT FO-FC FREE 0.878 REMARK REMARK RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT REMARK BOND LENGTHS REFINED ATOMS (A) 3328 ; • 0.012 j ; 0.022 REMARK BOND ANGLES REFINED ATOMS (DEGREES) 4492 ; • 1.453 , : 1.954 REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES) 418 6.864 5.000 REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES) 144 32.750 23.611 REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES) 586 20.512 15.000 REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES) 28 20.012 15.000 REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3) 506 0.102 0.200 REMARK 3 GENERAL PLANES REFINED ATOMS (A) 2460 0.004 0.020 REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A) 1638 0.235 0.200 REMARK 3 NON-BONDED TORSION REFINED ATOMS (A) 2185 0.308 0.200 REMARK 3 H-BOND (X...Y) REFINED ATOMS (A) 309 0.191 0.200 REMARK 3 SYMMETRY VDW REFINED ATOMS (A) 72 0.270 0.200 REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A) 30 0.292 0.200 REMARK 3 REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. COUNT RMS WEIGHT REMARK 3 MAIN-CHAIN BOND REFINED ATOMS (A**2) 2116 0.565 ; 1.500 REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2) 3350 1.077 ; 2.000 REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2) 1368 1.619 ; 3.000 REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2) 1142 2.840 ; 4.500 REMARK 3 REMARK 3 NCS RESTRAINTS STATISTICS REMARK 3 NUMBER OF NCS GROUPS : NULL REMARK 3 REMARK 3 REMARK 3 TLS DETAILS REMARK 3 NUMBER OF TLS GROUPS : 4 REMARK 3 ATOM RECORD CONTAINS RESIDUAL B FACTORS ONLY REMARK 3 REMARK 3 TLS GROUP : 1 REMARK 3 NUMBER OF COMPONENTS GROUP 1 REMARK 3 COMPONENTS C SSSEQI TO c SSSEQI REMARK 3 RESIDUE RANGE : A 1 A 111 REMARK 3 ORIGIN FOR THE GROUP (A) 42, 6420 2.7110 11.2850 REMARK 3 T TENSOR REMARK 3 Til -0. .0556 T22 -0. 1040 REMARK 3 T33 -0..1287 T12 -0.0331 REMARK 3 T13 0.,0426 T23 -0, 0163 REMARK 3 L TENSOR REMARK 3 Lll 6. ,4349 L22 9791 REMARK 3 L33 4.,6108 L12 -2, 9273 REMARK 3 L13 -0.,1563 L23 -1.8520 REMARK 3 S TENSOR REMARK 3 Sll ,2306 S12 0310 S13 -0 ,3199 REMARK 3 S21 ,4291 S22 2316 S23 0 ,0525 REMARK 3 S31 ,4464 S32 0357 S33 -0 ,0010 REMARK 3 REMARK 3 TLS GROUP : 2 REMARK 3 NUMBER OF COMPONENTS GROUP 1 REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI REMARK 3 RESIDUE RANGE : B 1 B 111 REMARK 3 ORIGIN FOR THE GROUP (A) : 57 2880 23.2710 9.5550 REMARK 3 T TENSOR REMARK 3 Til: - -0 1637 T22 0898 REMARK 3 T33: - -0 0233 T12 0302 REMARK 3 T13: - -0 0125 T23 0400 REMARK 3 TENSOR REMARK 3 Lll: 2 6012 L22 9682 REMARK 3 L33: 3 5725 L12 9543 REMARK 3 L13: - -1 1259 L23 8219 REMARK 3 TENSOR REMARK 3 Sll: 0 1344 S12 0679 S13 -0 ,0673 REMARK 3 S21: 0 3029 S22 0152 S23 -0 ,1821 REMARK 3 S31: 0 2191 S32 1304 S33 -0.1496 REMARK 3 REMARK 3 TLS GROUP : 3 REMARK 3 NUMBER OF COMPONENTS GROUP REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI
REMARK 3 RESIDUE RANGE : C 1 C 111
REMARK 3 ORIGIN FOR THE GROUP (A): 25.8060 22.8210 23.0520
REMARK 3 T TENSOR
REMARK 3 Til: -0.2263 T22 -0.1090
REMARK 3 T33: -0.0650 T12 0.0097
REMARK 3 T13: -0.0073 T23 0.0251
REMARK 3 L TENSOR
REMARK 3 Lll: 3.4989 L22 7.7019
REMARK 3 L33: 6.6253 L12 0.2165
REMARK 3 L13: -0.5468 L23 2.4276
REMARK 3 S TENSOR
REMARK 3 Sll: -0.0280 S12 -0.0752 S13: 0.2877
REMARK 3 S21: 0.1903 S22 0.2318 S23: -0.2761
REMARK 3 S31: -0.2228 S32 0.2336 S33: -0.2038
REMARK 3
REMARK 3 TLS GROUP : 4
REMARK 3 NUMBER OF COMPONENTS GROUP : 1
REMARK 3 COMPONENTS C SSSEQI TO C SSSEQI
REMARK 3 RESIDUE RANGE : D 1 D 111
REMARK 3 ORIGIN FOR THE GROUP (A): 19.7280 2.5210 36.8750
REMARK 3 T TENSOR
REMARK 3 Til: -0.1365 T22 -0.0747
REMARK 3 T33: -0.1289 T12 0.0351
REMARK 3 T13: 0.0176 T23 0.0351
REMARK 3 L TENSOR
REMARK 3 Lll: 3.3426 L22 9.8078
REMARK 3 L33: 4.5159 L12 0.8691
REMARK 3 L13: -0.2683 L23 -2.7373
REMARK 3 S TENSOR
REMARK 3 Sll: -0.1963 S12 0.1431 S13: -0.0334
REMARK 3 S21: 0.2425 S22 0.2293 S23: -0.2122
REMARK 3 S31: -0.1809 S32 -0.0589 S33: -0.0330
REMARK 3
REMARK 3
REMARK 3 BULK SOLVENT MODELLINC
REMARK 3 METHOD USED : BABINErr MODEL WITH MASK
REMARK 3 PARAMETERS FOR MASK ( :ALCULATION
REMARK 3 VDW PROBE RADIUS : 1.20
REMARK 3 ION PROBE RADIUS : 0.80
REMARK 3 SHRINKAGE RADIUS : 0.80
REMARK 3
REMARK 3 OTHER REFINEMENT REMAIKS:
REMARK 3 HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
REMARK 3
SSBOND 1 CYS A 22 CYS A ( 33
SSBOND 2 CYS B 22 CYS B i 33
SSBOND 3 CYS C 22 CYS C ! 33
SSBOND 4 CYS D 22 CYS D 33
CISPEP 1 THR A 6 PRO A 7 0.00
CISPEP 2 THR B 6 PRO B 7 0.00
LINK SER B 88 PRO B 99 gap
CISPEP 3 THR C 6 PRO C 7 0.00
CISPEP 4 THR D 6 PRO D 7 0.00
LINK SER D 88 PRO D 99 gap
CRYST1 8C .498 88.661 101.754 90.00 90.00 90.00 P 21 21 21
SCALE1 0.012423 0.000000 0 .000000 D.00000
SCALE2 0.000000 0.011279 0 .000000 3.00000
SCALE3 0.000000 0.000000 0 .009828 D.00000
ATOM 1 N ALA A 1 3 3.011 14.284 9.406 1.00 34 .46 N
ATOM 2 CA ALA A 1 3 L.036 13.509 8.624 1.00 35 .28 C
ATOM 3 CB ALA A 1 3; ..437 14.034 8.888 1.00 34 .84 C
ATOM 4 C ALA A 1 3 .972 11.997 8.877 1.00 35 .65 C ATOM 5 O ALA A 1 30.119 11.520 9.642 1.00 35.76 0
ATOM 6 N TRP A 2 31 .857 11 .254 8, .206 1 .00 35 .69 N
ATOM 7 CA TRP A 2 31 .947 9 .799 8 .343 1 .00 36 .00 C
ATOM 8 CB TRP A 2 30 .700 9 .112 7 .776 1 .00 35 .89 C
ATOM 9 CG TRP A 2 30.730 8.902 6.299 1.00 35.28 C
ATOM 10 CD1 TRP A 2 31, .303 7 .856 5, .637 1 .00 35 .33 C
ATOM 11 NE1 TRP A 2 31 .147 8. .010 4 .281 1 .00 35 .24 N
ATOM 12 CE2 TRP A 2 30,.442 9.158 4,.042 1.00 34.88 C
ATOM 13 CD2 TRP A 2 30,.168 9..753 5..293 1.00 34.55 C
ATOM 14 CE3 TRP A 2 29, .451 10 .952 5, .327 1 .00 34 .74 C
ATOM 15 CZ3 TRP A 2 29. .043 11, .525 4. .115 1, .00 36 .01 C
ATOM 16 CH2 TRP A 2 29, .341 10 .911 2, .884 1 .00 35 .59 C
ATOM 17 CZ2 TRP A 2 30. .026 9, .724 2. .830 1, .00 35 .60 C
ATOM 18 C TRP A 2 33, .206 9, .286 7, .641 1 .00 36 .83 C
ATOM 19 O TRP A 2 33..787 9,.979 6,.789 1,.00 37.05 O
ATOM 20 N VAL A 3 33, .620 8, .068 7, .986 1 .00 37 .68 N
ATOM 21 CA VAL A 3 34, .802 7, .463 7. .390 1, .00 38, .15 C
ATOM 22 CB VAL A 3 35, ,768 7, .048 8, .463 1 .00 37 .97 C
ATOM 23 CGI VAL A 3 36,.981 6,.394 7..857 1,.00 38,.96 C
ATOM 24 CG2 VAL A 3 36,.190 8,.253 9,.265 1,.00 37.45 C
ATOM 25 C VAL A 3 34, .433 6, .260 6. .529 1, .00 39, .32 c
ATOM 26 O VAL A 3 33..522 5,.496 6,.865 1,.00 39,.40 0
ATOM 27 N ASP A 4 35..127 6,,129 5..398 1,.00 40,,83 N
ATOM 28 CA ASP A 4 35..007 4,.981 4..485 1,.00 42,.50 C
ATOM 29 CB ASP A 4 35. .128 5, ,449 3. .040 1, .00 42, ,10 C
ATOM 30 CG ASP A 4 33. ,831 5, .916 2. .470 1, .00 44, .06 c
ATOM 31 OD1 ASP A 4 33.,877 6,.414 1..321 1,.00 46,.56 0
ATOM 32 OD2 ASP A 4 32. .771 5, .783 3, .148 1, .00 45, .25 0
ATOM 33 C ASP A 4 36. ,143 3. .997 4. .705 1, .00 43, .53 c
ATOM 34 O ASP A 4 37..294 4,.316 4,.382 1,.00 44,.43 0
ATOM 35 N GLN A 5 35. ,864 2, .805 5. .217 1, .00 44. .07 N
ATOM 36 CA GLN A 5 36. .966 1, .882 5, ,436 1, .00 44, .76 C
ATOM 37 CB GLN A 5 36.,924 1..313 6..842 1..00 45..18 C
ATOM 38 CG GLN A 5 38, .195 0, .608 7. .266 1, .00 47, .01 C
ATOM 39 CD GLN A 5 38..183 0.,219 8..737 1,.00 49..42 C
ATOM 40 OEl GLN A 5 37..411 0.,760 9,,527 1,.00 49.,45 O
ATOM 41 NE2 GLN A 5 39..043 -0..724 9.,108 1..00 50..74 N
ATOM 42 C GLN A 5 36.,945 0..779 4.,411 1,.00 44..79 C
ATOM 43 O GLN A 5 35. .876 0. .276 4, ,067 1, .00 45. .27 O
ATOM 44 N THR A 6 38. ,129 0. .398 3. ,937 1, .00 44. .76 N
ATOM 45 CA THR A 6 38.,278 -0..648 2,,915 1..00 44..58 C
ATOM 46 CB THR A 6 38. ,436 0. ,011 1. ,541 1, .00 44, ,58 C
ATOM 47 OG1 THR A 6 37, ,159 0. .471 1, ,104 1. .00 44, .70 O
ATOM 48 CG2 THR A 6 38. ,953 -0. .954 0. ,529 1, ,00 45. ,30 C
ATOM 49 C THR A 6 39.,488 -1,.551 3.,205 1,.00 44..30 C
ATOM 50 O THR A 6 40.,572 -1..043 3.,535 1..00 44.,75 O
ATOM 51 N PRO A 7 39.,318 -2..886 3. ,115 1,.00 43,.66 N
ATOM 52 CA PRO A 7 38. ,111 -3. ,683 2. ,896 1. .00 43. ,45 C
ATOM 53 CB PRO A 7 38. ,670 -5. .030 2. ,455 1, .00 43. ,29 C
ATOM 54 CG PRO A 7 39. ,953 -5. ,128 3. ,166 1. ,00 43. ,32 c
ATOM 55 CD PRO A 7 40. ,513 -3, .742 3. ,203 1. .00 43. ,44 c
ATOM 56 C PRO A 7 37.,274 -3.,903 4.,145 1.,00 43.,07 c
ATOM 57 O PRO A 7 37.,737 -3.,660 5.,254 1.,00 42.,77 o
ATOM 58 N ARG A 8 36. ,059 -4. ,400 3. 948 1. ,00 42. 89 N
ATOM 59 CA ARG A 8 35.,144 -4.,642 5.,056 1.,00 42.,68 C
ATOM 60 CB ARG A 8 33. ,701 -4. ,386 4. 626 1. ,00 42. 94 C
ATOM 61 CG ARG A 8 33. ,474 -2. ,897 4. ,307 1. ,00 44. ,84 C
ATOM 62 CD ARG A 8 33. ,522 -2. ,011 5. 573 1. ,00 46. 18 C
ATOM 63 NE ARG A 8 32. ,191 -1. ,984 6. ,180 1. ,00 49. 33 N
ATOM 64 CZ ARG A 8 31.770 -2.747 7.193 1.,00 49.53 C
ATOM 65 NH1 ARG A 8 32. ,579 -3. ,612 7.796 1..00 50..15 N
ATOM 66 NH2 ARG A 8 30.520 -2.623 7.616 1.00 49.55 N
ATOM 67 C ARG A 8 35.336 -6.007 5.690 1..00 42.02 C
ATOM 68 O ARG A 8 35. 204 -6. 143 6. 907 1. 00 41. 82 O ATOM 69 N SER A 9 35.653 -7.007 4.869 1..00 41.36 N
ATOM 70 CA SER A 9 36. .221 -8, .258 5 .372 1 .00 40 .81 C
ATOM 71 CB SER A 9 35.140 -9.293 5.702 1.00 40.66 C
ATOM 72 OG SER A 9 34, .610 -9, .877 4 .533 1, .00 41 .34 O
ATOM 73 C SER A 9 37,.244 -8,.811 4.386 1.00 40.42 C
ATOM 74 O SER A 9 37, .171 -8, .528 3, .186 1, .00 40 .20 O
ATOM 75 N VAL A 10 38, .196 -9, .593 4 .897 1 .00 39 .89 N
ATOM 76 CA VAL A 10 39..313 -10,.077 4,.095 1,.00 39.33 C
ATOM 77 CB VAL A 10 40,.314 -8,.932 3,.746 1,.00 39.54 C
ATOM 78 CGI VAL A 10 41..033 -8.,411 4,.992 1,.00 39,.50 c
ATOM 79 CG2 VAL A 10 41, .309 -9, .365 2, .663 1, .00 39 .48 c
ATOM 80 C VAL A 10 40. ,054 -11, .205 4, .782 1, .00 39, .05 c
ATOM 81 O VAL A 10 40, .350 -11, .144 5, .977 1, .00 38 .79 0
ATOM 82 N THR A 11 40. .337 -12. .241 3, .999 1, .00 38, .97 N
ATOM 83 CA THR A 11 41, .137 -13, .381 4 .431 1, .00 38 .52 C
ATOM 84 CB THR A 11 40. .544 -14, .672 3, .897 1. .00 38, .36 C
ATOM 85 OG1 THR A 11 39. .128 -14, .618 4, .075 1, .00 38 .78 O
ATOM 86 CG2 THR A 11 41. .095 -15. .879 4, .643 1, .00 38, .38 C
ATOM 87 C THR A 11 42. .542 -13, .197 3, .890 1, .00 38, .21 C
ATOM 88 O THR A 11 42..723 -12..656 2,.802 1..00 38,.36 O
ATOM 89 N LYS A 12 43. ,539 -13. .631 4, .650 1. .00 37, .69 N
ATOM 90 CA LYS A 12 44. .915 -13. .447 4. .235 1. .00 37, .08 C
ATOM 91 CB LYS A 12 45. .442 -12. .123 4, .774 1. .00 36, .91 C
ATOM 92 CG LYS A 12 46. .038 -11. ,223 3. .713 1. .00 37. .12 C
ATOM 93 CD LYS A 12 44.,965 -10..364 3,.059 1..00 37,.36 C
ATOM 94 CE LYS A 12 45. .533 -9. .095 2. .396 1. .00 37. .20 C
ATOM 95 NZ LYS A 12 46. .627 -9. .346 1, .416 1. .00 36, .82 N
ATOM 96 C LYS A 12 45. .779 -14. .600 4. .710 1. .00 36. .74 C
ATOM 97 O LYS A 12 45. .567 -15. .138 5, .790 1. .00 36, .56 O
ATOM 98 N GLU A 13 46. .748 -14. .983 3. .890 1. .00 36. .65 N
ATOM 99 CA GLU A 13 47. .662 -16, .063 4, .223 1. .00 36, .63 C
ATOM 100 CB GLU A 13 48. .443 -16, .476 2. ,982 1. .00 36. .88 C
ATOM 101 CG GLU A 13 48. .852 -17, .943 2, .921 1. .00 37, ,05 C
ATOM 102 CD GLU A 13 47. .914 -18. .746 2, ,053 1, .00 37, ,80 C
ATOM 103 OEl GLU A 13 48. .375 -19. .718 1, ,409 1, .00 36, .95 O
ATOM 104 OE2 GLU A 13 46. .712 -18. .387 2, .008 1, ,00 38. ,61 O
ATOM 105 C GLU A 13 48. .640 -15. .558 5, .257 1, .00 36. .50 C
ATOM 106 O GLU A 13 48.,973 -14,,381 5.,267 1.,00 36,,57 O
ATOM 107 N THR A 14 49, .104 -16. ,454 6. .119 1. ,00 36, ,57 N
ATOM 108 CA THR A 14 50..154 -16.,149 7.,087 1.,00 36,,76 C
ATOM 109 CB THR A 14 50..468 -17,,390 7..993 1..00 37,,06 C
ATOM 110 OG1 THR A 14 49,,284 -18.,190 8..178 1..00 37..72 O
ATOM 111 CG2 THR A 14 51..006 -16.,970 9..359 1..00 37,.11 C
ATOM 112 C THR A 14 51, .421 -15, ,708 6. ,338 1. .00 36, .68 C
ATOM 113 O THR A 14 51,.878 -16,,394 5.,419 1.,00 36..83 O
ATOM 114 N GLY A 15 51,.973 -14,,562 6..724 1.,00 36..57 N
ATOM 115 CA GLY A 15 53,.222 -14.,066 6..142 1.,00 36..88 C
ATOM 116 C GLY A 15 52,.988 -12.,938 5..160 1.,00 37..24 C
ATOM 117 O GLY A 15 53. .925 -12. ,306 4. .684 1. ,00 37. ,22 0
ATOM 118 N GLU A 16 51..719 -12..680 4..876 1.,00 37,,60 N
ATOM 119 CA GLU A 16 51. .313 -11. ,686 3, .901 1. 00 38. ,12 C
ATOM 120 CB GLU A 16 50. .036 -12, ,178 3, ,221 1. ,00 38, ,52 C
ATOM 121 CG GLU A 16 50. .043 -12. ,115 1, ,696 1. 00 39. ,20 C
ATOM 122 CD GLU A 16 49, .133 -13. ,160 1. ,081 1. ,00 38. ,58 C
ATOM 123 OEl GLU A 16 47.,934 -13.,224 1,,446 1.00 37.,91 O
ATOM 124 OE2 GLU A 16 49. .631 -13. ,922 0. ,231 1. ,00 39. ,94 O
ATOM 125 C GLU A 16 51.,078 -10,,307 4.,545 1. 00 38.,27 C
ATOM 126 O GLU A 16 51,,211 -10. ,149 5,.766 1. ,00 38.,17 O
ATOM 127 N SER A 17 50. ,733 -9. ,319 3. ,718 1. 00 38. ,22 N
ATOM 128 CA SER A 17 50.,527 -7.,952 4,,181 1.00 38.,25 C
ATOM 129 CB SER A 17 51. ,468 -7. ,012 3. ,449 1. 00 38. 04 C
ATOM 130 OG SER A 17 52.,526 -6.,633 4.,292 1.00 38.,21 O
ATOM 131 C SER A 17 49. ,100 -7. 463 4. ,016 1. 00 38. 42 C
ATOM 132 O SER A 17 48. ,468 -7. ,715 3. ,001 1. 00 38. 73 O ATOM 133 N LEU A 18 48.585 -6.763 5.017 1.00 38.75 N
ATOM 134 CA LEU A 18 47, .270 -6, .156 4 .874 1, .00 39 .12 C
ATOM 135 CB LEU A 18 46, .353 -6 .572 6 .022 1, .00 39 .04 C
ATOM 136 CG LEU A 18 44 .806 -6. .512 6 .021 1 .00 38 .73 C
ATOM 137 CD1 LEU A 18 44, .328 -5, .643 7 .149 1, .00 39 .79 C
ATOM 138 CD2 LEU A 18 44, .103 -6 .155 4 .705 1, .00 37 .22 C
ATOM 139 C LEU A 18 47, .373 -4 .634 4 .760 1 .00 39 .48 c
ATOM 140 O LEU A 18 48, .245 -4, .003 5 .382 1, .00 39 .45 0
ATOM 141 N THR A 19 46, .495 -4, .073 3 .928 1, .00 39 .47 N
ATOM 142 CA THR A 19 46, .365 -2 .639 3. .747 1 .00 39 .18 C
ATOM 143 CB THR A 19 46, .900 -2, .192 2, .371 1, .00 39, .41 c
ATOM 144 OGl THR A 19 48, .101 -2, .914 2 .076 1, .00 39 .32 0
ATOM 145 CG2 THR A 19 47, .174 -0, .670 2, .324 1, .00 38. .20 c
ATOM 146 C THR A 19 44. .892 -2, .293 3, .868 1, .00 39, .18 c
ATOM 147 O THR A 19 44, .060 -2, .770 3 .091 1, .00 38 .41 0
ATOM 148 N ILE A 20 44. .597 -1, .478 4, .876 1. .00 39, .56 N
ATOM 149 CA ILE A 20 43. .260 -0, .955 5, .138 1, .00 39, .76 C
ATOM 150 CB ILE A 20 42, ,903 -1, .040 6, .652 1, .00 39, .03 C
ATOM 151 CGI ILE A 20 42. .854 -2, ,492 7, ,109 1. .00 37, ,40 C
ATOM 152 GDI ILE A 20 42. .677 -2, .673 8, .576 1, .00 34, .93 C
ATOM 153 CG2 ILE A 20 41, .561 -0, .422 6, .915 1, .00 39, .48 C
ATOM 154 C ILE A 20 43, .270 0. .502 4, .705 1. .00 40, .70 c
ATOM 155 O ILE A 20 44, .093 1. .289 5, .200 1. .00 41, .44 0
ATOM 156 N ASN A 21 42, .378 0, .865 3, .784 1, .00 41, .34 N
ATOM 157 CA ASN A 21 42, .217 2. .277 3, .388 1, .00 41, ,97 c
ATOM 158 CB ASN A 21 41. .958 2, .394 1, ,892 1. .00 41, ,90 c
ATOM 159 CG ASN A 21 43, .155 1, .947 1, .059 1, .00 42, .52 c
ATOM 160 ODl ASN A 21 43. .117 0. ,905 0, .407 1, .00 43, .46 0
ATOM 161 ND2 ASN A 21 44. .224 2, .730 1, .085 1, ,00 43, .18 N
ATOM 162 C ASN A 21 41. ,136 2. .997 4. .190 1, ,00 42, ,22 C
ATOM 163 O ASN A 21 40. ,226 2. .370 4, .705 1, ,00 43, .14 O
ATOM 164 N CYS A 22 41. ,260 4', .305 4, .327 1, .00 42, .28 N
ATOM 165 CA CYS A 22 40. ,265 5. .101 5, ,027 1, ,00 42, .84 C
ATOM 166 CB CYS A 22 40, ,554 5, ,158 6. .527 1, ,00 43, .14 C
ATOM 167 SG CYS A 22 40, .171 3, .613 7, .438 1, ,00 48, .94 S
ATOM 168 C CYS A 22 40, .209 6. .508 4. .455 1, ,00 41. .89 C
ATOM 169 O CYS A 22 41, ,239 7. .124 4. .182 1, ,00 42. .35 O
ATOM 170 N ALA A 23 39, ,005 7. .014 4. .260 1, ,00 40. .70 N
ATOM 171 CA ALA A 23 38. ,848 8. ,380 3. ,803 1. .00 39. .76 C
ATOM 172 CB ALA A 23 38. .526 8. ,399 2. ,357 1, .00 39, .71 C
ATOM 173 C ALA A 23 37, .762 9. ,084 4. ,612 1. .00 39, .14 c
ATOM 174 O ALA A 23 36, ,691 8, .519 4. .843 1. ,00 38. ,80 0
ATOM 175 N LEU A 24 38, ,076 10. .305 5. .056 1. .00 38. ,04 N
ATOM 176 CA LEU A 24 37. .170 11. .133 5. .840 1. .00 37, .40 C
ATOM 177 CB LEU A 24 37. ,981 12. .023 6. .793 1. ,00 37. ,06 C
ATOM 178 CG LEU A 24 37. .310 13. .044 7. .730 1. ,00 37. ,11 C
ATOM 179 CD1 LEU A 24 38. .333 13, ,654 8, ,690 1. ,00 34. ,67 C
ATOM 180 CD2 LEU A 24 36. ,106 12, .470 8. ,501 1. ,00 35. ,66 C
ATOM 181 C LEU A 24 36. .265 11. .952 4, ,897 1. ,00 37. ,29 C
ATOM 182 O LEU A 24 36. ,746 12. .790 4. ,117 1. ,00 36. 95 O
ATOM 183 N LYS A 25 34. ,959 11. .695 4. ,951 1. ,00 36. ,83 •N
ATOM 184 CA LYS A 25 34. ,046 12, .329 4. ,008 1. ,00 36. ,82 C
ATOM 185 CB LYS A 25 33. ,225 11. ,273 3. ,268 1. ,00 36. 56 C
ATOM 186 CG LYS A 25 34. ,044 10. ,153 2. ,595 1. ,00 37. ,16 c
ATOM 187 CD LYS A 25 34. ,408 10, .422 1. ,143 1. ,00 37. ,46 c
ATOM 188 CE LYS A 25 35. ,722 11. ,217 1. ,064 1. ,00 41. 41 c
ATOM 189 NZ LYS A 25 36. ,517 11. ,096 -0. ,229 1. ,00 41. 89 N
ATOM 190 C LYS A 25 33. ,137 13. ,322 4. ,709 1. ,00 36. ,75 C
ATOM 191 O LYS A 25 32. ,758 13. ,096 5. ,854 1. 00 37. 04 O
ATOM 192 N ASN A 26 32. ,798 14. ,420 4. ,027 1. 00 36. 84 N
ATOM 193 CA ASN A 26 31. ,808 15. ,399 4. ,510 1. ,00 37. 02 C
ATOM 194 CB ASN A 26 30. 454 14. ,723 4. 775 1. 00 37. 06 C
ATOM 195 CG ASN A 26 29. ,262 15. ,664 4. ,557 1. 00 39. 15 C
ATOM 196 ODl ASN A 26 28. 344 15. 755 5. 390 1. 00 39. 26 O ATOM 197 ND2 ASN A 26 29.265 16,.361 3.422 1,.00 41.33 N
ATOM 198 C ASN A 26 32, .254 16. ,157 5, .759 1, .00 37 .24 C
ATOM 199 O ASN A 26 31, .420 16, .589 6, .551 1, .00 37 .14 O
ATOM 200 N ALA A 27 33 .567 16, .296 5 .941 1, .00 37 .46 N
ATOM 201 CA ALA A 27 34, .131 17. .028 7, .069 1, .00 37, .86 C
ATOM 202 CB ALA A 27 35, .300 16. .289 7 .631 1, .00 37 .64 C
ATOM 203 C ALA A 27 34 .557 18, .443 6 .673 1, .00 38 .63 C
ATOM 204 O ALA A 27 35, ,473 18. .630 5, .839 1, .00 39 .12 O
ATOM 205 N ALA A 28 33, .894 19. .425 7, .286 1, .00 38 .74 N
ATOM 206 CA ALA A 28 34, .201 20, .846 7 .127 1, .00 38 .77 C
ATOM 207 CB ALA A 28 33, .266 21. .675 7, .969 1. ,00 38, .26 C
ATOM 208 C ALA A 28 35, .650 21, .212 7, .468 1, .00 39 .27 c
ATOM 209 O ALA A 28 36. .238 22. .075 6, .800 1. .00 39, .84 0
ATOM 210 N ASP A 29 36, .227 20. .579 8, .495 1. .00 39, .15 N
ATOM 211 CA ASP A 29 37, .529 21, .012 9, .011 1. ,00 39 .27 C
ATOM 212 CB ASP A 29 37. .435 21. .193 10. .516 1. ,00 39, .55 C
ATOM 213 CG ASP A 29 36, .715 22. .467 10, .909 1. .00 40, .83 C
ATOM 214 ODl ASP A 29 36, .915 23, ,522 10, .253 1. .00 40, .47 O
ATOM 215 OD2 ASP A 29 35, .946 22, ,409 11. .894 1. ,00 43, .52 O
ATOM 216 C ASP A 29 38, .697 20, ,092 8, .639 1. ,00 39, .04 C
ATOM 217 O ASP A 29 38, .481 19. .056 8, .035 1. .00 39, .18 O
ATOM 218 N ASP A 30 39, .929 20. .464 8. .996 1. ,00 38, .80 N
ATOM 219 CA ASP A 30 41, .115 19. .660 8. .628 1. .00 38, .39 C
ATOM 220 CB ASP A 30 42, .418 20. .435 8, .838 1, ,00 38, .50 C
ATOM 221 CG ASP A 30 42, ,507 21. .699 7. .991 1. ,00 40. .29 C
ATOM 222 ODl ASP A 30 43, .012 22. .709 8. .523 1. .00 42, .73 O
ATOM 223 OD2 ASP A 30 42, .080 21. .708 6, .808 1. .00 41, .07 O
ATOM 224 C ASP A 30 41. ,210 18. ,370 9. .419 1. .00 37, ,92 C
ATOM 225 O ASP A 30 40, .802 18. ,325 10, .584 1. .00 37, .68 O
ATOM 226 N LEU A 31 41. ,751 17, ,332 8. .774 1. .00 37. ,28 N
ATOM 227 CA LEU A 31 42, ,173 16, ,113 9. .441 1. .00 36. .52 C
ATOM 228 CB LEU A 31 42, .727 15, .118 8, .438 1, .00 36, ,34 c
ATOM 229 CG LEU A 31 42, ,508 13. .612 8. .605 1. .00 35. ,92 c
ATOM 230 CD1 LEU A 31 42, ,219 13. .184 10. .047 1, .00 35. .84 c
ATOM 231 CD2 LEU A 31 43, .676 12. .876 8, .037 1, .00 35. .02 c
ATOM 232 C LEU A 31 43, .304 16, .505 10. .330 1. .00 36. ,82 c
ATOM 233 O LEU A 31 44, .265 17, .147 9. .883 1, .00 36. .89 0
ATOM 234 N GLU A 32 43. .213 16, .090 11, .583 1, .00 37. .16 N
ATOM 235 CA GLU A 32 44. .153 16, .520 12, .603 1. .00 37. ,77 C
ATOM 236 CB GLU A 32 43. .443 17, .502 13, .557 1, .00 37. .94 C
ATOM 237 CG GLU A 32 44. .338 18, .432 14, .370 1, .00 40, .70 C
ATOM 238 CD GLU A 32 45. .128 19. ,438 13, .530 1, .00 43, ,57 C
ATOM 239 OEl GLU A 32 46. .360 19. .572 13, .769 1, .00 43, ,94 0
ATOM 240 OE2 GLU A 32 44. .521 20. .097 12, .649 1. .00 44, ,41 0
ATOM 241 C GLU A 32 44. .820 15. .312 13. .319 1. ,00 37, ,53 c
ATOM 242 O GLU A 32 46. .000 15. .347 13. ,645 1. .00 37. ,47 0
ATOM 243 N ARG A 33 44. ,089 14. ,228 13. ,514 1. ,00 37. ,63 N
ATOM 244 CA ARG A 33 44, ,650 13. ,069 14, .176 1. ,00 38. ,59 C
ATOM 245 CB ARG A 33 44, ,330 13. .124 15. .668 1. ,00 38. ,27 C
ATOM 246 CG ARG A 33 45, ,405 12. ,524 16. ,561 1. ,00 39. ,74 C
ATOM 247 CD ARG A 33 44. ,978 12. ,402 18. ,023 1. ,00 40. ,86 C
ATOM 248 NE ARG A 33 43. ,765 11. ,591 18. .189 1. ,00 48. ,81 N
ATOM 249 CZ ARG A 33 42, ,619 12. ,005 18. ,751 1. ,00 51. ,82 C
ATOM 250 NH1 ARG A 33 42. .484 13. ,241 19. ,247 1. ,00 50. ,95 N
ATOM 251 NH2 ARG A 33 41. .589 11. ,161 18, .828 1. ,00 54. ,87 N
ATOM 252 C ARG A 33 44. ,081 11. ,800 13. ,573 1. ,00 38. ,68 C
ATOM 253 O ARG A 33 42. .887 11. ,731 13. ,269 1. ,00 38. ,65 O
ATOM 254 N THR A 34 44, .924 10. ,790 13. ,392 1. ,00 39. .54 N
ATOM 255 CA THR A 34 44. ,442 9. ,476 12. ,933 1. ,00 40. ,35 C
ATOM 256 CB THR A 34 44. ,987 9. ,118 11. ,559 1. ,00 40. ,18 C
ATOM 257 OGl THR A 34 46. ,414 9. ,263 11. ,560 1. ,00 39. ,67 O
ATOM 258 CG2 THR A 34 44! ,382 10. 023 10. 501 1. 00 40. 31 C
ATOM 259 C THR A 34 44. ,827 . 8. ,383 13. ,927 1. 00 41. ,31 C
ATOM 260 O THR A 34 45. ,953 8. 373 14. 447 1. 00 41. 94 O ATOM 261 N ASP A 35 43.891 7.478 14.210 ,00 41.83 N
ATOM 262 CA ASP A 35 44.126 6.393 15.161 ,00 42.20 C
ATOM 263 CB ASP A 35 43.274 6.571 16.421 ,00 42.42 C
ATOM 264 CG ASP A 35 43.737 7.747 17.302 ,00 46.01 c
ATOM 265 ODl ASP A 35 42.966 8.226 18.195 ,00 47.52 0
ATOM 266 OD2 ASP A 35 44.892 8.195 17.112 00 50.48 0
ATOM 267 C ASP A 35 43.762 .095 14.470 00 42.09 c
ATOM 268 O ASP A 35 43.012 .105 13.485 00 41.93 0
ATOM 269 N TRP A 36 44.322 .985 14.959 00 42.03 N
ATOM 270 CA TRP A 36 43.935 .646 14.501 00 41.95 C
ATOM 271 CB TRP A 36 44.964 .073 13.553 00 41.75 C
ATOM 272 CG TRP A 36 45.116 ,870 12.337 00 41.84 C
ATOM 273 GDI TRP A 36 45.928 .949 12.162 00 41.60 C
ATOM 274 NE1 TRP A 36 45.799 ,440 10.884 00 42.39 N
ATOM 275 CE2 TRP A 36 44.890 ,669 10.210 00 42.33 C
ATOM 276 CD2 TRP A 36 44.428 ,677 11.105 1.00 41.80 c
ATOM 277 CE3 TRP A 36 43.487 .749 10.660 00 40.90 c
ATOM 278 CZ3 TRP A 36 43.037 ,839 9.374 00 41.85 c
ATOM 279 CH2 TRP A 36 43.520 2.840 8.497 00 42.44 c
ATOM 280 CZ2 TRP A 36 44.442 3.758 8.900 00 41.87 c
ATOM 281 C TRP A 36 43.767 1.722 15.680 00 42.21 c
ATOM 282 O TRP A 36 44.588 1.736 16.604 00 42.22 0
ATOM 283 N TYR A 37 42.706 0.918 15.632 00 42.73 N
ATOM 284 CA TYR A 37 42.263 0.091 16.763 1.00 43.04 C
ATOM 285 CB TYR A 37 40.951 0.612 17.329 ,00 42.85 C
ATOM 286 CG TYR A 37 41.021 2..037 17.776 ,00 43.46 c
ATOM 287 CD1 TYR A 37 41.456 2. ,361 19.068 ,00 43.11 c
ATOM 288 CEl TYR A 37 41.548 3..664 19.490 .00 41.58 c
ATOM 289 CZ TYR A 37 41.189 4, .677 18.626 .00 43.27 c
ATOM 290 OH TYR A 37 41.261 5..989 19.050 ,00 44.70 0
ATOM 291 CE2 TYR A 37 40.746 4..390 17.333 .00 43.92 c
ATOM 292 CD2 TYR A 37 40.671 3.070 16.914 .00 43.64 c
ATOM 293 C TYR A 37 42.029 -1.325 16.317 .00 43.46 c
ATOM 294 O TYR A 37 41.591 -1.566 15.187 .00 44.17 0
ATOM 295 N ARG A 38 42.312 -2.259 17.206 .00 43.57 N
ATOM 296 CA ARG A 38 42.024 -3.648 16.947 .00 44.06 c
ATOM 297 CB ARG A 38 43.299 -4.422 16.565 .00 44.12 c
ATOM 298 CG ARG A 38 44.193 -4.794 17.743 .00 45.46 c
ATOM 299 CD ARG A 38 45.022 -6.017 17.472 ,00 48.46 c
ATOM 300 NE ARG A 38 46.019 -5.760 16.436 .00 51.96 N
ATOM 301 CZ ARG A 38 46.772 693 15.850 .00 53.24 C
ATOM 302 NH1 ARG A 38 47.654 345 14.908 ,00 52.53 N
ATOM 303 NH2 ARG A 38 46.645 970 16.203 ,00 54.34 N
ATOM 304 C ARG A 38 41.370 276 18.164 .00 44.18 C
ATOM 305 O ARG A 38 41.730 980 19.313 ,00 43.93 O
ATOM 306 N THR A 39 40.383 122 17.903 ,00 44.59 N
ATOM 307 CA THR A 39 39.980 -6.125 18.879 ,00 44.78 C
ATOM 308 CB THR A 39 38.506 -5.944 19.441 ,00 44.80 C
ATOM 309 OGl THR A 39 37.647 -6.999 18.988 ,00 45.17 O
ATOM 310 CG2 THR A 39 37.902 -4.568 19.101 ,00 44.19 C
ATOM 311 C THR A 39 40.241 -7.490 18.222 00 44.86 C
ATOM 312 O THR A 39 39.614 -7.850 17.217 00 44.92 O
ATOM 313 N THR A 40 41.211 -8.218 18.763 ,00 44.69 N
ATOM 314 CA THR A 40 41.535 -9.535 18.250 00 44.78 C
ATOM 315 CB THR A 40 42.888 -10.006 18.768 00 44.70 C
ATOM 316 OGl THR A 40 43.112 -9.450 20.065 00 43.69 0
ATOM 317 CG2 THR A 40 43.997 -9.535 17.823 00 44.71 c
ATOM 318 C THR A 40 40.429 -10.519 18.611 00 45.11 c
ATOM 319 O THR A 40 39.598 -10.220 19.467 00 45.36 0
ATOM 320 N LEU A 41 40.398 -11.666 17.930 00 45.34 N
ATOM 321 CA LEU A 41 39.405 -12.708 18.185 00 45.60 C
ATOM 322 CB LEU A 41 39.650 -13.923 17.284 00 45.75 C
ATOM 323 CG LEU A 41 39.027 -13.992 15.886 00 46.10 C
ATOM 324 CD1 LEU A 41 39.400 -15.309 15.218 00 45.39 C ATOM 325 CD2 LEU A 41 37,.504 -13..847 15,.936 1..00 46.64 c
ATOM 326 C LEU A 41 39, .377 -13. .162 19, .646 1, .00 45 .78 c
ATOM 327 O LEU A 41 40 .419 -13. .282 20, .296 1, .00 45 .53 0
ATOM 328 N GLY A 42 38, .171 -13. .406 20. .149 1, ,00 46, .12 N
ATOM 329 CA GLY A 42 37, .968 -13, .838 21, .526 1, .00 46 .62 c
ATOM 330 C GLY A 42 38, .330 -12. .787 22. .561 1. .00 46, .95 c
ATOM 331 O GLY A 42 38, .450 -13, .096 23, .744 1, .00 47 .22 0
ATOM 332 N SER A 43 38 .496 -11, .544 22, .120 1, .00 47 .14 N
ATOM 333 CA SER A 43 38, .904 -10. .461 23, .002 1, .00 47, .51 C
ATOM 334 CB SER A 43 40, .172 -9. .807 22, .452 1, .00 47 .44 C
ATOM 335 OG SER A 43 40, .588 -8. .718 23, .250 1. ,00 47, .84 O
ATOM 336 C SER A 43 37, .782 -9. .438 23, ,139 1, .00 47, .74 C
ATOM 337 O SER A 43 37, .201 -9, .029 22, ,138 1, .00 47 .93 O
ATOM 338 N THR A 44 37, .491 -9. .024 24, .374 1. .00 48, .06 N
ATOM 339 CA THR A 44 36, .372 -8, .104 24, .675 1, .00 48 .47 C
ATOM 340 CB THR A 44 36, .037 -8. .081 26. .193 1, .00 48, .56 C
ATOM 341 OGl THR A 44 36, .312 -9. ,358 26. .790 1. .00 49, .42 O
ATOM 342 CG2 THR A 44 34, .566 -7, .694 26, .424 1, .00 48 .79 C
ATOM 343 C THR A 44 36, .584 -6. .636 24. ,258 1. .00 48, .60 C
ATOM 344 O THR A 44 35, .606 -5. .879 24. .132 1, .00 48, .74 O
ATOM 345 N ASN A 45 37. .841 -6. ,227 24, ,064 1. .00 48, ,29 N
ATOM 346 CA ASN A 45 38, .146 -4. .801 23, ,989 1. .00 47, .93 C
ATOM 347 CB ASN A 45 38, .709 -4. .286 25, ,321 1, .00 48, .18 C
ATOM 348 CG ASN A 45 40, .194 -4. .610 25. .510 1. .00 47. .74 C
ATOM 349 ODl ASN A 45 40, .583 -5. .160 26. ,535 1. .00 48, .34 o
ATOM 350 ND2 ASN A 45 41, .024 -4. .252 24. .532 1. .00 47. .01 N
ATOM 351 C ASN A 45 39, .064 -4. .353 22. .875 1. .00 47, .68 c
ATOM 352 O ASN A 45 39, .969 -5. .080 22. .450 1, .00 47, .62 0
ATOM 353 N GLU A 46 38, ,830 -3. ,107 22. ,475 1. .00 47, .03 N
ATOM 354 CA GLU A 46 39, .563 -2, ,405 21. ,446 1. .00 46, .44 C
ATOM 355 CB GLU A 46 38, ,666 -1. ,289 20. ,929 1. ,00 46, .92 C
ATOM 356 CG GLU A 46 38, .808 -0. .975 19. ,478 1. .00 49, .14 C
ATOM 357 CD GLU A 46 37, .665 -0. .129 18. .953 1. ,00 52, .82 C
ATOM 358 OEl GLU A 46 36, .756 0. ,231 19. ,743 1. ,00 53, .98 O
ATOM 359 OE2 GLU A 46 37, .671 0. .181 17, ,738 1. .00 55, .31 0
ATOM 360 C GLU A 46 40. ,834 -1. ,792 22. ,019 1. ,00 45. .39 c
ATOM 361 O GLU A 46 40, .779 -1. .015 22. ,969 1. ,00 45, .55 0
ATOM 362 N GLN A 47 41, .979 -2. .146 21. ,452 1. .00 44, .11 N
ATOM 363 CA GLN A 47 43. .235 -1. .524 21. ,856 1. ,00 43. ,28 c
ATOM 364 CB GLN A 47 44, .246 -2. .584 22. ,324 1. ,00 43. ,08 c
ATOM 365 CG GLN A 47 44. .622 -3. .594 21. .239 1. .00 44. ,55 c
ATOM 366 CD GLN A 47 45. .149 -4. .939 21, .765 1. .00 45. ,07 c
ATOM 367 OEl GLN A 47 45. ,388 -5. ,115 22. .972 1. .00 48. .41 0
ATOM 368 NE2 GLN A 47 45. ,326 -5, ,899 20. .846 1. .00 45. .13 N
ATOM 369 C GLN A 47 43. .764 -0. ,656 20. .703 1, .00 41, .76 c
ATOM 370 O GLN A 47 43. .516 -0. .952 19. ,538 1. .00 41. .19 0
ATOM 371 N LYS A 48 44. .446 0. .438 21. ,035 1. .00 40, .40 N
ATOM 372 CA LYS A 48 45. .041 1, .298 20, .027 1, .00 39, .25 C
ATOM 373 CB LYS A 48 45. .258 2. ,703 20. ,566 1. .00 39. .55 C
ATOM 374 CG LYS A 48 46. .022 3. ,635 19. ,626 1, .00 41. .07 C
ATOM 375 CD LYS A 48 45, .976 5. ,054 20. ,154 1. ,00 44. .06 C
ATOM 376 CE LYS A 48 47, .037 5. ,918 19. ,518 1. ,00 45. .73 C
ATOM 377 NZ LYS A 48 46, .515 6, ,731 18. ,397 1. .00 47. .48 N
ATOM 378 C LYS A 48 46, .359 0. ,714 19. ,568 1. ,00 38. ,35 C
ATOM 379 O LYS A 48 47, .164 0. ,259 20. ,380 1. ,00 37. ,69 O
ATOM 380 N ILE A 49 46. .556 0. ,722 18. 251 .1- ,00 37. ,55 N
ATOM 381 CA ILE A 49 47. ,776 0. ,228 17. ,632 1. ,00 36. ,50 C
ATOM 382 CB ILE A 49 47, .546 -0. ,204 16. ,169 1. ,00 36. ,80 C
ATOM 383 CGI ILE A 49 46. ,439 -1. 272 16. 078 1. ,00 35. ,88 c
ATOM 384 CD1 ILE A 49 46. ,064 -1. ,701 14. ,656 1. ,00 35. ,50 c
ATOM 385 CG2 ILE A 49 48. ,895 -0. 667 15. 549 1. 00 36. ,79 c
ATOM 386 C ILE A 49 48. ,865 1. ,298 17. 664 1. ,00 36. ,12 c
ATOM 387 O ILE A 49 48, ,694 2. ,395 17. ,125 1. ,00 36. ,62 o
ATOM 388 N SER A 50 49. ,977 0. 995 18. 318 1. 00 35. ,10 N ATOM 389 CA SER A 50 51.,093 1..906 18..311 1,,00 34.,20 c
ATOM 390 CB SER A 50 51.,986 1.,645 19.,515 1,,00 33.,93 c
ATOM 391 OG SER A 50 53. ,288 2, ,161 19. ,314 1, .00 34. ,04 o
ATOM 392 C SER A 50 51. ,835 1. ,757 16. ,972 1. .00 33. ,93 c
ATOM 393 O SER A 50 52.,425 0.,706 16.,694 1..00 34.,24 0
ATOM 394 N ILE A 51 51.,770 2.,805 16..142 1,.00 33.,13 N
ATOM 395 CA ILE A 51 52.,425 2.,857 14.,825 1..00 32.,31 c
ATOM 396 CB ILE A 51 51. ,963 4. ,106 14. ,044 1, .00 32. ,15 c
ATOM 397 CGI ILE A 51 50. ,426 4. .185 13, .996 1, ,00 31, ,76 c
ATOM 398 CD1 ILE A 51 49. ,747 3. ,145 13. ,130 1. ,00 32. ,12 c
ATOM 399 CG2 ILE A 51 52. ,599 4. ,194 12. ,654 1, ,00 31. ,09 c
ATOM 400 C ILE A 51 53. ,954 2. ,829 14. ,912 1. .00 32. ,65 c
ATOM 401 O ILE A 51 54. ,564 3. ,433 15. ,791 1. ,00 32. ,80 0
ATOM 402 N GLY A 52 54. .567 2. .124 13, .976 1, ,00 33. ,09 N
ATOM 403 CA GLY A 52 56. ,002 1. ,887 13, .991 1, ,00 33. ,42 C
ATOM 404 C GLY A 52 56. .221 0. .399 13, ,838 1, ,00 33. ,74 C
ATOM 405 O GLY A 52 55..305 -0..393 14,,056 1..00 33.,66 O
ATOM 406 N GLY A 53 57..432 0..015 13,,460 1,,00 34.,29 N
ATOM 407 CA GLY A 53 57. .763 -1, .397 13, ,322 1, .00 35. ,04 C
ATOM 408 C GLY A 53 56. ,957 -1, ,991 12. ,195 1. .00 35, ,46 C
ATOM 409 O GLY A 53 56. .982 -1. .476 11, .080 1, .00 35, ,74 O
ATOM 410 N ARG A 54 56..213 -3..050 12..490 1..00 35.,90 N
ATOM 411 CA ARG A 54 55.,433 -3.,725 11.,461 1.,00 36.,34 C
ATOM 412 CB ARG A 54 55. .022 -5, ,121 11, ,923 1. .00 36. ,49 C
ATOM 413 CG ARG A 54 54..076 -5,.157 13,.113 1..00 37.,52 C
ATOM 414 CD ARG A 54 53. ,998 -6. .557 13. .716 1, .00 40. ,03 C
ATOM 415 NE ARG A 54 53. ,427 -7, .539 12, ,792 1, .00 41. ,16 N
ATOM 416 CZ ARG A 54 52, ,182 -8, .028 12, ,856 1, ,00 42. ,21 C
ATOM 417 NHl ARG A 54 51, ,329 -7, .666 13, .819 1, .00 40, ,89 N
ATOM 418 NH2 ARG A 54 51,,795 -8,.918 11,.953 1..00 42,.90 N
ATOM 419 C ARG A 54 54, ,217 -2, .927 10. ,989 1, .00 36, .53 C
ATOM 420 O ARG A 54 53,.644 -3,.246 9..948 1,,00 36,.70 O
ATOM 421 N TYR A 55 53, .822 -1. .902 11. .747 1, .00 36, .80 N
ATOM 422 CA TYR A 55 52, .639 -1, .088 11. .404 1, .00 37, .20 C
ATOM 423 CB TYR A 55 51,.798 -0,.746 12..635 1,.00 37,.76 C
ATOM 424 CG TYR A 55 51, ,512 -1, .949 13. .486 1, .00 38, .65 C
ATOM 425 CD1 TYR A 55 50,.408 -2,.756 13..232 1..00 39,.27 c
ATOM 426 CEl TYR A 55 50..159 -3..879 14,.009 1,.00 40,.17 c
ATOM 427 CZ TYR A 55 51. .043 -4, .206 15. .042 1, .00 39, .69 c
ATOM 428 OH TYR A 55 50. .821 -5, .328 15. ,824 1, ,00 40, .19 0
ATOM 429 CE2 TYR A 55 52. ,150 -3, ,421 15. ,296 1, .00 39. .05 c
ATOM 430 CD2 TYR A 55 52,.375 -2,.302 14.,528 1,.00 38.,92 c
ATOM 431 C TYR A 55 53..092 0,.188 10..765 1..00 36..81 c
ATOM 432 O TYR A 55 53. .922 0, .898 11. ,327 1, .00 36, .76 0
ATOM 433 N VAL A 56 52..554 0..483 9..586 1,.00 36..40 N
ATOM 434 CA VAL A 56 52..999 1,.679 8..866 1..00 35..90 C
ATOM 435 CB VAL A 56 54..262 1,.420 7.,938 1,.00 35..20 C
ATOM 436 CGI VAL A 56 54.,243 0,,050 7..360 1,.00 35,,04 c
ATOM 437 CG2 VAL A 56 54. .393 2. ,462 6. ,867 1, .00 34, .11 c
ATOM 438 C VAL A 56 51..859 2,,475 8..230 1,.00 35.,61 c
ATOM 439 O VAL A 56 51.,327 2,,092 7..216 1,.00 36..11 o
ATOM 440 N GLU A 57 51..515 3.,588 8.,863 1,.00 35..55 N
ATOM 441 CA GLU A 57 50..453 4,.475 8,,427 1,,00 35,.99 C
ATOM 442 CB GLU A 57 49..955 5,.271 9,,617 1,.00 36,.06 C
ATOM 443 CG GLU A 57 48..594 5,,851 9,.404 1,.00 36..87 C
ATOM 444 CD GLU A 57 48. ,199 6, .813 10, .501 1, ,00 38. .36 c
ATOM 445 OEl GLU A 57 49,.107 7,,427 11..114 1,,00 37.,22 o
ATOM 446 OE2 GLU A 57 46,.970 6,,965 10..720 1,,00 39,,11 0
ATOM 447 C GLU A 57 50. ,892 5, .463 7. .363 1, .00 36, .29 c
ATOM 448 O GLU A 57 51. ,989 6. .024 7. ,424 1, .00 36. ,57 0
ATOM 449 N THR A 58 50..011 5,.701 6.,404 1..00 36.,94 N
ATOM 450 CA THR A 58 50. .256 6, ,677 5. .354 1, .00 38. .04 C
ATOM 451 CB THR A 58 50,.400 5,,991 3.,978 1..00 38.,06 C
ATOM 452 OGl THR A 58 51, .539 5, .115 4. ,017 1, .00 38, ,61 0 ATOM 453 CG2 THR A 58 50,.600 7.,016 2..871 1.,00 37,.85 c
ATOM 454 C THR A 58 49, .101 7. ,656 5. .367 1. .00 38, .73 c
ATOM 455 O THR A 58 47, .935 7, .256 5, .228 1, .00 39, .47 o
ATOM 456 N VAL A 59 49, .412 8, .936 5, .581 1. .00 39, .11 N
ATOM 457 CA VAL A 59 48, .358 9, .934 5, .774 1. .00 38, .99 C
ATOM ' 458 CB VAL A 59 48. .384 10. .521 7. .203 1. .00 39. .19 C
ATOM 459 CGI VAL A 59 47. .438 11. .723 7, .355 1. .00 38, .40 C
ATOM 460 CG2 VAL A 59 48, .013 9, .435 8, .204 1. .00 39, .01 C
ATOM 461 C VAL A 59 48, .441 10. .994 4. .704 1. ,00 39, ,04 c
ATOM 462 O VAL A 59 49, .527 11. .445 4, .368 1. ,00 39, ,20 0
ATOM 463 N ASN A 60 47. .288 11. .329 4. .123 1. ,00 39. ,25 N
ATOM 464 CA ASN A 60 47. ,167 12. .432 3. .159 1. ,00 38, .89 C
ATOM 465 CB ASN A 60 46, .856 11, .903 1, .766 1, .00 38, .66 C
ATOM 466 CG ASN A 60 46, .808 13. .004 0. .716 1. .00 39. .92 C
ATOM 467 ODl ASN A 60 46, ,683 14, .195 1, .023 1. .00 40, .70 O
ATOM 468 ND2 ASN A 60 46, .898 12. .602 -0. .542 1. .00 41. .09 N
ATOM 469 C ASN A 60 46, .088 13. .417 3. .620 1. .00 38, .71 C
ATOM 470 O ASN A 60 44, .905 13, .256 3, .309 1. .00 38, .65 O
ATOM 471 N LYS A 61 46, .514 14, ,431 4. .370 1. ,00 38, .57 N
ATOM 472 CA LYS A 61 45, .602 15, .383 4, .996 1. .00 38, .16 C
ATOM 473 CB LYS A 61 46, .355 16, .271 5. .980 1. .00 37. .56 C
ATOM 474 CG LYS A 61 46, .886 15. .543 7. .172 1. .00 35, .28 C
ATOM 475 CD LYS A 61 47, .561 16, .502 8, .098 1. .00 32, .88 C
ATOM 476 CE LYS A 61 47, .572 15. .971 9. .495 1, .00 31. .84 C
ATOM 477 NZ LYS A 61 48, .779 16, .466 10, .203 1. .00 33, .28 N
ATOM 478 C LYS A 61 44. .841 16. ,234 3. ,966 1. .00 38. ,90 C
ATOM 479 0 LYS A 61 43, .655 16, .544 4, .180 1. .00 38, .97 O
ATOM 480 N GLY A 62 45, .521 16, .606 2, .869 1, ,00 39, .06 N
ATOM 481 CA GLY A 62 44, .897 17, .316 1, .742 1. .00 39, ,10 C
ATOM 482 C GLY A 62 43, .622 16, .614 1, .292 1. .00 39, .43 C
ATOM 483 0 GLY A 62 42, .535 17, ,195 1, .319 1. ,00 39. .28 O
ATOM 484 N SER A 63 43, .735 15, .345 0, .914 1. .00 39, .54 N
ATOM 485 CA SER A 63 42, .556 14, .614 0, .471 1, .00 39, .91 C
ATOM 486 CB SER A 63 42, .924 13, .630 -0, ,640 1. .00 40. .15 C
ATOM 487 OG SER A 63 43, .499 12, .450 -0, .115 1. ,00 40, .82 O
ATOM 488 C SER A 63 41, .827 13. .907 1. ,618 1. ,00 39, .94 C
ATOM 489 O SER A 63 40, .885 13, .162 1, ,382 1. .00 39, .93 O
ATOM 490 N LYS A 64 42, .260 14, .157 2, .853 1. ,00 39, .99 N
ATOM 491 CA LYS A 64 41, .631 13, .589 4, .054 1. ,00 40. .06 C
ATOM 492 CB LYS A 64 40, .267 14, ,231 4, .317 1. .00 39, ,53 C
ATOM 493 CG LYS A 64 40, .306 15. .555 5. .036 1, ,00 38, .57 C
ATOM 494 CD LYS A 64 39. .285 16. .496 4. .420 1, .00 38, .14 C
ATOM 495 CE LYS A 64 38, .478 17, ,277 5, ,453 1, ,00 37, .99 C
ATOM 496 NZ LYS A 64 38. .684 18. .747 5. ,347 1. ,00 38, .34 N
ATOM 497 C LYS A 64 41, .506 12, ,060 4. .015 1, .00 40, ,63 C
ATOM 498 O LYS A 64 40. .515 11. ,491 4, ,507 1, .00 40, ,91 O
ATOM 499 N SER A 65 42, .507 11. ,399 3. ,439 1. .00 40, ,85 N
ATOM 500 CA SER A 65 42, .524 9. .940 3, .393 1, .00 41, .61 C
ATOM 501 CB SER A 65 42, ,351 9. .465 1. ,974 1. .00 41. .33 C
ATOM 502 OG SER A 65 43, .517 9. .807 1. .261 1, .00 42. .19 O
ATOM 503 C SER A 65 43, .839 9. ,391 3, .938 1. ,00 42. .06 C
ATOM 504 O SER A 65 44, .880 10, ,055 3, .886 1. ,00 42. .51 O
ATOM 505 N PHE A 66 43, .797 8, ,164 4, .438 1, .00 42, .21 N
ATOM 506 CA PHE A 66 44, ,934 7. ,603 5, .135 1. ,00 42. ,56 C
ATOM 507 CB PHE A 66 45, .006 8, ,173 6. .554 1. ,00 42. .69 C
ATOM 508 CG PHE A 66 43, .749 7. ,977 7. ,340 1. ,00 43. ,57 C
ATOM 509 CD1 PHE A 66 43. .747 7. ,183 8. ,488 1. ,00 45. ,35 C
ATOM 510 CEl PHE A 66 42. .560 6, ,982 9. ,215 1. ,00 45, .15 C
ATOM 511 CZ PHE A 66 41. .365 7. ,585 8. ,792 1. ,00 44. ,06 C
ATOM 512 CE2 PHE A 66 41, .364 8, .380 7. ,656 1. ,00 43. ,63 C
ATOM 513 CD2 PHE A 66 42. .554 8. ,569 6. ,935 1. ,00 44. ,35 C
ATOM 514 C PHE A 66 44. .757 6. .106 5. ,157 1. ,00 42. ,46 C
ATOM 515 O PHE A 66 43. ,636 5. .617 5. ,036 1. ,00 42. ,37 0
ATOM 516 N SER A 67 45. ,859 5. .381 5. ,301 1. 00 42. ,29 N ATOM 517 CA SER A 67 45,.826 3,.926 5.227 1.00 42.43 c
ATOM 518 CB SER A 67 46 .278 3, .454 3 .846 1 .00 42 .23 c
ATOM 519 OG SER A 67 47 .595 3, .886 3 .538 1. .00 42 .43 0
ATOM 520 C SER A 67 46, .708 3, .319 6 .301 1 .00 42 .62 c
ATOM 521 O SER A 67 47 .547 4 .022 6 .869 1 .00 43 .30 0
ATOM 522 N LEU A 68 46, .503 2, .032 6, .599 1, .00 42 .30 N
ATOM 523 CA LEU A 68 47, .421 1, .276 7 .460 1 .00 41 .69 c
ATOM 524 CB LEU A 68 46 .731 0 .905 8 .771 1 .00 42 .08 c
ATOM 525 CG LEU A 68 47, .490 0, .038 9, .789 1, .00 41 .64 c
ATOM 526 CD1 LEU A 68 48, .609 0, .829 10 .433 1, .00 40 .86 c
ATOM 527 CD2 LEU A 68 46, .532 -0, .537 10, .837 1, .00 40, .59 c
ATOM 528 C LEU A 68 47, ,899 0, .010 6, .766 1, .00 41 .78 c
ATOM 529 O ' LEU A 68 47, .109 -0, .693 6 .130 1 .00 41 .90 0
ATOM 530 N ARG A 69 49, .188 -0, .286 6, .892 1, .00 41 .68 N
ATOM 531 CA ARG A 69 49, .758 -1, .526 6, .355 1, .00 41 .58 C
ATOM 532 CB ARG A 69 50. .780 -1, .257 5, .265 1, .00 41, .79 C
ATOM 533 CG ARG A 69 50, .930 -2, .417 4, .305 1, .00 44 .13 C
ATOM 534 CD ARG A 69 51, .683 -2, .018 3, .041 1, .00 48 .20 C
ATOM 535 NE ARG A 69 53. .069 -2, .481 3, .086 1, .00 52, .28 N
ATOM 536 CZ ARG A 69 54, .101 -1, .792 3, .584 1, .00 54, .41 C
ATOM 537 NHl ARG A 69 55. .322 -2, ,331 3, .571 1. .00 55, .41 N
ATOM 538 NH2 ARG A 69 53. ,933 -0, .569 4, .083 1, .00 54, .08 N
ATOM 539 C ARG A 69 50, .410 -2, .320 7, ,458 1, .00 41, .10 C
ATOM 540 O ARG A 69 51. ,175 -1. .776 8. .258 1. .00 41, .13 O
ATOM 541 N ILE A 70 50, .092 -3, .610 7, .501 1, .00 40, .76 N
ATOM 542 CA ILE A 70 50. .601 -4. .510 8. .535 1. .00 39, .88 C
ATOM 543 CB ILE A 70 49, .453 -5. .222 9, .325 1, .00 39, .36 C
ATOM 544 CGI ILE A 70 48, .347 -4, .228 9, .728 1, .00 37, .87 c
ATOM 545 GDI ILE A 70 47. .792 -4, .439 11, ,089 1, .00 35, .40 c
ATOM 546 CG2 ILE A 70 50, .006 -5, .964 10, .520 1, .00 38, .83 c
ATOM 547 C ILE A 70 51. .449 -5, .521 7, .808 1. .00 40, ,36 c
ATOM 548 O ILE A 70 50. .957 -6. .225 6. .941 1. .00 40, .44 0
ATOM 549 N ARG A 71 52, .733 -5, .552 8, .130 1, .00 41, .10 N
ATOM 550 CA ARG A 71 53, ,666 -6, ,476 7, .528 1. .00 41. .96 C
ATOM 551 CB ARG A 71 55, .068 -5, .884 7, .626 1, .00 42, .48 C
ATOM 552 CG ARG A 71 56, .093 -6, .426 6, .622 1. .00 46, ,49 c
ATOM 553 CD ARG A 71 56, ,065 -5, ,651 5, .276 1. .00 52, .49 c
ATOM 554 NE ARG A 71 57, .001 -6, ,185 4, .271 1, .00 55, .71 N
ATOM 555 CZ ARG A 71 57, .090 -5, .751 3, ,010 1. .00 57, .32 c
ATOM 556 NHl ARG A 71 56, .295 -4, .773 2, .577 1. .00 58, ,00 N
ATOM 557 NH2 ARG A 71 57, .975 -6, .293 2, .177 1. .00 57, ,14 N
ATOM 558 C ARG A 71 53, .606 -7, .790 8, ,309 1. .00 42, ,06 C
ATOM 559 O ARG A 71 53, .359 -7, .772 9, ,522 1. .00 41, ,88 O
ATOM 560 N ASP A 72 53, .816 -8, ,917 7. ,615 1. ,00 42, ,18 N
ATOM 561 CA ASP A 72 53, .979 -10, .243 8, ,237 1. .00 42, .19 C
ATOM 562 CB ASP A 72 55. .119 -10. ,225 9, .257 1, ,00 42, ,61 C
ATOM 563 CG ASP A 72 56. .476 -10. ,361 8. .625 1. ,00 44, ,47 C
ATOM 564 ODl ASP A 72 57. .153 -11. ,381 8, .916 1, ,00 45, ,25 O
ATOM 565 OD2 ASP A 72 56, .867 -9, .447 7, ,850 1. ,00 46, .70 O
ATOM 566 C ASP A 72 52. .756 -10. .734 8. ,969 1. ,00 41, .93 C
ATOM 567 O ASP A 72 52. ,819 -10. .966 10. ,178 1. ,00 41. .95 O
ATOM 568 N LEU A 73 51. .645 -10, .913 8. ,268 1. ,00 41. .73 N
ATOM 569 CA LEU A 73 50, .422 -11, .332 8. ,954 1. ,00 41. .47 C
ATOM 570 CB LEU A 73 49. ,222 -11. ,373 8. ,010 1. ,00 41. ,11 C
ATOM 571 CG LEU A 73 48. ,727 -9. .994 7. ,567 1. ,00 40. ,12 C
ATOM 572 CD1 LEU A 73 47. ,903 -10. ,146 6. 326 1. ,00 40. ,41 C
ATOM 573 CD2 LEU A 73 47. ,941 -9. ,265 8. 650 1. ,00 37. ,17 C
ATOM 574 C LEU A 73 50. ,648 -12. ,664 9. ,644 1. ,00 41. ,62 C
ATOM 575 O LEU A 73 51. ,502 -13. ,438 9. 224 1. 00 41. 48 O
ATOM 576 N ARG A 74 49. ,904 -12. ,903 10. 720 1. 00 42. 02 N
ATOM 577 CA ARG A 74 50. 122 -14. 067 11. 589 1. 00 42. 54 C
ATOM 578 CB ARG A 74 51. ,235 -13. ,788 12. 614 1. 00 42. 53 C
ATOM 579 CG ARG A 74 51. ,179 -12. ,388 13. 256 1. 00 43. 61 C
ATOM 580 CD ARG A 74 52. 125 -12. 257 14. 459 1. 00 43. 83 C ATOM 581 NE ARG A 74 53.394 -11,.580 14.167 1.00 46.03 N
ATOM 582 CZ ARG A 74 53 .748 -10 .386 14 .649 1 .00 46 .33 C
ATOM 583 NHl ARG A 74 52, .936 -9, .706 15, .457 1 .00 45 .42 N
ATOM 584 NH2 ARG A 74 54 .924 -9, .870 14, .317 1 .00 46 .76 N
ATOM 585 C ARG A 74 48 .833 -14, .489 12 .290 1 .00 42 .15 C
ATOM 586 O ARG A 74 47, .851 -13, .742 12, .296 1, .00 42 .15 O
ATOM 587 N VAL A 75 48, .839 -15, .691 12, .863 1 .00 41 .96 N
ATOM 588 CA VAL A 75 47 .655 -16, .259 13, .526 1 .00 41 .57 C
ATOM 589 CB VAL A 75 48, .010 -17. .568 14, .298 1, .00 41, .47 C
ATOM 590 CGI VAL A 75 46, .806 -18. ,116 15, .058 1, .00 41, .34 C
ATOM 591 CG2 VAL A 75 48, .559 -18, .619 13, .334 1 .00 41 .54 C
ATOM 592 C VAL A 75 47, .012 -15. ,202 14, .444 1, .00 41, .29 C
ATOM 593 O VAL A 75 45, .917 -14, .683 14, .150 1 .00 41 .52 0
ATOM 594 N GLU A 76 47, .737 -14, .853 15, .509 1 .00 40 .35 N
ATOM 595 CA GLU A 76 47. .289 -13. .910 16, .530 1, .00 39, .34 C
ATOM 596 CB GLU A 76 48, .455 -13. .586 17, .474 1, .00 39, .48 C
ATOM 597 CG GLU A 76 49, .647 -12. .919 16, .786 1, .00 41, .25 C
ATOM 598 CD GLU A 76 51. .012 -13. .380 17. .305 1, .00 43, .35 C
ATOM 599 OEl GLU A 76 51, .405 -14. .537 17. .015 1, .00 43, .69 0
ATOM 600 OE2 GLU A 76 51, .711 -12. .568 17, .962 1, .00 43, .92 o
ATOM 601 C GLU A 76 46. .646 -12. .637 15. .963 1, .00 38, ,30 c
ATOM 602 O GLU A 76 45, .830 -12. .017 16. .631 1, .00 38, ,03 0
ATOM 603 N ASP A 77 46, .995 -12. .285 14. .725 1, .00 37, .35 N
ATOM 604 CA ASP A 77 46. .562 -11. .037 14. .072 1. .00 36. .49 C
ATOM 605 CB ASP A 77 47, .430 -10. .761 12. .852 1. .00 36. .49 C
ATOM 606 CG ASP A 77 48, .581 -9. .848 13. .147 1, .00 37, .31 C
ATOM 607 ODl ASP A 77 48, .488 -9, ,031 14, .082 1, .00 39. .17 O
ATOM 608 OD2 ASP A 77 49. .587 -9, ,934 12, ,419 1. .00 37. .91 o
ATOM 609 C ASP A 77 45, .104 -10, ,946 13, ,614 1, .00 35. .90 c
ATOM 610 O ASP A 77 44. .686 -9, ,903 13, ,119 1, .00 35. .62 0
ATOM 611 N SER A 78 44, .338 -12, ,026 13, ,750 1, .00 35. .37 N
ATOM 612 CA SER A 78 42, .955 -12, .026 13, ,270 1, .00 34. .66 c
ATOM 613 CB SER A 78 42, .436 -13, .451 13. ,134 1, .00 34. .45 c
ATOM 614 OG SER A 78 43, .376 -14, .247 12. ,450 1. .00 34. .25 0
ATOM 615 C SER A 78 42. .050 -11, .228 14. ,199 1. .00 34. .40 c
ATOM 616 O SER A 78 42. .061 -11. .442 15. ,412 1, .00 34. ,25 0
ATOM 617 N GLY A 79 41, .277 -10. .307 13, ,625 1, .00 34. ,06 N
ATOM 618 CA GLY A 79 40, .327 -9, .506 14, ,395 1, .00 33. .98 C
ATOM 619 C GLY A 79 39, .751 -8. ,336 13, ,625 1, .00 34. .18 c
ATOM 620 O GLY A 79 39, .807 -8. ,317 12. ,390 1, .00 34. .12 0
ATOM 621. N THR A 80 39, .207 -7. .355 14, ,354 1, .00 34. .22 N
ATOM 622 CA THR A 80 38, ,551 -6. .189 13. ,742 1. .00 34. .52 C
ATOM 623 CB THR A 80 37. .118 -5. ,930 14. ,301 1. .00 34. .52 C
ATOM 624 OGl THR A 80 36. .338 -7. .125 14, ,215 1, .00 35. .18 O
ATOM 625 CG2 THR A 80 36. .405 -4. ,848 13. ,507 1, .00 34, ,49 C
ATOM . 626 C THR A 80 39. .387 -4. .922 13. ,888 1. .00 34, ,82 C
ATOM 627 O THR A 80 39, .666 -4. .458 15. ,003 1, .00 35. ,04 O
ATOM 628 N TYR A 81 39. ,775 -4. ,365 12. ,750 1, .00 34. ,80 N
ATOM 629 CA TYR A 81 40. .543 -3. ,143 12. ,732 1, .00 35. ,18 C
ATOM 630 CB TYR A 81 41. .690 -3, .274 11. ,738 1. .00 34. .34 C
ATOM 631 CG TYR A 81 42. ,654 -4. ,335 12. ,154 1. .00 33. ,32 C
ATOM 632 CD1 TYR A 81 43, ,933 -4. ,010 12. ,556 1. .00 33. ,55 C
ATOM 633 CEl TYR A 81 44, .822 -5. ,002 12. ,958 1, .00 33. ,31 C
ATOM 634 CZ TYR A 81 44. ,424 -6. ,321 12. 966 1. ,00 32. ,64 C
ATOM 635 OH TYR A 81 45. .292 -7. ,296 13. ,373 1. ,00 31. ,77 O
ATOM 636 CE2 TYR A 81 43. .147 -6. ,660 12. ,586 1. .00 32. ,62 C
ATOM 637 CD2 TYR A 81 42. ,275 -5. ,670 12. 182 1. ,00 32. ,26 c
ATOM 638 C TYR A 81 39. ,629 -1. ,958 12. 393 1. ,00 36. ,14 c
ATOM 639 O TYR A 81 38. ,818 -2. ,057 11. ,461 1. .00 36. ,07 0
ATOM 640 N LYS A 82 39. ,751 -0. ,865 13. 161 1. ,00 36. 60 N
ATOM 641 CA LYS A 82 38. ,958 0. ,330 12. 934 1. ,00 37. ,79 c
ATOM 642 CB LYS A 82 37. ,866 0. ,467 13. 980 1. ,00 37. ,18 c
ATOM 643 CG LYS A 82 36. 568 -0. 098 13. 582 1. ,00 36. 88 c
ATOM 644 CD LYS A 82 35. ,673 -0. ,167 14. 774 1. ,00 37. 48 c ATOM 645 CE LYS A 82 34.371 -0.857 14.437 1.00 38.70 c
ATOM 646 NZ LYS A 82 33 .540 -1 .153 15 .653 1 .00 40 .07 N
ATOM 647 C LYS A 82 39 .830 1, .555 12 .997 1 .00 39 .37 C
ATOM 648 O LYS A 82 40 .507 1 .786 14 .000 1 .00 40 .01 O
ATOM 649 N CYS A 83 39 .797 2 .358 11 .936 1 .00 41 .01 N
ATOM 650 CA CYS A 83 40, .517 3, .629 11, .915 1. .00 42 .65 C
ATOM 651 CB CYS A 83 40, .841 4, .047 10 .473 1 .00 43 .26 C
ATOM 652 SG CYS A 83 39 .421 4 .180 9 .326 1 .00 47 .78 s
ATOM 653 C CYS A 83 39, .696 4, .707 12, .617 1 .00 42 .57 c
ATOM 654 O CYS A 83 38, .468 4, .634 12, .641 1. .00 43 .03 0
ATOM 655 N GLY A 84 40, .365 5, .701 13 .197 1 .00 42 .24 N
ATOM 656 CA GLY A 84 39, .667 6, .825 13, .803 1 .00 41 .51 C
ATOM 657 C GLY A 84 40, .216 8, .090 13, .221 1 .00 41 .19 C
ATOM 658 O GLY A 84 41, .428 8, .307 13 .271 1 .00 41 .93 O
ATOM 659 N ALA A 85 39, ,338 8. .907 12, .640 1, .00 40, .68 N
ATOM 660 CA ALA A 85 39, .721 10, .194 12, .043 1 .00 40 .26 c
ATOM 661 CB ALA A 85 39, .171 10, .280 10, .648 1 .00 39 .48 c
ATOM 662 C ALA A 85 39, ,229 11, .380 12, .890 1, .00 40, .43 c
ATOM 663 O ALA A 85 38, .024 11, .524 13, .095 1, .00 40, .41 o
ATOM 664 N TYR A 86 40, .144 12, .217 13, .389 1 .00 40 .96 N
ATOM 665 CA TYR A 86 39. .770 13. .398 14. .230 1, .00 41, .74 C
ATOM 666 CB TYR A 86 40, .395 13. .287 15. .633 1, .00 42, .59 C
ATOM 667 CG TYR A 86 39, .840 12. .049 16. .256 1, .00 44, .45 C
ATOM 668 CD1 TYR A 86 40. .464 10. .820 16. .075 1, ,00 46, .20 C
ATOM 669 CEl TYR A 86 39. .898 9. .655 16. .575 1, .00 47. .13 C
ATOM 670 CZ TYR A 86 38. .677 9. .716 17. .243 1, .00 47, .00 C
ATOM 671 OH TYR A 86 38. .110 8. .570 17. ,743 1. .00 47. .11 0
ATOM 672 CE2 TYR A 86 38. .022 10. .920 17. ,411 1, .00 47. ,20 c
ATOM 673 CD2 TYR A 86 38. .602 12. .076 16. ,903 1, .00 46, .80 c
ATOM 674 C TYR A 86 40. .025 14, .730 13. ,541 1. ,00 41, ,34 c
ATOM 675 O TYR A 86 41. .040 14, .901 12. ,903 1. .00 41, .73 0
ATOM 676 N PHE A 87 39. .080 15, .650 13. ,608 1, .00 41, .28 N
ATOM 677 CA PHE A 87 39. .166 16, ,845 12. ,782 1. ,00 41, ,56 C
ATOM 678 CB PHE A 87 38. .374 16, .639 11. ,477 1. ,00 41, .06 C
ATOM 679 CG PHE A 87 36. ,932 16, .274 11. .676 1, .00 39, .53 C
ATOM 680 GDI PHE A 87 35. ,947 17. ,257 11. .679 1. .00 39. .73 c
ATOM 681 CEl PHE A 87 34. ,586 16. ,931 11, .869 1. .00 39. .72 c
ATOM 682 CZ PHE A 87 34. ,210 15. ,602 12, .037 1. .00 39. .61 c
ATOM 683 CE2 PHE A 87 35. ,196 14. .600 12. ,011 1, .00 39, ,83 c
ATOM 684 CD2 PHE A 87 36. ,550 14. .948 11. ,824 1, .00 39, .38 c
ATOM 685 C PHE A 87 38, ,748 18. .133 13. .494 1, .00 42, .67 c
ATOM 686 O PHE A 87 37. ,823 18. ,117 14. ,298 1, .00 42. .45 0
ATOM 687 N SER A 88 39, ,422 19. ,249 13. ,208 1. .00 44. .36 N
ATOM 688 CA SER A 88 38, ,983 20. .548 13. .756 1, .00 46. .58 C
ATOM 689 CB SER A 88 39. ,254 20. ,623 15. ,262 1. .00 46. ,54 C
ATOM 690 OG SER A 88 38. ,249 21. ,402 15. ,909 1, .00 47. ,58 O
ATOM 691 C SER A 88 39, ,537 21, .793 13. ,046 1, .00 47. ,83 c
ATOM 692 O SER A 88 40. ,136 21. ,682 11. ,982 1. ,00 48. ,24 0
ATOM 693 N ASP A 89 39. ,280 22. ,973 13. ,611 1. ,00 49. ,69 N
ATOM 694 CA ASP A 89 39. ,998 24. ,207 13. ,237 1, ,00 51. ,76 C
ATOM 695 CB ASP A 89 39. ,034 25. ,388 13. 018 1. ,00 51. 71 C
ATOM 696 CG ASP A 89 37. ,997 25. ,525 14. 126 1. ,00 52. ,05 C
ATOM 697 ODl ASP A 89 37. ,313 24. ,520 14. ,445 1. ,00 51. ,33 O
ATOM 698 OD2 ASP A 89 37. ,854 26. 652 14. 656 1. 00 52. 53 0
ATOM 699 C ASP A 89 41. ,078 24. ,545 14. 284 1. ,00 53. 06 C
ATOM 700 O ASP A 89 41. ,313 23. ,760 15. ,207 1. ,00 53. ,58 0
ATOM 701 N ALA A 90 41. ,754 25. 683 14. 147 1. 00 54. 40 N
ATOM 702 CA ALA A 90 42. ,727 26. 075 15. 167 1. ,00 55. 85 C
ATOM 703 CB ALA A 90 43. ,719 27. 092 14. 620 1. ,00 55. 91 C
ATOM 704 C ALA A 90 42. 008 26. 617 16. 406 1. 00 56. 94 C
ATOM 705 O ALA A 90 42. 408 26. 311 17. 536 1. 00 57. 01 O
ATOM 706 N MET A 91 40. 941 27. 391 16. 163 1. 00 58. 11 N
ATOM 707 CA MET A 91 40. 091 28. 038 17. 187 1. 00 59. 30 C
ATOM 708 CB MET A 91 38. 880 28. 721 16. 498 1. 00 59. 40 C ATOM 709 CG MET A 91 37.,535 28,.722 17,.267 1,.00 60,.45 c
ATOM 710 SD MET A 91 37. .156 30, .177 18, .308 1, .00 63, .23 s
ATOM 711 CE MET A 91 36. ,666 31. .394 17, .075 1, .00 61, .90 c
ATOM 712 C MET A 91 39. .652 27, .166 18, .396 1, .00 59, .86 c
ATOM 713 O MET A 91 39. .717 27, .622 19, .549 1, .00 59, .93 0
ATOM 714 N SER A 92 39. .226 25, .926 18, .131 1. .00 60, .49 N
ATOM 715 CA SER A 92 38. .665 25, .034 19, .166 1, .00 60, .99 C
ATOM 716 CB SER A 92 37. .804 23. .923 18, .536 1. ,00 61. .05 C
ATOM 717 OG SER A 92 37. .490 24, .177 17, .178 1, .00 61. .70 O
ATOM 718 C SER A 92 39. .749 24. .388 20, .036 1. .00 61. .12 c
ATOM 719 O SER A 92 40. ,158 23. .246 19, .782 1, .00 61. .30 0
ATOM 720 N ASN A 93 40. ,184 25, .096 21, .078 1, .00 61. .18 N
ATOM 721 CA ASN A 93 41, ,338 24. .655 21, .873 1. .00 61. .19 C
ATOM 722 CB ASN A 93 41, ,617 25, .608 23, .059 1, .00 61. .23 C
ATOM 723 CG ASN A 93 40. ,859 25. ,241 24, .321 1. .00 61. .10 C
ATOM 724 ODl ASN A 93 40. ,047 26, ,018 24, .809 1, .00 60. .02 O
ATOM 725 ND2 ASN A 93 41. .145 24, .065 24. .870 1. .00 61. ,37 N
ATOM 726 C ASN A 93 41. .293 23, .171 22, .270 1, .00 61. .09 C
ATOM 727 O ASN A 93 40. .238 22, .645 22, .631 1, .00 61, .14 O
ATOM 728 N TYR A 94 42. ,447 22, .513 22. .186 1. .00 61. .01 N
ATOM 729 CA TYR A 94 42. ,527 21. .044 22, .190 1, .00 60. .82 C
ATOM 730 CB TYR A 94 43. .727 20. ,577 21. .348 1. .00 61. .25 C
ATOM 731 CG TYR A 94 43. .596 20. ,802 19. .846 1. .00 62. ,15 C
ATOM 732 CD1 TYR A 94 43. .511 19, .718 18, .956 1, .00 62. .46 C
ATOM 733 CEl TYR A 94 43. .406 19. .923 17, .572 1. .00 62. .67 C
ATOM 734 CZ TYR A 94 43. .387 21. .228 17, .067 1, .00 62. .76 C
ATOM 735 OH TYR A 94 43. .280 21. .469 15. .707 1. .00 62. .36 O
ATOM 736 CE2 TYR A 94 43. .478 22. .312 17, .932 1. .00 63. .17 c
ATOM 737 CD2 TYR A . 94 43. .582 22. .096 19. .31.1 1. .00 62, ,95 c
ATOM 738 C TYR A 94 42, .581 20. ,366 23, .567 1. .00 60, ,23 c
ATOM 739 O TYR A 94 42, .718 19, .140 23, .641 1, .00 60, ,11 0
ATOM 740 N SER A 95 42, ,461 21. ,141 24, ,646 1. .00 59. ,52 N
ATOM 741 CA SER A 95 42, ,581 20, .582 26, .002 1. ,00 58, .81 C
ATOM 742 CB SER A 95 42, .852 21. .672 27, .042 1. .00 58. .71 c
ATOM 743 OG SER A 95 41, .818 22. .630 27, .053 1. .00 58. .55 o
ATOM 744 C SER A 95 41, .415 19. .669 26, .431 1. .00 58. .41 c
ATOM 745 O SER A 95 41, .552 18. .918 27, .404 1. ,00 58. .61 o
ATOM 746 N TYR A 96 40, .280 19. .744 25, .725 1, .00 57. .56 N
ATOM 747 CA TYR A 96 39, .262 18. .672 25, .743 1. .00 56, ,62 C
ATOM 748 CB TYR A 96 37, .920 19. .112 26, .373 1. .00 57. .07 C
ATOM 749 CG TYR A 96 37. .741 18. ,806 27, .868 1. .00 57. ,61 C
ATOM 750 CD1 TYR A 96 37, .940 17. .510 28, .391 1. .00 57. .75 C
ATOM 751 CEl TYR A 96 37. ,767 17, .247 29. .764 1. .00 57. ,76 c
ATOM 752 CZ TYR A 96 37, .377 18, .287 30. .616 1. .00 58. .09 c
ATOM 753 OH TYR A 96 37. ,191 18. .084 31. .966 1. .00 57. .64 o
ATOM 754 CE2 TYR A 96 37, ,167 19. .565 30. .118 1. .00 58. .28 c
ATOM 755 CD2 TYR A 96 37. ,343 19. .813 28. .753 1. .00 58. .03 c
ATOM 756 C TYR A 96 39. ,086 18. .199 24. ,297 1. .00 55. ,45 c
ATOM 757 O TYR A 96 39, ,520 18, .902 23, .381 1. .00 55. ,68 0
ATOM 758 N PRO A 97 38. ,437 17, ,029 24, ,084 1. ,00 54. ,13 N
ATOM 759 CA PRO A 97 38, ,603 16, ,250 22. ,842 1. ,00 52. ,71 C
ATOM 760 CB PRO A 97 37. ,814 14, .964 23. .119 1, .00 52. ,84 C
ATOM 761 CG PRO A 97 37. .584 14, .952 24, .598 1, .00 53. ,79 C
ATOM 762 CD PRO A 97 37. .472 16, .380 24. .989 1. .00 54. ,03 c
ATOM 763 C PRO A 97 38. ,060 16, .910 21. .592 1. .00 51. ,10 c
ATOM 764 O PRO A 97 37. .344 17, ,897 21, ,657 1. ,00 50. ,84 0
ATOM 765 N ILE A 98 38. ,401 16. ,347 20, .448 1, .00 49. .60 N
ATOM 766 CA ILE A 98 37. ,932 16, ,909 19. ,185 1. .00 47. ,94 C
ATOM 767 CB ILE A 98 39. ,116 17, .382 18, .274 1, .00 48. ,04 C
ATOM 768 CGI ILE A 98 40, ,146 16, ,264 18. .054 1. .00 47. ,50 C
ATOM 769 CD1 ILE A 98 41. .275 16, ,645 17. .088 1, .00 47. ,86 C
ATOM 770 CG2 ILE A 98 39. ,769 18, ,647 18. .881 1. .00 48. 04 C
ATOM 771 C ILE A 98 36. .983 15, ,953 18, .469 1. .00 46. ,38 c
ATOM 772 O ILE A 98 37, .126 14, .733 18. .617 1, .00 46. ,53 0 ATOM 773 N PRO A 99 35,.988 16,.498 17,.726 1,.00 44,.56 N
ATOM 774 CA PRO A 99 35, .087 15, .693 16. .891 1 .00 43 .02 C
ATOM 775 CB PRO A 99 34, .375 16. .736 16. .023 1, .00 42, .91 C
ATOM 776 CG PRO A 99 35, .076 18, .025 16. .282 1, .00 43 .57 c
ATOM 777 CD PRO A 99 35, .638 17. .922 17. .647 1, .00 44, .32 c
ATOM 778 C PRO A 99 35, .819 14, .672 16. .015 1, .00 41, .63 c
ATOM 779 O PRO A 99 36, .930 14. .920 15. .542 1, .00 41, .07 o
ATOM 780 N GLY A 100 35, .210 13, .515 15. .819 1, .00 40, .25 N
ATOM 781 CA GLY A 100 35, .838 12, .516 14. .992 1, .00 38 .90 C
ATOM 782 C GLY A 100 34, .862 11, .434 14. .664 1, ,00 38, .33 C
ATOM 783 O GLY A 100 33, .789 11, .369 15. .265 1, .00 38, .01 O
ATOM 784 N GLU A 101 35, .247 10, .592 13. .707 1, ,00 37, .69 N
ATOM 785 CA GLU A 101 34, .459 9, .460 13. .277 1, .00 37, .26 C
ATOM 786 CB GLU A 101 33, .817 9. .732 11. .925 1. ,00 37, .40 C
ATOM 787 CG GLU A 101 32, .802 10, ,844 11. .894 1, .00 39, .41 C
ATOM 788 CD GLU A 101 31, .489 10, .480 12. .574 1, ,00 42, .64 C
ATOM 789 OEl GLU A 101 31. .156 9, .266 12, .657 1, .00 44, .09 O
ATOM 790 OE2 GLU A 101 30. .784 11, .422 13. ,015 1. ,00 42, .76 O
ATOM 791 C GLU A 101 35, .362 8, ,271 13, .110 1, .00 37, .21 C
ATOM 792 O GLU A 101 36, .540 8, .394 12, .789 1, .00 36, .41 O
ATOM 793 N LYS A 102 34, .783 7. .098 13, .306 1, .00 38, .04 N
ATOM 794 CA LYS A 102 35, .478 5, .831 13, .085 1, .00 38, .38 C
ATOM 795 CB LYS A 102 35, .316 4, .910 14. .300 1. .00 38, .22 C
ATOM 796 CG LYS A 102 35, .999 5. .442 15. .541 1. .00 39, .05 C
ATOM 797 CD LYS A 102 35, .674 4, .610 16. .753 1. .00 41, .78 C
ATOM 798 CE LYS A 102 36, .545 3, .369 16. ,826 1. ,00 43, .99 C
ATOM 799 NZ LYS A 102 36. .106 2, .510 17, ,964 1. ,00 47. ,98 N
ATOM 800 C LYS A 102 34, .936 5, .168 11, ,823 1. ,00 38. .37 C
ATOM 801 O LYS A 102 33, .815 5, .468 11, .379 1, .00 38, .58 O
ATOM 802 N GLY A 103 35, .741 4, .289 11, .232 1. .00 38. .20 N
ATOM 803 CA GLY A 103 35, .315 3, .531 10. .069 1, .00 37, .94 C
ATOM 804 C GLY A 103 34, ,398 2, .432 10, .546 1. .00 37. .97 C
ATOM 805 O GLY A 103 34, .407 2, .098 11, .738 1. ,00 37. .93 O
ATOM 806 N ALA A 104 33. .597 1, .878 9, .631 1. ,00 37. .92 N
ATOM 807 CA ALA A 104 32, .750 0, .702 9, .939 1. .00 37. .58 C
ATOM 808 CB ALA A 104 31. .765 0, ,432 8, ,801 1. ,00 37. .08 C
ATOM 809 C ALA A 104 33, .551 -0, .583 10, .315 1. ,00 37. .23 C
ATOM 810 O ALA A 104 32, ,987 -1, .493 10, .913 1. .00 36. .83 O
ATOM 811 N GLY A 105 34. .848 -0, .639 9. ,980 1. .00 36. .70 N
ATOM 812 CA GLY A 105 35. .717 -1, .739 10. .405 1. .00 36. .63 C
ATOM 813 C GLY A 105 36. .121 -2. .751 9. ,334 1. .00 36. .82 C
ATOM 814 O GLY A 105 35. .447 -2, .898 8. ,310 1. .00 36. .82 O
ATOM 815 N THR A 106 37. .228 -3. .452 9. ,586 1, .00 36, ,84 N
ATOM 816 CA THR A 106 37. .735 -4, .539 8. .727 1. .00 36, .57 C
ATOM 817 CB THR A 106 39. .140 -4. .208 8. ,153 1, ,00 36, .36 C
ATOM 818 OGl THR A 106 39. .057 -3. .079 7. .270 1, .00 36, .90 O
ATOM 819 CG2 THR A 106 39. .716 -5, .390 7. .393 1, .00 36, .01 C
ATOM 820 C THR A 106 37. .848 -5, .826 9. .540 1. .00 36. .39 C
ATOM 821 O THR A 106 38. ,609 -5, .895 10. .499 1, ,00 36. .67 O
ATOM 822 N VAL A 107 37. ,093 -6, .848 9. ,183 1, ,00 36, ,21 N
ATOM 823 CA VAL A 107 37. ,282 -8, .113 9. .871 1, ,00 36, .14 C
ATOM 824 CB VAL A 107 35. ,938 -8. .872 10. ,219 1. ,00 36. ,19 C
ATOM 825 CGI VAL A 107 34. .747 -8, ,302 9. .454 1. ,00 36. ,06 C
ATOM 826 CG2 VAL A 107 36, .078 -10. ,400 10. ,048 1. ,00 35. ,72 C
ATOM 827 C VAL A 107 38, .315 -8. ,942 9. ,111 1. ,00 36. ,04 C
ATOM 828 O VAL A 107 38. ,114 -9. .330 7. .953 1. ,00 36. ,06 O
ATOM 829 N LEU A 108 39. ,439 -9. ,173 9. ,780 1. ,00 35. ,79 N
ATOM 830 CA LEU A 108 40. .553 -9. ,902 9. ,202 1, .00 35. ,32 C
ATOM 831 CB LEU A 108 41. .836 -9. ,135 9. ,469 1. .00 35. ,00 C
ATOM 832 CG LEU A 108 43. .135 -9. ,811 9. ,049 1. ,00 35. ,77 c
ATOM 833 CD1 LEU A 108 43. .114 -10. ,166 7. 569 1. ,00 34. 89 c
ATOM 834 CD2 LEU A 108 44, .303 -8. ,880 9. ,385 1. ,00 36. ,41 c
ATOM 835 C LEU A 108 40. ,665 -11. ,351 9. 707 1. 00 34. 96 c
ATOM 836 O LEU A 108 40. ,651 -11. ,607 10. ,914 1. ,00 34. 93 o ATOM 837 N THR A 109 40.763 -12,.291 8.771 1,.00 34.40 N
ATOM 838 CA THR A 109 41 .047 -13 .679 9 .108 1 .00 33 .95 C
ATOM 839 CB THR A 109 40 .034 -14, .648 8 .489 1, .00 33 .87 C
ATOM 840 OGl THR A 109 38 .720 -14, .118 8 .645 1, .00 34 .49 O
ATOM 841 CG2 THR A 109 40 .092 -15 .997 9 .177 1, .00 34 .16 C
ATOM 842 C THR A 109 42 .411 -13, .992 8, .553 1, .00 33, .64 c
ATOM 843 O THR A 109 42 .731 -13, .599 7 .432 1, .00_ 33 .51 0
ATOM 844 N VAL A 110 43, .214 -14, .689 9, .351 1, ,00* 33, .46 N
ATOM 845 CA VAL A 110 44 .557 -15, .120 8 .951 1, .00 33 .20 C
ATOM 846 CB VAL A 110 45, .644 -14, .520 9, .895 1, .00 33, .18 c
ATOM 847 CGI VAL A 110 47 .033 -14, .974 9 .497 1, .00 32, .89 c
ATOM 848 CG2 VAL A 110 45 .576 -12, .990 9. .876 1, .00 33 .11 c
ATOM 849 C VAL A 110 44, .628 -16, .662 8, .879 1. .00 33, .14 c
ATOM 850 O VAL A 110 43 .820 -17, .352 9 .508 1, .00 33, .15 0
ATOM 851 N LYS A 111 45, .569 -17, .176 8, .076 1, .00 32, .96 N
ATOM 852 CA LYS A 111 45 .863 -18, .614 7, .908 1, .00 32, .47 c
ATOM 853 CB LYS A 111 46, .047 -19, .310 9, .266 1. .00 32, .42 c
ATOM 854 CG LYS A 111 47, .301 -20, .173 9, .401 1. .00 32, .16 c
ATOM 855 CD LYS A 111 47 .322 -21, .337 8 .439 1, .00 30, .51 c
ATOM 856 CE LYS A 111 48, .666 -21, .373 7, .765 1. .00 29, .84 c
ATOM 857 NZ LYS A 111 48, .509 -21, .849 6, .325 1. ,00 28, .97 N
ATOM 858 C LYS A 111 44, .803 -19. .337 7, .075 1. ,00 32, .50 c
ATOM 859 O LYS A 111 43, .688 -18. .840 6, .886 1. .00 32, .44 0
ATOM 860 N ALA B 1 61, ,374 15, .952 26, .666 1. .00 40, ,58 N
ATOM 861 CA ALA B 1 61, .194 15. .867 25, .190 1, .00 40, .32 C
ATOM 862 CB ALA B 1 59, .746 15, .561 24, .857 1, .00 40, .27 C
ATOM 863 C ALA B 1 61, .595 17. .183 24. .574 1, .00 40, .31 C
ATOM 864 O ALA B 1 61, .451 18, .221 25, .207 1, .00 40, .46 O
ATOM 865 N TRP B 2 62, ,100 17. .137 23, .345 1. .00 40, .50 N
ATOM 866 CA TRP B 2 62, ,339 18, ,351 22, .545 1, .00 40. .64 C
ATOM 867 CB TRP B 2 63, .662 19, .036 22, .923 1, .00 40, ,90 C
ATOM 868 CG TRP B 2 64, ,853 18. .232 22, .538 1, .00 41. ,26 C
ATOM 869 GDI TRP B 2 65, .313 17, .111 23, .157 1, .00 41. .31 C
ATOM 870 NE1 TRP B 2 66. .415 16, .634 22. .506 1. .00 41. .61 N
ATOM 871 CE2 TRP B 2 66, .688 17, .445 21, .435 1, .00 41. .51 C
ATOM 872 CD2 TRP B 2 65. .721 18, .465 21, ,426 1. .00 41. .52 C
ATOM 873 CE3 TRP B 2 65. .776 19, .445 20, .419 1, .00 42. .43 C
ATOM 874 CZ3 TRP B 2 66, .798 19. .376 19, .467 1, .00 41. .87 C
ATOM 875 CH2 TRP B 2 67, .753 18. .344 19, ,507 1, .00 42. .06 C
ATOM 876 CZ2 TRP B 2 67. .716 17. .373 20, ,482 1, .00 42. .00 C
ATOM 877 C TRP B 2 62. ,302 18. .017 21. ,058 1. ,00 40. ,47 C
ATOM 878 O TRP B 2 62. ,361 16. .852 20. ,678 1. .00 40. ,26 O
ATOM 879 N VAL B 3 62. .187 19. .050 20. ,231 1. .00 40. ,69 N
ATOM 880 CA VAL B 3 62. .056 18. .889 18, .794 1. ,00 40. ,91 C
ATOM 881 CB VAL B 3 60. .770 19. .529 18, .257 1. .00 40. ,88 C
ATOM 882 CGI VAL B 3 60, ,727 19, .412 16. .755 1. ,00 40. ,86 C
ATOM 883 CG2 VAL B 3 59, .540 18, .863 18. .860 1. .00 40. ,88 C
ATOM 884 C VAL B 3 63. .222 19. .534 18. .093 1. ,00 41. ,36 C
ATOM 885 O VAL B 3 63. ,461 20. .727 18. .240 1. ,00 41. ,24 O
ATOM 886 N ASP B 4 63, ,942 18. .720 17. ,329 1. ,00 42. ,15 N
ATOM 887 CA ASP B 4 65. ,052 19. .174 16. .502 1. ,00 42. ,71 C
ATOM 888 CB ASP B 4 66. ,056 18, .034 16. .348 1. ,00 43. ,16 C
ATOM 889 CG ASP B 4 67, .427 18. ,503 15. ,884 1. ,00 45. 21 C
ATOM 890 ODl ASP B 4 68, .205 17. .616 15. ,462 1. ,00 47. 92 O
ATOM 891 OD2 ASP B 4 67. ,739 19. ,725 15. .948 1. 00 45. 46 O
ATOM 892 C ASP B 4 64. .510 19. ,559 15. ,141 1. ,00 42. 38 C
ATOM 893 O ASP B 4 64, ,014 18. ,697 14. .419 1. ,00 42. ,71 O
ATOM 894 N GLN B 5 64. ,585 20. ,842 14. ,795 1. ,00 42. 02 N
ATOM 895 CA GLN B 5 64. ,012 21. ,321 13. .537 1. ,00 42. ,00 C
ATOM 896 CB GLN B 5 62. ,884 22. ,316 13. ,775 1. 00 41. 95 C
ATOM 897 CG GLN B 5 62. ,484 23. ,088 12. ,544 1. ,00 42. 24 C
ATOM 898 CD GLN B 5 61. ,343 24. ,061 12. 775 1. 00 42. 53 C
ATOM 899 OEl GLN B 5 61. ,122 24. ,946 11. ,957 1. 00 44. 45 O
ATOM 900 NE2 GLN B 5 60. ,601 23. ,896 13. ,871 1. 00 42. 54 N ATOM 901 C GLN B 5 65,.070 21,.925 12.647 1.00 42.01 C
ATOM 902 O GLN B 5 65, .737 22. ,873 13, .020 1, .00 41 .81 O
ATOM 903 N THR B 6 65, .165 21, .383 11, .442 1 .00 42 .28 N
ATOM 904 CA THR B 6 66, .276 21. .604 10, .539 1, .00 42, .29 C
ATOM 905 CB THR B 6 67, .123 20, .300 10, .533 1, .00 42, .26 C
ATOM 906 OGl THR B 6 68, .506 20, .595 10, .360 1 .00 42 .75 O
ATOM 907 CG2 THR B 6 66. .646 19. .280 9, .494 1, .00 43, .12 C
ATOM 908 C THR B 6 65, .656 21. .970 9, .174 1, .00 42, .28 c
ATOM 909 O THR B 6 64, .656 21, .372 8, .774 1 .00 43 .46 0
ATOM 910 N PRO B 7 66. .161 23, .007 8, .485 1, .00 41, .61 N
ATOM 911 CA PRO B 7 67. .250 23. .902 8, .768 1, .00 41, .37 C
ATOM 912 CB PRO B 7 67. .673 24. .367 7. .382 1, .00 41, ,15 C
ATOM 913 CG PRO B 7 66. .448 24. .287 6, .546 1, .00 40, ,63 C
ATOM 914 CD PRO B 7 65, .479 23, .370 7, .229 1, .00 41, .21 C
ATOM 915 C PRO B 7 66. .795 25. ,105 9, .578 1, .00 41, .83 C
ATOM 916 O PRO B 7 65. .605 25. ,469 9, .587 1, .00 41, .92 0
ATOM 917 N ARG B 8 67, .767 25, .729 10, .227 1, .00 42, .11 N
ATOM 918 CA ARG B 8 67. .546 26. ,866 11, .084 1, .00 42, .31 C
ATOM 919 CB ARG B 8 68. .804 27. .107 11, .904 1, .00 42, .89 C
ATOM 920 CG ARG B 8 68. .536 27. ,677 13, .253 1, .00 46, .29 c
ATOM 921 CD ARG B 8 69. .820 27. ,906 14. .054 1, .00 52, .71 c
ATOM 922 NE ARG B 8 70. .453 26. .647 14, .446 1, .00 57, .86 N
ATOM 923 CZ ARG B 8 71. .641 26. .231 14. .005 1. .00 60. .60 C
ATOM 924 NHl ARG B 8 72. .133 25. .061 14. .415 1. .00 61. .06 N
ATOM 925 NH2 ARG B 8 72. .348 26. .988 13, .166 1, .00 61, .41 N
ATOM 926 C ARG B 8 67. .214 28, .067 10. .209 1. .00 41. .73 C
ATOM 927 0 ARG B 8 66. .308 28, .843 10, ,507 1, .00 42. .11 O
ATOM 928 N SER B 9 67. .934 28, ,205 9. ,109 1. .00 41. ,12 N
ATOM 929 CA SER B 9 67. .642 29, ,256 8. .158 1. ,00 41, .01 C
ATOM 930 CB SER B 9 68. .452 30, .518 8, ,468 1, .00 41, ,19 C
ATOM 931 OG SER B 9 69. .842 30. .315 8. .271 1. .00 40, ,95 O
ATOM 932 C SER B 9 67. .933 28. .761 6. .752 1. .00 40, ,85 C
ATOM 933 O SER B 9 68. ,813 27, ,924 6. ,553 1. ,00 41, .20 O
ATOM 934 N VAL B 10 67. ,174 29, .264 5. .780 1. .00 40, .24 N
ATOM 935 CA VAL B 10 67, ,441 28, .996 4. .368 1. .00 38, .90 C
ATOM 936 CB VAL B 10 66, ,828 27. .641 3. .924 1. .00 38. .87 C
ATOM 937 CGI VAL B 10 65, ,327 27. .586 4. .213 1. .00 38. .32 C
ATOM 938 CG2 VAL B 10 67, ,124 27. .343 2. .465 1. .00 38. .15 C
ATOM 939 C VAL B 10 66. ,940 30. .164 3. .519 1. .00 38. .48 C
ATOM 940 O VAL B 10 65, .913 30. .783 3. .827 1. .00 38. .34 O
ATOM 941 N THR B 11 67. ,686 30, ,501 2. ,476 1. ,00 37. ,98 N
ATOM 942 CA THR B 11 67. ,104 31. ,341 1. .447 1. ,00 37. ,86 C
ATOM 943 CB THR B 11 67. .902 32. .620 1. .151 1. .00 37. ,76 C
ATOM 944 OGl THR B 11 68. ,567 32. ,460 -0. .094 1. .00 39. .82 O
ATOM 945 CG2 THR B 11 68. .917 32. .956 2. .258 1. .00 37, ,12 C
ATOM 946 C THR B 11 66, .833 30. .522 0. .164 1. .00 37. ,54 C
ATOM 947 O THR B 11 67, ,627 29. ,640 -0. .225 1, .00 37. .27 O
ATOM 948 N LYS B 12 65. .683 30. .803 -0. ,457 1, ,00 36, .76 N
ATOM 949 CA LYS B 12 65. ,231 30. ,116 -1, ,671 1. ,00 35. ,59 C
ATOM 950 CB LYS B 12 64. ,089 29. ,143 -1. .356 1. ,00 35. ,82 C
ATOM 951 CG LYS B 12 64. .455 27. ,976 -0, .437 1. ,00 36, .08 C
ATOM 952 CD LYS B 12 65. ,410 27. ,000 -1. .110 1. ,00 35. ,78 C
ATOM 953 CE LYS B 12 65. ,351 25. ,656 -0, ,461 1. ,00 35. ,08 C
ATOM 954 NZ LYS B 12 66. .015 24. ,710 -1, ,348 1, ,00 35. ,28 N
ATOM 955 C LYS B 12 64. ,736 31. ,152 -2. ,664 1. ,00 34. ,87 C
ATOM 956 O LYS B 12 64. ,335 32. ,253 -2. ,247 1. .00 35. ,65 O
ATOM 957 N GLU B 13 64. ,771 30. ,801 -3. ,956 1. ,00 33. ,28 N
ATOM 958 CA GLU B 13 64. ,308 31. ,653 -5. ,056 1. .00 31. ,58 C
ATOM 959 CB GLU B 13 65. ,119 31. .370 -6, .306 1. .00 31. ,34 C
ATOM 960 CG GLU B 13 66. ,376 32. ,163 -6. ,380 1. ,00 31. ,28 C
ATOM 961 CD GLU B 13 67. ,229 31. ,761 -7. ,540 1. ,00 32. ,53 C
ATOM 962 OEl GLU B 13 68. ,028 30. ,799 -7. ,409 1. .00 32. ,67 O
ATOM 963 OE2 GLU B 13 67. ,106 32. ,426 -8. ,586 1. ,00 32. 70 O
ATOM 964 C GLU B 13 62. ,837 31. ,432 -5. ,359 1. ,00 31. ,03 C ATOM 965 O GLU B 13 62,.301 30,.362 -5,.087 1,.00 31.03 0
ATOM 966 N THR B 14 62. .184 32, .442 -5, .923 1. .00 30, .46 N
ATOM 967 CA THR B 14 60, .759 32, .369 -6, .200 1, .00 30 .13 C
ATOM 968 CB THR B 14 60. ,240 33, ,634 -6, .893 1. .00 29, .79 c
ATOM 969 OGl THR B 14 60, .521 34, .754 -6, .071 1. .00 29 .96 0
ATOM 970 CG2 THR B 14 58. .743 33, ,592 -7, .055 1. ,00 29, .82 c
ATOM 971 C THR B 14 60. .559 31. .177 -7, .101 1. .00 30, .18 c
ATOM 972 O THR B 14 61. ,333 30. .971 -8, .031 1. .00 30, .27 0
ATOM 973 N GLY B 15 59. .553 30. .369 -6, .791 1. .00 30, .03 N
ATOM 974 CA GLY B 15 59. ,248 29, .200 -7, ,588 1. .00 30, .02 c
ATOM 975 C GLY B 15 59. ,658 27. ,906 -6, .923 1. .00 30, .20 c
ATOM 976 O GLY B 15 59. ,023 26, .880 -7, .150 1. .00 31, .13 0
ATOM 977 N GLU B 16 60. ,707 27. .941 -6, .105 1. .00 30. .13 N
ATOM 978 CA GLU B 16 61. ,317 26, .720 -5, ,575 1, .00 30, ,09 C
ATOM 979 CB GLU B 16 62. ,734 26. .998 -5, .097 1, .00 29, .57 C
ATOM 980 CG GLU B 16 63. ,685 27, .421 -6, .154 1, .00 28, .93 C
ATOM 981 CD GLU B 16 65. ,140 27. .353 -5, ,687 1, .00 30. .00 C
ATOM 982 OEl GLU B 16 65. .563 28, .203 -4, .863 1, .00 28, .19 O
ATOM 983 OE2 GLU B 16 65. .877 26. .449 -6, .162 1. ,00 30. ,14 O
ATOM 984 C GLU B 16 60. .509 26, .160 -4, .421 1, .00 30, .54 C
ATOM 985 O GLU B 16 59. .576 26. .799 -3, .965 1. .00 30. ,94 0
ATOM 986 N SER B 17 60. .885 24, .966 -3. .961 1, ,00 31, .53 N
ATOM 987 CA SER B 17 60. .337 24. .316 -2, .742 1. ,00 32. .44 C
ATOM 988 CB SER B 17 60. .147 22, .809 -2. .963 1. ,00 32, .39 C
ATOM 989 OG SER B 17 59. .425 22, .522 -4, .143 1, .00 34. .08 O
ATOM 990 C SER B 17 61, .245 24, .448 -1, .511 1, .00 32, .74 C
ATOM 991 O SER B 17 62, .466 24, .648 -1, .628 1, .00 32. .92 O
ATOM 992 N LEU B 18 60, .647 24, .275 -0, .334 1, .00 33, .17 N
ATOM 993 CA LEU B 18 61, ,402 24, .112 0, .902 1, .00 33. ,49 C
ATOM 994 CB LEU B 18 61, .090 25, .264 1, .839 1, .00 33, .92 C
ATOM 995 CG LEU B 18 62, ,099 25, .810 2. .846 1, ,00 35. .15 C
ATOM 996 CD1 LEU B 18 61, .288 26, .335 4, .010 1, .00 36, ,95 C
ATOM 997 CD2 LEU B 18 63, .143 24, .818 3, .319 1, .00 36. .58 C
ATOM 998 C LEU B 18 60, ,962 22. .843 1, ,590 1. .00 33. .50 C
ATOM 999 O LEU B 18 59. ,751 22, .616 1, .741 1, .00 33. .48 O
ATOM 1000 N THR B 19 61. ,917 22. .020 2, .014 1, .00 33. ,67 N
ATOM 1001 CA THR B 19 61, .592 21, .011 3, .034 1, .00 34. .29 C
ATOM 1002 CB THR B 19 62, .028 19. .597 2, .665 1. .00 33, .80 C
ATOM 1003 OGl THR B 19 61, .709 19, .353 1, .297 1, .00 33, .83 O
ATOM 1004 CG2 THR B 19 61, .269 18, .597 3, ,500 1. .00 33, .92 C
ATOM 1005 C THR B 19 62, .128 21, .359 4, ,415 1, .00 34. .84 C
ATOM 1006 O THR B 19 63, .333 21. .594 4, ,583 1, .00 35. ,20 0
ATOM 1007 N ILE B 20 61, .213 21, .412 5, .382 1, .00 35. ,38 N
ATOM 1008 CA ILE B 20 61, .551 21. .554 6, ,789 1. .00 36. ,25 C
ATOM 1009 CB ILE B 20 60, .621 22, .549 7, .507 1, .00 36. .25 C
ATOM 1010 CGI ILE B 20 60. .585 23. ,884 6, .750 1. .00 35. .44 C
ATOM 1011 GDI ILE B 20 59. .842 25, .014 7, .450 1. .00 35. .83 c
ATOM 1012 CG2 ILE B 20 61. .041 22. .685 9, ,009 1, .00 36. .74 c
ATOM 1013 C ILE B 20 61. .369 20, ,187 7, ,443 1, ,00 37. .37 c
ATOM 1014 O ILE B 20 60. .321 19, .573 7, ,293 1. ,00 37. ,80 0
ATOM 1015 N ASN B 21 62. .393 19. .721 8, ,160 1. ,00 38. .67 N
ATOM 1016 CA ASN B 21 62, .363 18. .449 8. ,884 1. ,00 39. ,53 C
ATOM 1017 CB ASN B 21 63. .610 17. ,644 8, ,584 1. ,00 39. .82 C
ATOM 1018 CG ASN B 21 63, .536 16. ,947 7. ,256 1. ,00 41. ,31 C
ATOM 1019 ODl ASN B 21 64. .121 17. .392 6. ,280 1. .00 43. .13 O
ATOM 1020 ND2 ASN B 21 62, .793 15. .855 7. ,203 1. ,00 44. ,31 N
ATOM 1021 C ASN B 21 62. .315 18. .677 10. ,368 1, ,00 39. .99 C
ATOM 1022 O ASN B 21 62. .958 19. .585 10. .874 1. ,00 40. ,44 O
ATOM 1023 N CYS B 22 61. ,567 17. .835 11. .065 1. ,00 40. ,38 N
ATOM 1024 CA CYS B 22 61. .545 17. ,849 12. ,507 1. ,00 40. ,90 C
ATOM 1025 CB CYS B 22 60. ,276 18. ,529 13. ,026 1. ,00 41. .39 C
ATOM 1026 SG CYS B 22 60. .092 20, ,330 12. ,606 1. ,00 45. ,04 S
ATOM 1027 C CYS B 22 61. ,625 16, ,422 13. ,020 1. ,00 40. ,81 c
ATOM 1028 O CYS B 22 61. ,075 15, ,493 12. ,427 1. ,00 40. ,89 0 ATOM 1029 N ALA B 23 62.341 16.246 14.122 1.00 40.97 N
ATOM 1030 CA ALA B 23 62, .338 14 .972 14, .852 1 .00 40 .61 C
ATOM 1031 CB ALA B 23 63 .660 14 .228 14 .663 1 .00 40 .21 C
ATOM 1032 C ALA B 23 62, .056 15, .228 16, .333 1, .00 40 .31 C
ATOM 1033 0 ALA B 23 62, .728 16 .051 16, .970 1, .00 40 .42 O
ATOM 1034 N LEU B 24 61 .034 14 .558 16 .859 1 .00 39 .95 N
ATOM 1035 CA LEU B 24 60, .761 14, .558 18, .295 1, .00 40 .06 C
ATOM 1036 CB LEU B 24 59, .343 14 .053 18, .581 1, .00 39 .89 C
ATOM 1037 CG LEU B 24 58 .860 13 .966 20, .025 1, .00 39 .41 C
ATOM 1038 GDI LEU B 24 57, .522 13, .239 20, .086 1, .00 39 .03 C
ATOM 1039 CD2 LEU B 24 58, .767 15 .349 20, .667 1, .00 40 .01 C
ATOM 1040 C LEU B 24 61, .800 13, .669 18, .972 1, .00 40, .18 C
ATOM 1041 O LEU B 24 61, .938 12, .504 18, .625 1, .00 40 .40 O
ATOM 1042 N LYS B 25 62, .537 14, .230 19, .922 1, .00 40 .26 N
ATOM 1043 CA LYS B 25 63, .727 13, .593 20, .444 1. .00 40, .45 C
ATOM 1044 CB LYS B 25 64, .936 14, .452 20, .092 1, .00 40, .39 C
ATOM 1045 CG LYS B 25 66, .143 13, .668 19, .606 1, .00 41 .77 C
ATOM 1046 CD LYS B 25 66. ,036 13, .256 18, .143 1. .00 43, .39 c
ATOM 1047 CE LYS B 25 66. .106 14, .451 17, .218 1, .00 45, .53 c
ATOM 1048 NZ LYS B 25 67. .340 15, .285 17. .411 1, .00 46, ,91 N
ATOM 1049 C LYS B 25 63. .586 13, .471 21. .947 1. .00 40, .69 C
ATOM 1050 O LYS B 25 63, .041 14, .373 22, .579 1. .00 41, .02 O
ATOM 1051 N ASN B 26 64. .070 12. .364 22. ,512 1, .00 40. ,94 N
ATOM 1052 CA ASN B 26 63. .968 12, ,075 23. ,952 1, .00 41, .43 C
ATOM 1053 CB ASN B 26 64, .633 13, .169 24. ,793 1. .00 41, .74 C
ATOM 1054 CG ASN B 26 66. ,142 13. .104 24, ,770 1, .00 42. .51 C
ATOM 1055 ODl ASN B 26 66, .748 12, .119 25, .209 1, .00 43, .67 O
ATOM 1056 ND2 ASN B 26 66, ,766 14. .179 24. ,287 1, .00 42. .58 N
ATOM 1057 C ASN B 26 62, .544 11, .867 24. ,473 1, ,00 41. .54 C
ATOM 1058 O ASN B 26 62, ,279 12, .075 25. .662 1, .00 41, .37 O
ATOM 1059 N ALA B 27 61, .634 11, .468 23, .593 1. .00 41. .65 N
ATOM 1060 CA ALA B 27 60, .277 11, ,196 24, .010 1. .00 42. ,12 C
ATOM 1061 CB ALA B 27 59, ,331 12, .088 23. ,278 1. ,00 42, ,06 C
ATOM 1062 C ALA B 27 59, ,937 9, .734 23, .764 1. ,00 42, .77 C
ATOM 1063 O ALA B 27 60, .152 9, ,219 22, .665 1, ,00 43, .05 O
ATOM 1064 N ALA B 28 59, ,412 9, ,067 24. .792 1. ,00 43, .31 N
ATOM 1065 CA ALA B 28 59, ,003 7, ,658 24, ,693 1, ,00 43, .96 C
ATOM 1066 CB ALA B 28 59, ,334 6, .914 25, ,977 1, ,00 43, .78 C
ATOM 1067 C ALA B 28 57. ,512 7. ,525 24. ,359 1. ,00 44, .39 C
ATOM 1068 O ALA B 28 57, ,020 6, ,441 24. ,023 1. ,00 44, .65 O
ATOM 1069 N ASP B 29 56. ,803 8. ,641 24. ,445 1. ,00 44, ,56 N
ATOM 1070 CA ASP B 29 55, ,377 8. .684 24. ,176 1. ,00 44. ,63 C
ATOM 1071 CB ASP B 29 54. .830 9, .999 24. ,713 1. ,00 45. .08 C
ATOM 1072 CG ASP B 29 55. ,468 10. .387 26. ,038 1. ,00 47. ,13 c
ATOM 1073 ODl ASP B 29 56. ,306 11, .328 26. ,063 1. ,00 48. ,02 o
ATOM 1074 OD2 ASP B 29 55. ,154 9, .712 27. ,051 1. ,00 50, .45 0
ATOM 1075 C ASP B 29 55. ,147 8. .581 22. ,676 1. ,00 44. ,03 c
ATOM 1076 O ASP B 29 56. ,040 8, .913 21. ,893 1. ,00 43. ,92 0
ATOM 1077 N ASP B 30 53. ,968 8. ,112 22. ,277 1. 00 43. ,17 N
ATOM 1078 CA ASP B 30 53. ,645 8. .001 20. ,858 1. ,00 42. ,91 C
ATOM 1079 CB ASP B 30 52. ,414 7, .092 20. ,649 1. ,00 43. ,11 C
ATOM 1080 CG ASP B 30 52. ,744 5. ,580 20. 769 1. 00 43. ,85 C
ATOM 1081 ODl ASP B 30 53. ,889 5. .165 20. ,448 1. ,00 44. ,60 0
ATOM 1082 OD2 ASP B 30 51, ,845 4, .801 21. ,180 1. ,00 42. ,81 0
ATOM 1083 C ASP B 30 53. ,418 9. ,389 20. 238 1. 00 42. ,32 c
ATOM 1084 O ASP B 30 52. ,808 10. .239 20. ,871 1. 00 42. ,41 o
ATOM 1085 N LEU B 31 53. ,922 9. ,627 19. 024 1. 00 41. 59 N
ATOM 1086 CA LEU B 31 53. ,573 10. ,839 18. 262 1. 00 41. 02 C
ATOM 1087 CB LEU B 31 54. ,483 11. .003 17. ,049 1. 00 40. 87 C
ATOM 1088 CG LEU B 31 54. ,888 12. ,417 16. 609 1. 00 41. 41 C
ATOM 1089 CD1 LEU B 31 53. ,857 13. ,498 16. 958 1. 00 42. 54 C
ATOM 1090 CD2 LEU B 31 55. ,243 12. ,466 15. 126 1. 00 40. 70 C
ATOM 1091 C LEU B 31 52. 112 10. ,778 17. 776 1. 00 40. 93 c
ATOM 1092 O LEU B 31 51. ,776 9. ,952 16. 921 1. 00 40. 54 o ATOM 1093 N GLU B 32 51..260 11..658 18..309 1,.00 40,.64 N
ATOM 1094 CA GLU B 32 49. .828 11. .619 18, .018 1, .00 40, .28 C
ATOM 1095 CB GLU B 32 48. .993 11. .809 19. .287 1. .00 40, .23 C
ATOM 1096 CG GLU B 32 49. .122 10. .694 20, .299 1, .00 42, .07 C
ATOM 1097 CD GLU B 32 48. .607 9. .314 19, .806 1, .00 46, .47 c
ATOM 1098 OEl GLU B 32 48. .930 8. ,303 20. .502 1, .00 47, .39 0
ATOM 1099 OE2 GLU B 32 47. .886 9. .226 18, ,756 1, .00 45, .59 o
ATOM 1100 C GLU B 32 49. .390 12. .594 16. ,927 1, .00 39. .99 c
ATOM 1101 O GLU B 32 48. .651 12. .215 16. ,027 1, .00 39, .79 0
ATOM 1102 N ARG B 33 49. .824 13. .846 17. ,000 1. .00 40. .07 N
ATOM 1103 CA ARG B 33 49, .492 14, .790 15. .941 1. ,00 40. .54 C
ATOM 1104 CB ARG B 33 48, .153 15, .483 16. .185 1, .00 40, .81 C
ATOM 1105 CG ARG B 33 48, .136 16, .524 17. .257 1. .00 41, ,98 c
ATOM 1106 CD ARG B 33 46, .826 17, .280 17. .238 1, .00 45, .56 c
ATOM 1107 NE ARG B 33 46, .749 18, .207 18. .365 1. .00 49, ,98 N
ATOM 1108 CZ ARG B 33 47, .272 19, .437 18. .352 1. .00 53, .89 c
ATOM 1109 NHl ARG B 33 47, .168 20, .217 19. .434 1, .00 54, .30 N
ATOM 1110 NH2 ARG B 33 47, .903 19, .894 17. .255 1, .00 54, .63 N
ATOM llll C ARG B 33 50, .601 15, .780 15, ,708 1, .00 40, .70 C
ATOM 1112 O ARG B 33 51, .439 15, ,977 16, ,567 1. .00 40, ,72 O
ATOM 1113 N THR B 34 50, .607 16, ,390 14, .531 1, ,00 41, .39 N
ATOM 1114 CA THR B 34 51. .682 17, ,299 14, .136 1. .00 42, ,45 C
ATOM 1115 CB THR B 34 52. .565 16. ,654 13, .051 1. .00 42, .54 C
ATOM 1116 OGl THR B 34 51. .735 16. ,068 12, .036 1, ,00 43, .44 O
ATOM 1117 CG2 THR B 34 53. ,409 15. ,560 13, .650 1. .00 42, .44 C
ATOM 1118 C THR B 34 51. .123 18. .643 13. .657 1, .00 42, .88 C
ATOM 1119 O THR B 34 50. .017 18. .702 13. .129 1. .00 43, .42 O
ATOM 1120 N ASP B 35 51. .884 19. .715 13. .848 1. ,00 43, ,44 N
ATOM 1121 CA ASP B 35 51. ,423 21. .088 13. .586 1. .00 43, ,97 C
ATOM 1122 CB ASP B 35 51. ,229 21. .841 14. .892 1. .00 44, .87 C
ATOM 1123 CG ASP B 35 49. .801 21. .859 15. .358 1, .00 49. ,02 C
ATOM 1124 ODl ASP B 35 48. .923 21. .176 14. .748 1. .00 51. .38 O
ATOM 1125 OD2 ASP B 35 49. .570 22, .578 16. .366 1. .00 52. .82 O
ATOM 1126 C ASP B 35 52. .478 21. .866 12. .859 1. .00 43. .37 C
ATOM 1127 O ASP B 35 53. .678 21, .613 13. .029 1. .00 43. .51 O
ATOM 1128 N TRP B 36 52. .027 22. .850 12. .088 1. .00 42. .37 N
ATOM 1129 CA TRP B 36 52. .906 23. .794 11. .423 1. .00 41, .24 C
ATOM 1130 CB TRP B 36 53. .162 23. .366 9. ,974 1. .00 40, .25 C
ATOM 1131 CG TRP B 36 53, .820 22, ,010 9. ,910 1. .00 39, .18 C
ATOM 1132 CD1 TRP B 36 53, .189 20, .808 9, ,912 1. .00 39. .03 C
ATOM 1133 NE1 TRP B 36 54. .105 19. ,784 9. ,875 1. .00 39. .65 N
ATOM 1134 CE2 TRP B 36 55. .365 20, .311 9. ,861 1. .00 37. .81 C
ATOM 1135 CD2 TRP B 36 55. ,231 21. ,719 9. ,889 1. .00 37. .66 C
ATOM 1136 CE3 TRP B 36 56. .383 22, .508 9. ,886 1. ,00 36, .22 c
ATOM 1137 CZ3 TRP B 36 57. .604 21, .887 9, ,856 1. .00 38, .69 c
ATOM 1138 CH2 TRP B 36 57. .707 20. .471 9. .833 1. .00 39. .76 c
ATOM 1139 CZ2 TRP B 36 56, .593 19, .674 9, .839 1. ,00 38. .23 c
ATOM 1140 C TRP B 36 52. .325 25. .204 11, .545 1, ,00 41, .48 c
ATOM 1141 O TRP B 36 51, ,133 25. .424 11. .358 1. ,00 41. .17 0
ATOM 1142 N TYR B 37 53, ,187 26. .148 11, .899 1. .00 42. .11 N
ATOM 1143 CA TYR B 37 52. ,801 27. .525 12. .143 1, .00 42, ,12 C
ATOM 1144 CB TYR B 37 52. ,809 27. .793 13, .641 1, ,00 43. ,09 C
ATOM 1145 CG TYR B 37 51. .595 27. .209 14. .331 1. ,00 44. .97 C
ATOM 1146 CD1 TYR B 37 51. ,643 25, .957 14. .942 1. ,00 46. .07 c
ATOM 1147 CEl TYR B 37 50. ,518 25. ,408 15. .566 1. ,00 45, ,11 c
ATOM 1148 CZ TYR B 37 49, ,328 26. ,125 15. .579 1. ,00 45, .99 c
ATOM 1149 OH TYR B 37 48. ,193 25. ,612 16, ,193 1, ,00 47, .09 0
ATOM 1150 CE2 TYR B 37 49. ,256 27. ,373 14. ,979 1. ,00 46. .28 c
ATOM 1151 CD2 TYR B 37 50. ,383 27. ,902 14. .351 1, ,00 46. .48 c
ATOM 1152 C TYR B 37 53. .774 28. ,430 11. ,435 1. ,00 41. ,70 c
ATOM 1153 O TYR B 37 54. .956 28. ,087 11. .285 1, ,00 41. ,41 o
ATOM 1154 N ARG B 38 53. ,280 29. ,572 10. ,972 1. ,00 41. ,33 N
ATOM 1155 CA ARG B 38 54. ,138 30. ,506 10. ,257 1. ,00 41. ,41 C
ATOM 1156 CB ARG B 38 54. .109 30. .221 8. .748 1. ,00 41. ,64 C ATOM 1157 CG ARG B 38 52,.855 30,.715 8,.033 1.00 43.80 c
ATOM 1158 CD ARG B 38 52, .500 29, .877 6, .808 1, .00 48, .30 c
ATOM 1159 NE ARG B 38 53, .297 30, .168 5, .608 1 .00 51, .15 N
ATOM 1160 CZ ARG B 38 52, .875 30 .864 4 .545 1 .00 51 .98 C
ATOM 1161 NHl ARG B 38 51, .638 31, .388 4, .478 1, .00 48, .85 N
ATOM 1162 NH2 ARG B 38 53, .722 31, .042 3, .537 1 .00 52, .22 N
ATOM 1163 C ARG B 38 53, ,808 31, .967 10, .558 1, .00 40, .80 C
ATOM 1164 O ARG B 38 52, .644 32, .328 10, .714 1, .00 40, .56 o
ATOM 1165 N THR B 39 54, .855 32, .784 10, ,665 1, .00 40. .49 N
ATOM 1166 CA THR B 39 54, .737 34, .245 10, .769 1, .00 40, ,14 C
ATOM 1167 CB THR B 39 55. ,282 34, .757 12, .108 1, .00 39. ,95 c
ATOM 1168 OGl THR B 39 54, ,467 34, .241 13, .161 1, .00 40. ,90 0
ATOM 1169 CG2 THR B 39 55. ,296 36, .288 12. ,165 1. .00 38. ,83 c
ATOM 1170 C THR B 39 55, ,517 34, .853 9, .604 1, ,00 40. ,12 c
ATOM 1171 O THR B 39 56. ,759 34. .847 9. .588 1. .00 39. ,84 o
ATOM 1172 N THR B 40 54. ,787 35, .362 8, ,619 1, .00 39. .67 N
ATOM 1173 CA THR B 40 55. ,403 35. ,647 7. ,341 1. .00 39. .66 C
ATOM 1174 CB THR B 40 54, .873 34. ,699 6, .241 1, ,00 39. .69 C
ATOM 1175 OGl THR B 40 53, .465 34. ,856 6. ,095 1. ,00 40. ,00 0
ATOM 1176 CG2 THR B 40 55, .165 33. ,264 6. .577 1. .00 40. .25 c
ATOM 1177 C THR B 40 55, .161 37, .070 6, .941 1, .00 39. .57 c
ATOM 1178 O THR B 40 54, .336 37. .741 7. .553 1. .00 39. .87 o
ATOM 1179 N LEU B 41 55, .876 37, .529 5. .918 1. .00 39. .69 N
ATOM 1180 CA LEU B 41 55, .682 38. .881 5. ,389 1. .00 40. .14 C
ATOM 1181 CB LEU B 41 56. .620 39. .170 4. ,218 1. .00 39. .45 C
ATOM 1182 CG LEU B 41 58. .064 39. .377 4. ,651 1. ,00 38. .18 C
ATOM 1183 GDI LEU B 41 58, .992 39, ,498 3. .463 1. .00 36. .16 C
ATOM 1184 CD2 LEU B 41 58. .149 40. .591 5. .544 1, ,00 35, .87 C
ATOM 1185 C LEU B 41 54. ,248 39. ,101 4. .977 1. .00 41, .07 c
ATOM 1186 O LEU B 41 53. ,558 38. .183 4. .564 1. .00 40. .61 0
ATOM 1187 N GLY B 42 53. .803 40. .334 5. .132 1. .00 43. .06 N
ATOM 1188 CA GLY B 42 52. .443 40. .730 4, .778 1, ,00 45, .64 c
ATOM 1189 C GLY B 42 51. .375 40. .327 5, .791 1, .00 47, .14 c
ATOM 1190 O GLY B 42 50, .738 41. .196 6, .426 1, .00 47. .26 o
ATOM 1191 N SER B 43 51, .163 39. .008 5, .915 1. .00 48. .13 N
ATOM 1192 CA SER B 43 50, .160 38. .442 6, .811 1, ,00 48. ,78 C
ATOM 1193 CB SER B 43 50, .174 36, .927 6. .713 1. ,00 48. .76 C
ATOM 1194 OG SER B 43 49, .508 36, .361 7, .829 1, ,00 50, .24 O
ATOM 1195 C SER B 43 50, .424 38, .895 8. .242 1. ,00 49. ,01 C
ATOM 1196 O SER B 43 51, .549 38, .788 8, .734 1, ,00 49, .17 0
ATOM 1197 N THR B 44 49, .390 39. .417 8. .892 1. ,00 49. .44 N
ATOM 1198 CA THR B 44 49, .549 40. .109 10, .184 1, ,00 50, .08 c
ATOM 1199 CB THR B 44 48. .264 40. .935 10, ,579 1. ,00 50. .34 c
ATOM 1200 OGl THR B 44 47. .092 40. .110 10, ,468 1, ,00 50. .77 o
ATOM 1201 CG2 THR B 44 48. .093 42. .184 9. ,689 1. ,00 49. ,96 c
ATOM 1202 C THR B 44 50. ,054 39. .236 11. ,366 1, ,00 50, .19 c
ATOM 1203 O THR B 44 51. .145 39. ,497 11. ,902 1. ,00 50. ,45 0
ATOM 1204 N ASN B 45 49. .289 38. .202 11. ,747 1. .00 49. .88 N
ATOM 1205 CA ASN B 45 49. ,637 37. .347 12. ,898 1. ,00 49. ,63 c
ATOM 1206 CB ASN B 45 48. .430 37. .140 13. ,819 1, .00 50. ,02 c
ATOM 1207 CG ASN B 45 47. ,471 38. .339 13. ,840 1. ,00 50. ,87 c
ATOM 1208 ODl ASN B 45 47, .891 39. .490 13. ,728 1. ,00 51. ,82 0
ATOM 1209 ND2 ASN B 45 46. ,170 38, ,060 13. ,999 1. ,00 51. ,34 N
ATOM 1210 C ASN B 45 50. .178 35. ,982 12. ,492 1. .00 49. ,19 C
ATOM 1211 O ASN B 45 50. .131 35. ,621 11. .325 1. .00 48. ,90 O
ATOM 1212 N GLU B 46 50. .703 35. ,239 13. ,465 1. ,00 48. ,83 N
ATOM 1213 CA GLU B 46 51, .098 33, ,839 13. ,274 1. .00 48. ,89 C
ATOM 1214 CB GLU B 46 51. .616 33, ,236 14. ,602 1. ,00 48. ,72 C
ATOM 1215 CG GLU B 46 51. .589 31. ,680 14. ,656 1. .00 51. ,01 c
ATOM 1216 CD GLU B 46 52, ,026 31, ,059 16. ,009 1. ,00 51. 85 c
ATOM 1217 OEl GLU B 46 53. .085 30. ,355 16. ,022 1. ,00 55. 28 0
ATOM 1218 OE2 GLU B 46 51. ,310 31. ,250 17. 040 1. ,00 54. 03 0
ATOM 1219 C GLU B 46 49. ,877 33, .051 12. ,783. 1. ,00 47. 40 c
ATOM 1220 O GLU B 46 48. ,776 33. .279 13. 296' 1. 00 47. 31 0 ATOM 1221 N GLN B 47 50,.055 32..156 11,.797 1,.00 45.67 N
ATOM 1222 CA GLN B 47 48, .959 31. .256 11, .382 1, .00 44, .20 C
ATOM 1223 CB GLN B 47 48, .202 31, .758 10, .146 1, .00 44 .02 C
ATOM 1224 CG GLN B 47 49, .018 32, .205 8, .958 1, .00 44 .67 c
ATOM 1225 CD GLN B 47 48, .193 33. .053 7. .957 1, .00 45, .30 c
ATOM 1226 OEl GLN B 47 48, .624 33. .293 6. .825 1. .00 47, .08 o
ATOM 1227 NE2 GLN B 47 47, .014 33, .512 8, .383 1, .00 46 .34 N
ATOM 1228 C GLN B 47 49, .271 29, .767 11, .249 1, .00 42, .77 C
ATOM 1229 O GLN B 47 50, .388 29. .374 10. .902 1, .00 43, .17 O
ATOM 1230 N LYS B 48 48, .263 28, .948 11, .536 1, .00 40 .86 N
ATOM 1231 CA LYS B 48 48, .381 27, .516 11, .355 1, .00 39 .42 C
ATOM 1232 CB LYS B 48 47, .374 26, .754 12, ,192 1, .00 39, .66 C
ATOM 1233 CG LYS B 48 47. .668 25, .273 12, .204 1. ,00 40, .68 c
ATOM 1234 CD LYS B 48 46. .769 24, .546 13, .155 1, .00 44, .74 c
ATOM 1235 CE LYS B 48 46, .885 23. .054 12. .934 1, .00 47, .87 c
ATOM 1236 NZ LYS B 48 45. .989 22. .323 13. ,869 1. .00 51, .09 N
ATOM 1237 C LYS B 48 48. .188 27. .139 9. .908 1. .00 38. .04 c
ATOM 1238 O LYS B 48 47, .173 27, ,468 9, .302 1. ,00 38, .20 0
ATOM 1239 N ILE B 49 49, .164 26. .424 9. .371 1. .00 36, ,39 N
ATOM 1240 CA ILE B 49 49. ,139 25. .983 7. .993 1. .00 34, .41 C
ATOM 1241 CB ILE B 49 50, .536 25, .543 7. .541 1, .00 34, .65 C
ATOM 1242 CGI ILE B 49 51, .581 26. .630 7. .910 1. .00 33, ,56 C
ATOM 1243 CD1 ILE B 49 52, .977 26. .419 7. .414 1. .00 32, .67 C
ATOM 1244 CG2 ILE B 49 50. ,480 25. .172 6. .067 1. .00 34, .42 c
ATOM 1245 C ILE B 49 48, .189 24, .815 7. .822 1. .00 33, .90 c
ATOM 1246 O ILE B 49 48, .299 23, .837 8, .534 1. .00 33, .80 0
ATOM 1247 N SER B 50 47, .240 24, ,946 6, .897 1. ,00 33, .32 N
ATOM 1248 CA SER B 50 46, .433 23. .828 6. .427 1. .00 32, ,90 C
ATOM 1249 CB SER B 50 45, .206 24, .350 5, .696 1, ,00 32, .66 C
ATOM 1250 OG SER B 50 44, .029 24, .100 6, .418 1. .00 33, .04 O
ATOM 1251 C SER B 50 47, .225 22, ,981 5. .441 1. .00 32, ,69 C
ATOM 1252 O SER B 50 47, .443 23. .401 4. .317 1. ,00 33, .31 O
ATOM 1253 N ILE B 51 47, .659 21, .793 5, .842 1. ,00 32, .40 N
ATOM 1254 CA ILE B 51 48, .216 20, .831 4, .880 1. .00 31. .95 C
ATOM 1255 CB ILE B 51 48, .520 19, .488 5, .559 1. ,00 31. .82 C
ATOM 1256 CGI ILE B 51 49, .417 19, .700 6. ,788 1. .00 31, ,72 C
ATOM 1257 GDI ILE B 51 50, .781 20, .302 6. .518 1. .00 30, .73 C
ATOM 1258 CG2 ILE B 51 49, .112 18, .514 4. .573 1. .00 30, .78 C
ATOM 1259 C ILE B 51 47. .270 20, .612 3. .681 1. .00 31. .79 c
ATOM 1260 O ILE B 51 46, .052 20, .534 3. .839 1, .00 31. .18 0
ATOM 1261 N GLY B 52 47, .856 20, ,530 2. .493 1, .00 32, .00 N
ATOM 1262 CA GLY B 52 47. .115 20, ,377 1. .246 1. .00 32, .81 C
ATOM 1263 C GLY B 52 47. .671 21, ,388 0, .271 1. ,00 33, .29 C
ATOM 1264 O GLY B 52 48, .433 22, ,266 0, .701 1. .00 34, .33 O
ATOM 1265 N GLY B 53 47. .316 21, ,271 -1. .020 1. .00 32. .93 N
ATOM 1266 CA GLY B 53 47. .797 22, ,167 -2. ,079 1. ,00 32'. .74 C
ATOM 1267 C GLY B 53 49, .317 22, .310 -2, .101 1, .00 33, .58 C
ATOM 1268 O GLY B 53 50. .035 21, .328 -2, .253 1, .00 33, ,62 O
ATOM 1269 N ARG B 54 49. .800 23, ,545 -1. .957 1. ,00 33. ,84 N
ATOM 1270 CA ARG B 54 51. .210 23. ,856 -1. .783 1. ,00 34. ,22 C
ATOM 1271 CB ARG B 54 51. .356 25. .337 -1. .403 1. ,00 34. .14 C
ATOM 1272 CG ARG B 54 51. ,572 26. ,240 -2. .549 1. ,00 35. ,30 C
ATOM 1273 CD ARG B 54 50, ,951 27. ,636 -2. ,377 1. ,00 38. ,06 C
ATOM 1274 NE ARG B 54 51, ,387 28. ,432 -1. ,220 1. 00 38. 60 N
ATOM 1275 CZ ARG B 54 52, ,637 28. ,827 -0. ,962 1. ,00 38. ,97 C
ATOM 1276 NHl ARG B 54 53, ,655 28. ,462 -1. ,727 1. 00 37. 92 N
ATOM 1277 NH2 ARG B 54 52. ,877 29. 574 0. ,105 1. 00 39. 13 N
ATOM 1278 C ARG B 54 51. ,876 23. ,037 -0. ,670 1. .00 34. ,59 C
ATOM 1279 O ARG B 54 53. ,099 22. ,842 -0. ,690 1. 00 35. 21 O
ATOM 1280 N TYR B 55 51. ,096 22. 605 0. ,318 1. 00 34. 28 N
ATOM 1281 CA TYR B 55 51. ,680 22. 114 1. 558 1. 00 35. 05 C
ATOM 1282 CB TYR B 55 51. ,012 22. ,750 2. ,778 1. 00 35. 40 C
ATOM 1283 CG TYR B 55 51. ,104 24. 245 2. ,771 1. 00 36. 76 C
ATOM 1284 CD1 TYR B 55 49. ,993 25. 022 2. 453 1. 00 36. 78 C ATOM 1285 CEl TYR B 55 50,.076 26,.389 2,.425 1,.00 36,.81 c
ATOM 1286 CZ TYR B 55 51. .282 27. .001 2. .706 1, .00 36, .69 c
ATOM 1287 OH TYR B 55 51, .353 28, .363 2, ,682 1, .00 37, .75 0
ATOM 1288 CE2 TYR B 55 52. .408 26. .269 3. ,026 1, .00 36, .76 c
ATOM 1289 CD2 TYR B 55 52, .319 24, .893 3, ,053 1, .00 37, .99 c
ATOM 1290 C TYR B 55 51. .546 20. .621 1. ,650 1, .00 35, .30 c
ATOM 1291 O TYR B 55 50, .418 20, .093 1, .689 1, .00 35, .71 o
ATOM 1292 N VAL B 56 52. .691 19, .942 1. .680 1. .00 34, .77 N
ATOM 1293 CA VAL B 56 52. .700 18, .500 1. .816 1. .00 34, .57 C
ATOM 1294 CB VAL B 56 52. .930 17. ,723 0. .423 1, .00 34, .43 C
ATOM 1295 CGI VAL B 56 53. ,441 18. .632 -0. .682 1, .00 34. .03 c
ATOM 1296 CG2 VAL B 56 53. ,758 16. ,472 0. .581 1, .00 33. .69 c
ATOM 1297 C VAL B 56 53. ,522 18. .045 3. .026 1, .00 34, .81 c
ATOM 1298 O VAL B 56 54. ,724 18. .312 3. .129 1, .00 35, .06 o
ATOM 1299 N GLU B 57 52. .821 17. .406 3. .963 1. .00 35, .01 N
ATOM 1300 CA GLU B 57 53. .408 16. ,847 5. .178 1, .00 35, .49 C
ATOM 1301 CB GLU B 57 52. .474 17. .028 6. .364 1, .00 35, .34 C
ATOM 1302 CG GLU B 57 53. .180 16. .934 7. .704 1, .00 35, .90 C
ATOM 1303 CD GLU B 57 52, .231 17. .058 8. .896 1, .00 36. .90 C
ATOM 1304 OEl GLU B 57 51, .089 16. .531 8. .854 1, .00 38. .87 o
ATOM 1305 OE2 GLU B 57 52. ,642 17. ,678 9. .898 1, .00 39. .53 o
ATOM 1306 C GLU B 57 53. ,679 15. .368 5. .034 1, .00 35. .42 c
ATOM 1307 O GLU B 57 52. .834 14, .617 4, .549 1, .00 35. .57 0
ATOM 1308 N THR B 58 54. .863 14. .956 5. .458 1, ,00 35. ,55 N
ATOM 1309 CA THR B 58 55. .173 13. .552 5. .566 1, .00 36. .03 c
ATOM 1310 CB THR B 58 56. .332 13, .180 4. .668 1, .00 36. .37 c
ATOM 1311 OGl THR B 58 55. ,971 13, ,500 3. .324 1, .00 38. ,93 0
ATOM 1312 CG2 THR B 58 56. ,624 11, .680 4, ,753 1, .00 35. ,97 c
ATOM 1313 C THR B 58 55. ,510 13. ,227 6. .999 1, .00 35. ,82 c
ATOM 1314 O THR B 58 56. .478 13. .750 7, ,558 1. .00 35. ,98 0
ATOM 1315 N VAL B 59 54. ,708 12. .363 7. .597 1, .00 35. ,52 N
ATOM 1316 CA VAL B 59 54, .956 11. .955 8. .968 1, .00 35. ,20 C
ATOM 1317 CB VAL B 59 53, .757 12. ,247 9. .820 1. .00 35. ,04 C
ATOM 1318 CGI VAL B 59 53, .952 11. .715 11. ,241 1. .00 34. ,11 C
ATOM 1319 CG2 VAL B 59 53. .536 13. .760 9. .802 1, .00 35. ,87 C
ATOM 1320 C VAL B 59 55. .377 10. .504 9. .106 1, .00 34. ,93 c
ATOM 1321 O VAL B 59 54. .740 9. .610 8. .560 1, .00 35. ,10 0
ATOM 1322 N ASN B 60 56, ,471 10. .286 9, ,825 1, .00 34. ,54 N
ATOM 1323 CA ASN B 60 56, .872 8. ,949 10, ,196 1, .00 34. ,43 C
ATOM 1324 CB ASN B 60 58. ,304 8. ,695 9. ,772 1, .00 34. ,56 C
ATOM 1325 CG ASN B 60 58. ,665 7. .231 9, ,819 1. .00 34, ,65 C
ATOM 1326 ODl ASN B 60 58, ,226 6, ,482 10. ,704 1, .00 34. .77 O
ATOM 1327 ND2 ASN B 60 59. ,474 6. .812 8. ,867 1, .00 33, .75 N
ATOM 1328 C ASN B 60 56, ,707 8, .692 11. ,692 1. .00 34. .35 C
ATOM 1329 O ASN B 60 57. ,659 8, .801 12. ,473 1. .00 34. .37 O
ATOM 1330 N LYS B 61 55. ,486 8, .333 12, ,082 1, .00 34, .32 N
ATOM 1331 CA LYS B 61 55. ,153 8. .102 13. .496 1. .00 33. .79 C
ATOM 1332 CB LYS B 61 53. .712 7. .595 13, .640 1, ,00 33, .51 C
ATOM 1333 CG LYS B 61 52, .707 8, .696 13. .922 1. ,00 32. ,45 C
ATOM 1334 CD LYS B 61 51. .272 8. .203 13, ,746 1. ,00 31. .18 C
ATOM 1335 CE LYS B 61 50, .270 9. ,348 13. ,855 1. ,00 31. ,36 C
ATOM 1336 NZ LYS B 61 48. .882 8. .975 13. ,458 1. ,00 32. ,24 N
ATOM 1337 C LYS B 61 56. ,126 7, ,150 14. ,184 1. ,00 33. ,58 C
ATOM 1338 O LYS B 61 56, .344 7. .252 15, ,386 1. ,00 33. ,17 O
ATOM 1339 N GLY B 62 56. ,717 6. .248 13. ,402 1. ,00 33. ,71 N
ATOM 1340 CA GLY B 62 57. .582 5. .197 13. ,927 1. ,00 33. ,75 C
ATOM 1341 C GLY B 62 58. ,902 5. .716 14. ,449 1. ,00 33. 69 C
ATOM 1342 O GLY B 62 59. ,342 5. .338 15. ,535 1. ,00 33. ,29 0
ATOM 1343 N SER B 63 59. ,537 6, ,581 13. 669 1. 00 33. 94 N
ATOM 1344 CA SER B 63 60. ,816 7, .159 14. ,062 1. ,00 34. 47 C
ATOM 1345 CB SER B 63 61. ,758 7. ,243 12. 859 1. 00 34. 55 C
ATOM 1346 OG SER B 63 61. ,291 8. .202 11. ,912 1. 00 35. 26 O
ATOM 1347 C SER B 63 60. 605 8. ,538 14. 678 1. 00 34. 60 C
ATOM 1348 O SER B 63 61. ,561 9. ,279 14. 908 1. 00 35. 09 O ATOM 1349 N LYS B 64 59,,344 8..866 14.,939 1..00 34..69 N
ATOM 1350 CA LYS B 64 58, .925 10. .171 15. ,447 1. .00 34, .92 C
ATOM 1351 CB LYS B 64 59. .258 10. .326 16. .933 1. .00 34. .30 C
ATOM 1352 CG LYS B 64 58. .467 9, .412 17. .849 1. .00 34, .05 c
ATOM 1353 CD LYS B 64 59. .356 8. .857 18. .921 1. .00 34, .38 c
ATOM 1354 CE LYS B 64 58. .612 8. .736 20. .206 1. .00 35, .46 c
ATOM 1355 NZ LYS B 64 57. .842 7. .479 20. .278 1. .00 37. .44 N
ATOM 1356 C LYS B 64 59. ,430 11, .374 14, .647 1. .00 35. .47 C
ATOM 1357 O LYS B 64 59. ,438 12, .485 15, .153 1. .00 36. .15 O
ATOM 1358 N SER B 65 59. ,826 11, .185 13, .398 1. .00 35, .85 N
ATOM 1359 CA SER B 65 60. ,164 12, ,354 12, .588 1. .00 36. .57 C
ATOM 1360 CB SER B 65 61. ,428 12. .116 11, .773 1. .00 36, .71 C
ATOM 1361 OG SER B 65 61. .349 10. .872 11. ,103 1. .00 38. .46 O
ATOM 1362 C SER B 65 59. .000 12. .777 11, ,692 1. .00 36. .53 C
ATOM 1363 O SER B 65 58, .031 12. .039 11. .510 1. .00 36. .24 O
ATOM 1364 N PHE B 66 59, ,093 13, .983 11, .157 1. .00 36. .84 N
ATOM 1365 CA PHE B 66 58, ,081 14. .495 10, .254 1. .00 37. .54 C
ATOM 1366 CB PHE B 66 56, ,744 14. .728 10. .981 1. .00 38. .07 C
ATOM 1367 CG PHE B 66 56, ,815 15. .713 12. ,127 1. .00 38. .99 C
ATOM 1368 CD1 PHE B 66 56, ,073 16. .894 12. ,082 1. .00 39. .56 C
ATOM 1369 CEl PHE B 66 56, ,129 17. .808 13. ,131 1. .00 39. .86 C
ATOM 1370 CZ PHE B 66 56. ,932 17. .540 14. .245 1. .00 40. .09 C
ATOM 1371 CE2 PHE B 66 57. ,673 16. .363 14. .308 1. .00 39. .63 C
ATOM 1372 CD2 PHE B 66 57. ,603 15. .456 13. .253 1. .00 39. .81 c
ATOM 1373 C PHE B 66 58. ,567 15. .744 9. ,527 1. .00 37. .56 c
ATOM 1374 O PHE B 66 59, ,251 16. .573 10, .114 1. ,00 37. .86 0
ATOM 1375 N SER B 67 58, ,202 15, .868 8. .253 1. ,00 37. .40 N
ATOM 1376 CA SER B 67 58, ,668 16. .953 7, ,398 1. .00 37. .02 C
ATOM 1377 CB SER B 67 59. ,562 16. .388 6, ,297 1, .00 37. .25 C
ATOM 1378 OG SER B 67 58, .769 15. ,703 5, ,328 1. ,00 38. .81 O
ATOM 1379 C SER B 67 57, .522 17. .681 6, ,735 1. .00 36. ,30 C
ATOM 1380 O SER B 67 56, .477 17, ,113 6. ,508 1. .00 36. .04 O
ATOM 1381 N LEU B 68 57, ,747 18. ,944 6, .405 1. .00 36. .52 N
ATOM 1382 CA LEU B 68 56. .812 19, .747 5, .625 1. .00 36. .48 C
ATOM 1383 CB LEU B 68 56. .319 20. .943 6, .429 1. .00 35. .99 C
ATOM 1384 CG LEU B 68 55. ,589 22. .029 5, ,647 1. .00 36. .04 c
ATOM 1385 CD1 LEU B 68 54. .180 21, .550 5, .246 1. .00 38, .31 c
ATOM 1386 CD2 LEU B 68 55, .518 23, ,352 6, .412 1. .00 35, .68 c
ATOM 1387 C LEU B 68 57, .520 20. .240 4, .371 1. .00 37, .35 c
ATOM 1388 O LEU B 68 58, .662 20. .744 4. .436 1. .00 37, .12 0
ATOM 1389 N ARG B 69 56, .844 20. .082 3, .232 1. .00 37, .75 N
ATOM 1390 CA ARG B 69 57, .361 20. .564 1, .965 1. .00 38, .27 C
ATOM 1391 CB ARG B 69 57. .563 19, .402 1, .011 1. .00 38, ,49 C
ATOM 1392 CG ARG B 69 58. .147 19. .759 -0, .323 1. .00 40, .65 C
ATOM 1393 CD ARG B 69 58, .789 18, .518 -0, .879 1, .00 47. .79 C
ATOM 1394 NE ARG B 69 59. .309 18, .659 -2, .242 1, .00 54. .67 N
ATOM 1395 CZ ARG B 69 60. .446 19, .288 -2, .573 1, .00 57, .95 C
ATOM 1396 NHl ARG B 69 60. ,826 19, .348 -3, ,855 1. .00 57, .88 N
ATOM 1397 NH2 ARG B 69 61. .199 19. .877 -1, .634 1. .00 58. .92 N
ATOM 1398 C ARG B 69 56. .400 21. ,593 1, .387 1. .00 38. .17 C
ATOM 1399 O ARG B 69 55. .235 21. .297 1, .149 1. .00 37, .57 O
ATOM 1400 N ILE B 70 56. .908 22, .810 1, .184 1. .00 39, .05 N
ATOM 1401 CA ILE B 70 56. .128 23. .927 0. .615 1. .00 39, .54 C
ATOM 1402 CB ILE B 70 56. .290 25, .218 1. .432 1. ,00 39, .53 C
ATOM 1403 CGI ILE B 70 55. .884 24. .995 2, .883 1. .00 38, ,64 c
ATOM 1404 CD1 ILE B 70 56. ,532 25, .975 3, ,773 1. .00 40, .33 c
ATOM 1405 CG2 ILE B 70 55. .443 26. .333 0, .848 1. .00 40. .01 c
ATOM 1406 C ILE B 70 56. .579 24, .194 -0, ,810 1. ,00 39. .97 c
ATOM 1407 O ILE B 70 57. .765 24. .444 -1, .075 1. ,00 40. .13 o
ATOM 1408 N ARG B 71 55. ,633 24. .120 -1. ,732 1. ,00 40. .24 N
ATOM 1409 CA ARG B 71 55. .962 24. ,303 -3, .135 1. .00 40, .82 C
ATOM 1410 CB ARG B 71 55. ,148 23. ,348 -3, .993 1, .00 41. ,16 C
ATOM 1411 CG ARG B 71 55. .337 21. .888 -3, .639 1, .00 44, .57 C
ATOM 1412 CD ARG B 71 54. .725 20. .992 -4, .710 1. .00 49, ,70 C ATOM 1413 NE ARG B 71 54.807 21.588 -6.046 1.00 53.70 N
ATOM 1414 CZ ARG B 71 54 .572 20 .944 -7 .194 1 .00 55 .90 C
ATOM 1415 NHl ARG B 71 54 .674 21 .597 -8 .352 1 .00 56 .14 N
ATOM 1416 NH2 ARG B 71 54 .239 19 .652 -7 .198 1 .00 56 .04 N
ATOM 1417 C ARG B 71 55 .697 25 .725 -3 .590 1 .00 40 .23 C
ATOM 1418 O ARG B 71 54 .853 26 .410 -3 .043 1 .00 40 .21 O
ATOM 1419 N ASP B 72 56 .432 26 .166 -4 .598 1 .00 39 .99 N
ATOM 1420 CA ASP B 72 56 .074 27 .365 -5 .311 1 .00 39 .63 C
ATOM 1421 CB ASP B 72 54, .633 27 .247 -5 .794 1, .00 40 .12 C
ATOM 1422 CG ASP B 72 54 .453 27 .755 -7 .197 1 .00 43 .50 C
ATOM 1423 ODl ASP B 72 53, .897 26 .973 -8 .008 1, .00 47 .76 O
ATOM 1424 OD2 ASP B 72 54 .870 28 .909 -7 .500 1 .00 45 .42 O
ATOM 1425 C ASP B 72 56, .216 28 .575 -4 .419 1, .00 38 .78 C
ATOM 1426 O ASP B 72 55, .359 29, .435 -4 .391 1, .00 39, .10 O
ATOM 1427 N LEU B 73 57, .306 28, .639 -3 .681 1, .00 38, .19 N
ATOM 1428 CA LEU B 73 57, .606 29, .804 -2, .868 1, .00 37, .69 C
ATOM 1429 CB LEU B 73 59, .012 29 .684 -2 .307 1, .00 37, .08 C
ATOM 1430 CG LEU B 73 59, .129 28, .569 -1, .283 1, .00 35, .84 C
ATOM 1431 GDI LEU B 73 60, .549 28, .541 -0, .791 1, .00 37, .26 C
ATOM 1432 CD2 LEU B 73 58, .171 28, .844 -0, .129 1, .00 34, .44 C
ATOM 1433 C LEU B 73 57, .413 31. .156 -3, .563 1, .00 38, .01 C
ATOM 1434 O LEU B 73 57, .757 31, .336 -4, .733 1, .00 37, .97 O
ATOM 1435 N ARG B 74 56, .827 32, .090 -2, .822 1. .00 38. .54 N
ATOM 1436 CA ARG B 74 56, .692 33, .480 -3 .231 1, .00 39, .03 C
ATOM 1437 CB ARG B 74 55, .210 33, .868 -3, .329 1. .00 39, .96 C
ATOM 1438 CG ARG B 74 54. .303 32, .933 -4, .150 1, .00 42. .17 C
ATOM 1439 CD ARG B 74 53, ,881 31, .746 -3, .285 1, .00 46, .75 C
ATOM 1440 NE ARG B 74 52. ,745 30, .999 -3, .823 1, .00 50. .63 N
ATOM 1441 CZ ARG B 74 51, .483 31, .425 -3 .764 1, .00 53, .30 C
ATOM 1442 NHl ARG B 74 50. .499 30, .671 -4, .259 1, ,00 54, .24 N
ATOM 1443 NH2 ARG B 74 51, .201 32, ,612 -3, .214 1, .00 53, .43 N
ATOM 1444 C ARG B 74 57, .359 34, .300 -2, .150 1, ,00 38, .76 C
ATOM 1445 O ARG B 74 57, .595 33, .785 -1. .062 1, .00 38, .68 O
ATOM 1446 N VAL B 75 57, .666 35, .564 -2, .409 1, .00 39, .03 N
ATOM 1447 CA VAL B 75 58, .293 36, .391 -1, .348 1, .00 39, .94 C
ATOM 1448 CB VAL B 75 58, ,755 37. .808 -1. .812 1. .00 39, .90 C
ATOM 1449 CGI VAL B 75 59, .921 37. .712 -2, .824 1, .00 40, .00 C
ATOM 1450 CG2 VAL B 75 57, .599 38. .585 -2, ,382 1, .00 40, .10 C
ATOM 1451 C VAL B 75 57, .447 36. .512 -0, .072 1, .00 40, .09 C
ATOM 1452 O VAL B 75 57, .986 36. .505 1, .021 1, .00 40, .49 O
ATOM 1453 N GLU B 76 56, .131 36. .583 -0, ,212 1, .00 40, ,25 N
ATOM 1454 CA GLU B 76 55. .243 36. .585 0. .931 1. .00 41, ,00 C
ATOM 1455 CB GLU B 76 53. .794 36. .502 0. ,475 1. ,00 41. ,62 C
ATOM 1456 CG GLU B 76 53. .401 37. .530 -0. .549 1. .00 46, ,34 C
ATOM 1457 CD GLU B 76 53. .603 37. .033 -1. ,981 1. .00 51. ,96 C
ATOM 1458 OEl GLU B 76 52. .868 36, .077 -2. .374 1, .00 53. ,72 O
ATOM 1459 OE2 GLU B 76 54. .479 37, .611 -2. ,699 1, ,00 52. ,46 O
ATOM 1460 C GLU B 76 55. .488 35. ,438 1. ,899 1. ,00 40. ,60 C
ATOM 1461 O GLU B 76 55. ,188 35, .558 3. ,068 1. ,00 40. ,70 O
ATOM 1462 N ASP B 77 55. ,995 34, .314 1, ,412 1. ,00 40. ,65 N
ATOM 1463 CA ASP B 77 56. ,168 33, .140 2. ,261 1. .00 40. ,78 C
ATOM 1464 CB ASP B 77 56. ,366 31. .865 1. ,430 1. ,00 40. ,99 c
ATOM 1465 CG ASP B 77 55. ,160 31. ,509 0. ,593 1. ,00 42. ,47 c
ATOM 1466 ODl ASP B 77 54. ,012 31. ,891 0. ,925 1. ,00 43. 22 0
ATOM 1467 OD2 ASP B 77 55. 363 30. ,813 -0. ,417 1. 00 45. 98 0
ATOM 1468 C ASP B 77 57. ,349 33. ,282 3. ,203 1. 00 40. 48 c
ATOM 1469 O ASP B 77 57. 547 32. ,406 4. ,062 1. 00 41. 07 0
ATOM 1470 N SER B 78 58. ,144 34. ,343 3. ,026 1. 00 39. 20 N
ATOM 1471 CA SER B 78 59. 263 34. 613 3. 919 1. 00 38. 61 C
ATOM 1472 CB SER B 78 60. 034 35. 853 3. 479 1. 00 38. 59 C
ATOM 1473 OG SER B 78 60. 749 35. 584 2. 287 1. 00 39. 13 O
ATOM 1474 C SER B 78 58. 774 34. 798 5. 349 1. 00 38. 23 C
ATOM 1475 O SER B 78 57. 725 35. 412 5. 566 1. 00 38. 16 0
ATOM 1476 N GLY B 79 59. 526 34. 264 6. 310 1. 00 37. 06 N ATOM 1477 CA GLY B 79 59,.172 34.394 7.702 1.00 36.72 c
ATOM 1478 C GLY B 79 59, .642 33, .241 8, .571 1, .00 36 .81 c
ATOM 1479 O GLY B 79 60, .418 32 .386 8, .120 1 .00 37 .01 o
ATOM 1480 N THR B 80 59, .182 33. .215 9, .820 1. .00 35 .82 N
ATOM 1481 CA THR B 80 59, .539 32 .136 10, .723 1 .00 35 .70 C
ATOM 1482 CB THR B 80 59 .759 32 .708 12 .113 1 .00 35 .62 C
ATOM 1483 OGl THR B 80 60, .574 33, .869 11, .970 1, .00 35 .54 O
ATOM 1484 CG2 THR B 80 60, .452 31 .710 13 .024 1 .00 34 .98 C
ATOM 1485 C THR B 80 58, .516 30, .983 10, .729 1, .00 35, .72 C
ATOM 1486 O THR B 80 57, .311 31 .195 10 .948 1 .00 35 .81 0
ATOM 1487 N TYR B 81 59, .010 29, .773 10, .482 1, .00 35, .54 N
ATOM 1488 CA TYR B 81 58, .184 28 .569 10, .454 1 .00 36 .16 C
ATOM 1489 CB TYR B 81 58, .423 27, .801 9, .156 1, .00 36, .56 c
ATOM 1490 CG TYR B 81 57, .831 28, .448 7, .928 1, .00 36 .94 c
ATOM 1491 GDI TYR B 81 58. .527 29, .423 7, ,216 1, .00 36, .56 c
ATOM 1492 CEl TYR B 81 57, .963 30, .016 6, .076 1, .00 37, .63 c
ATOM 1493 CZ TYR B 81 56. .691 29, ,622 5. .665 1, .00 37, .70 c
ATOM 1494 OH TYR B 81 56. .095 30, .186 4, ,569 1, .00 38, .04 0
ATOM 1495 CE2 TYR B 81 55. .998 28, .655 6. .355 1, .00 37, .62 c
ATOM 1496 CD2 TYR B 81 56. .562 28, .078 7, .477 1, .00 37, .71 c
ATOM 1497 C TYR B 81 58, ,519 27. .653 11. .625 1, .00 36, .66 c
ATOM 1498 O TYR B 81 59, .681 27, .295 11. .816 1. .00 36, .33 0
ATOM 1499 N LYS B 82 57, ,512 27, .275 12, .416 1, .00 37, .35 N
ATOM 1500 CA LYS B 82 57. ,738 26, .370 13. ,551 1, .00 37, .75 c
ATOM 1501 CB LYS B 82 57, .561 27, .102 14. ,872 1, .00 37, .28 c
ATOM 1502 CG LYS B 82 58. .401 28, .335 15. ,050 1, .00 36. .86 c
ATOM 1503 CD LYS B 82 58. .600 28, .661 16. .530 1, .00 37, .26 c
ATOM 1504 CE LYS B 82 59. .231 30, .041 16. .696 1, .00 38. .77 c
ATOM 1505 NZ LYS B " 82 60. ,333 30, .124 17. .734 1, .00 38, .13 N
ATOM 1506 C LYS B 82 56. .820 25, .141 13, .513 1, .00 38. .47 C
ATOM 1507 O LYS B 82 55, .628 25, .258 13. .236 1. .00 39, .02 O
ATOM 1508 N CYS B 83 57. .376 23. .967 13. .795 1, .00 39. .00 N
ATOM 1509 CA CYS B 83 56. .578 22, .739 13. .854 1. ,00 39, .64 C
ATOM 1510 CB CYS B 83 57. .339 21. .546 13. .248 1, .00 39. .79 C
ATOM 1511 SG CYS B 83 58. ,916 21, .142 14. .085 1, .00 41. .25 S
ATOM 1512 C CYS B 83 56. ,183 22. .432 15. ,302 1, .00 39. ,76 C
ATOM 1513 O CYS B 83 56. .962 22. .700 16, ,229 1, .00 39. ,86 O
ATOM 1514 N GLY B 84 54. ,981 21. ,879 15, ,487 1, ,00 39, ,61 N
ATOM 1515 CA GLY B 84 54. ,527 21. .428 16. ,805 1, ,00 39, ,36 C
ATOM 1516 C GLY B 84 54. ,312 19. .928 16. ,816 1, ,00 39. .37 C
ATOM 1517 O GLY B 84 53. ,726 19. .372 15. ,893 1, ,00 39. .74 0
ATOM 1518 N ALA B 85 54. .809 19. .262 17, ,846 1, .00 39, .35 N
ATOM 1519 CA ALA B 85 54. ,593 17. .833 18. ,008 1. .00 39, .38 C
ATOM 1520 CB ALA B 85 55. .897 17. .091 17, ,945 1, .00 39, .21 C
ATOM 1521 C ALA B 85 53, .871 17. .562 19. ,327 1, .00 39. .54 C
ATOM 1522 O ALA B 85 54, .252 18. ,090 20, ,364 1, .00 39. .26 O
ATOM 1523 N TYR B 86 52, .814 16. ,755 19. ,253 1. .00 40. ,01 N
ATOM 1524 CA TYR B 86 51, .962 16. .400 20. ,392 1, .00 40. .48 C
ATOM 1525 CB TYR B 86 50. .556 16, .923 20. ,161 1. .00 40. ,34 C
ATOM 1526 CG TYR B 86 50, .584 18. .401 19. ,902 1. .00 40, .96 C
ATOM 1527 CD1 TYR B 86 51. ,003 18. .895 18. ,666- 1. ,00 41. ,70 C
ATOM 1528 CEl TYR B 86 51. .062 20. .246 18. ,420 1. .00 42. ,23 C
ATOM 1529 CZ TYR B 86 50. ,698 21. ,129 19. 424 1. ,00 41. ,82 C
ATOM 1530 OH TYR B 86 50. ,760 22, .479 19. ,169 1. ,00 42. ,60 O
ATOM 1531 CE2 TYR B 86 50. ,269 20. ,667 20. 660 1. ,00 40. ,71 C
ATOM 1532 CD2 TYR B 86 50. ,227 19. ,312 20. 896 1. ,00 40. ,41 C
ATOM 1533 C TYR B 86 51. .951 14. .894 20. ,626 1. .00 41. ,00 C
ATOM 1534 O TYR B 86 51. ,743 14. ,103 19. 693 1. ,00 40. 55 O
ATOM 1535 N PHE B 87 52. ,190 14. .506 21. 877 1. ,00 41. ,83 N
ATOM 1536 CA PHE B 87 52. ,457 13. ,106 22. 201 1. ,00 42. 83 C
ATOM 1537 CB PHE B 87 53. ,977 12. ,835 22. 309 1. ,00 42. 90 C
ATOM 1538 CG PHE B 87 54. ,726 13. ,842 23. 133 1. 00 43. 47 C
ATOM 1539 CD1 PHE B 87 55. ,350 14. ,932 22. 522 1. ,00 43. 68 C
ATOM 1540 CEl PHE B 87 56. 058 15. ,887 23. 293 1. 00 45. 01 C ATOM 1541 CZ PHE B 87 56..141 15..741 24.,701 1,,00 45,.10 c
ATOM 1542 CE2 PHE B 87 55. .516 14. .636 25. ,316 1, .00 45, .18 c
ATOM 1543 CD2 PHE B 87 54. .817 13. .699 24. .524 1, ,00 43, .90 c
ATOM 1544 C PHE B 87 51, .726 12. .583 23. .432 1. ,00 43, .25 c
ATOM 1545 O PHE B 87 51. .548 13. .314 24. .408 1, ,00 43, .61 0
ATOM 1546 N SER B 88 51, .315 11. .312 23. .360 1, .00 43, .83 N
ATOM 1547 CA SER B 88 50. .744 10. .558 24. .482 1, .00 44. .35 C
ATOM 1548 CB SER B 88 49. .311 10. .125 24. .156 1, .00 44, .34 C
ATOM 1549 OG SER B 88 49. .310 9. .090 23. .186 1, .00 44. .40 O
ATOM 1550 C SER B 88 51. .610 9. .322 24. .808 1, .00 44, .75 C
ATOM 1551 O SER B 88 51, ,280 8. .488 25. .676 1, .00 45. .27 0
ATOM 1552 N PRO B 99 50, ,592 16. .449 26, ,451 1. .00 49. .45 N
ATOM 1553 CA PRO B 99 51, ,216 17. ,750 26, .211 1, .00 48. .89 C
ATOM 1554 CB PRO B 99 52. ,227 17. .885 27, .369 1, .00 49. .12 C
ATOM 1555 CG PRO B 99 52. ,424 16. .435 27. .917 1, .00 49. .96 C
ATOM 1556 CD PRO B 99 51. ,517 15. .505 27. .109 1. .00 49. .56 C
ATOM 1557 C PRO B 99 51. .926 17, .713 24. .875 1, .00 48. .30 C
ATOM 1558 O PRO B 99 51. ,682 16. .788 24. .100 1, .00 47. .97 O
ATOM 1559 N GLY B 100 52. ,795 18, .696 24. ,616 1, .00 47. .85 N
ATOM 1560 CA GLY B 100 53. ,472 18, .823 23. .322 1, .00 47. .04 C
ATOM 1561 C GLY B 100 54. ,567 19, .872 23, .223 1, .00 46, .58 C
ATOM 1562 O GLY B 100 54. ,601 20. .824 23, .997 1, .00 46. .58 0
ATOM 1563 N GLU B 101 55. .432 19. .709 22, .226 1. .00 46, .07 N
ATOM 1564 CA GLU B 101 56, .662 20. ,482 22, ,107 1, .00 45. .71 c
ATOM 1565 CB GLU B 101 57. .818 19. ,564 22, ,490 1, .00 45. .87 c
ATOM 1566 CG GLU B 101 58. .927 20. .251 23, .221 1, .00 47. .85 c
ATOM 1567 CD GLU B 101 58. .610 20. .469 24, ,686 1, .00 50. .59 c
ATOM 1568 OEl GLU B 101 58. ,886 21. .582 25, .191 1, .00 52. .40 0
ATOM 1569 OE2 GLU B 101 58. .096 19. .533 25, .337 1, .00 51. ,15 0
ATOM 1570 C GLU B 101 56. .892 21. .092 20, .691 1, ,00 44, .89 c
ATOM 1571 O GLU B 101 56. .642 20. .439 19. .685 1, .00 44. ,67 0
ATOM 1572 N LYS B 102 57, .376 22. .336 20, .630 1, .00 44. .18 N
ATOM 1573 CA LYS B 102 57. .632 23. .060 19. .367 1, .00 43. .65 C
ATOM 1574 CB LYS B 102 57, .152 24, .511 19, .470 1, ,00 43, .65 C
ATOM 1575 CG LYS B 102 55. .651 24. .743 19, .306 1. .00 44. .74 C
ATOM 1576 CD LYS B 102 55. .342 26. ,238 19, .111 1, .00 45. .16 c
ATOM 1577 CE LYS B 102 53, .864 26. .562 19, .392 1, .00 49, .60 c
ATOM 1578 NZ LYS B 102 53, .568 28. .028 19, .318 1, .00 50. .55 N
ATOM 1579 C LYS B 102 59, .113 23. .095 18, .990 1. .00 42, .61 C
ATOM 1580 O LYS B 102 59, .981 23. .114 19, .859 1, .00 42. .56 O
ATOM 1581 N GLY B 103 59, .410 23. .128 17. .696 1, .00 41. .72 N
ATOM 1582 CA GLY B 103 60. .808 23. .232 17. .259 1, .00 40. .69 C
ATOM 1583 C GLY B 103 61, ,291 24. .672 17. .305 1, .00 39. .71 c
ATOM 1584 O GLY B 103 60, ,478 25. .592 17. .294 1, .00 39. .87 0
ATOM 1585 N ALA B 104 62. ,601 24. .884 17. .338 1, .00 38, ,38 N
ATOM 1586 CA ALA B 104 63. .122 26. .246 17. .337 1, .00 37, ,74 C
ATOM 1587 CB ALA B 104 64. .632 26, .254 17, .379 1, .00 37, .58 C
ATOM 1588 C ALA B 104 62, .620 27. .082 16. .151 1, ,00 37, .52 C
ATOM 1589 O ALA B 104 62, .298 28. ,245 16. .315 1. ,00 38. .11 O
ATOM 1590 N GLY B 105 62, .558 26. .513 14. .957 1, ,00 36, .98 N
ATOM 1591 CA GLY B 105 62, ,085 27. .286 13. .830 1. ,00 36, .46 C
ATOM 1592 C GLY B 105 63, .021 27. .273 12. .645 1, ,00 36, .61 C
ATOM 1593 O GLY B 105 64. .185 26. .891 12. .750 1. ,00 36, .81 O
ATOM 1594 N THR B 106 62. .488 27. .689 11. .507 1. ,00 36. .30 N
ATOM 1595 CA THR B 106 63. .245 27. .842 10. .289 1. ,00 35. ,99 C
ATOM 1596 CB THR B 106 62. .713 26. .880 9, .195 1. ,00 36. .37 C
ATOM 1597 OGl THR B 106 62. ,974 25. .531 9. ,571 1. ,00 35. ,72 O
ATOM 1598 CG2 THR B 106 63. .395 27, .128 7, ,874 1. ,00 37. ,55 C
ATOM 1599 C THR B 106 62. .994 29. .269 9, ,859 1. ,00 35. ,39 C
ATOM 1600 O THR B 106 61. .844 29. ,677 9. ,772 1. ,00 35. 20 O
ATOM 1601 N VAL B 107 64. .051 30. .042 9. ,624 1. ,00 34. ,99 N
ATOM 1602 CA VAL B 107 63. ,879 31. ,398 9. ,085 1. 00 34. 84 C
ATOM 1603 CB VAL B 107 64. .838 32. .416 9. ,701 1. ,00 34. ,41 C
ATOM 1604 CGI VAL B 107 64. .662 33. .759 9. ,026 1. 00 33. 11 C ATOM 1605 CG2 VAL B 107 64,.589 32.524 11,.189 1.00 33.77 c
ATOM 1606 C VAL B 107 64, .046 31, .362 7, .568 1 .00 35 .66 c
ATOM 1607 O VAL B 107 65, .165 31 .227 7, .029 1 .00 35 .61 0
ATOM 1608 N LEU B 108 62, .914 31, .458 6, .879 1, .00 36, .39 N
ATOM 1609 CA LEU B 108 62, .894 31, .320 5, .427 1 .00 37 .02 C
ATOM 1610 CB LEU B 108 61, .650 30, .552 4. .959 1, .00 36, .96 C
ATOM 1611 CG LEU B 108 61, .371 30, .622 3, .453 1, .00 37 .20 C
ATOM 1612 CD1 LEU B 108 62. .500 29, .997 2. .636 1, .00 36, .00 c
ATOM 1613 CD2 LEU B 108 60, ,030 29, .999 3. .113 1, .00 36 .84 c
ATOM 1614 C LEU B 108 62. .908 32, .685 4. .794 1, .00 37, .27 c
ATOM 1615 O LEU B 108 62. .029 33, .513 5. .069 1, .00 37, .99 0
ATOM 1616 N THR B 109 63. .897 32, .932 3. .951 1, .00 37, ,20 N
ATOM 1617 CA THR B 109 63. .800 34, .092 3. .081 1, .00 37, .29 c
ATOM 1618 CB THR B 109 64. .859 35. .169 3. .392 1, .00 37, .40 c
ATOM 1619 OGl THR B 109 65. .039 35, ,985 2. .230 1, .00 38, ,63 o
ATOM 1620 CG2 THR B 109 66. .182 34. .552 3. .782 1, .00 37, ,84 c
ATOM 1621 C THR B 109 63. .716 33. .702 1. .584 1, .00 36, .85 c
ATOM 1622 O THR B 109 64. .405 32. .776 1. .110 1, .00 36. .94 o
ATOM 1623 N VAL B 110 62, .823 34. ,388 0. .867 1, .00 36, .01 N
ATOM 1624 CA VAL B 110 62, .546 34. ,084 -0, .551 1. .00 35. ,02 c
ATOM 1625 CB VAL B 110 61, ,059 33. .691 -0, .773 1, .00 34, .55 c
ATOM 1626 CGI VAL B 110 60. .822 33. .302 -2, .206 1, .00 33. ,34 c
ATOM 1627 CG2 VAL B 110 60, ,697 32. .549 0, .109 1, .00 34, .63 c
ATOM 1628 C VAL B 110 62, ,946 35. .212 -1, .532 1, .00 34. .56 c
ATOM 1629 O VAL B 110 62, ,394 36. .325 -1, .477 1, .00 34. .65 0
ATOM 1630 N LYS B 111 63. ,918 34. .887 -2. ,390 1, .00 33. .54 N
ATOM 1631 CA LYS B 111 64. .353 35. .612 -3, .609 1, .00 32. .70 C
ATOM 1632 CB LYS B 111 63. .710 36. .984 -3, ,859 1, ,00 32. .41 C
ATOM 1633 CG LYS B 111 62. .878 37. .004 -5, .146 1, .00 31, .57 C
ATOM 1634 CD LYS B 111 62. .464 38. .390 -5, .630 1, ,00 31. ,59 C
ATOM 1635 CE LYS B 111 63. .615 39. .127 -6, .288 1, .00 29. .56 c
ATOM 1636 NZ LYS B 111 64. .096 38. .345 -7, .446 1, .00 28. .53 N
ATOM 1637 C LYS B 111 65. .872 35. .660 -3, .696 1, .00 33. ,30 c
ATOM 1638 O LYS B 111 66. .523 36. .251 -2, ,841 1, .00 33. ,69 0
ATOM 1639 N ALA C 1 27. .731 10. .932 10, ,845 1, ,00 36. .73 N
ATOM 1640 CA ALA C 1 26. .819 11. .600 11, ,783 1, ,00 37. ,06 C
ATOM 1641 CB ALA c 1 26, .956 10, .995 13, ,140 1, ,00 36, .58 C
ATOM 1642 C ALA c 1 27, ,172 13, ,073 11, ,784 1, .00 37, ,88 C
ATOM 1643 O ALA c 1 28, .275 13, ,436 11, ,393 1. ,00 38, ,55 O
ATOM 1644 N TRP c 2 26. .234 13, .929 12. ,184 1, ,00 38, .85 N
ATOM 1645 CA TRP c 2 26. .434 15, ,391 12, ,169 1, .00 39, ,92 C
ATOM 1646 CB TRP c 2 26, ,369 15. ,963 10. ,730 1. .00 39. .79 C
ATOM 1647 CG TRP c 2 25. ,004 15, ,897 10. ,161 1. .00 39. .52 C
ATOM 1648 CD1 TRP c 2 24. .3.94 14. .800 9. ,651 1. .00 39, .33 C
ATOM 1649 NE1 TRP c 2 23. .119 15, ,102 9, ,263 1. .00 39, .75 N
ATOM 1650 CE2 TRP c 2 22. .882 16, .424 9, ,523 1, .00 40, .28 C
ATOM 1651 CD2 TRP c 2 24. .048 16. .955 10. ,092 1. ,00 39, .55 C
ATOM 1652 CE3 TRP c 2 24, .067 18. .304 10. ,444 1, .00 39, .87 C
ATOM 1653 CZ3 TRP c 2 22. .936 19. .067 10. ,220 1, .00 38. ,76 C
ATOM 1654 CH2 TRP c 2 21. .800 18, .517 9, ,656 1, .00 39. .45 C
ATOM 1655 CZ2 TRP c 2 21. ,745 17. ,196 9. ,298 1, .00 40. ,40 C
ATOM 1656 C TRP c 2 25, .350 16. .008 13. ,051 1. .00 40. ,73 C
ATOM 1657 O TRP c 2 24. ,265 15. ,425 13. ,181 1. .00 41. ,56 O
ATOM 1658 N VAL c 3 25. ,635 17, .161 13. ,664 1. .00 41. ,60 N
ATOM 1659 CA VAL c 3 24. ,695 17. ,809 14. ,601 1. ,00 42. ,64 C
ATOM 1660 CB VAL c 3 25. ,381 18. ,237 15. ,920 1. .00 42. ,63 C
ATOM 1661 CGI VAL c 3 24. ,368 18. ,848 16. 874 1. ,00 43. 03 C
ATOM 1662 CG2 VAL c 3 26. ,027 17. ,038 16. ,593 1. ,00 42. ,94 C
ATOM 1663 C VAL c 3 23. 982 19. 013 13. 975 1. ,00 43. 23 C
ATOM 1664 O VAL c 3 24. ,639 19. ,915 13. ,460 1. ,00 44. 10 O
ATOM 1665 N ASP c 4 22. 646 19. 001 14. 000 1. ,00 43. 73 N
ATOM 1666 CA ASP c 4 21. ,816 20. ,094 13. 498 1. ,00 43. 97 C
ATOM 1667 CB ASP c 4 20. 470 19. 545 13. 016 1. 00 43. 97 C
ATOM 1668 CG ASP c 4 19. 696 20. ,533 12. 151 1. 00 45. 56 C ATOM 1669 ODl ASP C 4 18.573 20.188 11.732 1.00 46.90 0
ATOM 1670 OD2 ASP C 4 20 .190 21 .651 11 .867 1 .00 48 .30 0
ATOM 1671 C ASP C 4 21 .575 21 .057 14 .651 1 .00 44 .27 c
ATOM 1672 O ASP C 4 20 .836 20 .719 15 .580 1 .00 44 .63 0
ATOM 1673 N GLN C 5 22, .187 22, .245 14 .611 1 .00 44 .42 N
ATOM 1674 CA GLN C 5 21 .982 23 .243 15 .675 1 .00 44 .16 C
ATOM 1675 CB GLN C 5 23 .317 23, .653 16 .240 1 .00 44 .58 c
ATOM 1676 CG GLN C 5 23, .245 24, .644 17, .374 1, .00 44 .79 c
ATOM 1677 CD GLN C 5 24 .625 25, .031 17 .833 1 .00 45 .01 c
ATOM 1678 OEl GLN C 5 25, .593 24, .300 17, .586 1 .00 42 .96 0
ATOM 1679 NE2 GLN C 5 24, .733 26, .188 18, .496 1, .00 45 .43 N
ATOM 1680 C GLN c 5 21, .209 24, .490 15, .245 1, .00 43 .80 c
ATOM 1681 O GLN c 5 21. .529 25, .095 14, .240 1, .00 43 .89 0
ATOM 1682 N THR c 6 20, .190 24, .850 16, .020 1 .00 43 .48 N
ATOM 1683 CA THR c 6 19, ,359 26, .039 15, .793 1, .00 43 .34 C
ATOM 1684 CB THR c 6 17. .908 25, .659 15, ,350 1, .00 43 .54 C
ATOM 1685 OGl THR c 6 17, .288 24, .832 16, .341 1, .00 42 .46 O
ATOM 1686 CG2 THR c 6 17, .890 24. .904 14, .013 1, .00 43 .93 C
ATOM 1687 C THR c 6 19. .277 26, .803 17, ,122 1, .00 43, .40 C
ATOM 1688 O THR c 6 19, .339 26, .165 18. ,188 1, .00 43 .20 O
ATOM 1689 N PRO c 7 19. .166 28. ,159 17. .086 1. .00 43, .22 N
ATOM 1690 CA PRO c 7 19. .201 29. ,027 15. ,922 1. .00 43, .33 C
ATOM 1691 CB PRO c 7 18. .603 30. ,348 16. .434 1, ,00 43, .14 C
ATOM 1692 CG PRO c 7 18. .411 30. ,213 17. .881 1. ,00 42, .62 C
ATOM 1693 CD PRO c 7 19. .035 28. ,945 18, .329 1, .00 43, .17 C
ATOM 1694 C PRO c 7 20. .644 29. .269 15, .507 1, ,00 43, ,73 c
ATOM 1695 O PRO c 7 21. ,538 29. .273 16, .358 1. .00 44, ,00 0
ATOM 1696 N ARG c 8 20. .875 29. .441 14, ,213 1, .00 43, .91 N
ATOM 1697 CA ARG c 8 22. .203 29. .804 13, .741 1, .00 44, .42 C
ATOM 1698 CB ARG c 8 22. ,288 29. .736 12, .203 1. .00 44, .66 C
ATOM 1699 CG ARG c 8 21. .908 28, .355 11, .559 1, .00 47, .05 c
ATOM 1700 CD ARG c 8 23. .002 27, .235 11, .669 1. .00 48, .64 c
ATOM 1701 NE ARG c 8 24. .326 27. .765 12. ,042 1. .00 50, ,62 N
ATOM 1702 CZ ARG c 8 25. .368 27. .927 11, ,221 1. .00 49, .49 C
ATOM 1703 NHl ARG c 8 26. .492 28. .442 11, .696 1. .00 47, .43 N
ATOM 1704 NH2 ARG c 8 25. ,306 27. .560 9, ,943 1. .00 49, .11 N
ATOM 1705 C ARG c 8 22. .622 31. .191 14, ,313 1. ,00 43. .96 C
ATOM 1706 O ARG c 8 23. .704 31. .331 14, .886 1. ,00 44. .32 O
ATOM 1707 N SER c 9 21. .774 32. .205 14, .189 1. ,00 43. .09 N
ATOM 1708 CA SER c 9 22. .056 33, .463 14, .876 1. ,00 42. .40 C
ATOM 1709 CB SER c 9 22. .735 34. .495 13. ,951 1. ,00 42. .53 C
ATOM 1710 OG SER c 9 21. .816 35. .166 13. .109 1. ,00 42. .75 O
ATOM 1711 C SER c 9 20, .802 34, .007 15. ,545 1, ,00 41. .72 C
ATOM 1712 O SER c 9 19. ,681 33. ,687 15. ,126 1. .00 41. ,94 O
ATOM 1713 N VAL c 10 20. .995 34. .806 16. .593 1. ,00 40, ,57 N
ATOM 1714 CA VAL c 10 19. .877 35. .325 17. ,371 1. ,00 39. .60 C
ATOM 1715 CB VAL c 10 19, ,254 34, ,205 18. .270 1, .00 39. .41 C
ATOM 1716 CGI VAL c 10 20. .299 33, .568 19. ,163 1. .00 39. .02 C
ATOM 1717 CG2 VAL c 10 18. ,079 34. ,712 19. ,075 1. .00 38. ,83 C
ATOM 1718 C VAL c 10 20. ,258 36. .565 18. ,174 1, .00 39. .27 C
ATOM 1719 O VAL c 10 21. .374 36. ,694 18. ,670 1. .00 39. ,55 O
ATOM 1720 N THR c 11 19. ,317 37. ,488 18. ,275 1. ,00 38. ,96 N
ATOM 1721 CA THR c 11 19. ,461 38. ,661 19. ,129 1. .00 38. ,39 C
ATOM 1722 CB THR c 11 19. ,299 39. ,939 18. ,320 1. ,00 38. ,22 C
ATOM 1723 OGl THR c 11 20. ,199 39. ,883 17. ,211 1. ,00 38. ,20 O
ATOM 1724 CG2 THR c 11 19. ,625 41. ,165 19. 161 1. ,00 38. ,24 C
ATOM 1725 C THR c 11 18. 445 38. 597 20. 269 1. ,00 38. 23 C
ATOM 1726 O THR c 11 17. ,265 38. ,289 20. 052 1. ,00 38. ,08 O
ATOM 1727 N LYS c 12 18. 924 38. 844 21. 485 1. 00 38. 02 N
ATOM 1728 CA LYS c 12 18. 089 38. 828 22. 677 1. 00 38. 13 C
ATOM 1729 CB LYS c 12 18. 255 37. 518 23. 457 1. 00 38. 13 C
ATOM 1730 CG LYS c 12 17. 558 36. 338 22. 799 1. 00 38. 06 C
ATOM 1731 CD LYS c 12 16. 847 35. 434 23. 786 1. 00 37. 36 C
ATOM 1732 CE LYS c 12 15. 673 34. 699 23. 122 1. 00 36. 90 C ATOM 1733 NZ LYS C 12 14,.422 35,.519 23,.128 1,.00 37.18 N
ATOM 1734 C LYS C 12 18 .465 39 .995 23 .549 1 .00 38 .34 C
ATOM 1735 O LYS C 12 19, .636 40, .304 23, .688 1, .00 38 .48 O
ATOM 1736 N GLU C 13 17 .473 40, .650 24 .134 1 .00 38 .77 N
ATOM 1737 CA GLU C 13 17, .743 41, .773 25, .018 1 .00 39 .16 C
ATOM 1738 CB GLU C 13 16, .521 42, .674 25, .120 1, .00 39 .34 C
ATOM 1739 CG GLU C 13 16, .396 43, .631 23, .945 1 .00 40 .22 C
ATOM 1740 CD GLU C 13 14, .957 43. .847 23, .517 1, .00 41 .71 C
ATOM 1741 OEl GLU C 13 14, .657 44, .910 22, .915 1, .00 41 .36 O
ATOM 1742 OE2 GLU C 13 14, ,126 42. .948 23. .784 1, .00 42, .65 O
ATOM 1743 C GLU C 13 18, .207 41. .306 26, .391 1, .00 39 .19 C
ATOM 1744 O GLU c 13 17, .979 40. .158 26. .771 1, .00 39, .29 O
ATOM 1745 N THR c 14 18, .884 42. .194 27. .111 1, .00 39, .39 N
ATOM 1746 CA THR c 14 19, .417 41. .901 28. .436 1, .00 39, .66 C
ATOM 1747 CB THR c 14 20, .096 43. .159 29. .020 1, .00 39, .57 C
ATOM 1748 OGl THR c 14 21, ,151 43. .562 28, ,138 1, .00 39, .75 O
ATOM 1749 CG2 THR c 14 20, ,671 42. .907 30, .415 1, .00 39, .37 C
ATOM 1750 C THR c 14 18, ,313 41. .392 29, ,358 1, .00 40, .11 C
ATOM 1751 O THR c 14 17, ,199 41. .920 29, ,347 1, .00 40, .08 O
ATOM 1752 N GLY c 15 18, .614 40, .346 30, .124 1, .00 40, .51 N
ATOM 1753 CA GLY c 15 17. ,666 39. .811 31, .098 1, .00 41, .18 C
ATOM 1754 C GLY c 15 16. .780 38, .700 30. .563 1, .00 41, ,82 C
ATOM 1755 O GLY c 15 16. .190 37, .945 31. .337 1, .00 42, .17 O
ATOM 1756 N GLU c 16 16, .679 38, .593 29. .241 1. .00 42, .08 N
ATOM 1757 CA GLU c 16 15. .961 37, .491 28. .613 1, .00 42, .31 C
ATOM 1758 CB GLU c 16 15. .680 37, .811 27. .148 1, .00 42. .35 C
ATOM 1759 CG GLU c 16 14, ,839 39, .050 26. .948 1, .00 42, .99 C
ATOM 1760 CD GLU c 16 14. ,079 39, .046 25. .640 1, .00 44. .31 C
ATOM 1761 OEl GLU c 16 13. ,949 40. ,129 25, .026 1, .00 44. .89 O
ATOM 1762 OE2 GLU c 16 13. ,600 37, .966 25, .232 1, .00 44. .98 0
ATOM 1763 C GLU c 16 16. ,795 36, ,222 28. .738 1, .00 42. ,46 c
ATOM 1764 O GLU c 16 17. .864 36, .247 29. .343 1, .00 42. .47 o
ATOM 1765 N SER c 17 16. .311 35, .115 28. .180 1, .00 42. .67 N
ATOM 1766 CA SER c 17 17. .070 33, .867 28. .200 1, .00 43. .22 C
ATOM 1767 CB SER c 17 16. .598 32, .956 29. ,336 1, ,00 43. .10 C
ATOM 1768 OG SER c 17 15. .213 32. ,696 29, ,259 1. ,00 44. ,15 O
ATOM 1769 C SER c 17 17. .028 33. ,133 26. ,867 1, ,00 43. .49 C
ATOM 1770 O SER c 17 16. .053 33. ,244 26. ,138 1, ,00 43, .98 O
ATOM 1771 N LEU c 18 18, .088 32. ,386 26. ,559 1, ,00 43, .91 N
ATOM 1772 CA LEU c 18 18. .195 31. ,625 25, ,300 1. ,00 44, .39 C
ATOM 1773 CB LEU c 18 19. .588 31. .817 24. .686 1, ,00 43, .94 C
ATOM 1774 CG LEU c 18 19. .822 32. .059 23, .187 1, ,00 43, .64 C
ATOM 1775 GDI LEU c 18 21. .247 31. .649 22. .849 1, ,00 44, .22 C
ATOM 1776 CD2 LEU c 18 18. .821 31. .411 22, .214 1, ,00 42, .64 C
ATOM 1777 C LEU c 18 17. .988 30. ,115 25. ,485 1, ,00 44. .89 C
ATOM 1778 O LEU c 18 18. .428 29, .525 26. ,491 1. ,00 45, .55 O
ATOM 1779 N THR c 19 17. .345 29, .491 24. .507 1. ,00 44, .93 N
ATOM 1780 CA THR c 19 17. .395 28. .044 24. ,375 1. ,00 45. .04 C
ATOM 1781 CB THR c 19 15, .991 27, ,418 24, ,390 1. ,00 44. ,97 C
ATOM 1782 OGl THR c 19 15, ,299 27, .824 25. ,571 1. ,00 45. .74 O
ATOM 1783 CG2 THR c 19 16, ,080 25, ,921 24. ,401 1. ,00 45. ,54 C
ATOM 1784 C THR c 19 18. ,080 27. ,704 23. ,066 1. ,00 45. ,01 C
ATOM 1785 O THR c 19 17. ,667 28. ,159 22. ,012 1. ,00 45. ,60 O
ATOM 1786 N ILE c 20 19. ,137 26. ,919 23. ,135 1. ,00 45. ,26 N
ATOM 1787 CA ILE c 20 19. ,728 26. ,320 21. ,949 1. ,00 45. ,56 C
ATOM 1788 CB ILE c 20 21. ,280 26. ,416 21. ,988 1. ,00 45. ,39 C
ATOM 1789 CGI ILE c 20 21. .706 27. ,836 22. ,365 1. ,00 45. ,10 C
ATOM 1790 CD1 ILE c 20 23. ,194 28. 035 22. 546 1. ,00 45. ,39 C
ATOM 1791 CG2 ILE c 20 21. ,888 26. 037 20. 644 1. 00 45. ,52 C
ATOM 1792 C ILE c 20 19. ,255 24. 851 21. 904 1. 00 46. ,07 C
ATOM 1793 O ILE c 20 19. ,294 24. 158 22. 916 1. 00 46. 16 O
ATOM 1794 N ASN c 21 18. ,781 24. 393 20. 747 1. 00 46. 49 N
ATOM 1795 CA ASN c 21 18. ,442 22. 980 20. 551 1. 00 46. 90 C
ATOM 1796 CB ASN c 21 17. ,019 22. 815 20. 012 1. 00 46. 94 C ATOM 1797 CG ASN C 21 15.994 23.612 20.799 1.00 48.31 c
ATOM 1798 ODl ASN C 21 15, .564 24, .676 20, .361 1 .00 49 .34 0
ATOM 1799 ND2 ASN C 21 15, .592 23 .100 21, .965 1 .00 49 .90 N
ATOM 1800 C ASN C 21 19, .390 22 .387 19 .542 1 .00 46 .87 C
ATOM 1801 O ASN C 21 19, .539 22, .928 18, .468 1, .00 47, .41 O
ATOM 1802 N CYS C 22 20, .035 21, .282 19, .883 1 .00 46 .92 N
ATOM 1803 CA CYS C 22 20, .816 20 .516 18 .917 1 .00 46 .98 C
ATOM 1804 CB CYS C 22 22. .261 20, .348 19, .412 1, .00 47, .47 C
ATOM 1805 SG CYS C 22 23, .260 21, .888 19, .588 1 .00 53, .20 S
ATOM 1806 C CYS C 22 20, .188 19, .123 18, .685 1 .00 45 .66 C
ATOM 1807 O CYS c 22 19. .582 18, .548 19, .599 1, .00 45, .62 O
ATOM 1808 N ALA c 23 20, .335 18, .579 17, .477 1, .00 43, .90 N
ATOM 1809 CA ALA c 23 19. .989 17. .185 17. .252 1, .00 42, .45 C
ATOM 1810 CB ALA c 23 18, .682 17, .045 16, .532 1, .00 42, .68 C
ATOM 1811 C ALA c 23 21, .095 16, .436 16, .524 1, .00 42, .11 C
ATOM 1812 O ALA c 23 21. .709 16. ,947 15, .561 1, .00 41, .96 O
ATOM 1813 N LEU c 24 21. .359 15, ,222 17, .019 1, .00 40, .74 N
ATOM 1814 CA LEU c 24 22, .336 14, .323 16, .417 1, .00 39, .93 c
ATOM 1815 CB LEU c 24 22, .925 13. ,351 17. .474 1, .00 39, .48 c
ATOM 1816 CG LEU c 24 24. .008 12. .327 17, ,060 1, .00 38, .90 c
ATOM 1817 GDI LEU c 24 24, .451 11, .459 18, ,251 1, .00 36, .33 c
ATOM 1818 CD2 LEU c 24 25. .205 12, .958 16, ,367 1. ,00 32. ,90 c
ATOM 1819 C LEU c 24 21. .636 13, .575 15, ,281 1, .00 39, ,20 c
ATOM 1820 O LEU c 24 20, .666 12, .842 15, .537 1, .00 38, .96 0
ATOM 1821 N LYS c 25 22. .095 13, .789 14, .042 1, .00 37, .85 N
ATOM 1822 CA LYS c 25 21, .501 13, .105 12, .903 1, .00 37, .40 C
ATOM 1823 CB LYS c 25 20, .947 14, .081 11, .875 1, .00 37, .17 C
ATOM 1824 CG LYS c 25 20, .575 15, .394 12, .436 1, .00 38. .56 C
ATOM 1825 CD LYS c 25 19, .242 15, .866 11, .907 1, .00 41, .52 C
ATOM 1826 CE LYS c 25 18. .086 15. .341 12, ,746 1, .00 41. ,53 C
ATOM 1827 NZ LYS c 25 17, .003 16, .347 12. .725 1, ,00 44. .19 N
ATOM 1828 C LYS c 25 22, .475 12, .155 12, .219 1, ,00 37, .29 C
ATOM 1829 O LYS c 25 23, ,690 12. .393 12. .187 1, .00 36. .68 O
ATOM 1830 N ASN c 26 21. .899 11, ,096 11. ,648 1. .00 37. .08 N
ATOM 1831 CA ASN c 26 22, .619 10, .045 10, .951 1, .00 36, .94 C
ATOM 1832 CB ASN c 26 23. .183 10. .554 9. .637 1, .00 36. .73 C
ATOM 1833 CG ASN c 26 23. .422 9. .445 8. .640 1, ,00 36. .96 C
ATOM 1834 ODl ASN c 26 24, .386 9, .500 7. ,886 1, .00 37, .38 O
ATOM 1835 ND2 ASN c 26 22. .554 8. .429 8. ,630 1, .00 37. ,00 N
ATOM 1836 C ASN c 26 23. .693 9. .383 11. ,800 1, .00 37. ,21 C
ATOM 1837 O ASN c 26 24. ,818 9. ,162 11. .347 1. .00 37, ,58 O
ATOM 1838 N ALA c 27 23. .324 9. ,063 13. .036 1, .00 37, ,26 N
ATOM 1839 CA ALA c 27 24. .168 8. .297 13, ,926 1, .00 37, ,54 C
ATOM 1840 CB ALA c 27 24, .279 9. .001 15. .233 1, .00 37, .73 C
ATOM 1841 C ALA c 27 23. .610 6. .889 14. .126 1, .00 37, .64 C
ATOM 1842 O ALA c 27 22. .456 6. .720 14. ,500 1, .00 37, .87 O
ATOM 1843 N ALA c 28 24. .427 5. .877 13. .860 1, ,00 38. ,19 N
ATOM 1844 CA ALA c 28 24. .031 4. .483 14, .114 1, .00 38. .86 C
ATOM 1845 CB ALA c 28 25. .016 3. .490 13, ,457 1, .00 38. .12 C
ATOM 1846 C ALA c 28 23. .966 4, .271 15, ,621 1. ,00 39. .37 C
ATOM 1847 O ALA c 28 23. .060 3, .640 16, ,125 1. .00 39. .79 O
ATOM 1848 N ASP c 29 24. .917 4, ,867 16, ,329 1. .00 39, .97 N
ATOM 1849 CA ASP c 29 25, .115 4. ,646 17, ,740 1. ,00 40. ,44 C
ATOM 1850 CB ASP c 29 26, .597 4. ,825 18. ,041 1. ,00 40. ,96 C
ATOM 1851 CG ASP c 29 27, .479 3. ,880 17. ,226 1. .00 43. .39 C
ATOM 1852 ODl ASP c 29 27. .169 2. ,654 17. ,165 1. ,00 44. ,27 O
ATOM 1853 OD2 ASP c 29 28. ,495 4. ,369 16. ,657 1. ,00 46. ,39 O
ATOM 1854 C ASP c 29 24, .293 5. ,571 18. ,634 1. ,00 40. ,24 C
ATOM 1855 O ASP c 29 23. ,689 6. ,523 18. ,171 1. ,00 39. 90 O
ATOM 1856 N ASP c 30 24. ,312 5. ,275 19. ,929 1. ,00 40. ,41 N
ATOM 1857 CA ASP c 30 23. ,546 5. ,989 20. ,938 1. ,00 40. ,34 C
ATOM 1858 CB ASP c 30 23. ,311 5. ,049 22. 117 1. 00 40. 32 C
ATOM 1859 CG ASP c 30 22. ,420 3. ,865 21. 764 1. ,00 42. 22 C
ATOM 1860 ODl ASP c 30 22. ,419 2. 885 22. 530 1. 00 43. 42 O ATOM 1861 OD2 ASP C 30 21.694 3.901 20.742 00 45.93 O
ATOM 1862 C ASP C 30 24.234 7.271 21.441 00 40.30 C
ATOM 1863 O ASP C 30 25.457 7.289 21.620 00 40.36 O
ATOM 1864 N LEU C 31 23.444 8.326 21.680 00 40.03 N
ATOM 1865 CA LEU C 31 23.909 9.550 22.316 00 40.03 C
ATOM 1866 CB LEU C 31 22.763 10.513 22.468 00 39.83 C
ATOM 1867 CG LEU C 31 22.910 12.041 22.408 1.00 40.23 C
ATOM 1868 GDI LEU C 31 24.306 12.606 22.614 00 38.68 C
ATOM 1869 CD2 LEU C 31 21.917 12.646 23.374 00 39.10 C
ATOM 1870 C LEU C 31 24.411 9.204 23.703 00 40.85 C
ATOM 1871 O LEU c 31 23.685 8.625 24.518 00 40.98 O
ATOM 1872 N GLU c 32 25.657 9.566 23.973 00 41.58 N
ATOM 1873 CA GLU c 32 26.345 9.082 25.147 00 42.36 C
ATOM 1874 CB GLU c 32 27.489 8.170 24.722 00 42.52 C
ATOM 1875 CG GLU c 32 28.036 284 25.826 00 45.19 C
ATOM 1876 CD GLU c 32 27.062 205 26.317 00 48.72 C
ATOM 1877 OEl GLU c 32 27.214 790 27.491 00 49.89 O
ATOM 1878 OE2 GLU c 32 26.165 763 25.549 00 49.60 O
ATOM 1879 C GLU c 32 26.868 10.200 26.015 00 42.59 C
ATOM 1880 O GLU c 32 26.954 10.040 27.222 1.00 42.66 O
ATOM 1881 N ARG c 33 27.219 11.326 25.400 1.00 43.15 N
ATOM 1882 CA ARG c 33 27.768 12.463 26.119 1.00 44.02 C
ATOM 1883 CB ARG c 33 29.297 12.366 26.188 1.00 43.78 C
ATOM 1884 CG ARG c 33 29.835 12.760 27.549 1.00 45.32 C
ATOM 1885 CD ARG c 33 31.358 12.861 27.670 1.00 45.61 C
ATOM 1886 NE ARG c 33 31.932 13.600 26.555 1.00 50.54 N
ATOM 1887 CZ ARG c 33 32.936 13.160 25.790 1.00 53.62 C
ATOM 1888 NHl ARG c 33 33.538 11.995 26.050 1 00 53.13 N
ATOM 1889 NH2 ARG c 33 33.358 13.903 24.765 1 00 55.14 N
ATOM 1890 C ARG c 33 27.351 13.751 25.436 1 00 44.08 C
ATOM 1891 O ARG c 33 27.274 13.827 24.214 1 00 43.84 O
ATOM 1892 N THR c 34 27.061 14.775 26.222 1 00 44.90 N
ATOM 1893 CA THR c 34 26.716 16.070 25.638 1 00 45.49 C
ATOM 1894 CB THR c 34 25.222 16.398 25.769 1 00 45.88 C
ATOM 1895 OGl THR c 34 24.788 16.134 27.120 1 00 46.31 O
ATOM 1896 CG2 THR c 34 24.389 15.552 24.764 1 00 45.54 C
ATOM 1897 C THR c 34 27.523 17.126 26.324 1 00 45.65 C
ATOM 1898 O THR c 34 27.620 17.130 27.542 1.00 46.28 O
ATOM 1899 N ASP c 35 28.131 17.987 25.526 00 45.98 N
ATOM 1900 CA ASP c 35 28.961 19.075 25.991 00 46.47 C
ATOM 1901 CB ASP c 35 30.409 18.798 25.635 00 47.14 C
ATOM 1902 CG ASP c 35 31.034 17.710 26.502 00 50.19 C
ATOM 1903 ODl ASP c 35 32.229 17.369 26.281 00 53.29 O
ATOM 1904 OD2 ASP c 35 30.348 17.206 27.421 00 52.72 O
ATOM 1905 C ASP c 35 28.517 20.367 25.319 00 46.41 C
ATOM 1906 O ASP c 35 27.873 20.354 24.265 00 46.40 O
ATOM 1907 N TRP c 36 28.838 21.493 25.944 00 46.29 N
ATOM 1908 CA TRP c 36 28.516 22.792 25.370 00 45.80 C
ATOM 1909 CB TRP c 36 27.312 23.395 26.055 00 45.82 C
ATOM 1910 CG TRP c 36 26.112 22.609 25.833 00 45.99 C
ATOM 1911 CD1 TRP c 36 25.717 21.508 26.528 00 46.28 C
ATOM 1912 NE1 TRP c 36 24.519 21.038 26.036 00 46.83 N
ATOM 1913 CE2 TRP c 36 24.122 21.842 25.002 00 46.87 C
ATOM 1914 CD2 TRP c 36 25.113 22.844 24.843 00 47.02 C
ATOM 1915 CE3 TRP c 36 24.947 23.815 23.840 00 46.90 C
ATOM 1916 CZ3 TRP c 36 23.798 23.755 23.030 00 46.94 C
ATOM 1917 CH2 TRP c 36 22.833 22.738 23.216 00 47.13 C
ATOM 1918 CZ2 TRP c 36 22.979 21.776 24.197 00 46.61 C
ATOM 1919 C TRP c 36 29.697 23.706 25.502 00 45.48 C
ATOM 1920 O TRP c 36 30.303 23.798 26.569 00 45.64 O
ATOM 1921 N TYR c 37 30.034 24.366 24.403 00 45.28 N
ATOM 1922 CA TYR c 37 31.184 25.251 24.366 00 45.14 C
ATOM 1923 CB TYR c 37 32.265 24.695 23.430 00 45.42 C
ATOM 1924 CG TYR c 37 32.608 23.242 23.684 00 46.04 c ATOM 1925 GDI TYR C 37 33..584 22..885 24,.635 1,.00 47.25 c
ATOM 1926 CEl TYR C 37 33. .911 21, .545 24. .887 1, .00 46 .32 c
ATOM 1927 CZ TYR C 37 33. .257 20. .541 24. .177 1, .00 47 .31 c
ATOM 1928 OH TYR C 37 33. .571 19, ,210 24. .415 1, .00 47 .35 0
ATOM 1929 CE2 TYR C 37 32. .278 20, .869 23. .222 1, .00 47 .25 c
ATOM 1930 CD2 TYR C 37 31, .962 22, .218 22. .984 1, .00 45. .98 c
ATOM 1931 C TYR C 37 30, .748 26, .670 23. .972 1, .00 44 .95 c
ATOM 1932 0 TYR C 37 29, .651 26. .877 23. ,426 1. .00 44, .59 o
ATOM 1933 N ARG C 38 31. .610 27, .641 24. .278 1, .00 44 .40 N
ATOM 1934 CA ARG C 38 31. .307 29. .039 24. .092 1, .00 43, .78 c
ATOM 1935 CB ARG C 38 30. .628 29, .570 25. .337 1, .00 43 .85 c
ATOM 1936 CG ARG C 38 30. .200 31. .012 25. .249 1, .00 45, .64 c
ATOM 1937 CD ARG C 38 29. .858 31, .527 26. .618 1, .00 49 .42 c
ATOM 1938 NE ARG C 38 31. .043 31. .607 27. .462 1, .00 53, .90 N
ATOM 1939 CZ ARG C 38 31. .040 31. .582 28. .791 1. .00 56, .65 C
ATOM 1940 NHl ARG C 38 29. .903 31. .460 29. .479 1, .00 57, .56 N
ATOM 1941 NH2 ARG C 38 32. .193 31. .662 29. .440 1. .00 58, .12 N
ATOM 1942 C ARG C 38 32. .576 29. .832 23. .839 1, .00 43, .49 C
ATOM 1943 O ARG C 38 33. .589 29. .651 24. .519 1. .00 42, ,68 O
ATOM 1944 N THR C 39 32. .510 30, .716 22. .849 1, .00 43, .42 N
ATOM 1945 CA THR c 39 33. .577 31, .660 22. .624 1, .00 43, .33 C
ATOM 1946 CB THR c 39 34. .408 31, .326 21, .347 1. .00 43. .01 C
ATOM 1947 OGl THR c 39 35. .397 32, .334 21, .135 1. .00 42, .59 O
ATOM 1948 CG2 THR c 39 33. .536 31, .219 20. .132 1. .00 43. .58 C
ATOM 1949 C THR c 39 33. .029 33, .087 22. .701 1. .00 43, .51 c
ATOM 1950 O THR c 39 32. .229 33, .508 21. .877 1. .00 43, .35 0
ATOM 1951 N THR c 40 33. ,459 33, .781 23. ,756 1, .00 44, .12 N
ATOM 1952 CA THR c 40 33. .087 35. .157 24. .122 1, .00 44, .52 C
ATOM 1.953 CB THR c 40 33. ,779 35. ,506 25. ,480 1. .00 44, .65 C
ATOM 1954 OGl THR c 40 33. .014 34. ,951 26. .554 1, .00 45, .14 O
ATOM 1955 CG2 THR c 40 33. ,954 37. .006 25. .708 1. .00 44, .21 C
ATOM 1956 C THR c 40 33. ,487 36. .188 23. .076 1, .00 44, .68 C
ATOM 1957 O THR c 40 34. .551 36. .065 22. .477 1. ,00 44, .77 O
ATOM 1958 N LEU c 41 32, .643 37. .201 22. .864 1, .00 45, .08 N
ATOM 1959 CA LEU c 41 33. .025 38. .378 22. .051 1, .00 45. .59 C
ATOM 1960 CB LEU c 41 31, .924 39. .452 22. .017 1, .00 45, .38 C
ATOM 1961 CG LEU c 41 30. ,982 39. .627 20. .817 1, ,00 45, .01 C
ATOM 1962 CD1 LEU c 41 30. ,413 41. .035 20. .861 1. .00 44. .32 c
ATOM 1963 CD2 LEU c 41 31. .648 39. .368 19. .461 1, .00 44, .21 c
ATOM 1964 C LEU c 41 34. .334 39. .029 22. .525 1. .00 46. .09 c
ATOM 1965 O LEU c 41 34. .413 39. .563 23. .642 1. .00 46, .07 o
ATOM 1966 N GLY c 42 35. .345 38. ,988 21. .658 1. .00 46. .41 N
ATOM 1967 CA GLY c 42 36. .662 39. ,511 21. .981 1. .00 46. .86 C
ATOM 1968 C GLY c 42 37. .653 38. ,393 22. .218 1, ,00 47. .32 C
ATOM 1969 O GLY c 42 38. .805 38. ,480 21. .808 1. ,00 47. .49 O
ATOM 1970 N SER c 43 37, .196 37. ,334 22. .875 ι; .00 47. .84 N
ATOM 1971 CA SER c 43 38, .051 36, ,205 23. .232 1, .00 48. .37 C
ATOM 1972 CB SER c 43 37, .381 35, ,356 24, .333 1, .00 48. .73 C
ATOM 1973 OG SER c 43 38, .327 34, ,801 25, .247 1, .00 49. .16 O
ATOM 1974 C SER c 43 38, .353 35, ,339 22, .008 1, .00 48. .25 C
ATOM 1975 O SER c 43 37, .471 35, ,057 21. .198 1, .00 48. .08 O
ATOM 1976 N THR c 44 39. ,608 34. ,932 21. .881 1. .00 48. .32 N
ATOM 1977 CA THR c 44 40. .017 34, ,007 20. .826 1, .00 48. ,49 C
ATOM 1978 CB THR c 44 41. .540 34. ,209 20. ,436 1. ,00 48. ,64 C
ATOM 1979 OGl THR c 44 42. .070 33. ,032 19. .818 1. .00 48. ,40 O
ATOM 1980 CG2 THR c 44 42. ,410 34. ,586 21. ,648 1. ,00 48. ,71 C
ATOM 1981 C THR c 44 39. .665 32. ,550 21. .192 1. .00 48. ,58 C
ATOM 1982 O THR c 44 39. .325 31. ,741 20. ,315 1. ,00 48. ,51 O
ATOM 1983 N ASN c 45 39. .702 32. ,245 22. ,493 1. .00 48. ,49 N
ATOM 1984 CA ASN c 45 39. ,609 30. ,870 22. ,991 1. .00 48. ,39 C
ATOM 1985 CB ASN c 45 40. ,476 30. 692 24. 234 1. 00 48. 45 C
ATOM 1986 CG ASN c 45 41. ,908 30. 257 23. ,900 1. 00 48. ,98 c
ATOM 1987 ODl ASN c 45 42. ,128 29. 275 23. 172 1. 00 50. 20 0
ATOM 1988 ND2 ASN c 45 42. ,884 30. 978 24. ,444 1. 00 47. ,76 N ATOM 1989 c ASN C 45 38,.205 30,,403 23.,290 1,.00 48,.21 c
ATOM 1990 O ASN C 45 37 .398 31, .158 23, .829 1 .00 48, .83 0
ATOM 1991 N GLU C 46 37, .926 29. .153 22, .935 1, .00 47, .64 N
ATOM 1992 CA GLU C 46 36 .613 28, ,541 23, .128 1 .00 47 .23 C
ATOM 1993 CB GLU C 46 36, .369 27. .536 22, .021 1, .00 47, .36 C
ATOM 1994 CG GLU C 46 34, .963 27. ,003 21. .947 1, .00 49. .62 C
ATOM 1995 CD GLU C 46 34, .877 25. ,764 21, .083 1, .00 52, .95 C
ATOM 1996 OEl GLU C 46 35, ,885 25. ,005 21, ,073 1, .00 54, .92 O
ATOM 1997 OE2 GLU C 46 33, .822 25. .558 20, .419 1, .00 52, .26 O
ATOM 1998 C GLU C 46 36, .576 27. .839 24. .480 1, .00 46, ,59 C
ATOM 1999 O GLU C 46 37, .566 27. .244 24, .880 1, .00 46, .90 O
ATOM 2000 N GLN C 47 35, ,442 27. .896 25, ,174 1, ,00 45, ,60 N
ATOM 2001 CA GLN C 47 35, .379 27. .529 26, .589 1, .00 45, .13 c
ATOM 2002 CB GLN C 47 35, .248 28. .810 27, ,441 1, ,00 45, .06 c
ATOM 2003 CG GLN C 47 34, ,469 28. .693 28. ,769 1. .00 46. .54 c
ATOM 2004 CD GLN C 47 34, .892 29. .728 29, .833 1, .00 47, .69 c
ATOM 2005 OEl GLN C 47 35, ,066 29, .383 31. ,013 1, ,00 50. .91 O
ATOM 2006 NE2 GLN c 47 35, .058 30, .998 29, .422 1, .00 50, .13 N
ATOM 2007 C GLN c 47 34, .267 26, ,542 26, ,895 1, ,00 43, ,75 C
ATOM 2008 O GLN c 47 33, .147 26, .682 26, .408 1, .00 43, .68 O
ATOM 2009 N LYS c 48 34, .558 25, .546 27. .717 1, .00 42, .65 N
ATOM 2010 CA LYS c 48 33, .512 24, .584 28. .070 1. ,00 42, .13 C
ATOM 2011 CB LYS c 48 34, .111 23, .260 28. .577 1, .00 42, ,14 C
ATOM 2012 CG LYS c 48 33. .146 22. .080 28. .531 1. .00 42, ,28 C
ATOM 2013 CD LYS c 48 33, .755 20. .854 29, .227 1, .00 42, .97 C
ATOM 2014 CE LYS c 48 32, .995 19. .550 28. .896 1. .00 44, .44 C
ATOM 2015 NZ LYS c 48 31. .730 19. .382 29, .689 1, .00 41, .90 N
ATOM 2016 C LYS c 48 32, .529 25. .167 29, .088 1, .00 40, .86 C
ATOM 2017 O LYS c 48 32. .927 25. ,559 30, .186 1. ,00 41, .16 O
ATOM 2018 N ILE c 49 31. .258 25, ,234 28, .704 1, .00 39, ,24 N
ATOM 2019 CA ILE c 49 30. ,177 25, ,610 29, ,612 1. .00 38, .21 C
ATOM 2020 CB ILE c 49 28, .876 25. .902 28, .832 1, .00 38. .04 C
ATOM 2021 CGI ILE c 49 29, .063 27. .160 27, ,970 1, .00 37. .36 c
ATOM 2022 GDI ILE c 49 27, .998 27, .395 26, .955 1, .00 35, .52 c
ATOM 2023 CG2 ILE c 49 27, .708 26. .058 29, .785 1, .00 37, ,96 c
ATOM 2024 C ILE c 49 29, .946 24, .511 30, ,657 1. .00 37, .86 c
ATOM 2025 O ILE c 49 29, .840 23, .332 30, .336 1, .00 38. ,22 0
ATOM 2026 N SER c 50 29, ,871 24, .893 31, .914 1. .00 36. ,99 N
ATOM 2027 CA SER c 50 29, .823 23, .911 32. .974 1, .00 36. .24 C
ATOM 2028 CB SER c 50 30. .936 24, ,211 33. .985 1. .00 36. ,03 C
ATOM 2029 OG SER c 50 30, ,705 23. ,597 35. .226 1, .00 35. .67 O
ATOM 2030 C SER c 50 28, .423 23. ,953 33. .586 1. .00 36. .12 C
ATOM 2031 O SER c 50 28, .101 24. .893 34. .305 1. .00 36. .47 0
ATOM 2032 N ILE c 51 27, ,604 22, .937 33. ,276 1. .00 35. .77 N
ATOM 2033 CA ILE c 51 26. .161 22. .887 33, .591 1. .00 35. .08 c
ATOM 2034 CB ILE c 51 25. .489 21, ,636 32. ,962 1. .00 34. .76 c
ATOM 2035 CGI ILE c 51 25. .814 21. ,504 31. ,470 1. .00 35. .07 c
ATOM 2036 CD1 ILE c 51 25. .313 22. ,612 30. ,586 1. .00 34, .14 c
ATOM 2037 CG2 ILE c 51 23. .998 21, ,633 33. ,170 1. ,00 34, ,35 c
ATOM 2038 C ILE c 51 25. ,862 22, ,927 35. ,089 1. .00 35. .53 c
ATOM 2039 O ILE c 51 26. ,594 22. ,356 35. ,904 1. .00 36. .01 0
ATOM 2040 N GLY c 52 24. ,764 23. ,590 35. ,433 1. .00 35. ,65 N
ATOM 2041 CA GLY c 52 24. ,432 23. ,962 36. ,802 1, .00 36. ,14 C
ATOM 2042 C GLY c 52 24, ,077 25. ,434 36. ,781 1, ,00 36. ,66 C
ATOM 2043 O GLY c 52 24. ,461 26. ,143 35. ,855 1. .00 37. ,19 O
ATOM 2044 N GLY c 53 23. .337 25. ,905 37. ,775 1. ,00 37. ,19 N
ATOM 2045 CA GLY c 53 23, ,034 27. ,339 37. ,883 1. .00 38. ,04 C
ATOM 2046 C GLY c 53 22. ,202 27. ,937 36. ,755 1. ,00 38. ,59 C
ATOM 2047 O GLY c 53 21. ,063 27. ,520 36. ,526 1. .00 38. .17 O
ATOM 2048 N ARG c 54 22. ,770 28. ,924 36. ,058 1. ,00 39. 36 N
ATOM 2049 CA ARG c 54 22. ,070 29. 587 34. 952 1. ,00 40. 47 C
ATOM 2050 CB ARG c 54 22. ,486 31. ,070 34. ,796 1. ,00 40. 52 C
ATOM 2051 CG ARG c 54 23. ,987 31. 389 34. 836 1. ,00 42. 08 c
ATOM 2052 CD ARG c 54 24. ,603 31. ,668 33. ,450 1. ,00 44. 40 c ATOM 2053 NE ARG C 54 24.062 32,.872 32.798 1.00 45.39 N
ATOM 2054 CZ ARG C 54 24, .681 33, .569 31, .840 1, .00 44 .83 C
ATOM 2055 NHl ARG C 54 25 .889 33, .225 31 .399 1 .00 43 .88 N
ATOM 2056 NH2 ARG C 54 24, .083 34, .626 31 .317 1, .00 44 .61 N
ATOM 2057 C ARG C 54 22 .091 28 .819 33 .612 1, .00 40 .93 C
ATOM 2058 O ARG C 54 21. .457 29, .234 32 .642 1 .00 41 .07 O
ATOM 2059 N TYR C 55 22, .801 27, .699 33, .559 1, .00 41, .75 N
ATOM 2060 CA TYR C 55 22, .718 26, .824 32 .397 1 .00 42 .73 C
ATOM 2061 CB TYR C 55 24, .098 26, .431 31, .892 1, .00 43, .59 C
ATOM 2062 CG TYR C 55 25. .028 27. .569 31. .597 1, ,00 45, .26 c
ATOM 2063 CD1 TYR C 55 25, .972 27, .983 32, .547 1, .00 46, .23 c
ATOM 2064 CEl TYR C 55 26. .853 29. .032 32. .277 1. ,00 47, .06 c
ATOM 2065 CZ TYR c 55 26, .803 29, .669 31. .035 1, .00 47, .17 c
ATOM 2066 OH TYR c 55 27, .678 30. .699 30, .758 1, .00 47, .13 0
ATOM 2067 CE2 TYR c 55 25, .877 29. .270 30. ,072 1, .00 47, ,60 c
ATOM 2068 CD2 TYR c 55 24, .994 28, .220 30, .356 1, .00 46, .94 c
ATOM 2069 C TYR c 55 21, .971 25. .549 32. .739 1, .00 42, ,70 c
ATOM 2070 O TYR c 55 22, .483 24, .719 33, .478 1, .00 42, .39 0
ATOM 2071 N VAL c 56 20, ,765 25. .382 32, .209 1. .00 43, .05 N
ATOM 2072 CA VAL c 56 20, ,072 24. .108 32. .374 1, .00 43, ,44 C
ATOM 2073 CB VAL c 56 18, .679 24, .247 33, .084 1, .00 43, .19 c
ATOM 2074 CGI VAL c 56 18. .404 25, .681 33. .477 1. .00 42, .32 c
ATOM 2075 CG2 VAL c 56 17. .554 23, .658 32, ,252 1, .00 43, .66 c
ATOM 2076 C VAL c 56 20, .073 23. .330 31. ,053 1, .00 43, ,90 c
ATOM 2077 O VAL c 56 19. .914 23. .910 29. .984 1, .00 44, .29 0
ATOM 2078 N GLU c 57 20, ,332 22. .029 31. .134 1, ,00 44, .13 N
ATOM 2079 CA GLU c 57 20. ,446 21. .205 29. .944 1, .00 44, ,49 c
ATOM 2080 CB GLU c 57 21. ,808 20. .522 29. .886 1, ,00 44, ,65 c
ATOM 2081 CG GLU c 57 22, ,020 19, .738 28, .595 1, .00 46, .62 c
ATOM 2082 CD GLU c 57 23, .221 18. .801 28, .631 1, .00 48, .99 c
ATOM 2083 OEl GLU c 57 23, ,449 18, .116 29, .660 1, ,00 50, .79 o
ATOM 2084 OE2 GLU c 57 23, ,929 18. .739 27, .609 1, ,00 48, .49 0
ATOM 2085 C GLU c 57 19, ,371 20. .151 29. .952 1, ,00 44, ,38 c
ATOM 2086 O GLU c 57 19. .189 19. .466 30, .957 1, ,00 44, .68 0
ATOM 2087 N THR c 58 18. .659 20. .008 28. .842 1, .00 44, .32 N
ATOM 2088 CA THR c 58 17. .661 18. .956 28. .754 1, .00 44, .58 C
ATOM 2089 CB THR c 58 16. .228 19. ,474 28. .495 1, .00 44, .59 C
ATOM 2090 OGl THR c 58 15. .977 20. ,647 29. .276 1, ,00 44, .71 o
ATOM 2091 CG2 THR c 58 15. .209 18. .400 28, .881 1, .00 44, .79 c
ATOM 2092 C THR c 58 18. .065 18. ,005 27. .661 1, .00 44, .55 c
ATOM 2093 O THR c 58 18, .231 18. .413 26. .525 1, .00 44, .96 0
ATOM 2094 N VAL c 59 18, .233 16. ,736 28. .016 1, ,00 44, .53 N
ATOM 2095 CA VAL c 59 18, ,661 15. ,736 27. ,054 1. ,00 44, .23 C
ATOM 2096 CB VAL c 59 20, .023 15. .095 27. .445 1, .00 44, .24 C
ATOM 2097 CGI VAL c 59 20. .517 14. .143 26. .360 1, .00 41. .77 C
ATOM 2098 CG2 VAL c 59 21. ,062 16. .196 27. ,706 1. .00 44. ,53 C
ATOM 2099 C VAL c 59 17, .587 14, ,681 26. .850 1. .00 44, .53 c
ATOM 2100 O VAL c 59 16, .892 14. ,274 27. ,784 1, .00 44. ,23 o
ATOM 2101 N ASN c 60 17, .454 14, ,271 25. .594 1. .00 44. .94 N
ATOM 2102 CA ASN c 60 16. .609 13, ,153 25. ,202 1, .00 44, ,74 c
ATOM 2103 CB ASN c 60 15. .389 13. ,655 24, ,428 1. .00 44. ,71 c
ATOM 2104 CG ASN c 60 14, .358 12, ,588 24, ,221 1. .00 45, ,15 c
ATOM 2105 ODl ASN c 60 14. ,689 11. ,424 24. ,010 1. .00 45. ,39 0
ATOM 2106 ND2 ASN c 60 13. ,085 12. ,974 24. ,284 1. ,00 46. ,47 N
ATOM 2107 C ASN c 60 17. ,438 12. ,204 24. ,346 1. ,00 44. ,60 C
ATOM 2108 O ASN c 60 17. ,329 12. ,215 23. ,106 1. ,00 44. ,87 O
ATOM 2109 N LYS c 61 18. ,315 11. ,434 25. ,004 1. ,00 44. ,25 N
ATOM 2110 CA LYS c 61 18. ,902 10. ,245 24. ,388 1. ,00 43. ,60 C
ATOM 2111 CB LYS c 61 19. 676 9. 391 25. ,396 1. 00 42. 97 C
ATOM 2112 CG LYS c 61 20. ,685 10. ,109 26. ,240 1. ,00 41. 15 C
ATOM 2113 CD LYS c 61 21. 355 9. 167 27. ,219 1. 00 36. 07 C
ATOM 2114 CE LYS c 61 22. ,521 9. ,853 27. ,842 1. ,00 33. 75 C
ATOM 2115 NZ LYS c 61 22. 941 9. 168 29. ,069 1. 00 33. 84 N
ATOM 2116 C LYS c 61 17. 678 9. 457 23. ,981 1. 00 44. 03 C ATOM 2117 O LYS C 61 16,.789 9,.233 24.809 1.00 45.15 o
ATOM 2118 N GLY C 62 17, .578 9, .052 22, .733 1, .00 43 .61 N
ATOM 2119 CA GLY c 62 16, .386 8, .324 22 .349 1 .00 43 .74 C
ATOM 2120 C GLY c 62 15, ,924 8, .921 21, .068 1, .00 43, .99 C
ATOM 2121 O GLY c 62 15, .804 8, .220 20 .077 1 .00 44 .34 O
ATOM 2122 N SER c 63 15, ,682 10. .226 21, .085 1, .00 44, .18 N
ATOM 2123 CA SER c 63 15, .540 10, .990 19, .854 1, .00 44, .37 C
ATOM 2124 CB SER c 63 14, .384 11, ,981 19, .985 1, .00 44, .33 C
ATOM 2125 OG SER c 63 14, .601 12, ,876 21, .053 1. .00 45, ,03 O
ATOM 2126 C SER c 63 16, .865 11, .692 19, .512 1, .00 44, .34 C
ATOM 2127 O SER c 63 16, .941 12, .475 18. .573 1, .00 44, ,35 O
ATOM 2128 N LYS c 64 17, .910 11, .374 20, .278 1, .00 44, .70 N
ATOM 2129 CA LYS c 64 19, .263 11, .956 20. .120 1. .00 44, .84 C
ATOM 2130 CB LYS c 64 20, ,001 11, .365 18. .913 1, .00 44, .66 C
ATOM 2131 CG LYS c 64 20, ,685 10. ,054 19, .177 1, .00 43. .38 C
ATOM 2132 CD LYS c 64 20. ,732 9. .199 17, .938 1. .00 40, .42 C
ATOM 2133 CE LYS c 64 20. ,708 7. .747 18, .313 1, .00 39, ,27 C
ATOM 2134 NZ LYS c 64 20. .923 6. .914 17, .106 1, .00 40, .81 N
ATOM 2135 C LYS c 64 19. ,224 13. .475 20, .021 1, .00 45. .39 C
ATOM 2136 O LYS c 64 19. ,916 14. .079 19, .195 1. .00 45, .63 O
ATOM 2137 N SER c 65 18. ,391 14. .092 20, .853 1, .00 45. .61 N
ATOM 2138 CA SER c 65 18. .313 15. .543 20, .860 1. .00 45, .22 C
ATOM 2139 CB SER c 65 17. .015 16. .014 20. .197 1, ,00 45. .32 C
ATOM 2140 OG SER c 65 15. .940 15, .981 21, ,107 1. .00 45, .97 O
ATOM 2141 C SER c 65 18. .483 16, .105 22. .275 1, .00 44. .72 C
ATOM 2142 O SER c 65 18. .097 15, .479 23, .274 1, .00 44, .33 0
ATOM 2143 N PHE c 66 19. .082 17, .285 22. .341 1. .00 44. .16 N
ATOM 2144 CA PHE c 66 19. .394 17, .928 23, .606 1, .00 43. .60 C
ATOM 2145 CB PHE c 66 20. ,721 17, ,387 24. .160 1, .00 44. .01 c
ATOM 2146 CG PHE c 66 21. .873 17, .540 23, .220 1, .00 44, .66 c
ATOM 2147 GDI PHE c 66 22, ,961 18, .342 23, .571 1, ,00 46, ,00 c
ATOM 2148 CEl PHE c 66 24, .045 18, .504 22, .703 1, .00 47, .22 c
ATOM 2149 CZ PHE c 66 24, .025 17. .865 21, .454 1, ,00 47, ,14 c
ATOM 2150 CE2 PHE c 66 22, ,922 17. ,064 21, .084 1, .00 45. .67 c
ATOM 2151 CD2 PHE c 66 21, ,866 16. .904 21, .974 1, .00 45. .23 c
ATOM 2152 C PHE c 66 19, ,448 19. .431 23, .413 1, .00 42. .65 c
ATOM 2153 O PHE c 66 19, ,643 19, .916 22, .290 1, ,00 41, ,90 0
ATOM 2154 N SER c 67 19. ,265 20, .164 24. .508 1, .00 42, ,04 N
ATOM 2155 CA SER c 67 19, ,212 21, .634 24, .453 1. .00 41, .52 C
ATOM 2156 CB SER c 67 17, ,773 22, .110 24. .283 1. .00 41, ,21 c
ATOM 2157 OG SER c 67 17, ,141 22, .180 25. .545 1, .00 41, .07 0
ATOM 2158 C SER c 67 19. ,821 22. .316 25. ,671 1, .00 40, .87 c
ATOM 2159 O SER c 67 19, ,828 21, .765 26. .756 1, .00 40, .62 0
ATOM 2160 N LEU c 68 20, ,314 23. .528 25. ,474 1. .00 40, .64 N
ATOM 2161 CA LEU c 68 20, ,846 24. .326 26. .563 1, ,00 41, .10 C
ATOM 2162 CB LEU c 68 22. ,261 24, .794 26. .222 1. ,00 40, .90 C
ATOM 2163 CG LEU c 68 22, ,953 25, .633 27. ,287 1, .00 40, .77 C
ATOM 2164 CD1 LEU c 68 23. ,220 24. .788 28, .519 1. .00 40, .99 C
ATOM 2165 CD2 LEU c 68 24, ,238 26. .207 26, .730 1, .00 41, .39 c
ATOM 2166 C LEU c 68 19, ,965 25, .529 26, .797 1. .00 41. .39 c
ATOM 2167 O LEU c 68 19. .555 26. .174 25, .862 1, .00 41. .94 0
ATOM 2168 N ARG c 69 19. ,657 25, ,835 28, .038 1. .00 42. ,12 N
ATOM 2169 CA ARG c 69 18. .930 27. .057 28, .318 1, .00 43, ,31 C
ATOM 2170 CB ARG c 69 17. ,610 26. ,778 29. .037 1. .00 43. ,32 C
ATOM 2171 CG ARG c 69 16. ,830 28, .037 29. ,423 1, .00 43. ,69 C
ATOM 2172 CD ARG c 69 15. ,456 27. ,700 29, ,985 1. ,00 44. ,45 C
ATOM 2173 NE ARG c 69 14. ,953 28. .792 30, ,821 1. ,00 49. ,97 N
ATOM 2174 CZ ARG c 69 13. 979 29. ,651 30. ,485 1. ,00 52. ,04 C
ATOM 2175 NHl ARG c 69 13. .348 29. .550 29. .313 1. ,00 52. ,62 N
ATOM 2176 NH2 ARG c 69 13. 619 30. .613 31. ,337 1. ,00 51. 20 N
ATOM 2177 C ARG c 69 19. 820 27. 926 29. 177 1. 00 43. ,74 C
ATOM 2178 O ARG c 69 20. 365 27. 445 30. 181 1. 00 43. 66 O
ATOM 2179 N ILE c 70 19. 986 29. 190 28. 775 1. 00 44. 17 N
ATOM 2180 CA ILE c 70 20. 771 30. 139 29. 568 1. 00 44. 24 C ATOM 2181 CB ILE C 70 21,.924 30,.764 28.766 1.00 44.29 c
ATOM 2182 CGI ILE C 70 22, .500 29, .748 27, .767 1, .00 44 .55 c
ATOM 2183 CD1 ILE C 70 23, .618 30, .268 26 .893 1, .00 44 .09 c
ATOM 2184 CG2 ILE C 70 22, .985 31. .293 29, .727 1, .00 44, .12 c
ATOM 2185 C ILE C 70 19, .888 31, .247 30 .090 1, .00 44 .26 c
ATOM 2186 O ILE C 70 19, .388 32. .025 29, .305 1, .00 44, .12 0
ATOM 2187 N ARG C 71 19, .689 31, ,296 31, .406 1, .00 44, .56 N
ATOM 2188 CA ARG C 71 18, .986 32. .406 32, .067 1, .00 45, .41 C
ATOM 2189 CB ARG C 71 18, .490 31. .964 33. .444 1, .00 46. .04 C
ATOM 2190 CG ARG C 71 17. .001 31. .601 33, .524 1. .00 49, .75 c
ATOM 2191 CD ARG C 71 16. .720 30. .125 33. .165 1, .00 54. .75 c
ATOM 2192 NE ARG C 71 17. .547 29. .154 33, .902 1, .00 58, .55 N
ATOM 2193 CZ ARG C 71 17. .526 28. .965 35. .227 1, .00 60. ,09 C
ATOM 2194 NHl ARG C 71 18. .324 28. .047 35, .771 1. .00 60, .34 N
ATOM 2195 NH2 ARG C 71 16. .729 29. .700 36, .014 1, .00 60. .07 N
ATOM 2196 C ARG C 71 19. .818 33. .693 32, .251 1, .00 45. .00 C
ATOM 2197 O ARG C 71 21. ,059 33. .651 32, .249 1, ,00 44. .88 O
ATOM 2198 N ASP c 72 19. .118 34. .823 32, ,420 1, .00 44. ,67 N
ATOM 2199 CA ASP c 72 19. .710 36. .111 32, .831 1. ,00 44. ,50 C
ATOM 2200 CB ASP c 72 20. .197 36. .015 34, .283 1, .00 44. .75 C
ATOM 2201 CG ASP c 72 20. .246 37, .369 34, .988 1. .00 47. .01 C
ATOM 2202 ODl ASP c 72 20. .443 37, .358 36. .224 1, .00 49. .08 O
ATOM 2203 OD2 ASP c 72 20. .089 38, .440 34. .337 1. .00 48. .36 O
ATOM 2204 C ASP c 72 20. .829 36, .639 31. .906 1, .00 43. .99 C
ATOM 2205 O ASP c 72 21. .917 36, .997 32. .360 1. .00 43. .48 0
ATOM 2206 N LEU c 73 20. ,536 36, .697 30. .612 1, .00 43. .65 N
ATOM 2207 CA LEU c 73 21. ,500 37. .109 29. .608 1, .00 43. .40 c
ATOM 2208 CB LEU c 73 20. .887 36. .973 28, .222 1, .00 43. .00 c
ATOM 2209 CG LEU c 73 20. .582 35. .582 27. .701 1, .00 42. .57 c
ATOM 2210 CD1 LEU c 73 19. .672 35. .690 26, .497 1, .00 42. .05 c
ATOM 2211 CD2 LEU c 73 21. .878 34. .850 27. .348 1, .00 42. .76 c
ATOM 2212 C LEU c 73 21, ,970 38. .546 29, .785 1, .00 43, .85 c
ATOM 2213 O LEU c 73 21. .148 39. .456 29. .963 1, .00 44. .05 0
ATOM 2214 N ARG c 74 23. ,288 38. ,744 29. .738 1, ,00 44. ,09 N
ATOM 2215 CA ARG c 74 23. .878 40. .083 29. .681 1, ,00 44. .58 C
ATOM 2216 CB ARG c 74 24. .739 40. .384 30. .906 1, ,00 45, .11 C
ATOM 2217 CG ARG c 74 24. .366 39, .609 32. .152 1, .00 48, .62 C
ATOM 2218 CD ARG c 74 25. .269 38, .395 32. ,294 1, .00 54, .44 c
ATOM 2219 NE ARG c 74 24. .804 37, .482 33. .336 1, .00 59, .52 N
ATOM 2220 CZ ARG c 74 25. .390 36, .322 33. .637 1. .00 62, .37 C
ATOM 2221 NHl ARG c 74 26. ,477 35, .920 32. .979 1, .00 63, .92 N
ATOM 2222 NH2 ARG c 74 24. ,877 35, .550 34. ,589 1. .00 62, .66 N
ATOM 2223 C ARG c 74 24. ,720 40, .168 28, ,423 1. .00 43. .88 C
ATOM 2224 O ARG c 74 25. .009 39, .136 27, ,822 1, .00 43, .92 O
ATOM 2225 N VAL c 75 25. .100 41, .389 28, .028 1. .00 43. .11 N
ATOM 2226 CA VAL c 75 25. .871 41, .629 26, .797 1. .00 42. .05 C
ATOM 2227 CB VAL c 75 26. .188 43. .144 26, .576 1. .00 42, .25 C
ATOM 2228 CGI VAL c 75 24. .909 43, .964 26. .518 1. .00 41. .91 C
ATOM 2229 CG2 VAL c 75 27. .026 43, .369 25, .298 1. .00 42. .12 C
ATOM 2230 C VAL c 75 27. .152 40. .794 26. .807 1. ,00 41, .41 C
ATOM 2231 O VAL c 75 27. ,569 40, .274 25. .766 1. ,00 41. .57 O
ATOM 2232 N GLU c 76 27, ,742 40. .634 27. .990 1. ,00 40. .22 N
ATOM 2233 CA GLU c 76 28, ,939 39. .824 28. ,146 1, ,00 39, ,57 C
ATOM 2234 CB GLU c 76 29, .438 39. .893 29. ,583 1. ,00 39. ,22 C
ATOM 2235 CG GLU c 76 28, .705 38. .991 30, ,548 1, ,00 38. ,56 C
ATOM 2236 CD GLU c 76 29. .132 39. ,200 31. ,985 1, ,00 37. ,76 C
ATOM 2237 OEl GLU c 76 28, .491 38. ,596 32, ,881 1, ,00 37. .15 O
ATOM 2238 OE2 GLU c 76 30, ,098 39. ,971 32, ,217 1, ,00 36. ,57 O
ATOM 2239 C GLU c 76 28. .770 38. ,353 27. ,706 1. .00 39. ,68 C
ATOM 2240 O GLU c 76 29. ,759 37. ,642 27. ,548 1. ,00 39. 67 0
ATOM 2241 N ASP c 77 27. ,529 37. ,906 27. ,511 1. 00 39. 47 N
ATOM 2242 CA ASP c 77 27. ,264 36. ,553 27. ,029 1. ,00 39. 18 C
ATOM 2243 CB ASP c 77 25. ,975 36. 015 27. 621 1. 00 39. 36 C
ATOM 2244 CG ASP c 77 26. ,069 35. ,792 29. ,095 1. 00 40. 54 C ATOM 2245 ODl ASP C 77 27..103 35..279 29..564 1,.00 43,.00 0
ATOM 2246 OD2 ASP C 77 25. .097 36. .120 29. .795 1, ,00 42, .29 0
ATOM 2247 C ASP C 77 27. .187 36. .459 25. .510 1, .00 38, .97 c
ATOM 2248 O ASP C 77 26. .956 35. .371 24. .969 1, ,00 38, .86 0
ATOM 2249 N SER C 78 27. .362 37. .590 24. .823 1, .00 38, .67 N
ATOM 2250 CA SER C 78 27. .479 37. ,581 23. .362 1, .00 38. .39 c
ATOM 2251 CB SER c 78 27. .564 38. .997 22. .814 1, .00 38, .08 c
ATOM 2252 OG SER c 78 26. .390 39. .703 23. .145 1. ,00 37. .55 0
ATOM 2253 C SER c 78 28. .691 36. .771 22. ..905 1, .00 38, .40 c
ATOM 2254 O SER c 78 29. ,781 36. .858 23. .489 1, .00 38. .36 0
ATOM 2255 N GLY c 79 28. ,490 35. ,973 21, ,867 1. .00 38. .28 N
ATOM 2256 CA GLY c 79 29. ,555 35, ,151 21, ,334 1. .00 38. .15 C
ATOM 2257 C GLY c 79 28, .959 33, ,959 20. ,654 1. .00 38. .36 C
ATOM 2258 O GLY c 79 27, .741 33, .866 20. ,490 1. .00 38. .35 O
ATOM 2259 N THR c 80 29, .823 33, ,041 20. .249 1. .00 38. .98 N
ATOM 2260 CA THR c 80 29, .392 31, .847 19. ,538 1. .00 39, ,37 C
ATOM 2261 CB THR c 80 30, .273 31. .554 18, ,304 1. .00 39, ,13 C
ATOM 2262 OGl THR c 80 30. .166 32, .641 17, .377 1, ,00 38, ,93 O
ATOM 2263 CG2 THR c 80 29. .814 30. .290 17. ,600 1. ,00 39, ,77 C
ATOM 2264 C THR c 80 29. .366 30. .674 20, .496 1. .00 39, .89 C
ATOM 2265 O THR c 80 30. .323 30, ,457 21. ,243 1. .00 40, .12 O
ATOM 2266 N TYR c 81 28. .245 29. .946 20. .463 1. .00 40, .31 N
ATOM 2267 CA TYR c 81 27. .987 28. .748 21. ,270 1. .00 40, .42 C
ATOM 2268 CB TYR c 81 26. .673 28. .921 22. .051 1. .00 40, .48 C
ATOM 2269 CG TYR c 81 26. .736 29. ,991 23. ,111 1. .00 40, .67 c
ATOM 2270 GDI TYR c 81 26, ,667 29, .655 24. .463 1. .00 39, .50 c
ATOM 2271 CEl TYR c 81 26, .752 30, .623 25. .444 1. .00 38, .60 c
ATOM 2272 CZ TYR c 81 26. .911 31. .954 25. .085 1, .00 40. .20 c
ATOM 2273 OH TYR c 81 26. ,993 32. .905 26. .065 1. .00 41. .07 0
ATOM 2274 CE2 TYR c 81 26, ,992 32. .330 23, .753 1, .00 40, .63 c
ATOM 2275 CD2 TYR c 81 26. .905 31. .344 22. .767 1, ,00 41. ,34 c
ATOM 2276 C TYR c 81 27, .887 27. .500 20, .384 1, .00 40, .61 c
ATOM 2277 O TYR c 81 27. .270 27. .534 19, .317 1. ,00 40. ,48 0
ATOM 2278 N LYS c 82 28, .486 26. .400 20, .830 1, .00 40, .98 N
ATOM 2279 CA LYS c 82 28. .456 25. ,142 20, .082 1, .00 41. .31 C
ATOM 2280 CB LYS c 82 29, .769 24. ,890 19. .354 1, .00 40, .81 c
ATOM 2281 CG LYS c 82 29, .929 25. .735 18. .144 1, .00 41. ,85 c
ATOM 2282 CD LYS c 82 31, .152 25. .386 17. .339 1. ,00 42. ,31 c
ATOM 2283 CE LYS c 82 31, .591 26. .597 16, ,549 1. .00 42. .93 c
ATOM 2284 NZ LYS c 82 32, .191 26. .236 15, ,242 1, .00 45. ,16 N
ATOM 2285 C LYS c 82 28, .209 23. .989 21, ,020 1. .00 42. ,03 C
ATOM 2286 O LYS c 82 28, .641 24. .009 22, .173 1. .00 42. ,66 O
ATOM 2287 N CYS c 83 27, .522 22. .976 20, .513 1. .00 42. .37 N
ATOM 2288 CA CYS c 83 27, .318 21. .760 21, .230 1. .00 42. .93 C
ATOM 2289 CB CYS c 83 25, ,854 21. .368 21. .137 1. .00 43. .61 C
ATOM 2290 SG CYS c 83 25, .278 21. .291 19. .462 1. .00 48, ,55 S
ATOM 2291 C CYS c 83 28, .179 20. ,680 20. .613 1, .00 42, ,42 C
ATOM 2292 O CYS c 83 28, .563 20. ,766 19, ,447 1. .00 41, ,85 O
ATOM 2293 N GLY c 84 28, ,480 19. .664 21, .418 1, .00 42, ,34 N
ATOM 2294 CA GLY c 84 29, ,137 18. .459 20, .952 1. .00 41, ,90 C
ATOM 2295 C GLY c 84 28, .389 17. ,233 21, .437 1. .00 41, .74 C
ATOM 2296 O GLY c 84 28, .168 17. ,077 22, .622 1. .00 41, .50 O
ATOM 2297 N ALA c 85 28. .009 16. .359 20, .510 1, ,00 42, .01 N
ATOM 2298 CA ALA c 85 27. .327 15. .111 20, .825 1, .00 42, .63 C
ATOM 2299 CB ALA c 85 26. ,066 14. .957 19, .949 1, .00 41, .98 C
ATOM 2300 C ALA c 85 28. .298 13. .972 20, ,576 1. .00 43, .38 C
ATOM 2301 O ALA c 85 28. .840 13, ,859 19. .484 1. .00 43, .85 O
ATOM 2302 N TYR c 86 28. ,538 13. ,138 21. .580 1, .00 44. .65 N
ATOM 2303 CA TYR c 86 29. .488 12. ,036 21. .454 1, .00 46, .09 C
ATOM 2304 CB TYR c 86 30, .651 12. ,223 22. .446 1, .00 47, ,37 C
ATOM 2305 CG TYR c 86 31. .336 13. .560 22. .219 1. .00 49, .85 C
ATOM 2306 CD1 TYR c 86 32, .450 13. .669 21. ,367 1. ,00 52. ,79 C
ATOM 2307 CEl TYR c 86 33, ,072 14. ,925 21. ,103 1. ,00, 53. ,92 C
ATOM 2308 CZ TYR c 86 32. ,554 16. ,087 21. ,694 1. ,00 53. ,39 C ATOM 2309 OH TYR C 86 33,.154 17,.324 21,.465 1,.00 52,.01 0
ATOM 2310 CE2 TYR C 86 31, .438 15, .995 22, .552 1, .00 53, .89 c
ATOM 2311 CD2 TYR c 86 30, .838 14. .734 22, .804 1, .00 52, .16 c
ATOM 2312 C TYR c 86 28. .726 10. .721 21, .616 1. .00 46, .42 c
ATOM 2313 O TYR c 86 27, .858 10, .622 22, .476 1, .00 46, .61 0
ATOM 2314 N PHE c 87 29. .009 9. ,738 20, .760 1. .00 46. .89 N
ATOM 2315 CA PHE c 87 28. .226 8, .492 20, .697 1, .00 47, .55 C
ATOM 2316 CB PHE c 87 27. .264 8. .519 19. .513 1. .00 46. .60 C
ATOM 2317 CG PHE c 87 27. .872 9. .054 18, .263 1, .00 45, ,28 C
ATOM 2318 CD1 PHE c 87 27. ,886 10. .413 18. .012 1. .00 44. ,33 C
ATOM 2319 CEl PHE c 87 28, .459 10. ,907 16, .867 1, .00 43. .16 c
ATOM 2320 CZ PHE c 87 29, .027 10. .041 15. .963 1. .00 43. .21 c
ATOM 2321 CE2 PHE c 87 29, .017 8. .699 16, .203 1, .00 42, .62 c
ATOM 2322 CD2 PHE c 87 28. .445 8. ,208 17. .344 1. .00 43, .83 c
ATOM 2323 C PHE c 87 29. .105 7, .274 20. .573 1. .00 49, .03 c
ATOM 2324 O PHE c 87 30, .146 7. .331 19. .944 1. .00 49, ,13 0
ATOM 2325 N SER c 88 28, .684 6. .162 21, ,157 1. ,00 51, ,17 N
ATOM 2326 CA SER c 88 29. .484 4. .956 21. .068 1. .00 53, ,66 c
ATOM 2327 CB SER c 88 30. .316 4. .764 22, ,341 1. ,00 53, .69 c
ATOM 2328 OG SER c 88 31. ,025 3. ,521 22. ,304 1. ,00 54, .67 0
ATOM 2329 C SER c 88 28. ,667 3. .707 20. .792 1. .00 55, .16 c
ATOM 2330 0 SER c 88 27. ,476 3. .658 21. .088 1. .00 55. .08 o
ATOM 2331 N ASP c 89 29. ,326 2. .710 20. .206 1. .00 57. .59 N
ATOM 2332 CA ASP c 89 28. ,792 1. .345 20. ,138 1. .00 60, .14 C
ATOM 2333 CB ASP c 89 29. .255 0. .596 18, .860 1. .00 60, .31 C TOM 2334 CG ASP c 89 30. .771 0, .736 18, .578 1. .00 60. .98 c
ATOM 2335 ODl ASP c 89 31. .489 -0. .289 18, .629 1. .00 60. .55 0
ATOM 2336 OD2 ASP c 89 31. .242 1. .864 18. ,295 1. .00 61. .88 o
ATOM 2337 C ASP c 89 29. .230 0, .615 21, .407 1. .00 61. .54 c
ATOM 2338 O ASP c 89 30. .423 0. .368 21, .598 1. .00 61. .77 0
ATOM 2339 N ALA c 90 28. .262 0, ,298 22, .270 1. .00 63, .36 N
ATOM 2340 CA ALA c 90 28. .512 -0. .238 23, .625 1, .00 65, .20 c
ATOM 2341 CB ALA c 90 27. .406 -1. .231 24, .018 1. .00 65, .05 c
ATOM 2342 C ALA c 90 29. .919 -0. .852 23, ,843 1. ,00 66. ,45 c
ATOM 2343 O ALA c 90 30. ,731 -0. .331 24, .634 1. .00 66. .70 0
ATOM 2344 N MET c 91 30. ,199 -1. .945 23, ,131 1, .00 67. ,72 N
ATOM 2345 CA MET c 91 31. .524 -2. .562 23, .135 1, .00 68, .99 C
ATOM 2346 CB MET c 91 31. ,458 -4, ,008 22, .613 1, ,00 69. .19 C
ATOM 2347 CG MET c 91 32. .749 -4. .832 22. ,774 1, .00 70, .93 C
ATOM 2348 SD MET c 91 33. .834 -4. ,849 21. ,310 1, ,00 74. .22 S
ATOM 2349 CE MET c 91 35. .173 -3. .747 21. .787 1, ,00 74. .42 c
ATOM 2350 C MET c 91 32. ,507 -1. .714 22. .319 1. ,00 69. .40 c
ATOM 2351 O MET c 91 32. .507 -1. .744 21. .080 1, ,00 69, .57 0
ATOM 2352 N SER c 92 33. .308 -0. ,929 23. .035 1, .00 69, .79 N
ATOM 2353 CA SER c 92 34. .469 -0. ,223 22. .475 1. .00 70. .05 C
ATOM 2354 CB SER c 92 34, .066 0. .939 21, ,541 1, ,00 69, .93 c
ATOM 2355 OG SER c 92 32, .806 1. .491 21, .881 1, ,00 70. .35 0
ATOM 2356 C SER c 92 35, .356 0, ,249 23, .627 1, ,00 70, .02 c
ATOM 2357 O SER c 92 36, .583 0. ,306 23, .506 1, ,00 70, .09 0
ATOM 2358 N ASN c 93 34, .704 0. .541 24. .750 1, .00 70. .00 N
ATOM 2359 CA ASN c 93 35, .333 1, .018 25. .993 1, ,00 69, .95 c
ATOM 2360 CB ASN c 93 36, .362 0. .031 26. .561 1, .00 69. .90 c
ATOM 2361 CG ASN c 93 36, ,387 0. .021 28. ,090 1, .00 69. ,71 c
ATOM 2362 ODl ASN c 93 37, ,241 -0. .629 28, .699 1, .00 69. ,74 0
ATOM 2363 ND2 ASN c 93 35. ,444 0, .729 28. .715 1. ,00 68. ,27 N
ATOM 2364 C ASN c 93 35. ,884 2. .439 25, .943 1, ,00 69. ,86 C
ATOM 2365 O ASN c 93 36. ,587 2, .838 25. ,004 1. ,00 69. ,97 O
ATOM 2366 N TYR c 94 35. ,549 3. .185 26. ,993 1. ,00 69. ,43 N
ATOM 2367 CA TYR c 94 35. ,704 4. ,627 27. ,041 1. 00 68. 88 C
ATOM 2368 CB TYR c 94 34. ,510 5, .236 27. ,776 1. ,00 69. 45 C
ATOM 2369 CG TYR c 94 33. 164 4. ,883 27. ,172 1. 00 70. 37 C
ATOM 2370 CD1 TYR c 94 32. ,364 5. ,872 26. ,584 1. 00 71. 10 C
ATOM 2371 CEl TYR c 94 31. 121 5. 562 26. 038 1. 00 71. 14 C
ATOM 2372 CZ TYR c 94 30. ,669 4. ,244 26. ,062 1. 00 71. 31 C ATOM 2373 OH TYR C 94 29..439 3..939 25.516 1,.00 71.43 0
ATOM 2374 CE2 TYR C 94 31. .448 3. .238 26, .634 1, .00 71 .20 c
ATOM 2375 CD2 TYR C 94 32. .684 3. .563 27 .190 1, .00 70 .47 c
ATOM 2376 C TYR C 94 37. .018 5. .019 27, .706 1, .00 68 .05 c
ATOM 2377 0 TYR C 94 37. .054 5, .864 28 .607 1, .00 67 .95 o
ATOM 2378 N SER C 95 38. .092 4. .370 27, .262 1, .00 67 .01 N
ATOM 2379 CA SER C 95 39. .454 4, .775 27 .598 1, .00 65 .81 C
ATOM 2380 CB SER C 95 40. .366 3. .558 27, .764 1, .00 65, .66 C
ATOM 2381 OG SER C 95 39. .725 2. .552 28, .519 1, .00 65 .34 O
ATOM 2382 C SER C 95 39. .966 5. .672 26, .471 1. ,00 64, .95 C
ATOM 2383 O SER C 95 40. .638 6. .676 26, .716 1, .00 65 .24 0
ATOM 2384 N TYR C 96 39. .641 5. .301 25, .234 1. ,00 63, .43 N
ATOM 2385 CA TYR C 96 40. .027 6. ,088 24, .083 1, .00 61, .77 c
ATOM 2386 CB TYR C 96 40. .629 5. .210 22, .985 1. ,00 62, .04 c
ATOM 2387 CG TYR c 96 42. .014 4. .706 23, .347 1, .00 62, .12 c
ATOM 2388 CD1 TYR c 96 43. .086 5. .598 23, .492 1. .00 62, .12 c
ATOM 2389 CEl TYR c 96 44. .360 5. .147 23, .841 1, .00 62, .47 c
ATOM 2390 CZ TYR c 96 44. .572 3. .786 24, .046 1. .00 62, ,64 c
ATOM 2391 OH TYR c 96 45. .834 3. .324 24, .384 1, .00 62, .52 0
ATOM 2392 CE2 TYR c 96 43. .517 2. .882 23, .907 1. ,00 62, ,40 c
ATOM 2393 CD2 TYR c 96 42. .249 3. .347 23, .564 1, .00 61, .75 c
ATOM 2394 C TYR c 96 38. .817 6. .849 23. .608 1. .00 60, .49 c
ATOM 2395 O TYR c 96 37. .695 6. .345 23, ,720 1. .00 60, .66 o
ATOM 2396 N PRO c 97 39. .038 8. .077 23, .094 1. .00 59, .03 N
ATOM 2397 CA PRO c 97 37. .958 8, .995 22, .751 1. .00 57, .45 c
ATOM 2398 CB PRO c 97 38. .693 10. .221 22, .199 1. .00 57. .62 c
ATOM 2399 CG PRO c 97 40. .034 9. .721 21, .798 1, .00 58, .56 c
ATOM 2400 CD PRO c 97 40. .359 8. ,663 22, .798 1. .00 59. .07 c
ATOM 2401 C PRO c 97 36. .994 8. .426 21, .718 1, .00 55, .87 c
ATOM 2402 O PRO c 97 37. .393 7. .996 20, .634 1. ,00 55, .50 0
ATOM 2403 N ILE c 98 35. .723 8, ,421 22, .096 1, .00 54, .16 N
ATOM 2404 CA ILE c 98 34. .623 8. .020 21, .222 1. .00 52, .19 c
ATOM 2405 CB ILE c 98 33. .325 7. ,702 22, .058 1, .00 52, .52 c
ATOM 2406 CGI ILE c 98 32. .930 8. .888 22, .953 1. .00 51, .84 c
ATOM 2407 CD1 ILE c 98 31. .665 8. .676 23, .761 1, .00 51, ,89 c
ATOM 2408 CG2 ILE c 98 33. ,536 6. .406 22. .894 1. .00 53. ,12 c
ATOM 2409 C ILE c 98 34. .371 9. .087 20. .141 1, .00 50, .11 c
ATOM 2410 O ILE c 98 34. .661 10. .264 20. .364 1. ,00 49. .77 0
ATOM 2411 N PRO c 99 33. .874 8. .671 18, .954 1. .00 48, .00 N
ATOM 2412 CA PRO c 99 33, ,470 9. .652 17. ,944 1. .00 46. .52 C
ATOM 2413 CB PRO c 99 32, .852 8. .782 16. .836 1. .00 46. .16 C
ATOM 2414 CG PRO c 99 32. .689 7, .435 17. .411 1. .00 46. ,14 C
ATOM 2415 CD PRO c 99 33. .698 7, .291 18. .470 1. .00 47, ,41 c
ATOM 2416 C PRO c 99 32. .465 10, .715 18. .468 1. ,00 45. ,21 c
ATOM 2417 O PRO c 99 31. .867 10, .534 19. ,526 1. .00 44. ,67 0
ATOM 2418 N GLY c 100 32. ,312 11, ,816 17, ,733 1. .00 43. ,96 N
ATOM 2419 CA GLY c 100 31, ,368 12, .871 18, .082 1, .00 42. ,29 C
ATOM 2420 C GLY c 100 31, ,376 13, .977 17, ,049 1. .00 41. .74 C
ATOM 2421 O GLY c 100 32, ,229 13, .994 16, .162 1, .00 41. ,65 O
ATOM 2422 N GLU c 101 30. .427 14. ,900 17. ,162 1, .00 41, .32 N
ATOM 2423 CA GLU c 101 30, .302 16. ,039 16, .238 1, .00 41. .63 C
ATOM 2424 CB GLU c 101 29. .265 15. ,742 15. .137 1, .00 41. .77 C
ATOM 2425 CG GLU c 101 29. .525 14, ,511 14, .274 1. .00 42, .85 C
ATOM 2426 CD GLU c 101 30, .562 14. .728 13, .171 1, .00 44. .72 C
ATOM 2427 OEl GLU c 101 30. ,820 15, .899 12, .792 1. .00 46. .56 O
ATOM 2428 OE2 GLU c 101 31. ,107 13. .715 12. .671 1, .00 43, .10 O
ATOM 2429 C GLU c 101 29. ,874 17. ,319 16. ,981 1, ,00 41. ,54 C
ATOM 2430 O GLU c 101 29. ,267 17. ,249 18. .056 1, ,00 41. ,68 O
ATOM 2431 N LYS c 102 30. 163 18. ,483 16. ,402 1. ,00 41. ,21 N
ATOM 2432 CA LYS c 102 29. ,770 19. ,770 16. ,988 1. ,00 40. ,46 C
ATOM 2433 CB LYS c 102 30. 967 20. ,706 17. ,088 1. 00 40. 30 C
ATOM 2434 CG LYS c 102 32. 213 20. ,088 17. ,663 1. ,00 39. 49 c
ATOM 2435 CD LYS c 102 32. 482 20. 613 19. 048 1. 00 41. 83 c
ATOM 2436 CE LYS c 102 33. 185 21. ,983 19. 030 1. 00 42. 84 c ATOM 2437 NZ LYS C 102 34..685 21..860 19..033 1.,00 43,.61 N
ATOM 2438 C LYS C 102 28. .754 20. .404 16. .071 1. ,00 40. .70 C
ATOM 2439 O LYS C 102 28. .812 20. .218 14. .849 1. .00 40. .87 O
ATOM 2440 N GLY C 103 27. .818 21. .152 16. .645 1. .00 40. .80 N
ATOM 2441 CA GLY c 103 26. .904 21. .976 15. ,847 1. .00 40. .56 C
ATOM 2442 C GLY c 103 27. .714 23. .051 15. .128 1. .00 40. .72 C
ATOM 2443 O GLY c 103 28. .852 23. .346 15, .515 1. .00 41. .01 0
ATOM 2444 N ALA c 104 27. .147 23. .618 14. .066 1. .00 40. .34 N
ATOM 2445 CA ALA c 104 27. .760 24. .720 13. .340 1. .00 39. .68 C
ATOM 2446 CB ALA c 104 26. .978 24. .993 12. .093 1. ,00 39. .30 C
ATOM 2447 C ALA c 104 27. .870 25. .986 14. ,218 1. ,00 39. ,81 C
ATOM 2448 O ALA c 104 28. .731 26. .839 13. .982 1. ,00 39. .91 O
ATOM 2449 N GLY c 105 26. ,994 26. ,091 15, ,225 1, ,00 39. ,76 N
ATOM 2450 CA GLY c 105 27. .052 27. .139 16, ,252 1, ,00 39. ,33 C
ATOM 2451 C GLY c 105 25. .873 28. .105 16. .348 1. ,00 39. ,20 C
ATOM 2452 O GLY c 105 25. .136 28. .310 15. ,380 1. ,00 39. ,37 0
ATOM 2453 N THR c 106 25. .699 28. .711 17. .521 1, ,00 38. ,80 N
ATOM 2454 CA THR c 106 24. .851 29. .894 17, ,654 1, ,00 38. .05 C
ATOM 2455 CB THR c 106 23, .814 29. .727 18. .751 1, ,00 38. .38 C
ATOM 2456 OGl THR c 106 22, ,999 28. .579 18. ,467 1, ,00 38. ,76 O
ATOM 2457 CG2 THR c 106 22. ,944 30. .990 18. .828 1, .00 38. .21 C
ATOM 2458 C THR c 106 25. ,658 31. .154 17. .950 1. .00 37. .36 c
ATOM 2459 O THR c 106 26. ,361 31. .242 18. .955 1, .00 36. .52 O
ATOM 2460 N VAL c 107 25. ,558 32. .130 17. .057 1. .00 37, .43 N
ATOM 2461 CA VAL c 107 26. ,119 33. .466 17. .343 1, .00 37, .35 c
ATOM 2462 CB VAL c 107 26. .932 34. .118 16. .152 1, .00 36, .69 C
ATOM 2463 CGI VAL c 107 26. .857 33, .283 14, .897 1, .00 36, .10 C
ATOM 2464 CG2 VAL c 107 26. .520 35, .538 15. .904 1, ,00 35. .96 C
ATOM 2465 C VAL c 107 25. .050 34, ,350 18, .024 1, ,00 37. .47 C
ATOM 2466 O VAL c 107 24. ,023 34, ,712 17, .424 1, ,00 37. .06 O
ATOM 2467 N LEU c 108 25. .290 34, .607 19, .313 1, .00 37. .38 N
ATOM 2468 CA LEU c 108 24. .324 35, ,267 20, .170 1. .00 37. .59 C
ATOM 2469 CB LEU c 108 24, ,245 34, .574 21. .537 1, .00 37. .38 C
ATOM 2470 CG LEU c 108 23, ,406 35, .266 22, .624 1, .00 37. .81 C
ATOM 2471 CD1 LEU c 108 21, .924 35, .419 22, .243 1, ,00 37. .73 C
ATOM 2472 CD2 LEU c 108 23, .539 34, .545 23, .957 1, .00 37. .81 C
ATOM 2473 C LEU c 108 24, .675 36, ,743 20, .326 1, .00 37. .73 C
ATOM 2474 O LEU c 108 25, ,790 37, ,083 20, .743 1. .00 38, .29 O
ATOM 2475 N THR c 109 23, ,732 37, ,615 19. .976 1, ,00 37, .18 N
ATOM 2476 CA THR c 109 23, .913 39, .038 20. .198 1, ,00 36, .88 C
ATOM 2477 CB THR c 109 23, .741 39, ,834 18. .895 1, ,00 36, .94 C
ATOM 2478 OGl THR c 109 24, .714 39. ,382 17. .947 1, ,00 36, .86 O
ATOM 2479 CG2 THR c 109 23, .935 41. ,315 19. .139 1, ,00 35, .69 C
ATOM 2480 C THR c 109 22, .941 39. .512 21, ,265 1, ,00 36, .68 C
ATOM 2481 O THR c 109 21, .738 39. .344 21. .123 1, ,00 36. .74 O
ATOM 2482 N VAL c 110 23, .458 40. .079 22, ,344 1, ,00 36. .39 N
ATOM 2483 CA VAL c 110 22, .571 40, .545 23, ,397 1. ,00 36. ,75 C
ATOM 2484 CB VAL c 110 22, .731 39, .744 24, .730 1. ,00 37. .01 C
ATOM 2485 CGI VAL c 110 24, .026 38, .942 24, ,754 1, ,00 37. .71 C
ATOM 2486 CG2 VAL c 110 22. ,567 40. ,628 25, ,965 1, ,00 36. .58 C
ATOM 2487 C VAL c 110 22. ,527 42. ,067 23, .571 1, ,00 36. .82 c
ATOM 2488 O VAL c 110 23. ,561 42. .727 23. .705 1, ,00 36. .88 0
ATOM 2489 N LYS c 111 21. ,293 42. .581 23. .564 1. ,00 36. ,66 N
ATOM 2490 CA LYS c 111 20. ,954 44. .004 23. .539 1. ,00 36. ,40 C
ATOM 2491 CB LYS c 111 21, ,921 44, .857 24. .364 1. ,00 36. ,13 c
ATOM 2492 CG LYS c 111 21. ,539 45. ,007 25, .813 1. ,00 34. ,53 c
ATOM 2493 CD LYS c 111 21. ,941 46. ,406 26, .332 1. ,00 31. ,44 c
ATOM 2494 CE LYS c 111 20. ,798 47. .369 26. .236 1. ,00 28. ,66 c
ATOM 2495 NZ LYS c 111 19. ,648 46. ,791 26. ,962 1. ,00 27. 06 N
ATOM 2496 C LYS c 111 20. ,864 44. ,514 22. ,100 1. ,00 36. 68 c
ATOM 2497 O LYS c 111 19. ,774 44. ,832 21. ,605 1. ,00 36. .91 0
ATOM 2498 N ALA D 1 34. ,772 10. ,109 45. ,854 1. 00 43. 36 N
ATOM 2499 CA ALA D 1 33. ,646 9. ,989 44. ,886 1. 00 43. 10 C
ATOM 2500 CB ALA D 1 34. 122 10. 324 43. 477 1. 00 42. 95 C ATOM 2501 C ALA D 1 33..055 8,.587 44,.935 1.,00 43,.06 c
ATOM 2502 O ALA D 1 33, ,793 7, .610 44, .856 1, .00 42, .97 o
ATOM 2503 N TRP D 2 31. .730 8. .511 45, .084 1. .00 43, .13 N
ATOM 2504 CA TRP D 2 30, .958 7, .260 45, .071 1. .00 43, .20 C
ATOM 2505 CB TRP D 2 31. .000 6, .574 46, .443 1. .00 43, .77 C
ATOM 2506 CG TRP D 2 30. .328 7, .378 47, .539 1. .00 44, .78 C
ATOM 2507 CD1 TRP D 2 30. .826 8, .489 48, .173 1. .00 45, .33 c
ATOM 2508 NE1 TRP D 2 29. .927 8, .949 49, .107 1, ,00 45, ,42 N
ATOM 2509 CE2 TRP D 2 28. .816 8. .146 49, .089 1. ,00 45. .11 C
ATOM 2510 CD2 TRP D 2 29. .033 7. .138 48, .115 1, .00 45, .97 C
ATOM 2511 CE3 TRP D 2 28, ,032 6. .169 47, .901 1. .00 46, .79 C
ATOM 2512 CZ3 TRP D 2 26. ,866 6. .236 48, .668 1. .00 45, ,73 C
ATOM 2513 CH2 TRP D 2 26, .684 7. .263 49, .630 1, .00 45, .13 C
ATOM 2514 CZ2 TRP D 2 27, .643 8. .218 49, .850 1. .00 44, ,55 C
ATOM 2515 C TRP D 2 29, .512 7. .575 44, .695 1. .00 43, ,00 C
ATOM 2516 O TRP D 2 29, .031 8. .676 44, .936 1. .00 42, ,89 0
ATOM 2517 N VAL D 3 28, .820 6. .609 44, ,107 1, ,00 43, ,01 N
ATOM 2518 CA VAL D 3 27, .434 6. .802 43, .677 1. ,00 42, ,86 C
ATOM 2519 CB VAL D 3 27, .170 6. .184 42, ,285 1, ,00 42, .67 C
ATOM 2520 CGI VAL D 3 25. ,709 6. .364 41. .868 1. ,00 42. .34 c
ATOM 2521 CG2 VAL D 3 28. ,087 6, .780 41, .255 1, ,00 41. .96 c
ATOM 2522 C VAL D 3 26. ,463 6. .196 44. .687 1, ,00 43. .26 c
ATOM 2523 O VAL D 3 26. .535 5, .004 45, .005 1. .00 43, ,57 0
ATOM 2524 N ASP D 4 25. .562 7, .033 45, .187 1, .00 43, ,43 N
ATOM 2525 CA ASP D 4 24. .540 6. .614 46. .132 1, .00 43, ,57 C
ATOM 2526 CB ASP D 4 24. ,272 7, .750 47, .116 1, .00 44, ,05 C
ATOM 2527 CG ASP D 4 23. ,139 7. .448 48. .077 1. .00 45. ,86 C
ATOM 2528 ODl ASP D 4 22. .408 8, .395 48, .442 1, .00 49. ,43 O
ATOM 2529 OD2 ASP D 4 22. .971 6. .279 48. .479 1, .00 48. ,18 O
ATOM 2530 C ASP D 4 23. .274 6, .245 45, .368 1, .00 43. .18 C
ATOM 2531 O ASP D 4 22. ,517 7, .130 44, .958 1, .00 43. .45 O
ATOM 2532 N GLN D 5 23. ,051 4, .944 45, .176 1, .00 42. .32 N
ATOM 2533 CA GLN D 5 21. ,927 4, .460 44, .372 1, .00 41. .43 C
ATOM 2534 CB GLN D 5 22. ,409 3, .374 43, .385 1, .00 41. .53 C
ATOM 2535 CG GLN D 5 21. ,300 2, .779 42. ,500 1, .00 40, .66 C
ATOM 2536 CD GLN D 5 21, ,731 1. .644 41, .584 1. .00 40. ,39 C
ATOM 2537 OEl GLN D 5 20, .885 0, .938 41, ,081 1, .00 40. ,73 O
ATOM 2538 NE2 GLN D 5 23, .029 1, .467 41. ,362 1. .00 39. ,34 N
ATOM 2539 C GLN D 5 20, .789 3, .935 45. .253 1, .00 41, ,27 C
ATOM 2540 O GLN D 5 21. .027 3, .140 46. .160 1. .00 41, ,45 O
ATOM 2541 N THR D 6 19. .564 4, .389 44. .996 1, .00 40, ,95 N
ATOM 2542 CA THR D 6 18. .367 3. .871 45. .687 1. .00 41, ,01 C
ATOM 2543 CB THR D 6 17. ,824 4, .824 46. .783 1, .00 40, ,94 C
ATOM 2544 OGl THR D 6 17, ,629 6. ,131 46. .236 1. .00 40, ,98 O
ATOM 2545 CG2 THR D 6 18, .770 4, .899 47. .984 1, .00 41. ,61 C
ATOM 2546 C THR D 6 17, .236 3. .649 44. .699 1, .00 41, .11 c
ATOM 2547 O THR D 6 17. .199 4, .313 43. .654 1, .00 41. .48 0
ATOM 2548 N PRO D 7 16. .303 2. .724 45. .022 1, .00 40, .93 N
ATOM 2549 CA PRO D 7 16. .351 1. .883 46, ,205 1, .00 40. ,58 c
ATOM 2550 CB PRO D 7 14. .889 1. .449 46, .374 1. .00 40. .12 c
ATOM 2551 CG PRO D 7 14, .425 1. .292 45. .019 1. .00 40. ,41 c
ATOM 2552 CD PRO D 7 15, .090 2. .435 44. .234 1, .00 40. ,87 c
ATOM 2553 C PRO D 7 17, ,252 0. .669 45. .987 1. .00 40. ,46 c
ATOM 2554 O PRO D 7 17, .582 0. ,319 44, .854 1. .00 40. ,53 0
ATOM 2555 N ARG D 8 17. .633 0. ,048 47, .093 1. .00 40. ,39 N
ATOM 2556 CA ARG D 8 18. .525 -1. .089 47, .134 1. .00 40. ,01 C
ATOM 2557 CB ARG D 8 18, .900 -1. ,298 48, .590 1, .00 39. ,76 C
ATOM 2558 CG ARG D 8 20, .053 -2. ,176 48, .842 1, .00 39. ,97 C
ATOM 2559 CD ARG D 8 20, .407 -2. ,076 50. .299 1. .00 42. 10 C
ATOM 2560 NE ARG D 8 19. ,339 -2, ,586 51. ,160 1. ,00 42. 46 N
ATOM 2561 CZ ARG D 8 19. ,409 -2, ,597 52. .485 1. .00 43. 23 C
ATOM 2562 NHl ARG D 8 20. ,498 -2. .134 53. ,081 1. ,00 44. 37 N
ATOM 2563 NH2 ARG D 8 18. ,413 -3, .086 53. .215 1. ,00 43. 34 N
ATOM 2564 C ARG D 8 17. ,789 -2, ,303 46. .598 1. ,00 39. 86 C ATOM 2565 O ARG D 8 18.333 -3,.081 45,.830 1,.00 39.97 0
ATOM 2566 N SER D 9 16 .543 -2 .452 47, .026 1 .00 39 .86 N
ATOM 2567 CA SER D 9 15 .663 -3, .511 46, .557 1, .00 39 .98 C
ATOM 2568 CB SER D 9 15 .726 -4 .729 47, .481 1, .00 39 .97 c
ATOM 2569 OG SER D 9 14 .958 -4, .536 48, .652 1, .00 39, .70 o
ATOM 2570 C SER D 9 14 .240 -2, .982 46, .491 1 .00 39 .96 c
ATOM 2571 O SER D 9 13 .845 -2, .127 47, .288 1, .00 39, .56 o
ATOM 2572 N VAL D 10 13 .480 -3 .485 45, .529 1, .00 40 .04 N
ATOM 2573 CA VAL D 10 12 .106 -3, .059 45, .352 1, .00 40, .38 C
ATOM 2574 CB VAL D 10 12 .034 -1 .736 44, .553 1, .00 40, .44 C
ATOM 2575 CGI VAL D 10 12 .452 -1, .947 43, .106 1, .00 40, .88 C
ATOM 2576 CG2 VAL D 10 10, .643 -1, .117 44. .642 1. .00 40, .75 C
ATOM 2577 C VAL D 10 11 .319 -4, .173 44, .665 1, .00 40, .45 c
ATOM 2578 O VAL D 10 11. .888 -4, .981 43. .919 1. .00 40, .68 0
ATOM 2579 N THR D 11 10, .021 -4, .245 44, .932 1, .00 40, .08 N
ATOM 2580 CA THR D 11 9, .202 -5. .202 44. .212 1. .00 40. .05 C
ATOM 2581 CB THR D 11 8, .863 -6, .446 45. .065 1. ,00 39, ,92 C
ATOM 2582 OGl THR D 11 7, .702 -7, .098 44. .549 1. ,00 39. .40 O
ATOM 2583 CG2 THR D 11 8 .615 -6, .066 "46, .497 1, .00 41, .25 C
ATOM 2584 C THR D 11 7, .981 -4, .526 43. .622 1. .00 40. .02 C
ATOM 2585 O THR D 11 7, .228 -3, .871 44. ,327 1, .00 40, .41 O
ATOM 2586 N LYS D 12 7, .815 -4. .662 42. ,312 1. .00 40. .23 N
ATOM 2587 CA LYS D 12 6, .727 -4. .003 41. ,595 1. ,00 40. .27 C
ATOM 2588 CB LYS D 12 7, .298 -3, .086 40. ,521 1. ,00 39. .94 C
ATOM 2589 CG LYS D 12 8, .109 -1. ,918 41, ,063 1. ,00 39. .68 c
ATOM 2590 CD LYS D 12 7, .202 -0, .867 41. .722 1. ,00 39. .52 c
ATOM 2591 CE LYS D 12 7. .858 0, ,503 41. .808 1. ,00 38. .17 c
ATOM 2592 NZ LYS D 12 7, .254 1, .335 42. .866 1. .00 36. .86 N
ATOM 2593 C LYS D 12 5, .831 -5. .056 40, ,965 1. .00 40. .58 C
ATOM 2594 O LYS D 12 6, .268 -6, .194 40, ,790 1. .00 41. .22 O
ATOM 2595 N GLU D 13 4, .587 -4. .696 40, .645 1. .00 40. .41 N
ATOM 2596 CA GLU D 13 3, .679 -5, .590 39, .909 1, .00 40. .35 C
ATOM 2597 CB GLU D 13 2, .225 -5, .341 40, .311 1. .00 40. .65 C
ATOM 2598 CG GLU D 13 1. .969 -5, .174 41. .814 1. .00 43. .08 C
ATOM 2599 CD GLU D 13 1, .647 -6. .484 42, .499 1. ,00 47. .17 C
ATOM 2600 OEl GLU D 13 1, .336 -6. .478 43. .720 1. ,00 48. .20 O
ATOM 2601 OE2 GLU D 13 1, .706 -7. .529 41. .808 1. .00 49. .59 O
ATOM 2602 C GLU D 13 3, .832 -5, .363 38. .400 1, .00 39, .74 c
ATOM 2603 O GLU D 13 4. .165 -4. ,257 37. .979 1, .00 40, .12 0
ATOM 2604 N THR D 14 3. .605 -6. ,407 37. .598 1. .00 38, .94 N
ATOM 2605 CA THR D 14 3. .528 -6. .298 36, .137 1, .00 38, .18 C
ATOM 2606 CB THR D 14 2. .909 -7. .588 35, .497 1. .00 38. .05 C
ATOM 2607 OGl THR D 14 3. .918 -8. .583 35, .345 1. .00 37. .69 O
ATOM 2608 CG2 THR D 14 2. .344 -7, ,322 34. .125 1. .00 38. .04 C
ATOM 2609 C THR D 14 2. .702 -5, .071 35, .754 1, .00 38. .15 C
ATOM 2610 O THR D 14 1. .628 -4. ,827 36, .318 1. .00 38. .34 O
ATOM 2611 N GLY D 15 3. ,201 -4, ,294 34. ,804 1. ,00 37. ,78 N
ATOM 2612 CA GLY D 15 2. .475 -3, ,124 34, .362 1. ,00 38. ,18 C
ATOM 2613 C GLY D 15 2. ,970 -1, ,835 34. .984 1. .00 38. ,45 C
ATOM 2614 O GLY D 15 3. .058 -0, ,818 34. .305 1. ,00 38. .92 O
ATOM 2615 N GLU D 16 3, .302 -1. ,866 36. .269 1. ,00 38. ,44 N
ATOM 2616 CA GLU D 16 3. .815 -0, ,684 36. .957 1. ,00 38. ,61 C
ATOM 2617 CB GLU D 16 3, .957 -0, ,971 38. ,448 1. ,00 38. ,77 C
ATOM 2618 CG GLU D 16 2, .671 -1. .434 39. .101 1. ,00 39. ,56 c
ATOM 2619 CD GLU D 16 2. .848 -1. ,834 40. ,546 1. ,00 40. ,65 c
ATOM 2620 OEl GLU D 16 3. .990 -2. ,076 40. ,972 1. ,00 41. ,80 0
ATOM 2621 OE2 GLU D 16 1. ,831 -1. ,915 41. ,264 1. 00 42. 46 0
ATOM 2622 C GLU D 16 5. ,161 -0. ,247 36. ,396 1. 00 38. 77 c
ATOM 2623 O GLU D 16 5. 758 -0. 944 35. 574 1. 00 38. 73 0
ATOM 2624 N SER D 17 5. 638 0. 910 36. 847 1. 00 39. 08 N
ATOM 2625 CA SER D 17 6. 974 1. 402 36. 472 1. 00 39. 29 c
ATOM 2626 CB SER D 17 6. 871 2. 684 35. 627 1. 00 39. 33 c
ATOM 2627 OG SER D 17 6. 001 3. 630 36. 215 1. 00 39. 01 0
ATOM 2628 C SER D 17 7. 920 1. 603 37. 664 1. 00 39. 41 c ATOM 2629 O SER D 17 7.495 1.628 38.822 1.00 39.97 O
ATOM 2630 N LEU D 18 9.204 1.764 37.373 00 39.54 N
ATOM 2631 CA LEU D 18 10.223 1.787 38.410 00 39.59 C
ATOM 2632 CB LEU D 18 10.987 0.468 38.377 00 39.57 C
ATOM 2633 CG LEU D 18 12.098 0.062 39.357 00 39.70 C
ATOM 2634 GDI LEU D 18 13.508 0.127 38.738 00 39.39 C
ATOM 2635 CD2 LEU D 18 11.996 0.804 40.688 00 39.58 c
ATOM 2636 C LEU D 18 11.172 2.963 38.222 00 39.76 c
ATOM 2637 O LEU D 18 11.634 3.225 37.116 00 39.81 0
ATOM 2638 N THR D 19 11.450 3.681 39.304 00 39.94 N
ATOM 2639 CA THR D 19 12.433 4.755 39.250 00 40.07 c
ATOM 2640 CB THR D 19 11.777 6.130 39.561 00 39.79 c
ATOM 2641 OGl THR D 19 10.617 6.287 38.738 00 39.06 0
ATOM 2642 CG2 THR D 19 12.730 7.279 39.253 00 39.70 c
ATOM 2643 C THR D 19 13.671 4.441 40.125 00 40.27 c
ATOM 2644 O THR D 19 13.560 ,176 41.308 00 40.53 0
ATOM 2645 N ILE D 20 14.842 ,427 39.512 00 40.71 N
ATOM 2646 CA ILE D 20 16.089 ,283 40.245 00 41.31 C
ATOM 2647 CB ILE D 20 17.049 ,257 39.606 00 41.02 C
ATOM 2648 CGI ILE D 20 16.387 ,881 39.544 00 41.44 C
ATOM 2649 GDI ILE D 20 17.149 0.833 38.810 00 40.40 c
ATOM 2650 CG2 ILE D 20 18.309 3.165 40.424 00 41.51 c
ATOM 2651 C ILE D 20 16.757 5. ,637 40.264 00 41.93 c
ATOM 2652 O ILE D 20 16.885 6, ,291 39.231 1.00 41.92 0
ATOM 2653 N ASN D 21 17.181 6. 046 41.448 00 42.92 N
ATOM 2654 CA ASN D 21 17.777 7, .347 41.653 00 43.80 c
ATOM 2655 CB ASN D 21 17.076 8.052 42.802 00 44.06 c
ATOM 2656 CG ASN D 21 15.876 8.846 42.345 00 45.31 c
ATOM 2657 ODl ASN D 21 14.749 8.618 42.794 00 46.50 0
ATOM 2658 ND2 ASN D 21 16.108 9.790 41.439 00 47.41 N
ATOM 2659 C ASN D 21 19.242 7.193 41.974 00 44.17 C
ATOM 2660 O ASN D 21 19.605 6.366 42.809 00 44.37 O
ATOM 2661 N CYS D 22 20.077 7.977 41.299 00 44.32 N
ATOM 2662 CA CYS D 22 21.512 7.971 41.546 00 44.68 C
ATOM 2663 CB CYS D 22 22.230 7.277 40.411 00 44.52 C
ATOM 2664 SG CYS D 22 21.830 5.539 40.404 00 47.27 S
ATOM 2665 C CYS D 22 22.081 9.369 41.775 00 44.46 C
ATOM 2666 O CYS D 22 21.656 10.338 41.146 00 45.03 O
ATOM 2667 N ALA D 23 23.031 9.484 42.690 00 43.59 N
ATOM 2668 CA ALA D 23 23.610 10.769 42.961 00 43.17 C
ATOM 2669 CB ALA D 23 22.952 11.383 44.181 00 43.11 C
ATOM 2670 C ALA D 23 25.104 10.613 43.162 00 42.94 C
ATOM 2671 O ALA D 23 25.533 9.852 44.016 00 43.43 O
ATOM 2672 N LEU D 24 25.893 11.319 42.366 00 42.39 N
ATOM 2673 CA LEU D 24 27.329 11.290 42.510 00 42.25 C
ATOM 2674 CB LEU D 24 28.014 11.786 41.226 00 41.99 C
ATOM 2675 CG LEU D 24 29.546 11.743 41.100 00 41.36 C
ATOM 2676 CD1 LEU D 24 29.985 12.221 39.726 00 39.92 C
ATOM 2677 CD2 LEU D 24 30.137 10.363 41.416 00 40.07 C
ATOM 2678 C LEU D 24 27.694 12.139 43.726 00 42.66 C
ATOM 2679 O LEU D 24 27.288 13.293 43.825 00 42.82 O
ATOM 2680 N LYS D 25 28.459 11.549 44.643 00 43.03 N
ATOM 2681 CA LYS D 25 28.717 12.120 45.961 00 43.39 C
ATOM 2682 CB LYS D 25 28.177 11.174 47.035 00 43.45 C
ATOM 2683 CG LYS D 25 26.648 11.033 47.048 00 45.23 C
ATOM 2684 CD LYS D 25 26.001 11.935 48.110 00 48.02 C
ATOM 2685 CE LYS D 25 24.522 12.163 47.822 00 49.24 C
ATOM 2686 NZ LYS D 25 24.301 13.275 46.839 00 49.27 N
ATOM 2687 C LYS D 25 30.211 12.354 46.178 00 43.55 C
ATOM 2688 O LYS D 25 31.033 11.601 45.656 00 43.60 O
ATOM 2689 N ASN D 26 30.549 13.387 46.961 00 43.74 N
ATOM 2690 CA ASN D 26 31.936 13.792 47.222 00 43.66 C
ATOM 2691 CB ASN D 26 32.611 12.840 48.205 1.00 44.13 C
ATOM 2692 CG ASN D 26 31.987 12.885 49.585 1.00 45.64 C ATOM 2693 ODl ASN D 26 31..277 11.,955 49..994 1..00 46..22 o
ATOM 2694 ND2 ASN D 26 32. .248 13. .975 50. .318 1. .00 47, .54 N
ATOM 2695 C ASN D 26 32. .743 13. ,883 45. .941 1. .00 43. .44 C
ATOM 2696 O ASN D 26 33. .828 13. ,314 45. .828 1, .00 43, .10 O
ATOM 2697 N ALA D 27 32. .181 14, ,601 44. .975 1, .00 43. .45 N
ATOM 2698 CA ALA D 27 32. .735 14. ,706 43. .637 1. .00 43. .52 C
ATOM 2699 CB ALA D 27 31. .751 14. .115 42. .613 1. .00 43. .25 c
ATOM 2700 C ALA D 27 33. ,016 16. .171 43. .334 1, .00 43. .60 c
ATOM 2701 O ALA D 27 32. .096 16. ,926 43. ,022 1. .00 44, ,03 o
ATOM 2702 N ALA D 28 34. ,281 16. ,576 43. ,429 1. .00 43, ,66 N
ATOM 2703 CA ALA D 28 34. ,687 17. ,981 43. .175 1, ,00 43, .69 c
ATOM 2704 CB ALA D 28 35. ,955 18. .348 44. .014 1. .00 43. .65 c
ATOM 2705 C ALA D 28 34. .909 18. ,282 41. .678 1, .00 43, ,33 c
ATOM 2706 O ALA D 28 35. .829 19, ,028 41. .310 1. .00 43, ,35 0
ATOM 2707 N ASP D 29 34. .044 17, ,709 40. .837 1, .00 42, .76 N
ATOM 2708 CA ASP D 29 34. .268 17. ,592 39. .389 1. .00 42, .30 C
ATOM 2709 CB ASP D 29 35. .440 16. .633 39. .099 1, .00 42, .53 C
ATOM 2710 CG ASP D 29 35. .551 15, .492 40. .124 1, .00 43, .66 C
ATOM 2711 ODl ASP D 29 34. .729 14, .549 40, .059 1, .00 43, .69 O
ATOM 2712 OD2 ASP D 29 36, .465 15, .537 40, .993 1, .00 44, .75 O
ATOM 2713 C ASP D 29 32. .979 17. .162 38, .661 1. .00 41, .65 c
ATOM 2714 O ASP D 29 32, .044 16, .666 39. .294 1, .00 41, .73 0
ATOM 2715 N ASP D 30 32. .942 17. .338 37. .337 1. .00 40, .69 N
ATOM 2716 CA ASP D 30 31, .681 17. .393 36. .577 1, ,00 39. .53 C
ATOM 2717 CB ASP D 30 31. .845 18. .356 35. .405 1, .00 39. .73 C
ATOM 2718 CG ASP D 30 31. .748 19. .795 35. ,824 1, ,00 39. .85 c
ATOM 2719 ODl ASP D 30 30. .886 20. .105 36. ,669 1, ,00 41. .59 0
ATOM 2720 OD2 ASP D 30 32, .519 20. .618 35. .302 1, .00 39. .35 0
ATOM 2721 C ASP D 30 31, .146 16. .090 36, .022 1. .00 38, .75 c
ATOM 2722 O ASP D 30 31, .856 15, .384 35. .318 1. .00 38, ,85 0
ATOM 2723 N LEU D 31 29, .876 15, .803 36, ,293 1. .00 37, .73 N
ATOM 2724 CA LEU D 31 29, .184 14. .694 35. .646 1. .00 36, .84 c
ATOM 2725 CB LEU D 31 27, .740 14, .595 36. .132 1. .00 36, .24 c
ATOM 2726 CG LEU D 31 27, .011 13. .284 35. .847 1. .00 33. ,49 c
ATOM 2727 CD1 LEU D 31 27, .607 12, .166 36. .663 1, ,00 31, .25 c
ATOM 2728 CD2 LEU D 31 25, .556 13. .427 36. .163 1. .00 30, ,41 c
ATOM 2729 C LEU D 31 29, .209 14, .870 34. .133 1. .00 37. .41 c
ATOM 2730 O LEU D 31 28. .792 15. ,918 33. .607 1, .00 37, .39 0
ATOM 2731 N GLU D 32 29. ,713 13. .849 33. .441 1, .00 37, .95 N
ATOM 2732 CA GLU D 32 29, .931 13, ,924 31. .995 1. .00 38. .71 C
ATOM 2733 CB GLU D 32 31, .416 13. ,801 31. .645 1, .00 39. .12 C
ATOM 2734 CG GLU D 32 32, .193 15. ,115 31. .740 1, .00 41. .10 C
ATOM 2735 CD GLU D 32 31. .764 16. ,157 30. .685 1, .00 44. .44 C
ATOM 2736 OEl GLU D 32 32, .662 16. .820 30. .113 1, .00 45. .38 0
ATOM 2737 OE2 GLU D 32 30, .539 16. .313 30. .421 1. .00 45. .39 0
ATOM 2738 C GLU D 32 29, .149 12, .895 31. ,241 1, .00 38. .85 c
ATOM 2739 O GLU D 32 28, .616 13, .177 30. ,188 1, ,00 39. ,30 0
ATOM 2740 N ARG D 33 29, .058 11, .702 31. ,808 1, .00 39, .42 N
ATOM 2741 CA ARG D 33 28 .430 10, .574 31, .160 1, ,00 39, ,72 c
ATOM 2742 CB ARG D 33 29, .499 9. ,789 30. .410 1, ,00 39, .85 c
ATOM 2743 CG ARG D 33 28, .985 8, .742 29. ,472 1, ,00 41, .45 c
ATOM 2744 CD ARG D 33 30, .062 8, .322 28. .491 1, ,00 43, .89 c
ATOM 2745 NE ARG D 33 31, .197 7, .689 29. .152 1, ,00 47, .25 N
ATOM 2746 CZ ARG D 33 31. ,193 6, .455 29. .661 1, ,00 49. .38 c
ATOM 2747 NHl ARG D 33 32, ,292 5, .974 30, ,243 1, ,00 49. .45 N
ATOM 2748 NH2 ARG D 33 30. ,099 5, .694 29, ,593 1. ,00 50, .00 N
ATOM 2749 C ARG D 33 27. .774 9, .727 32. ,243 1. ,00 39, .94 C
ATOM 2750 O ARG D 33 28. .273 9, .661 33. ,356 1. .00 39. .64 O
ATOM 2751 N THR D 34 26. .638 9, .112 31. ,915 1. ,00 40, .75 N
ATOM 2752 CA THR D 34 25. .871 8, .276 32. ,835 1. ,00 41. .14 C
ATOM 2753 CB THR D 34 24. .679 9, ,027 33. ,461 1. ,00 40. ,95 C
ATOM 2754 OGl THR D 34 24. .020 9. .814 32. .468 1. ,00 41. ,22 0
ATOM 2755 CG2 THR D 34 25. .134 9. ,920 34. ,570 1. 00 41. ,33 C
ATOM 2756 C THR D 34 25. .310 7. ,031 32. ,141 1. ,00 41. ,81 c ATOM 2757 O THR D 34 24,.571 7,.142 31,.161 1,.00 42..34 0
ATOM 2758 N ASP D 35 25, .639 5, .850 32, .671 1, .00 42, .29 N
ATOM 2759 CA ASP D 35 25, .209 4, .573 32. .092 1. ,00 42. .11 C
ATOM 2760 CB ASP D 35 26, .425 3, .829 31. .537 1, .00 42. .03 C
ATOM 2761 CG ASP D 35 26, .968 4, .499 30, .278 1, .00 43, .56 C
ATOM 2762 ODl ASP D 35 27. .842 3, .941 29. .560 1, ,00 46. .61 O
ATOM 2763 OD2 ASP D 35 26. .498 5, .615 29. ,983 1, .00 44, .89 O
ATOM 2764 C ASP D 35 24. .354 3. .722 33. .035 1. ,00 41. .77 C
ATOM 2765 O ASP D 35 24. .261 4, .011 34. .230 1, .00 41, .58 0
ATOM 2766 N TRP D 36 23. .696 2. .711 32. .472 1. .00 41, .34 N
ATOM 2767 CA TRP D 36 22. .739 1, .884 33. .202 1. ,00 41, .40 C
ATOM 2768 CB TRP D 36 21, .307 2, .381 32, ,986 1, .00 40, .76 c
ATOM 2769 CG TRP D 36 21. .035 3, .735 33. .560 1. .00 39, .98 c
ATOM 2770 CD1 TRP D 36 21. .121 4, .928 32. .914 1, .00 39, .38 c
ATOM 2771 NE1 TRP D 36 20. ,809 5. .962 33. ,768 1. .00 39, .12 N
ATOM 2772 CE2 TRP D 36 20. ,510 5, .439 34. .996 1. .00 39, .10 C
ATOM 2773 CD2 TRP D 36 20. ,639 4. .035 34. ,901 1. ,00 39. ,48 C
ATOM 2774 CE3 TRP D 36 20. .366 3. .252 36. .030 1. ,00 40. ,06 C
ATOM 2775 CZ3 TRP D 36 19. ,991 3, .894 37. .212 1. .00 40. .06 C
ATOM 2776 CH2 TRP D 36 19. ,874 5, .295 37. .269 1. .00 40. .13 C
ATOM 2777 CZ2 TRP D 36 20. .125 6, .080 36. .173 1. .00 39. .66 C
ATOM 2778 C TRP D 36 22. ,849 0, .462 32. .690 1. .00 41. .89 c
ATOM 2779 O TRP D 36 22. .709 0, .233 31. .494 1. .00 41. .74 o
ATOM 2780 N TYR D 37 23. ,125 -0, .482 33. .591 1. .00 42. .42 N
ATOM 2781 CA TYR D 37 23. .262 -1. .892 33. .219 1. .00 42. .74 c
ATOM 2782 CB TYR D 37 24. .695 -2, .390 33. .386 1, .00 43, .39 c
ATOM 2783 CG TYR D 37 25. .702 -1, .467 32. ,789 1. .00 44. .09 c
ATOM 2784 CD1 TYR D 37 26. .041 -0, .301 33. .448 1, .00 47. .02 c
ATOM 2785 CEl TYR D 37 26. .962 0, .583 32. .913 1. .00 47, .92 c
ATOM 2786 CZ TYR D 37 27. .550 0, .293 31. .705 1. .00 45, ,40 c
ATOM 2787 OH TYR D 37 28, .443 1, .214 31, ,238 1, .00 46. .33 0
ATOM 2788 CE2 TYR D 37 27. .242 -0, .871 31. .016 1. .00 43. ,86 c
ATOM 2789 CD2 TYR D 37 26, .314 -1, .746 31, .569 1, .00 44. ,21 c
ATOM 2790 C TYR D 37 22. .333 -2, .758 34. .028 1. ,00 42. ,45 c
ATOM 2791 O TYR D 37 22. .056 -2, .467 35. .184 1. .00 42. ,79 0
ATOM 2792 N ARG D 38 21. .846 -3, .817 33. .399 1. .00 42, ,06 N
ATOM 2793 CA ARG D 38 20. .942 -4, .754 34. .029 1, ,00 41, ,73 c
ATOM 2794 CB ARG D 38 19, .524 -4, .627 33. ,446 1, .00 41, .95 c
ATOM 2795 CG ARG D 38 19. ,491 -4, .486 31. ,905 1. .00 43, .17 c
ATOM 2796 CD ARG D 38 18, ,362 -5, .245 31. .218 1. .00 45, .32 c
ATOM 2797 NE ARG D 38 17. .039 -4, .888 31. .732 1. ,00 48, ,41 N
ATOM 2798 CZ ARG D 38 15. .878 -5, .170 31. .133 1, .00 48. ,65 c
ATOM 2799 NHl ARG D 38 15. .851 -5, .819 29. .974 1. .00 48. .23 N
ATOM 2800 NH2 ARG D 38 14. .736 -4, .786 31, ,697 1. .00 48. ,73 N
ATOM 2801 C ARG D 38 21, .486 -6, .137 33. ,744 1, .00 41. ,23 C
ATOM 2802 O ARG D 38 21. .930 -6, .399 32. ,625 1. .00 40. .92 O
ATOM 2803 N THR D 39 21. .494 -6, .983 34, .776 1. ,00 40, .78 N
ATOM 2804 CA THR D 39 21. .560 -8, .433 34. .640 1. ,00 40, ,44 C
ATOM 2805 CB THR D 39 22. .682 -9, .065 35. .492 1, .00 40. .56 C
ATOM 2806 OGl THR D 39 23, ,930 -8. ,409 35, ,236 1. ,00 40. ,48 0
ATOM 2807 CG2 THR D 39 22, .824 -10, .534 35, ,161 1. .00 40. .93 c
ATOM 2808 C THR D 39 20, .201 -8, .971 35. ,094 1. .00 39. ,94 c
ATOM 2809 O THR D 39 19, .828 -8, ,841 36. .243 1, ,00 39. ,94 0
ATOM 2810 N THR D 40 19, ,466 -9, .575 34, .178 1, ,00 40. .03 N
ATOM 2811 CA THR D 40 18, ,077 -9, .928 34. ,414 1, ,00 39. ,98 C
ATOM 2812 CB THR D 40 17, ,135 -9, ,038 33. ,601 1. ,00 40. ,00 C
ATOM 2813 OGl THR D 40 17. ,394 -9, ,208 32. .198 1. ,00 39. ,47 O
ATOM 2814 CG2 THR D 40 17. ,323 -7. .590 33. ,990 1. ,00 40. ,09 C
ATOM 2815 C THR D 40 17. ,780 -11, .357 34. ,040 1. ,00 40. ,30 c
ATOM 2816 O THR D 40 18. ,631 -12. ,051 33. 494 1. ,00 40. 34 0
ATOM 2817 N LEU D 41 16. ,557 -11. .788 34. ,341 1. ,00 41. 15 N
ATOM 2818 CA LEU D 41 16. ,086 -13. ,107 33. 976 1. 00 42. 05 C
ATOM 2819 CB LEU D 41 14. ,669 -13. ,308 34. 496 1. 00 41. 61 C
ATOM 2820 CG LEU D 41 14. ,465 -13. ,519 36. 001 1. .00 41. 14 C ATOM 2821 GDI LEU D 41 12..964 -13..520 36.,401 1.,00 37..89 C ATOM 2822 CD2 LEU D 41 15..160 -14..796 36..463 1..00 40,.23 C
ATOM 2823 C LEU D 41 16. .127 -13. .290 32. ,459 1. .00 43, .36 C
ATOM 2824 O LEU D 41 16. .391 -14. .387 31. .969 1. .00 43, ,43 O
ATOM 2825 N GLY D 42 15. .891 -12, ,198 31. .729 1. .00 44, .83 N
ATOM 2826 CA GLY D 42 15. .787 -12. ,219 30. .271 1. .00 46. .70 C
ATOM 2827 C GLY D 42 17. .086 -12, ,250 29, .483 1. .00 48, .04 C
ATOM 2828 O GLY D 42 17. .183 -12. .965 28, ,491 1. .00 48, .50 0
ATOM 2829 N SER D 43 18. .054 -11. .433 29. .897 1. .00 49, .46 N
ATOM 2830 CA SER D 43 19. .426 -11. .415 29. .360 1. .00 50, ,33 C
ATOM 2831 CB SER D 43 20. .173 -10. .173 29. .896 1. .00 51. .06 C
ATOM 2832 OG SER D 43 20. .572 -10. .313 31. .275 1. ,00 50. .27 O
ATOM 2833 C SER D 43 20, .176 -12. .646 29, ,828 1. .00 50, .79 C
ATOM 2834 O SER D 43 19, .790 -13. .264 30. .819 1. .00 50. .86 O
ATOM 2835 N THR D 44 21, .262 -12. .985 29. .149 1. .00 51, .44 N
ATOM 2836 CA THR D 44 22, .135 -14. .060 29. ,625 1, .00 52. .24 C
ATOM 2837 CB THR D 44 22, .661 -14. .911 28. .462 1, .00 52. .50 C
ATOM 2838 OGl THR D 44 21, .557 -15. .301 27. .637 1, .00 53, .69 0
ATOM 2839 CG2 THR D 44 23. .363 -16. ,167 28, ,971 1. .00 52. .93 c
ATOM 2840 C THR D 44 23. .284 -13. .459 30, ,431 1, .00 52, .40 c
ATOM 2841 O THR D 44 23. .462 -13. .767 31, .617 1. ,00 52. .64 0
ATOM 2842 N ASN D 45 24. .050 -12. .589 29, .781 1. ,00 52. .56 N
ATOM 2843 CA ASN D 45 25. .082 -11. .803 30, .456 1, ,00 52, .43 C
ATOM 2844 CB ASN D 45 26. .345 -11. .710 29, .582 1. ,00 52. .75 C
ATOM 2845 CG ASN D 45 27. .157 -13. .001 29. .571 1, ,00 53. .08 C
ATOM 2846 ODl ASN D 45 27. .717 -13, .380 28. .538 1, ,00 54. .49 O
ATOM 2847 ND2 ASN D 45 27. .247 -13. .667 30. .723 1, ,00 52. .75 N
ATOM 2848 C ASN D 45 24. ,558 -10. .406 30, .782 1, .00 51, .79 C
ATOM 2849 O ASN 'D 45 23. .413 -10. .080 30. ,457 1, .00 51, .44 O
ATOM 2850 N GLU D 46 25. .403 -9. .596 31, .422 1. .00 51, .23 N
ATOM 2851 CA GLU D 46 25, ,113 -8. .184 31. .685 1, ,00 50. ,85 C
ATOM 2852 CB GLU D 46 26, .312 -7. .517 32. .370 1, ,00 51, .14 C ATOM 2853 CG GLU D 46 26,.299 -5,.989 32,.412 1..00 53,.38 c
ATOM 2854 CD GLU D 46 27. ,037 -5, .420 33, .640 1, .00 57, ,60 c
ATOM 2855 OEl GLU D 46 26, .496 -5, .533 34, .777 1. .00 58, .34 0
ATOM 2856 OE2 GLU D 46 28. ,148 -4. .847 33, .465 1, .00 58, .29 0
ATOM 2857 C GLU D 46 24. .796 -7. .485 30, ,376 1, .00 50, .00 c ATOM 2858 O GLU D 46 25,.308 -7,.888 29,.321 1..00 50, .44 0
ATOM 2859 N GLN D 47 23. .941 -6. .464 30, ,433 1. .00 48, .59 N
ATOM 2860 CA GLN D 47 23. ,627 -5. .672 29, .242 1. ,00 47, .33 C
ATOM 2861 CB GLN D 47 22. ,468 -6. .295 28, .442 1. ,00 47. .28 C
ATOM 2862 CG GLN D 47 21. .113 -6. .289 29, .144 1. ,00 48, .85 C
ATOM 2863 CD GLN D 47 19, .949 -6. .605 28, ,208 1. ,00 48, .87 C
ATOM 2864 OEl GLN D 47 20. .006 -6. .316 27, ,011 1. ,00 50. .60 0 ATOM 2865 NE2 GLN D 47 18,.884 -7..200 28,,755 1..00 49..96 N ATOM 2866 C GLN D 47 23,.384 -4.,190 29,.540 1..00 45..66 C ATOM 2867 O GLN D 47 22,,830 -3..834 30,.581 1..00 45..01 O
ATOM 2868 N LYS D 48 23, .817 -3. .340 28, .611 1. ,00 44, ,18 N
ATOM 2869 CA LYS D 48 23. .660 -1. .897 28, .723 1. ,00 42. .86 C ATOM 2870 CB LYS D 48 24,.693 -1,.174 27,.859 1..00 43..14 C
ATOM 2871 CG LYS D 48 24. .906 0. .292 28, ,233 1. .00 44. .48 C ATOM 2872 CD LYS D 48 25..770 1..001 27,,209 1..00 46..74 C
ATOM 2873 CE LYS D 48 25, .329 2. .458 27. .073 1. .00 48, ,04 C ATOM 2874 NZ LYS D 48 25..345 2..926 25.,633 1..00 49,.15 N
ATOM 2875 C LYS D 48 22. .258 -1. .496 28. .311 1. .00 41, .75 C
ATOM 2876 O LYS D 48 21. .802 -1, ,823 27. .217 1. ,00 41. .56 O ATOM 2877 N ILE D 49 21..562 -0.,811 29..206 1,,00 40..59 N
ATOM 2878 CA ILE D 49 20. .252 -0. ,283 28. .889 1, ,00 39. .63 C
ATOM 2879 CB ILE D 49 19, .520 0. ,215 30. .119 1. ,00 39. ,09 C ATOM 2880 CGI ILE D 49 19,.200 -0,,969 31.,043 1.,00 38.,06 C
ATOM 2881 CD1 ILE D 49 18. .812 -0. ,625 32. ,475 1. ,00 34. ,62 C
ATOM 2882 CG2 ILE D 49 18. ,277 0. .944 29. ,668 1. ,00 38. ,69 C ATOM 2883 C ILE D 49 20. .412 0,.859 27..889 1.,00 39.,78 C
ATOM 2884 O ILE D 49 21. ,253 1. ,747 28. ,064 1. 00 40. ,00 O ATOM 2885 N SER D 50 19,.629 0,.801 26,.819 1,.00 39.45 N
ATOM 2886 CA SER D 50 19. .691 1, .788 25, .771 1. .00 39, .01 C
ATOM 2887 CB SER D 50 19, .518 1, .088 24, .433 1, .00 39, .12 C
ATOM 2888 OG SER D 50 20. .086 1. .839 23, .372 1, .00 40, ,32 o
ATOM 2889 C SER D 50 18. .545 2, .751 26, .011 1. .00 38, .51 c
ATOM 2890 O SER D 50 17. .384 2, ,349 25, .909 1, .00 39, ,42 o
ATOM 2891 N ILE D 51 18. .853 4, .004 26, .340 1. .00 37, ,35 N
ATOM 2892 CA ILE D 51 17. .814 4, ,982 26. .670 1. .00 36, ,74 C
ATOM 2893 CB ILE D 51 18. .406 6. .284 27. .263 1. .00 36, ,75 C
ATOM 2894 CGI ILE D 51 19. .193 5. .982 28. .542 1. .00 34. .81 C
ATOM 2895 GDI ILE D 51 18. .418 5. .319 29. .576 1. .00 32. .25 C
ATOM 2896 CG2 ILE D 51 17. .315 7. .328 27, .527 1, .00 36, .15 C
ATOM 2897 C ILE D 51 16. .914 5. .303 25, .475 1, .00 36. .75 C
ATOM 2898 O ILE D 51 17. .390 5, .558 24, .373 1, .00 36, .49 O
ATOM 2899 N GLY D 52 15. .609 5. .287 25, .718 1. .00 36, ,69 N
ATOM 2900 CA GLY D 52 14, .612 5. ,423 24, ,670 1, .00 36. .76 C
ATOM 2901 C GLY D 52 13, .431 4. .548 25, ,008 1. .00 37. ,07 c
ATOM 2902 O GLY D 52 13, .513 3. .681 25, ,896 1, .00 36. .81 0
ATOM 2903 N GLY D 53 12, .323 4. .777 24, ,313 1, .00 37. .51 N
ATOM 2904 CA GLY D 53 11. .138 3. .932 24. .472 1, .00 38. .10 C
ATOM 2905 C GLY D 53 10. .635 3. .891 25. .902 1. .00 38. .54 C
ATOM 2906 O GLY D 53 10. .205 4, .914 26. .438 1, .00 38. .60 O
ATOM 2907 N ARG D 54 10. .703 2. .718 26. .530 1. .00 38. .89 N
ATOM 2908 CA ARG D 54 10. .225 2, ,570 27. .904 1, .00 39. .33 C
ATOM 2909 CB ARG D 54 9. .540 1. .219 28. .116 1, .00 38. .67 C
ATOM 2910 CG ARG D 54 10. ,409 0, .023 27, .897 1, .00 38. .93 C
ATOM 2911 CD ARG D 54 9. .664 -1. .276 28. .255 1. .00 39. .46 C
ATOM 2912 NE ARG D 54 10. ,631 -2, .322 28, ,599 1, .00 39. .95 N
ATOM 2913 CZ ARG D 54 10. .716 -2, ,956 29. .769 1, .00 39. ,82 C
ATOM 2914 NHl ARG D 54 9, .870 -2, .722 30, .766 1, .00 40, .34 N
ATOM 2915 NH2 ARG D 54 11, .658 -3, .860 29. .935 1. .00 40, .00 N
ATOM 2916 C ARG D 54 11, .296 2, .863 28, .973 1. .00 40, ,11 C
ATOM 2917 O ARG D 54 11, .017 2, .779 30, .177 1, .00 40, .31 O
ATOM 2918 N TYR D 55 12. .501 3. .236 28. .536 1. ,00 40, .47 N
ATOM 2919 CA TYR D 55 13, .535 3. .637 29, .467 1. ,00 41, .02 C
ATOM 2920 CB TYR D 55 14. .841 2, .917 29. .181 1. ,00 41, .30 C
ATOM 2921 CG TYR D 55 14, .767 1, .417 29. .167 1. ,00 41, .64 C
ATOM 2922 GDI TYR D 55 15. .056 0, ,676 30. .308 1. ,00 41, .45 C
ATOM 2923 CEl TYR D 55 15. ,006 -0, .716 30. .285 1. ,00 41, .62 C
ATOM 2924 CZ TYR D 55 14. .665 -1. ,364 29. .103 1. ,00 42, .18 c
ATOM 2925 OH TYR D 55 14. .611 -2, .741 29. .054 1. ,00 42, .97 0
ATOM 2926 CE2 TYR D 55 14. .376 -0, .646 27, .965 1, .00 40, .93 c
ATOM 2927 CD2 TYR D 55 14, .437 0, .733 27. .999 1, ,00 41. .27 c
ATOM 2928 C TYR D 55 13. .753 5, .128 29, .311 1, .00 41. .65 c
ATOM 2929 O TYR D 55 14, .221 5, .585 28, .259 1. ,00 42. .12 o
ATOM 2930 N VAL D 56 13. .413 5, .902 30, .338 1, ,00 41. .86 N
ATOM 2931 CA VAL D 56 13, .590 7, .350 30, .237 1, ,00 42. .12 c
ATOM 2932 CB VAL D 56 12, ,245 8, ,166 30, ,156 1. ,00 41. ,91 c
ATOM 2933 CGI VAL D 56 11, .098 7, .449 30. .817 1, ,00 42. .53 c
ATOM 2934 CG2 VAL D 56 12, .407 9, .551 30. .750 1. ,00 42, .26 c
ATOM 2935 C VAL D 56 14, .521 7, .827 31. .335 1, .00 42, .34 c
ATOM 2936 O VAL D 56 14, .225 7. .655 32. .532 1. .00 42. .74 0
ATOM 2937 N GLU D 57 15, .656 8, .391 30, .899 1, .00 42. ,10 N
ATOM 2938 CA GLU D 57 16, .706 8. ,880 31. ,786 1, .00 41. ,85 C
ATOM 2939 CB GLU D 57 18, .105 8, .616 31. .218 1, ,00 41. .42 C
ATOM 2940 CG GLU D 57 19, ,172 8. ,651 32. .301 1, ,00 41. .99 C
ATOM 2941 CD GLU D 57 20. .576 8. ,851 31. .778 1, ,00 44. .29 C
ATOM 2942 OEl GLU D 57 20. ,726 9. ,397 30. .666 1, ,00 44. .38 0
ATOM 2943 OE2 GLU D 57 21. ,540 8. ,478 32. ,494 1. ,00 45. .27 0
ATOM 2944 C GLU D 57 16. ,539 10. ,365 32. ,055 1. ,00 41. .91 c
ATOM 2945 O GLU D 57 16. ,238 11. ,144 31. ,147 1. 00 42. ,23 0
ATOM 2946 N THR D 58 16. ,725 10. .743 33, ,315 1. 00 41. ,83 N
ATOM 2947 CA THR D 58 16, .747 12. ,142 33, ,726 1. 00 41. 66 C
ATOM 2948 CB THR D 58 15. .622 12, ,454 34. ,708 1. 00 41. ,70 C ATOM 2949 OGl THR D 58 14..383 12..354 34,.006 1.00 42.93 0
ATOM 2950 CG2 THR D 58 15. .756 13. .871 35, .282 1, .00 41, .32 c
ATOM 2951 C THR D 58 18. .086 12. .473 34, .355 1, .00 41, .29 c
ATOM 2952 O THR D 58 18. .552 11. .779 35, .263 1, .00 41, .34 0
ATOM 2953 N VAL D 59 18. .705 13. .533 33. .851 1, .00 40, .74 N
ATOM 2954 CA VAL D 59 19. .994 13. .939 34. .347 1, .00 40, .11 C
ATOM 2955 CB VAL D 59 21, .116 13. .635 33. .336 1, .00 40, .28 C
ATOM 2956 CGI VAL D 59 22, .440 14. .177 33. .838 1. .00 41. .06 C
ATOM 2957 CG2 VAL D 59 21, .237 12. .132 33. .094 1, .00 40, .21 C
ATOM 2958 C VAL D 59 19, .979 15. .409 34, .728 1. .00 39. .52 C
ATOM 2959 O VAL D 59 19. .682 16. .284 33. .904 1, ,00 39, .63 0
ATOM 2960 N ASN D 60 20, ,266 15, .642 36. .005 1, .00 38. .53 N
ATOM 2961 CA ASN D 60 20, .559 16, .944 36. .555 1, .00 37, .66 C
ATOM 2962 CB ASN D 60 19, .751 17, .135 37. .841 1. .00 37. .63 C
ATOM 2963 CG ASN D 60 19. .879 18, .540 38. .439 1, .00 39. .15 C
ATOM 2964 ODl ASN D 60 20. .786 19. .322 38. .112 1. .00 39. .45 O
ATOM 2965 ND2 ASN D 60 18. .965 18. .856 39. .347 1. .00 41, .24 N
ATOM 2966 C ASN D 60 22. .066 16. .991 36. .835 1. .00 37. .07 C
ATOM 2967 O ASN D 60 22. .523 16. ,526 37. .895 1. .00 37, .14 O
ATOM 2968 N LYS D 61 22. .833 17, .522 35. ,877 1. .00 36, .02 N
ATOM 2969 CA LYS D 61 24. .284 17, .681 36. ,029 1. .00 35. .34 C
ATOM 2970 CB LYS D 61 24. .936 18, .076 34. ,708 1. .00 35. .26 C
ATOM 2971 CG LYS D 61 25. .277 16, .898 33. .825 1, ,00 35, .03 c
ATOM 2972 CD LYS D 61 25. .896 17. .347 32. .532 1. .00 34. .29 c
ATOM 2973 CE LYS D 61 25, .631 16. .329 31. .473 1, .00 34. .80 c
ATOM 2974 NZ LYS D 61 26, .224 16, .730 30. .180 1. .00 36. .67 N
ATOM 2975 C LYS D 61 24, .681 18. .683 37. .112 1. .00 35. .17 C
ATOM 2976 O LYS D 61 25, .735 18, .538 37. ,727 1. .00 34. .89 O
ATOM 2977 N GLY D 62 23, .841 19. .692 37. .330 1. .00 35. .04 N
ATOM 2978 CA GLY D 62 24, .057 20, .680 38. ,374 1. .00 35. .15 C
ATOM 2979 C GLY D 62 24, .137 20. .076 39. .763 1. .00 35. ,56 C
ATOM 2980 O GLY D 62 24, .998 20. .443 40. ,553 1. .00 35. .83 O
ATOM 2981 N SER D 63 23, .240 19. ,153 40. .073 1, .00 35. .78 N
ATOM 2982 CA SER D 63 23, .276 18. ,484 41. ,369 1, .00 36. .29 C
ATOM 2983 CB SER D 63 21, .865 18. ,429 41. ,969 1, .00 36, .47 C
ATOM 2984 OG SER D 63 21, .008 17. ,558 41. ,243 1. .00 36. ,43 O
ATOM 2985 C SER D 63 23, .919 17, .080 41. .311 1, ,00 36. ,71 C
ATOM 2986 O SER D 63 23, ,928 16. .350 42. .300 1. ,00 36. ,84 O
ATOM 2987 N LYS D 64 24, ,440 16, .710 40, .140 1. .00 37. .00 N
ATOM 2988 CA LYS D 64 25, ,120 15, .441 39, .923 1. ,00 36. .80 C
ATOM 2989 CB LYS D 64 26, ,417 15, .374 40, .727 1. .00 36. .46 C
ATOM 2990 CG LYS D 64 27, ,422 16. .390 40. .240 1. .00 36. .86 C
ATOM 2991 CD LYS D 64 28, ,631 16, .570 41. .140 1. .00 37. .76 C
ATOM .2992 CE LYS D 64 29, ,298 17. .884 40. .778 1. .00 38. .56 C
ATOM 2993 NZ LYS. D 64 30, ,669 18. ,028 41. .305 1. .00 39. .73 N
ATOM 2994 C LYS D 64 24, ,221 14. ,261 40. ,206 1. ,00 37. ,38 C
ATOM 2995 O LYS D 64 24, ,690 13. ,185 40. .558 1. ,00 37, .70 O
ATOM 2996 N SER D 65 22, ,921 14. ,451 40. .037 1, ,00 37. .84 N
ATOM 2997 CA SER D 65 21, .999 13, ,328 40. .174 1, ,00 38, ,63 C
ATOM 2998 CB SER D 65 20, ,867 13. ,671 41. .136 1, ,00 38, .71 C
ATOM 2999 OG SER D 65 20, ,203 14, ,855 40. .734 1, ,00 39. ,23 O
ATOM 3000 C SER D 65 21, ,435 12. ,895 38. .821 1. ,00 39. .05 C
ATOM 3001 O SER D 65 21, ,436 13, ,658 37. .864 1, ,00 39. .10 O
ATOM 3002 N PHE D 66 20, ,971 11. ,657 38. .754 1, .00 39. .85 N
ATOM 3003 CA PHE D 66 20, ,360 11. ,089 37, .548 1, .00 41, .06 C
ATOM 3004 CB PHE D 66 21. ,412 10. ,655 36. .503 1. .00 41, .00 C
ATOM 3005 CG PHE- D 66 22. ,515 9. ,791 37. .048 1. ,00 41. .25 C
ATOM 3006 GDI PHE D 66 22. .626 8. ,465 36. .655 1. ,00 42. .36 C
ATOM 3007 CEl PHE D 66 23. .663 7. ,659 37. ,153 1. ,00 43. ,09 C
ATOM 3008 CZ PHE D 66 24. ,609 8. ,184 38. .060 1. ,00 42. ,16 c
ATOM 3009 CE2 PHE D 66 24. ,506 9. ,495 38. ,458 1. ,00 41. ,78 c
ATOM 3010 CD2 PHE D 66 23. ,465 10. ,303 37. .939 1. ,00 42. ,07 c
ATOM 3011 C PHE D 66 19. ,460 9. 917 37. ,913 1. ,00 41. 66 c
ATOM 3012 O PHE D 66 19. ,774 9. .158 38. ,838 1. ,00 42. ,19 0 ATOM 3013 N SER D 67 18,.351 9,.760 37..201 1,.00 41,.87 N
ATOM 3014 CA SER D 67 17 .450 8, .665 37. .497 1, .00 42 .54 C
ATOM 3015 CB SER D 67 16, .204 9, .199 38. .191 1, .00 42, .49 C
ATOM 3016 OG SER D 67 15 .374 9, .911 37. .288 1, .00 44 .07 O
ATOM 3017 C SER D 67 17, .064 7. .866 36. .257 1, .00 42, .81 C
ATOM 3018 O SER D 67 17 .043 8. .393 35. .153 1, .00 43 .06 O
ATOM 3019 N LEU D 68 16, .750 6. .591 36. .430 1. .00 43, .18 N
ATOM 3020 CA LEU D 68 16, .133 5, .850 35. .341 1, .00 43, .39 C
ATOM 3021 CB LEU D 68 16, .901 4. .558 35. .088 1, .00 43, .37 C
ATOM 3022 CG LEU D 68 16, .498 3, .717 33. .876 1, .00 43, .64 c
ATOM 3023 CD1 LEU D 68 17, .017 4. .352 32. .605 1, .00 41, .74 c
ATOM 3024 CD2 LEU D 68 17, .029 2, .290 34. .025 1, .00 43, .05 c
ATOM 3025 C LEU D 68 14, .698 5. .525 35. .718 1, .00 43, .63 c
ATOM 3026 O LEU D 68 14. .450 5. ,025 36. .813 1. ,00 43, .33 o
ATOM 3027 N ARG D 69 13. .750 5. .842 34. .833 1, .00 44, .30 N
ATOM 3028 CA ARG D 69 12, .365 5. .310 34. .934 1. .00 44, .40 C
ATOM 3029 CB ARG D 69 11, .340 6, .429 34. .790 1, .00 44, .69 C
ATOM 3030 CG ARG D 69 9, ,877 6. .025 34. ,925 1. .00 46, .02 C
ATOM 3031 CD ARG D 69 9, .059 7. ,243 35. ,313 1, ,00 49, .63 c
ATOM 3032 NE ARG D 69 7. .640 7. ,148 34. ,949 1. .00 54, .97 N
ATOM 3033 CZ ARG D 69 6. .625 6. .943 35. ,805 1, ,00 56, .63 C
ATOM 3034 NHl ARG D 69 5, .374 6. .895 35. ,352 1. .00 56, .12 N
ATOM 3035 NH2 ARG D 69 6, .842 6, .782 37. ,112 1, .00 57, .83 N
ATOM 3036 C ARG D 69 12, .135 4. .234 33. ,869 1. .00 44, .07 C
ATOM 3037 O ARG D 69 12. ,376 4. ,469 32. ,672 1, ,00 44. ,43 O
ATOM 3038 N ILE D 70 11, .704 3. ,056 34. ,307 1. .00 43. ,70 N
ATOM 3039 CA ILE D 70 11. .388 1. ,938 33. ,396 1. .00 43. ,53 C
ATOM 3040 CB ILE D 70 12, .112 0. .620 33. .790 1. .00 43. .04 c
ATOM 3041 CGI ILE D 70 13, .468 0. .916 34. .429 1. .00 42. .40 c
ATOM 3042 CD1 ILE D 70 14, .198 -0. .309 34. .860 1, .00 41. ,81 c
ATOM 3043 CG2 ILE D 70 12. .273 -0. .268 32. .582 1. .00 42. ,18 c
ATOM 3044 C ILE D 70 9, .878 1, .693 33. .352 1. ,00 43. ,87 c
ATOM 3045 O ILE D 70 9, .278 1, .301 34. .343 1. ,00 44, ,08 0
ATOM 3046 N ARG D 71 9, .268 1, .947 32. ,205 1. .00 44. .38 N
ATOM 3047 CA ARG D 71 7, .823 1. .787 32. ,037 1, ,00 44. .93 C
ATOM 3048 CB ARG D 71 7. .364 2. .627 30. ,851 1, .00 45. ,25 C
ATOM 3049 CG ARG D 71 7, .092 4. .069 31. .159 1, .00 47. .04 C
ATOM 3050 CD ARG D 71 5, .746 4. .407 30. .570 1. ,00 51. .66 c
ATOM 3051 NE ARG D 71 5, .701 4. .424 29. .099 1, .00 55. .58 N
ATOM 3052 CZ ARG D 71 4. .705 3. .918 28. .359 1, .00 57. .76 C
ATOM 3053 NHl ARG D 71 3. .666 3. .300 28. .933 1. .00 57. .56 N
ATOM 3054 NH2 ARG D 71 4. .749 4. .010 27. .029 1. .00 58. .57 N
ATOM 3055 C ARG D 71 7, ,423 0. .337 31. .789 1. ,00 44. .65 C
ATOM 3056 0 ARG D 71 8. .277 -0. .498 31. .542 1. .00 45. .26 O
ATOM 3057 N ASP D 72 6, .128 0. .054 31. .863 1. .00 44, .46 N
ATOM 3058 CA ASP D 72 5. .533 -1. .215 31. .422 1. .00 44. .72 C
ATOM 3059 CB ASP D 72 5, .390 -1, ,223 29. .901 1. ,00 45, .19 C
ATOM 3060 CG ASP D 72 4, .368 -0. .194 29. .403 1. .00 48. .24 C
ATOM 3061 ODl ASP D 72 4. .666 0. .561 28. .434 1. ,00 50. ,91 O
ATOM 3062 OD2 ASP D 72 3. .258 -0. .133 29. .989 1. ,00 50. ,87 O
ATOM 3063 C ' ASP D 72 6. .250 -2. .472 31. .887 1. ,00 44. ,13 C
ATOM 3064 O ASP D 72 6, .593 -3. .322 31. .066 1. ,00 44. ,33 O
ATOM 3065 N LEU D 73 6. .459 -2. .588 33. .201 1. ,00 43. ,44 N
ATOM 3066 CA LEU D 73 7. .242 -3. .683 33. .799 1. .00 42. ,68 C
ATOM 3067 CB LEU D 73 7. .412 -3. ,464 35. .296 1. .00 42. ,53 C
ATOM 3068 CG LEU D 73 8. ,521 -2. .493 35. .707 1, ,00 41. ,94 C
ATOM 3069 GDI LEU D 73 8. ,482 -2. ,245 37. ,198 1. ,00 40. ,56 C
ATOM 3070 CD2 LEU D 73 9. .864 -3. ,036 35. .297 1, .00 40. ,62 C
ATOM 3071 C LEU D 73 6. ,699 -5. ,082 33. ,556 1. ,00 42. 39 C
ATOM 3072 O LEU D 73 5. ,500 -5. ,278 33. ,396 1. ,00 42. ,53 O
ATOM 3073 N ARG D 74 7. ,610 -6. ,044 33. ,521 1. ,00 42. 33 N
ATOM 3074 CA ARG D 74 7. 276 -7. 445 33. 280 1. 00 42. 60 C
ATOM 3075 CB ARG D 74 7. ,176 -7. 727 31. ,777 1. 00 42. 97 C
ATOM 3076 CG ARG D 74 8. 472 -7. 524 31. 014 1. 00 45. 79 C ATOM 3077 CD ARG D 74 8,.253 -7,.753 29,.528 1,.00 50,.87 c
ATOM 3078 NE ARG D 74 9. .227 -7. .043 28. ,690 1, .00 54, .09 N
ATOM 3079 CZ ARG D 74 9, .095 -5, .784 28. ,264 1. .00 55, .43 C
ATOM 3080 NHl ARG D 74 8, .034 -5, .050 28. .605 1, .00 55, .13 N
ATOM 3081 NH2 ARG D 74 10, .038 -5. .251 27. .493 1, .00 56. .35 N
ATOM 3082 C ARG D 74 8, .301 -8, .378 33, .935 1, .00 42, .04 C
ATOM 3083 O ARG D 74 9. .455 -7, .974 34. .172 1, .00 41, ,78 O
ATOM 3084 N VAL D 75 7, .881 -9, .619 34. .204 1, .00 41, .25 N
ATOM 3085 CA VAL D 75 8, .697 -10, .608 34. .943 1, .00 40, .84 C
ATOM 3086 CB VAL D 75 8. .015 -12, .017 34. .960 1, .00 40, .73 C
ATOM 3087 CGI VAL D 75 8, .891 -13. ,070 35. .649 1, .00 41, .36 c
ATOM 3088 CG2 VAL D 75 6. .686 -11, .937 35. .672 1, ,00 40, .25 c
ATOM 3089 C VAL D 75 10, .190 -10. ,658 34. ,529 1, ,00 40, .38 c
ATOM 3090 O VAL D 75 11. .079 -10, .478 35. .365 1, .00 39, .84 0
ATOM 3091 N GLU D 76 10. ,423 -10. .882 33. .236 1, .00 40, .29 N
ATOM 3092 CA GLU D 76 11. .719 -10. ,705 32. .549 1, .00 40. .14 C
ATOM 3093 CB GLU D 76 11. .477 -10. ,467 31. .046 1, .00 41. .10 C
ATOM 3094 CG GLU D 76 10. .730 -11. .599 30. .304 1, .00 45. .43 C
ATOM 3095 CD GLU D 76 11. ,612 -12. .855 30, .054 1, .00 50. .46 C
ATOM 3096 OEl GLU D 76 11. ,360 -13. .603 29. .063 1, .00 51. .40 O
ATOM 3097 OE2 GLU D 76 12, .559 -13. .087 30. .851 1. .00 52. .29 O
ATOM 3098 C GLU D 76 12, .602 -9. .568 33. .052 1. .00 38. .84 c
ATOM 3099 O GLU D 76 13, ,825 -9. .670 32. .995 1. .00 38. .75 0
ATOM 3100 N ASP D 77 11. .995 -8. .475 33. .503 1, ,00 37. .42 N
ATOM 3101 CA ASP D 77 12, .781 -7, .340 33. ,974 1, .00 36. .19 C
ATOM 3102 CB ASP D 77 11, ,960 -6. .041 34. ,024 1. .00 36. .54 C
ATOM 3103 CG ASP D 77 11, .370 -5. ,644 32. ,675 1. .00 37. .48 C
ATOM 3104 ODl ASP D 77 12, .078 -5. .751 31. ,648 1. .00 37. .44 O
ATOM 3105 OD2 ASP D 77 10, .192 -5, .205 32. .656 1. .00 38. .17 O
ATOM 3106 C ASP D 77 13, ,424 -7. .582 35. .330 1. .00 35, .12 C
ATOM 3107 O ASP D 77 14, .403 -6. .903 35. .649 1. .00 35, .09 0
ATOM 3108 N SER D 78 12. .882 -8. .525 36. .118 1. .00 33, .83 N
ATOM 3109 CA SER D 78 13, .417 -8, .869 37. .458 1. .00 33, .11 C
ATOM 3110 CB SER D 78 12, ,750 -10. .123 38. .039 1, .00 33, .10 C
ATOM 3111 OG SER D 78 11, ,349 -9, .982 38. .232 1. ,00 34, .27 O
ATOM 3112 C SER D 78 14, ,918 -9. .101 37, ,418 1. .00 32. .47 C
ATOM 3113 O SER D 78 15, .403 -9. .818 36, .552 1. ,00 32. .51 O
ATOM 3114 N GLY D 79 15. .663 -8. .499 38, ,339 1. .00 32. .25 N
ATOM 3115 CA GLY D 79 17, .132 -8. .599 38, ,302 1. .00 31. .92 C
ATOM 3116 C GLY D 79 17, .871 -7, .446 38, ,939 1, .00 31. .96 C
ATOM 3117 O GLY D 79 17. .330 -6. ,760 39, ,809 1. .00 31. .58 O
ATOM 3118 N THR D 80 19, .104 -7. .229 38, ,479 1. .00 32. .63 N
ATOM 3119 CA THR D 80 20. ,058 -6. .318 39, ,129 1. .00 33. .50 C
ATOM 3120 CB THR D 80 21, .328 -7. .039 39, ,539 1. .00 33. .20 C
ATOM 3121 OGl THR D 80 20. ,986 -8. .131 40. ,393 1. .00 34. .33 O
ATOM 3122 CG2 THR D 80 22, .228 -6, .116 40. ,289 1. .00 33, .40 C
ATOM 3123 C THR D 80 20. ,442 -5. .192 38. ,197 1. .00 34. .18 C
ATOM 3124 O THR D 80 20, .919 -5, .434 37. ,087 1. .00 33. .90 O
ATOM 3125 N TYR D 81 20, ,210 -3. .965 38. ,668 1. .00 35. .19 N
ATOM 3126 CA TYR D 81 20, .462 -2, ,735 37. ,913 1. ,00 35, .91 C
ATOM 3127 CB TYR D 81 19, .195 -1. ,912 37. ,803 1. .00 35. .33 C
ATOM 3128 CG TYR D 81 18, .114 -2. .593 37. ,010 1. .00 34. .85 C
ATOM 3129 CD1 TYR D 81 17, .492 -3. ,747 37. ,488 1. .00 35. ,35 C
ATOM 3130 CEl TYR D 81 16, .506 -4, ,389 36. ,753 1. .00 35. .81 C
ATOM 3131 CZ TYR D 81 16. ,132 -3. .866 35. ,535 1. ,00 35. .53 C
ATOM 3132 OH TYR D 81 15. ,167 -4, .496 34. ,808 1, ,00 35. ,83 O
ATOM 3133 CE2 TYR D 81 16. .733 -2, .724 35. ,044 1, ,00 35. .04 C
ATOM 3134 CD2 TYR D 81 17. .707 -2. .091 35. ,787 1. .00 33. ,32 C
ATOM 3135 C TYR D 81 21. .536 -1. .939 38. ,647 1. .00 37. ,21 C
ATOM 3136 O TYR D 81 21. .466 -1. ,770 39. 868 1. ,00 37. 81 0
ATOM 3137 N LYS D 82 22. .553 -1. .501 37. ,913 1. ,00 37. ,74 N
ATOM 3138 CA LYS D 82 23. .568 -0. ,638 38. 456 1. ,00 38. 35 C
ATOM 3139 CB LYS D 82 24. .934 -1. ,323 38. ,424 1. ,00 38. 34 C
ATOM 3140 CG LYS D 82 25. ,392 -1. ,989 39. 709 1. ,00 37. 40 C ATOM 3141 CD LYS D 82 25..142 -3..457 39.,649 1..00 36,.64 c
ATOM 3142 CE LYS D 82 26. .282 -4. ,240 40. ,237 1. .00 34. .73 c
ATOM 3143 NZ LYS D 82 26. .197 -4. ,327 41. ,696 1. .00 35. .21 N
ATOM 3144 C LYS D 82 23. .595 0. ,578 37. ,557 1. .00 39. .27 C
ATOM 3145 O LYS D 82 23. .505 0. ,452 36, ,339 1. .00 39. .29 O
ATOM 3146 N CYS D 83 23. .701 1. .753 38. .161 1. .00 40. .62 N
ATOM 3147 CA CYS D 83 23. .967 2. .977 37. .427 1. .00 42. .31 C
ATOM 3148 CB CYS D 83 23. .147 4. .119 38. .004 1. .00 42. .45 C
ATOM 3149 SG CYS D 83 23. .539 4. .543 39, ,737 1. .00 47. .14 S
ATOM 3150 C CYS D 83 25. .454 3. .320 37, .525 1. .00 42. .64 C
ATOM 3151 O CYS D 83 26. .065 3. .098 38, .561 1, .00 43. .32 O
ATOM 3152 N GLY D 84 26. .019 3. .871 36, .450 1, .00 43. .26 N
ATOM 3153 CA GLY D 84 27. .425 4. .309 36, .406 1. .00 42. .90 C
ATOM 3154 C GLY D 84 27. .562 5. ,762 35, .971 1, .00 42, .52 C
ATOM 3155 O GLY D 84 26, .877 6. ,201 35. .065 1. .00 41, .68 O
ATOM 3156 N ALA D 85 28. .464 6. ,488 36. .633 1, .00 42, .86 N
ATOM 3157 CA ALA D 85 28. .713 7, ,918 36. .403 1. .00 43. .03 C
ATOM 3158 CB ALA D 85 28. .307 8, ,728 37. .624 1, .00 42. .74 C
ATOM 3159 C ALA D 85 30, .183 8. ,120 36. ,126 1. .00 43, .30 C
ATOM 3160 O ALA D 85 31. .014 7, ,609 36. ,860 1, ,00 43, .69 O
ATOM 3161 N TYR D 86 30. ,510 8. ,847 35. ,065 1. .00 43, ,66 N
ATOM 3162 CA TYR D 86 31. .899 9, ,105 34. ,716 1, .00 44, ,36 C
ATOM 3163 CB TYR D 86 32. .219 8. .530 33. .340 1, ,00 44, ,95 C
ATOM 3164 CG TYR D 86 31. .761 7. .096 33. .251 1, .00 46, .16 C
ATOM 3165 CD1 TYR D 86 30. .403 6. .796 33. .028 1, ,00 47, .23 C
ATOM 3166 CEl TYR D 86 29. .940 5, .482 32. .973 1, ,00 47. .72 c
ATOM 3167 CZ TYR D 86 30. .837 4, ,423 33. .142 1, .00 48. .22 c
ATOM 3168 OH TYR D 86 30. ,343 3, ,123 33. .084 1. .00 47. .41 0
ATOM 3169 CE2 TYR D 86 32, .210 4, .688 33. ,366 1, ,00 48. .08 c
ATOM 3170 CD2 TYR D 86 32, .657 6, .033 33. ,432 1, .00 46. .88 c
ATOM 3171 C TYR D 86 32, .105 10, .602 34. .795 1, .00 44. .66 c
ATOM 3172 O TYR D 86 31, ,162 11, .360 34. .575 1, .00 44. .79 0
ATOM 3173 N PHE D 87 33, .307 11. ,041 35. .162 1, .00 44, .81 N
ATOM 3174 CA PHE D 87 33, ,464 12. .442 35. .542 1, ,00 45, ,11 c
ATOM 3175 CB PHE D 87 33, ,095 12. .677 37. .019 1, ,00 45, .03 c
ATOM 3176 CG PHE D 87 33, ,602 11. .621 37. ,964 1, ,00 45, .21 c
ATOM 3177 CD1 PHE D 87 34. ,890 11. .693 38. .486 1, .00 45, .51 c
ATOM 3178 CEl PHE D 87 35. ,358 10. .728 39. ,372 1, .00 45, ,00 c
ATOM 3179 CZ PHE D 87 34. .536 9. .690 39. ,747 1, .00 45, ,07 c
ATOM 3180 CE2 PHE D 87 33. .246 9. .611 39, .238 1. .00 44. .96 c
ATOM 3181 CD2 PHE D 87 32. .784 10. .576 38. .357 1, .00 44. .46 c
ATOM 3182 C PHE D 87 34. .782 13, .115 35. .188 1. .00 45. .34 c
ATOM 3183 O PHE D 87 35. .762 12, .444 34. .866 1, .00 45. .54 0
ATOM 3184 N SER D 88 34. ,756 14, ,451 35. .255 1, .00 45. .64 N
ATOM 3185 CA SER D 88 35. .821 15, .349 34. .811 1, .00 45. .97 c
ATOM 3186 CB SER D 88 35. ,297 16, .247 33. .694 1, ,00 46. .20 c
ATOM 3187 OG SER D 88 35. .337 15, .595 32. .433 1, ,00 47. .34 0
ATOM 3188 C SER D 88 36. .310 16. ,234 35. .951 1, .00 45, .99 c
ATOM 3189 O SER D 88 37. .402 16. .800 35. .897 1, .00 46. .11 0
ATOM 3190 N PRO D 99 37. .620 8. .378 34. .147 1, .00 41, .32 N
ATOM 3191 CA PRO D 99 37. .333 7. .914 35. .515 1, ,00 41. .01 C
ATOM 3192 CB PRO D 99 37. .997 8. ,983 36. .403 1, .00 41. .21 C
ATOM 3193 CG PRO D 99 38, .437 10. ,142 35. .447 1. .00 41. .32 C
ATOM 3194 CD PRO D 99 37, .888 9. .829 34. .076 1, ,00 41. .24 C
ATOM 3195 C PRO D 99 35. .827 7. .848 35, ,777 1. ,00 40, ,76 C
ATOM 3196 O PRO D 99 35. .075 8. .620 35. .183 1. ,00 40, ,78 0
ATOM 3197 N GLY D 100 35. .390 6. .940 36. .652 1. .00 40, ,55 N
ATOM 3198 CA GLY D 100 33, .944 6. .725 36. ,897 1, ,00 39, ,88 C
ATOM 3199 C GLY D 100 33. .600 5. .794 38. .049 1, .00 39. ,22 C
ATOM 3200 O GLY D 100 34. ,461 5. .086 38. .544 1. ,00 39. ,19 O
ATOM 3201 N GLU D 101 32, .337 5. .793 38. ,470 1. ,00 38. ,90 N
ATOM 3202 CA GLU D 101 31. ,895 5. ,043 39. ,662 1. ,00 38. 56 C
ATOM 3203 CB GLU D 101 31. .795 5, .959 40. ,905 1. ,00 38. ,61 C
ATOM 3204 CG GLU D 101 33. ,089 6. .543 41. ,423 1. ,00 39. 35 C ATOM 3205 CD GLU D 101 34,.049 5..477 41..957 1..00 42,.48 c
ATOM 3206 OEl GLU D 101 35. .275 5. .773 42. .085 1. .00 41. .06 0
ATOM 3207 OE2 GLU D 101 33. .573 4, .341 42. ,244 1. .00 43, .54 0
ATOM 3208 C GLU D 101 30. .543 4. .392 39. .440 1. .00 38. .05 c
ATOM 3209 O GLU D 101 29. .660 4, .997 38. .864 1. .00 37, .16 0
ATOM 3210 N LYS D 102 30. .373 3. .170 39. .926 1. .00 38, .57 N
ATOM 3211 CA LYS D 102 29. .047 2. .525 39. ,897 1. .00 39. .26 C
ATOM 3212 CB LYS D 102 29. .134 1. .086 39. .354 1. .00 39. .72 C
ATOM 3213 CG LYS D 102 29. ,719 0. ,974 37. .951 1. ,00 42. ,83 c
ATOM 3214 CD LYS D 102 28. ,973 -0. ,064 37. .104 1. ,00 47. .99 c
ATOM 3215 CE LYS D 102 29. ,772 -1. ,371 36. .971 1. ,00 51. ,61 c
ATOM 3216 NZ LYS D 102 29. ,020 -2. .452 36. .233 1. .00 53, ,94 N
ATOM 3217 C LYS D 102 28, .308 2. ,529 41. .252 1. ,00 38, .60 C
ATOM 3218 O LYS D 102 28. ,917 2. ,359 42. ,306 1. .00 38, .71 O
ATOM 3219 N GLY D 103 26. ,992 2. ,723 41. ,207 1. ,00 38. ,22 N
ATOM 3220 CA GLY D 103 26. ,136 2. .526 42. .382 1, .00 38, .12 C
ATOM 3221 C GLY D 103 26. .009 1. ,054 42. .739 1. ,00 37, ,72 C
ATOM 3222 O GLY D 103 26. .248 0, .185 41. .891 1, .00 38, .11 o
ATOM 3223 N ALA D 104 25. .641 0. .759 43. .984 1. ,00 37. .10 N
ATOM 3224 CA ALA D 104 25. .685 -0. .624 44. .471 1, .00 36. .84 c
ATOM 3225 CB ALA D 104 25. .466 -0. ,683 45. .965 1. ,00 36, .58 c
ATOM 3226 C ALA D 104 24. .693 -1, .513 43. .722 1, .00 36, .89 c
ATOM 3227 O ALA D 104 24. .991 -2. ,652 43. .389 1. ,00 37. .36 0
ATOM 3228 N GLY D 105 23. .519 -0. .972 43. .432 1, ,00 36. .98 N
ATOM 3229 CA GLY D 105 22. .539 -1. .667 42. .623 1. ,00 36. .50 c
ATOM 3230 C GLY D 105 21. .135 -1. .498 43. .141 1. .00 36. ,28 c
ATOM 3231 O GLY D 105 20. ,917 -0. .997 44, ,244 1. .00 36. ,50 0
ATOM 3232 N THR D 106 20. .186 -1, .911 42. .314 1, .00 36. ,08 N
ATOM 3233 CA THR D 106 18. .810 -2, .125 42. .713 1, .00 36. ,15 C
ATOM 3234 CB THR D 106 17, .874 -1, .220 41, .895 1, .00 36. .33 C
ATOM 3235 OGl THR D 106 18. .229 0, .156 42. .089 1. .00 36. .72 O
ATOM 3236 CG2 THR D 106 16, .445 -1, .409 42, .311 1, .00 37. .11 C
ATOM 3237 C THR D 106 18. .515 -3, .595 42. .386 1, .00 36. .03 c
ATOM 3238 O THR D 106 18, .806 -4, ,034 41, .267 1. ,00 36. ,46 o
ATOM 3239 N VAL D 107 17, .995 -4. .382 43, .338 1, ,00 35. .53 N
ATOM 3240 CA VAL D 107 17, .420 -5, .678 42, .927 1. ,00 34. ,79 C
ATOM 3241 CB VAL D 107 18, .049 -6, .952 43, ,597 1, .00 34. .54 C
ATOM 3242 CGI VAL D 107 17, .254 -7, .451 44, ,711 1. .00 35. .41 C
ATOM 3243 CG2 VAL D 107 19, .488 -6, ,698 44, ,027 1, .00 35. .64 C
ATOM 3244 C VAL D 107 15, .882 -5, .626 42, ,821 1. .00 34. .18 C
ATOM 3245 O VAL D 107 15, .153 -5, .489 43, .816 1, .00 33. .80 O
ATOM 3246 N LEU D 108 15. .427 -5, .672 41, .572 1. .00 33. .40 N
ATOM 3247 CA LEU D 108 14. .026 -5, .543 41, .235 1, .00 33. .01 C
ATOM 3248 CB LEU D 108 13. .892 -4, .831 39, .896 1. .00 33. .00 C
ATOM 3249 CG LEU D 108 12. .566 -4, .235 39, .374 1, .00 33. .86 C
ATOM 3250 CD1 LEU D 108 11. .301 -4, .627 40, .135 1. .00 34. .10 C
ATOM 3251 CD2 LEU D 108 12, .415 -4, .524 37, .875 1, .00 32. .03 C
ATOM 3252 C LEU D 108 13, .417 -6, ,919 41, .091 1. .00 32. .57 C
ATOM 3253 O LEU D 108 14, .015 -7, .807 40, .508 1, .00 32. .64 O
ATOM 3254 N THR D 109 12. .217 -7. .098 41, ,605 1, .00 32, .14 N
ATOM 3255 CA THR D 109 11, .490 -8, .306 41, .295 1, .00 31, ,94 C
ATOM 3256 CB THR D 109 11. .619 -9, ,413 42, ,407 1, .00 31, ,81 C
ATOM 3257 OGl THR D 109 10, .369 -10, .076 42, .596 1, .00 32, ,13 O
ATOM 3258 CG2 THR D 109 12. .071 -8. .856 43, .724 1, ,00 31. ,42 C
ATOM 3259 C THR D 109 10, .069 -7. .932 40, .901 1. ,00 31. .92 C
ATOM 3260 O THR D 109 9. ,408 -7. ,153 41, .587 1. ,00 31, .68 O
ATOM 3261 N VAL D 110 9. .635 -8. .446 39, .751 1, ,00 31. .95 N
ATOM 3262 CA VAL D 110 8. .332 -8. .099 39, ,186 1. ,00 31. .54 C
ATOM 3263 CB VAL D 110 8. ,383 -7. .936 37. ,656 1. .00 31. .65 c
ATOM 3264 CGI VAL D 110 7. ,082 -7. .284 37, ,146 1. ,00 30. .75 c
ATOM 3265 CG2 VAL D 110 9. .628 -7. .129 37. ,216 1. ,00 30. ,44 c
ATOM 3266 C VAL D 110 7. ,340 -9, .184 39, ,512 1, ,00 31. ,88 c
ATOM 3267 O VAL D 110 7. ,635 -10, .367 39, .325 1. ,00 32. ,39 0
ATOM 3268 N LYS D 111 6. .160 -8. .771 39, .977 1. ,00 31. ,88 N ATOM 3269 CA LYS D 111 5..113 -9.,670 40.,445 1.,00 31..62 c
ATOM 3270 CB LYS D 111 4. .924 -10. .844 39. ,488 1. .00 31. .59 c
ATOM 3271 CG LYS D 111 4. .107 -10. .551 38. ,264 1. .00 30. .11 c
ATOM 3272 CD LYS D 111 3. .470 -11. .863 37. ,787 1. ,00 27, .97 c
ATOM 3273 CE LYS D 111 2. .016 -11. .633 37. .521 1. ,00 26, .09 c
ATOM 3274 NZ LYS D 111 1. .418 -11. .163 38. ,781 1. ,00 24, .52 N
ATOM 3275 C LYS D 111 5. .422 -10. .184 41. .856 1. ,00 31. .99 c
ATOM 3276 O LYS D 111 4. .582 -10. .094 42. .774 1, ,00 32, .43 0
ATOM 3277 O HOH W 1 20. .434 11. .911 29. ,836 1. ,00 28. .88 0
ATOM 3278 O HOH W 2 51. .173 8. .997 9. .730 1. ,00 44, .36 o
ATOM 3279 O HOH W 3 47. .689 11. .742 13. ,593 1. ,00 27. ,86 0
ATOM 3280 O HOH W 4 11, .612 -6. .756 46, ,515 1. ,00 30. .22 0
ATOM 3281 O HOH W 5 50. .210 12. .148 9. ,875 1, .00 31, .20 0
ATOM 3282 O HOH W 6 49. .395 14. .702 4. .881 1. ,00 23, .52 0
ATOM 3283 O HOH W 7 32. .057 7. .039 10. .045 1. .00 27, .86 0
ATOM 3284 O HOH W 8 13. .846 -7. .318 45. ,160 1. ,00 37. .92 0
ATOM 3285 O HOH W 9 45. .367 -5. .972 1, .806 1. .00 56. .96 o
ATOM 3286 O HOH W 10 50. .323 2. ,945 4. .830 1, .00 31. .28 0
ATOM 3287 O HOH w 11 50. .653 13. ,787 7, .807 1. ,00 31. .34 o
ATOM 3288 O HOH w 12 55. .639 7, ,497 18, .084 1, .00 28. .59 0
ATOM 3289 O HOH w 13 50. .800 -9, ,586 17. ,024 1. ,00 31, .78 0
ATOM 3290 O HOH w 14 30. .173 21, ,846 12, ,570 1, ,00 47. .23 0
ATOM 3291 O HOH w 15 22. .770 -0, ,220 48. .758 1. .00 43. .83 0
ATOM 3292 O HOH w 16 14. .574 24, ,569 28. .773 1, ,00 50. .25 0
ATOM 3293 O HOH w 17 17. .273 23, .275 28. ,770 1. .00 32. .25 0
ATOM 3294 0 HOH w 18 15. .628 9, .857 28. ,519 1. .00 31. .38 0
ATOM 3295 0 HOH w 19 47. .486 29, .840 6. .150 1, .00 53. .53 0
ATOM 3296 0 HOH w 20 64, .546 22, .854 17. .164 1. .00 47. .54 0
ATOM 3297 0 HOH w 21 13. .831 9, .756 34. .661 1, .00 48, .11 o
ATOM 3298 0 HOH w 22 53. .874 4, ,595 9. .539 1. .00 29, .77 0
ATOM 3299 0 HOH w 23 17. ,826 11, ,221 28, .000 1, .00 37. .97 0
ATOM 3300 0 HOH w 24 21. .478 16. .649 31, .244 1. ,00 29. .30 0
ATOM 3301 0 HOH w 25 61, .648 23, .163 -6, .346 1. ,00 41. .07 0
ATOM 3302 0 HOH w 26 17. .685 -4. .024 28, .143 1. ,00 45. .65 0
ATOM 3303 0 HOH w 27 18, ,676 48, .553 28, .572 1. .00 49. .95 0
ATOM 3304 0 HOH w 28 28. .883 35, .475 31, .748 1. .00 65. ,90 0
ATOM 3305 0 HOH w 29 26, .495 13, .768 28, ,887 1. .00 28. .89 0
ATOM 3306 0 HOH w 30 20, .570 7, .084 21. .442 1. .00 45, .88 0
ATOM 3307 0 HOH w 31 25, ,634 10, .403 29. ,395 1. .00 35. .32 0
ATOM 3308 0 HOH w 32 62, ,535 39, .022 -0. ,570 1. .00 46. .92 0
ATOM 3309 0 HOH w 33 67. ,283 26, .093 -4. ,127 1. .00 33. ,73 0
ATOM 3310 0 HOH w 34 27, .566 41, ,774 33. .161 1, .00 68. .26 0
ATOM 3311 0 HOH w 35 24, .143 13, .706 28, .178 1. ,00 29. ,46 0
ATOM 3312 0 HOH w 36 30. .372 26, ,293 12, .250 1. .00 72. .48 0
ATOM 3313 0 HOH w 37 45, .656 20, .943 8, .052 1. ,00 33. .27 o
ATOM 3314 0 HOH w 38 48, .649 7, .010 15, ,549 1. .00 53. .94 0
ATOM 3315 0 HOH w 39 31, .570 18, .599 13, .713 1. .00 41. .28 0
ATOM 3316 0 HOH w 40 53, .663 7, .208 10, .450 1, ,00 34, .57 0
ATOM 3317 0 HOH w 41 38, ,580 12, .260 2, .002 1. ,00 37. .67 0
ATOM 3318 0 HOH w 42 68, .611 36, .093 1, .637 1. .00 58. .68 0
ATOM 3319 0 HOH w 43 66, .806 32, ,948 6, .043 1. .00 28. ,02 0
ATOM 3320 0 HOH w 44 50, .597 16, .056 2, .995 1. ,00 20. .92 0
ATOM 3321 0 HOH w 45 32, .402 18, .632 9, .245 1. ,00 57. .58 0
ATOM 3322 0 HOH w 46 17, .826 -1, .585 26, .168 1. ,00 33. .42 o
ATOM 3323 0 HOH w 47 27, .978 18, .431 13, .061 1. .00 32. ,36 0
ATOM 3324 0 HOH w 48 31. .130 23, ,731 14, .541 1, ,00 49. ,15 0
ATOM 3325 0 HOH w 49 42. ,973 18, ,176 6, .181 1. ,00 33, .87 0
ATOM 3326 0 HOH w 50 32, .854 1, .573 13, ,656 1. ,00 69. .40 o
ATOM 3327 0 HOH w 51 61. .024 21, ,580 -8, .223 1. .00 33. .81 0
ATOM 3328 0 HOH w 52 21. .853 18, .003 33, .363 1, .00 35, .88 0
ATOM 3329 0 HOH w 53 28. .214 18, ,749 29, .985 1. ,00 36. .72 0
ATOM 3330 0 HOH w 54 47. .190 27, ,455 4, .981 1. ,00 33. ,48 0
ATOM 3331 0 HOH w 55 48. .698 14. ,899 12. ,805 1, .00 36, .47 0
ATOM 3332 0 HOH w 56 22. .007 13, .901 29. .964 1. ,00 43. ,41 0 ATOM 3333 O HOH W 57 22,.817 3,.633 29..513 1,.00 56,.91 O
ATOM 3334 O HOH W 58 58, .369 24, .559 -5, .982 1, .00 20, .15 O
ATOM 3335 O HOH W 59 24, .791 22. .275 12. .738 1. .00 29, .00 O
ATOM 3336 O HOH W 60 32, .506 39, .375 33. .303 1. .00 38, .43 O
ATOM 3337 0 HOH W 61 53, .833 40, .967 1, .428 1, .00 45, .08 O
ATOM 3338 O HOH W 62 57, .058 27. .269 -9. .143 1. .00 40. .00 O
ATOM 3339 O HOH W 63 69, .526 32. .652 5, .064 1. .00 33, .59 O
ATOM 3340 O HOH W 64 26. .026 46, ,491 29. .214 1. .00 49, .43 O
ATOM 3341 O HOH W 65 7. .535 -12, .277 43, .624 1. .00 38. .83 O
ATOM 3342 O HOH W 66 57. .673 36. .036 -4, .990 1. ,00 58. .18 O
ATOM 3343 O HOH W 67 25. .219 2, .698 45, .646 1. ,00 63. .61 O
ATOM 3344 O HOH W 68 15, .224 15, .226 16, ,533 1. .00 44, .99 O
ATOM 3345 O HOH W 69 14. .303 30, .312 26. .773 1. ,00 55. .43 O
ATOM 3346 O HOH W 70 27, .473 17, .640 8. .014 1. .00 44, ,24 O
ATOM 3347 O HOH W 71 33. .541 14, .753 28. ,074 1. .00 57. ,64 O
ATOM 3348 O HOH W 72 24. .106 -5, .245 36. .422 1. .00 35. .69 O
ATOM 3349 O HOH W 73 19, .945 -3. .453 25. .718 1. ,00 62. .43 O
ATOM 3350 O HOH W 74 27, .055 43, ,217 29. .667 1. .00 36. .48 O
ATOM 3351 O HOH W 75 61, ,808 21. .334 21. .511 1. .00 41, ,05 O
ATOM 3352 O HOH W 76 28, ,392 -1, .577 41. ,924 1. ,00 40. .31 O
ATOM 3353 O HOH W 77 41. .700 24, .432 10. ,528 1. ,00 50. ,92 O
ATOM 3354 O HOH W 78 56. ,356 17. .804 -2. ,343 1. ,00 37. ,41 O
ATOM 3355 O HOH W 79 36. ,787 28. .401 12. ,252 1. ,00 59. .49 O
ATOM 3356 O HOH W 80 47, ,719 11. .922 11. ,398 1. .00 44. ,13 O
ATOM 3357 O HOH w 81 4. .122 -2. .877 44. .501 1. .00 47. ,12 O
ATOM 3358 O HOH w 82 52, ,740 31, .000 -8. .756 1. .00 43. .99 0
ATOM 3359 O HOH w 83 7, .919 -11. .057 46. .234 1. .00 41. ,46 0
ATOM 3360 0 HOH w 84 32, ,706 34, .935 19. .255 1. .00 42. ,71 0
ATOM 3361 0 HOH w 85 59, .882 27. .603 19. .759 1. .00 61. .63 0
ATOM 3362 0 HOH w 86 32. .168 6, .815 13. .604 1. .00 49. .25 0
ATOM 3363 0 HOH w 87 59. ,729 2, .501 13, .133 1. ,00 38. ,27 0
ATOM 3364 0 HOH w 88 56. .064 4. .299 10. .903 1. ,00 35. .41 0
ATOM 3365 0 HOH w 89 30, .138 -2, .702 33. .252 1. ,00 47. .19 0
ATOM 3366 0 HOH w 90 38. .708 21, .593 5. .409 1. ,00 46. .41 0
ATOM 3367 0 HOH w 91 28. .192 17, .922 37. .236 1. .00 50. .27 0
ATOM 3368 0 HOH w 92 29. .568 3. .973 44. .497 1. ,00 56. .59 0
ATOM 3369 0 HOH w 93 34. .862 20, .140 13. .615 1. .00 58. ,79 0
ATOM 3370 0 HOH w 94 68, .056 37, .171 -4, .566 1. .00 46, .07 0
ATOM 3371 0 HOH w 95 20. .067 -18. .415 28. .488 1. .00 39. ,57 0
ATOM 3372 0 HOH w 96 64. .699 22, .658 1. .365 1. .00 35. .36 0
ATOM 3373 0 HOH w 97 66. .830 20. .070 6. .461 1. .00 40. .73 0
ATOM 3374 0 HOH w 98 21. .629 21. .137 36. .271 1. .00 45, ,67 0
ATOM 3375 0 HOH w 99 35, .422 2. .703 41. .956 1, .00 52, ,70 0
ATOM 3376 0 HOH w 100 24, ,037 1. .650 19. .799 1, .00 58, ,56 0
ATOM 3377 0 HOH w 101 61, .498 2. .982 15. .930 1. .00 55, ,15 0
ATOM 3378 0 HOH w 102 35, .953 15. .608 4, .118 1. .00 25, ,75 0
ATOM 3379 0 HOH w 103 25, .517 31. .363 12, .480 1, .00 39, ,04 0
ATOM 3380 0 HOH w 104 16, .726 21, ,992 15. ,197 1. .00 52, .30 0
ATOM 3381 0 HOH w 105 52, .552 23, .250 25, .811 1, .00 48, .16 0
ATOM 3382 0 HOH w 106 24, .153 12, ,188 30. .527 1. ,00 27, ,39 0
ATOM 3383 0 HOH w 107 53, .933 -9, ,516 4. .486 1, .00 42, .89 0
ATOM 3384 0 HOH w 108 23, .827 37, ,285 16, .265 1. ,00 54, .62 0
ATOM 3385 0 HOH w 109 28. .396 33, ,187 28. ,407 1. ,00 53. ,09 0
ATOM 3386 0 HOH w 110 31. .985 20. ,657 32. .687 1, ,00 58. ,85 0
ATOM 3387 0 HOH w 111 18. ,171 -15. ,401 30. ,507 1. ,00 56. ,89 0
ATOM 3388 0 HOH w 112 22. ,082 0. ,773 46. ,243 1. ,00 48. ,16 0
ATOM 3389 0 HOH w 113 34. ,526 22. ,736 14. 520 1. 00 41. ,26 0
ATOM 3390 0 HOH w 114 22. ,419 6. ,371 28. ,995 1. 00 56. 85 0
ATOM 3391 0 HOH w 115 67. ,422 16. ,825 11. ,168 1. ,00 60. 46 0
ATOM 3392 0 HOH w 116 67. 448 23. ,130 0. 776 1. 00 33. 43 0
ATOM 3393 0 HOH w 117 18. ,592 16. ,299 30. 811 1. 00 42. 83 0
ATOM 3394 0 HOH w 118 34. 587 24. 867 10. 841 1. 00 54. 23 0
ATOM 3395 0 HOH w 119 30. ,859 34. ,219 31. 592 1. 00 42. 88 0
ATOM 3396 0 HOH w 120 49. 605 4. 517 19. 934 1. 00 62. 19 0 ATOM 3397 O HOH W 121 5..422 -5.,622 26..696 1..00 68..49 0
ATOM 3398 O HOH W 122 17. .557 13. .571 16. .130 1. .00 43. .21 0
ATOM 3399 O HOH W 123 27, ,902 37. ,884 19. .254 1. .00 64. .98 0
ATOM 3400 O HOH W 124 17, ,490 12. .457 13. .620 1. .00 56. .86 0
ATOM 3401 O HOH W 125 25, .374 44. .666 33. .403 1. .00 46. .35 0
ATOM 3402 O HOH W 126 12. ,246 0. .705 24. .754 1. .00 56. .61 0
ATOM 3403 O HOH W 127 22, ,142 5. .206 26. .086 1. .00 40. .68 0
ATOM 3404 O HOH W 128 37. ,638 -12. ,506 6. .296 1. .00 57. .01 0
ATOM 3405 O HOH W 129 48. ,345 16. .352 1. .698 1. .00 30. .83 0
ATOM 3406 O HOH W 130 20. ,648 20. ,480 33. .583 1. .00 34. .60 0
ATOM 3407 O HOH W 131 64. ,275 41. ,462 -8. .991 1. .00 47. .63 0
ATOM 3408 O HOH W 132 60, ,760 12. .924 7. ,514 1. .00 49. .20 0
ATOM 3409 O HOH W 133 50. ,675 6. ,054 17. ,267 1. .00 41. .28 0
ATOM 3410 O HOH W 134 33. .273 -5, .842 12. ,720 1. ,00 54. .10 0
ATOM 3411 O HOH W 135 32. ,026 34. .506 33. ,860 1. .00 62. .11 0
ATOM 3412 O HOH W 136 30. ,538 27. .830 33. .165 1. .00 49. .21 0
ATOM 3413 O HOH W 137 46. ,775 19. .029 10. .612 1. .00 52. .46 0
ATOM 3414 O HOH W 138 67. ,563 23, ,044 3. .123 1. .00 36, .24 0
ATOM 3415 O HOH W 139 39, ,108 16. ,251 0. .823 1, .00 51, .06 0
ATOM 3416 O HOH W 140 20. ,593 22. .210 39. .321 1. .00 53. .90 0
ATOM 3417 O HOH W 141 46. ,106 8. .016 1. .533 1. .00 37. .88 0
ATOM 3418 O HOH W 142 52. ,095 35. ,903 9. .125 1. .00 32, .61 0
ATOM 3419 O HOH W 143 75. ,389 25. .371 16. .968 1. .00 35. .99 0
ATOM 3420 O HOH W 144 15, ,057 9. .817 16. ,549 1. ,00 65. .48 0
ATOM 3421 0 HOH w 145 37, ,631 28. .173 28, ,732 1. .00 38. .60 0
ATOM 3422 0 HOH w 146 66. ,515 22, .664 20. ,027 1. .00 52. .17 0
ATOM 3423 0 HOH w 147 42. ,528 -7. .022 23. ,940 1. .00 71. .26 0
ATOM 3424 0 HOH w 148 54. ,947 -3, .340 6, .545 1. .00 55. .11 0
ATOM 3425 0 HOH w 149 28, ,775 -10. .352 32. .112 1. .00 44. .73 0
ATOM 3426 0 HOH w 150 18. ,892 31. .401 12. .777 1. .00 37. .43 0
ATOM 3427 0 HOH w 151 9. ,905 -12. .495 39, .620 1. .00 32. .28 0
ATOM 3428 0 HOH w 152 38, ,303 -19. .018 4. .482 1. .00 70. .97 0
ATOM 3429 0 HOH w 153 15. ,856 34. .267 36. .720 1. .00 58. .14 0
ATOM 3430 0 HOH w 154 30. ,760 5. ,017 7. .768 1, .00 43. ,73 0
ATOM 3431 0 HOH w 155 16. .890 20. .222 33. .788 1. .00 49. .43 0
ATOM 3432 0 HOH w 156 33. .273 2. .733 7. .110 1, ,00 39. ,05 0
ATOM 3433 0 HOH w 157 49. .572 43. .793 7. .514 1. ,00 43. .22 0
ATOM 3434 0 HOH w 158 30. ,541 3, .798 48, .182 1, .00 55, .17 o
ATOM 3435 0 HOH w 159 16. ,015 34. .924 32. ,024 1. .00 48. .83 0
ATOM 3436 0 HOH w 160 51. .712 35, .074 -4, ,804 1. .00 64. .25 0
ATOM 3437 0 HOH w 161 36. .464 -3, .007 -0. ,285 1. .00 38. .44 0
ATOM 3438 0 HOH w 162 16. .182 15, .269 31. ,037 1. .00 66. .49 0
ATOM 3439 0 HOH w 163 35. .025 8, .191 26. ,758 1. .00 58. .94 0
ATOM 3440 0 HOH w 164 66. .113 10, .299 20. ,931 1. .00 56. .12 0
ATOM 3441 0 HOH w 165 55. ,630 -22, .839 7, .058 1, .00 40. .94 0
ATOM 3442 0 HOH w 166 70. .597 24, .001 10. .339 1. .00 38. .15 0
ATOM 3443 0 HOH w 167 33. .827 8, .257 29, .433 1. .00 47, .62 0
ATOM 3444 0 HOH w 168 38. .651 3, .562 1. .821 1. .00 46, .00 0
ATOM 3445 0 HOH w 169 17. ,931 8, .596 15. .903 1. ,00 63, .55 0
ATOM 3446 0 HOH w 170 53. ,590 12, .112 2. .058 1. ,00 52, .40 0
ATOM 3447 0 HOH w 171 12. .498 6, .890 22. .243 1. ,00 48, .61 0
ATOM 3448 0 HOH w 172 45. ,282 16, ,726 -1, .766 1. .00 53, .43 0
ATOM 3449 0 HOH w 173 33. ,374 0, .766 3. .579 1. ,00 48. .57 0
ATOM 3450 0 HOH w 174 17. .563 13, ,972 38. .450 1. ,00 48. .25 0
ATOM 3451 0 HOH w 175 68, ,951 20. ,742 22. .836 1. ,00 58. .59 0
ATOM 3452 0 HOH w 176 37. .600 -19, .066 -0. .214 1. ,00 54. ,28 0
ATOM 3453 0 HOH w 177 58, .850 2, ,171 16. ,664 1. ,00 66. ,83 o
ATOM 3454 0 HOH w 178 37, .338 -18, .592 14. ,900 1. .00 66. ,88 0
ATOM 3455 0 HOH w 179 9. .482 6, .134 21. .968 1. .00 71, ,18 0
ATOM 3456 0 HOH w 180 15. .502 31, ,876 18. .773 1. ,00 54, ,02 0
ATOM 3457 0 HOH w 181 14. .514 -4, .130 26. .924 1. .00 55, ,36 0
ATOM 3458 0 HOH w 182 70. .672 29, .846 -1. .684 1. ,00 60. ,93 0
ATOM 3459 0 HOH w 183 51. .258 13, .722 1. .255 1, ,00 43. .34 0
ATOM 3460 0 HOH w 184 10. ,716 1. ,766 47. ,290 1. ,00 67. .75 0 ATOM 3461 O HOH W 185 58..832 8.,512 6..813 1.,00 53..65 0
ATOM 3462 O HOH W 186 -4. .086 -12. ,572 36. ,744 1. ,00 62. .79 0
ATOM 3463 O HOH w 187 46. .508 24. ,691 2. .250 1. .00 47. .04 o
ATOM 3464 O HOH w 188 13. .873 5. .882 44. .387 1. .00 58. .50 0
ATOM 3465 O HOH w 189 51. .139 28. .495 18. .297 1. .00 57. .53 0
ATOM 3466 O HOH w 190 30. .947 10. .141 52, .110 1. .00 57. ,16 0
ATOM 3467 O HOH w 191 65. .605 25. .389 14, .283 1. .00 43. .24 0
ATOM 3468 O HOH w 192 18. .126 13. .182 30. .638 1. .00 41. .72 0
ATOM 3469 O HOH w 193 55. .794 -1. .873 17. .214 1. .00 36. .16 0
ATOM 3470 O HOH w 194 33. .783 33. .110 17. .457 1. .00 54. .55 0
ATOM 3471 O HOH w 195 38, ,853 -14. .910 11. .939 1. ,00 63. .88 0
ATOM 3472 O HOH w 196 49, ,456 22. .757 10. .865 1. ,00 63. .46 o
ATOM 3473 O HOH w 197 28. ,587 7. .862 11, .381 1. .00 52, .03 0
ATOM 3474 O HOH w 198 34. ,947 35, ,941 19, .703 1. .00 70, .80 o
ATOM 3475 O HOH w 199 55. ,475 24. .490 -7, .980 1, .00 51, .18 0
ATOM 3476 O HOH w 200 56. .743 13, ,758 -6, .598 1. ,00 65. .21 0
ATOM 3477 O HOH w 201 12. .911 -7, ,264 23, ,286 1, .00 60. .82 0
ATOM 3478 O HOH w 202 5. .138 2, ,264 22, .647 1, ,00 62. .03 o
ATOM 3479 O HOH w 203 13. .304 35. ,163 27. ,777 1, .00 46. .47 0
ATOM 3480 O HOH w 204 25. .888 -4. ,844 26, ,526 1, .00 48. .34 0
ATOM 3481 O HOH w 205 14. .760 20. .897 17. ,935 1. .00 40, .89 0
ATOM 3482 O HOH w 206 53. .987 26. .147 -11. ,062 1, ,00 49, .82 0
ATOM 3483 O HOH w 207 68. .989 21. .658 5. ,489 1, ,00 44, .82 o
ATOM 3484 O HOH w 208 4. .346 1, .281 33. .781 1. ,00 35. .17 0
ATOM 3485 O HOH w 209 43. .654 22, .216 2. .326 1, ,00 56. .61 0
ATOM 3486 O HOH w 210 57. .660 -0. ,011 17. .662 1. ,00 57, .39 0
ATOM 3487 0 HOH w 211 21. .597 34, .434 36. .749 1, ,00 53, .23 0
ATOM 3488 0 HOH w 212 14, ,578 8, ,819 26. .105 1, .00 36, .35 o
ATOM 3489 0 HOH w 213 13. .688 13. ,351 16. .929 1, ,00 60, .60 0
ATOM 3490 0 HOH w 214 6, .756 -7. .170 24. ,322 1, ,00 56, .84 0
ATOM 3491 0 HOH w 215 67. .898 11. .572 28. .182 1, ,00 55, .11 0
ATOM 3492 0 HOH w 216 57, .714 24, ,233 22. .731 1, ,00 44, .21 0
ATOM 3493 0 HOH w 217 58, .213 41, .336 -4, .038 1, .00 57. ,86 o
ATOM 3494 0 HOH w 218 12, .270 -5, .061 48, ,893 1, ,00 43. .21 0
ATOM 3495 0 HOH w 219 70, .379 28, .854 2, .049 1, .00 42. .00 o
ATOM 3496 0 HOH w 220 50. .260 -5, .040 1, ,589 1, ,00 48. .18 0
ATOM 3497 0 HOH w 221 56, .271 31, .125 -7, .728 1, .00 52, .70 o
ATOM 3498 0 HOH w 222 14, .596 5, .260 21, .037 1. ,00 66, ,32 0
ATOM 3499 0 HOH w 223 34, .755 -8, .144 17, .238 1. .00 51, .05 o
ATOM 3500 0 HOH w 224 48, .049 -5, .297 0, .350 1. .00 51, ,97 0
ATOM 3501 0 HOH w 225 39. .891 10, .372 -0, .744 1. .00 57, .12 0
ATOM 3502 0 HOH w 226 56. .777 16, .253 3. .098 1. .00 44, .22 o
ATOM 3503 0 HOH w 227 41, .686 6, .425 30, .801 1. .00 58, .48 0
ATOM 3504 0 HOH w 228 31, .152 3, ,461 14. .490 1. ,00 61, .32 o
ATOM 3505 0 HOH w 229 20, .483 5, .907 24, .097 1. .00 54. .34 0
ATOM 3506 0 HOH w 230 19, .242 7, .120 14. .031 1, ,00 41. .44 0
ATOM 3507 0 HOH w 231 31, .016 13, .010 -0, .673 1. .00 38. .51 0
ATOM 3508 0 HOH w 232 70 .871 26, .732 9, .211 1. .00 50, .35 0
ATOM 3509 0 HOH w 233 62, .530 5, .381 16, .924 1. .00 69. .00 0
ATOM 3510 0 HOH w 234 58 .689 10, .135 26, .681 1. .00 61, .24 0
ATOM 3511 0 HOH w 235 48, .099 28, .707 -1, ,499 1. .00 41. .34 0
ATOM 3512 0 HOH w 236 56, .075 11, .436 -8, .202 1. .00 72. .01 o
ATOM 3513 0 HOH w 237 44 .741 25, .584 8, .874 1. .00 56, .34 0
ATOM 3514 0 HOH w 238 25, .074 2, ,290 49. ,071 1. ,00 61. .02 0
ATOM 3515 0 HOH w 239 13, .166 21, .601 29. .112 1. .00 61. .73 0
ATOM 3516 0 HOH w 240 27, ,871 0, ,758 7. .409 1. .00 58. .43 0
ATOM 3517 0 HOH w 241 29, .447 3, ,216 9. .465 1. .00 45, .36 0
ATOM 3518 0 HOH w 242 33, .613 -4, .885 10. .263 1, .00 47, .86 0
ATOM 3519 0 HOH w 243 53, ,720 6, .429 0. .325 1. ,00 57. .39 0
ATOM 3520 0 HOH w 244 29, .614 2, .734 6. .372 1. .00 50. .86 0
ATOM 3521 0 HOH w 245 17, .179 1, .833 49. .731 1. ,00 29. ,82 0
ATOM 3522 0 HOH w 246 19, .272 8, .281 10. .603 1. .00 48. ,32 0
ATOM 3523 0 HOH w 247 40, .725 -15, .193 24. .266 1, .00 53. .01 0
ATOM 3524 0 HOH w 248 29. .119 -7, .888 30. .396 1. ,00 49, ,32 0 ATOM 3525 O HOH W 249 49.,189 23.,307 -5..216 1.,00 42..80 0
ATOM 3526 O HOH W 250 54. ,694 28. .682 -11, .150 1. ,00 66. .83 0
ATOM 3527 O HOH W 251 60. ,944 16. .846 0, .662 1, .00 52. .36 0
ATOM 3528 O HOH W 252 16. ,228 18. .028 33. .087 1. .00 49. .65 0
ATOM 3529 O HOH W 253 45. .158 30. .281 11. .427 1. .00 45. .27 0
ATOM 3530 O HOH W 254 26. .898 6. .397 13, .473 1. ,00 50, .93 0
ATOM 3531 O HOH W 255 57. .476 -18. .207 3, .515 1, .00 68. ,56 0
ATOM 3532 O HOH W 256 32, .813 19. .282 2, .967 1. .00 36. ,17 0
ATOM 3533 O HOH W 257 9, .491 2. .419 44. .597 1. ,00 52. ,45 0
ATOM 3534 O HOH W 258 35, .271 -3. .932 16, .911 1, .00 66. ,53 0
ATOM 3535 O HOH W 259 49, .732 14. ,842 -2. .401 1. ,00 43. .97 0
ATOM 3536 O HOH W 260 27, .521 20, .972 11, .308 1. .00 47. .00 0
ATOM 3537 O HOH W 261 43. .115 10, ,114 -1, .913 1, .00 35. ,84 0
ATOM 3538 O HOH w 262 21. .275 0, .044 21. .585 1. ,00 67. .57 o
ATOM 3539 O HOH w 263 37. .120 20, .797 18. .864 1. .00 79. .96 0
ATOM 3540 O HOH w 264 47. .410 -17. .381 18, .378 1. .00 74. .12 0
ATOM 3541 O HOH w 265 62. .924 21, .666 -0, .960 1. .00 50. .01 0
ATOM 3542 O HOH w 266 35. .999 -1. .885 -2, .786 1, ,00 49. .94 o
ATOM 3543 O HOH w 267 74. .941 28. .538 16, ,431 1, .00 59. .06 0
ATOM 3544 O HOH w 268 46. ,761 1, .281 -0, .475 1. .00 67, .06 0
ATOM 3545 O HOH w 269 48. ,670 8. .707 0. .836 1, .00 49, .88 0
ATOM 3546 O HOH w 270 66. ,079 13, .752 6, .762 1, ,00 42, .69 0
ATOM 3547 O HOH w 271 16, .090 16. .729 37, .464 1, .00 69, .24 o
ATOM 3548 O HOH w 272 77. .143 27, ,199 11, ,644 1, .00 52, .10 0
ATOM 3549 O HOH w 273 51. .882 22, .494 -6, ,310 1, .00 59, .08 0
ATOM 3550 O HOH w 274 50. .771 43, .361 4, ,510 1. .00 48, .05 0
ATOM 3551 O HOH w 275 46. .898 34, .616 12, ,107 1, .00 65, .71 0
ATOM 3552 0 HOH w 276 23, .075 46, .450 29, .289 1, .00 47, .04 0
ATOM 3553 0 HOH w 277 14, .404 12, .889 31, ,126 1, .00 57, .95 0
ATOM 3554 0 HOH w 278 36, .453 -11. .467 1, .613 1, .00 57, .63 o
ATOM 3555 0 HOH w 279 8, .112 9. .700 21. .211 1. ,00 59, ,50 0
ATOM 3556 0 HOH w 280 46, .998 14. ,682 -2. .760 1, .00 52, .71 0
ATOM 3557 0 HOH w 281 17, .921 3. ,335 17. .731 1, .00 49, ,98 0
ATOM 3558 0 HOH w 282 32, .865 28. .042 19. .693 1, .00 50, .59 0
ATOM 3559 0 HOH w 283 25, .586 31. .869 10, .003 1. .00 63. .81 0
ATOM 3560 0 HOH w 284 31, .186 -6. .345 2, .371 1, ,00 49. ,17 0
ATOM 3561 0 HOH w 285 15, .416 17, ,750 24, .533 1, .00 48. ,35 o
ATOM 3562 0 HOH w 286 38, .078 -16, .872 18. .075 1, .00 71, .42 0
ATOM 3563 0 HOH w 287 9, .244 3. .329 41. .771 1, .00 50. .93 0
ATOM 3564 0 HOH w 288 52, .401 34, .885 3. .571 1, .00 60, ,33 0
ATOM 3565 0 HOH w 289 31, ,377 39. .196 25. .255 1, .00 51. .58 o
ATOM 3566 0 HOH w 290 14, .500 17. .886 22. .018 1, .00 50. ,10 0
ATOM 3567 0 HOH w 291 40, .282 7, .206 17. .126 1, ,00 42. ,88 0
ATOM 3568 0 HOH w 292 30, .260 17, ,132 9. .954 1, .00 55. .27 o
ATOM 3569 0 HOH w 293 38, .681 -1. ,970 -2. .008 1. .00 60. .38 0
ATOM 3570 0 HOH w 294 19, .629 9, .142 21. ,868 1, .00 62. .74 0
ATOM 3571 0 HOH w 295 15, .109 -8, .962 30. ,732 1, ,00 50. .70 o
ATOM 3572 0 HOH w 296 20 .081 2, .438 49. .837 1, ,00 47. ,62 0
ATOM 3573 0 HOH w 297 56, .603 15. .529 -0. ,198 1, .00 46. .06 0
ATOM 3574 0 HOH w 298 27, .818 6. .514 7. .376 1, .00 50. .96 o
ATOM 3575 0 HOH w 299 24, .897 22. ,369 9, ,701 1. .00 32. ,90 0
ATOM 3576 0 HOH w 300 54, .872 -12. .316 12, ,229 1, .00 64. ,45 0
ATOM 3577 0 HOH w 301 47, .153 -4, .394 19, ,519 1, ,00 51. ,72 o
ATOM 3578 0 HOH w 302 28, .548 27. .445 38, ,300 1, .00 57. ,61 0
ATOM 3579 0 HOH w 303 44, .013 -17. .633 4, ,722 1, .00 75. .42 0
ATOM 3580 0 HOH w 304 48. ,151 26. .251 -1, .702 1. ,00 38, .80 o
ATOM 3581 0 HOH w 305 19, ,193 10. .914 11, ,697 1, .00 47, .15 o
ATOM 3582 0 HOH w 306 22, .985 24. .448 10, .233 1, .00 42, ,45 0
ATOM 3583 0 HOH w 307 37. .607 -9. .929 15. ,371 1, .00 54. ,35 0
ATOM 3584 0 HOH w 308 53, ,957 -16, .667 11. .106 1, .00 73. .02 o
ATOM 3585 0 HOH w 309 11, ,604 28. .463 23. ,443 1, .00 76. ,29 o
ATOM 3586 0 HOH w 310 31, .389 2. .126 35, ,240 1. .00 54. ,80 0
ATOM 3587 0 HOH w 311 41, .669 -17, ,196 13. ,469 1. .00 55. ,16 0
ATOM 3588 0 HOH w 312 23, .733 40. ,464 35, ,441 1, .00 58. 58 0 ATOM 3589 O HOH W 313 20.071 8.403 45.139 1.00 55.44 O
ATOM 3590 O HOH W 314 68 .778 28 .533 17 .512 1 .00 45 .32 o
ATOM 3591 O HOH W 315 64 .181 14 .152 10 .857 1 .00 51 .72 0
ATOM 3592 O ' HOH W 316 29 .049 1 .903 46 .292 1 .00 43 .97 o
ATOM 3593 O HOH W 317 62 .143 14 .172 9 .271 1 .00 63 .02 o
ATOM 3594 O HOH W 318 24 .107 -2, .007 49 .865 1, .00 38 .66 o
ATOM 3595 O HOH W 319 41 .007 -7, .072 0 .043 1, .00 56 .35 o
ATOM 3596 O HOH W 320 68, .195 21, .721 14, .142 1, .00 46 .50 o
ATOM 3597 O HOH W 321 22, .462 39, .174 37, .178 1, .00 69 .52 0
ATOM 3598 O HOH W 322 17, .783 6, .183 19, .862 1, .00 54, .61 o
ATOM 3599 O HOH W 323 46, .953 22, .632 18, .131 1, .00 51, .51 o
ATOM 3600 O HOH W 324 30, .988 -1, .282 12, .374 1, .00 50, .56 o
ATOM 3601 O HOH W 325 46, .824 9, .645 16, .570 1, .00 76, .67 o
ATOM 3602 O HOH W 326 47, .709 3, .790 27, .072 1, .00 52, .42 o
ATOM 3603 O HOH W 327 37, ,100 14, ,801 1, .681 1. .00 49, .38 0
ATOM 3604 O HOH W 328 41, ,476 -1, ,502 0, .396 1, ,00 58, .29 o
ATOM 3605 O HOH W 329 67, .547 38. .430 -0, .728 1. .00 44, .88 o
ATOM 3606 O HOH W 330 62, .517 25, .184 21, .058 1, .00 64, .10 o
ATOM 3607 O HOH W 331 -0, .557 -2. .635 37, .863 1. .00 45, .19 o
ATOM 3608 O HOH W 332 69, .664 27, ,202 -0, .020 1. ,00 51, ,53 o
ATOM 3609 O HOH W 333 30, .130 -0. .340 29, .038 1, .00 57. .18 o
ATOM 3610 O HOH W 334 51. .237 27. .533 -6, ,173 1. .00 47. ,91 0
ATOM 3611 O HOH w 335 0. .933 -1. .230 32. .070 1. .00 57, .36 0
ATOM 3612 O HOH w 336 31, .115 -13. .376 -0, .361 1, .00 45. .10 0
ATOM 3613 0 HOH w 337 45, .532 6. .225 27, .169 1, .00 66. .83 0
ATOM 3614 0 HOH w 338 38. .789 -3. .517 28, ,225 1. .00 63. .88 0
ATOM 3615 0 HOH w 339 21. .603 23. .747 35, .437 1, .00 58. .20 0
ATOM 3616 0 HOH w 340 51. ,744 32. .705 1, ,437 1, .00 69. .55 0
ATOM 3617 0 HOH w 341 53. .285 23. .459 20, .176 1, .00 50, .19 0
ATOM 3618 0 HOH w 342 50. .116 30. .832 6, .312 1, .00 31, .41 0
ATOM 3619 0 HOH w 343 56, ,433 5, .701 7, .393 1. .00 42, .02 0
ATOM 3620 0 HOH w 344 37, .416 20, .918 24, .575 1. .00 55, .74 0
ATOM 3621 0 HOH w 345 67, .567 26. ,023 15, .813 1, .00 43, .48 0
ATOM 3622 0 HOH w 346 14, .406 44. .657 26, .427 1, .00 65, .51 0
ATOM 3623 0 HOH w 347 17. .703 5. ,856 16, .750 1. .00 45, .27 0
ATOM 3624 0 HOH w 348 44. .529 25. .367 21, .896 1, .00 61, .22 0
ATOM 3625 0 HOH w 349 43. .676 8. .317 25. .804 1. .00 47, .68 0
ATOM 3626 0 HOH w 350 59. .266 11. ,361 7. .848 1, .00 69, .95 0
ATOM 3627 0 HOH w 351 50. .382 13. ,506 12. .091 1, .00 35, .61 0
ATOM 3628 0 HOH w 352 52. .344 20. ,190 -3. ,908 1, .00 41, ,33 0
ATOM 3629 0 HOH w 353 70. .633 22. ,306 8. .035 1, .00 49, ,69 0
ATOM 3630 0 HOH w 354 20. .918 9. .448 14. ,526 1, ,00 49. ,51 0
ATOM 3631 0 HOH w 355 46. .850 29. .538 -5. .784 1, ,00 55. ,83 0
ATOM 3632 0 HOH w 356 7. .257 -10. .627 28. .472 1, ,00 75, ,56 0
ATOM 3633 0 HOH w 357 29. .522 21. .084 28. .772 1, ,00 29. ,76 0
ATOM 3634 0 HOH w 358 58. .141 -5. .422 8. .999 1, ,00 72. ,75 0
ATOM 3635 0 HOH w 359 44, .287 32, .961 31. .887 1. ,00 52. ,80 0
ATOM 3636 0 HOH w 360 52, .292 13. .939 -1. .485 1. ,00 45. ,87 0
ATOM 3637 0 HOH w 361 38. .838 -12. .010 13. .154 1. .00 53. ,39 0
ATOM 3638 0 HOH w 362 71. .746 29. .166 11, .917 1. .00 66. ,84 0
ATOM 3639 0 HOH w 363 34. ,791 26. .989 17. .836 1. .00 58. ,17 0
ATOM 3640 0 HOH w 364 49. ,720 18. .422 10. .244 1. .00 58. .39 0
ATOM 3641 0 HOH w 365 36. ,609 -19. .691 18. .159 1. .00 56. ,62 o
ATOM 3642 0 HOH w 366 52. ,019 34. ,567 -0. ,128 1. ,00 62. ,35 0
ATOM 3643 0 HOH w 367 8. ,099 4. ,733 38. ,644 1. ,00 59. ,14 0
ATOM 3644 0 HOH w 368 24. ,162 43. 585 29. ,340 1. ,00 54. 80 0
ATOM 3645 0 HOH w 369 12. ,065 11. 038 40. 551 1. 00 50. 21 0
ATOM 3646 0 HOH w 370 51. ,445 34. 226 7. 596 1. 00 46. 49 o
ATOM 3647 0 HOH w 371 46. ,917 37. 194 10. 718 1. 00 47. 06 0
ATOM 3648 0 HOH w 372 37. ,530 8. 417 -1. 409 1. 00 50. 26 0
ATOM 3649 0 HOH w 373 16. ,046 20. 046 23. 951 1. 00 62. 38 0
ATOM 3650 0 HOH w 374 31. ,497 29. 299 30. 333 1. 00 55. 86 0
ATOM 3651 0 HOH w 375 55. ,680 31. 078 13. 913 1. 00 66. 00 0
ATOM 3652 0 HOH w 376 -1. ,126 -12. 205 37. 405 1. 00 46. 93 o ATOM 3653 O HOH W 377 57,.780 19.,822 -4,.481 1,,00 52,.77 0
ATOM 3654 O HOH w 378 20, .558 24. ,848 11, ,749 1. .00 44. .63 o
ATOM 3655 O HOH w 379 18, .424 49. .479 19. .940 1. .00 56. .67 0
ATOM 3656 O HOH w 380 22, .486 31. .556 10. .000 1, .00 50. .34 0
ATOM 3657 O HOH w 381 53, ,741 23. .702 -9. .251 1. ,00 48. .43 0
ATOM 3658 O HOH w 382 34, .525 24. .186 16. .557 1. ,00 65. .32 o
ATOM 3659 O HOH w 383 17, .235 19. .518 21. .375 1, .00 58. .33 0
ATOM 3660 O HOH w 384 57. .882 3. .621 8. .079 1. ,00 39. .82 o
ATOM 3661 O HOH w 385 26. .561 28. .879 35. .275 1, .00 73, .69 0
ATOM 3662 O HOH w 386 45. .960 30. .047 14. .517 1. .00 40, .29 o
ATOM 3663 O HOH w 387 24. ,745 5. .242 28. .231 1. ,00 77, .59 0
ATOM 3664 O HOH w 388 38. .843 -22. .197 1. .181 1. .00 69. .86 0
ATOM 3665 O HOH w 389 24. ,914 45. .052 21. ,953 1. ,00 47, ,80 o
ATOM 3666 O HOH w 390 23. ,968 5. .180 9. ,472 1, ,00 36. ,09 0
ATOM 3667 O HOH w 391 45. .167 22. .341 10. .168 1. .00 58. ,85 0
ATOM 3668 O HOH w 392 63. ,994 23. .103 -6. ,623 1. ,00 41. .36 0
ATOM 3669 O HOH w 393 43, .211 28. .094 26. ,866 1. .00 64. .82 0
ATOM 3670 O HOH w 394 12, .463 10. .420 17. ,753 1, .00 51. .83 0
ATOM 3671 O HOH w 395 23. .822 27. .573 41. ,487 1, ,00 37. .27 0
ATOM 3672 O HOH w 396 13. .987 41. .496 29. .635 1, .00 62. .16 0
ATOM 3673 O HOH w 397 33. .026 22. .598 37. .699 1, .00 51. .26 0
ATOM 3674 O HOH w 398 64. .548 15. ,778 25. .784 1. .00 73. .76 0
ATOM 3675 0 HOH w 399 4. .456 6. .820 31. .188 1. .00 52. .61 0
ATOM 3676 0 HOH w 400 56. .245 22, .603 -12. .779 1, .00 69. .18 0
ATOM 3677 0 HOH w 401 21. .852 21. .246 43. .752 1, .00 49. .06 0
ATOM 3678 0 HOH w 402 53, .672 -4. ,770 2. .592 1, .00 66. .30 0
ATOM 3679 0 HOH w 403 40, ,577 22, ,543 17, ,517 1. .00 55. ,37 0
ATOM 3680 0 HOH w 404 39, ,682 23. ,255 9, .179 1, ,00 40, ,71 0
ATOM 3681 0 HOH w 405 26, .738 24, .263 8. .013 1, .00 54, .59 0
ATOM 3682 0 HOH w 406 50. .210 0. .374 1. .209 1. .00 50, ,49 0
ATOM 3683 0 HOH w 407 60. .590 19. .355 27. .471 1. .00 47, ,33 0
ATOM 3684 0 HOH w 408 4. .171 -0, .693 25. .748 1, .00 66. .54 0
ATOM 3685 0 HOH w 409 45. .385 8. .836 27. .640 1. .00 48. ,88 0
ATOM 3686 0 HOH w 410 37. ,725 11, .971 26. .053 1, .00 62. ,01 o
ATOM 3687 0 HOH w 411 45, ,832 8, .800 -1. .281 1, .00 46. .54 0
ATOM 3688 0 HOH w 412 13. ,221 11, .782 28. .251 1, .00 39. .21 0
ATOM 3689 0 HOH w 413 23, .976 47, .982 18. .021 1, ,00 53. .62 0
ATOM 3690 0 HOH w 414 63, .898 17, .108 27. .312 1, ,00 46, .28 0
ATOM 3691 0 HOH w 415 5, .585 -10, .312 33. ,042 1, ,00 48. .81 0
ATOM 3692 0 HOH w 416 38, .213 2, .921 -0. .615 1, .00 52. .43 0
ATOM 3693 0 HOH w 417 11, ,363 8, .700 42. .372 1, .00 63, ,77 0
ATOM 3694 0 HOH w 418 38, .189 -2, ,578 16. .862 1, .00 48. .54 0
ATOM 3695 0 HOH w 419 35. .880 21, .127 45. .601 1, .00 56. .00 0
ATOM 3696 0 HOH w 420 57. .494 8, .004 2. .119 1. ,00 53. ,09 0
ATOM 3697 0 HOH w 421 59. .320 -4, .060 11. .061 1, .00 53. .50 0
ATOM 3698 0 HOH w 422 31, .364 1, .362 44. .832 1, .00 47. .58 0
ATOM 3699 0 HOH w 423 64. ,047 11, .643 27. .376 1, .00 58. .29 0
ATOM 3700 0 HOH w 424 32. .930 3, .782 19. .596 1, .00 51. .49 0
ATOM 3701 0 HOH w 425 38, .784 17, .343 41. .490 1, .00 60, ,60 0
ATOM 3702 0 HOH w 426 37. .274 22, .305 27. .368 1, .00 46, ,16 0
ATOM 3703 0 HOH w 427 2. ,920 3, .818 31. .574 1, .00 48, ,85 0
ATOM 3704 0 HOH w 428 31, .322 4, .264 17. ,113 1, ,00 61, ,45 0
ATOM 3705 0 HOH w 429 37. .349 2, .399 44. .067 1, ,00 59, ,80 0
ATOM 3706 0 HOH w 430 30. .656 -2, .719 19. .246 1, ,00 52, .57 0
ATOM 3707 0 HOH w 431 45, .180 15, .640 19. ,348 1, .00 58, .43 0
ATOM 3708 0 HOH w 432 5. .372 -7, .792 47. ,576 1. .00 69, ,85 0
ATOM 3709 0 HOH w 433 25. .527 -3, .157 21. .992 1, .00 66, ,96 0
ATOM 3710 0 HOH w 434 44. .619 27, .583 -3. .072 1, .00 47, .84 0
ATOM 3711 0 HOH w 435 13. .783 30, .570 33. .920 1. .00 58, .04 0
ATOM 3712 0 HOH w 436 34. .166 8, .815 47. .993 1. .00 56. .17 0
ATOM 3713 0 HOH w 437 43. .341 -13, .044 19, .673 1. ,00 57. ,24 0
ATOM 3714 0 HOH w 438 73, .346 13, .204 25, ,504 1. ,00 60. ,85 0
ATOM 3715 0 HOH w 439 46. .736 20, .265 31, ,497 1. ,00 68. ,57 0
ATOM 3716 0 HOH w 440 3. .829 1, ,129 41. ,666 1. ,00 52. ,32 0 ATOM 3717 O HOH W 441 52,.231 13..277 -7,.024 1..00 64..60 o
ATOM 3718 0 HOH W 442 40, .476 19. .912 31, .528 1, .00 38, .49 0
ATOM 3719 O HOH W 443 42. .835 -13. .097 16, .910 1. .00 50. .34 o
ATOM 3720 O HOH W 444 28. .031 15. .763 48, .184 1. .00 40. .06 o
ATOM 3721 O HOH W 445 9, .673 -9. .229 46, .054 1, .00 51. .46 0
ATOM 3722 O HOH W 446 29, .683 -16. .115 27. .350 1. .00 54. .29 0
ATOM 3723 O HOH W 447 54, .239 5. .891 5, .248 1. .00 61. .23 0
ATOM 3724 O HOH W 448 19. .031 2. .254 54. .929 1. .00 48. .57 0
ATOM 3725 O HOH W 449 61. .677 7. .330 6. .963 1. .00 74. .94 0
ATOM 3726 O HOH W 450 31. .932 44. .220 19. .866 1. .00 59, .36 0
ATOM 3727 O HOH W 451 10. .482 48, .704 30. .828 1. .00 65, .80 0
ATOM 3728 O HOH W 452 6. .561 11, .748 10. .662 1. ,00 54, .13 0
ATOM 3729 O HOH W 453 15. .435 -0, .867 49. .670 1. ,00 45, .56 0
ATOM 3730 O HOH W 454 51. .570 37, .652 4. .006 1. .00 42, .09 0
ATOM 3731 O HOH w 455 23. .910 26, .874 14. .030 1. .00 52. .57 o
ATOM 3732 O HOH w 456 27. .085 29. .781 13. .934 1. .00 25, .46 0
ATOM 3733 O HOH w 457 27. ,900 28. ,627 9. .182 1. .00 45. .79 o
ATOM 3734 O HOH w 458 32. .738 29. .266 13. .968 1. ,00 42. .91 0
ATOM 3735 O HOH w 459 29, .835 30. ,314 13. .852 1. ,00 48. .08 0
ATOM 3736 O HOH w 460 30. .248 -10. .934 4. .378 1. ,00 51. ,32 o
ATOM 3737 O HOH w 461 32. .581 -10. .951 9. .228 1. .00 64. ,63 0
ATOM 3738 O HOH w 462 32. .498 -10. .742 12. .543 1. .00 54. ,22 0
ATOM 3739 O HOH w 463 11. .813 -0. .334 48. .643 1. ,00 57. ,91 0
ATOM 3740 O HOH w 464 4. ,172 -6. ,148 31. .453 1. ,00 65. ,05 o
ATOM 3741 O HOH w 465 38. .613 13, .637 20. .404 1. ,00 83, ,38 0
ATOM 3742 O HOH w 466 25, .868 -18. .454 28. .422 1. .00 60, ,00 0
ATOM 3743 0 HOH w 467 65. .059 16. .988 12. .215 1, .00 49. ,23 o
ATOM 3744 0 HOH w 468 30. .433 21. .112 45, .165 1. .00 58. ,66 0
ATOM 3745 0 HOH w 469 63. .211 34. .666 -5, .360 1. .00 44, ,44 0
ATOM 3746 0 HOH w 470 46, ,034 24. .452 16, .370 1. .00 47, ,25 0
ATOM 3747 0 HOH w 471 38. ,317 37. ,251 29, ,410 1. ,00 57, ,97 0
ATOM 3748 0 HOH w 472 45. .601 16. ,935 22, ,457 1. ,00 50. ,56 o
ATOM 3749 0 HOH w 473 57, .386 3, .823 5, .277 1. ,00 47. ,98 0
ATOM 3750 0 HOH w 474 48. .907 41, .483 3, .217 1. ,00 46. ,27 0
ATOM 3751 0 HOH w 475 60, ,742 15. .315 -2. .406 1. .00 47. ,15 0
ATOM 3752 0 HOH w 476 11. .472 30, ,114 17. .903 1. .00 50. ,81 0
ATOM 3753 0 HOH w 477 27. .442 -5. .736 4, .830 1. ,00 50. ,01 o
ATOM 3754 0 HOH w 478 15, .963 19. .233 13, .604 1. ,00 40. ,24 0
ATOM 3755 0 HOH w 479 11, ,847 16. .803 29, .315 1. ,00 51. ,87 0
ATOM 3756 0 HOH w 480 25, ,373 -1. .129 6, .145 1. .00 69. ,33 0
ATOM 3757 0 HOH w 481 21, ,061 27, ,210 7. .262 1. .00 43. ,87 0
ATOM 3758 0 HOH w 482 11. .657 12. ,994 20, .711 1. .00 62. .23 0
ATOM 3759 0 HOH w 483 55. .094 2, ,305 -3, .240 1. .00 66, ,83 0
ATOM 3760 0 HOH w 484 19. .281 0. ,887 18, .463 1. .00 65. ,62 o
ATOM 3761 0 HOH w 485 44, .026 16. .214 28, .232 1. .00 64. .82 o
ATOM 3762 0 HOH w 486 53. .605 24. ,910 16. .745 1. .00 73. ,45 0
ATOM 3763 0 HOH w 487 15, .314 30. .821 22. .775 1. .00 45, .14 0
ATOM 3764 0 HOH w 488 20, .855 2. ,452 52, .883 1. ,00 51. ,84 o
ATOM 3765 0 HOH w 489 32, .918 5. ,487 -2. .045 1, ,00 45. ,08 0

Claims

Claims
1. A method of altering a property of an IgNAR variable domain comprising eight β-strand regions, designated A, A', B, C, D, E, F and G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2, said method comprising modifying the IgNAR variable domain within at least one of the β- strand regions or loop regions.
2. The method according to claim 1, wherein the modification alters the binding characteristics of the IgNAR variable domain.
3. The method according to claim 1, wherein the modification improves the solubility of the IgNAR variable domain.
4. The method according to claim 1, wherein the modification improves the stability of the IgNAR variable domain.
5. The method according to claim 1, wherein the modification increases or decreases the propensity for the IgNAR variable domain to form homodimers.
6. The method according to any preceding claim, in which the unmodified β- strand regions and loop regions have the amino acid residue numbering according to Table 3.
7. The method according to any preceding claim, in which the unmodified loop region 5 comprises two β-strand regions designated C and D' according to Figure 3 and three loop regions designated 5a, 5b and 5c according to Figure 3.
8. The method according to claim 7, in which the unmodified β-strand regions C, C and D' have the amino acid residue numbering according to Table 3 A.
9. The method according to claim 7 or claim 8, in which the Cα trace of loop region 5b in the unmodified IgNAR variable domain is no more than 5A above the plane formed by the Cα trace of residues 22, 83 and 36 as defined in Table 1.
10. The method according to any preceding claim, in which the amino acid sequence of the unmodified β-strand regions A, A', B, C, D, E, F and G and loop regions 1, 2, 3, 6, 7 and 9 comprises an amino acid sequence according to Figure 1 and/or Table 1.
11. The method according to any preceding claim, in which the unmodified IgNAR is a Type 2 or Type 3 IgNAR.
12. The method according to any preceding claim, in which the unmodified IgNAR is derived from a shark.
13. The method according to any one of claims 1 to 10, in which the amino acid sequence of the unmodified IgNAR variable domain is a sequence shown in Figure 1.
14. The method according to any one of claims 1 to 10, in which the unmodified IgNAR variable domain is 12Y-1, 12Y-2, 12A-9 or 1A-7.
15. The method according to any preceding claim, in which the modification is a substitution, insertion, deletion or combination thereof.
16. The method according to any preceding claim, in which the modification comprises the substitution of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acids.
17. The method according to any preceding claim, in which the modification comprises deletion of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acids.
18. The method according to any preceding claim, in which the modification comprises insertion of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more amino acids.
19. The method according to any preceding claim, in which one or more loop regions of the IgNAR are modified.
20. The method according to any preceding claim, in which loop region 4, or part thereof, and/or loop region 8, or part thereof, are modified.
21. The method according to claim 20, in which loop region 8 is modified by point mutations.
22. The method according to claim 20, in which loop region 8 is modified by randomisation.
23. The method according to claim 20, in which loop region 8 is modified so as to facilitate the adoption of β-strand configurations at the C- and/or N-terminal ends.
24. The method according to claim 23, in which loop region 8 is modified by addition or substitution of one or more amino acid residues at the C- and/or N- terminal ends of the loop region
25. The method according to claim 24, in which from 2 to 10 amino acid residues are added or substituted at the C- and/or N-terminal ends of the loop region.
26. The method according to any one of claims 1 to 20 and 23 to 25, in which the IgNAR variable domain is modified by grafting a CDR loop or portion thereof from a V-set or an I-set domain into a loop region of the IgNAR variable domain.
27. The method according to claim 26, in which the CDR loop or portion thereof is grafted into loop region 4 and/or 8 of the IgNAR variable domain.
28. The method according to claim 27, in which amino acids from loop region 8 are replaced by a CDR3 loop or portion thereof from a V-set or an I-set domain.
29. The method according to any one of claims 28, in which amino acids 86 to 103 as defined in Table 1 or a portion thereof are replaced.
30. The method according to claim 27, in which amino acids from loop region 4 are replaced by a CDRl loop or portion thereof from a V-set or an I-set domain.
31. The method according to claim 30, in which amino acids 28 to 33 as defined in Table 1 or a portion thereof are replaced.
32. The method according to any preceding claim, in which one or more amino acid residues within the patch defined by residues 33, 37, 46, 48, 50, 51, 59, 61, 86, 94, 95, 96, 98, 99 and 101 as shown in Table 1 are modified.
33. The method according to any preceding claim, in which at least one of the β- strand regions or loop regions 1-3, 5-7 or 9 is modified when loop region 4 and/or loop region 8 of the IgNAR is modified.
34. The method according to claim 33, in which at least one of β-strand regions C, D, E or F or loop regions 5, 6 or 7 is modified.
35. The method according to claim 34, in which at least one of β-strand regions C or D or loop region 5 is modified.
36. The method according to claim 35, in which loop region 5 is modified.
37. The method according to any preceding claim, in which the IgNAR is a Type 2 or Type 3.
38. The method or binding moiety according to any preceding claim, in which the IgNAR is derived from a shark.
39. A binding moiety comprising a modified IgNAR variable domain produced by a method according to any one of claims 1 to 38.
40. A binding moiety comprising an IgNAR variable domain comprising eight β- strand regions, designated A, A', B, C, D, E, F and G according to Figure 2, and nine loop regions, designated 1 to 9 according to Figure 2, wherein the IgNAR variable domain has been modified within at least one of the β-strand regions or loop regions.
41. A method of modifying an I- or V-set domain, said method comprising inserting and/or substituting one or more structural features from an IgNAR variable domain into the I- or V-set domain.
42. The method according to claim 41, in which the structural feature is a loop region from an IgNAR variable domain according to Figure 2.
43. The method according to claim 42, in which the loop region is loop region 4 or 8 from an IgNAR variable domain.
44. The method according to claim 43, in which loop region 8 and/or loop region 4 are grafted onto the I-set or V-set domain.
45. The method according to claim 44, in which suitably predetermined amino acids of the I- or V-set domain are replaced with an insert comprising amino acids 86 to 103 from the IgNAR variable domain as defined by Table 1.
46. The method according to any one of claims 41 to 45, in which all or a portion of the CDR2 loop of the I-set or V-set domain is removed.
47. The method according to claim 41, in which the structural feature is the solvent exposed face at the C-terminus of the loop region 4 and in the C and D β-strands from an IgNAR variable domain according to Figure 2.
48. The method according to any one of claims 41 to 47, in which amino acids of the I- or V-set domain equivalent to amino acids 32, 33, 34, 35, 55, 57 and 58 as defined in Table 1 or a portion thereof are modified.
49. The method according to claim 48, in which the modification introduces charged or polar amino acids at these positions.
50. The method according to any one of claims 41 to 49, in which the modification improves the solubility of the I- or V-set domain.
51. The method of modifying an I-set domain according to any one of claims 41 to 50.
52. The method according claim 51, in which the I-set domain is selected from NCAM, VCAM, ICAM, Telokin, MADCAM-1, Twitchin and Titin.
53. The method of modifying a V-set domain according to any one of claims 41 to 50.
54. The method according claim 53, in which the V-set domain is selected from antibodies, T cell receptors (TCRs), CTLA-4, CD28, ICOS, CD2, CD4, Cd7, CD22, CD33, CD80, CD86, CD48 and CD58.
55. The method according claim 53 or claim 54, in which the V-set domain is a TCRVα or Vβ domain and the equivalent amino acids to the solvent exposed surface of an IgNAR variable domain are Gly30, Ser31, Phe32, Phe33, Phe62, Thr63, Ala64 and Gln65.
56. The method according claim 53 or claim 54, in which the V-set domain is a TCRVα or Vβ domain and the one or more residues located at the interface between the Vα and Vβ domains are modified.
57. The method according claim 56, in which the one or more amino acid residues are selected from the group consisting of Ser31, Pro43, Leu89 and Phel06 and combinations thereof.
58. A binding domain comprising a modified I- or V-set domain produced according to a method of any one of claims 41 to 57.
59. A binding moiety comprising an I- or V-set domain, wherein the I- or V-set domain has been modified by substitution or insertion of one or more structural features from an IgNAR variable domain into the I- or V-set domain.
60. A binding moiety comprising an I- or V-set domain, wherein the I- or V-set domain has been modified by introducing a modification into a region equivalent to loop region 4 or loop region 8 of an IgNAR variable domain.
61. A binding moiety comprising a multimer comprising: (i) at least two IgNAR domains, which may be the same or different, and at least one of which is a IgNAR variable domain; (ii) at least two I-set domains, which may be the same or different, and at least one of which is a I-set domain according to the present invention; or (iii) at least two V-set domains, which may be the same or different, and at least one of which is a V-set domain accordmg to the present invention.
62. A binding moiety according to the invention linked to a diagnostic reagent.
63. A binding moiety according to the invention immobilised on a solid support or coupled to a biosensor surface.
64. A polynucleotide encoding a binding moiety according to the invention.
65. A vector comprising a polynucleotide according to the present invention.
66. A host cell comprising a vector according to the invention.
67. A method of producing a binding moiety according to the invention which comprises culturing a host cell of the present invention under conditions enabling expression of the binding moiety according to the invention and optionally recovering the a binding moiety.
68. A pharmaceutical composition comprising a binding moiety according to the invention and a pharmaceutically acceptable carrier or diluent.
69. A method of treating a pathological condition in a subject, which method comprises administering to the subject a binding moiety according to the invention.
70. A method of selecting a binding moiety according to the invention with an affinity for a target molecule which comprises screening a library of polynucleotides of the present invention for expression of a binding moiety according to the invention with an affinity for the target molecule.
71. A polynucleotide library comprising a plurality of polynucleotides encoding binding moieties according to the invention, which polynucleotides comprise one or more modifications in the IgNAR variable domain, I set domain or V-set domain.
72. A crystal of a variable domain of a Type 2 IgNAR that effectively diffracts X- rays for the determination of the atomic coordinates of the variable domain of the IgNAR to a resolution of better than 4.θA, wherein the variable domain of the Type 2 IgNAR consists of 105 to 125 amino acid residues and comprises an amino acid sequence according to Table 1 and/or Figure 1.
73. A crystal of a variable domain of a Type 2 IgNAR comprising a structure defined by all or a portion of the coordinates of Appendix 1(a), (b), (c) or (d) + a root mean square deviation from the Cα atoms of less than 0.5 A.
74. A method of homology modelling comprising the steps of: (a) aligning a representation of an amino acid sequence of an IgSF domain with the amino acid sequence of 12Y-1, 12Y-2, 12A-9 or 1A-7 as shown in Figure 1 to match homologous regions of the amino acid sequences; (b) modelling the structure of the matched homologous regions of said IgSF domain on the corresponding regions of the 12Y-1, 12Y-2, 12A-9 or 1A-7 structure as defined by Appendix 1(a), (b), (c) or (d); and (c) determining a conformation (e.g. so that favourable interactions are formed within the IgSF domain and/or so that a low energy conformation is formed) for said IgSF domain which substantially preserves the structure of said matched homologous regions.
75. A method for determining the structure of a protein, which method comprises providing the co-ordinates of Appendix 1(a), (b), (c) or (d), and either (a) positioning the co-ordinates in the crystal unit cell of said protein so as to provide a structure for said protein; or (b) assigning NMR spectra Peaks of said protein by manipulating the coordinates of Appendix 1(a), (b), (c) or (d).
76. A system containing at least one of the following: (a) atomic coordinate data according to Appendix I, said data defining the three-dimensional structure of 12Y-1, 12 Y-2, 12A-9 or 1A-7 or at least selected coordinates thereof; (b) structure factor data (where a structure factor comprises the amplitude and phase of the diffracted wave) for 12Y-1, 12Y-2, 12A-9 or 1A-7, said structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of an IgSF domain generated by homology modelling of the IgSF domain based on the data of Appendix I; (d) atomic coordinate data of the IgSF domain generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Appendix I; and (e) structure factor data derivable from the atomic coordinate data of (c) or (d).
77. A computer-readable storage medium, comprising a data storage material encoded with computer readable data, wherein the data are defined by all or a portion of the structure coordinates of 12Y-1, 12 Y-2, 12A-9 or 1A-7, or a variant of 12Y-1, 12Y-2, 12A-9 or 1A-7, wherein said variant comprises backbone atoms that have a root mean square deviation from the Cα or backbone atoms (nitrogen-carbonα-carbon) of Appendix I of less than 2 A
78. A computer-readable storage medium according to claim 77, in which the root mean square deviation from the Cα or backbone atoms of Appendix I is not more than 1.5 A, preferably less than 1.5 A, more preferably less than 1.0 A, even more preferably less than 0.74 A, even more preferably less than 0.72 A and most preferably less than 0.5 A.
79. A computer-readable data storage medium comprising a data storage material encoded with a first set of computer-readable data comprising a Fourier transform of at least a portion (e.g. selected coordinates as defined herein) of the structural coordinates for 12Y-1, 12Y-2, 12A-9 or 1A-7 according to Appendix I; which, when combined with a second set of machine readable data comprising an X-ray diffraction pattern of a molecule or molecular complex of unknown structure, using a machine programmed with the instructions for using said first set of data and said second set of data, can determine at least a portion of the structure coordinates corresponding to the second set of machine readable data.
80. A computer readable media with at least one of: ,< : (a) atomic coordinate data according to Appendix I recorded thereon, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1 A-7, or at least selected coordinates thereof; , (b) structure factor data for 12Y-1, 12Y-2, 12A-9 or 1A-7 recorded thereon, the structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of a target IgSF domain generated by homology modelling of the IgSF domain based on the data of Appendix 1 ; (d) atomic coordinate data of a modified IgSF domain generated by interpreting X-ray crystallographic data or NMR data by reference to the data of Appendix I; and \ (e) structure factor data derivable from the atomic coordinate data of (c) or (d). A method of providing data for generating structures and/or performing rational drug design for IgSF domains, the method comprising:
(i) establishing communication with a remote device containing computer- readable data comprising at least one of: (a) atomic coordinate data according to Appendix I, said data defining the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, at least one sub-domain of the three-dimensional structure of 12Y-1, 12Y-2, 12A-9 or 1A-7, or the coordinates of a plurality of atoms of 12Y-1, 12Y-2, 12A-9 or 1A-7; (b) structure factor data for 12Y-1, 12Y-2, 12A-9 or 1A-7, said structure factor data being derivable from the atomic coordinate data of Appendix I; (c) atomic coordinate data of a modified IgSF domain generated by homology modelling of the domain based on the data of Appendix I; (d) atomic coordinate data of a protein generated by interpreting X- ray crystallographic data or NMR data by reference to the data of Appendix I; and (e) structure factor data derivable from the atomic coordinate data of (c) or (d); and
(ii) receiving said computer-readable data from said remote device.
PCT/AU2005/000789 2004-06-02 2005-06-02 BINDING MOIETIES BASED ON SHARK IgNAR DOMAINS WO2005118629A1 (en)

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AU2005250055A AU2005250055B2 (en) 2004-06-02 2005-06-02 Binding moieties based on shark IgNAR domains
CA2567655A CA2567655C (en) 2004-06-02 2005-06-02 Binding moieties based on shark ignar domains
US11/628,475 US7977071B2 (en) 2004-06-02 2005-06-02 Binding moieties based on shark ignar domains
JP2007513617A JP2008511286A (en) 2004-06-02 2005-06-02 Binding components based on the IgNAR domain of sharks
EP05744734A EP1751181B1 (en) 2004-06-02 2005-06-02 BINDING MOIETIES BASED ON SHARK IgNAR DOMAINS
DK05744734.4T DK1751181T3 (en) 2004-06-02 2005-06-02 BINDING PARTS BASED ON HAJ IgNAR DOMAINS
AU2008229687A AU2008229687B2 (en) 2004-06-02 2008-09-29 Binding moieties based on shark IgNAR domains
AU2009201692A AU2009201692B2 (en) 2004-06-02 2009-04-28 Binding moieties based on shark IgNAR domains
US13/157,205 US20120003214A1 (en) 2004-06-02 2011-06-09 Binding Moieties Based On Shark IgNAR Domains
US15/044,731 US20160237169A1 (en) 2004-06-02 2016-02-16 Binding Moieties Based On Shark IgNAR Domains

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