WO2003096985A2 - 3d structure of the tsg101 uev domain - Google Patents

3d structure of the tsg101 uev domain Download PDF

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Publication number
WO2003096985A2
WO2003096985A2 PCT/US2003/015616 US0315616W WO03096985A2 WO 2003096985 A2 WO2003096985 A2 WO 2003096985A2 US 0315616 W US0315616 W US 0315616W WO 03096985 A2 WO03096985 A2 WO 03096985A2
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atom
tsgioi
tsg
interaction
ubiquitin
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PCT/US2003/015616
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French (fr)
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WO2003096985A3 (en
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Wesley I. Sundquist
Darrell R. Davis
Steven L. Alam
Owen W. Pornillos
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University Of Utah Research Foundation
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Priority to AU2003231782A priority Critical patent/AU2003231782A1/en
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Publication of WO2003096985A3 publication Critical patent/WO2003096985A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length

Definitions

  • TsglOl plays key roles in HIV budding and in cellular vacuolar protein sorting (Vps) In performing these functions, Tsgl Ol binds both ubtquitin (Ub) and the PTAP tetrapeptide "late domain" motif located within the viral Gag protein These interactions are mediated by the N-terminal domain of TsglOl, which belongs to the catalytically inactive ubiquitin E2 variant (UEV) family
  • TsglOl has recently been identified as the functional receptor required for budding of the enveloped human immunodeficiency (HIV) and Ebola viruses (VerPlank et al , 2001, 2001, Martin-Serrano et al , 2001, all of which are herein incorporated by reference at least for material related to TSGIOI) (Garrus et al )Tsgl01 is recruited to the sites of virus budding by binding to a PTAP tetrapeptide motif (the "late domain") located within the p6 region of HIV Gag and the Ebola Vp40 matrix structural proteins Once there, TsglOl appears to recruit other cellular factors that help to complete the budding process (Garrus et al , 2001 , Martin-Serrano et al , 2001) In the absence of TsglOl, the final membrane fission step(s) fail and HIV release is arrested at a very late stage, in which the assembled viral particles remain attached to the plasma membrane (and to one another
  • Figure 1 shows the sequence and structure of TsglOl
  • Figure la shows the domain organization of TsglOl, showing the approximate domain boundaries of the UEV domain, proline- ⁇ ch domain (PRD), putative coiled coil domain (COIL) and "steadiness box” (SBOX) (Feng et al., 2000).
  • PRD proline- ⁇ ch domain
  • COIL putative coiled coil domain
  • SBOX steadyiness box
  • TsglOl UEV The secondary structures of TsglOl UEV, uncomplexed human Mms2 (Moraes et al , 2001), and uncomplexed yeast Ubcl3 (VanDemark et al., 2001) are shown at the top, middle and bottom, respectively. conserveed residues are shaded gray, identical residues black
  • the active site cysteine of catalytic E2 enzymes and the equivalent residues in UEV proteins are green TsglOl UEV residues that are important for binding PTAP and Ub are colored red and blue, respectively.
  • Figure lc shows a stereoview superposition of the final 20 NMR structures of the TsglOl UEV domain Secondary structures are colored as in b
  • Figure 2 shows the structures of E2-fold proteins.
  • Figures 2a, b, c show ribbon representations of TsglOl UEV (a), Mms2 (->), and Ubcl3 (c). Secondary structure elements are colored as in Figure 1. Black arrows indicate residues that correspond to the active site cysteine of Ubcl3.
  • Figure 2d shows supe ⁇ osition of the three structures.
  • TsglOl is colored yellow, Mms2 green, and Ubcl 3 pu ⁇ le
  • the three major structural differences between TsglOl and the other two proteins are highlighted by arrows * the extra N-terminal helix (red arrow), the ⁇ -hai ⁇ in "tongue” (blue arrow), and the missing C-terminal helices (green arrow).
  • Figure 3 shows the chemical shift mapping of the PTAP binding site on TsglOl UEV.
  • Figure 3a shows an overlay of the ⁇ / I5 N-HSQC spectra of TsglOl UEV in the absence (gray) or presence of 1.0 molar equivalent of PTAP peptide (red).
  • FIG. 3b shows a biosensor binding of TsglOl UEV to immobilized full-length p6 (upper left panel and closed circles) and PTAP peptide to immobilized Tsgl Ol UEV (lower left panel and open circles)
  • the near-supe ⁇ mposition of the two curves demonstrates that TsglOl UEV binds p6 and the PTAP peptide with the same affinity.
  • Figure 3c shows the 27 residues with the greatest change in chemical shift ( ⁇ > 1.8) mapped onto a surface representation of the TsglOl UEV structure.
  • Figure 3d shows a Ribbon representation of TsglOl UEV showing residues important for binding.
  • the Mms2 (green) and Ubcl 3 (pu ⁇ le) structures have been superimposed in this figure, but only the C-terminal residues are shown, to illustrate how the binding groove of TsglOl UEV is filled in cis by C-terminal residues in E2 enzymes and in Mms2 UEV
  • the C-terminus of TsglOl, which points away from the PTAP binding site, is indicated by the blank arrowhead
  • FIG. 4 shows a mutagenic analysis of TsglOl UEV binding to p6, p6-Ub and Ub.
  • Biosensor binding isotherms are shown for putative PTAP-binding mutants (left) and Ub-btnding mutants (right) Binding isotherms for p6 (top panels), p6-Ub (middle panels) and Ub (bottom panels) are shown. Mutants that significantly reduced p6 binding are shown in red, those that significantly reduced Ub binding are shown in blue (see Table 4) Mutations that had no significant effect are in green The wildtype binding isotherms are in black
  • Figure 5 shows a mapping the TsglOl UEV and Ub interaction sites
  • Figure 5a shows an overlay of the ⁇ /' 5 N-HSQC spectra of TsglOl UEV in the absence (gray) or presence of 2 0 molar equivalents of Ub
  • FIG. 6 shows the comparison of the ubiquitin binding site (blue residues) on TsglOl UEV (yellow) to models for the two distinct ubiquitin binding sites (pu ⁇ le) on the Ubcl3/Mms2 heterodimer (gray) (VanDemark et al , 2001)
  • TsglOl UEV was superimposed on either the Ubcl3 E2 (see Figure 6a) or the Mms2 UEV (see Figure 6b) subunits of the Ubcl3/Mms2 heterodimer
  • the figure illustrates the fact that the Ub binding surface on TsglOl is distinct from previously characterized Ub binding sites on either E2 or UEV domains, but does roughly correspond to the Mms2 binding site on Ubcl 3
  • Figure 7 shows the structure of the TsglOl UEV-PTAP peptide complex
  • Figure 7a shows an overlaid 1H/15N-HSQC spectra of the tsN-
  • Figure 10 shows strips from of ⁇ H/ ⁇ C-NOESY-HSQC spectra of the TsglOl UEV-PTAP peptide complex.
  • the left panels (boxed in green) show nC ⁇ sN-labeled PTAP peptide and unlabeled UEV domain.
  • Intrapeptide NOE correlations are colored green and intermolecular molecular NOE correlations are colored red.
  • the right panels (boxed in black) show nC/isN-labeled UEV domain and unlabeled PTAP peptide.
  • Intramolecular (UEV-UEV) NOE correlations are colored black, and intermolecular NOE correlations are colored red. Resonance assignments are indicated at the bottom and sides of the figure, with peptide resonances labeled in green and UEV resonances labeled in black.
  • Figure 10b shows a sequence and secondary structure of TsglOl UEV. Residues that contact the PTAP peptide are shaded in yellow.
  • Figure 10c shows a stereoview supe ⁇ osition of the 20 final structures (C ⁇ trace) of TsglOl UEV (gray) and PTAP peptide (dark green).
  • Ranges may be expressed herein as from “about” one particular value, and/or to "about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent "about,” it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10" is also disclosed.
  • Reducing means lowering or decreasing. It can be any amount of reduction, and would typically be determined as “reducing” by comparing amount of interest to a reference amount For example, if a "reducing viral budding with an inhibitor” would be any decrease in viral budding in the presence of an inhibitor as compared to the amount of viral budding in the absence of the inhibitor or a control. Any of he assays disclosed herein or known can be used to determine whether something is "reducing.”
  • Set of molecules Disclosed are sets of molecules. These sets comprise at least two different molecules disclosed herein The molecules can differ by as little as single atom up to being made up of completely different atoms The sets can be made up of any of the disclosed compositions or combinations of compositions disclosed herein A set of molecules can be referred to as a library of molecules.
  • a system as used herein refers to any combination of components that has a set of desired characteristics
  • a system might be a cell that has been transfected with a particular gene or combination of genes so that the cell has certain properties
  • the system could be a cell type that has been developed so as being capable of being used in viral budding analysis
  • the system could also be a, for example, chromatographic column having certain properties that would for example, include the covalent attachment of one of the disclosed proteins, such as TSG 101
  • compositions and Methods 30 Disclosed are solution structures of TSGIOI and regions of TSGIOI, as well as regions of GAG, such as the PTAP region, as well as solution structures of complexes involving these molecules
  • These solution structures have produced sets of coordinates that define the position of the atoms making up TSGIOI UEV and PTAP and UB, and the TSG 101 UEV complexed with PTAP. These coordinates can be used to produce three dimensional representations of the these molecules, which can be used in a variety of ways, including, for example, drug screening and variant TSGIOI or PTAP structure determination
  • the methods involve producing solutions of TSGIOI UEV and solutions of the complexes such that solution structure data can be obtained, and then assigning coordinate values to the various atoms forming the TSGIOI UEV optionally including the PTAP and or Ub binding regions and their complexes.
  • the scalable three dimensional set of points is derived from structure coordinates of at least coordinates associated with Y63, V89, M95, and VI 41 for the PTAP binding domain and V43, F44, N45, D46, W75, and F88 for the UB binding domain.
  • the scalable three dimensional set of points is derived from structure coordinates of at least coordinates associated with Thr58, Val ⁇ l, Tyr63, Tyr68, Asn69, Ile70, Pro71 , Thr92, Met95, Prol39, Val 141, Phel42, Serl43, and Argl44 alone or in combination.
  • Two points are considered structurally homologous if they have RMS of less than 5 A 0 , 4 A°, 3 A°, 2 A 0 ., or 1 0A°.
  • a structurally homologous structure would have an average of less than 5 A°, 4 A°, 3 A°, 2 A 0 , or 1 0A° RMS.
  • TSGIOI UEV molecules that include at least a portion of the PTAP and/or Ub binding regions.
  • the molecules could include the amino acids Y63, V89, M95, and V141 for the PTAP binding domain and V43, F44, N45, D46, W75, and F88 for the UB binding domain
  • the molecules could also include the amino acids, Thr58, Val ⁇ l, Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol39,
  • the TSGIOI UEV structure can be defined by the coordinates set forth in Tables 5 or fraction of these coordinates, or coordinates producing a homologous structure.
  • the PTAP binding domain of TSGIOI can be defined by the coordinates set forth in Table 5, or other Tables herein.
  • the coordinates for the 40 lowest energy structures (20 from CNS, 20 from DYANA) are set forth in Tables 8-47 and they set forth structural information about amino acids Thr58, Val ⁇ l, Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol 39, Vall41 , Phel42, Serl43, and Argl44 alone or in combination, or fraction of these coordinates, or coordinates producing a homologous structure of the PTAP binding domain
  • the Ub binding domain of TSGIOI can be defined by the coordinates set forth in Table 5 related to amino acids V43, F44, N45, D46, W75, and F88 or a fraction of these coordinates, or coordinates producing a homologous structure of the Ub binding domain
  • molecules or molecular complexes and their cognate coordinates that are structurally homologous to TSGIOI UEV optionally including the PTAP and/or Ub binding regions and their complexes.
  • the methods include producing a solution of the molecule or molecular complex, generating a solution structure aided by the information disclosed herein, and applying at least a portion of the structure coordinates set forth Table 5 or the data related to the molecule or molecule complex to generate a three-dimensional structure of at least a portion of the molecule or molecular complex
  • Each of the constituent amino acids of TSGIOI UEV or the PTAP and/or Ub binding regions can be defined by a set of structure coordinates or fraction thereof as set forth in Table 5, or any of the coordinate tables disclosed herein
  • structure coordinates refers to a Cartesian coordinate of a particular atom It is understood that for any reference to Table 5, unless specifically indicated otherwise, the description applies equally to all of the coordinate tables contained herein, including those on the included CD-Rs.
  • Coordinates 43 Structure coordinates define a unique configuration of points in space Those of skill in the art understand that a set of structure coordinates for protein or an protein/hgand complex, or a portion thereof, define a relative set of points that, in turn, define a configuration in three dimensions A key piece of information obtained from the coordinates is the position of the atoms that make up the composition The position of the atoms is defined in a Cartesian form, such that there are x-y-z positions which allow for a determination of distances and angles between two or more atoms Thus, a similar or identical configuration, l e structure, can be defined by an entirely different set of coordinates, provided the distances and angles between coordinates remain essentially the same By manipulating the distances and angles in a like manner a scalable representation can be obtained
  • scalable three-dimensional configurations derived from the structure coordinates obtained from the disclosed molecules such as TSGIOI UEV
  • coordinates representing other low energy structures of the TSG101-UEV domain The data represented in Table 3 was derived from performing standard calculations of the coordinates as disclosed herein It is understood that once given the coordinate sets herein, the RMS, for example, for any atom or subset of atoms can be calculated and is considered herein disclosed
  • the various coordinates set forth in Tables 5, 6, and 8-26 for any given individual atom represent a range for which that atom could take place in a coordinate representation of TSGIOI -UEV or fragment thereof
  • Tables 8-47 are coordinates representing low energy structures of the complex of the TSG 101 -UEV domain and the PTAP
  • Comparisons between different structures, different conformations of the same structure, and different parts of the same structure can be performed in a variety of ways For example, typically the structures (coordinates making up the structure) are loaded, the atom equivalences in these structures are defined; the structures are fit, and then the resulting comparisons are reviewed.
  • Root mean square deviation means the square root of the arithmetic mean of the squares of the deviations. This allows for comparison of two sets of data for example or the cognate position in two configurations or structures.
  • the hardware architecture used for structural analysis and manipulation according to the present invention will include a system processor potentially including multiple processing elements where each processing element may be supported via a MIPS R10000 or R4400 processor such as provided in a SILICON GRAPHICS INDIGO 2 IMPACT workstation; alternative processors such as Intel-compatible processor platforms using at least one PENTIUM III or CELERON (Intel Co ⁇ ., Santa Clara, CA) class processor, UltraSPARC (Sun Microsystems, Palo Alto, CA) or other equivalent processors could be used in other embodiments.
  • the system processor may include combinations of different processors from different vendors.
  • analysis and manipulation functionality, as further described below, may be distributed across multiple processing elements.
  • the term processing element may refer to (1) a process running on a particular piece, or across particular pieces, of hardware, (2) a particular piece of hardware, or either (1) or (2) as the context allows.
  • the hardware includes a system data store (SDS) that could include a variety of primary and secondary storage elements.
  • SDS would include RAM as part of the primary storage; the amount of RAM might range from 32 MB to 640 MB although these amounts could vary and represent overlapping use.
  • the primary storage may in some embodiments include other forms of memory such as cache memory, registers, non-volatile memory (e.g., FLASH, ROM, EPROM, etc.), etc.
  • the SDS may also include secondary storage including single, multiple and/or varied servers and storage elements.
  • the SDS may use internal storage devices connected to the system processor.
  • a local hard disk drive may serve as the secondary storage of the SDS, and a disk operating system executing on such a single processing element may act as a data server receiving and servicing data requests.
  • database(s) may be used to store and manipulate the data, in some such embodiments, one or more relational database management systems, such as DB2 (IBM, White Plains, NY), SQL Server (Microsoft, Redmond, WA), ACCESS (Microsoft, Redmond, WA), ORACLE 81 (Oracle Co ⁇ , Redwood Shores, CA), Ingres (Computer Associates, Islandia, NY), MySQL (MySQL AB, Sweden) or Adaptive Server Ente ⁇ se (Sybase Inc , Emeryville, CA), may be used in connection with a variety of storage devices/file servers that may include one or more standard magnetic and/or optical disk drives using any appropriate interface including, without limitation, IDE, EISA and SCSI
  • a tape library such as Exabyte X80 (Exabyte Co ⁇ oration, Boulder, CO)
  • SAN storage attached network
  • the data store may use database systems with other architectures such as object-oriented, spatial, object-relational or hierarchical or may use other storage implementations such as hash tables or flat files or combinations of such architectures
  • Such alternative approaches may use data servers other than database management systems such as a hash table look-up server, procedure and/or process and or a flat file retrieval server, procedure and/or process
  • the SDS may use a combination of any of such approaches in organizing its secondary storage architecture
  • coordinate data is stored in flat ASCII files according to a standardize format
  • the standardized format is PDB as which is used through out the protein structure industry
  • the column content of the Tables containing coordinate data disclosed herein follows the PDB formatting and nomenclature
  • the hardware platform would have an appropriate operating system such as WINDOWS/NT, WINDOWS 2000 or WINDOWS/XP Server (Microsoft, Redmond, WA), Solans (Sun Microsystems, Palo Alto, CA), or IRIX (or other UNIX/LINUX variant)
  • the hardware platform includes an IRIX operating system running on a SILICON GRAPHICS INDIGO 2 IMPACT workstation 3. Structural coordinates and storage of same
  • Structural coordinates, such as atomic coordinates, of this invention can be stored in a machine- readable form on machine-readable storage medium
  • machine-readable storage medium examples include, but are not limited to, computer hard drive, diskette, DAT tape, CD-ROM, and the like
  • the information stored on this media can be used for display as a three-dimensional shape or representation thereof or for other uses based on the structural coordinates, the spatial relationships between atoms described by the structural coordinates or the three- dimensional structures that they define
  • Such uses can include the use of a computer capable of reading the data from the storage media and executing instructions to generate and/or manipulate structures defined by the data
  • Commonly used sets of instructions, 1 e computer programs, for viewing or otherwise manipulating structures include, but are not limited to, Midas (UCSF), MidasPlus (UCSF), MOIL (University of Illinois), Yummie (Yale University), Sybyl (Tripos, Inc ), Insight/Discover (Biosym Technologies), MacroModel (Columbia
  • Disclosed are machine-readable storage mediums comprising a data storage material encoded with machine readable data. Furthermore, the data can be extracted and manipulated by machines configured to read the data stored on the machine readable storage media, and in fact, when performing the molecular modeling, such as displaying a configuration of the disclosed compositions, as discussed herein, typically the data will be retrieved or stored on a machine readable storage media.
  • Disclosed are machine readable storage media comprising the coordinates set forth in Table 5 or a subset of these coordinates, or coordinates of any of tables 6, and 8-47 or subsets of these, or any of the tables disclosed herein, or coordinates producing equivalent configurations of the disclosed compositions or their variants as discussed herein.
  • the disclosed coordinates and data can be manipulated on any appropriate machine, having for example, a processor, memory, and a monitor.
  • the data can also be manipulated and accessed by a variety of connected items, including printers, LCDs, for example.
  • Modeling of variants 65 Structures of variant TSGIOI or GAG or PTAP or Ub or P6 molecules or PTAP, for example, can be produced without obtaining individual coordinates for the variant. In essence the coordinates of the molecules disclosed herein or coordinates that produce a structure homolog are used as a starting point and the variant atom or atoms of the variant disclosed molecule are substituted into the simulated structure and their relative position to the original unchanging atoms, i.e. coordinates, are determined through any of a variety of energy minimization functions. Thus, sequence alignment, secondary structure prediction, the screening of structural libraries of TSGIOI or P6 or any of the other disclosed molecules, produced from the disclosed coordinates, or any combination of these can be used to overlay the variant structure.
  • the variant atom or atoms can also be modeled from any structural library having coordinates of similar or identical atoms.
  • the initial structure to undergo energy minimization can be arrived at by modeling known coordinates for a given for the given atom or atoms.
  • These libraries of structures can be screened for the optimal structure.
  • a side chain rotomer library can be used to model a given side chain or set of side chains.
  • Computational techniques can be used to screen, identify, select and design chemical entities capable of associating with TSGIOI , the TSG 101 UEV, the TSGIOI PTAP binding domain, or the TSGIOI Ub binding domain, for example, or structurally homologous molecules, or complexes of the same.
  • the disclosed coordinates and those that produce structurally homologous molecules can be used to model potential ligands for modulators, such as inhibitors, of TSGIOI -GAG interactions.
  • Atoms of the potential ligand can be included in modeling simulation involving the TSGIOI, and other molecules as disclosed herein, and the contacts that arise between the potential ligand in a variety of positions with the disclosed compositions, or with a region, such as the TSGIOI PTAP binding domain, can be investigated. Energy minimization of these contacts between the potential ligand and the disclosed molecules can indicate potential ligands having, for example a desired affinity or a desired specificity.
  • the ligands identified as having a desired number of contacts, with atoms of the disclosed compositions, such as TSGIOI UEV, as positioned by the coordinates or homologs disclosed herein, can be chosen and then optionally further tested by synthesizing or making the ligand and the disclosed compositions and performing standard biochemistry to assay binding activity or functional activity, such as those that use kinetic or thermodynamic methodology, such as, equilibrium dialysis, microcalorimetry, circular dichroism, capillary zone electrophoresis, nuclear magnetic resonance spectroscopy, fluorescence spectroscopy, and combinations thereof.
  • kinetic or thermodynamic methodology such as, equilibrium dialysis, microcalorimetry, circular dichroism, capillary zone electrophoresis, nuclear magnetic resonance spectroscopy, fluorescence spectroscopy, and combinations thereof.
  • Drug designing typically involves computer-assisted design of chemical entities that associate with TSGIOI or GAG, their homologs, or portions thereof. Chemical entities can be designed in a step-wise fashion, one fragment at a time, or may be designed as a whole or "de novo.”
  • the binding sites of TSGIOI and GAG molecules, such as the PTAP binding site, the Ub binding site, and the TSGIOI binding site, as disclosed herein set forth the position of target atoms for interaction with ligands which will be able to bind or inhibit the disclosed interactions.
  • the conformation of the TSG101- PTAP binding site and the TSGIOI-Ub binding site allow for a precise three dimensional map for rationally designing molecules that will form, for example, a set number of contacts with the atoms defining the binding regions as disclosed herein.
  • a contact as used herein means any position between two atoms, typically one atom of a ligand and one atom of the disclosed compositions, such as the TSG101-PTAP or Ub binding domains, that when positioned by an energy minimization program, for example, are less than 5A°, 4A°, 3A°, 2A°, or 1 A° apart.
  • a contact can for example, correlate with, for example, non-covalent interactions, such as a hydrogen bonds, Vander Walls interactions, hydrophobic interactions, and electrostatic interactions, between two atoms.
  • a contact will add to the binding energy between two atoms, but it can also be repulsive, typically more repulsive the closer the two atoms become.
  • a contact is defined herein as being a relationship of two atoms, the molecules, components and compounds of which the atoms are a part can be referred to as having "contacts" with each other.
  • a ligand having an atom that forms a contact with an atom in a TSGIOI domain can be said to have a contact with the TSGIOI domain (and, more broadly, a contact with the TSGIOI)
  • an inhibitor having an atom that forms a contact with an atom in an amino acid in a protein (such as TSGIOI) can be said to have a contact with the amino acid in the protein
  • the contacts involved are the contacts between the atoms as described above It is understood that for a ligand to be a potential therapeutic candidate, it must have an appropriate level or quality of contacts, such that an interaction occurs, but that it should not cause ste ⁇ c and energetic problems Conformational considerations include the overall three-dimensional structure and orientation of the chemical entity in relation to the binding pocket, and the spacing between various functional
  • the efficiency of a potential hgand's interaction with the disclosed compositions can be evaluated and optimized For example, typically a preferred ligand will cause little perturbation to the three dimensional positioning of the atoms of disclosed compositions that are in the vicinity of the interaction or are somehow alloste ⁇ cally affected
  • the level of perturbation can be determined by comparing the energy state of the disclosed structural conformations for the bound and unbound states Typically the smaller the change the less perturbation and the less perturbation the higher the likelihood that the ligand will be desirable as for example, a competitive inhibitor
  • This perturbation energy can be, for example, less than or equal to about 30 kcal/mole, 20 kcal/mole, 15 kcal/mole, 10 kcal/mole, 8 kcal/mole, 6 kcal/mole, 5 kcal/mole, 4 kcal/mole, 3 kcal/mole, 2 kcal/mole, or 1 kcal/mole TSGIOI or GAG ligands may interact
  • TSGIOI or GAG An entity designed or selected as binding to TSGIOI or GAG may be further computationally optimized so that in its bound state it would preferably lack repulsive electrostatic interaction with the target enzyme and with the surrounding water molecules Such non-complementary electrostatic interactions include repulsive charge-charge, dipole-dtpole, and charge-dipole interactions
  • the disclosed structures and coordinates can also be used to screen potential ligands, for example, as drug candidates, which interact with, I e form contacts with, the TSGIOI or GAG
  • Small molecule databases such as structure databases can be used for this Not only whole molecules can be screened, but subparts of molecule, for example, various functional groups can also be screen to find preferred functional groups for forming contacts with the TSG 101 or GAG structures disclosed herein
  • Functional groups that make a desired set of contacts, for example, with a desired or particular region of the TSGIOI or GAG molecule can then be used to further build combinations of these and other types of functional groups to design ligands containing the functional groups or combinations of functional groups 77
  • iterative approaches which use successive performance of the various steps disclosed herein to optimize molecules and/or isolate molecules from sets of molecules This can also be done with multiple coordinate sets that have been obtained, for example, from the solution of structures involving a ligand or series of structures involving a series of ligands For example,
  • compositions that are identified or designed as a result of any of these methods can be obtained (or synthesized) and tested for its biological activity, e g , inhibition of TSGIOI -GAG interaction activity C.
  • TSGIOI can have a PTAP binding domain, which functions to interact with the PTAP region of a retroviral GAG protein. It is understood that the TSGIOI PTAP binding domain can bind any protein containing the PTAP region. This region is a part of retroviral GAG proteins as well as proteins in enveloped viruses. TSGIOI also can have ubtquitin binding domain, which can interact with ubtquitin
  • TsglOl and the PTAP late domain motifs on the viral structural proteins is mediated by the N-terminal ubiquitin E2 variant (UEV) domain of TsglOl (VerPlank et al , 2001 , Garrus et al , 2001 ; Martin-Serrano et al , 2001), whereas the remaining C-terminal two-thirds of Tsgl Ol interacts with other proteins (Fig.
  • UUV N-terminal ubiquitin E2 variant
  • TsglOl UEV shows significant sequence similarity to E2 ubiquitin hgases but is unable to catalyze ubtquitin transfer, as it lacks the active site cysteine that forms the transient thioester bond with the C-terminus of ubiquitin (Ub) (Koonin and Abagyan, 1997, Ponting et al , 1997) (Fig. ⁇ b).
  • UEVs have retained the ability to bind Ub, and appear to act either as co-factors in ubiquitination reactions, or as ubiquitin sensors (Hofmann and Pickart, 1999, VerPlank et al , 2001 ; Katzmann et al., 2001 , VanDemark et al., 2001 , Garrus et al., 2001)
  • UEV domains also frequently contain other protein recognition motifs, and may generally serve to couple protein and Ub binding functions to facilitate the formation of multiprotein complexes
  • Tsg 101 was initially discovered in a screen for potential tumor suppressors (Li and Cohen, 1996), and the protein appears to perform multiple functions, including down-regulating p53 via the MDM2/p53 pathway (Li et al , 2001; Ruland et al , 2001). TsglOl also plays a central role in vacuolar protein sorting.
  • the Vps pathway sorts membrane-bound proteins for eventual degradation in the lysosome (vacuole in yeast) ((Lemmon and Traub, 2000) and references therein)
  • Two alternative entrees into the Vps pathway are via vesicular trafficking from the Golgi (e g , in destroying misfolded membrane proteins) or via endocytosis from the plasma membrane (e.g., in downregulating surface receptors)
  • Vesicles carrying proteins from either source can enter the Vps pathway by fusing with endosomes As these endosomes mature, their cargos are sorted for lysosomal degradation via the formation of structures called multivesicular bodies (MVB).
  • MVB multivesicular bodies
  • MVB are created when surface patches on late endosomes bud into the lumen, forming small (-50-100 nm) vesicles.
  • a maturing MVB can contain tens or even hundreds of these vesicles.
  • the MVB then fuses with the lysosome, releasing the vesicles for degradation in this hydrolytic organelle 82 Ub also plays an important role in the budding of retroviruses and other enveloped viruses (Harty et al., 2000; Patnaik et al., 2000; Schubert et al , 2000, Strack et al , 2000; Vogt, 2000, Harty et al , 2001 ; Kikonyogo et al , 2001) Retroviruses contain high levels of ubiquitin, and 2-5% of Gag proteins in the vi ⁇ on are monoubiquitinated (Putterman et al , 1990, Ott et al., 1998; Ott et al., 2000).
  • HIV-1 Like other enveloped viruses, HIV-1 uses cellular machinery to bud from infected cells
  • TsglOl protein functions in vacuolar protein sorting (Vps) and is required for HIV-1 budding
  • Vps vacuolar protein sorting
  • PTAP essential tetrapeptide
  • PTAP essential tetrapeptide
  • Depletion of cellular TsglOl by a small interfering RNA arrests HIV-1 budding at a late stage, and budding is rescued by reintroduction of TsglOl
  • Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV budding
  • HIV-1 assembly is driven by the viral Gag protein, which is actively trafficked to the plasma membrane where it associates into enveloped, spherical particles that bud from the cell (reviewed in (Freed, 1998))
  • Gag is processed by the viral protease at a series of sites to produce four new structural proteins that perform essential functions in the mature, infectious vi ⁇ on (denoted MA, CA, NC, and p6, Fig 1 A) Proteolytic processing is not required for particle production, however, as HIV-1 Gag can assemble and bud in the absence of any other viral proteins
  • the budding of an enveloped virus can be viewed as a fission event in which the continuous cell membrane is broken and resealed to create discrete viral and cellular membranes
  • HIV-1 does not encode its own membrane fission machinery and presumably therefore must recruit and reprogram cellular proteins to assist in the budding process
  • a potential docking site for such cellular factor(s) has been mapped to a conserved P(T/S)AP motif located in the p6 domain of HIV-1 Gag Point mutations within this "PTAP" motif arrest viral release at a very late stage (Gott nger et al , 1991 , Huang et al , 1995), and it has therefore been termed a "late domain" (Wills and Craven, 1991)
  • Virus assembly appears to initiate normally in the late domain mutants, but the continuous membrane that connects the budding particles to the cell (or to other budding particles) is not severed, resulting in abnormal or severely attenuated virus release
  • Ubiquitin (Ub) also plays an essential, albeit poorly understood, role in retroviral budding (Patnaik et al , 2000, Schubert et al , 2000b, Strack et al , 2000, Vogt, 2000)
  • retrovirus budding can be blocked at a late stage by depleting cellular pools of free ubiquitin with proteasome inhibitors
  • the functionally relevant substrate for ubiquit ation is Gag itself or a cellular factor HIV-1 p6 and other retroviral Gag proteins are monoubiquitinated at low levels (Ott et al , 2000) and there is a general correlation between Gag ubiquitmation and virus release (Schubert et al , 2000b, Strack et al , 2000)
  • the block imposed by proteasome inhibitors can be at least partially alleviated by covalently fusing Ub to the C-terminal end of Rous sarcoma virus
  • Gag ubiquitmation could facilitate budding either by targeting defective Gag molecules for proteolytic degradation and thereby preventing them from interfering with viral budding (Schubert et al , 2000a), or by creating docking sites for cellular factors that actively participate in viral budding
  • Functional nucleic acids are nucleic acid molecules that have a specific function, such as binding a target molecule or catalyzing a specific reaction
  • Functional nucleic acid molecules can be divided into the following categories, which are not meant to be limiting
  • functional nucleic acids include antisense molecules, aptamers, ⁇ bozymes, triplex forming molecules, and external guide sequences
  • the functional nucleic acid molecules can act as affecters, inhibitors, modulators, and stimulators of a specific activity possessed by a target molecule, or the functional nucleic acid molecules can possess a de novo activity independent of any other molecules
  • Functional nucleic acid molecules can interact with any macromolecule, such as DNA, RNA, polypeptides, or carbohydrate chains
  • functional nucleic acids can interact with the mRNA of TSGIOI or fragment thereof, or the genomic DNA of TSGIOI or fragment thereof or they can interact with the polypeptide TSGIOI or fragment thereof, such as the PTAP binding domain or the UB binding domain
  • functional nucleic acids are designed to interact with other nucleic acids based on sequence homology between the target molecule and the functional nucleic acid molecule
  • the specific recognition between the functional nucleic acid molecule and the target molecule is not based on sequence homology between the functional nucleic acid molecule and the target molecule, but rather is based on the formation of tertiary structure that allows specific recognition to take place
  • Antisense molecules are designed to interact with a target nucleic acid molecule through either canonical or non-canonical base pairing The interaction of the antisense molecule and the target molecule is designed to promote the destruction of the
  • the antisense molecules bind the target molecule with a k d less than 10 "12 .
  • a representative sample of methods and techniques which aid in the design and use of antisense molecules can be found in the following non-limiting list of United States patents: 5,135,917, 5,294,533, 5,627,158, 5,641,754, 5,691,317, 5,780,607, 5,786,138, 5,849,903, 5,856,103, 5,919,772, 5,955,590, 5,990,088, 5,994,320, 5,998,602, 6,005,095, 6,007,995, 6,013,522, 6,017,898, 6,018,042, 6,025,198, 6,033,910, 6,040,296, 6,046,004, 6,046,319, and 6,057,437.
  • Aptamers are molecules that interact with a target molecule, preferably in a specific way.
  • aptamers are small nucleic acids ranging from 15-50 bases in length that fold into defined secondary and tertiary structures, such as stem-loops or G-quartets.
  • Aptamers can bind small molecules, such as ATP (United States patent 5,631,146) and theophiline (United States patent 5,580,737), as well as large molecules, such as reverse transcriptase (United States patent 5,786,462) and thrombin (United States patent 5,543,293).
  • Aptamers can bind very tightly with kas from the target molecule of less than 10 " ' 2 M.
  • the aptamers bind the target molecule with a k d less than 10 "6 . It is more preferred that the aptamers bind the target molecule with a k d less than 10 "8 . It is also more preferred that the aptamers bind the target molecule with a kj less than 10 " . It is also preferred that the aptamers bind the target molecule with a k_ less than 10 "12 . Aptamers can bind the target molecule with a very high degree of specificity.
  • aptamers have been isolated that have greater than a 10000 fold difference in binding affinities between the target molecule and another molecule that differ at only a single position on the molecule (United States patent 5,543,293). It is preferred that the aptamer have a k d with the target molecule at least 10 fold lower than the k d with a background binding molecule. It is more preferred that the aptamer have a k d with the target molecule at least 100 fold lower than the l with a background binding molecule. It is more preferred that the aptamer have a k d with the target molecule at least 1000 fold lower than the k d with a background binding molecule.
  • the aptamer have a k d with the target molecule at least 10000 fold lower than the k d with a background binding molecule. It is preferred when doing the comparison for a polypeptide for example, that the background molecule be a different polypeptide. For example, when determining the specificity of
  • TSGIOI aptamers such as TSGIOI PTAP binding domain or UB binding domain aptamers
  • the background protein could be albumin.
  • Representative examples of how to make and use aptamers to bind a variety of different target molecules can be found in the following non-limiting list of United States patents: 5,476,766, 5,503,978, 5,631 ,146, 5,731,424 , 5,780,228, 5,792,613, 5,795,721, 5,846,713, 5,858,660 , 5,861,254, 5,864,026, 5,869,641, 5,958,691 , 6,001,988, 6,01 1,020, 6,013,443, 6,020,130, 6,028,186, 6,030,776, and 6,051 ,698.
  • Ribozymes are nucleic acid molecules that are capable of catalyzing a chemical reaction, either intramolecularly or intermolecularly. Ribozymes are thus catalytic nucleic acid. It is preferred that the ribozymes catalyze intermolecular reactions.
  • ribozymes that catalyze nuclease or nucleic acid polymerase type reactions which are based on ribozymes found in natural systems, such as hammerhead ribozymes, (for example, but not limited to the following United States patents: 5,334,71 1, 5,436,330, 5,616,466, 5,633,133, 5,646,020, 5,652,094, 5,712,384, 5,770,715, 5,856,463, 5,861,288, 5,891 ,683, 5,891 ,684, 5,985,621, 5,989,908, 5,998,193, 5,998,203, WO 9858058 by Ludwig and Sproat, WO 9858057 by Ludwig and Sproat, and WO 9718312 by Ludwig and Sproat) hai ⁇ in ribozymes (for example, but not limited to the following United States patents: 5,631 ,1 15, 5 " ,646,031 , 5,683,902, 5,712,384,
  • ribozymes cleave RNA or DNA substrates, and more preferably cleave RNA substrates. Ribozymes typically cleave nucleic acid substrates through recognition and binding of the target substrate with subsequent cleavage. This recognition is often based mostly on canonical or non-canonical base pair interactions. This property makes ribozymes particularly good candidates for target specific cleavage of nucleic acids because recognition of the target substrate is based on the target substrates sequence.
  • Triplex forming functional nucleic acid molecules are molecules that can interact with either double-stranded or single-stranded nucleic acid. When triplex molecules interact with a target region, a structure called a triplex is formed, in which there are three strands of DNA forming a complex dependant on both Watson-Crick and Hoogsteen base-pairing. Triplex molecules are preferred because they can bind target regions with high affinity and specificity. It is preferred that the triplex forming molecules bind the target molecule with a k d less than 10 "6 . It is more preferred that the triplex forming molecules bind with a k d less than 10 "8 .
  • the triplex forming molecules bind the target molecule with a k d less than 10 ' . It is also preferred that the triplex forming molecules bind the target molecule with a k d less than 10 "12 .
  • Representative examples of how to make and use triplex forming molecules to bind a variety of different target molecules can be found in the following non-limiting list of United States patents: 5,176,996, 5,645,985, 5,650,316, 5,683,874, 5,693,773, 5,834,185, 5,869,246, 5,874,566, and 5,962,426. 95.
  • EGSs External guide sequences
  • RNase P RNase P
  • EGSs can be designed to specifically target a RNA molecule of choice.
  • RNAse P aids in processing transfer RNA (tRNA) within a cell.
  • Bacterial RNAse P can be recruited to cleave virtually any RNA sequence by using an EGS that causes the target RNA:EGS complex to mimic the natural tRNA substrate. (WO 92/03566 by Yale, and Forster and Altman, Science 238:407-409 ( 1990)).
  • RNAse P-directed cleavage of RNA can be utilized to cleave desired targets within eukaryotic cells.
  • antibodies is used herein in a broad sense and includes both polyclonal and monoclonal antibodies. In addition to intact immunoglobulin molecules, also included in the term “antibodies” are fragments or polymers of those immunoglobulin molecules, and human or humanized versions of immunoglobulin molecules or fragments thereof, as long as they are chosen for their ability to interact with TSGIOI such that TSGIOI is inhibited from interacting with a viral GAG protein, such as HIV or Ebola GAG. Antibodies that bind the disclosed regions of TSGIOI involved in the interaction between TSG IOI and GAG are also disclosed. The antibodies can be tested for their desired activity using the in vitro assays described herein, or by analogous methods, after which their in vivo therapeutic and/or prophylactic activities are tested according to known clinical testing methods. Also disclosed are functional equivalents of antibodies.
  • the term "monoclonal antibody” as used herein refers to an antibody obtained from a substantially homogeneous population of antibodies, i.e., the individual antibodies within the population are identical except for possible naturally occurring mutations that may be present in a small subset of the antibody molecules.
  • the monoclonal antibodies herein specifically include "chimeric" antibodies in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, as long as they exhibit the desired antagonistic activity (See, U.S. Pat. No. 4,816,567 and Morrison et al., Proc. Natl. Acad. Sci. USA, 81 :6851-6855 (1984)).
  • monoclonal antibodies can be made using any procedure which produces mono clonal antibodies.
  • monoclonal antibodies of the invention can be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256:495 ( 1975).
  • a hybridoma method a mouse or other appropriate host animal is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent.
  • the monoclonal antibodies may also be made by recombinant DNA methods, such as those described in U.S. Pat. No. 4,816,567 (Cabilly et al.).
  • DNA encoding the disclosed monoclonal antibodies can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies).
  • Libraries of antibodies or active antibody fragments can also be generated and screened using phage display techniques, e.g., as described in U.S. Patent No. 5,804,440 to Burton et al. and U.S. Patent No. 6,096,441 to Barbas et al.
  • In vitro methods are also suitable for preparing monovalent antibodies.
  • Digestion of antibodies to produce fragments thereof, particularly, Fab fragments can be accomplished using routine techniques known in the art. For instance, digestion can be performed using papain. Examples of papain digestion are described in WO 94/29348 published Dec. 22, 1994 and U.S. Pat. No. 4,342,566.
  • Papain digestion of antibodies typically produces two identical antigen binding fragments, called Fab fragments, each with a single antigen binding site, and a residual Fc fragment. Pepsin treatment yields a fragment that has two antigen combining sites and is still capable of cross-linking antigen.
  • the fragments can also include insertions, deletions, substitutions, or other selected modifications of particular regions or specific amino acids residues, provided the activity of the antibody or antibody fragment is not significantly altered or impaired compared to the non- modified antibody or antibody fragment. These modifications can provide for some additional property, such as to remove/add amino acids capable of disulfide bonding, to increase its bio-longevity, to alter its secretory characteristics, etc.
  • the antibody or antibody fragment must possess a bioactive property, such as specific binding to its cognate antigen. Functional or active regions of the antibody or antibody fragment may be identified by mutagenesis of a specific region of the protein, followed by expression and testing of the expressed polypeptide.
  • antibody or “antibodies” can also refer to a human antibody and/or a humanized antibody.
  • Many non-human antibodies e.g., those derived from mice, rats, or rabbits
  • are naturally antigenic in humans and thus can give rise to undesirable immune responses when administered to humans. Therefore, the use of human or humanized antibodies in the methods of the invention serves to lessen the chance that an antibody administered to a human will evoke an undesirable immune response.
  • the human antibodies of the invention can be prepared using any technique. Examples of techniques for human monoclonal antibody production include those described by Cole et al. (Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77, 1985) and by Boerner et al. (J. Immunol., 147(l):86-95, 1991). Human antibodies of the invention (and fragments thereof) can also be produced using phage display libraries (Hoogenboom et al., J. Mol. Biol., 227:381, 1991 ; Marks et al., J. Mol. Biol., 222:581, 1991).
  • the human antibodies of the invention can also be obtained from transgenic animals.
  • transgenic, mutant mice that are capable of producing a full repertoire of human antibodies, in response to immunization, have been described (see, e.g., Jakobovits et al., Proc. Natl. Acad. Sci. USA, 90:2551-255 (1993); Jakobovits et al., Nature, 362:255-258 (1993); Bruggermann et al., Year in Immunol., 7:33 (1993)).
  • the homozygous deletion of the antibody heavy chain joining region (3(H)) gene in these chimeric and germ-line mutant mice results in complete inhibition of endogenous antibody production, and the successful transfer of the human germ-line antibody gene array into such germ-line mutant mice results in the production of human antibodies upon antigen challenge.
  • Humanized antibodies 106 generally involve the use of recombinant DNA technology to manipulate the DNA sequence encoding one or more polypeptide chains of an antibody molecule.
  • a humanized form of a non-human antibody is a chimeric antibody or antibody chain (or a fragment thereof, such as an Fv, Fab, Fab', or other antigen-binding portion of an antibody) which contains a portion of an antigen binding site from a non-human (donor) antibody integrated into the framework of a human (recipient) antibody.
  • a humanized antibody residues from one or more complementarity dete ⁇ nining regions (CDRs) of a recipient (human) antibody molecule are replaced by residues from one or more CDRs of a donor (non-human) antibody molecule that is known to have desired antigen binding characteristics (e.g., a certain level of specificity and affinity for the target antigen).
  • CDRs complementarity dete ⁇ nining regions
  • donor non-human antibody molecule that is known to have desired antigen binding characteristics (e.g., a certain level of specificity and affinity for the target antigen).
  • Fv framework (FR) residues of the human antibody are replaced by corresponding non-human residues.
  • Humanized antibodies may also contain residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences.
  • a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human.
  • humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies.
  • Humanized antibodies generally contain at least a portion of an antibody constant region (Fc), typically that of a human antibody (Jones et al., Nature, 321 :522-525 (1986), Reichmann et al., Nature, 332:323-327 (1988), and Presta, Curr. Opin. Struct. Biol., 2:593-596 (1992)).
  • Fc antibody constant region
  • humanized antibodies can be generated according to the methods of Winter and co-workers (Jones et al., Nature, 321 :522-525 (1986), Riechmann et al., Nature, 332:323-327 (1988), Verhoeyen et al., Science, 239: 1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody.
  • Methods that can be used to produce humanized antibodies are also described in U.S. Patent No. 4,816,567 (Cabilly et al), U.S. Patent No. 5,565,332 (Hoogenboom et al.), U.S. Patent No.
  • the antibodies can be done as disclosed herein, as the delivery of any non- nucleic acid composition or pharmaceutical.
  • Nucleic acid approaches for antibody delivery also exist.
  • the broadly neutralizing anti TSGIOI antibodies and antibody fragments of the invention can also be administered to patients or subjects as a nucleic acid preparation (e.g., DNA or RNA) that encodes the antibody or antibody fragment, such that the patient's or subject's own cells take up the nucleic acid and produce and secrete the encoded antibody or antibody fragment.
  • the delivery of the nucleic acid can be by any means, as disclosed herein, for example.
  • compositions can be used as targets for any combinatorial technique to identify molecules or macromolecular molecules that interact with the disclosed compositions in a desired way.
  • the nucleic acids, peptides, and related molecules disclosed herein can be used as targets for the combinatorial approaches.
  • compositions that are identified through combinatorial techniques or screening techniques, or through computer modeling techniques, in which the compositions herein disclosed and their structural information, or portions thereof, are used as the target in a combinatorial or screening protocol, or can direct combinatorial or screening protocols
  • Combinatorial chemistry includes but is not limited to all methods for isolating small molecules or macromolecules that are capable of binding either a small molecule or another macromolecule, typically in an iterative process
  • Proteins, oligonucleotides, and sugars are examples of macromolecules
  • oligonucleotide molecules with a given function, catalytic or hgand-binding can be isolated from a complex mixture of random oligonucleotides in what has been referred to as "in vitro genetics" (Szostak, TIBS 19 89, 1992)
  • In vitro genetics Szostak, TIBS 19 89, 1992
  • One synthesizes a large pool of molecules bearing random and defined sequences and subjects that complex mixture for example, approximately l ⁇ ' individual sequences in 100 ⁇ g of a 100 nucleotide RNA, to some selection and enrichment process
  • Ellington and Szostak (1990) estimated that 1 in 10 1 RNA molecules folded in
  • phage display libraries have been used to isolate numerous peptides that interact with a specific target (See for example, United States Patent No 6,031,071 , 5,824,520, 5,596,079, and 5,565,332 which are herein incorporated by reference at least for their material related to phage display and methods relate to combinatorial chemistry)
  • compositions can be used as targets for any molecular modeling technique to identify either the structure of the disclosed compositions or to identify potential or actual molecules, such as small molecules, which interact in a desired way with the disclosed compositions
  • the structural information disclosed herein for any of the disclosed compositions can be used in computer related analysis to design compositions which interact with either TSG-101 binding domain, the PTAP ligand, the UB binding domain, the UB or a combination
  • the compositions disclosed herein can be used as target in computer simulations of potential ligand binding through molecular modeling
  • the disclosed compositions and structures related to the compositions can be used to compare other structural formations comprising the compositions disclosed herein
  • Computer modeling technology allows visualization of the three-dimensional atomic structure of a selected molecule and the rational design of new compounds that will interact with the molecule
  • the three-dimensional construct typically depends on data from x-ray crystallographic analyses or NMR imaging of the selected molecule
  • the molecular dynamics require force field data
  • the computer graphics systems enable prediction of how a new compound will link to the target molecule and allow experimental manipulation of the structures of the compound and target molecule to perfect binding specificity Prediction of what the molecule-compound interaction will be when small changes are made in one or both requires molecular mechanics software and computationally intensive computers, usually coupled with user-friendly, menu-driven interfaces between the molecular design program and the user
  • nucleic acids and proteins can be represented as a sequence consisting of the nucleotides of amino acids There are a variety of ways to display these sequences, for example the nucleotide guanosine can be represented by G or g Likewise the amino acid valine can be represented by Val or V Those of skill in the art understand how to display and express any nucleic acid or protein sequence in any of the variety of ways that exist, each of which is considered herein disclosed
  • Computer readable mediums comprising the sequences and information regarding the sequences set forth herein Also disclosed are computer readable mediums comprising the structural coordinates or a subset of the structure coordinates disclosed in Table 5-47 These coordinates can be displayed in a variety of ways 5.
  • General composition information a) Sequence similarities
  • variants of genes and proteins herein disclosed typically have at least, about 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 91 , 92, 93, 94, 95, 96, 97, 98, or 99 percent homology to the stated sequence or the native sequence.
  • the homology can be calculated after aligning the two sequences so that the homology is at its highest level. 131. Another way of calculating homology can be performed by published algorithms.
  • Optimal alignment of sequences for comparison may be conducted by the local homology algorithm of Smith and Waterman Adv. Appl. Math. 2: 482 (1981), by the homology alignment algorithm of Needleman and Wunsch, J. MoL Biol. 48: 443 (1970), by the search for similarity method of Pearson and Lipman, Proc. Natl. Acad. Sci. U.S.A. 85: 2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by inspection. 132.
  • the same types of homology can be obtained for nucleic acids by for example the algorithms disclosed in Zuker, M.
  • a sequence recited as having a particular percent homology to another sequence refers to sequences that have the recited homology as calculated by any one or more of the calculation methods described above.
  • a first sequence has 80 percent homology, as defined herein, to a second sequence if the first sequence is calculated to have 80 percent homology to the second sequence using the Zuker calculation method even if the first sequence does not have 80 percent homology to the second sequence as calculated by any of the other calculation methods
  • a first sequence has 80 percent homology, as defined herein, to a second sequence if the first sequence is calculated to have 80 percent homology to the second sequence using both the Zuker calculation method and the Pearson and Lipman calculation method even if the first sequence does not have 80 percent homology to the second sequence as calculated by the Smith and Waterman calculation method, the Needleman and Wunsch calculation method, the Jaeger calculation methods, or any of the other calculation methods
  • a first sequence has 80 percent homology, as defined herein, to
  • hybridization typically means a sequence driven interaction between at least two nucleic acid molecules, such as a primer or a probe and a gene
  • Sequence driven interaction means an interaction that occurs between two nucleotides or nucleotide analogs or nucleotide derivatives in a nucleotide specific manner
  • G interacting with C or A interacting with T are sequence driven interactions
  • sequence driven interactions occur on the Watson-Crick face or Hoogsteen face of the nucleotide
  • the hybridization of two nucleic acids is affected by a number of conditions and parameters known to those of skill in the art For example, the salt concentrations, pH, and temperature of the reaction all affect whether two nucleic acid molecules will hybridize
  • selective hybridization conditions can be defined as stringent hybridization conditions
  • stringency of hybridization is controlled by both temperature and salt concentration of either or both of the hybridization and washing steps
  • the conditions of hybridization to achieve selective hybridization may involve hybridization in high ionic strength solution (6X SSC or 6X SSPE) at a temperature that is about 12-25°C below the Tm (the melting temperature at which half of the molecules dissociate from their hybridization partners) followed by washing at a combination of temperature and salt concentration chosen so that the washing temperature is about 5°C to 20°C below the Tm
  • Tm the melting temperature at which half of the molecules dissociate from their hybridization partners
  • the temperature and salt conditions are readily determined empirically in preliminary experiments in which samples of reference DNA immobilized on filters are hybridized to a labeled nucleic acid of interest and then washed under conditions of different stringencies
  • Hybridization temperatures are typically higher for DNA-RNA and RNA-RNA hybridizations
  • the conditions can be used as described above to achieve stringency
  • a preferable stringent hybridization condition for a DNA DNA hybridization can be at about 68°C (in aqueous solution) in 6X SSC or 6X SSPE followed by washing at 68°C Stringency of hybridization and washing, if desired, can be reduced accordingly as the degree of _ . , .
  • selective hybridization is by looking at the amount (percentage) of one of the nucleic acids bound to the other nucleic acid
  • selective hybridization conditions would be when at least about, 60, 65, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85,
  • the non-limiting primer is in for example, 10 or 100 or 1000 fold excess This type of assay can be performed at under conditions where both the limiting and non-limiting primer are for example, 10 fold or 100 fold or 1000 fold below their k d , or where only one of the nucleic acid molecules is 10 fold or 100 fold or 1000 fold or where one or both nucleic acid molecules are above their k d
  • selective hybridization conditions would be when at least about, 60, 65, 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 percent of the primer is enzymatically manipulated under conditions which promote the enzymatic manipulation, for example if the enzymatic manipulation is DNA extension, then selective hybridization conditions would be when at least about 60, 65, 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89
  • nucleic acid based there are a variety of molecules disclosed herein that are nucleic acid based, including for example the nucleic acids that encode, for example TSGIOI, as well as various functional nucleic acids
  • the disclosed nucleic acids are made up of, for example, nucleotides, nucleotide analogs, or nucleotide substitutes Non-limiting examples of these and other molecules are discussed herein It is understood that for example, when a vector is expressed in a cell, that the expressed mRNA will typically be made up of A, C, G, and U Likewise, it is understood that if, for example, an antisense molecule is introduced into a cell or cell environment through for example exogenous delivery, it is advantagous that the antisense molecule be made up of nucleotide analogs that reduce the degradation of the antisense molecule in the cellular environment.
  • a nucleotide is a molecule that contains a base moiety, a sugar moiety and a phosphate moiety. Nucleotides can be linked together through their phosphate moieties and sugar moieties creating an internucleoside linkage.
  • the base moiety of a nucleotide can be adenin-9-yl (A), cytosin-1-yl (C), guanin-9-yl (G), uracil-1-yl (U), and thymin-1 -yl (T).
  • the sugar moiety of a nucleotide is a ribose or a deoxyribose.
  • the phosphate moiety of a nucleotide is pentavalent phosphate.
  • nucleotide An non-limiting example of a nucleotide would be 3'-AMP (3'-adenosine monophosphate) or 5'-GMP (5'-guanosine monophosphate). 142.
  • a nucleotide analog is a nucleotide which contains some type of modification to either the base, sugar, or phosphate moieties. Modifications to nucleotides are well known in the art and would include for example, 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, and 2-aminoadenine as well as modifications at the sugar or phosphate moieties.
  • Nucleotide substitutes are molecules having similar functional properties to nucleotides, but which do not contain a phosphate moiety, such as peptide nucleic acid (PNA). Nucleotide substitutes are molecules that will recognize nucleic acids in a Watson-Crick or Hoogsteen manner, but which are linked together through a moiety other than a phosphate moiety. Nucleotide substitutes are able to conform to a double helix type structure when interacting with the appropriate target nucleic acid.
  • PNA peptide nucleic acid
  • conjugates can be link other types of molecules to nucleotides or nucleotide analogs to enhance for example, cellular uptake.
  • Conjugates can be chemically linked to the nucleotide or nucleotide analogs.
  • conjugates include but are not limited to lipid moieties such as a cholesterol moiety.
  • a Watson-Crick interaction is at least one interaction with the Watson-Crick face of a nucleotide, nucleotide analog, or nucleotide substitute.
  • the Watson-Crick face of a nucleotide, nucleotide analog, or nucleotide substitute includes the C2, NI , and C6 positions of a purine based nucleotide, nucleotide analog, or nucleotide substitute and the C2, N3, C4 positions of a pyrimidine based nucleotide, nucleotide analog, or nucleotide substitute.
  • a Hoogsteen interaction is the interaction that takes place on the Hoogsteen face of a nucleotide or nucleotide analog, which is exposed in the major groove of duplex DNA.
  • the Hoogsteen face includes the N7 position and reactive groups (NH2 or O) at the C6 position of purine nucleotides.
  • compositions including primers and probes which are capable of interacting with the TSGIOI gene or GAG as disclosed herein
  • the primers are used to support DNA amplification reactions
  • the primers will be capable of being extended in a sequence specific manner
  • Extension of a primer in a sequence specific manner includes any methods wherein the sequence and/or composition of the nucleic acid molecule to which the primer is hybridized or otherwise associated directs or influences the composition or sequence of the product produced by the extension of the primer Extension of the primer in a sequence specific manner therefore includes, but is not limited to, PCR, DNA sequencing, DNA extension, DNA polymerization, RNA transcription, or reverse transcription Techniques and conditions that amplify the primer in a sequence specific manner are preferred
  • the primers are used for the DNA amplification reactions, such as PCR or direct sequencing It is understood that in certain embodiments the primers can also be extended using non-enzymatic techniques, where for example, the nucleotides or oligonucleotides used to extend the
  • compositions and methods which can be used to deliver nucleic acids to cells, either in vitro or in vivo
  • these methods and compositions can largely be broken down into two classes viral based delivery systems and non-viral based delivery systems
  • the nucleic acids can be delivered through a number of direct delivery systems such as, electroporation, hpofection, calcium phosphate precipitation, plasmids, viral vectors, viral nucleic acids, phage nucleic acids, phages, cosmids, or via transfer of genetic material in cells or carriers such as cationic liposomes
  • direct delivery systems such as, electroporation, hpofection, calcium phosphate precipitation, plasmids, viral vectors, viral nucleic acids, phage nucleic acids, phages, cosmids, or via transfer of genetic material in cells or carriers such as cationic liposomes
  • the nucleic acids of the present invention can be in the form of naked DNA or RNA, or the nucleic acids can be in a vector for delivering the nucleic acids to the cells, whereby the encoding DNA or DNA or fragment is under the transcriptional regulation of a promoter, as would be well understood by one of ordinary skill in the art as well as enhancers
  • the vector can be a commercially available preparation, such as an adenovirus vector (Quantum Biotechnologies, Inc (Laval, Quebec, Canada) 152
  • vector delivery can be via a viral system, such as a retroviral vector system which can package a recombinant retroviral genome (see e g , Pastan et al , Proc Natl Acad Sci USA 85 4486, 1988, Miller et al , Mol Cell Biol 6 2895, 1986) The re
  • the dosage for administration of adenovirus to humans can range from about 10 to 10 plaque forming units (pfu) per injection but can be as high as 10 12 pfu per injection (Crystal, Hum Gene Ther 8 985-1001 , 1997, Alvarez and Cu ⁇ el, Hum Gene Ther 8 597-613, 1997)
  • a subject can receive a single injection, or, if additional injections are necessary, they can be repeated at six month intervals (or other appropriate time intervals, as determined by the skilled practitioner) for an indefinite period and/or until the efficacy of the treatment has been established
  • Parenteral administration of the nucleic acid or vector of the present invention is generally characterized by injection Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution of suspension in liquid prior to injection, or as emulsions
  • injection Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution of suspension in liquid prior to injection, or as emulsions
  • a more recently revised approach for parenteral administration involves use of a slow release or sustained release system such that a constant dosage is maintained See, e g , U S Patent No 3,610,795, which is inco ⁇ orated by reference herein
  • suitable formulations and various routes of administration of therapeutic compounds see, e g , Remington The Science and Practice of Pharmacy (19th ed ) ed A R Gennaro, Mack Publishing Company, Easton, PA 1995
  • Nucleic acids that are delivered to cells which are to be integrated into the host cell genome typically contain integration sequences These sequences are often viral related sequences, particularly when viral based systems are used These viral integration systems can also be inco ⁇ orated into nucleic acids which are to be delivered using a non-nucleic acid based system of deliver, such as a liposome, so that the nucleic acid contained in the delivery system can be come integrated into the host genome
  • compositions can be delivered to the target cells in a variety of ways.
  • the compositions can be delivered through electroporation, or through lipofection, or through calcium phosphate precipitation.
  • the delivery mechanism chosen will depend in part on the type of cell targeted and whether the delivery is occurring for example in vivo or in vitro.
  • compositions can comprise, in addition to the disclosed compositions or vectors for example, lipids such as liposomes, such as cationic liposomes (e.g., DOTMA, DOPE, DC-cholesterol) or anionic liposomes.
  • liposomes can further comprise proteins to facilitate targeting a particular cell, if desired.
  • Administration of a composition comprising a compound and a cationic liposome can be administered to the blood afferent to a target organ or inhaled into the respiratory tract to target cells of the respiratory tract.
  • liposomes see, e.g., Brigham et al. Am. J. Resp. Cell. Mol. Biol.
  • the compound can be administered as a component of a microcapsule that can be targeted to specific cell types, such as macrophages, or where the diffusion of the compound or delivery of the compound from the microcapsule is designed for a specific rate or dosage.
  • delivery of the compositions to cells can be via a variety of mechanisms.
  • delivery can be via a liposome, using commercially available liposome preparations such as LIPOFECTIN, LIPOFECT AMINE (GIBCO-BRL, Inc, Gaithersburg, MD), SUPERFECT (Qiagen, Inc. Hilden, Germany) and TRANSFECTAM (Promega Biotec, Inc, Madison, WI), as well as other liposomes developed according to procedures standard in the art.
  • nucleic acid or vector of this invention can be delivered in vivo by electroporation, the technology for which is available from Genetronics, Inc. (San Diego, CA) as well as by means of a SONOPORATION machine (ImaRx Pharmaceutical Co ⁇ , Arlington, AZ). 160.
  • the materials may be in solution, suspension (for example, inco ⁇ orated into microparticles, liposomes, or cells). These may be targeted to a particular cell type via antibodies, receptors, or receptor ligands.
  • the following references are examples of the use of this technology to target specific proteins to tumor tissue (Senter, et al, Bioconiugate Chem.. 2:447-451 , (1991); Bagshawe, K.D, Br. J.
  • Vehicles such as "stealth” and other antibody conjugated liposomes (including lipid mediated drug targeting to colonic carcinoma), receptor mediated targeting of DNA through cell specific ligands, lymphocyte directed tumor targeting, and highly specific therapeutic retroviral targeting of murine glioma cells in vivo.
  • the following references are examples of the use of this technology to target specific proteins to tumor tissue (Hughes et al. Cancer Research. 49:6214-6220, ( 1989); and Litzinger and Huang, Biochimica et Biophvsica Acta. 1 104: 179- 187, (1992)).
  • receptors are involved in pathways of endocytosis, either constitutive or ligand induced.
  • receptors cluster in clathrin-coated pits, enter the cell via clathrin-coated vesicles, pass through an acidified endosome in which the receptors are sorted, and then either recycle to the cell surface, become stored intracellularly, or are degraded in lysosomes.
  • the intemalization pathways serve a variety of functions, such as nutrient uptake, removal of activated proteins, clearance of macromolecules, opportunistic entry of viruses and toxins, dissociation and degradation of ligand, and receptor-level regulation. Many receptors follow more than one intracellular pathway, depending on the cell type, receptor concentration, type of ligand, ligand valency, and ligand concentration. Molecular and cellular mechanisms of receptor-mediated endocytosis has been reviewed (Brown and Greene, DNA and Cell Biology 10:6, 399-409 (1991)).
  • compositions can be administered in a pharmaceutically acceptable carrier and can be delivered to the subjects cells in vivo and/or ex vivo by a variety of mechanisms well known in the art (e.g., uptake of naked DNA, liposome fusion, intramuscular injection of DNA via a gene gun, endocytosis and the like).
  • cells or tissues can be removed and maintained outside the body according to standard protocols well known in the art.
  • the compositions can be introduced into the cells via any gene transfer mechanism, such as, for example, calcium phosphate mediated gene delivery, electroporation, microinjection or proteoliposomes.
  • the transduced cells can then be infused (e.g., in a pharmaceutically acceptable carrier) or homotopically transplanted back into the subject per standard methods for the cell or tissue type. Standard methods are known for transplantation or infusion of various cells into a subject.
  • Expression systems are known for transplantation or infusion of various cells into a subject.
  • the nucleic acids that are delivered to cells typically contain expression controlling systems.
  • the inserted genes in viral and retroviral systems usually contain promoters, and/or enhancers to help control the expression of the desired gene product.
  • a promoter is generally a sequence or sequences of DNA that function when in a relatively fixed location in regard to the transcription start site.
  • a promoter contains core elements required for basic interaction of RNA polymerase and transcription factors, and may contain upstream elements and response elements.
  • Preferred promoters controlling transcription from vectors in mammalian host cells may be obtained from various sources, for example, the genomes of viruses such as: polyoma, Simian Virus 40 (SV40), adenovirus, retroviruses, hepatitis-B virus and most preferably cytomegalovirus, or from heterologous mammalian promoters, e.g. beta actin promoter.
  • viruses such as: polyoma, Simian Virus 40 (SV40), adenovirus, retroviruses, hepatitis-B virus and most preferably cytomegalovirus, or from heterologous mammalian promoters, e.g. beta actin promoter.
  • the early and late promoters of the SV40 virus are conveniently obtained as an SV40 restriction fragment which also contains the SV40 viral origin of replication (Fiers et al. Nature. 273: 1 13 (1978)).
  • the immediate early promoter of the human cytomegalovirus is conveniently obtained as a Hindlll E restriction fragment (Greenway, P.J. et al. Gene 18: 355-360 (1982)).
  • promoters from the host cell or related species also are useful herein.
  • Enhancer generally refers to a sequence of DNA that functions at no fixed distance from the transcription start site and can be either 5' (Laimins, L. et al, Proc. Natl. Acad. Sci. 78: 993 (1981)) or 3' (Lusky, M.L, et al, Mol. Cell Bio. 3: 1 108 (1983)) to the transcription unit. Furthermore, enhancers can be within an intron (Banerji, J.L. et al.
  • Enhancers also often contain response elements that mediate the regulation of transcription Promoters can also contain response elements that mediate the regulation of transcription Enhancers often determine the regulation of expression of a gene While many enhancer sequences are now known from mammalian genes (globin, elastase, albumin, -fetoprotein and insulin), typically one will use an enhancer from a eukaryotic cell virus for general expression Examples are the SV40 enhancer on the late side of the replication origin (bp 100-270), the cytomegalovirus early promoter enhancer, the polyoma enhancer on the late side of the replication origin, and adenovirus enhancers 166
  • the promotor and/or enhancer may be specifically activated
  • the promoter and/or enhancer region can act as a constitutive promoter and/or enhancer to maximize expression of the region of the transcription unit to be transcribed
  • the promoter and/or enhancer region be active in all eukaryotic cell types, even if it is only expressed in a particular type of cell at a particular time
  • a preferred promoter of this type is the CMV promoter (650 bases)
  • Other preferred promoters are SV40 promoters, cytomegalovirus (full length promoter), and retroviral vector LTF 168 It has been shown that all specific regulatory elements can be cloned and used to construct expression vectors that are selectively expressed in specific cell types such as melanoma cells
  • the ghal fib ⁇ llary acetic protein (GFAP) promoter has been used to selectively express genes in cells of ghal origin 169
  • Expression vectors used in eukaryotic host cells may also contain sequences necessary
  • the vectors can include nucleic acid sequence encoding a marker product This marker product is used to determine if the gene has been delivered to the cell and once delivered is being expressed Preferred marker genes are the E Coli lacZ gene, which encodes ⁇ -galactosidase, and green fluorescent protein
  • the marker may be a selectable marker
  • suitable selectable markers for mammalian cells are dihydrofolate reductase (DHFR), thymidine kinase, neomycin, neomycin analog G418, hydromycin, and puromycin
  • DHFR dihydrofolate reductase
  • thymidine kinase thymidine kinase
  • neomycin neomycin analog G418, hydromycin
  • puromycin When such selectable markers are successfully transferred into a mammalian host cell, the transformed mammalian host cell can survive if placed under selective pressure
  • Two examples are CHO DHFR- cells and mouse LTK- cells These cells lack the ability to grow without the addition of such nutrients as thymidine or hypoxanthin
  • the second category is dominant selection which refers to a selection scheme used in any cell type and does not require the use of a mutant cell line These schemes typically use a drug to arrest growth of a host cell Those cells which have a novel gene would express a protein conveying drug resistance and would survive the selection Examples of such dominant selection use the drugs neomycin, (Southern P and Berg, P .
  • TSGIOI protein and GAG protein there are numerous variants of the TSGIOI protein and GAG protein that are known and herein contemplated
  • TSGIOI and GAG strain variants there are derivatives of the TSGIOI and GAG proteins which also function in the disclosed methods and compositions
  • Protein variants and derivatives are well understood to those of skill in the art and in can involve amino acid sequence modifications
  • amino acid sequence modifications typically fall into one or more of three classes substituttonal, insertional or deletional variants
  • Insertions include amino and/or carboxyl terminal fusions as well as intrasequence insertions of single or multiple amino acid residues Insertions ordinarily will be smaller insertions than those of amino or carboxyl terminal fusions, for example, on the order of one to four residues
  • Immunogenic fusion protein derivatives such as those described in the examples, are made by fusing a polypeptide sufficiently large to confer immunogenicity to the target sequence by cross-linking in vitro or by recombinant cell culture transformed with DNA
  • Deletions or insertions preferably are made in adjacent pairs, i.e. a deletion of 2 residues or insertion of 2 residues. Substitutions, deletions, insertions or any combination thereof may be combined to arrive at a final construct. The mutations must not place the sequence out of reading frame and preferably will not create complementary regions that could produce secondary mRNA structure. Substitutional variants are those in which at least one residue has been removed and a different residue inserted in its place. Such substitutions generally are made in accordance with the following Tables 1 and 2 and are referred to as conservative substitutions.
  • Substantial changes in function or immunological identity are made by selecting substitutions that are less conservative than those in Table 2, i.e., selecting residues that differ more significantly in their effect on maintaining (a) the structure of the polypeptide backbone in the area of the substitution, for example as a sheet or helical conformation, (b) the charge or hydrophobicity of the molecule at the target site or (c) the bulk of the side chain.
  • substitutions which in general are expected to produce the greatest changes in the protein properties will be those in which (a) a hydrophilic residue, e.g. seryl or threonyl, is substituted for (or by) a hydrophobic residue, e.g.
  • an electropositive side chain e.g., lysyl, arginyl, or histidyl
  • an electronegative residue e.g., glutamyl or aspartyl
  • substitutional or deletional mutagenesis can be employed to insert sites for N-glycosylation
  • Deletions of cysteine or other labile residues also may be desirable.
  • Deletions or substitutions of potential proteolysis sites, e.g. Arg is accomplished for example by deleting one of the basic residues or substituting one by glutaminyl or histidyl residues.
  • Certain post-translational derivatizations are the result of the action of recombinant host cells on the expressed polypeptide. Glutaminyl and asparaginyl residues are frequently post-translational ly deamidated to the corresponding glutamyl and asparyl residues. Alternatively, these residues are deamidated under mildly acidic conditions. Other post-translational modifications include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of the o-amino groups of lysine, arginine, and histidine side chains (T.E. Creighton, Proteins: Structure and Molecular Properties, W. H. Freeman & Co, San Francisco pp 79-86 [1983]), acetylation of the N-terminal amine and, in some instances, amidation of the C-terminal carboxyl.
  • variants and derivatives of the disclosed proteins herein are through defining the variants and derivatives in terms of homology/identity to specific known sequences.
  • SEQ ID NO: 1 sets forth a particular sequence of TSGIOI
  • SEQ ID NO:5 sets forth a particular sequence of a retroviral GAG protein.
  • variants of these and other proteins herein disclosed which have at least, 70% or 75% or 80% or 85% or 90% or 95% homology to the stated sequence.
  • the homology can be calculated after aligning the two sequences so that the homology is at its highest level.
  • compositions can also be administered in vivo in a pharmaceutically acceptable carrier.
  • pharmaceutically acceptable is meant a material that is not biologically or otherwise undesirable, i.e., the material may be administered to a subject, along with the nucleic acid or vector, without causing any undesirable biological effects or interacting in a deleterious manner with any of the other components of the pharmaceutical composition in which it is contained.
  • the carrier would naturally be selected to minimize any degradation of the active ingredient and to minimize any adverse side effects in the subject, as would be well known to one of skill in the art.
  • compositions may be administered orally, parenterally (e.g., intravenously), by intramuscular injection, by intraperitoneal injection, transdermally, extraco ⁇ oreally, topically or the like, including topical intranasal administration or administration by inhalant.
  • topical intranasal administration means delivery of the compositions into the nose and nasal passages through one or both of the nares and can comprise delivery by a spraying mechanism or droplet mechanism, or through aerosolization of the composition.
  • Administration of the compositions by inhalant can be through the nose or mouth via delivery by a spraying or droplet mechanism.
  • compositions required will vary from subject to subject, depending on the species, age, weight and general condition of the subject, the seventy of the allergic disorder being treated, the particular nucleic acid or vector used, its mode of administration and the like Thus, it is not possible to specify an exact amount for every composition However, an appropriate amount can be determined by one of ordinary skill in the art using only routine experimentation given the teachings herein
  • Parenteral administration of the composition is generally characterized by injection Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution of suspension in liquid prior to injection, or as emulsions
  • injection Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution of suspension in liquid prior to injection, or as emulsions
  • a more recently revised approach for parenteral administration involves use of a slow release or sustained release system such that a constant dosage is maintained See, e g , U S Patent No 3,610,795, which is inco ⁇ orated by reference herein
  • the materials may be in solution, suspension (for example, inco ⁇ orated into microparticles, liposomes, or cells) These may be targeted to a particular cell type via antibodies, receptors, or receptor ligands
  • the following references are examples of the use of this technology to target specific proteins to tumor tissue (Senter, et al , Bioconiugate Chem , 2 447-451 , ( 1991 ), Bagshawe, K D , Br J Cancer, 60 275- 281, (1989), Bagshawe, et al , Br J Cancer. 58 700-703, (1988), Senter, et al , Bioconiugate Chem . 4 3-9, (1993), Battelli, et al , Cancer Immunol Immunother .
  • Vehicles such as "stealth” and other antibody conjugated liposomes (including lipid mediated drug targeting to colonic carcinoma), receptor mediated targeting of DNA through cell specific ligands, lymphocyte directed tumor targeting, and highly specific therapeutic retroviral targeting of murine glioma cells in vivo
  • stealth and other antibody conjugated liposomes (including lipid mediated drug targeting to colonic carcinoma), receptor mediated targeting of DNA through cell specific ligands, lymphocyte directed tumor targeting, and highly specific therapeutic retroviral targeting of murine glioma cells in vivo
  • stealth and other antibody conjugated liposomes (including lipid mediated drug targeting to colonic carcinoma), receptor mediated targeting of DNA through cell specific ligands, lymphocyte directed tumor targeting, and highly specific therapeutic retroviral targeting of murine glioma cells in vivo
  • lymphocyte directed tumor targeting and highly specific therapeutic retroviral targeting of murine glioma cells in vivo
  • receptors are involved in pathways of endocytosis, either constitutive or ligand induced These receptors cluster in clathrin-coated pits, enter the cell via clathrin-coated vesicles, pass through an acidified endosome in which the receptors are sorted, and then either recycle to the cell surface, become stored intracellularly, or are degraded in lysosomes
  • the intemalization pathways serve a variety of functions, such as nutrient uptake, removal of activated proteins, clearance of macromolecules, opportunistic entry of viruses and toxins, dissociation and degradation of ligand, and receptor-level regulation Many receptors follow more than one intracellular pathway, depending on the cell type, receptor concentration, type of ligand, ligand valency, and ligand concentration Molecular and cellular mechanisms of receptor-mediated end
  • compositions including antibodies or other compositions which interact with TSGIOI such that TSG I OI cannot interact with the retroviral GAG, can be used therapeutically in combination with a pharmaceutically acceptable carrier
  • Suitable carriers and their formulations are described in Remington The Science and Practice of Pharmacy (19th ed ) ed A R Gennaro, Mack Publishing Company, Easton, PA 1995 Typically, an appropriate amount of a pharmaceutically-acceptable salt is used in the formulation to render the formulation isotonic
  • the pharmaceutically-acceptable carrier include, but are not limited to, saline, Ringer's solution and dextrose solution
  • the pH of the solution is preferably from about 5 to about 8, and more preferably from about 7 to about 7 5
  • Further carriers include sustained release preparations such as semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e g , films, liposomes or microparticles It will be apparent to those persons skilled in the art that certain carriers may be more preferable depending upon, for instance, the route of administration and concentration of composition being administered
  • compositions can be administered intramuscularly or subcutaneously Other compounds will be administered according to standard procedures used by those skilled in the art
  • compositions may include carriers, thickeners, diluents, buffers, preservatives, surface active agents and the like in addition to the molecule of choice Pharmaceutical compositions may also include one or more active ingredients such as antimicrobial agents, antnnfiammatory agents, anesthetics, and the like
  • the pharmaceutical composition may be administered in a number of ways depending on whether local or systemic treatment is desired, and on the area to be treated Administration may be topically (including ophthalmically, vaginally, rectally, intranasally), orally, by inhalation, or parenterally, for example by intravenous dnp, subcutaneous, lntrape ⁇ toneal or intramuscular injection
  • the disclosed antibodies can be administered intravenously, tntrape ⁇ toneally, intramuscularly, subcutaneously, intracavity, or transdermally
  • Preparations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions
  • non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate
  • Aqueous carriers include water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media
  • Parenteral vehicles include sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's, or fixed oils
  • Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer's dextrose), and the like
  • Preservatives and other additives may also be present such as, for example, antimicrobials, anti-oxidants, chelating agents, and inert gases and the like
  • Formulations for topical administration may include ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders
  • Conventional pharmaceutical earners, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable
  • compositions for oral administration include powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets, or tablets Thickeners, flavorings, diluents, emulsifiers, dispersing aids or binders may be desirable
  • compositions may potentially be administered as a pharmaceutically acceptable acid- or base- addition salt, formed by reaction with inorganic acids such as hydrochloric acid, hydrobromic acid, perchloric acid, nitric acid, thiocyanic acid, sulfunc acid, and phosphoric acid, and organic acids such as formic acid, acetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, oxalic acid, malonic acid, succinic acid, maleic acid, and fumaric acid, or by reaction with an inorganic base such as sodium hydroxide, ammonium hydroxide, potassium hydroxide, and organic bases such as mono-, di-, trialkyl and aryl amines and substituted ethanolamines.
  • inorganic acids such as hydrochloric acid, hydrobromic acid, perchloric acid, nitric acid, thiocyanic acid, sulfunc acid, and phosphoric acid
  • organic acids such as formic acid, acetic acid, propi
  • Effective dosages and schedules for administering the compositions may be determined empirically, and making such determinations is within the skill in the art.
  • the dosage ranges for the administration of the compositions are those large enough to produce the desired effect in which the symptoms disorder are effected.
  • the dosage should not be so large as to cause adverse side effects, such as unwanted cross-reactions, anaphylactic reactions, and the like.
  • the dosage will vary with the age, condition, sex and extent of the disease in the patient, route of administration, or whether other drugs are included in the regimen, and can be determined by one of skill in the art.
  • the dosage can be adjusted by the individual physician in the event of any counterindications. Dosage can vary, and can be administered in one or more dose administrations daily, for one or several days.
  • Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products. For example, guidance in selecting appropriate doses for antibodies can be found in the literature on therapeutic uses of antibodies, e.g., Handbook of Monoclonal Antibodies, Ferrone et al, eds, Noges Publications, Park Ridge, N.J, (1985) ch. 22 and pp, 303-357; Smith et al. Antibodies in Human Diagnosis and Therapy, Haber et al, eds. Raven Press, New York (1977) pp. 365- 389.
  • a typical daily dosage of the antibody used alone might range from about 1 ⁇ g/kg to up to 100 mg/kg of body weight or more per day, depending on the factors mentioned above.
  • compositions disclosed herein are efficacious in treating or inhibiting an HIV infection in a subject by observing that the composition reduces viral load or prevents a further increase in viral load.
  • Viral loads can be measured by methods that are known in the art, for example, using polymerase chain reaction assays to detect the presence of HIV nucleic acid or antibody assays to detect the presence of HIV protein in a sample (e.g., but not limited to, blood) from a subject or patient, or by measuring the level of circulating anti-HIV antibody levels in the patient.
  • Efficacy of the administration of the disclosed composition may also be determined by measuring the number of CD4 + T cells in the HIV-infected subject.
  • An antibody treatment that inhibits an initial or further decrease in CD4 + T cells in an HIV-positive subject or patient, or that results in an increase in the number of CD4 + T cells in the HIV-positive subject, is an efficacious antibody treatment.
  • compositions that inhibit TSG 101 -PTAP interactions disclosed herein may be administered prophylactically to patients or subjects who are at risk for being exposed to HIV or who have been newly exposed to HIV.
  • efficacious treatment with an antibody of the invention partially or completely inhibits the appearance of the virus in the blood or other body fluid.
  • compositions and methods can also be used for example as tools to isolate and test new drug candidates for a variety of PTAP motif containing retroviral related diseases They can also be used for the continued isolation and study, for example, the cell cycle
  • chips where at least one address is the sequences or part of the sequences set forth in any of the nucleic acid sequences disclosed herein Also disclosed are chips where at least one address is the sequences or portion of sequences set forth in any of the peptide sequences disclosed herein
  • chips where at least one address is a variant of the sequences or part of the sequences set forth in any of the nucleic acid sequences disclosed herein
  • chips where at least one address is a variant of the sequences or portion of sequences set forth in any of the peptide sequences disclosed herein
  • kits that are drawn to reagents that can be used in practicing the methods disclosed herein
  • the kits can include any reagent or combination of reagent discussed herein or that would be understood to be required or beneficial in the practice of the disclosed methods
  • the kits could include primers to perform the amplification reactions discussed in certain embodiments of the methods, as well as the buffers and enzymes required to use the primers as intended D.
  • compositions disclosed herein and the compositions necessary to perform the disclosed methods can be made using any method known to those of skill in the art for that particular reagent or compound unless otherwise specifically noted 1. Nucleic acid synthesis
  • the nucleic acids such as, the oligonucleotides to be used as primers can be made using standard chemical synthesis methods or can be produced using enzymatic methods or any other known method Such methods can range from standard enzymatic digestion followed by nucleotide fragment isolation (see for example, Sambrook et al , Molecular Cloning A Laboratory Manual, 2nd Edition (Cold
  • Protein nucleic acid molecules can be made using known methods such as those described by Nielsen et al , Bioconjug Chem 5 3-7 (1994) 2. Peptide synthesis
  • One method of producing the disclosed proteins is to link two or more peptides or polypeptides together by protein chemistry techniques
  • peptides or polypeptides can be chemically synthesized using currently available laboratory equipment using either Fmoc (9-fluorenylmethyloxycarbonyl) or Boc (tert -butyloxycarbonoyl) chemistry (Applied Biosystems, Inc , Foster City, CA)
  • Fmoc (9-fluorenylmethyloxycarbonyl) or Boc (tert -butyloxycarbonoyl) chemistry Applied Biosystems, Inc , Foster City, CA
  • a peptide or polypeptide corresponding to the disclosed proteins for example, can be synthesized by standard chemical reactions
  • a peptide or polypeptide can be synthesized and not cleaved from its synthesis resin whereas the other fragment of a peptide or protein can be synthesized and subsequently cleaved from the resin, thereby exposing a terminal group which is functionally blocked on the
  • enzymatic ligation of cloned or synthetic peptide segments allow relatively short peptide fragments to be joined to produce larger peptide fragments, polypeptides or whole protein domains (Abrahmsen L et al , Biochemistry, 30 4151 (1991))
  • native chemical ligation of synthetic peptides can be utilized to synthetically construct large peptides or polypeptides from shorter peptide fragments This method consists of a two step chemical reaction (Dawson et al Synthesis of Proteins by Native Chemical Ligation Science, 266 776-779 (1994))
  • the first step is the chemoselective reaction of an unprotected synthetic pepttde-thioester with another unprotected peptide segment containing an amino-terminal Cys residue to give a thtoester-hnked intermediate as the initial covalent product Without a change in the reaction conditions, this intermediate undergoes spontaneous, rapid intramolecular reaction to form a native peptide bond
  • unprotected peptide segments are chemically linked where the bond formed between the peptide segments as a result of the chemical ligation is an unnatural (non-peptide) bond
  • Process for making the compositions 210 Disclosed are processes for making the compositions as well as making the intermediates leading to the compositions There are a variety of methods that can be used for making these compositions, such as synthetic chemical methods and standard molecular biology methods It is understood that the methods of making these and the other disclosed compositions are specifically disclosed E. Methods of using the compositions
  • compositions can be used in a variety of ways as research tools
  • the disclosed coordinates and storage media containing them can be used to isolate molecules that interact with the TSG 101 or GAG molecule.
  • compositions can be used for example as targets in combinatorial chemistry protocols or other screening protocols to isolate molecules that possess desired functional properties related to binding TSGIOI, such that TSGIOI cannot interact with retroviral GAG proteins.
  • Exemplary Embodiments 213 Disclosed is a method for reducing interactions between TSGIOI and GAG. Some forms of the method comprise incubating an inhibitor with TSGIOI, GAG, or TSGIOI and GAG, where the inhibitor is an inhibitor of the interaction between TSGIOI and GAG.
  • the inhibitor can interact with amino acid Thr58, Val61 , Tyr63, Tyr68, Asn69, Ile70, Pro71 , Thr92, Met95, Pro 139, Val 141, Phe 142, Serl43, and/or Argl44 of SEQ ID NO 1
  • the inhibitor can interact with at least one atom from amino acids Thr58, Val ⁇ l , Tyr63, Tyr68, Asn69, Ile70, Pro71 , Thr92, Met95, Prol39, Val l41 ,
  • Some forms of the method comprise administering an inhibitor of the interaction between TSGI OI and HIV GAG, where the inhibitor can interact with an amino acid Thr58, Val ⁇ l , Tyr63, Tyr68, Asn69, Ile70, Pro71 , Thr92, Met95, Prol39, Vall41 , Phel42, Serl43, and/or Argl44 of SEQ ID NO: l.
  • Some forms of the method comprise administering an inhibitor of the interaction between TSGIOI and HIV GAG, where the inhibitor can interact with at least one atom of amino acids Thr58, Val ⁇ l , Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol39, Vall41, Phel42, Serl43, and/or Argl44 set forth in Table 5 or in Table 6 or any of the Tables disclosed herein, such as Tables 8-47
  • a method of treating a subject comprising administering to the subject an inhibitor of HIV budding, where the inhibitor reduces the interaction between TSGIOI and HIV GAG, and where the subject is in need of such treatment
  • the inhibitor can interact with an amino acid Thr58, Val ⁇ l , Tyr63, Tyr68, Asn69, Ile70, Pro71 , Thr92, Met95, Prol39, Vall41 , Phel42, Serl43, and/or Argl44 of SEQ ID NO 1
  • the inhibitor can interact with at least one atom of amino acids Thr58, Val ⁇ l , Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol39, Vall41, Phel42, Serl43, and/or Argl44 set forth in Table 5 or in Table 6 or any of the Tables disclosed herein, such as Tables 8-47
  • the GAG can comprise a P6 region, where the inhibitor disrupts an interaction between TSG IOI and the P6 region of GAG; or the GAG can comprise a PTAP domain, where the inhibitor disrupts an interaction between TSGIOI and the PTAP domain.
  • the inhibitor can interact with the UEV domain of TSGIOI
  • the UEV domain can comprise a PTAP binding groove
  • the groove can comprise amino acids found in three non- contiguous regions of TSGIOI
  • the groove can comprise a region selected from the group consisting of a loop connecting strands 2 and 3, a N-termtnal third of the vestigial active site loop, and a C-terminal end
  • the inhibitor can interact with a region selected from the group consisting of the loop connecting strands 2 and 3, the N-terminal third of the vestigial active site loop, and the C-terminal end
  • the active site loop can include a five residue insertion in the active site loop
  • the loop connecting strands 2 and 3 can be displaced
  • the C-terminal end can comprise two glycine residues that create irregularities in the C-terminal helix geometry
  • the groove can comprise a hydrophobic region
  • the hydrophobic region can reside in strands 3 and 4 of TSG 101 Strands 3 and 4 can
  • the inhibitor can interact with amino acid Thr58, Val ⁇ l, Tyr63, Tyr68, Asn69, Ile70, Pro71 , Thr92, Met95, Prol39, Vall41, Phel42, Serl43, and/or Argl44 of SEQ ID NO 1 and/or the inhibitor can disrupt an interaction between amino acid Thr58, Val ⁇ l, Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol39, Vall41, Phel42, Serl43, and/or Argl44 of SEQ ID NO 1 and a PTAP domain
  • the inhibitor can interact with at least one atom of amino acid Thr58, Val ⁇ l , Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol39, Vall41, Phel42, Serl43, and/or Argl44 set forth in Table 5 or in Table 6 or any of the Tables disclosed herein, such as Tables 8-47, and/or the inhibitor can disrupt an interaction between at least one atom of amino acid Thr58, Val ⁇ l , Tyr63, Tyr68, Asn69, Ile70, Pro71 , Thr92, Met95, Prol39, Vall41 , Phel42, Serl43, and/or Argl44 set forth in Table 5 or in Table 6, or any of the Tables disclosed herein, such as Tables 8-47, and a PTAP domain
  • the method comprises incubating a set of molecules with TSGIOI, a conserved variant thereof, a fragment thereof, or a combination thereof, forming a mixture, and isolating the molecules that can disrupt the interaction between TSGIOI and retroviral GAG
  • the method comprises incubating a library of molecules with retroviral GAG, a conserved variant thereof, a fragment thereof, or a combination thereof, forming a mixture, and isolating the molecules that can disrupt the interaction between retroviral GAG and TSGIOI
  • the interaction disrupted can comprise an interaction between the retroviral GAG and an amino acid of TSGIOI , where the amino acid is Thr58, Val ⁇ l, Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol39, Vall41, Phel42, Serl43, and or Argl44 of SEQ ID
  • the step of isolating can comprise incubating the mixture with a molecule comprising a PTAP binding domain
  • the method comprises displaying the structure of the TSGIOI , TSGIOI -UEV, TSGIOI PTAP binding domain, or TSGIOI Ub binding domain in a computer medium, and identifying a molecule that interacts with the displayed structure
  • the method can further comprise performing molecular modeling activities with the structure and a ligand or potential ligand
  • a method of identifying an inhibitor of TSG 101 -GAG interaction comprising, (a) administering a composition to a system, wherein the system supports TSG101-GAG interaction, (b) assaying the effect of the composition on the amount of TSG 101 -GAG in the system, and (c) selecting a composition which causes a decrease in the amount of TSG 101 -GAG present in the system relative to the system without the addition of the composition
  • a method of identifying an inhibitor of HIV budding comprising, (a) administering a composition to a system, wherein the system supports HIV budding via a TSG 101 -GAG interaction, (b) assaying the effect of the composition on the amount of HIV budding in the system, and (c) selecting a composition which causes a decrease in the amount of HIV budding present in the system because of an inhibition of the TSGIOI -GAG interaction relative to the system without the addition of the composition
  • the retroviral GAG can be HIV GAG, or the retroviral GAG can be Ebola GAG
  • the method can further comprise incubating the mixture with Ubiquitin
  • inhibitors identified by the methods and inhibitors capable of being identified by the methods Also disclosed is a method of manufacturing a composition for inhibiting the interaction between TSGIOI and GAG comprising synthesizing an inhibitor identified by the methods of identifying an inhibitor described above
  • This method can further comprise mixing a pharmaceutical carrier with the inhibitor
  • a method of manufacturing a composition for inhibiting the interaction between TSGIOI and GAG comprising admixing the inhibitor with a pharmaceutical carrier
  • the method comprises administering a composition that reduces HIV budding
  • the composition is defined as a composition capable of being identified by administering the composition to a system, where the system supports HIV budding via a TSGIOI -GAG interaction, assaying the effect of the composition on the amount of HIV budding in the system, and selecting a composition which causes a decrease in the amount of HIV budding present in the system because of an inhibition of the TSG 101 -GAG interaction relative to the system without the addition of the composition
  • the method compnses administering a composition that reduces an interaction between TSGIOI and GAG
  • a composition capable of inhibiting HIV budding comprising admixing a compound with a pharmaceutically acceptable carrier, where the compound is identified by administering the compound to a system, where the system supports HIV budding via a TSG 101- GAG interaction, assaying the effect of the compound on the amount of HIV budding in the system, and selecting a compound which causes a decrease in the amount of HIV budding in the system because of an inhibition of the TSG 101 -GAG interaction, relative to the system without the addition of the compound
  • the method can further comprise the step of admixing the composition with a pharmaceutical carrier
  • a method of manufacturing an inhibitor to HIV budding comprising, (a) administering a composition to a system, wherein the system supports HIV budding via a TSG 101 -GAG interaction, (b) assaying the effect of the composition on the amount of HIV budding in the system, (c) selecting a composition which causes a decrease in the amount of HIV budding present in the system because of an inhibition of the TSGIOI -GAG interaction, relative to the system without the addition of the composition, and (d) synthesizing the composition 227 Also disclosed is a method of identifying an inhibitor of an interaction between TSGIOI and
  • the inhibitor can interact with amino acid Thr58, Val ⁇ l, Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol39, Vall41, Phel42, Serl43, and/or Argl44 of SEQ ID NO 1
  • the GAG can comprise a P6 region, where the inhibitor disrupts an interaction between TSGIOI and the P6 region of HIV GAG
  • the GAG can comprise a PTAP domain, where the inhibitor disrupts an interaction between TSGIOI and the PTAP domain
  • the inhibitor can interact with at least one atom of amino acids Thr58, Val ⁇ l, Tyr63, Tyr68, Asn
  • a cell comprising, (a) an exogenous nucleic acid comprising sequence encoding a TSGIOI gene, conserved variant, or fragment thereof, and (b) a nucleic acid comprising sequence encoding a GAG gene, conserved variant, or fragment thereof Also disclosed is a cell comprising, an exogenous nucleic acid comprising sequence encoding a TSGIOI gene, a conserved variant thereof, or fragment thereof and sequence comprising a GAG gene, a conserved variant thereof, or fragment thereof Such cells can further comprise an inhibitor of a TSG101-GAG interaction
  • polypeptide comprising the amino acid sequence of the TSGIOI PTAP binding domain, where the polypeptide does not comprise the polypeptide set forth in SEQ ID NO 1
  • the amino acid sequence of the TSGIOI PTAP binding domain can comprise amino acids positioned in three dimensional space as defined by coordinates set forth in Table 5 or in Table 6, or coordinates forming a homologous structure, wherein the polypeptide does not comprise the polypeptide set forth in SEQ ID NO 1
  • the structure of the TSGIOI PTAP binding domain can be defined by the coordinates set forth in Table 5 or in Table 6, or coordinates forming a homologous structure, and wherein the polypeptide does not comprise the polypeptide set forth in SEQ ID NO 1
  • a method of characterizing protein structures comprising the steps (a) determining a TSGIOI PTAP binding domain three-dimensional structure, (b) determining an experimental protein three-dimensional structure , (c) comparing the experimental protein three-dimensional structure to the TSGIOI PTAP binding domain three-dimensional structure, and (d) recording variances between the TSGIOI PTAP binding domain three-dimensional structure and the experimental protein three-dimensional structure
  • the three-dimensional structure of the TSGIOI PTAP binding domain can be defined by the atomic structure coordinates of Table 5 or Table 6 or coordinates producing a homologous structure
  • the TSG 101 PTAP binding domain three-dimensional structure can be derived from the structure of a polypeptide comprising the amino acid sequence of the TSGIOI PTAP binding domain, where the polypeptide does not comprise the polypeptide set forth in SEQ ID NO 1
  • the amino acid sequence of the TSGIOI PTAP binding domain can comprise amino acids positioned in three dimensional space as defined by coordinates set forth in Table 5 or in Table 6, or coordinates forming a homologous structure, wherein the polypeptide does not comprise the polypeptide set forth in SEQ ID NO 1
  • the structure of the TSGIOI PTAP binding domain can be defined by the coordinates set forth in Table 5 or in Table 6, or coordinates forming a homologous structure, and wherein the polypeptide does not comprise the polypeptide set forth in SEQ ID NO:l .
  • a method of displaying a representation of a TSGIOI PTAP binding domain on a computer having a processing means, a memory means, an input means and an output means comprising: receiving the three-dimensional coordinates of atoms of a TSGIOI PTAP binding domain; producing a representation of the TSGIOI PTAP binding domain based upon the received coordinates; and displaying the representation of the TSGIOI PTAP binding domain on the visual display means.
  • a method of displaying a representation of an analog of a TSG 101 PTAP binding domain comprising: (a) determining the three-dimensional coordinates of atoms of a TSGIOI PTAP binding domain; (b) providing a computer having a memory means, a data input means, a visual display means, the memory means containing three-dimensional molecular simulation software operable to retrieve coordinate data from the memory means and to display a three-dimensional representation of a molecule on the visual display means and being operable to produce a representation of an analog of the molecule responsive to operator-selected changes to the chemical structure of the molecule and to display the representation of the analog; (c) inputting three-dimensional coordinate data of the atoms of the TSGIOI PTAP binding domain into the computer and storing the data in the memory means; (d) displaying the representation of the TSGIOI PTAP binding domain on the visual display means; (e) inputting into the data input means of the computer at least one operator-selected change in chemical structure of the TSG
  • the method can further comprise repeating step (d) forming a second TSGIOI PTAP binding domain analog structure and then repeating steps (f)-(g)-
  • the method can further comprising selecting one of the analog structures obtaining a selected analog structure, where selecting the analog structure comprises displaying on the visual display means the three-dimensional structure of the TSGIOI PTAP binding domain analog and the second TSG 101 PTAP binding domain analog, visually comparing the configuration and spatial arrangement of the TSGIOI PTAP binding domain, and selecting an analog structure where the domains are substantially the same.
  • the method can further comprise steps synthesizing the selected analog by means of recombinant DNA technology; and determining the TSGIOI PTAP binding domain function of the synthesized TSGIOI PTAP binding domain function analog, whereby an analog having the activity is a mimic of the three-dimensional structure of the TSGIOI PTAP binding domain.
  • Also disclosed is a method for identifying the TSGIOI PTAP binding domain analogs that mimic the three-dimensional structure of the TSGIOI PTAP binding domain comprising: producing a multiplicity of analog structures of the TSGIOI PTAP binding domain by the method of method of displaying a representation of an analog of a TSGIOI PTAP binding domain described above, and selecting an analog structure with a structure of the PTAP binding domain which is substantially like the TSGIOI PTAP binding domain.
  • Disclosed are methods for identifying a potential ligand of a protein comprising a TSGIOI PTAP binding domain comprising: (a) using a three-dimensional structure of the TSGIOI PTAP binding domain function or portions thereof formed from the atomic coordinates of the TSGIOI PTAP binding domain; (b) employing the three-dimensional structure to design or select the potential ligand.
  • Also disclosed are methods, further comprising a method for identifying a potential ligand of a protein comprising a TSGIOI PTAP binding domain comprising: (c) synthesizing the potential ligand; and (d) contacting the potential ligand with the TSGI OI PTAP binding domain function containing protein; and (e) determining whether the potential ligand binds to the TSGIOI PTAP binding domain containing protein.
  • the step of employing the three-dimensional structure to design or select the ligand comprises: identifying chemical functionalities capable of associating with the TSGIOI PTAP binding domain; and assembling the identified chemical functionalities into a single molecule to provide the structure of the TSGIOI PTAP binding domain potential ligand.
  • an apparatus for determining whether a compound will interact with a protein containing a TSGI OI PTAP binding domain comprising: (a) a memory that stores a set of coordinates and identities of the atoms of the TSGIOI PTAP binding domain that together form a solvent-accessible surface; and executable instructions; and (b) a processor, wherein the executes instructions to receive structural information for a candidate compound; determine if the structure of the candidate compound is complementary to the structure of the solvent-accessible surface of the TSGIOI PTAP binding domain; and output the results of the determination.
  • apparati wherein the set of coordinates and identities of the atoms of the TSGIOI
  • PTAP binding domain are derived from the structure of amino acid residue 1 through amino acid residue 145 set forth in SEQ ID NO: l , and/or wherein the set of coordinates and identities of atoms of the TSGIOI PTAP binding domain are derived from a solution, and/or wherein the set of coordinates and identities of atoms of the TSG 101 PTAP binding domain are the atomic coordinates set forth in Table 5 or in Table 6 or any of the coordinate Tables disclosed herein or a portion thereof.
  • Disclosed are computer-readable storage media comprising one or more computer readable media storing digitally-encoded structural data, wherein the data comprise the identity and three-dimensional coordinates, or coordinates providing a structural homolog, of at least 2 amino acids set forth in SEQ ID NO: 1. 250.
  • an apparatus comprising: (a) a system data store capable of storing coordinate sets; and (b) a system processor in communication with the system data store that: (i) receives and stores a subject set of coordinates for a subject structure; (ii) compares the subject set of coordinates to a reference set of coordinates related to the TSG 101 PTAP binding domain by: (1) calculating the root mean squared deviation of the subject set of coordinates from the reference set of coordinates; and (2) comparing the root mean squared deviation to limit values; and (iii) assigns the subject structure a function based on the subject structure's similarity to the reference structures if the root mean squared deviation is less than or equal to the limit values.
  • the reference set of coordinates comprises the coordinates in Table 5 or a portion thereof or Table 6 or any of the coordinate tables disclosed herein or a portion thereof.
  • methods of determining relationships between two or more polypeptide structures comprising: (a) obtaining a reference structure, wherein the reference structure is a structure of a polypeptide comprising the TSGIOI PTAP binding domain or a portion thereof; (b) obtaining at least one subject structure; (c) determining a reference structure topology diagram and a subject structure topology diagram; (d) comparing the reference structure topology diagram and the subject structure topology diagram; and (e) assigning a relationship between the reference structure and any subject structure based on deviations between the reference structure and subject structure.
  • the reference structure is a structure defined by the atomic coordinates of Table 5 or a portion thereof or Table 6 or any of the Tables disclosed herein or a portion thereof.
  • the step of determining considers secondary structural elements, spatial adjacency within fold and approximate orientation, and/or wherein the step of determining neglects the length of loop elements, and/or wherein the step of determining neglects the structure of loop elements, and/or wherein the step of determining neglects spatial orientations of secondary structural elements, and/or wherein the step of determining comprises using TOPS protein topology search, discovering patterns and comparing structures.
  • Provisional Application Serial No. 60/276,259 filed on Mar. 14, 2001 , U.S. Provisional Application Serial No. 60/304,101 filed on Jul. 10, 2001, U.S. Provisional Application filed on Oct. 22, 2001 , and U.S. Provisional Application filed on Jan. 7, 2002 discusses TSGIOI . All of these applications are inco ⁇ orated herein by reference in their entirety at least for material related to TSGI OI and molecules and methods related to TSG 101 and the proteins and molecules that interact with TSG 101. United States Patent Application Publication No.
  • 20020177207 indicates that TSGIOI and fragments of TSGIOI interact with kinectin, AKAP13, TPM4, KIAA0674, motor protein, OS-9, ROCK1, CYLN2, plectin, DAP5, GEF-H1, BAP31, zinc finger protein 231 , HCAP, PACSIN2, PIBF1 , Golgin-67, ACTN4, GAS7B, TOM1L1 , PIG7, PN9667, AA300702, AKNA, desmoplakin I, synexin, Golgin-95, restin, keratin 5, keratin 6C, keratin 8, GTPase- activating protein 1, endosome-associated protein 1, 88-kDa Golgi protein, centromere protein F, serum deprivation response, mitotic spindle coiled-coil related protein, Golgin-84, FLJ 10540, VPS28, hook2, intersectin 1, pallid, catenin, ACT
  • TsglOl UEV domain This fragment was residues 1 -145 of SEQ ID NO 1 and was chosen based on multiple sequence alignments and preliminary NMR analyses (see Example 4)
  • This construct (TsglOl UEV) was expressed and purified, and its NMR solution structure was calculated from a total of 1861 NOE inte ⁇ roton restraints, 76 hydrogen bonding restraints derived from amide proton exchange protection experiments, and
  • the TsglOl UEV fold is generally similar to E2 ligases and to Mms2, the only other structurally characterized UEV (Cook et al , 1992, Cook et al , 1993, Cook et al , 1997, Tong et al , 1997, Worthylake et al , 1998, Huang et al , 1999, Jiang and Basavappa, 1999, Zheng et al , 2000, Hamilton et al , 2001 , Moraes et al , 2001, VanDemark et al , 2001)
  • This "E2 fold” consists of four helices packed against one side of a four- stranded antiparallel ⁇ -sheet (Fig 2)
  • the structural similarity is greatest around the central active site region of the structure (residues 53-138), where TsglOl UEV superimposes with hMms2 (Fig 2b) and yUbcl3 (a canonical E2,
  • TsglOl UEV lacks the two C-terminal helices found in all structurally characterized E2 proteins (Fig 2c, gray helices, Fig 2d, green arrow) Mms2 also lacks these helices, and sequence analyses suggest that they are missing from other UEV domains (Koonin and Abagyan, 1997), indicating that this is a general difference between UEV and canonical E2 proteins (Fig ⁇ b)
  • Mms2 and TsglOl UEV lack C-terminal helices, their structures differ in this region because the C-terminal residues of human and yeast Mms2 adopt extended, but ordered conformations that occupy the same site as the final E2 helix, whereas the equivalent residues in TsglOl UEV project off into solution and are disordered
  • TsglOl UEV differs from Mms2 and canonical E2 proteins in two additional ways 1) TsglOl contains two N-terminal helices (colored red and orange in Fig 2a), whereas Ubcl 3 and Mms2 contain only one (Fig 2d, red arrow) The general disposition of TsglOl UEV helix 2 (orange) is similar to the N-terminal helices of Ubcl 3 and Mms2, but is shifted slightly towards the center of the sheet (Fig 2d) 2) The disposition of the first two strands in TsglOl UEV is quite different from that of Mms2 and Ubcl3 In TsglOl, strand 1 is twisted and displaced toward the N-terminal end of strand 2, and these two strands form an extended ⁇ -hai ⁇ in "tongue" that projects 1 1 residues beyond the main body of the domain and terminates in a type I glycine turn
  • This beta-tongue is well-defined by strong interstrand H ⁇ -to-H ⁇ and H ⁇ -to-HN NOEs, as well as interstrand backbone hydrogen bonds that protect the backbone amide protons from rapid deuterium exchange
  • the extended beta-tongue can be a functionally important feature because it forms part of the Ub binding site
  • the disposition of the first two strands also allows extensive packing interactions between the TsglOl UEV N-terminal helices and the ⁇ -sheet, which are not possible in Ubcl 3 or Mms2
  • the loop connecting TsglOl helices 1 and 2 inserts a tyrosine side chain hydroxyl (Tyrl5) between strands 2 and 3, bridging the hydrogen bonding interaction between the amide proton of Met53 (strand 2) and the carboxyl oxygen of Lys76 (strand 3), and thereby terminating the hydrogen bonding network of the ⁇ -sheet
  • TsglOl UEV is similar to canonical E2 enzymes in the hydrophobic core and "active site" regions, but differs significantly at both its N- and C-termim Although some of these structural differences are shared by the TsglOl and Mms2 UEV domains (e g , the lack of C-terminal helices), it is clear that Tsgl Ol has diverged even further from the canonical E2 fold than has Mms2 a) — p6 Binding
  • Val89 which is located at the bottom of the pocket, had no effect on p6 binding. Therefore, although the Val89 amide showed the greatest chemical shift change upon addition of p ⁇ (Fig. 3a), the Val89 methyl groups do not contribute appreciable binding energy, perhaps because the PTAP peptide does not reach down to the very bottom of the pocket. Importantly, the Tyr63— >Ala and Met95— >Ala mutations, which decreased p6 binding affinity by 14- and 52-fold, respectively, also significantly impaired the ability of Tsgl Ol to support HIV- 1 budding, whereas the Val89 ⁇ Ala mutation had no effect on budding.
  • TsglOl UEV N-termmal UEV domain of human TsglOl conforms to the general E2 fold, but with several distinctive features that allow it to bind PTAP and ubiquitin TsglOl UEV is the first example of an E2/UEV domain with a peptide binding motif, and disclosed herein it is shown that residues from five different secondary structural elements come together to create a PTAP binding "groove" Analogous sites in other E2/UEV proteins are buried, either by a C-terminal helix (in canonical E2 enzymes) or by the ordered C-terminal residues of Mms2 UEV (Fig 3b), explaining why these domains do not have peptide binding activities 273
  • the importance of the TsglOl /PTAP interaction in the release of HIV particles seems clear because mutations in either the p ⁇ PTAP motif (Gotthnger et al , 1991, Huang et al , 1995) or in TsglOl UEV that
  • TsglOl-binding proteins also carry PTAP motifs (Garrus et al , 2001 , Strack et al , 2000), these include plasma membrane proteins known to be downregulated via the vacuolar protein sorting pathway (Berthoud et al , 2000, Strack et al , 2000), as well as proteins that function in the Vps pathway, including Hgs (Vps27) (Garrus et al , 2001 , Komada and Kitamura, 2001) TsglOl contains its own PTAP motif, which is located in a predicted loop region connecting the apparent binding sites for the Vps37 and Vps28 proteins (Fig ⁇ a) The TsglOl UEV domain could fold back and bind to this PTAP sequence, perhaps creating an "auto-inhibited" conformation Thus, regulated PTAP binding may be important for normal
  • the Ub and PTAP binding sites appear to be distinct, and indeed can be simultaneously occupied as evidenced by the fact that direct fusion of Ub to p6 enhances the binding affinity over that of either ligand alone (l e , the ligands bind cooperatively, Fig 4)
  • titration with Ub produced chemical shift changes in a distinct, but slightly overlapping subset of TsglOl UEV amides, consistent with the idea that PTAP and Ub bind to different sites (compare Figures 3a and 5a)
  • Significant amide chemical shift changes ( ⁇ > 1 8) were observed for only 13 residues, suggesting that Ub does not contact a large surface area or cause large conformational changes upon binding (Fig 5a) Consistent with the weak affinity of TsglOl UEV for (
  • the complementary TsglOl UEV-interacting surface on ubiquitin was also mapped by chemical shift perturbation experiments. As expected, titration of unlabeled TsglOl UEV into 15 N-labeled Ub shifted a small subset of Ub amides, and the complex was again in fast exchange (Fig. 5d). The greatest chemical shift changes ( ⁇ > 1.0) mapped to the two shortest strands (3 and 4) of the antiparallel ⁇ -sheet of Ub, and the N- terminal end of strand 5 (Fig. 5eJ). This region contains a number of polar and charged residues, which may form ionic and/or hydrogen bonding interactions with TsglOl UEV beta-tongue residues.
  • the shifted ubiquitin residues include Lys48, which is used for the formation of polyubiquitin chains that target proteins for proteasomal degradation (Hershko and Ciechanover, 1998).
  • the active site cysteine of Ubcl 3 forms a transient thioester bond with the C-terminus of Ub in the process of transferring Ub from an El enzyme onto the lysine side chain of a protein substrate (Lys63 of another Ub molecule in this case).
  • This covalent chemistry implies that the C-terminal "tail" of Ub must bind near the active site cysteine residue, and there is direct evidence that tail residues form the major contacts when Ub binds to the Ubcl and HsUbc2b E2 enzymes (Hamilton et al, 2001 ; Miura et al, 1999).
  • Mms2 UEV subunit of the Ubcl3/Mms2 complex binds Ub quite differently.
  • the role of Mms2 is to position the acceptor Ub Lys-63 side chain to attack the C-terminus of the donor ubiquitin.
  • this binding site is the beta-tongue projection, and mutations of residues at the tip of the tongue reduce Ub binding.
  • this site is distinct from both previously characterized Ub binding surfaces in E2/UEV proteins, it does roughly match the Mms2 binding site on the Ubcl 3 protein (Fig. 6a).
  • Ub binds
  • TsglOl UEV using a convex surface that encompasses strands 3 and 4, and it is therefore proposed that shape complementarity may play an important role in recognition.
  • the Lys48 residue at the N-terminal end of Ub strand 4 is likely to be sequestered at the TsglOl UEV/Ub interface, which likely precludes polyubiqutination via Lys48 linkages (the targeting signal for proteasomal degradation). 281.
  • the Ub-binding surface of TsglOl differs from that used by other E2/UEV proteins, leading to the su ⁇ rising conclusion that although E2/UEV domains utilize a conserved three dimensional fold to bind ubiquitin, they have evolved at least three distinct surfaces to mediate these interactions.
  • TsglOl UEV domain 282 TsglOl UEV domain constructs were designed based on an alignment of TsglOl homologoues obtained from the NCBI protein database (A. thaliana, BAB03147; C. elegans, AAC25822; C. mydas, AAF87776; D. melanogaster, AAG29564; H. sapiens, AAC52083; M. musculus, AAH05424; and S. cerevisiae, AAB62820 all of which are inco ⁇ orated herein by reference for the protein sequences of the TSGIOI homologoues).
  • NCBI protein database A. thaliana, BAB03147; C. elegans, AAC25822; C. mydas, AAF87776; D. melanogaster, AAG29564; H. sapiens, AAC52083; M. musculus, AAH05424; and S. cerevisiae, AAB62820 all
  • TsglOl residue 150 Since canonical E2 enzymes are ⁇ 150 residues in length, gaps in the alignment near TsglOl residue 150 were inte ⁇ reted as potential domain boundaries. Based on the alignments, constructs spanning residues 1-145, 1-150, 1-157, and 1-161 of TsglOl were cloned and expressed from a pETl ld vector (Novagen). The three shortest constructs expressed soluble proteins at high levels in BL21(DE3) E. coli cells. To purify the proteins, cells were lysed using lysozyme and sonication, and insoluble material was removed from the lysate by centrifugation.
  • TsglOl UEV was precipitated from the soluble fraction with ammonium sulfate at 28-55% saturation. The precipitate was redissolved in buffer containing 25 mM MOPS, pH 6.5, and fractionated on an SP-Sepharose column (Pharmacia). TsglOl UEV eluted at ⁇ 300 mM NaCl linear salt gradient (50 to 1000 mM NaCl over 400 mL). Fractions containing TsglOl were pooled, adjusted to 1 M ammonium sulfate, and re-fractionated on a Phenyl-Sepharose column (Pharmacia).
  • TsglOl UEV eluted near the beginning of a linear salt gradient (1 to 0 M ammonium sulfate over 200 mL), with typical yields of 15-20 mg of pure protein per liter of E. coli culture.
  • N-terminal amino acid sequencing and mass spectrometry analyses showed that the N-terminal methionine was quantitatively removed during expression, and the masses of all purified proteins were within 1-3 Da of expected. The ⁇ / 15 N-HSQC spectra of TsglOl .
  • TsglOl 1 - 150 , and TsglOl ⁇ _ ⁇ 57 were completely superimposable (except for C-terminal residues), and amide protons beyond Phel42 displayed limited proton chemical shift dispersion and sha ⁇ peaks with half-height linewidths of 14-19 Hz (versus 21-24 Hz for structured residues of the domain), indicating that they are disordered.
  • all three UEV constructs bound with same affinities to p6, p6-Ub and Ub. TsglOl residues 1-145 therefore appear to encompass the entire ordered UEV domain. Hence, all reported structural and biochemical analyses were performed on this defined domain. Mutant TsglOl UEV constructs were cloned using the megaprimer PCR method (Picard et al, 1994), and purified as described for wildtype. (2) Other protein samples
  • GST-p6 constructs and the free p6 domain of the HIV-1 Gag protein were purified as described (Jenkins et al, 2001).
  • the PTAP peptide (NH 2 -PEPTAPPEE-COOH) was obtained by solid-phase synthesis and purified using reverse phase HPLC.
  • Bovine ubiquitin which is identical in sequence to human ubiquitin, was purchased from Sigma and purified using size exclusion chromatography. 15 N-labeled ubiquitin was purchased from VLI Research, Inc.
  • Samples for structure determination were approximately 1.5 mM TsglOl UEV in 20 mM sodium phosphate, 50 mM NaCl, pH 5.5 in 90%H 2 O/10%D 2 O. Spectra were recorded at 25 °C on a Varian Inova 600 MHz spectrometer equipped with a triple-resonance ⁇ / 1 C/ I5 N probe and z-axis pulsed field gradient capability.
  • NOE data were used to generate distance restraints: 3D 15 N-edited NOESY-HSQC (Mori et al, 1995; Zhang et al, 1994), and 3D l 3 C-edited NOESY-HSQC (Muhandiram et al, 1993; Pascal et al, 1994). NOESY mixing times were 80 ms.
  • Three-bond coupling constants VH N -H A ) were obtained from a 3D HNHA experiment (Kuboniwa et al, 1994). Hydrogen-bonded amides were identified using deuterium exchange as previously described (Bai et al, 1997). All spectra were processed using FELIX (MSI). Structure coordinates and chemical shifts have been deposited (1KPP, CNS ensemble; 1KPQ, DYANA ensemble).
  • Binding affinities of purified wildtype and mutant TsglOl UEV domains for immobilized GST- p6 ⁇ - 27 , GST-p6'. 27 -Ub, and GST-Ub were quantified using a Biacore biosensor as described (Garrus et al, 2001). Measurements were performed at 20 °C in 20 mM sodium phosphate, 150 mM NaCl, 0.05% BSA, 0.01 % P20, pH 7.2.
  • Table 5 sets forth coordinates and related information for the TSG I OI UEV.
  • ATOM 70 CA MET 11 11.70 -13.15 -8.454 1 00 0 00
  • ATOM 112 CA LYS 16 -6.357 -13.28 2 .130 1 .00 0 .00
  • ATOM 140 CZ ARG 18 13.75 -12.57 1 265 1 00 0 00
  • ATOM 181 CZ ARG 23 15.56 -3 .859 3 .146 1 .00 0 .00
  • ATOM 238 CA LEU 31 -10.81 9.511 -4.373 1.00 0.00
  • ATOM 246 CA TYR 32 -9.647 9.068 -7.945 1.00 0.00
  • ATOM 258 CA LYS 33 -11.65 7.066 -10.45 1.00 0.00
  • ATOM 292 CA PRO 37 -8.970 -2.476 -10.94 1.00 0.00
  • ATOM 306 CA LEU 39 ⁇ 7 .658 -8.930 -12.84 1 .00 0 .00
  • ATOM 328 CA TYR 42 ⁇ 1, .722 -15.23 -11.77 1, .00 0. ,00
  • ATOM 374 CA GLY 47 2 .776 -21 .49 -18.14 1 .00 0 .00
  • ATOM 410 CA LEU 52 4 206 -12. 32 -9.541 1. 00 0. 00
  • ATOM 434 CA LEU 55 -4.351 -2.066 -10.53 1.00 0.00
  • ATOM 442 CA THR 56 -4.389 -0.624 -14.03 1.00 0.00
  • ATOM 449 CA GLY 57 -5.363 2.993 -14.57 1.00 0.00
  • ATOM 482 CA PRO 62 0.265 18.443 -12.55 1.00 0.00
  • ATOM 531 CA TYR 68 -0.562 14.601 -17.99 1.00 0.00
  • ATOM 542 N ASN 69 -1.805 12.537 -17.94 1.00 0.00
  • ATOM 543 CA ASN 69 -2.321 11.310 -17.36 1.00 0.00
  • ATOM 574 CA CYS 73 -0.207 -1.137 -14.20 1.00 0.00
  • ATOM 610 CA LEU 77 -0 .089 -9.665 -3 .632 1 .00 0 .00

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Abstract

Disclosed are compositions and methods for inhibiting interactions of TSG101 and GAG.

Description

3D STRUCTURE OF THE TSGIOI UEV DOMAIN
This application claims the benefit of and priority to United States Provisional Application No 60/381,087 filed on May 15, 2002 for 3D Structure of the TSGIOI UEV Domain, United States Provisional Application No 60/381,318 filed on May 15, 2002 for 3D Structure of the TSGIOI UEV Domain, and United States Provisional Application No 60/412,462 filed on September 19, 2002 for 3D Structure of the TSGIOI UEV Domain These applications are specifically herein incorporated by reference in their entireties, including the CD-Roms filed with these applications and the material on the CD-Roms
I. ACKNOWLEDGEMENT
1 This invention was made with government support under federal grant ROl AI45405 awarded by the NIH The Government has certain rights to this invention
II. BACKGROUND OF THE INVENTION
2 Human TsglOl plays key roles in HIV budding and in cellular vacuolar protein sorting (Vps) In performing these functions, Tsgl Ol binds both ubtquitin (Ub) and the PTAP tetrapeptide "late domain" motif located within the viral Gag protein These interactions are mediated by the N-terminal domain of TsglOl, which belongs to the catalytically inactive ubiquitin E2 variant (UEV) family
3 Human TsglOl has recently been identified as the functional receptor required for budding of the enveloped human immunodeficiency (HIV) and Ebola viruses (VerPlank et al , 2001, 2001, Martin-Serrano et al , 2001, all of which are herein incorporated by reference at least for material related to TSGIOI) (Garrus et al )Tsgl01 is recruited to the sites of virus budding by binding to a PTAP tetrapeptide motif (the "late domain") located within the p6 region of HIV Gag and the Ebola Vp40 matrix structural proteins Once there, TsglOl appears to recruit other cellular factors that help to complete the budding process (Garrus et al , 2001 , Martin-Serrano et al , 2001) In the absence of TsglOl, the final membrane fission step(s) fail and HIV release is arrested at a very late stage, in which the assembled viral particles remain attached to the plasma membrane (and to one another) via thin membrane stalks (Garrus et al , 2001) 4 Disclosed herein is the structure of Tsgl Ol UEV and chemical shift mapping of the Ub and PTAP binding sites TsglOl UEV resembles canonical E2 ubiquitin conjugating enzymes, but has an additional N- terminal helix, an extended β-hairpin that links strands 1 and 2, and lacks the two C-terminal helices normally found in E2 enzymes PTAP-containing peptides bind in a hydrophobic cleft exposed by the absence of the C- terminal helices, whereas ubiquitin binds in a different binding site surrounding the β-hairpin Disclosed herein is a structural framework for understanding how TsglOl mediates the protein-protein interactions required for HIV budding and vacuolar protein sorting
III. SUMMARY OF THE INVENTION 5 In accordance with the purposes of this invention, as embodied and broadly described herein, this invention, in one aspect, relates to the structure of TSGIOI 6 Additional advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention The advantages of the invention will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed.
IV. BRIEF DESCRIPTION OF THE DRAWINGS
7 The accompanying drawings, which are incoφorated in and constitute a part of this specification, illustrate several embodiments of the invention and together with the description, serve to explain the principles of the invention.
8 Figure 1 shows the sequence and structure of TsglOl Figure la shows the domain organization of TsglOl, showing the approximate domain boundaries of the UEV domain, proline-πch domain (PRD), putative coiled coil domain (COIL) and "steadiness box" (SBOX) (Feng et al., 2000). The internal PTAP sequence between the coiled coil domain and the steadiness box is shown explicitly. Figure lb, shows a structure-based sequence alignment of UEV and E2 proteins. The secondary structures of TsglOl UEV, uncomplexed human Mms2 (Moraes et al , 2001), and uncomplexed yeast Ubcl3 (VanDemark et al., 2001) are shown at the top, middle and bottom, respectively. Conserved residues are shaded gray, identical residues black The active site cysteine of catalytic E2 enzymes and the equivalent residues in UEV proteins are green TsglOl UEV residues that are important for binding PTAP and Ub are colored red and blue, respectively. Figure lc, shows a stereoview superposition of the final 20 NMR structures of the TsglOl UEV domain Secondary structures are colored as in b
9. Figure 2 shows the structures of E2-fold proteins. Figures 2a, b, c, show ribbon representations of TsglOl UEV (a), Mms2 (->), and Ubcl3 (c). Secondary structure elements are colored as in Figure 1. Black arrows indicate residues that correspond to the active site cysteine of Ubcl3. Figure 2d shows supeφosition of the three structures. TsglOl is colored yellow, Mms2 green, and Ubcl 3 puφle The three major structural differences between TsglOl and the other two proteins are highlighted by arrows* the extra N-terminal helix (red arrow), the β-haiφin "tongue" (blue arrow), and the missing C-terminal helices (green arrow).
10. Figure 3 shows the chemical shift mapping of the PTAP binding site on TsglOl UEV. Figure 3a shows an overlay of the Η/I5N-HSQC spectra of TsglOl UEV in the absence (gray) or presence of 1.0 molar equivalent of PTAP peptide (red). The lower panels show an expansion of the boxed region with an additional titration point indicating that the TsglOl UEV/PTAP complex is in slow exchange Figure 3b shows a biosensor binding of TsglOl UEV to immobilized full-length p6 (upper left panel and closed circles) and PTAP peptide to immobilized Tsgl Ol UEV (lower left panel and open circles) The near-supeπmposition of the two curves demonstrates that TsglOl UEV binds p6 and the PTAP peptide with the same affinity. Figure 3c shows the 27 residues with the greatest change in chemical shift (δ > 1.8) mapped onto a surface representation of the TsglOl UEV structure. Figure 3d shows a Ribbon representation of TsglOl UEV showing residues important for binding. The Mms2 (green) and Ubcl 3 (puφle) structures have been superimposed in this figure, but only the C-terminal residues are shown, to illustrate how the binding groove of TsglOl UEV is filled in cis by C-terminal residues in E2 enzymes and in Mms2 UEV The C-terminus of TsglOl, which points away from the PTAP binding site, is indicated by the blank arrowhead
1 1. Figure 4 shows a mutagenic analysis of TsglOl UEV binding to p6, p6-Ub and Ub. Biosensor binding isotherms are shown for putative PTAP-binding mutants (left) and Ub-btnding mutants (right) Binding isotherms for p6 (top panels), p6-Ub (middle panels) and Ub (bottom panels) are shown. Mutants that significantly reduced p6 binding are shown in red, those that significantly reduced Ub binding are shown in blue (see Table 4) Mutations that had no significant effect are in green The wildtype binding isotherms are in black
12 Figure 5 shows a mapping the TsglOl UEV and Ub interaction sites Figure 5a shows an overlay of the Η/'5N-HSQC spectra of TsglOl UEV in the absence (gray) or presence of 2 0 molar equivalents of Ub
(blue) The lower panels show an expansion of the boxed region, with an additional titration point, indicating that the TsglOl UEV/Ub complex is in fast exchange Figure 5b shows the 13 residues with the greatest changes in chemical shift (δ > 1 8) are mapped onto a surface representation of the TsglOl UEV structure Figure 5c shows a ribbon representation of TsglOl UEV showing residues important for binding Figure 5d shows an overlay of the Η/15N-HSQC spectra of Ub in the absence (gray) or presence of TsglOl UEV
(magenta) The lower panels show an expansion of the boxed region showing that the Lys48 amide is shifted Figure 5e, and f show the 15 residues with the greatest change in chemical shift (δ > 1 0) are mapped onto a surface (e) and ribbon ( ) representation of Ub Lys48 and Lys63 are shown explicitly in yellow (/)
13 Figure 6 shows the comparison of the ubiquitin binding site (blue residues) on TsglOl UEV (yellow) to models for the two distinct ubiquitin binding sites (puφle) on the Ubcl3/Mms2 heterodimer (gray) (VanDemark et al , 2001) To create the figure, TsglOl UEV was superimposed on either the Ubcl3 E2 (see Figure 6a) or the Mms2 UEV (see Figure 6b) subunits of the Ubcl3/Mms2 heterodimer The figure illustrates the fact that the Ub binding surface on TsglOl is distinct from previously characterized Ub binding sites on either E2 or UEV domains, but does roughly correspond to the Mms2 binding site on Ubcl 3 14 Figure 7 shows the structure of the TsglOl UEV-PTAP peptide complex Figure 7a shows an overlaid 1H/15N-HSQC spectra of the tsN-labeled PTAP peptide either free (black) or bound to TsglOl UEV (green) The five peptide amide protons are labeled Multiple peaks in the unbound peptide spectrum reflect differing magnetic environments of minor proline isomers All prohnes in the bound state are in trans conformations Upper panel a corresponding region of a 2D 15N filtered NOESY-HSQC spectrum of the 15N- PTAP peptide-TsglOl UEV complex showing intermolecular, interresidue, and intraresidue NOE correlations (in red, green, and black, respectively) Figure 7b shows a supeφosition of the free (yellow) and PTAP peptide-bound (gray) structures of the TsglOl UEV domain Note that TsglOl UEV residues surrounding the PTAP peptide (green) binding site shift significantly to accommodate the peptide (residues 58-71 , 91-107, and 139-144 shift by an average of 3 4 A) Peptide binding buries a total surface area of 1350 A2 15 Figure 8 shows a molecular recognition in the TsglOl UEV-PTAP peptide complex Figure 8a shows a Summary of contacts between the TsglOl UEV domain and the PTAP peptide (dark green) ( Wallace, A C , et al , Protein Eng 8, 127-34 (1995)) Figures 8b and c shows views of the PTAP peptide (dark green) in its binding groove on TsglOl UEV The "Pro" pocket, which binds Pro7 of p6 7PTAP10, and the "Ala-Pro" pocket, which binds the 9Ala-Proιo dιpeptιde, are labeled in (c) 16 Figure 9 shows proline recognition by TsglOl UEV Figures 9a, b shows expanded views of the
Pro (a) and Ala-Pro (b) binding pockets, viewed along the binding groove from the N- terminal end of the peptide c, Similarities between X-Pro proline recognition in the TsglOl UEV (dark green), SH3 (yellow), and WW (orange) domains In every case, "key" prolines of bound ligands are sandwiched between two aromatic rings The figure was created by superimposing key ligand prolines Pro 10 in the TsglOl UEV-PTAP complex, Pro3 in the Dystrophin WW-a-Dystroglycan PPXY complex (Huang, X. et al., Nat Struct Biol 7,
634-8 (2000)), and Pro3 in the Grb2 SH3-Sos PXXP complex (Wittekind, M. et al., J Mol Biol 267, 933-
52 (1997)).
17. Figure 10 shows strips from of ιH/πC-NOESY-HSQC spectra of the TsglOl UEV-PTAP peptide complex. The left panels (boxed in green) show nCΛsN-labeled PTAP peptide and unlabeled UEV domain.
Intrapeptide NOE correlations are colored green and intermolecular molecular NOE correlations are colored red. The right panels (boxed in black) show nC/isN-labeled UEV domain and unlabeled PTAP peptide.
Intramolecular (UEV-UEV) NOE correlations are colored black, and intermolecular NOE correlations are colored red. Resonance assignments are indicated at the bottom and sides of the figure, with peptide resonances labeled in green and UEV resonances labeled in black. Figure 10b shows a sequence and secondary structure of TsglOl UEV. Residues that contact the PTAP peptide are shaded in yellow. Figure 10c shows a stereoview supeφosition of the 20 final structures (Cα trace) of TsglOl UEV (gray) and PTAP peptide (dark green).
V. DETAILED DESCRIPTION 18. The present invention may be understood more readily by reference to the following detailed description of preferred embodiments of the invention and the Examples included therein and to the Figures and their previous and following description.
19. Before the present compounds, compositions, articles, devices, and/or methods are disclosed and described, it is to be understood that this invention is not limited to specific synthetic methods, specific recombinant biotechnology methods unless otherwise specified, or to particular reagents unless otherwise specified, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting. A. Definitions
20. As used in the specification and the appended claims, the singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a pharmaceutical carrier" includes mixtures of two or more such carriers, and the like.
21. Ranges may be expressed herein as from "about" one particular value, and/or to "about" another particular value. When such a range is expressed, another embodiment includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent "about," it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as "about" that particular value in addition to the value itself. For example, if the value "10" is disclosed, then "about 10" is also disclosed. It is also understood that when a value is disclosed that "less than or equal to" the value, "greater than or equal to the value" and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value "10" is disclosed the "less than or equal to 10"as well as "greater than or equal to 10" is also disclosed. 22 In this specification and in the claims which follow, reference will be made to a number of terms which shall be defined to have the following meanings:
23. "Optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not
24 Throughout this application, various publications are referenced. The disclosures of these publications in their entireties are hereby incoφorated by reference into this application in order to more fully describe the state of the art to which this invention pertains. The references disclosed are also individually and specifically incoφorated by reference herein for the material contained in them that is discussed in the sentence in which the reference is relied upon
25 It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.
26 Reducing means lowering or decreasing. It can be any amount of reduction, and would typically be determined as "reducing" by comparing amount of interest to a reference amount For example, if a "reducing viral budding with an inhibitor" would be any decrease in viral budding in the presence of an inhibitor as compared to the amount of viral budding in the absence of the inhibitor or a control. Any of he assays disclosed herein or known can be used to determine whether something is "reducing."
27 Set of molecules. Disclosed are sets of molecules. These sets comprise at least two different molecules disclosed herein The molecules can differ by as little as single atom up to being made up of completely different atoms The sets can be made up of any of the disclosed compositions or combinations of compositions disclosed herein A set of molecules can be referred to as a library of molecules. 28 A system as used herein refers to any combination of components that has a set of desired characteristics For example, a system might be a cell that has been transfected with a particular gene or combination of genes so that the cell has certain properties Or for example, the system could be a cell type that has been developed so as being capable of being used in viral budding analysis The system, could also be a, for example, chromatographic column having certain properties that would for example, include the covalent attachment of one of the disclosed proteins, such as TSG 101
29 Disclosed are the components to be used to prepare the disclosed compositions as well as the compositions themselves to be used within the methods disclosed herein. These and other materials are disclosed herein, and it is understood that when combinations, subsets, interactions, groups, etc. of these materials are disclosed that while specific reference of each various individual and collective combinations and permutation of these compounds may not be explicitly disclosed, each is specifically contemplated and described herein For example, if a particular TSG 101 variant is disclosed and discussed and a number of modifications that can be made to a number of molecules including the TSG 101 variant are discussed, specifically contemplated is each and every combination and permutation of the TSG 101 variant and the modifications that are possible unless specifically indicated to the contrary. Thus, if a class of molecules A, B, and C are disclosed as well as a class of molecules D, E, and F and an example of a combination molecule, A-
D is disclosed, then even if each is not individually recited each is individually and collectively contemplated meaning combinations, A-E, A-F, B-D, B-E, B-F, C-D, C-E, and C-F are considered disclosed Likewise, any subset or combination of these is also disclosed. Thus, for example, the sub-group of A-E, B-F, and C-E would be considered disclosed. This concept applies to all aspects of this application including, but not limited to, steps in methods of making and using the disclosed compositions. Thus, if there are a variety of additional steps that can be performed it is understood that each of these additional steps can be performed with any specific embodiment or combination of embodiments of the disclosed methods. B. Compositions and Methods 30 Disclosed are solution structures of TSGIOI and regions of TSGIOI, as well as regions of GAG, such as the PTAP region, as well as solution structures of complexes involving these molecules These solution structures have produced sets of coordinates that define the position of the atoms making up TSGIOI UEV and PTAP and UB, and the TSG 101 UEV complexed with PTAP. These coordinates can be used to produce three dimensional representations of the these molecules, which can be used in a variety of ways, including, for example, drug screening and variant TSGIOI or PTAP structure determination
31 Thus, disclosed are methods for solving a solution structure of the TSGIOI UEV optionally including the PTAP and/or Ub binding regions, as well as the solution structures of the complexes of the same. The methods involve producing solutions of TSGIOI UEV and solutions of the complexes such that solution structure data can be obtained, and then assigning coordinate values to the various atoms forming the TSGIOI UEV optionally including the PTAP and or Ub binding regions and their complexes.
32 Disclosed are solutions capable of being used to solve the solution structure of TSGIOI UEV optionally including the PTAP and/or Ub binding regions and their complexes
33. Also disclosed are scalable three dimensional configurations of points derived from structure coordinates of at least a portion of TSGIOI UEV optionally including the PTAP and/or Ub binding regions and their complexes In one embodiment, the scalable three dimensional set of points is derived from structure coordinates of at least coordinates associated with Y63, V89, M95, and VI 41 for the PTAP binding domain and V43, F44, N45, D46, W75, and F88 for the UB binding domain.
34 In one embodiment, the scalable three dimensional set of points is derived from structure coordinates of at least coordinates associated with Thr58, Valόl, Tyr63, Tyr68, Asn69, Ile70, Pro71 , Thr92, Met95, Prol39, Val 141, Phel42, Serl43, and Argl44 alone or in combination.
35 Also disclosed are scalable three dimensional sets of points derived from structure coordinates of at least a portion of a molecule or a molecular complex that is structurally homologous to TSGIOI UEV optionally including the PTAP and/or Ub binding regions and their complexes. Two points are considered structurally homologous if they have RMS of less than 5 A0, 4 A°, 3 A°, 2 A0., or 1 0A°. A structurally homologous structure would have an average of less than 5 A°, 4 A°, 3 A°, 2 A0 , or 1 0A° RMS.
36 Also disclosed are TSGIOI UEV molecules that include at least a portion of the PTAP and/or Ub binding regions. For example, the molecules could include the amino acids Y63, V89, M95, and V141 for the PTAP binding domain and V43, F44, N45, D46, W75, and F88 for the UB binding domain The molecules could also include the amino acids, Thr58, Valόl, Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol39,
Val 141, Phe 142, Ser 143, and Arg 144 alone or in combination.
37. The TSGIOI UEV structure can be defined by the coordinates set forth in Tables 5 or fraction of these coordinates, or coordinates producing a homologous structure. The PTAP binding domain of TSGIOI can be defined by the coordinates set forth in Table 5, or other Tables herein. The coordinates for the 40 lowest energy structures (20 from CNS, 20 from DYANA) are set forth in Tables 8-47 and they set forth structural information about amino acids Thr58, Valόl, Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol 39, Vall41 , Phel42, Serl43, and Argl44 alone or in combination, or fraction of these coordinates, or coordinates producing a homologous structure of the PTAP binding domain The Ub binding domain of TSGIOI can be defined by the coordinates set forth in Table 5 related to amino acids V43, F44, N45, D46, W75, and F88 or a fraction of these coordinates, or coordinates producing a homologous structure of the Ub binding domain
38. Also disclosed are molecules or molecular complexes and their cognate coordinates that are structurally homologous to TSGIOI UEV optionally including the PTAP and/or Ub binding regions and their complexes.
39. Also disclosed are methods involving molecular replacement, substitution, deletion, or alteration to obtain structural information about a molecule or molecular complex of unknown structure, but which is related to the disclosed structures, through for example, amino acid identity. The methods include producing a solution of the molecule or molecular complex, generating a solution structure aided by the information disclosed herein, and applying at least a portion of the structure coordinates set forth Table 5 or the data related to the molecule or molecule complex to generate a three-dimensional structure of at least a portion of the molecule or molecular complex
40. Also disclosed are methods for variant modeling a TSGIOI UEV or PTAP or Ub homolog.
41. Each of the constituent amino acids of TSGIOI UEV or the PTAP and/or Ub binding regions can be defined by a set of structure coordinates or fraction thereof as set forth in Table 5, or any of the coordinate tables disclosed herein The term "structure coordinates" refers to a Cartesian coordinate of a particular atom It is understood that for any reference to Table 5, unless specifically indicated otherwise, the description applies equally to all of the coordinate tables contained herein, including those on the included CD-Rs.
42 Disclosed are representations of variations in structure coordinates which can be generated by mathematically manipulating the disclosed structure coordinates of the TSG 101 UEV or PTAP binding domain or UB binding domain or PTAP molecule, for example For example, the structure coordinates set forth in Table 5 could be manipulated by permutations of the structure coordinates, fractionalization of the structure coordinates, integer additions or subtractions to sets of the structure coordinates, inversion of the structure coordinates or any combination of the above Alternatively, modifications in the crystal structure due to mutations, additions, substitutions, and or deletions of amino acids, or other changes in any of the components that make up composition from which the coordinates were produced, could also yield variations in structure coordinates Such variations in the individual coordinates will have little effect on the global shape. Furthermore, when variations are made in a concentrated region of the composition or in the structural representation of the composition, the effect on other structural regions of the molecule typically is minimal One way of judging the effect the variations in one part of the composition or structure have on another part of the composition or structure is to compare the cognate regions to the disclosed structures standard error and judge whether the differences are in an acceptable range, for example, within the same error range for that region in the original structure If the error is within the disclosed error ranges, the structures or compared regions of the structure can be said to be equivalent The alterations and modifications discussed herein, in connection with the discussion of protein modifications and discussed herein indicate that modifications which will not alter, for example the properties of the disclosed compositions, such as binding between TSGIOI and GAG, can be made and are disclosed 1. Coordinates 43 Structure coordinates define a unique configuration of points in space Those of skill in the art understand that a set of structure coordinates for protein or an protein/hgand complex, or a portion thereof, define a relative set of points that, in turn, define a configuration in three dimensions A key piece of information obtained from the coordinates is the position of the atoms that make up the composition The position of the atoms is defined in a Cartesian form, such that there are x-y-z positions which allow for a determination of distances and angles between two or more atoms Thus, a similar or identical configuration, l e structure, can be defined by an entirely different set of coordinates, provided the distances and angles between coordinates remain essentially the same By manipulating the distances and angles in a like manner a scalable representation can be obtained
44 Disclosed are scalable three-dimensional configurations derived from structure coordinates set forth in Table 5, or portion thereof, or from coordinates producing a configuration with essentially the same angles and distances between the atoms Also disclosed are scalable three-dimensional configurations derived from the structure coordinates obtained from the disclosed molecules such as TSGIOI UEV Also disclosed in tables 6 and 8-26 are coordinates representing other low energy structures of the TSG101-UEV domain The data represented in Table 3 was derived from performing standard calculations of the coordinates as disclosed herein It is understood that once given the coordinate sets herein, the RMS, for example, for any atom or subset of atoms can be calculated and is considered herein disclosed Furthermore, it is understood that the various coordinates set forth in Tables 5, 6, and 8-26 for any given individual atom represent a range for which that atom could take place in a coordinate representation of TSGIOI -UEV or fragment thereof Disclosed in Tables 8-47 are coordinates representing low energy structures of the complex of the TSG 101 -UEV domain and the PTAP binding domain, submitted on a CD-ROM
45 Also disclosed are scalable three-dimensional configurations of points derived from structure coordinates of molecules or molecular complexes that are structurally homologous to TSGIOI UEV, the UB binding domain, the PTAP binding domain, or PTAP, as well as structurally equivalent configurations
46 The configurations of points in space derived from structure coordinates according to the invention can be visualized as, for example, a holographic image, a stereodiagram, a model or a computer- displayed image, and the invention thus includes such images, diagrams or models
47 Comparisons between different structures, different conformations of the same structure, and different parts of the same structure can be performed in a variety of ways For example, typically the structures (coordinates making up the structure) are loaded, the atom equivalences in these structures are defined; the structures are fit, and then the resulting comparisons are reviewed.
48. Modeling programs typically also allow for a determination of the variances, the root mean square deviations, and statistical significance of the various structures. 49. The term "root mean square deviation" means the square root of the arithmetic mean of the squares of the deviations. This allows for comparison of two sets of data for example or the cognate position in two configurations or structures.
50. The tables disclosed herein that contain structure data follow the PDB format of the protein database. The formatting and nomenclature is that standard used throughout the industry. 2. Hardware
51. The hardware architecture used for structural analysis and manipulation according to the present invention will include a system processor potentially including multiple processing elements where each processing element may be supported via a MIPS R10000 or R4400 processor such as provided in a SILICON GRAPHICS INDIGO2 IMPACT workstation; alternative processors such as Intel-compatible processor platforms using at least one PENTIUM III or CELERON (Intel Coφ., Santa Clara, CA) class processor, UltraSPARC (Sun Microsystems, Palo Alto, CA) or other equivalent processors could be used in other embodiments. The system processor may include combinations of different processors from different vendors. In some embodiments, analysis and manipulation functionality, as further described below, may be distributed across multiple processing elements. The term processing element may refer to (1) a process running on a particular piece, or across particular pieces, of hardware, (2) a particular piece of hardware, or either (1) or (2) as the context allows.
52. The hardware includes a system data store (SDS) that could include a variety of primary and secondary storage elements. In one preferred embodiment, the SDS would include RAM as part of the primary storage; the amount of RAM might range from 32 MB to 640 MB although these amounts could vary and represent overlapping use. The primary storage may in some embodiments include other forms of memory such as cache memory, registers, non-volatile memory (e.g., FLASH, ROM, EPROM, etc.), etc.
53. The SDS may also include secondary storage including single, multiple and/or varied servers and storage elements. For example, the SDS may use internal storage devices connected to the system processor. In embodiments where a single processing element supports all of the analysis and manipulation functionality, a local hard disk drive may serve as the secondary storage of the SDS, and a disk operating system executing on such a single processing element may act as a data server receiving and servicing data requests.
54. It will be understood by those skilled in the art that the different information used in the processes and systems according to the present invention may be logically or physically segregated within a single device serving as secondary storage for the SDS; multiple related data stores accessible through a unified management system, which together serve as the SDS; or multiple independent data stores individually accessible through disparate management systems, which may in some embodiments be collectively viewed as the SDS. The various storage elements that comprise the physical architecture of the SDS may be centrally located, or distributed across a variety of diverse locations. ___
55 The architecture of the secondary storage of the system data store may vary significantly in different embodiments In several embodiments, database(s) may be used to store and manipulate the data, in some such embodiments, one or more relational database management systems, such as DB2 (IBM, White Plains, NY), SQL Server (Microsoft, Redmond, WA), ACCESS (Microsoft, Redmond, WA), ORACLE 81 (Oracle Coφ , Redwood Shores, CA), Ingres (Computer Associates, Islandia, NY), MySQL (MySQL AB, Sweden) or Adaptive Server Enteφπse (Sybase Inc , Emeryville, CA), may be used in connection with a variety of storage devices/file servers that may include one or more standard magnetic and/or optical disk drives using any appropriate interface including, without limitation, IDE, EISA and SCSI In some embodiments, a tape library such as Exabyte X80 (Exabyte Coφoration, Boulder, CO), a storage attached network (SAN) solution such as available from (EMC, Inc , Hopkinton, MA), a network attached storage (NAS) solution such as a NetApp Filer 740 (Network Appliances, Sunnyvale, CA), or combinations thereof may be used
56 In other embodiments, the data store may use database systems with other architectures such as object-oriented, spatial, object-relational or hierarchical or may use other storage implementations such as hash tables or flat files or combinations of such architectures Such alternative approaches may use data servers other than database management systems such as a hash table look-up server, procedure and/or process and or a flat file retrieval server, procedure and/or process Further, the SDS may use a combination of any of such approaches in organizing its secondary storage architecture
57 In one preferred embodiment, coordinate data is stored in flat ASCII files according to a standardize format In one such embodiment, the standardized format is PDB as which is used through out the protein structure industry The column content of the Tables containing coordinate data disclosed herein follows the PDB formatting and nomenclature
58 The hardware platform would have an appropriate operating system such as WINDOWS/NT, WINDOWS 2000 or WINDOWS/XP Server (Microsoft, Redmond, WA), Solans (Sun Microsystems, Palo Alto, CA), or IRIX (or other UNIX/LINUX variant) In one preferred embodiment, the hardware platform includes an IRIX operating system running on a SILICON GRAPHICS INDIGO2 IMPACT workstation 3. Structural coordinates and storage of same
59 Structural coordinates, such as atomic coordinates, of this invention can be stored in a machine- readable form on machine-readable storage medium Examples of such media include, but are not limited to, computer hard drive, diskette, DAT tape, CD-ROM, and the like The information stored on this media can be used for display as a three-dimensional shape or representation thereof or for other uses based on the structural coordinates, the spatial relationships between atoms described by the structural coordinates or the three- dimensional structures that they define Such uses can include the use of a computer capable of reading the data from the storage media and executing instructions to generate and/or manipulate structures defined by the data Commonly used sets of instructions, 1 e , computer programs, for viewing or otherwise manipulating structures include, but are not limited to, Midas (UCSF), MidasPlus (UCSF), MOIL (University of Illinois), Yummie (Yale University), Sybyl (Tripos, Inc ), Insight/Discover (Biosym Technologies), MacroModel (Columbia University), Quanta (Molecular Simulations, Inc ), Ceπus (Molucular Simulations, Inc ), Alchemy (Tripos, Inc ), LabVision (Tripos, Inc ), Rasmol (Glaxo Research and Development), Ribbon (University of Alabama), NAOMI (Oxford University), Explorer Eyechem (Silicon Graphics, Inc.), Univision (Cray
Research), Molscript (Uppsala University), Chem-3D (Cambridge Scientific), Chain (Baylor College of
Medicine), O (Uppsala University), GRASP (Columbia University), X-Plor (Molecular Simulations, Inc.;
Yale University), Spartan (Wavefunction, Inc.), Catalyst (Molecular Simulations, Inc.), Molcadd (Tripos, Inc.), VMD (University of Illinois/Beckman Institute), Sculpt (Interactive Simulations, Inc.), Procheck
(Brookhaven National Laboratory), DGEOM (QCPE), RE VIEW (Brunei University), Modeller (Birbeck
College, University of London), Xmol (Minnesota Supercomputing Center), Protein Expert (Cambridge
Scientific), HyperChem (Hypercube), MD Display (University of Washington), PKB (National Center for
Biotechnology Information, NIH), ChemX (Chemical Design, Ltd.), Cameleon (Oxford Molecular, Inc.), and Iditis (Oxford Molecular, Inc.).
4. Machine Readable Storage Media
60. Disclosed are machine-readable storage mediums comprising a data storage material encoded with machine readable data. Furthermore, the data can be extracted and manipulated by machines configured to read the data stored on the machine readable storage media, and in fact, when performing the molecular modeling, such as displaying a configuration of the disclosed compositions, as discussed herein, typically the data will be retrieved or stored on a machine readable storage media.
61. Disclosed are machine readable storage media comprising the coordinates set forth in Table 5 or a subset of these coordinates, or coordinates of any of tables 6, and 8-47 or subsets of these, or any of the tables disclosed herein, or coordinates producing equivalent configurations of the disclosed compositions or their variants as discussed herein.
62. The disclosed coordinates and data can be manipulated on any appropriate machine, having for example, a processor, memory, and a monitor. The data can also be manipulated and accessed by a variety of connected items, including printers, LCDs, for example.
63. Disclosed are methods of utilizing molecular replacement to obtain structural information about a molecule or molecular complex whose structure is unknown comprising the steps of:
64. (a) producing coordinates of the molecule or molecular complex of unknown structure, and (b) applying at least a portion of the structure coordinates set forth in Table 5 to the coordinates of the unknown structure to generate a configuration of the unknown structure.
5. Modeling of variants 65. Structures of variant TSGIOI or GAG or PTAP or Ub or P6 molecules or PTAP, for example, can be produced without obtaining individual coordinates for the variant. In essence the coordinates of the molecules disclosed herein or coordinates that produce a structure homolog are used as a starting point and the variant atom or atoms of the variant disclosed molecule are substituted into the simulated structure and their relative position to the original unchanging atoms, i.e. coordinates, are determined through any of a variety of energy minimization functions. Thus, sequence alignment, secondary structure prediction, the screening of structural libraries of TSGIOI or P6 or any of the other disclosed molecules, produced from the disclosed coordinates, or any combination of these can be used to overlay the variant structure. For example, the variant atom or atoms can also be modeled from any structural library having coordinates of similar or identical atoms. Thus, the initial structure to undergo energy minimization can be arrived at by modeling known coordinates for a given for the given atom or atoms. These libraries of structures can be screened for the optimal structure. A side chain rotomer library can be used to model a given side chain or set of side chains.
After initial energy minimization iterative or new energy minimizations may be necessary if the structure produced after energy minimization violates a physical constraint, such as correct stereochemistry. 6. Computer Drug Design
66. Computational techniques can be used to screen, identify, select and design chemical entities capable of associating with TSGIOI , the TSG 101 UEV, the TSGIOI PTAP binding domain, or the TSGIOI Ub binding domain, for example, or structurally homologous molecules, or complexes of the same. The disclosed coordinates and those that produce structurally homologous molecules can be used to model potential ligands for modulators, such as inhibitors, of TSGIOI -GAG interactions. Atoms of the potential ligand can be included in modeling simulation involving the TSGIOI, and other molecules as disclosed herein, and the contacts that arise between the potential ligand in a variety of positions with the disclosed compositions, or with a region, such as the TSGIOI PTAP binding domain, can be investigated. Energy minimization of these contacts between the potential ligand and the disclosed molecules can indicate potential ligands having, for example a desired affinity or a desired specificity. The ligands identified as having a desired number of contacts, with atoms of the disclosed compositions, such as TSGIOI UEV, as positioned by the coordinates or homologs disclosed herein, can be chosen and then optionally further tested by synthesizing or making the ligand and the disclosed compositions and performing standard biochemistry to assay binding activity or functional activity, such as those that use kinetic or thermodynamic methodology, such as, equilibrium dialysis, microcalorimetry, circular dichroism, capillary zone electrophoresis, nuclear magnetic resonance spectroscopy, fluorescence spectroscopy, and combinations thereof.
67. Drug designing typically involves computer-assisted design of chemical entities that associate with TSGIOI or GAG, their homologs, or portions thereof. Chemical entities can be designed in a step-wise fashion, one fragment at a time, or may be designed as a whole or "de novo." 68. The binding sites of TSGIOI and GAG molecules, such as the PTAP binding site, the Ub binding site, and the TSGIOI binding site, as disclosed herein set forth the position of target atoms for interaction with ligands which will be able to bind or inhibit the disclosed interactions. The conformation of the TSG101- PTAP binding site and the TSGIOI-Ub binding site allow for a precise three dimensional map for rationally designing molecules that will form, for example, a set number of contacts with the atoms defining the binding regions as disclosed herein.
69. A contact as used herein means any position between two atoms, typically one atom of a ligand and one atom of the disclosed compositions, such as the TSG101-PTAP or Ub binding domains, that when positioned by an energy minimization program, for example, are less than 5A°, 4A°, 3A°, 2A°, or 1 A° apart. Thus, a contact can for example, correlate with, for example, non-covalent interactions, such as a hydrogen bonds, Vander Walls interactions, hydrophobic interactions, and electrostatic interactions, between two atoms. Typically a contact will add to the binding energy between two atoms, but it can also be repulsive, typically more repulsive the closer the two atoms become. Although a contact is defined herein as being a relationship of two atoms, the molecules, components and compounds of which the atoms are a part can be referred to as having "contacts" with each other. Thus, for example, a ligand having an atom that forms a contact with an atom in a TSGIOI domain can be said to have a contact with the TSGIOI domain (and, more broadly, a contact with the TSGIOI) By further example, an inhibitor having an atom that forms a contact with an atom in an amino acid in a protein (such as TSGIOI) can be said to have a contact with the amino acid in the protein The contacts involved are the contacts between the atoms as described above It is understood that for a ligand to be a potential therapeutic candidate, it must have an appropriate level or quality of contacts, such that an interaction occurs, but that it should not cause steπc and energetic problems Conformational considerations include the overall three-dimensional structure and orientation of the chemical entity in relation to the binding pocket, and the spacing between various functional groups of an entity that directly interact with the TSG101-PTAP binding domain or homologs thereof 70 A contact between atoms, molecules, components or compounds is a form of interaction between the atom, molecules, components and compounds involved in the contact Thus, an atom, molecule, component or compound can be said to "interact with" another atom, molecule, component or compound Such an interaction can be referred to at any level Thus, for example, an interaction (or contact) between two atoms in two different molecules results in a relationship between the two molecules that can be referred to as an interaction between the two molecules containing the atoms Similarly, an interaction between, for example, an inhibitor and an amino acid of a protein results in a relationship between the inhibitor and the protein that can be referred to as an interaction between the inhibitor and the protein Unless the context clearly indicates otherwise, reference to an interaction between atoms, molecules, components or compounds is not intended to exclude the existence of other, unstated interactions between the atoms, molecules, components or compounds at issue or with other atoms, molecules, components or compounds Thus, for example, reference to an interaction between an inhibitor and one specific amino acid of a protein does not indicate that there are not other interactions or contacts between the inhibitor and the protein or with other atoms, molecules, components or compounds
71 Unless the context clearly indicates otherwise, reference to the capability of atoms, molecules, components or compounds to interact with other atoms, molecules, components or compounds refers to the possibility of such an interaction should the atoms, molecules, components or compounds be brought into contact and not to any actual, presently existing interaction Thus, for example, a statement that an inhibitor "can interact with" an amino acid of a protein refers to the fact that the inhibitor and amino acid would interact if brought into contact not that the inhibitor and amino acid are presently interacting 72 The modeling and display of the disclosed compositions can be accomplished using any modeling program, such as QUANTA, SYBYL, CHARMM, and AMBER, Insight II/Discover (Molecular Simulations, Inc , San Diego, Calif 92121), DelPhi (Molecular Simulations, Inc , San Diego, Calif 92121), and AMSOL (Quantum Chemistry Program Exchange, Indiana University) These programs may be implemented, for example, using a Silicon Graphics workstation such as an Indigo with "IMPACT" graphics Other hardware systems and software packages will be known to those skilled in the art Drug design programs, such as, GRID (P J Goodford. J Med Chem 28 849-857 (1985), available from Oxford University, Oxford, UK), MCSS (A Miranker et al , Proteins Struct Funct Gen , 1 1 29-34 (1991), available from Molecular Simulations, San Diego, Calif), AUTODOCK (D S Goodsell et al , Proteins Struct Funct Genet 8 195-202 (1990), available from Scπpps Research Institute, La Jolla, Calif), and DOCK (I D Kuntz et al , J Mol Biol 161 269-288 (1982), available from University of California, San Francisco, Calif), LUDI (H -J Bohm, J Comp Aid
Molec Design 6 61 -78 (1992), available from Molecular Simulations Inc , San Diego, Calif ), LEGEND (Y Ntshibata et al , Tetrahedron, 47 8985 (1991 ), available from Molecular Simulations Inc , San Diego, Calif), LeapFrog (available from Tripos Associates, St Louis, Mo ), and SPROUT (V Gtllet et al , J Comput Aided Mol Design 7 127-153 (1993), available from the University of Leeds, UK), can also be used
73 The efficiency of a potential hgand's interaction with the disclosed compositions can be evaluated and optimized For example, typically a preferred ligand will cause little perturbation to the three dimensional positioning of the atoms of disclosed compositions that are in the vicinity of the interaction or are somehow allosteπcally affected The level of perturbation can be determined by comparing the energy state of the disclosed structural conformations for the bound and unbound states Typically the smaller the change the less perturbation and the less perturbation the higher the likelihood that the ligand will be desirable as for example, a competitive inhibitor This perturbation energy can be, for example, less than or equal to about 30 kcal/mole, 20 kcal/mole, 15 kcal/mole, 10 kcal/mole, 8 kcal/mole, 6 kcal/mole, 5 kcal/mole, 4 kcal/mole, 3 kcal/mole, 2 kcal/mole, or 1 kcal/mole TSGIOI or GAG ligands may interact with the TSGIOI or GAG molecule in more than one conformation that is similar in overall binding energy In those cases, the perturbation energy of binding can be taken as the difference between the energy of the free entity and the average energy of the conformations observed when the ligand binds to the TSGIOI or GAG molecule
74 An entity designed or selected as binding to TSGIOI or GAG may be further computationally optimized so that in its bound state it would preferably lack repulsive electrostatic interaction with the target enzyme and with the surrounding water molecules Such non-complementary electrostatic interactions include repulsive charge-charge, dipole-dtpole, and charge-dipole interactions
75 Specific computer software is available in the art to evaluate compound deformation energy and electrostatic interactions Examples of programs designed for such uses include Gaussian 94, revision C (M J Fπsch, Gaussian, Inc , Pittsburgh, Pa 15106), AMBER, version 4 1 (P A Kollman, University of California at San Francisco, 94143), QUANTA/CHARMM (Molecular Simulations, Inc , San Diego, Calif 92121 ),
76 The disclosed structures and coordinates can also be used to screen potential ligands, for example, as drug candidates, which interact with, I e form contacts with, the TSGIOI or GAG Small molecule databases, such as structure databases can be used for this Not only whole molecules can be screened, but subparts of molecule, for example, various functional groups can also be screen to find preferred functional groups for forming contacts with the TSG 101 or GAG structures disclosed herein Functional groups that make a desired set of contacts, for example, with a desired or particular region of the TSGIOI or GAG molecule, can then be used to further build combinations of these and other types of functional groups to design ligands containing the functional groups or combinations of functional groups 77 It is understood that also disclosed are iterative approaches which use successive performance of the various steps disclosed herein to optimize molecules and/or isolate molecules from sets of molecules This can also be done with multiple coordinate sets that have been obtained, for example, from the solution of structures involving a ligand or series of structures involving a series of ligands For example, molecules known to have preferred biochemical properties, such as binding TSGIOI or GAG as disclosed herein, can be solved in a co-structure, and then the structure information obtained from this can be used to select potential ligands for function
78. A compound that is identified or designed as a result of any of these methods can be obtained (or synthesized) and tested for its biological activity, e g , inhibition of TSGIOI -GAG interaction activity C. Compositions
1. TSGIOI
79 TSGI OI comprises a number of domains. TSGIOI can have a PTAP binding domain, which functions to interact with the PTAP region of a retroviral GAG protein. It is understood that the TSGIOI PTAP binding domain can bind any protein containing the PTAP region. This region is a part of retroviral GAG proteins as well as proteins in enveloped viruses. TSGIOI also can have ubtquitin binding domain, which can interact with ubtquitin
80 The direct interaction between TsglOl and the PTAP late domain motifs on the viral structural proteins is mediated by the N-terminal ubiquitin E2 variant (UEV) domain of TsglOl (VerPlank et al , 2001 , Garrus et al , 2001 ; Martin-Serrano et al , 2001), whereas the remaining C-terminal two-thirds of Tsgl Ol interacts with other proteins (Fig. \a) Like other UEV domains, TsglOl UEV shows significant sequence similarity to E2 ubiquitin hgases but is unable to catalyze ubtquitin transfer, as it lacks the active site cysteine that forms the transient thioester bond with the C-terminus of ubiquitin (Ub) (Koonin and Abagyan, 1997, Ponting et al , 1997) (Fig. \b). Nevertheless, at least some UEVs have retained the ability to bind Ub, and appear to act either as co-factors in ubiquitination reactions, or as ubiquitin sensors (Hofmann and Pickart, 1999, VerPlank et al , 2001 ; Katzmann et al., 2001 , VanDemark et al., 2001 , Garrus et al., 2001) UEV domains also frequently contain other protein recognition motifs, and may generally serve to couple protein and Ub binding functions to facilitate the formation of multiprotein complexes
81. Tsg 101 was initially discovered in a screen for potential tumor suppressors (Li and Cohen, 1996), and the protein appears to perform multiple functions, including down-regulating p53 via the MDM2/p53 pathway (Li et al , 2001; Ruland et al , 2001). TsglOl also plays a central role in vacuolar protein sorting.
The Vps pathway sorts membrane-bound proteins for eventual degradation in the lysosome (vacuole in yeast) ((Lemmon and Traub, 2000) and references therein) Two alternative entrees into the Vps pathway are via vesicular trafficking from the Golgi (e g , in destroying misfolded membrane proteins) or via endocytosis from the plasma membrane (e.g., in downregulating surface receptors) Vesicles carrying proteins from either source can enter the Vps pathway by fusing with endosomes As these endosomes mature, their cargos are sorted for lysosomal degradation via the formation of structures called multivesicular bodies (MVB). MVB are created when surface patches on late endosomes bud into the lumen, forming small (-50-100 nm) vesicles. A maturing MVB can contain tens or even hundreds of these vesicles. The MVB then fuses with the lysosome, releasing the vesicles for degradation in this hydrolytic organelle 82 Ub also plays an important role in the budding of retroviruses and other enveloped viruses (Harty et al., 2000; Patnaik et al., 2000; Schubert et al , 2000, Strack et al , 2000; Vogt, 2000, Harty et al , 2001 ; Kikonyogo et al , 2001) Retroviruses contain high levels of ubiquitin, and 2-5% of Gag proteins in the viπon are monoubiquitinated (Putterman et al , 1990, Ott et al., 1998; Ott et al., 2000). Moreover, treatment of infected cells with proteasome inhibitors, which decreases the intracellular concentration of free Ub, also inhibits virus release at a late stage (Schubert et al., 2000; Harty et al., 2001). In some cases this effect can be partially rescued either by overexpressing free Ub or by fusing Ub to the C-terminal end of the viral Gag protein (Patnaik et al., 2000). 83.
2. HIV budding
84 Like other enveloped viruses, HIV-1 uses cellular machinery to bud from infected cells
Disclosed herein TsglOl protein functions in vacuolar protein sorting (Vps) and is required for HIV-1 budding The UEV domain of TsglOl binds to an essential tetrapeptide (PTAP) motif within the p6 domain of the structural Gag protein and also to ubtquitin Depletion of cellular TsglOl by a small interfering RNA arrests HIV-1 budding at a late stage, and budding is rescued by reintroduction of TsglOl Dominant negative mutant Vps4 proteins that inhibit vacuolar protein sorting also arrest HIV-1 and MLV budding These observations are consistent with retroviruses budding by appropriating cellular machinery normally used in the
Vps pathway to form multivesicular bodies 85 HIV-1 assembly is driven by the viral Gag protein, which is actively trafficked to the plasma membrane where it associates into enveloped, spherical particles that bud from the cell (reviewed in (Freed, 1998)) During viral assembly, Gag is processed by the viral protease at a series of sites to produce four new structural proteins that perform essential functions in the mature, infectious viπon (denoted MA, CA, NC, and p6, Fig 1 A) Proteolytic processing is not required for particle production, however, as HIV-1 Gag can assemble and bud in the absence of any other viral proteins
86 The budding of an enveloped virus can be viewed as a fission event in which the continuous cell membrane is broken and resealed to create discrete viral and cellular membranes Like other enveloped viruses, HIV-1 does not encode its own membrane fission machinery and presumably therefore must recruit and reprogram cellular proteins to assist in the budding process A potential docking site for such cellular factor(s) has been mapped to a conserved P(T/S)AP motif located in the p6 domain of HIV-1 Gag Point mutations within this "PTAP" motif arrest viral release at a very late stage (Gott nger et al , 1991 , Huang et al , 1995), and it has therefore been termed a "late domain" (Wills and Craven, 1991) Virus assembly appears to initiate normally in the late domain mutants, but the continuous membrane that connects the budding particles to the cell (or to other budding particles) is not severed, resulting in abnormal or severely attenuated virus release
87 The recruitment of cellular machinery to facilitate virus budding seems to be a general phenomenon, and distinct late domains have been identified in the structural proteins of many enveloped viruses (Vogt, 2000) Two well characterized late domains are the "PY" motif (consensus sequence PPXY, X= any ammo acid) found in membrane-associated proteins from filo-, orbi-, rhabdo- and oncoretroviruses (Craven et al , 1999, Harty et al , 2000, Harty et al , 1999, Jayakar et al , 2000), and the "YL" motif (YXXL) found in the Gag protein of equine infectious anemia virus (EIAV) (Puffer et al , 1997, Puffer et al , 1998) The various late domains can still function when moved to different positions within retroviral Gag proteins, supporting the idea that they are docking sites for cellular factors rather than structural elements (Parent et al , 1995, Yuan et al , 2000) Moreover, the different late domains can function interchangeably and multiple late domains are often found in close proximity within viral coat proteins, suggesting that they may act synergistically (Parent et al , 1995, Strack et al , 2000, Yuan et al , 2000)
88 Ubiquitin (Ub) also plays an essential, albeit poorly understood, role in retroviral budding (Patnaik et al , 2000, Schubert et al , 2000b, Strack et al , 2000, Vogt, 2000) For example, retrovirus budding can be blocked at a late stage by depleting cellular pools of free ubiquitin with proteasome inhibitors It is not yet certain, however, whether the functionally relevant substrate for ubiquit ation is Gag itself or a cellular factor HIV-1 p6 and other retroviral Gag proteins are monoubiquitinated at low levels (Ott et al , 2000) and there is a general correlation between Gag ubiquitmation and virus release (Schubert et al , 2000b, Strack et al , 2000) Moreover, the block imposed by proteasome inhibitors can be at least partially alleviated by covalently fusing Ub to the C-terminal end of Rous sarcoma virus (RSV) Gag (Patnaik et al , 2000)
However, virus release and replication are not affected by mutation of the two HIV-1 p6 lysine residues (Lys- 27 and Lys-33) that are the major sites for Gag ubiquitmation (Ott et al , 2000) The functional role of Gag ubiquitmation therefore remains uncertain In principle, Gag ubiquitmation could facilitate budding either by targeting defective Gag molecules for proteolytic degradation and thereby preventing them from interfering with viral budding (Schubert et al , 2000a), or by creating docking sites for cellular factors that actively participate in viral budding
3. Molecules that can interact with TSGIOI and/or PTAP and/or Ub a) Functional Nucleic Acids
89 Functional nucleic acids are nucleic acid molecules that have a specific function, such as binding a target molecule or catalyzing a specific reaction Functional nucleic acid molecules can be divided into the following categories, which are not meant to be limiting For example, functional nucleic acids include antisense molecules, aptamers, πbozymes, triplex forming molecules, and external guide sequences The functional nucleic acid molecules can act as affecters, inhibitors, modulators, and stimulators of a specific activity possessed by a target molecule, or the functional nucleic acid molecules can possess a de novo activity independent of any other molecules
90 Functional nucleic acid molecules can interact with any macromolecule, such as DNA, RNA, polypeptides, or carbohydrate chains Thus, functional nucleic acids can interact with the mRNA of TSGIOI or fragment thereof, or the genomic DNA of TSGIOI or fragment thereof or they can interact with the polypeptide TSGIOI or fragment thereof, such as the PTAP binding domain or the UB binding domain Often functional nucleic acids are designed to interact with other nucleic acids based on sequence homology between the target molecule and the functional nucleic acid molecule In other situations, the specific recognition between the functional nucleic acid molecule and the target molecule is not based on sequence homology between the functional nucleic acid molecule and the target molecule, but rather is based on the formation of tertiary structure that allows specific recognition to take place 91 Antisense molecules are designed to interact with a target nucleic acid molecule through either canonical or non-canonical base pairing The interaction of the antisense molecule and the target molecule is designed to promote the destruction of the target molecule through, for example, RNAseH mediated RNA- DNA hybrid degradation Alternatively the antisense molecule is designed to interrupt a processing function that normally would take place on the target molecule, such as transcription or replication Antisense molecules can be designed based on the sequence of the target molecule Numerous methods for optimization of antisense efficiency by finding the most accessible regions of the target molecule exist Exemplary methods would be m vitro selection expeπments and DNA modification studies using DMS and DEPC It is preferred that antisense molecules bind the target molecule with a dissociation constant (k_)less than 10 It is more preferred that antisense molecules bind with a kj less than 108 It is also more preferred that the antisense molecules bind the target molecule with a kd less than id'10. It is also preferred that the antisense molecules bind the target molecule with a kd less than 10"12. A representative sample of methods and techniques which aid in the design and use of antisense molecules can be found in the following non-limiting list of United States patents: 5,135,917, 5,294,533, 5,627,158, 5,641,754, 5,691,317, 5,780,607, 5,786,138, 5,849,903, 5,856,103, 5,919,772, 5,955,590, 5,990,088, 5,994,320, 5,998,602, 6,005,095, 6,007,995, 6,013,522, 6,017,898, 6,018,042, 6,025,198, 6,033,910, 6,040,296, 6,046,004, 6,046,319, and 6,057,437.
92. Aptamers are molecules that interact with a target molecule, preferably in a specific way. Typically aptamers are small nucleic acids ranging from 15-50 bases in length that fold into defined secondary and tertiary structures, such as stem-loops or G-quartets. Aptamers can bind small molecules, such as ATP (United States patent 5,631,146) and theophiline (United States patent 5,580,737), as well as large molecules, such as reverse transcriptase (United States patent 5,786,462) and thrombin (United States patent 5,543,293). Aptamers can bind very tightly with kas from the target molecule of less than 10"'2 M. It is preferred that the aptamers bind the target molecule with a kd less than 10"6. It is more preferred that the aptamers bind the target molecule with a kd less than 10"8. It is also more preferred that the aptamers bind the target molecule with a kj less than 10" . It is also preferred that the aptamers bind the target molecule with a k_ less than 10"12. Aptamers can bind the target molecule with a very high degree of specificity. For example, aptamers have been isolated that have greater than a 10000 fold difference in binding affinities between the target molecule and another molecule that differ at only a single position on the molecule (United States patent 5,543,293). It is preferred that the aptamer have a kd with the target molecule at least 10 fold lower than the kd with a background binding molecule. It is more preferred that the aptamer have a kd with the target molecule at least 100 fold lower than the l with a background binding molecule. It is more preferred that the aptamer have a kd with the target molecule at least 1000 fold lower than the kd with a background binding molecule. It is preferred that the aptamer have a kd with the target molecule at least 10000 fold lower than the kd with a background binding molecule. It is preferred when doing the comparison for a polypeptide for example, that the background molecule be a different polypeptide. For example, when determining the specificity of
TSGIOI aptamers, such as TSGIOI PTAP binding domain or UB binding domain aptamers, the background protein could be albumin. Representative examples of how to make and use aptamers to bind a variety of different target molecules can be found in the following non-limiting list of United States patents: 5,476,766, 5,503,978, 5,631 ,146, 5,731,424 , 5,780,228, 5,792,613, 5,795,721, 5,846,713, 5,858,660 , 5,861,254, 5,864,026, 5,869,641, 5,958,691 , 6,001,988, 6,01 1,020, 6,013,443, 6,020,130, 6,028,186, 6,030,776, and 6,051 ,698.
93. Ribozymes are nucleic acid molecules that are capable of catalyzing a chemical reaction, either intramolecularly or intermolecularly. Ribozymes are thus catalytic nucleic acid. It is preferred that the ribozymes catalyze intermolecular reactions. There are a number of different types of ribozymes that catalyze nuclease or nucleic acid polymerase type reactions which are based on ribozymes found in natural systems, such as hammerhead ribozymes, (for example, but not limited to the following United States patents: 5,334,71 1, 5,436,330, 5,616,466, 5,633,133, 5,646,020, 5,652,094, 5,712,384, 5,770,715, 5,856,463, 5,861,288, 5,891 ,683, 5,891 ,684, 5,985,621, 5,989,908, 5,998,193, 5,998,203, WO 9858058 by Ludwig and Sproat, WO 9858057 by Ludwig and Sproat, and WO 9718312 by Ludwig and Sproat) haiφin ribozymes (for example, but not limited to the following United States patents: 5,631 ,1 15, 5",646,031 , 5,683,902, 5,712,384,
5,856,188, 5,866,701 , 5,869,339, and 6,022,962), and tetrahymena ribozymes (for example, but not limited to the following United States patents: 5,595,873 and 5,652,107). There are also a number of ribozymes that are not found in natural systems, but which have been engineered to catalyze specific reactions de novo (for example, but not limited to the following United States patents: 5,580,967, 5,688,670, 5,807,718, and
5,910,408). Preferred ribozymes cleave RNA or DNA substrates, and more preferably cleave RNA substrates. Ribozymes typically cleave nucleic acid substrates through recognition and binding of the target substrate with subsequent cleavage. This recognition is often based mostly on canonical or non-canonical base pair interactions. This property makes ribozymes particularly good candidates for target specific cleavage of nucleic acids because recognition of the target substrate is based on the target substrates sequence.
Representative examples of how to make and use ribozymes to catalyze a variety of different reactions can be found in the following non-limiting list of United States patents: 5,646,042, 5,693,535, 5,731,295, 5,811,300, 5,837,855, 5,869,253, 5,877,021, 5,877,022, 5,972,699, 5,972,704, 5,989,906, and 6,017,756.
94. Triplex forming functional nucleic acid molecules are molecules that can interact with either double-stranded or single-stranded nucleic acid. When triplex molecules interact with a target region, a structure called a triplex is formed, in which there are three strands of DNA forming a complex dependant on both Watson-Crick and Hoogsteen base-pairing. Triplex molecules are preferred because they can bind target regions with high affinity and specificity. It is preferred that the triplex forming molecules bind the target molecule with a kd less than 10"6. It is more preferred that the triplex forming molecules bind with a kd less than 10"8. It is also more preferred that the triplex forming molecules bind the target molecule with a kd less than 10' . It is also preferred that the triplex forming molecules bind the target molecule with a kd less than 10"12. Representative examples of how to make and use triplex forming molecules to bind a variety of different target molecules can be found in the following non-limiting list of United States patents: 5,176,996, 5,645,985, 5,650,316, 5,683,874, 5,693,773, 5,834,185, 5,869,246, 5,874,566, and 5,962,426. 95. External guide sequences (EGSs) are molecules that bind a target nucleic acid molecule forming a complex, and this complex is recognized by RNase P, which cleaves the target molecule. EGSs can be designed to specifically target a RNA molecule of choice. RNAse P aids in processing transfer RNA (tRNA) within a cell. Bacterial RNAse P can be recruited to cleave virtually any RNA sequence by using an EGS that causes the target RNA:EGS complex to mimic the natural tRNA substrate. (WO 92/03566 by Yale, and Forster and Altman, Science 238:407-409 ( 1990)).
96. Similarly, eukaryotic EGS/RNAse P-directed cleavage of RNA can be utilized to cleave desired targets within eukaryotic cells. (Yuan et al., Proc. Natl. Acad. Sci. USA 89:8006-8010 (1992); WO 93/22434 by Yale; WO 95/24489 by Yale; Yuan and Altman, EMBO J 14: 159-168 (1995), and Carrara et al.. Proc. Natl. Acad. Sci. (USA) 92:2627-2631 (1995)). Representative examples of how to make and use EGS molecules to facilitate cleavage of a variety of different target molecules be found in the following non-limiting list of United States patents: 5,168,053, 5,624,824, 5,683,873, 5,728,521 , 5,869,248, and 5,877,162 b) Antibodies
(1) Antibodies Generally
97. The term "antibodies" is used herein in a broad sense and includes both polyclonal and monoclonal antibodies. In addition to intact immunoglobulin molecules, also included in the term "antibodies" are fragments or polymers of those immunoglobulin molecules, and human or humanized versions of immunoglobulin molecules or fragments thereof, as long as they are chosen for their ability to interact with TSGIOI such that TSGIOI is inhibited from interacting with a viral GAG protein, such as HIV or Ebola GAG. Antibodies that bind the disclosed regions of TSGIOI involved in the interaction between TSG IOI and GAG are also disclosed. The antibodies can be tested for their desired activity using the in vitro assays described herein, or by analogous methods, after which their in vivo therapeutic and/or prophylactic activities are tested according to known clinical testing methods. Also disclosed are functional equivalents of antibodies.
98. The term "monoclonal antibody" as used herein refers to an antibody obtained from a substantially homogeneous population of antibodies, i.e., the individual antibodies within the population are identical except for possible naturally occurring mutations that may be present in a small subset of the antibody molecules. The monoclonal antibodies herein specifically include "chimeric" antibodies in which a portion of the heavy and/or light chain is identical with or homologous to corresponding sequences in antibodies derived from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical with or homologous to corresponding sequences in antibodies derived from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, as long as they exhibit the desired antagonistic activity (See, U.S. Pat. No. 4,816,567 and Morrison et al., Proc. Natl. Acad. Sci. USA, 81 :6851-6855 (1984)).
99. The disclosed monoclonal antibodies can be made using any procedure which produces mono clonal antibodies. For example, monoclonal antibodies of the invention can be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256:495 ( 1975). In a hybridoma method, a mouse or other appropriate host animal is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent.
100. The monoclonal antibodies may also be made by recombinant DNA methods, such as those described in U.S. Pat. No. 4,816,567 (Cabilly et al.). DNA encoding the disclosed monoclonal antibodies can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). Libraries of antibodies or active antibody fragments can also be generated and screened using phage display techniques, e.g., as described in U.S. Patent No. 5,804,440 to Burton et al. and U.S. Patent No. 6,096,441 to Barbas et al.
101. In vitro methods are also suitable for preparing monovalent antibodies. Digestion of antibodies to produce fragments thereof, particularly, Fab fragments, can be accomplished using routine techniques known in the art. For instance, digestion can be performed using papain. Examples of papain digestion are described in WO 94/29348 published Dec. 22, 1994 and U.S. Pat. No. 4,342,566. Papain digestion of antibodies typically produces two identical antigen binding fragments, called Fab fragments, each with a single antigen binding site, and a residual Fc fragment. Pepsin treatment yields a fragment that has two antigen combining sites and is still capable of cross-linking antigen.
102. The fragments, whether attached to other sequences or not, can also include insertions, deletions, substitutions, or other selected modifications of particular regions or specific amino acids residues, provided the activity of the antibody or antibody fragment is not significantly altered or impaired compared to the non- modified antibody or antibody fragment. These modifications can provide for some additional property, such as to remove/add amino acids capable of disulfide bonding, to increase its bio-longevity, to alter its secretory characteristics, etc. In any case, the antibody or antibody fragment must possess a bioactive property, such as specific binding to its cognate antigen. Functional or active regions of the antibody or antibody fragment may be identified by mutagenesis of a specific region of the protein, followed by expression and testing of the expressed polypeptide. Such methods are readily apparent to a skilled practitioner in the art and can include site-specific mutagenesis of the nucleic acid encoding the antibody or antibody fragment. (Zoller, M.J. Curr. Opin. Biotechnol. 3:348-354, 1992). 103. As used herein, the term "antibody" or "antibodies" can also refer to a human antibody and/or a humanized antibody. Many non-human antibodies (e.g., those derived from mice, rats, or rabbits) are naturally antigenic in humans, and thus can give rise to undesirable immune responses when administered to humans. Therefore, the use of human or humanized antibodies in the methods of the invention serves to lessen the chance that an antibody administered to a human will evoke an undesirable immune response. (2) Human antibodies
104. The human antibodies of the invention can be prepared using any technique. Examples of techniques for human monoclonal antibody production include those described by Cole et al. (Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77, 1985) and by Boerner et al. (J. Immunol., 147(l):86-95, 1991). Human antibodies of the invention (and fragments thereof) can also be produced using phage display libraries (Hoogenboom et al., J. Mol. Biol., 227:381, 1991 ; Marks et al., J. Mol. Biol., 222:581, 1991).
105. The human antibodies of the invention can also be obtained from transgenic animals. For example, transgenic, mutant mice that are capable of producing a full repertoire of human antibodies, in response to immunization, have been described (see, e.g., Jakobovits et al., Proc. Natl. Acad. Sci. USA, 90:2551-255 (1993); Jakobovits et al., Nature, 362:255-258 (1993); Bruggermann et al., Year in Immunol., 7:33 (1993)). Specifically, the homozygous deletion of the antibody heavy chain joining region (3(H)) gene in these chimeric and germ-line mutant mice results in complete inhibition of endogenous antibody production, and the successful transfer of the human germ-line antibody gene array into such germ-line mutant mice results in the production of human antibodies upon antigen challenge.
(3) Humanized antibodies 106. Antibody humanization techniques generally involve the use of recombinant DNA technology to manipulate the DNA sequence encoding one or more polypeptide chains of an antibody molecule. Accordingly, a humanized form of a non-human antibody (or a fragment thereof) is a chimeric antibody or antibody chain (or a fragment thereof, such as an Fv, Fab, Fab', or other antigen-binding portion of an antibody) which contains a portion of an antigen binding site from a non-human (donor) antibody integrated into the framework of a human (recipient) antibody.
107. To generate a humanized antibody, residues from one or more complementarity deteπnining regions (CDRs) of a recipient (human) antibody molecule are replaced by residues from one or more CDRs of a donor (non-human) antibody molecule that is known to have desired antigen binding characteristics (e.g., a certain level of specificity and affinity for the target antigen). In some instances, Fv framework (FR) residues of the human antibody are replaced by corresponding non-human residues. Humanized antibodies may also contain residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies. Humanized antibodies generally contain at least a portion of an antibody constant region (Fc), typically that of a human antibody (Jones et al., Nature, 321 :522-525 (1986), Reichmann et al., Nature, 332:323-327 (1988), and Presta, Curr. Opin. Struct. Biol., 2:593-596 (1992)). 108. Methods for humanizing non-human antibodies are well known in the art. For example, humanized antibodies can be generated according to the methods of Winter and co-workers (Jones et al., Nature, 321 :522-525 (1986), Riechmann et al., Nature, 332:323-327 (1988), Verhoeyen et al., Science, 239: 1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Methods that can be used to produce humanized antibodies are also described in U.S. Patent No. 4,816,567 (Cabilly et al), U.S. Patent No. 5,565,332 (Hoogenboom et al.), U.S. Patent No. 5,721,367 (Kay et al.), U.S. Patent No. 5,837,243 (Deo et al.), U.S. Patent No. 5, 939,598 (Kucherlapati et al.), U.S. Patent No. 6,130,364 (Jakobovits et al.), and U.S. Patent No. 6,180,377 (Morgan et al.).
(4) Administration of antibodies
109. Administration of the antibodies can be done as disclosed herein, as the delivery of any non- nucleic acid composition or pharmaceutical. Nucleic acid approaches for antibody delivery also exist. The broadly neutralizing anti TSGIOI antibodies and antibody fragments of the invention can also be administered to patients or subjects as a nucleic acid preparation (e.g., DNA or RNA) that encodes the antibody or antibody fragment, such that the patient's or subject's own cells take up the nucleic acid and produce and secrete the encoded antibody or antibody fragment. The delivery of the nucleic acid can be by any means, as disclosed herein, for example. c) Compositions identified by screening with disclosed compositions / combinatorial chemistry or by using the structure information (1) Combinatorial chemistry
1 10. The disclosed compositions can be used as targets for any combinatorial technique to identify molecules or macromolecular molecules that interact with the disclosed compositions in a desired way. The nucleic acids, peptides, and related molecules disclosed herein can be used as targets for the combinatorial approaches. Also disclosed are the compositions that are identified through combinatorial techniques or screening techniques, or through computer modeling techniques, in which the compositions herein disclosed and their structural information, or portions thereof, are used as the target in a combinatorial or screening protocol, or can direct combinatorial or screening protocols
111 It is understood that when using the disclosed compositions in combinatorial techniques or screening methods, molecules, such as macromolecular molecules, will be identified that have particular desired properties such as inhibition or stimulation or the target molecule's function The molecules identified and isolated when using the disclosed compositions, such as, TSGIOI or GAG, are also disclosed Thus, the products produced using the combinatorial or screening approaches that involve the disclosed compositions, such as, TSGIOI and GAG, are also considered herein disclosed
1 12 Combinatorial chemistry includes but is not limited to all methods for isolating small molecules or macromolecules that are capable of binding either a small molecule or another macromolecule, typically in an iterative process Proteins, oligonucleotides, and sugars are examples of macromolecules For example, oligonucleotide molecules with a given function, catalytic or hgand-binding, can be isolated from a complex mixture of random oligonucleotides in what has been referred to as "in vitro genetics" (Szostak, TIBS 19 89, 1992) One synthesizes a large pool of molecules bearing random and defined sequences and subjects that complex mixture, for example, approximately l θ' individual sequences in 100 μg of a 100 nucleotide RNA, to some selection and enrichment process Through repeated cycles of affinity chromatography and PCR amplification of the molecules bound to the ligand on the column, Ellington and Szostak (1990) estimated that 1 in 101 RNA molecules folded in such a way as to bind a small molecule dyes DNA molecules with such hgand-binding behavior have been isolated as well (Ellington and Szostak, 1992, Bock et al, 1992) Techniques aimed at similar goals exist for small organic molecules, proteins, antibodies and other macromolecules known to those of skill in the art Screening sets of molecules for a desired activity whether based on small organic libraries, oligonucleotides, or antibodies is broadly referred to as combinatorial chemistry Combinatorial techniques are particularly suited for defining binding interactions between molecules and for isolating molecules that have a specific binding activity, often called aptamers when the macromolecules are nucleic acids
1 13 There are a number of methods for isolating proteins which either have de novo activity or a modified activity For example, phage display libraries have been used to isolate numerous peptides that interact with a specific target (See for example, United States Patent No 6,031,071 , 5,824,520, 5,596,079, and 5,565,332 which are herein incorporated by reference at least for their material related to phage display and methods relate to combinatorial chemistry)
1 14 A preferred method for isolating proteins that have a given function is described by Roberts and Szostak (Roberts R W and Szostak J W Proc Natl Acad Sci USA, 94(23)12997-302 (1997) This combinatorial chemistry method couples the functional power of proteins and the genetic power of nucleic acids An RNA molecule is generated in which a puromycin molecule is covalently attached to the 3 '-end of the RNA molecule An in vitro translation of this modified RNA molecule causes the correct protein, encoded by the RNA to be translated In addition, because of the attachment of the puromycin, a peptidyl acceptor which cannot be extended, the growing peptide chain is attached to the puromycin which is attached to the RNA Thus, the protein molecule is attached to the genetic material that encodes it Normal in vitro selection procedures can now be done to isolate functional peptides Once the selection procedure for peptide function is complete traditional nucleic acid manipulation procedures are performed to amplify the nucleic acid that codes for the selected functional peptides After amplification of the genetic material, new RNA is transcribed with puromycin at the 3 '-end, new peptide is translated and another functional round of selection is performed Thus, protein selection can be performed in an iterative manner just like nucleic acid selection techniques The peptide which is translated is controlled by the sequence of the RNA attached to the puromycin This sequence can be anything from a random sequence engineered for optimum translation (I e no stop codons etc ) or it can be a degenerate sequence of a known RNA molecule to look for improved or altered function of a known peptide The conditions for nucleic acid amplification and in vitro translation are well known to those of ordinary skill in the art and are preferably performed as in Roberts and Szostak (Roberts R W and Szostak J W Proc Natl Acad Sci USA, 94(23)12997-302 (1997))
115 Another preferred method for combinatorial methods designed to isolate peptides is described in Cohen et al (Cohen B A , et al , Proc Natl Acad Sci USA 95(24) 14272-7 (1998)) This method utilizes and modifies two-hybrid technology Yeast two-hybrid systems are useful for the detection and analysis of protein protein interactions The two-hybrid system, initially described in the yeast Saccharomyces cerevisiae, is a powerful molecular genetic technique for identifying new regulatory molecules, specific to the protein of interest (Fields and Song, Nature 340 245-6 (1989)) Cohen et al , modified this technology so that novel interactions between synthetic or engineered peptide sequences could be identified which bind a molecule of choice The benefit of this type of technology is that the selection is done in an intracellular environment The method utilizes a library of peptide molecules that attached to an acidic activation domain A peptide of choice, for example a portion of TSG IOI, such as the TSGIOI PTAP binding domain, is attached to a DNA binding domain of a transcriptional activation protein, such as Gal 4 By performing the two-hybrid technique on this type of system, molecules that bind the TSGIOI PTAP binding domain can be identified
1 16 Using methodology well known to those of skill in the art, in combination with various combinatorial libraries, one can isolate and characterize those small molecules or macromolecules, which bind to or interact with the desired target The relative binding affinity of these compounds can be compared and optimum compounds identified using competitive binding studies, which are well known to those of skill in the art
1 17 Techniques for making combinatorial libraries and screening combinatorial libraries to isolate molecules which bind a desired target are well known to those of skill in the art Representative techniques and methods can be found in but are not limited to United States patents 5,084,824, 5,288,514, 5,449,754, 5,506,337, 5,539,083, 5,545,568, 5,556,762, 5,565,324, 5,565,332, 5,573,905, 5,618,825, 5,619,680, 5,627,210, 5,646,285, 5,663,046, 5,670,326, 5,677,195, 5,683,899, 5,688,696, 5,688,997, 5,698,685, 5,712,146, 5,721 ,099, 5,723,598, 5,741 ,713, 5,792,431 , 5,807,683, 5,807,754, 5,821,130, 5,831,014, 5,834,195, 5,834,318, 5,834,588, 5,840,500, 5,847,150, 5,856,107, 5,856,496, 5,859,190, 5,864,010, 5,874,443, 5,877,214, 5,880,972, 5,886,126, 5,886,127, 5,891,737, 5,916,899, 5,919,955, 5,925,527, 5,939,268, 5,942,387, 5,945,070, 5,948,696, 5,958,702, 5,958,792, 5,962,337, 5,965,719, 5,972,719, 5,976,894, 5,980,704, 5,985,356, 5,999,086, 6,001 ,579, 6,004,617, 6,008,321 , 6,017,768, 6,025,371, 6,030,917, 6,040,193, 6,045,671 , 6,045,755, 6,060,596, and 6,061 ,636 118 Combinatorial libraries can be made from a wide array of molecules using a number of different synthetic techniques For example, libraries containing fused 2,4-pyπmιdιnedιones (United States patent 6,025,371) dihydrobenzopyrans (United States Patent 6,017,768and 5,821,130), amide alcohols (United States Patent 5,976,894), hydroxy-amino acid amides (United States Patent 5,972,719) carbohydrates (United States patent 5,965,719), l ,4-benzodιazepιn-2,5-dιones (United States patent 5,962,337), cyclics (United
States patent 5,958,792), biaryl amino acid amides (United States patent 5,948,696), thiophenes (United States patent 5,942,387), tπcychc Tetrahydroquinohnes (United States patent 5,925,527), benzofurans (United States patent 5,919,955), isoquinolines (United States patent 5,916,899), hydantoin and thiohydantoin (United States patent 5,859,190), indoles (United States patent 5,856,496), lmidazol-pyπdo-indole and lmidazol-pyπdo- benzothiophenes (United States patent 5,856,107) substituted 2-methylene-2, 3-dιhydrothιazoles (United
States patent 5,847,150), quinohnes (United States patent 5,840,500), PNA (United States patent 5,831,014), containing tags (United States patent 5,721 ,099), polyketides (United States patent 5,712,146), moφholino- subumts (United States patent 5,698,685 and 5,506,337), sulfamides (United States patent 5,618,825), and benzodiazepines (United States patent 5,288,514) 1 19 As used herein combinatorial methods and libraries included traditional screening methods and libraries as well as methods and libraries used in iterative processes
(2) Computer assisted design
120 The disclosed compositions can be used as targets for any molecular modeling technique to identify either the structure of the disclosed compositions or to identify potential or actual molecules, such as small molecules, which interact in a desired way with the disclosed compositions The structural information disclosed herein for any of the disclosed compositions, such as the TSG-101 PTAP binding domain and the PTAP ligand or the UB binding domain and UB, can be used in computer related analysis to design compositions which interact with either TSG-101 binding domain, the PTAP ligand, the UB binding domain, the UB or a combination Thus, the compositions disclosed herein can be used as target in computer simulations of potential ligand binding through molecular modeling The disclosed compositions and structures related to the compositions can be used to compare other structural formations comprising the compositions disclosed herein
121 It is understood that when using the disclosed compositions in modeling techniques, molecules, such as macromolecular molecules, will be identified that have particular desired properties such as inhibition or stimulation or the target molecule's function The molecules identified and isolated when using the disclosed compositions, such as, TSGIOI, GAG, the PTAP region of GAG, or the UB binding region of GAG or UB, are also disclosed Thus, the products produced using the molecular modeling approaches that involve the disclosed compositions, such as, TSGIOI, GAG, the PTAP region of GAG, or the UB binding region of GAG or UB, are also considered herein disclosed 122 Thus, one way to isolate molecules that bind a molecule of choice is through rational design
This is achieved through structural information and computer modeling Computer modeling technology allows visualization of the three-dimensional atomic structure of a selected molecule and the rational design of new compounds that will interact with the molecule The three-dimensional construct typically depends on data from x-ray crystallographic analyses or NMR imaging of the selected molecule The molecular dynamics require force field data The computer graphics systems enable prediction of how a new compound will link to the target molecule and allow experimental manipulation of the structures of the compound and target molecule to perfect binding specificity Prediction of what the molecule-compound interaction will be when small changes are made in one or both requires molecular mechanics software and computationally intensive computers, usually coupled with user-friendly, menu-driven interfaces between the molecular design program and the user
123 Examples of molecular modeling systems are the CHARMm and QUANTA programs, Polygen Coφoratton, Waltham, MA CHARMm performs the energy minimization and molecular dynamics functions QUANTA performs the construction, graphic modeling and analysis of molecular structure QUANTA allows interactive construction, modification, visualization, and analysis of the behavior of molecules with each other
124 A number of articles review computer modeling of drugs interactive with specific proteins, such as Rotivinen, et al , 1988 Acta Pharmaceutica Fennica 97, 159-166, Ripka, New Scientist 54-57 (June 16, 1988), McKinaly and Rossmann, 1989 Annu Rev Pharmacol Toxiciol 29, 1 1 1-122, Perry and Davies, OSAR Quantitative Structure-Activity Relationships in Drug Design pp 189-193 (Alan R Liss, Inc 1989), Lewis and Dean, 1989 Proc R Soc Lond 236, 125-140 and 141-162, and, with respect to a model enzyme for nucleic acid components, Askew, et al , 1989 J Am Chem Soc 111, 1082-1090 Other computer programs that screen and graphically depict chemicals are available from companies such as BioDesign, Inc , Pasadena, CA , Allelix, Inc, Mississauga, Ontario, Canada, and Hypercube, Inc , Cambridge, Ontario Although these are primarily designed for application to drugs specific to particular proteins
125 Although described above with reference to design and generation of compounds which could alter binding, one could also screen libraries of known compounds, including natural products or synthetic chemicals, and biologically active materials, including proteins, for compounds which alter substrate binding or enzymatic activity 4. Computer readable mediums
126 It is understood that the disclosed nucleic acids and proteins can be represented as a sequence consisting of the nucleotides of amino acids There are a variety of ways to display these sequences, for example the nucleotide guanosine can be represented by G or g Likewise the amino acid valine can be represented by Val or V Those of skill in the art understand how to display and express any nucleic acid or protein sequence in any of the variety of ways that exist, each of which is considered herein disclosed
Specifically contemplated herein is the display of these sequences on computer readable mediums, such as, commercially available floppy disks, tapes, chips, hard drives, compact disks, and video disks, or other computer readable mediums Also disclosed are the binary code representations of the disclosed sequences Those of skill in the art understand what computer readable mediums Thus, computer readable mediums on which the nucleic acids or protein sequences are recorded, stored, or saved
127 Disclosed are computer readable mediums comprising the sequences and information regarding the sequences set forth herein Also disclosed are computer readable mediums comprising the structural coordinates or a subset of the structure coordinates disclosed in Table 5-47 These coordinates can be displayed in a variety of ways 5. General composition information a) Sequence similarities
128. It is understood that as discussed herein the use of the terms homology and identity mean the same thing as similarity. Thus, for example, if the use of the word homology is used between two non-natural sequences it is understood that this is not necessarily indicating an evolutionary relationship between these two sequences, but rather is looking at the similarity or relatedness between their nucleic acid sequences. Many of the methods for determining homology between two evolutionarily related molecules are routinely applied to any two or more nucleic acids or proteins for the puφose of measuring sequence similarity regardless of whether they are evolutionarily related or not. 129. SEQ ID NO: l represents a truncated version of TSTG101 called TSGIOI UEV. It is understood that the numbering of the amino acids discussed herein is in reference to SEQ ID NO: l when discussing TSGIOI UEV, but that full length TSGIOI also has analogous amino acids and that for example, amino acid Y63 has an analogous amino acid in the full length molecule and can easily be determined for the information contained herein and known. All fragments of both TSG101-URV and TSGIOI are considered disclosed. 130. In general, it is understood that one way to define any known variants and derivatives or those that might arise, of the disclosed genes and proteins herein, is through defining the variants and derivatives in terms of homology to specific known sequences. This identity of particular sequences disclosed herein is also discussed elsewhere herein. In general, variants of genes and proteins herein disclosed typically have at least, about 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85, 86, 87, 88, 89, 90, 91 , 92, 93, 94, 95, 96, 97, 98, or 99 percent homology to the stated sequence or the native sequence. Those of skill in the art readily understand how to determine the homology of two proteins or nucleic acids, such as genes. For example, the homology can be calculated after aligning the two sequences so that the homology is at its highest level. 131. Another way of calculating homology can be performed by published algorithms. Optimal alignment of sequences for comparison may be conducted by the local homology algorithm of Smith and Waterman Adv. Appl. Math. 2: 482 (1981), by the homology alignment algorithm of Needleman and Wunsch, J. MoL Biol. 48: 443 (1970), by the search for similarity method of Pearson and Lipman, Proc. Natl. Acad. Sci. U.S.A. 85: 2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by inspection. 132. The same types of homology can be obtained for nucleic acids by for example the algorithms disclosed in Zuker, M. Science 244:48-52, 1989, Jaeger et al. Proc. Natl. Acad. Sci. USA 86:7706-7710, 1989, Jaeger et al. Methods Enzymol. 183:281 -306, 1989 which are herein incoφorated by reference for at least material related to nucleic acid alignment. It is understood that any of the methods typically can be used and that in certain instances the results of these various methods may differ, but the skilled artisan understands if identity is found with at least one of these methods, the sequences would be said to have the stated identity, and be disclosed herein.
133. For example, as used herein, a sequence recited as having a particular percent homology to another sequence refers to sequences that have the recited homology as calculated by any one or more of the calculation methods described above. For example, a first sequence has 80 percent homology, as defined herein, to a second sequence if the first sequence is calculated to have 80 percent homology to the second sequence using the Zuker calculation method even if the first sequence does not have 80 percent homology to the second sequence as calculated by any of the other calculation methods As another example, a first sequence has 80 percent homology, as defined herein, to a second sequence if the first sequence is calculated to have 80 percent homology to the second sequence using both the Zuker calculation method and the Pearson and Lipman calculation method even if the first sequence does not have 80 percent homology to the second sequence as calculated by the Smith and Waterman calculation method, the Needleman and Wunsch calculation method, the Jaeger calculation methods, or any of the other calculation methods As yet another example, a first sequence has 80 percent homology, as defined herein, to a second sequence if the first sequence is calculated to have 80 percent homology to the second sequence using each of calculation methods
(although, in practice, the different calculation methods will often result in different calculated homology percentages) b) Hybridization
134 The term hybridization typically means a sequence driven interaction between at least two nucleic acid molecules, such as a primer or a probe and a gene Sequence driven interaction means an interaction that occurs between two nucleotides or nucleotide analogs or nucleotide derivatives in a nucleotide specific manner For example, G interacting with C or A interacting with T are sequence driven interactions Typically sequence driven interactions occur on the Watson-Crick face or Hoogsteen face of the nucleotide The hybridization of two nucleic acids is affected by a number of conditions and parameters known to those of skill in the art For example, the salt concentrations, pH, and temperature of the reaction all affect whether two nucleic acid molecules will hybridize
135 Parameters for selective hybridization between two nucleic acid molecules are well known to those of skill in the art For example, in some embodiments selective hybridization conditions can be defined as stringent hybridization conditions For example, stringency of hybridization is controlled by both temperature and salt concentration of either or both of the hybridization and washing steps For example, the conditions of hybridization to achieve selective hybridization may involve hybridization in high ionic strength solution (6X SSC or 6X SSPE) at a temperature that is about 12-25°C below the Tm (the melting temperature at which half of the molecules dissociate from their hybridization partners) followed by washing at a combination of temperature and salt concentration chosen so that the washing temperature is about 5°C to 20°C below the Tm The temperature and salt conditions are readily determined empirically in preliminary experiments in which samples of reference DNA immobilized on filters are hybridized to a labeled nucleic acid of interest and then washed under conditions of different stringencies Hybridization temperatures are typically higher for DNA-RNA and RNA-RNA hybridizations The conditions can be used as described above to achieve stringency, or as is known in the art (Sambrook et al , Molecular Cloning A Laboratory Manual, 2nd Ed , Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1989, Kunkel et al
Methods Enzymol 1987 154 367, 1987 which is herein incoφorated by reference for material at least related to hybridization of nucleic acids) A preferable stringent hybridization condition for a DNA DNA hybridization can be at about 68°C (in aqueous solution) in 6X SSC or 6X SSPE followed by washing at 68°C Stringency of hybridization and washing, if desired, can be reduced accordingly as the degree of _ . , . complementarity desired is decreased, and further, depending upon the G-C or A-T richness of any area wherein variability is searched for Likewise, stringency of hybridization and washing, if desired, can be increased accordingly as homology desired is increased, and further, depending upon the G-C or A-T richness of any area wherein high homology is desired, all as known in the art 136 Another way to define selective hybridization is by looking at the amount (percentage) of one of the nucleic acids bound to the other nucleic acid For example, in some embodiments selective hybridization conditions would be when at least about, 60, 65, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81 , 82, 83, 84, 85,
86, 87, 88, 89, 90, 91 , 92, 93, 94, 95, 96, 97, 98, 99, 100 percent of the limiting nucleic acid is bound to the non-limiting nucleic acid Typically, the non-limiting primer is in for example, 10 or 100 or 1000 fold excess This type of assay can be performed at under conditions where both the limiting and non-limiting primer are for example, 10 fold or 100 fold or 1000 fold below their kd, or where only one of the nucleic acid molecules is 10 fold or 100 fold or 1000 fold or where one or both nucleic acid molecules are above their kd
137 Another way to define selective hybridization is by looking at the percentage of primer that gets enzymatically manipulated under conditions where hybridization is required to promote the desired enzymatic manipulation For example, in some embodiments selective hybridization conditions would be when at least about, 60, 65, 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 percent of the primer is enzymatically manipulated under conditions which promote the enzymatic manipulation, for example if the enzymatic manipulation is DNA extension, then selective hybridization conditions would be when at least about 60, 65, 70, 71 , 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91 , 92, 93, 94, 95, 96, 97, 98, 99, 100 percent of the primer molecules are extended Preferred conditions also include those suggested by the manufacturer or indicated in the art as being appropriate for the enzyme performing the manipulation
138 Just as with homology, it is understood that there are a variety of methods herein disclosed for determining the level of hybridization between two nucleic acid molecules It is understood that these methods and conditions may provide different percentages of hybridization between two nucleic acid molecules, but unless otherwise indicated meeting the parameters of any of the methods would be sufficient For example if 80% hybridization was required and as long as hybridization occurs within the required parameters in any one of these methods it is considered disclosed herein
139 It is understood that those of skill in the art understand that if a composition or method meets any one of these criteria for determining hybridization either collectively or singly it is a composition or method that is disclosed herein c) Nucleic acids
140 There are a variety of molecules disclosed herein that are nucleic acid based, including for example the nucleic acids that encode, for example TSGIOI, as well as various functional nucleic acids The disclosed nucleic acids are made up of, for example, nucleotides, nucleotide analogs, or nucleotide substitutes Non-limiting examples of these and other molecules are discussed herein It is understood that for example, when a vector is expressed in a cell, that the expressed mRNA will typically be made up of A, C, G, and U Likewise, it is understood that if, for example, an antisense molecule is introduced into a cell or cell environment through for example exogenous delivery, it is advantagous that the antisense molecule be made up of nucleotide analogs that reduce the degradation of the antisense molecule in the cellular environment.
(1) Nucleotides and related molecules
141. A nucleotide is a molecule that contains a base moiety, a sugar moiety and a phosphate moiety. Nucleotides can be linked together through their phosphate moieties and sugar moieties creating an internucleoside linkage. The base moiety of a nucleotide can be adenin-9-yl (A), cytosin-1-yl (C), guanin-9-yl (G), uracil-1-yl (U), and thymin-1 -yl (T). The sugar moiety of a nucleotide is a ribose or a deoxyribose. The phosphate moiety of a nucleotide is pentavalent phosphate. An non-limiting example of a nucleotide would be 3'-AMP (3'-adenosine monophosphate) or 5'-GMP (5'-guanosine monophosphate). 142. A nucleotide analog is a nucleotide which contains some type of modification to either the base, sugar, or phosphate moieties. Modifications to nucleotides are well known in the art and would include for example, 5-methylcytosine (5-me-C), 5-hydroxymethyl cytosine, xanthine, hypoxanthine, and 2-aminoadenine as well as modifications at the sugar or phosphate moieties.
143. Nucleotide substitutes are molecules having similar functional properties to nucleotides, but which do not contain a phosphate moiety, such as peptide nucleic acid (PNA). Nucleotide substitutes are molecules that will recognize nucleic acids in a Watson-Crick or Hoogsteen manner, but which are linked together through a moiety other than a phosphate moiety. Nucleotide substitutes are able to conform to a double helix type structure when interacting with the appropriate target nucleic acid.
144. It is also possible to link other types of molecules (conjugates) to nucleotides or nucleotide analogs to enhance for example, cellular uptake. Conjugates can be chemically linked to the nucleotide or nucleotide analogs. Such conjugates include but are not limited to lipid moieties such as a cholesterol moiety. (Letsinger et al., Proc. Natl. Acad. Sci. USA, 1989,86, 6553-6556),
145. A Watson-Crick interaction is at least one interaction with the Watson-Crick face of a nucleotide, nucleotide analog, or nucleotide substitute. The Watson-Crick face of a nucleotide, nucleotide analog, or nucleotide substitute includes the C2, NI , and C6 positions of a purine based nucleotide, nucleotide analog, or nucleotide substitute and the C2, N3, C4 positions of a pyrimidine based nucleotide, nucleotide analog, or nucleotide substitute.
146. A Hoogsteen interaction is the interaction that takes place on the Hoogsteen face of a nucleotide or nucleotide analog, which is exposed in the major groove of duplex DNA. The Hoogsteen face includes the N7 position and reactive groups (NH2 or O) at the C6 position of purine nucleotides.
(2) Sequences
147. There are a variety of sequences related to the TSGIOI gene having the following Genbank Accession Numbers and these sequences and others are herein incoφorated by reference in their entireties as well as for individual subsequences contained therein. 148. There are many sequences of TSGIOI which can be found for example in Genbank Accession
Nos: Q99816, Q61 187 NP_006283, NP_057292, NP_068684 all of which are herein incoφorated by reference. It is understood that the description related to this sequence is applicable to any sequence related to TSGIOI or retroviral GAG, for example, unless specifically indicated otherwise. Those of skill in the art understand how to resolve sequence discrepancies and differences and to adjust the compositions and methods relating to a particular sequence to other related sequences (1 e sequences of TSGIOI) Primers and/or probes can be designed for any TSGIOI sequence given the information disclosed herein and known in the art
(3) Primers and probes
149 Disclosed are compositions including primers and probes, which are capable of interacting with the TSGIOI gene or GAG as disclosed herein In certain embodiments the primers are used to support DNA amplification reactions Typically the primers will be capable of being extended in a sequence specific manner Extension of a primer in a sequence specific manner includes any methods wherein the sequence and/or composition of the nucleic acid molecule to which the primer is hybridized or otherwise associated directs or influences the composition or sequence of the product produced by the extension of the primer Extension of the primer in a sequence specific manner therefore includes, but is not limited to, PCR, DNA sequencing, DNA extension, DNA polymerization, RNA transcription, or reverse transcription Techniques and conditions that amplify the primer in a sequence specific manner are preferred In certain embodiments the primers are used for the DNA amplification reactions, such as PCR or direct sequencing It is understood that in certain embodiments the primers can also be extended using non-enzymatic techniques, where for example, the nucleotides or oligonucleotides used to extend the primer are modified such that they will chemically react to extend the primer in a sequence specific manner Typically the disclosed primers hybridize with the TSGIOI nucleic acid or region of the TSGIOI nucleic acid or they hybridize with the complement of the TSGIOI nucleic acid or complement of a region of the TSGIOI nucleic acid d) Delivery of the compositions to cells (1) Nucleic Acid Delivery
150 There are a number of compositions and methods which can be used to deliver nucleic acids to cells, either in vitro or in vivo These methods and compositions can largely be broken down into two classes viral based delivery systems and non-viral based delivery systems For example, the nucleic acids can be delivered through a number of direct delivery systems such as, electroporation, hpofection, calcium phosphate precipitation, plasmids, viral vectors, viral nucleic acids, phage nucleic acids, phages, cosmids, or via transfer of genetic material in cells or carriers such as cationic liposomes Appropriate means for transfection, including viral vectors, chemical transfectants, or phystco-mechanical methods such as electroporation and direct diffusion of DNA, are described by, for example, Wolff, J A , et al , Science, 247, 1465-1468, (1990), and Wolff, J A Nature, 352, 815-818, (1991 ) Such methods are well known in the art and readily adaptable for use with the compositions and methods described herein In certain cases, the methods will be modified to specifically function with large DNA molecules Further, these methods can be used to target certain diseases and cell populations by using the targeting characteristics of the carrier
151 In the methods described herein, which include the administration and uptake of exogenous DNA into the cells of a subject (I e , gene transduction or transfection), the nucleic acids of the present invention can be in the form of naked DNA or RNA, or the nucleic acids can be in a vector for delivering the nucleic acids to the cells, whereby the encoding DNA or DNA or fragment is under the transcriptional regulation of a promoter, as would be well understood by one of ordinary skill in the art as well as enhancers The vector can be a commercially available preparation, such as an adenovirus vector (Quantum Biotechnologies, Inc (Laval, Quebec, Canada) 152 As one example, vector delivery can be via a viral system, such as a retroviral vector system which can package a recombinant retroviral genome (see e g , Pastan et al , Proc Natl Acad Sci USA 85 4486, 1988, Miller et al , Mol Cell Biol 6 2895, 1986) The recombinant retrovirus can then be used to infect and thereby deliver to the infected cells nucleic acid encoding a broadly neutralizing antibody (or active fragment thereof) of the invention The exact method of introducing the altered nucleic acid into mammalian cells is, of course, not limited to the use of retroviral vectors Other techniques are widely available for this procedure including the use of adenoviral vectors (Mitani et al , Hum Gene Ther 5 941-948, 1994), adeno- associated viral (AAV) vectors (Goodman et al , Blood 84 1492-1500, 1994), lenti viral vectors (Naidtni et al , Science 272 263-267, 1996), pseudotyped retroviral vectors (Agrawal et al , Exper Hematol 24 738-747, 1996) Physical transduction techniques can also be used, such as liposome delivery and receptor-mediated and other endocytosis mechanisms (see, for example, Schwartzenberger et al , Blood 87 472-478, 1996) This invention can be used in conjunction with any of these or other commonly used gene transfer methods
153 As one example, if the antibody-encoding nucleic acid or some other nucleic acid encoding an inhibitor of the TSG101-GAG interactions of the invention is delivered to the cells of a subject in an adenovirus vector, the dosage for administration of adenovirus to humans can range from about 10 to 10 plaque forming units (pfu) per injection but can be as high as 1012 pfu per injection (Crystal, Hum Gene Ther 8 985-1001 , 1997, Alvarez and Cuπel, Hum Gene Ther 8 597-613, 1997) A subject can receive a single injection, or, if additional injections are necessary, they can be repeated at six month intervals (or other appropriate time intervals, as determined by the skilled practitioner) for an indefinite period and/or until the efficacy of the treatment has been established
154 Parenteral administration of the nucleic acid or vector of the present invention, if used, is generally characterized by injection Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution of suspension in liquid prior to injection, or as emulsions A more recently revised approach for parenteral administration involves use of a slow release or sustained release system such that a constant dosage is maintained See, e g , U S Patent No 3,610,795, which is incoφorated by reference herein For additional discussion of suitable formulations and various routes of administration of therapeutic compounds, see, e g , Remington The Science and Practice of Pharmacy (19th ed ) ed A R Gennaro, Mack Publishing Company, Easton, PA 1995
155 Nucleic acids that are delivered to cells which are to be integrated into the host cell genome, typically contain integration sequences These sequences are often viral related sequences, particularly when viral based systems are used These viral integration systems can also be incoφorated into nucleic acids which are to be delivered using a non-nucleic acid based system of deliver, such as a liposome, so that the nucleic acid contained in the delivery system can be come integrated into the host genome
156 Other general techniques for integration into the host genome include, for example, systems designed to promote homologous recombination with the host genome These systems typically rely on sequence flanking the nucleic acid to be expressed that has enough homology with a target sequence within the host cell genome that recombination between the vector nucleic acid and the target nucleic acid takes place, causing the delivered nucleic acid to be integrated into the host genome These systems and the methods necessary to promote homologous recombination are known to those of skill in the art (2) Non-nucleic acid based systems
157. The disclosed compositions can be delivered to the target cells in a variety of ways. For example, the compositions can be delivered through electroporation, or through lipofection, or through calcium phosphate precipitation. The delivery mechanism chosen will depend in part on the type of cell targeted and whether the delivery is occurring for example in vivo or in vitro.
158. Thus, the compositions can comprise, in addition to the disclosed compositions or vectors for example, lipids such as liposomes, such as cationic liposomes (e.g., DOTMA, DOPE, DC-cholesterol) or anionic liposomes. Liposomes can further comprise proteins to facilitate targeting a particular cell, if desired. Administration of a composition comprising a compound and a cationic liposome can be administered to the blood afferent to a target organ or inhaled into the respiratory tract to target cells of the respiratory tract. Regarding liposomes, see, e.g., Brigham et al. Am. J. Resp. Cell. Mol. Biol. 1 :95-100 (1989); Feigner et al. Proc. Natl. Acad. Sci USA 84:7413-7417 (1987); U.S. Pat. No.4,897,355. Furthermore, the compound can be administered as a component of a microcapsule that can be targeted to specific cell types, such as macrophages, or where the diffusion of the compound or delivery of the compound from the microcapsule is designed for a specific rate or dosage.
159. In the methods described above which include the administration and uptake of exogenous DNA into the cells of a subject (i.e., gene transduction or transfection), delivery of the compositions to cells can be via a variety of mechanisms. As one example, delivery can be via a liposome, using commercially available liposome preparations such as LIPOFECTIN, LIPOFECT AMINE (GIBCO-BRL, Inc, Gaithersburg, MD), SUPERFECT (Qiagen, Inc. Hilden, Germany) and TRANSFECTAM (Promega Biotec, Inc, Madison, WI), as well as other liposomes developed according to procedures standard in the art. In addition, the nucleic acid or vector of this invention can be delivered in vivo by electroporation, the technology for which is available from Genetronics, Inc. (San Diego, CA) as well as by means of a SONOPORATION machine (ImaRx Pharmaceutical Coφ, Tucson, AZ). 160. The materials may be in solution, suspension (for example, incoφorated into microparticles, liposomes, or cells). These may be targeted to a particular cell type via antibodies, receptors, or receptor ligands. The following references are examples of the use of this technology to target specific proteins to tumor tissue (Senter, et al, Bioconiugate Chem.. 2:447-451 , (1991); Bagshawe, K.D, Br. J. Cancer. 60:275-281, (1989); Bagshawe, et al, Br. J. Cancer. 58:700-703, (1988); Senter, et al, Bioconiugate Chem.. 4:3-9, (1993); Battelli, et al. Cancer Immunol. Immunother.. 35:421-425, (1992); Pietersz and McKenzie, Immunolog. Reviews. 129:57-80, (1992); and Roffler, et al, Biochem. Pharmacol. 42:2062-2065, (1991)). These techniques can be used for a variety of other specific cell types. Vehicles such as "stealth" and other antibody conjugated liposomes (including lipid mediated drug targeting to colonic carcinoma), receptor mediated targeting of DNA through cell specific ligands, lymphocyte directed tumor targeting, and highly specific therapeutic retroviral targeting of murine glioma cells in vivo. The following references are examples of the use of this technology to target specific proteins to tumor tissue (Hughes et al. Cancer Research. 49:6214-6220, ( 1989); and Litzinger and Huang, Biochimica et Biophvsica Acta. 1 104: 179- 187, (1992)). In general, receptors are involved in pathways of endocytosis, either constitutive or ligand induced. These receptors cluster in clathrin-coated pits, enter the cell via clathrin-coated vesicles, pass through an acidified endosome in which the receptors are sorted, and then either recycle to the cell surface, become stored intracellularly, or are degraded in lysosomes. The intemalization pathways serve a variety of functions, such as nutrient uptake, removal of activated proteins, clearance of macromolecules, opportunistic entry of viruses and toxins, dissociation and degradation of ligand, and receptor-level regulation. Many receptors follow more than one intracellular pathway, depending on the cell type, receptor concentration, type of ligand, ligand valency, and ligand concentration. Molecular and cellular mechanisms of receptor-mediated endocytosis has been reviewed (Brown and Greene, DNA and Cell Biology 10:6, 399-409 (1991)).
(3) In vivo/ex vivo
161. As described above, the compositions can be administered in a pharmaceutically acceptable carrier and can be delivered to the subjects cells in vivo and/or ex vivo by a variety of mechanisms well known in the art (e.g., uptake of naked DNA, liposome fusion, intramuscular injection of DNA via a gene gun, endocytosis and the like).
162. If e vivo methods are employed, cells or tissues can be removed and maintained outside the body according to standard protocols well known in the art. The compositions can be introduced into the cells via any gene transfer mechanism, such as, for example, calcium phosphate mediated gene delivery, electroporation, microinjection or proteoliposomes. The transduced cells can then be infused (e.g., in a pharmaceutically acceptable carrier) or homotopically transplanted back into the subject per standard methods for the cell or tissue type. Standard methods are known for transplantation or infusion of various cells into a subject. e) Expression systems
163. The nucleic acids that are delivered to cells typically contain expression controlling systems. For example, the inserted genes in viral and retroviral systems usually contain promoters, and/or enhancers to help control the expression of the desired gene product. A promoter is generally a sequence or sequences of DNA that function when in a relatively fixed location in regard to the transcription start site. A promoter contains core elements required for basic interaction of RNA polymerase and transcription factors, and may contain upstream elements and response elements.
(1) Viral Promoters and Enhancers
164. Preferred promoters controlling transcription from vectors in mammalian host cells may be obtained from various sources, for example, the genomes of viruses such as: polyoma, Simian Virus 40 (SV40), adenovirus, retroviruses, hepatitis-B virus and most preferably cytomegalovirus, or from heterologous mammalian promoters, e.g. beta actin promoter. The early and late promoters of the SV40 virus are conveniently obtained as an SV40 restriction fragment which also contains the SV40 viral origin of replication (Fiers et al. Nature. 273: 1 13 (1978)). The immediate early promoter of the human cytomegalovirus is conveniently obtained as a Hindlll E restriction fragment (Greenway, P.J. et al. Gene 18: 355-360 (1982)). Of course, promoters from the host cell or related species also are useful herein.
165. Enhancer generally refers to a sequence of DNA that functions at no fixed distance from the transcription start site and can be either 5' (Laimins, L. et al, Proc. Natl. Acad. Sci. 78: 993 (1981)) or 3' (Lusky, M.L, et al, Mol. Cell Bio. 3: 1 108 (1983)) to the transcription unit. Furthermore, enhancers can be within an intron (Banerji, J.L. et al. Cell 33: 729 (1983)) as well as within the coding sequence itself (Osborne, T F , et al , Mol Cell Bio 4 1293 (1984)) They are usually between lO and 300 bp in length, and they function in cis Enhancers f unction to increase transcription from nearby promoters Enhancers also often contain response elements that mediate the regulation of transcription Promoters can also contain response elements that mediate the regulation of transcription Enhancers often determine the regulation of expression of a gene While many enhancer sequences are now known from mammalian genes (globin, elastase, albumin, -fetoprotein and insulin), typically one will use an enhancer from a eukaryotic cell virus for general expression Examples are the SV40 enhancer on the late side of the replication origin (bp 100-270), the cytomegalovirus early promoter enhancer, the polyoma enhancer on the late side of the replication origin, and adenovirus enhancers 166 The promotor and/or enhancer may be specifically activated either by light or specific chemical events which trigger their function Systems can be regulated by reagents such as tetracycline and dexamethasone There are also ways to enhance viral vector gene expression by exposure to irradiation, such as gamma irradiation, or alkylating chemotherapy drugs
167 In certain embodiments the promoter and/or enhancer region can act as a constitutive promoter and/or enhancer to maximize expression of the region of the transcription unit to be transcribed In certain constructs the promoter and/or enhancer region be active in all eukaryotic cell types, even if it is only expressed in a particular type of cell at a particular time A preferred promoter of this type is the CMV promoter (650 bases) Other preferred promoters are SV40 promoters, cytomegalovirus (full length promoter), and retroviral vector LTF 168 It has been shown that all specific regulatory elements can be cloned and used to construct expression vectors that are selectively expressed in specific cell types such as melanoma cells The ghal fibπllary acetic protein (GFAP) promoter has been used to selectively express genes in cells of ghal origin 169 Expression vectors used in eukaryotic host cells (yeast, fungi, insect, plant, animal, human or nucleated cells) may also contain sequences necessary for the termination of transcription which may affect mRNA expression These regions are transcribed as polyadenylated segments in the untranslated portion of the mRNA encoding tissue factor protein The 3' untranslated regions also include transcription termination sites It is preferred that the transcription unit also contain a polyadenylation region One benefit of this region is that it increases the likelihood that the transcribed unit will be processed and transported like mRNA The identification and use of polyadenylation signals in expression constructs is well established It is preferred that homologous polyadenylation signals be used in the transgene constructs In certain transcription units, the polyadenylation region is derived from the SV40 early polyadenylation signal and consists of about 400 bases It is also preferred that the transcribed units contain 'other standard sequences alone or in combination with the above sequences improve expression from, or stability of, the construct
(2) Markers 170 The vectors can include nucleic acid sequence encoding a marker product This marker product is used to determine if the gene has been delivered to the cell and once delivered is being expressed Preferred marker genes are the E Coli lacZ gene, which encodes β-galactosidase, and green fluorescent protein
171 In some embodiments the marker may be a selectable marker Examples of suitable selectable markers for mammalian cells are dihydrofolate reductase (DHFR), thymidine kinase, neomycin, neomycin analog G418, hydromycin, and puromycin When such selectable markers are successfully transferred into a mammalian host cell, the transformed mammalian host cell can survive if placed under selective pressure There are two widely used distinct categories of selective regimes The first category is based on a cell's metabolism and the use of a mutant cell line which lacks the ability to grow independent of a supplemented media Two examples are CHO DHFR- cells and mouse LTK- cells These cells lack the ability to grow without the addition of such nutrients as thymidine or hypoxanthine Because these cells lack certain genes necessary for a complete nucleotide synthesis pathway, they cannot survive unless the missing nucleotides are provided in a supplemented media An alternative to supplementing the media is to introduce an intact DHFR or TK gene into cells lacking the respective genes, thus altering their growth requirements Individual cells which were not transformed with the DHFR or TK gene will not be capable of survival in non-supplemented media
172 The second category is dominant selection which refers to a selection scheme used in any cell type and does not require the use of a mutant cell line These schemes typically use a drug to arrest growth of a host cell Those cells which have a novel gene would express a protein conveying drug resistance and would survive the selection Examples of such dominant selection use the drugs neomycin, (Southern P and Berg, P . J Molec Appl Genet 1 327 (1982)), mycophenoltc acid, (Mulligan, R C and Berg, P Science 209 1422 ( 1980)) or hygro ycin, (Sugden, B et al , Mol Cell Biol 5 410-413 (1985)) The three examples employ bacterial genes under eukaryotic control to convey resistance to the appropriate drug G418 or neomycin (geneticin), xgpt (mycophenolic acid) or hygromycin, respectively Others include the neomycin analog G418 and puromycin f) Peptides
(1) Protein variants
173 As discussed herein there are numerous variants of the TSGIOI protein and GAG protein that are known and herein contemplated In addition, to the known functional TSGIOI and GAG strain variants there are derivatives of the TSGIOI and GAG proteins which also function in the disclosed methods and compositions Protein variants and derivatives are well understood to those of skill in the art and in can involve amino acid sequence modifications For example, amino acid sequence modifications typically fall into one or more of three classes substituttonal, insertional or deletional variants Insertions include amino and/or carboxyl terminal fusions as well as intrasequence insertions of single or multiple amino acid residues Insertions ordinarily will be smaller insertions than those of amino or carboxyl terminal fusions, for example, on the order of one to four residues Immunogenic fusion protein derivatives, such as those described in the examples, are made by fusing a polypeptide sufficiently large to confer immunogenicity to the target sequence by cross-linking in vitro or by recombinant cell culture transformed with DNA encoding the fusion Deletions are characterized by the removal of one or more amino acid residues from the protein sequence Typically, no more than about from 2 to 6 residues are deleted at any one site within the protein molecule These variants ordinarily are prepared by site specific mutagenesis of nucleotides in the DNA encoding the protein, thereby producing DNA encoding the variant, and thereafter expressing the DNA in recombinant cell culture Techniques for making substitution mutations at predetermined sites in DNA having a known sequence are well known, for example Ml 3 primer mutagenesis and PCR mutagenesis Amino acid substitutions are typically of single residues, but can occur at a number of different locations at once; insertions usually will be on the order of about from 1 to 10 amino acid residues; and deletions will range about from 1 to 30 residues. Deletions or insertions preferably are made in adjacent pairs, i.e. a deletion of 2 residues or insertion of 2 residues. Substitutions, deletions, insertions or any combination thereof may be combined to arrive at a final construct. The mutations must not place the sequence out of reading frame and preferably will not create complementary regions that could produce secondary mRNA structure. Substitutional variants are those in which at least one residue has been removed and a different residue inserted in its place. Such substitutions generally are made in accordance with the following Tables 1 and 2 and are referred to as conservative substitutions.
174. TABLE 1 : Amino Acid Abbreviations
Figure imgf000039_0001
Table 2.
Original Residue Exemplary Conservative Substitutions, others are known in the art.
Ala ser
Arg lys, gin Asn gin; his
Asp glu
Cys ser
Gin asn, lys
Glu asp Gly pro
His asn;gln
He leu; val
Leu ile; val
Lys arg; gin; Met Leu; ile
Phe met; leu; tyr
Ser thr
Thr ser
Tφ tyr Tyr tφ; phe Val ile; leu
175. Substantial changes in function or immunological identity are made by selecting substitutions that are less conservative than those in Table 2, i.e., selecting residues that differ more significantly in their effect on maintaining (a) the structure of the polypeptide backbone in the area of the substitution, for example as a sheet or helical conformation, (b) the charge or hydrophobicity of the molecule at the target site or (c) the bulk of the side chain. The substitutions which in general are expected to produce the greatest changes in the protein properties will be those in which (a) a hydrophilic residue, e.g. seryl or threonyl, is substituted for (or by) a hydrophobic residue, e.g. leucyl, isoleucyl, phenylalanyl, valyl or alanyl; (b) a cysteine or proline is substituted for (or by) any other residue; (c) a residue having an electropositive side chain, e.g., lysyl, arginyl, or histidyl, is substituted for (or by) an electronegative residue, e.g., glutamyl or aspartyl; or (d) a residue having a bulky side chain, e.g., phenylalanine, is substituted for (or by) one not having a side chain, e.g., glycine, in this case, (e) by increasing the number of sites for sulfation and/or glycosylation.
176. For example, the replacement of one amino acid residue with another that is biologically and/or chemically similar is known to those skilled in the art as a conservative substitution. For example, a conservative substitution would be replacing one hydrophobic residue for another, or one polar residue for another. The substitutions include combinations such as, for example, Gly, Ala; Val, Ile, Leu; Asp, Glu; Asn, Gin; Ser, Thr; Lys, Arg; and Phe, Tyr. Such conservatively substituted variations of each explicitly disclosed sequence are included within the mosaic polypeptides provided herein. 177. Substitutional or deletional mutagenesis can be employed to insert sites for N-glycosylation
(Asn-X-Thr/Ser) or O-glycosylation (Ser or Thr). Deletions of cysteine or other labile residues also may be desirable. Deletions or substitutions of potential proteolysis sites, e.g. Arg, is accomplished for example by deleting one of the basic residues or substituting one by glutaminyl or histidyl residues.
178. Certain post-translational derivatizations are the result of the action of recombinant host cells on the expressed polypeptide. Glutaminyl and asparaginyl residues are frequently post-translational ly deamidated to the corresponding glutamyl and asparyl residues. Alternatively, these residues are deamidated under mildly acidic conditions. Other post-translational modifications include hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of the o-amino groups of lysine, arginine, and histidine side chains (T.E. Creighton, Proteins: Structure and Molecular Properties, W. H. Freeman & Co, San Francisco pp 79-86 [1983]), acetylation of the N-terminal amine and, in some instances, amidation of the C-terminal carboxyl.
179. It is understood that one way to define the variants and derivatives of the disclosed proteins herein is through defining the variants and derivatives in terms of homology/identity to specific known sequences. For example, SEQ ID NO: 1 sets forth a particular sequence of TSGIOI and SEQ ID NO:5 sets forth a particular sequence of a retroviral GAG protein. Specifically disclosed are variants of these and other proteins herein disclosed which have at least, 70% or 75% or 80% or 85% or 90% or 95% homology to the stated sequence. Those of skill in the art readily understand how to determine the homology of two proteins. For example, the homology can be calculated after aligning the two sequences so that the homology is at its highest level. _ _ _ ^ ^
180. Another way of calculating homology can be performed by published algorithms. Optimal alignment of sequences for comparison may be conducted by the local homology algorithm of Smith and Waterman Adv. Appl. Math. 2: 482 (1981), by the homology alignment algorithm of Needleman and Wunsch, J. MoL Biol. 48: 443 (1970), by the search for similarity method of Pearson and Lipman, Proc. Natl. Acad. Sci. U.S.A. 85: 2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by inspection.
181. The same types of homology can be obtained for nucleic acids by for example the algorithms disclosed in Zuker, M. Science 244:48-52, 1989, Jaeger et al. Proc. Natl. Acad. Sci. USA 86:7706-7710, 1989, Jaeger et al. Methods Enzymol. 183:281 -306, 1989 which are herein incoφorated by reference for at least material related to nucleic acid alignment.
182. It is understood that the description of conservative mutations and homology can be combined together in any combination, such as embodiments that have at least 70% homology to a particular sequence wherein the variants are conservative mutations. 183. As this specification discusses various proteins and protein sequences it is understood that the nucleic acids that can encode those protein sequences are also disclosed. This would include all degenerate sequences related to a specific protein sequence, i.e. all nucleic acids having a sequence that encodes one particular protein sequence as well as all nucleic acids, including degenerate nucleic acids, encoding the disclosed variants and derivatives of the protein sequences. Thus, while each particular nucleic acid sequence may not be written out herein, it is understood that each and every sequence is in fact disclosed and described herein through the disclosed protein sequence. It is also understood that while no amino acid sequence indicates what particular DNA sequence encodes that protein within an organism, where particular variants of a disclosed protein are disclosed herein, the known nucleic acid sequence that encodes that protein in the particular organism from which that protein arises is also known and herein disclosed and described. g) Pharmaceutical carriers/Delivery of pharmaceutical products
184. As described herein, the compositions can also be administered in vivo in a pharmaceutically acceptable carrier. By "pharmaceutically acceptable" is meant a material that is not biologically or otherwise undesirable, i.e., the material may be administered to a subject, along with the nucleic acid or vector, without causing any undesirable biological effects or interacting in a deleterious manner with any of the other components of the pharmaceutical composition in which it is contained. The carrier would naturally be selected to minimize any degradation of the active ingredient and to minimize any adverse side effects in the subject, as would be well known to one of skill in the art.
185. The compositions may be administered orally, parenterally (e.g., intravenously), by intramuscular injection, by intraperitoneal injection, transdermally, extracoφoreally, topically or the like, including topical intranasal administration or administration by inhalant. As used herein, "topical intranasal administration" means delivery of the compositions into the nose and nasal passages through one or both of the nares and can comprise delivery by a spraying mechanism or droplet mechanism, or through aerosolization of the composition. Administration of the compositions by inhalant can be through the nose or mouth via delivery by a spraying or droplet mechanism. Delivery can also be directly to any area of the respiratory system (e g , lungs) via intubation The exact amount of the compositions required will vary from subject to subject, depending on the species, age, weight and general condition of the subject, the seventy of the allergic disorder being treated, the particular nucleic acid or vector used, its mode of administration and the like Thus, it is not possible to specify an exact amount for every composition However, an appropriate amount can be determined by one of ordinary skill in the art using only routine experimentation given the teachings herein
186 Parenteral administration of the composition, if used, is generally characterized by injection Injectables can be prepared in conventional forms, either as liquid solutions or suspensions, solid forms suitable for solution of suspension in liquid prior to injection, or as emulsions A more recently revised approach for parenteral administration involves use of a slow release or sustained release system such that a constant dosage is maintained See, e g , U S Patent No 3,610,795, which is incoφorated by reference herein
187 The materials may be in solution, suspension (for example, incoφorated into microparticles, liposomes, or cells) These may be targeted to a particular cell type via antibodies, receptors, or receptor ligands The following references are examples of the use of this technology to target specific proteins to tumor tissue (Senter, et al , Bioconiugate Chem , 2 447-451 , ( 1991 ), Bagshawe, K D , Br J Cancer, 60 275- 281, (1989), Bagshawe, et al , Br J Cancer. 58 700-703, (1988), Senter, et al , Bioconiugate Chem . 4 3-9, (1993), Battelli, et al , Cancer Immunol Immunother . 35 421-425, (1992), Pietersz and McKenzie, I munolog Reviews. 129 57-80, (1992), and Roffler, et al , Biochem Pharmacol. 42 2062-2065, (1991)) Vehicles such as "stealth" and other antibody conjugated liposomes (including lipid mediated drug targeting to colonic carcinoma), receptor mediated targeting of DNA through cell specific ligands, lymphocyte directed tumor targeting, and highly specific therapeutic retroviral targeting of murine glioma cells in vivo The following references are examples of the use of this technology to target specific proteins to tumor tissue (Hughes et al , Cancer Research. 49 6214-6220, (1989), and Litzinger and Huang, Biochimica et Biophvsica Acta, 1104 179-187, (1992)) In general, receptors are involved in pathways of endocytosis, either constitutive or ligand induced These receptors cluster in clathrin-coated pits, enter the cell via clathrin-coated vesicles, pass through an acidified endosome in which the receptors are sorted, and then either recycle to the cell surface, become stored intracellularly, or are degraded in lysosomes The intemalization pathways serve a variety of functions, such as nutrient uptake, removal of activated proteins, clearance of macromolecules, opportunistic entry of viruses and toxins, dissociation and degradation of ligand, and receptor-level regulation Many receptors follow more than one intracellular pathway, depending on the cell type, receptor concentration, type of ligand, ligand valency, and ligand concentration Molecular and cellular mechanisms of receptor-mediated endocytosis has been reviewed (Brown and Greene, DNA and Cell Biology 10 6, 399-409 (1991))
(1) Pharmaceutically Acceptable Carriers 188 The compositions, including antibodies or other compositions which interact with TSGIOI such that TSG I OI cannot interact with the retroviral GAG, can be used therapeutically in combination with a pharmaceutically acceptable carrier
189 Suitable carriers and their formulations are described in Remington The Science and Practice of Pharmacy (19th ed ) ed A R Gennaro, Mack Publishing Company, Easton, PA 1995 Typically, an appropriate amount of a pharmaceutically-acceptable salt is used in the formulation to render the formulation isotonic Examples of the pharmaceutically-acceptable carrier include, but are not limited to, saline, Ringer's solution and dextrose solution The pH of the solution is preferably from about 5 to about 8, and more preferably from about 7 to about 7 5 Further carriers include sustained release preparations such as semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e g , films, liposomes or microparticles It will be apparent to those persons skilled in the art that certain carriers may be more preferable depending upon, for instance, the route of administration and concentration of composition being administered
190 Pharmaceutical carriers are known to those skilled in the art These most typically would be standard carriers for administration of drugs to humans, including solutions such as sterile water, saline, and buffered solutions at physiological pH The compositions can be administered intramuscularly or subcutaneously Other compounds will be administered according to standard procedures used by those skilled in the art
191 Pharmaceutical compositions may include carriers, thickeners, diluents, buffers, preservatives, surface active agents and the like in addition to the molecule of choice Pharmaceutical compositions may also include one or more active ingredients such as antimicrobial agents, antnnfiammatory agents, anesthetics, and the like
192 The pharmaceutical composition may be administered in a number of ways depending on whether local or systemic treatment is desired, and on the area to be treated Administration may be topically (including ophthalmically, vaginally, rectally, intranasally), orally, by inhalation, or parenterally, for example by intravenous dnp, subcutaneous, lntrapeπtoneal or intramuscular injection The disclosed antibodies can be administered intravenously, tntrapeπtoneally, intramuscularly, subcutaneously, intracavity, or transdermally
193 Preparations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions Examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate Aqueous carriers include water, alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media Parenteral vehicles include sodium chloride solution, Ringer's dextrose, dextrose and sodium chloride, lactated Ringer's, or fixed oils Intravenous vehicles include fluid and nutrient replenishers, electrolyte replenishers (such as those based on Ringer's dextrose), and the like Preservatives and other additives may also be present such as, for example, antimicrobials, anti-oxidants, chelating agents, and inert gases and the like
194 Formulations for topical administration may include ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders Conventional pharmaceutical earners, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable
195 Compositions for oral administration include powders or granules, suspensions or solutions in water or non-aqueous media, capsules, sachets, or tablets Thickeners, flavorings, diluents, emulsifiers, dispersing aids or binders may be desirable
196 Some of the compositions may potentially be administered as a pharmaceutically acceptable acid- or base- addition salt, formed by reaction with inorganic acids such as hydrochloric acid, hydrobromic acid, perchloric acid, nitric acid, thiocyanic acid, sulfunc acid, and phosphoric acid, and organic acids such as formic acid, acetic acid, propionic acid, glycolic acid, lactic acid, pyruvic acid, oxalic acid, malonic acid, succinic acid, maleic acid, and fumaric acid, or by reaction with an inorganic base such as sodium hydroxide, ammonium hydroxide, potassium hydroxide, and organic bases such as mono-, di-, trialkyl and aryl amines and substituted ethanolamines. (2) Therapeutic Uses
197. Effective dosages and schedules for administering the compositions may be determined empirically, and making such determinations is within the skill in the art. The dosage ranges for the administration of the compositions are those large enough to produce the desired effect in which the symptoms disorder are effected. The dosage should not be so large as to cause adverse side effects, such as unwanted cross-reactions, anaphylactic reactions, and the like. Generally, the dosage will vary with the age, condition, sex and extent of the disease in the patient, route of administration, or whether other drugs are included in the regimen, and can be determined by one of skill in the art. The dosage can be adjusted by the individual physician in the event of any counterindications. Dosage can vary, and can be administered in one or more dose administrations daily, for one or several days. Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products. For example, guidance in selecting appropriate doses for antibodies can be found in the literature on therapeutic uses of antibodies, e.g., Handbook of Monoclonal Antibodies, Ferrone et al, eds, Noges Publications, Park Ridge, N.J, (1985) ch. 22 and pp, 303-357; Smith et al. Antibodies in Human Diagnosis and Therapy, Haber et al, eds. Raven Press, New York (1977) pp. 365- 389. A typical daily dosage of the antibody used alone might range from about 1 μg/kg to up to 100 mg/kg of body weight or more per day, depending on the factors mentioned above.
198. Following administration of a disclosed composition, such as an antibody or molecule that inhibits TSGIOI from interacting with GAG, for treating, inhibiting, or preventing an HIV infection, the efficacy of the therapeutic composition can be assessed in various ways well known to the skilled practitioner. For instance, one of ordinary skill in the art will understand that the compositions disclosed herein are efficacious in treating or inhibiting an HIV infection in a subject by observing that the composition reduces viral load or prevents a further increase in viral load. Viral loads can be measured by methods that are known in the art, for example, using polymerase chain reaction assays to detect the presence of HIV nucleic acid or antibody assays to detect the presence of HIV protein in a sample (e.g., but not limited to, blood) from a subject or patient, or by measuring the level of circulating anti-HIV antibody levels in the patient. Efficacy of the administration of the disclosed composition may also be determined by measuring the number of CD4+ T cells in the HIV-infected subject. An antibody treatment that inhibits an initial or further decrease in CD4+ T cells in an HIV-positive subject or patient, or that results in an increase in the number of CD4+ T cells in the HIV-positive subject, is an efficacious antibody treatment.
199. The compositions that inhibit TSG 101 -PTAP interactions disclosed herein may be administered prophylactically to patients or subjects who are at risk for being exposed to HIV or who have been newly exposed to HIV. In subjects who have been newly exposed to HIV but who have not yet displayed the presence of the virus (as measured by PCR or other assays for detecting the virus) in blood or other body fluid, efficacious treatment with an antibody of the invention partially or completely inhibits the appearance of the virus in the blood or other body fluid. 200 Other molecules that interact with TSGIOI to inhibit TSG101/PTAP/GAG interactions which do not have a specific pharmaceutical function, but which may be used for tracking changes within cells or for the delivery of diagnostic tools for example can be delivered in ways similar to those described for the pharmaceutical products 201 The disclosed compositions and methods can also be used for example as tools to isolate and test new drug candidates for a variety of PTAP motif containing retroviral related diseases They can also be used for the continued isolation and study, for example, the cell cycle
6. Chips and micro arrays
202 Disclosed are chips where at least one address is the sequences or part of the sequences set forth in any of the nucleic acid sequences disclosed herein Also disclosed are chips where at least one address is the sequences or portion of sequences set forth in any of the peptide sequences disclosed herein
203 Also disclosed are chips where at least one address is a variant of the sequences or part of the sequences set forth in any of the nucleic acid sequences disclosed herein Also disclosed are chips where at least one address is a variant of the sequences or portion of sequences set forth in any of the peptide sequences disclosed herein
7. Kits
204 Disclosed herein are kits that are drawn to reagents that can be used in practicing the methods disclosed herein The kits can include any reagent or combination of reagent discussed herein or that would be understood to be required or beneficial in the practice of the disclosed methods For example, the kits could include primers to perform the amplification reactions discussed in certain embodiments of the methods, as well as the buffers and enzymes required to use the primers as intended D. Methods of making the compositions
205 The compositions disclosed herein and the compositions necessary to perform the disclosed methods can be made using any method known to those of skill in the art for that particular reagent or compound unless otherwise specifically noted 1. Nucleic acid synthesis
206 For example, the nucleic acids, such as, the oligonucleotides to be used as primers can be made using standard chemical synthesis methods or can be produced using enzymatic methods or any other known method Such methods can range from standard enzymatic digestion followed by nucleotide fragment isolation (see for example, Sambrook et al , Molecular Cloning A Laboratory Manual, 2nd Edition (Cold
Spring Harbor Laboratory Press, Cold Spring Harbor, N Y , 1989) Chapters 5, 6) to purely synthetic methods, for example, by the cyanoethyl phosphoramidite method using a Milhgen or Beckman System lPlus DNA synthesizer (for example, Model 8700 automated synthesizer of Milhgen-Biosearch, Burlington, MA or ABI Model 380B) Synthetic methods useful for making oligonucleotides are also described by Ikuta et al , Ann Rev Biochem 53 323-356 (1984), (phosphotπester and phosphite-tπester methods), and Narang et al ,
Methods Enzymol , 65 610-620 (1980), (phosphotπester method) Protein nucleic acid molecules can be made using known methods such as those described by Nielsen et al , Bioconjug Chem 5 3-7 (1994) 2. Peptide synthesis
207 One method of producing the disclosed proteins, is to link two or more peptides or polypeptides together by protein chemistry techniques For example, peptides or polypeptides can be chemically synthesized using currently available laboratory equipment using either Fmoc (9-fluorenylmethyloxycarbonyl) or Boc (tert -butyloxycarbonoyl) chemistry (Applied Biosystems, Inc , Foster City, CA) One skilled in the art can readily appreciate that a peptide or polypeptide corresponding to the disclosed proteins, for example, can be synthesized by standard chemical reactions For example, a peptide or polypeptide can be synthesized and not cleaved from its synthesis resin whereas the other fragment of a peptide or protein can be synthesized and subsequently cleaved from the resin, thereby exposing a terminal group which is functionally blocked on the other fragment By peptide condensation reactions, these two fragments can be covalently joined via a peptide bond at their carboxyl and ammo termini, respectively, to form an antibody, or fragment thereof (Grant GA (1992) Synthetic Peptides A User Guide W H Freeman and Co , N Y (1992), Bodansky M and Trost B , Ed (1993) Principles of Peptide Synthesis Springer- Verlag Inc , NY (which is herein incoφorated by reference at least for material related to peptide synthesis) Alternatively, the peptide or polypeptide is independently synthesized in vivo as described herein Once isolated, these independent peptides or polypeptides may be linked to form a peptide or fragment thereof via similar peptide condensation reactions
208 For example, enzymatic ligation of cloned or synthetic peptide segments allow relatively short peptide fragments to be joined to produce larger peptide fragments, polypeptides or whole protein domains (Abrahmsen L et al , Biochemistry, 30 4151 (1991)) Alternatively, native chemical ligation of synthetic peptides can be utilized to synthetically construct large peptides or polypeptides from shorter peptide fragments This method consists of a two step chemical reaction (Dawson et al Synthesis of Proteins by Native Chemical Ligation Science, 266 776-779 (1994)) The first step is the chemoselective reaction of an unprotected synthetic pepttde-thioester with another unprotected peptide segment containing an amino-terminal Cys residue to give a thtoester-hnked intermediate as the initial covalent product Without a change in the reaction conditions, this intermediate undergoes spontaneous, rapid intramolecular reaction to form a native peptide bond at the hgatton site (Baggiolint M et al (1992) FEBS Lett 307 97-101, Clark-Lewis I et al , J Biol Chem , 269 16075 (1994), Clark-Lewis I et al , Biochemistry, 30 3128 (1991), Rajarathnam K et al , Biochemistry 33 6623-30 (1994))
209 Alternatively, unprotected peptide segments are chemically linked where the bond formed between the peptide segments as a result of the chemical ligation is an unnatural (non-peptide) bond
(Schnolzer, M et al Science, 256 221 (1992)) This technique has been used to synthesize analogs of protein domains as well as large amounts of relatively pure proteins with full biological activity (deLisle Milton RC et al , Techniques in Protein Chemistry IV Academic Press, New York, pp 257-267 (1992))
3. Process for making the compositions 210 Disclosed are processes for making the compositions as well as making the intermediates leading to the compositions There are a variety of methods that can be used for making these compositions, such as synthetic chemical methods and standard molecular biology methods It is understood that the methods of making these and the other disclosed compositions are specifically disclosed E. Methods of using the compositions
1. Methods of using the compositions as research tools
211. The disclosed compositions can be used in a variety of ways as research tools For example, the disclosed coordinates and storage media containing them, can be used to isolate molecules that interact with the TSG 101 or GAG molecule.
212. The compositions can be used for example as targets in combinatorial chemistry protocols or other screening protocols to isolate molecules that possess desired functional properties related to binding TSGIOI, such that TSGIOI cannot interact with retroviral GAG proteins.
F. Exemplary Embodiments 213 Disclosed is a method for reducing interactions between TSGIOI and GAG. Some forms of the method comprise incubating an inhibitor with TSGIOI, GAG, or TSGIOI and GAG, where the inhibitor is an inhibitor of the interaction between TSGIOI and GAG. In some embodiments, the inhibitor can interact with amino acid Thr58, Val61 , Tyr63, Tyr68, Asn69, Ile70, Pro71 , Thr92, Met95, Pro 139, Val 141, Phe 142, Serl43, and/or Argl44 of SEQ ID NO 1 In some embodiments, the inhibitor can interact with at least one atom from amino acids Thr58, Valόl , Tyr63, Tyr68, Asn69, Ile70, Pro71 , Thr92, Met95, Prol39, Val l41 ,
Phel42, Serl43, and or Argl44 set forth in Table 5 or in Table 6 or any of the Tables set forth herein, such as Tables 8-47
214. Also disclosed is a method for inhibiting HIV budding. Some forms of the method comprise administering an inhibitor of the interaction between TSGI OI and HIV GAG, where the inhibitor can interact with an amino acid Thr58, Valόl , Tyr63, Tyr68, Asn69, Ile70, Pro71 , Thr92, Met95, Prol39, Vall41 , Phel42, Serl43, and/or Argl44 of SEQ ID NO: l. Some forms of the method comprise administering an inhibitor of the interaction between TSGIOI and HIV GAG, where the inhibitor can interact with at least one atom of amino acids Thr58, Valόl , Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol39, Vall41, Phel42, Serl43, and/or Argl44 set forth in Table 5 or in Table 6 or any of the Tables disclosed herein, such as Tables 8-47
215. Also disclosed is a method of treating a subject comprising administering to the subject an inhibitor of HIV budding, where the inhibitor reduces the interaction between TSGIOI and HIV GAG, and where the subject is in need of such treatment In some forms of the method, the inhibitor can interact with an amino acid Thr58, Valόl , Tyr63, Tyr68, Asn69, Ile70, Pro71 , Thr92, Met95, Prol39, Vall41 , Phel42, Serl43, and/or Argl44 of SEQ ID NO 1 In some forms of the method, the inhibitor can interact with at least one atom of amino acids Thr58, Valόl , Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol39, Vall41, Phel42, Serl43, and/or Argl44 set forth in Table 5 or in Table 6 or any of the Tables disclosed herein, such as Tables 8-47
216 These methods can be performed in various modes and with various features For example, the GAG can comprise a P6 region, where the inhibitor disrupts an interaction between TSG IOI and the P6 region of GAG; or the GAG can comprise a PTAP domain, where the inhibitor disrupts an interaction between TSGIOI and the PTAP domain.
217. In some embodiments, the inhibitor can interact with the UEV domain of TSGIOI The UEV domain can comprise a PTAP binding groove The groove can comprise amino acids found in three non- contiguous regions of TSGIOI The groove can comprise a region selected from the group consisting of a loop connecting strands 2 and 3, a N-termtnal third of the vestigial active site loop, and a C-terminal end In such a case, the inhibitor can interact with a region selected from the group consisting of the loop connecting strands 2 and 3, the N-terminal third of the vestigial active site loop, and the C-terminal end The active site loop can include a five residue insertion in the active site loop The loop connecting strands 2 and 3 can be displaced The C-terminal end can comprise two glycine residues that create irregularities in the C-terminal helix geometry The groove can comprise a hydrophobic region The hydrophobic region can reside in strands 3 and 4 of TSG 101 Strands 3 and 4 can comprise Ile70, Val89, and Pro91 of TSG 101 The groove can comprise a charged region The charged region can further comprise two charged residues The charged region can comprise Arg64 and Arg44 of TSGIOI The charged region and the hydrophobic region can be asymmetrical
218 In some embodiments, the inhibitor can interact with amino acid Thr58, Valόl, Tyr63, Tyr68, Asn69, Ile70, Pro71 , Thr92, Met95, Prol39, Vall41, Phel42, Serl43, and/or Argl44 of SEQ ID NO 1 and/or the inhibitor can disrupt an interaction between amino acid Thr58, Valόl, Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol39, Vall41, Phel42, Serl43, and/or Argl44 of SEQ ID NO 1 and a PTAP domain
219 In some embodiments, the inhibitor can interact with at least one atom of amino acid Thr58, Valόl , Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol39, Vall41, Phel42, Serl43, and/or Argl44 set forth in Table 5 or in Table 6 or any of the Tables disclosed herein, such as Tables 8-47, and/or the inhibitor can disrupt an interaction between at least one atom of amino acid Thr58, Valόl , Tyr63, Tyr68, Asn69, Ile70, Pro71 , Thr92, Met95, Prol39, Vall41 , Phel42, Serl43, and/or Argl44 set forth in Table 5 or in Table 6, or any of the Tables disclosed herein, such as Tables 8-47, and a PTAP domain
220 Also disclosed is a method of identifying an inhibitor of an interaction between TSGIOI and retroviral GAG In some forms, the method comprises incubating a set of molecules with TSGIOI, a conserved variant thereof, a fragment thereof, or a combination thereof, forming a mixture, and isolating the molecules that can disrupt the interaction between TSGIOI and retroviral GAG In some forms, the method comprises incubating a library of molecules with retroviral GAG, a conserved variant thereof, a fragment thereof, or a combination thereof, forming a mixture, and isolating the molecules that can disrupt the interaction between retroviral GAG and TSGIOI The interaction disrupted can comprise an interaction between the retroviral GAG and an amino acid of TSGIOI , where the amino acid is Thr58, Valόl, Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol39, Vall41, Phel42, Serl43, and or Argl44 of SEQ ID
NO 1 The step of isolating can comprise incubating the mixture with a molecule comprising a PTAP binding domain
221 Also disclosed is a method of identifying an inhibitor of an interaction between TSGIOI and retroviral GAG In some forms, the method comprises displaying the structure of the TSGIOI , TSGIOI -UEV, TSGIOI PTAP binding domain, or TSGIOI Ub binding domain in a computer medium, and identifying a molecule that interacts with the displayed structure The method can further comprise performing molecular modeling activities with the structure and a ligand or potential ligand
222 Also disclosed is a method of identifying an inhibitor of TSG 101 -GAG interaction comprising, (a) administering a composition to a system, wherein the system supports TSG101-GAG interaction, (b) assaying the effect of the composition on the amount of TSG 101 -GAG in the system, and (c) selecting a composition which causes a decrease in the amount of TSG 101 -GAG present in the system relative to the system without the addition of the composition Also disclosed is a method of identifying an inhibitor of HIV budding comprising, (a) administering a composition to a system, wherein the system supports HIV budding via a TSG 101 -GAG interaction, (b) assaying the effect of the composition on the amount of HIV budding in the system, and (c) selecting a composition which causes a decrease in the amount of HIV budding present in the system because of an inhibition of the TSGIOI -GAG interaction relative to the system without the addition of the composition
223 These methods can be performed in various modes and with various features For example, the retroviral GAG can be HIV GAG, or the retroviral GAG can be Ebola GAG The method can further comprise incubating the mixture with Ubiquitin Also disclosed are inhibitors identified by the methods and inhibitors capable of being identified by the methods Also disclosed is a method of manufacturing a composition for inhibiting the interaction between TSGIOI and GAG comprising synthesizing an inhibitor identified by the methods of identifying an inhibitor described above This method can further comprise mixing a pharmaceutical carrier with the inhibitor Also disclosed is a method of manufacturing a composition for inhibiting the interaction between TSGIOI and GAG comprising admixing the inhibitor with a pharmaceutical carrier
224 Also disclosed is a method of inhibiting HIV budding In some forms, the method comprises administering a composition that reduces HIV budding The composition is defined as a composition capable of being identified by administering the composition to a system, where the system supports HIV budding via a TSGIOI -GAG interaction, assaying the effect of the composition on the amount of HIV budding in the system, and selecting a composition which causes a decrease in the amount of HIV budding present in the system because of an inhibition of the TSG 101 -GAG interaction relative to the system without the addition of the composition In some forms, the method compnses administering a composition that reduces an interaction between TSGIOI and GAG
225 Also disclosed is a method of making a composition capable of inhibiting HIV budding comprising admixing a compound with a pharmaceutically acceptable carrier, where the compound is identified by administering the compound to a system, where the system supports HIV budding via a TSG 101- GAG interaction, assaying the effect of the compound on the amount of HIV budding in the system, and selecting a compound which causes a decrease in the amount of HIV budding in the system because of an inhibition of the TSG 101 -GAG interaction, relative to the system without the addition of the compound The method can further comprise the step of admixing the composition with a pharmaceutical carrier
226 Also disclosed is a method of manufacturing an inhibitor to HIV budding comprising, (a) administering a composition to a system, wherein the system supports HIV budding via a TSG 101 -GAG interaction, (b) assaying the effect of the composition on the amount of HIV budding in the system, (c) selecting a composition which causes a decrease in the amount of HIV budding present in the system because of an inhibition of the TSGIOI -GAG interaction, relative to the system without the addition of the composition, and (d) synthesizing the composition 227 Also disclosed is a method of identifying an inhibitor of an interaction between TSGIOI and
GAG comprising (a) administering a composition to a system, wherein the system comprises TSGIOI , (b) assaying the effect of the composition on a TSGIOI -GAG interaction, and (c) selecting a composition which inhibits the TSG 101 -GAG interaction 228 These methods can be performed in various modes and with various features For example, the inhibitor can interact with amino acid Thr58, Valόl, Tyr63, Tyr68, Asn69, Ile70, Pro71, Thr92, Met95, Prol39, Vall41, Phel42, Serl43, and/or Argl44 of SEQ ID NO 1 , the GAG can comprise a P6 region, where the inhibitor disrupts an interaction between TSGIOI and the P6 region of HIV GAG, the GAG can comprise a PTAP domain, where the inhibitor disrupts an interaction between TSGIOI and the PTAP domain, and/or the inhibitor can interact with at least one atom of amino acids Thr58, Valόl, Tyr63, Tyr68, Asn69, Ile70,
Pro71, Thr92, Met95, Prol39, Vall41 , Phel42, Serl43, and/or Argl44 as set forth in Table 5 or in Table 6 or any of the Tables disclosed herein, such as Tables 8-47
229 Also disclosed is a cell comprising, (a) an exogenous nucleic acid comprising sequence encoding a TSGIOI gene, conserved variant, or fragment thereof, and (b) a nucleic acid comprising sequence encoding a GAG gene, conserved variant, or fragment thereof Also disclosed is a cell comprising, an exogenous nucleic acid comprising sequence encoding a TSGIOI gene, a conserved variant thereof, or fragment thereof and sequence comprising a GAG gene, a conserved variant thereof, or fragment thereof Such cells can further comprise an inhibitor of a TSG101-GAG interaction
230 Also disclosed is a polypeptide comprising the amino acid sequence of the TSGIOI PTAP binding domain, where the polypeptide does not comprise the polypeptide set forth in SEQ ID NO 1 The amino acid sequence of the TSGIOI PTAP binding domain can comprise amino acids positioned in three dimensional space as defined by coordinates set forth in Table 5 or in Table 6, or coordinates forming a homologous structure, wherein the polypeptide does not comprise the polypeptide set forth in SEQ ID NO 1 The structure of the TSGIOI PTAP binding domain can be defined by the coordinates set forth in Table 5 or in Table 6, or coordinates forming a homologous structure, and wherein the polypeptide does not comprise the polypeptide set forth in SEQ ID NO 1
231 Also disclosed is a method of characterizing protein structures comprising the steps (a) determining a TSGIOI PTAP binding domain three-dimensional structure, (b) determining an experimental protein three-dimensional structure , (c) comparing the experimental protein three-dimensional structure to the TSGIOI PTAP binding domain three-dimensional structure, and (d) recording variances between the TSGIOI PTAP binding domain three-dimensional structure and the experimental protein three-dimensional structure The three-dimensional structure of the TSGIOI PTAP binding domain can be defined by the atomic structure coordinates of Table 5 or Table 6 or coordinates producing a homologous structure
232 The TSG 101 PTAP binding domain three-dimensional structure can be derived from the structure of a polypeptide comprising the amino acid sequence of the TSGIOI PTAP binding domain, where the polypeptide does not comprise the polypeptide set forth in SEQ ID NO 1 The amino acid sequence of the TSGIOI PTAP binding domain can comprise amino acids positioned in three dimensional space as defined by coordinates set forth in Table 5 or in Table 6, or coordinates forming a homologous structure, wherein the polypeptide does not comprise the polypeptide set forth in SEQ ID NO 1 The structure of the TSGIOI PTAP binding domain can be defined by the coordinates set forth in Table 5 or in Table 6, or coordinates forming a homologous structure, and wherein the polypeptide does not comprise the polypeptide set forth in SEQ ID NO:l .
233. Also disclosed is a method of evaluating two or more experimental proteins in respect to the TSGIOI PTAP binding domain, comprising: (i) evaluating the variances for a first experimental protein; (ii) evaluating the variances of for a second experimental protein; and (iii) ranking the experimental protein with the least variance from the structure of TSG IOI PTAP binding domain as being most similar.
234. Also disclosed is computer readable media storing instructions that upon execution by a computer causes the computer to perform any of the methods described above. 235. Also disclosed is a method of displaying a representation of a TSGIOI PTAP binding domain on a computer having a processing means, a memory means, an input means and an output means comprising: receiving the three-dimensional coordinates of atoms of a TSGIOI PTAP binding domain; producing a representation of the TSGIOI PTAP binding domain based upon the received coordinates; and displaying the representation of the TSGIOI PTAP binding domain on the visual display means. 236. Also disclosed is a method of displaying a representation of an analog of a TSG 101 PTAP binding domain comprising: (a) determining the three-dimensional coordinates of atoms of a TSGIOI PTAP binding domain; (b) providing a computer having a memory means, a data input means, a visual display means, the memory means containing three-dimensional molecular simulation software operable to retrieve coordinate data from the memory means and to display a three-dimensional representation of a molecule on the visual display means and being operable to produce a representation of an analog of the molecule responsive to operator-selected changes to the chemical structure of the molecule and to display the representation of the analog; (c) inputting three-dimensional coordinate data of the atoms of the TSGIOI PTAP binding domain into the computer and storing the data in the memory means; (d) displaying the representation of the TSGIOI PTAP binding domain on the visual display means; (e) inputting into the data input means of the computer at least one operator-selected change in chemical structure of the TSGIOI PTAP binding domain forming a TSGIOI PTAP binding domain analog structure; (f) executing the molecular simulation software to produce a modified three-dimensional molecular representation of the analog structure; and(g) displaying the representation of the analog structure on the visual display means, whereby changes in three-dimensional structure of the TSGIOI PTAP binding domain consequent on changes in chemical structure can be visually determined.
237. In some forms, the method can further comprise repeating step (d) forming a second TSGIOI PTAP binding domain analog structure and then repeating steps (f)-(g)- The method can further comprising selecting one of the analog structures obtaining a selected analog structure, where selecting the analog structure comprises displaying on the visual display means the three-dimensional structure of the TSGIOI PTAP binding domain analog and the second TSG 101 PTAP binding domain analog, visually comparing the configuration and spatial arrangement of the TSGIOI PTAP binding domain, and selecting an analog structure where the domains are substantially the same. The method can further comprise steps synthesizing the selected analog by means of recombinant DNA technology; and determining the TSGIOI PTAP binding domain function of the synthesized TSGIOI PTAP binding domain function analog, whereby an analog having the activity is a mimic of the three-dimensional structure of the TSGIOI PTAP binding domain.
238. Also disclosed is a method for identifying the TSGIOI PTAP binding domain analogs that mimic the three-dimensional structure of the TSGIOI PTAP binding domain, comprising: producing a multiplicity of analog structures of the TSGIOI PTAP binding domain by the method of method of displaying a representation of an analog of a TSGIOI PTAP binding domain described above, and selecting an analog structure with a structure of the PTAP binding domain which is substantially like the TSGIOI PTAP binding domain.
239. Disclosed are methods for identifying a potential ligand of a protein comprising a TSGIOI PTAP binding domain comprising: (a) using a three-dimensional structure of the TSGIOI PTAP binding domain function or portions thereof formed from the atomic coordinates of the TSGIOI PTAP binding domain; (b) employing the three-dimensional structure to design or select the potential ligand.
240. Also disclosed are methods, further comprising a method for identifying a potential ligand of a protein comprising a TSGIOI PTAP binding domain comprising: (c) synthesizing the potential ligand; and (d) contacting the potential ligand with the TSGI OI PTAP binding domain function containing protein; and (e) determining whether the potential ligand binds to the TSGIOI PTAP binding domain containing protein.
241. Also disclosed are methods, wherein the step of employing the three-dimensional structure to design or select the ligand comprises: identifying chemical functionalities capable of associating with the TSGIOI PTAP binding domain; and assembling the identified chemical functionalities into a single molecule to provide the structure of the TSGIOI PTAP binding domain potential ligand.
242. Disclosed are methods, wherein the potential ligand is designed de novo and/or, wherein the potential ligand is designed from a known compound, and/or wherein the set of atomic coordinates are set forth in Table 5 or in Table 6 or any of the coordinate Tables herein.
243. Disclosed are computer readable media storing instructions that upon execution by a computer causes the computer to perform the disclosed methods.
244. Disclosed are analogs of the TSGIOI PTAP binding domain made by methods according to any one of claims methods disclosed herein or using the disclosed structural information.
245. Disclosed are analog structures of a domain produced according to the disclosed methods or using the disclosed structural information. 246. Disclosed are ligands of a TSGIOI PTAP binding domain containing polypeptides made according to the disclosed methods or using the disclosed structural information.
247. Disclosed is an apparatus for determining whether a compound will interact with a protein containing a TSGI OI PTAP binding domain, comprising: (a) a memory that stores a set of coordinates and identities of the atoms of the TSGIOI PTAP binding domain that together form a solvent-accessible surface; and executable instructions; and (b) a processor, wherein the executes instructions to receive structural information for a candidate compound; determine if the structure of the candidate compound is complementary to the structure of the solvent-accessible surface of the TSGIOI PTAP binding domain; and output the results of the determination. 248. Disclosed are apparati, wherein the set of coordinates and identities of the atoms of the TSGIOI
PTAP binding domain are derived from the structure of amino acid residue 1 through amino acid residue 145 set forth in SEQ ID NO: l , and/or wherein the set of coordinates and identities of atoms of the TSGIOI PTAP binding domain are derived from a solution, and/or wherein the set of coordinates and identities of atoms of the TSG 101 PTAP binding domain are the atomic coordinates set forth in Table 5 or in Table 6 or any of the coordinate Tables disclosed herein or a portion thereof.
249. Disclosed are computer-readable storage media comprising one or more computer readable media storing digitally-encoded structural data, wherein the data comprise the identity and three-dimensional coordinates, or coordinates providing a structural homolog, of at least 2 amino acids set forth in SEQ ID NO: 1. 250. Disclosed are media, wherein the data comprise the set of coordinates, or coordinates providing a structural homolog, of at least 8 amino acids set forth in SEQ ID NO: l, and/or wherein the data comprise the set of coordinates, or coordinates providing a structural homolog, of at least 8 amino acids set forth in SEQ ID NO:l, and/or wherein the data comprise the set of coordinates, or coordinates providing a structural homolog, of at least 8 amino acids set forth in SEQ ID NO: l , and/or wherein the data comprise the set of coordinates, or coordinates providing a structural homolog, of at least 8 amino acids set forth in SEQ ID NO: 1 , and/or wherein the data comprises the atomic coordinates in Table 5 or a portion thereof, Table 6 or a portion thereof, or coordinates providing a structural homolog.
251. Disclosed is an apparatus comprising: (a) a system data store capable of storing coordinate sets; and (b) a system processor in communication with the system data store that: (i) receives and stores a subject set of coordinates for a subject structure; (ii) compares the subject set of coordinates to a reference set of coordinates related to the TSG 101 PTAP binding domain by: (1) calculating the root mean squared deviation of the subject set of coordinates from the reference set of coordinates; and (2) comparing the root mean squared deviation to limit values; and (iii) assigns the subject structure a function based on the subject structure's similarity to the reference structures if the root mean squared deviation is less than or equal to the limit values.
252. Disclosed are apparati, wherein the reference set of coordinates comprises the coordinates in Table 5 or a portion thereof or Table 6 or any of the coordinate tables disclosed herein or a portion thereof.
253. Disclosed are apparati, wherein the limit values correspond to values less than or equal to 3 A, 2.5 A, 2 A, 1.5 A, 1 A, or 0.5 A. 254. Disclosed are methods of determining relationships between two or more polypeptide structures, comprising: (a) obtaining a reference structure, wherein the reference structure is a structure of a polypeptide comprising the TSGIOI PTAP binding domain or a portion thereof; (b) obtaining at least one subject structure; (c) determining a reference structure topology diagram and a subject structure topology diagram; (d) comparing the reference structure topology diagram and the subject structure topology diagram; and (e) assigning a relationship between the reference structure and any subject structure based on deviations between the reference structure and subject structure.
255. Disclosed are methods, wherein the reference structure is a structure defined by the atomic coordinates of Table 5 or a portion thereof or Table 6 or any of the Tables disclosed herein or a portion thereof. 256. Also disclosed are methods, wherein the step of determining considers secondary structural elements, spatial adjacency within fold and approximate orientation, and/or wherein the step of determining neglects the length of loop elements, and/or wherein the step of determining neglects the structure of loop elements, and/or wherein the step of determining neglects spatial orientations of secondary structural elements, and/or wherein the step of determining comprises using TOPS protein topology search, discovering patterns and comparing structures.
257. Disclosed are computer readable media storing instructions that upon execution by a computer causes the computer to perform and of the disclosed methods.
258. United States Patent Applications Publication No. 20020177207, published on November 28, 2002 from United States patent application 09/098979 filed on March 14 2002, and claiming priority to U.S.
Provisional Application Serial No. 60/276,259 filed on Mar. 14, 2001 , U.S. Provisional Application Serial No. 60/304,101 filed on Jul. 10, 2001, U.S. Provisional Application filed on Oct. 22, 2001 , and U.S. Provisional Application filed on Jan. 7, 2002 discusses TSGIOI . All of these applications are incoφorated herein by reference in their entirety at least for material related to TSGI OI and molecules and methods related to TSG 101 and the proteins and molecules that interact with TSG 101. United States Patent Application Publication No. 20020177207 indicates that TSGIOI and fragments of TSGIOI interact with kinectin, AKAP13, TPM4, KIAA0674, motor protein, OS-9, ROCK1, CYLN2, plectin, DAP5, GEF-H1, BAP31, zinc finger protein 231 , HCAP, PACSIN2, PIBF1 , Golgin-67, ACTN4, GAS7B, TOM1L1 , PIG7, PN9667, AA300702, AKNA, desmoplakin I, synexin, Golgin-95, restin, keratin 5, keratin 6C, keratin 8, GTPase- activating protein 1, endosome-associated protein 1, 88-kDa Golgi protein, centromere protein F, serum deprivation response, mitotic spindle coiled-coil related protein, Golgin-84, FLJ 10540, VPS28, hook2, intersectin 1, pallid, catenin, ACTN1, MYH9, KIF5A, PN 19062, ABP620. These proteins and their accession numbers, as well as specific fragments of interaction are denoted in Table 48. Table 48 sets forth the fragments and positions of TSGIOI and proteins ans fragments found to interact with TSGIOI in a yeast two- hybrid experiment.
TABLE 48
Binding Regions of TsglOl and Its Interacting Partners
Figure imgf000054_0001
Figure imgf000055_0001
Figure imgf000056_0001
Figure imgf000057_0001
259 It is understood that in certain embodiments disclosed herein, the embodiments do not include these proteins and/or fragments disclosed in Table 48 as set forth in United States Patent Applications Publication No 20020177207 United States Patent Applications Publication No 20020177207 is also specifically incoφorated for claims 1-38 and any supporting material that is present in the application for these claims
260 United States Patent Applications Publication No 20020173622, published on November 21 , 2002 from United States patent application 09/ 972035 filed on October 4, 2001 , and claiming priority to U S Provisional Application Serial No 60/276,259 filed on Mar 14, 2001 discusses TSG IOI and molecules that interact with TSG IOI United States Patent Applications Publication No 20020173622 provides a table, reproduced below as Table 49 which provides a number of proteins and fragments of proteins that were found to interact with TSGIOI in a Yeast two-hybrid experiment
TABLE 49
Figure imgf000057_0002
Figure imgf000058_0001
Figure imgf000059_0001
Figure imgf000060_0001
261. It is understood that in certain embodiments disclosed herein, the embodiments do not include these proteins and/or fragments disclosed in Table 49 as set forth in United States Patent Applications Publication No. 20020173622. United States Patent Applications Publication No. 20020173622 is also specifically incoφorated for claims 1-60 and any supporting material that is present in the application for these claims.
C. Examples
262. The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how the compounds, compositions, articles, devices and/or methods claimed herein are made and evaluated, and are intended to be purely exemplary of the invention and are not intended to limit the scope of what the inventors regard as their invention. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.), but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in °C or is at ambient temperature, and pressure is at or near atmospheric. 1. Example 1 Structure of the TsglOl N-terminal UEV domain" "~
263 For the structural determinations, a fragment of the TSGIOI was used which contained the
TsglOl UEV domain This fragment was residues 1 -145 of SEQ ID NO 1 and was chosen based on multiple sequence alignments and preliminary NMR analyses (see Example 4) This construct (TsglOl UEV) was expressed and purified, and its NMR solution structure was calculated from a total of 1861 NOE inteφroton restraints, 76 hydrogen bonding restraints derived from amide proton exchange protection experiments, and
146 phi and psi dihedral angle restraints A stereoview of the supeφosition of the 20 lowest-penalty structures is shown in Figure lc The structures superimpose over the mean coordinate position of all ordered residues
» of the domain (4-142) with rmsds of 0 69 A and 0 99 A for backbone and nonhydrogen atoms, respectively
(see Table 3 for structure statistics)
Table3. Structure statistics for Tsg 101 UEV
Figure imgf000061_0001
K, 1000 slow-cooling steps to 0 K, and 2000 steps of restrained Powell minimization in cartesian space
(anneal mp protocol) (Brunger et al , 1998) bOnly meaningful and non-redundant restraints as determined by the DYANA CALIBA function °Two upper-limit distance restraints were used to define each hydrogen bond "Energies for structures input into CNS (from DYANA) were estimated within the generate_easy mp program after the first regulaπzation without restraints
"Violation energies from DYANA have units of A or °, while energies from CNS are in kcal/mol 'Determined using PROCHECK-N R (Laskowski et al , 1996)
--Superposition and overall rmsds were calculated using the program MOLMOL (Koradi et al , 1996) hAII structured residues minus the vestigial active site loop (residues 91-123)
264 The TsglOl UEV fold is generally similar to E2 ligases and to Mms2, the only other structurally characterized UEV (Cook et al , 1992, Cook et al , 1993, Cook et al , 1997, Tong et al , 1997, Worthylake et al , 1998, Huang et al , 1999, Jiang and Basavappa, 1999, Zheng et al , 2000, Hamilton et al , 2001 , Moraes et al , 2001, VanDemark et al , 2001) This "E2 fold", consists of four helices packed against one side of a four- stranded antiparallel β-sheet (Fig 2) The structural similarity is greatest around the central active site region of the structure (residues 53-138), where TsglOl UEV superimposes with hMms2 (Fig 2b) and yUbcl3 (a canonical E2, Fig 2c) with rmsds over equivalent Cα positions of 2 22 A and 1 97 A, respectively (Fig. 2d) However, there are important differences between TsglOl UEV and other E2 and UEV proteins outside of this region
265 Most significantly, TsglOl UEV lacks the two C-terminal helices found in all structurally characterized E2 proteins (Fig 2c, gray helices, Fig 2d, green arrow) Mms2 also lacks these helices, and sequence analyses suggest that they are missing from other UEV domains (Koonin and Abagyan, 1997), indicating that this is a general difference between UEV and canonical E2 proteins (Fig \b) Although both Mms2 and TsglOl UEV lack C-terminal helices, their structures differ in this region because the C-terminal residues of human and yeast Mms2 adopt extended, but ordered conformations that occupy the same site as the final E2 helix, whereas the equivalent residues in TsglOl UEV project off into solution and are disordered We considered the possibility that these residues might be ordered in longer TsglOl constructs, and therefore analyzed proteins that contained an additional 5 or 12 residues (Tsg 1011 150 residues 1 - 150, of SEQ ID NO 1 , and TsglOl 1 157, residues 1-157 of SEQ ID NO 1, respectively), but could find no evidence for additional order in these longer constructs (see Examples herein) Thus, the C-terminal end of TsglOl UEV differs from other known proteins with E2 folds and, as discussed herein, this difference allows Tsgl Ol UEV to bind PTAP-containtng peptides
266 TsglOl UEV differs from Mms2 and canonical E2 proteins in two additional ways 1) TsglOl contains two N-terminal helices (colored red and orange in Fig 2a), whereas Ubcl 3 and Mms2 contain only one (Fig 2d, red arrow) The general disposition of TsglOl UEV helix 2 (orange) is similar to the N-terminal helices of Ubcl 3 and Mms2, but is shifted slightly towards the center of the sheet (Fig 2d) 2) The disposition of the first two strands in TsglOl UEV is quite different from that of Mms2 and Ubcl3 In TsglOl, strand 1 is twisted and displaced toward the N-terminal end of strand 2, and these two strands form an extended β-haiφin "tongue" that projects 1 1 residues beyond the main body of the domain and terminates in a type I glycine turn
(Fig 2d, blue arrow) This beta-tongue is well-defined by strong interstrand Hα-to-Hα and Hα-to-HN NOEs, as well as interstrand backbone hydrogen bonds that protect the backbone amide protons from rapid deuterium exchange As discussed herein, the extended beta-tongue can be a functionally important feature because it forms part of the Ub binding site The disposition of the first two strands also allows extensive packing interactions between the TsglOl UEV N-terminal helices and the β-sheet, which are not possible in Ubcl 3 or Mms2 For example, the loop connecting TsglOl helices 1 and 2 inserts a tyrosine side chain hydroxyl (Tyrl5) between strands 2 and 3, bridging the hydrogen bonding interaction between the amide proton of Met53 (strand 2) and the carboxyl oxygen of Lys76 (strand 3), and thereby terminating the hydrogen bonding network of the β-sheet
267 In summary, TsglOl UEV is similar to canonical E2 enzymes in the hydrophobic core and "active site" regions, but differs significantly at both its N- and C-termim Although some of these structural differences are shared by the TsglOl and Mms2 UEV domains (e g , the lack of C-terminal helices), it is clear that Tsgl Ol has diverged even further from the canonical E2 fold than has Mms2 a) — p6 Binding
268 NMR chemical shift perturbation experiments were used to map the binding site of the HIV-1 p6 protein on the TsglOl UEV domain (Fig 3) Our previous binding studies showed that the TsglOl UEV domain binds p6 with moderate affinity under physiological conditions (Kd = 27±5 μM) (Garrus et al , 2001), and the TsglOl UEV/p6 interaction is even tighter under the low salt conditions used in our NMR titration experiments (A"d = 4 3±1 6 μM at 50 mM NaCl, 20 mM sodium phosphate, pH 6,) suggesting an ionic component to the interaction Heteronuclear single quantum coherence (HSQC) spectra of 5N-labeled TsglOl UEV were collected during stepwise addition of unlabeled p6, and sites of H- 5N chemical shift changes were monitored The majority of TsglOl UEV amide protons (71/130) changed chemical shift significantly suggesting the possibility that local conformational changes may accompany binding [normalized chemical shift, δ > 0 5 (Cheever et al , 2001)] A nine-residue peptide spanning the p6 PTAP motif (sPEPTAPPEEn) produced very similar chemical shift changes as full-length p6 (Fig 3a), and bound with the same affinity as full-length pό (Fig 3b) This indicates that this "PTAP peptide" contains all of the relevant residues for TsglOl binding Upon addition of 0 5 molar equivalents of either p6 or PTAP peptide, two distinct peaks were observed for each shifted amide, indicating that both complexes were in slow exchange on the NMR time scale (Fig 3a, lower panels) As expected, complex formation proceeded to completion upon addition of a second 0 5 molar equivalent of peptide, and additional shifts were not observed when supersaturating levels of p6 (>4-fold) were added
269 Residues exhibiting the greatest chemical shift changes (δ > 1 8) were clustered about a groove defined by residues from three different structural elements 1) the loop connecting strands 2 and 3, 2) the N- terminal third of the vestigial active site loop, and 3) the C-terminal residues of the domain (Fig 3c,d) The groove is opened up by a 5 residue insertion in the active site loop (Fig lc), displacement of the loop connecting strands 2 and 3 (Fig 2d), and irregularities in C-terminal helix geometry created by two glycine residues (Glyl26 and Glyl36) Hydrophobic residues from strands 3 and 4 (Ile70, Val89, Pro91) line the bottom of the groove, while one end is flanked by charged residues (Arg64, Argl44) This asymmetric charge distribution may help orient the bound peptide, possibly by interacting with complementary charged residues that flank the PTAP motif
270 Mutational analyses were used to confirm that residues in the binding groove make energetically significant interactions in the TsglOl UEV/p6 complex (Fig 3d and 4) Four TsglOl UEV residues located around the putative PTAP binding site were mutated to alanine and tested for their effect on TsglOl binding affinity in Biacore biosensor experiments (Garrus et al, 2001). As expected, alanine substitutions in three residues that surround the rim of the groove (Tyr63, Met95 and Val 141 ) all reduced p6 binding significantly
(Fig. 4 and Table 4).
Table 4. Binding of wildtype and Tsg101 UEV domain mutants to HIV-1 p6, Ub, and a p6-Ub fusion construct.
Figure imgf000064_0001
Figure imgf000064_0002
"Affinities of wildtype TsglOl UEV domain for p6, p6- ubiquitin and ubiquitin are reported as dissociation constants (Kd), averaged from sixteen, eight, and three independent measurements, respectively. Affinities of mutant constructs are reported as fold decrease relative to wildtype binding. Dissociation constants for Ub binding to TsglOl UEV were estimated by extrapolating binding isotherms in which 50% saturation was not achieved.
271. Mutation of Val89, which is located at the bottom of the pocket, had no effect on p6 binding. Therefore, although the Val89 amide showed the greatest chemical shift change upon addition of pό (Fig. 3a), the Val89 methyl groups do not contribute appreciable binding energy, perhaps because the PTAP peptide does not reach down to the very bottom of the pocket. Importantly, the Tyr63— >Ala and Met95— >Ala mutations, which decreased p6 binding affinity by 14- and 52-fold, respectively, also significantly impaired the ability of Tsgl Ol to support HIV- 1 budding, whereas the Val89→Ala mutation had no effect on budding. The excellent correspondence between the viral budding phenotypes and in vitro binding activities of both PTAP and Tsgl Ol UEV mutants strongly supports the idea that PTAP-mediated recruitment of Tsgl Ol to HIV-1 budding sites at the plasma membrane is a prerequisite for the efficient release of virus particles from infected cells
272 The structure presented herein demonstrates that the N-termmal UEV domain of human TsglOl conforms to the general E2 fold, but with several distinctive features that allow it to bind PTAP and ubiquitin TsglOl UEV is the first example of an E2/UEV domain with a peptide binding motif, and disclosed herein it is shown that residues from five different secondary structural elements come together to create a PTAP binding "groove" Analogous sites in other E2/UEV proteins are buried, either by a C-terminal helix (in canonical E2 enzymes) or by the ordered C-terminal residues of Mms2 UEV (Fig 3b), explaining why these domains do not have peptide binding activities 273 The importance of the TsglOl /PTAP interaction in the release of HIV particles seems clear because mutations in either the pό PTAP motif (Gotthnger et al , 1991, Huang et al , 1995) or in TsglOl UEV that block virus release are shown herein to also block the interaction The TsglOl UEV domain represents an attractive target for therapeutic intervention against HIV and Ebola as these viruses require TsglOl for budding (Garrus et al , 2001 , Martin-Serrano et al , 2001) and because the cellular TsglOl protein will not experience selective pressure to mutate in response to drug treatment The disclosed structure therefore provides target binding sites for small molecule inhibitors designed to block viral egress by inhibiting TsglOl binding
274 The role(s) of PTAP binding in normal cellular TsglOl functions remains an open question A number of candidate cellular TsglOl-binding proteins also carry PTAP motifs (Garrus et al , 2001 , Strack et al , 2000), these include plasma membrane proteins known to be downregulated via the vacuolar protein sorting pathway (Berthoud et al , 2000, Strack et al , 2000), as well as proteins that function in the Vps pathway, including Hgs (Vps27) (Garrus et al , 2001 , Komada and Kitamura, 2001) TsglOl contains its own PTAP motif, which is located in a predicted loop region connecting the apparent binding sites for the Vps37 and Vps28 proteins (Fig \a) The TsglOl UEV domain could fold back and bind to this PTAP sequence, perhaps creating an "auto-inhibited" conformation Thus, regulated PTAP binding may be important for normal TsglOl function, and viruses like HIV and Ebola can simply mimic this natural binding interaction a) — Ubiquitin Binding
275 The TsglOl UEV domain also binds ubiquitin, although the interaction is quite weak (Kά = -500 μM) (Garrus et al , 2001) The Ub and PTAP binding sites appear to be distinct, and indeed can be simultaneously occupied as evidenced by the fact that direct fusion of Ub to p6 enhances the binding affinity over that of either ligand alone (l e , the ligands bind cooperatively, Fig 4) As compared to pό, titration with Ub produced chemical shift changes in a distinct, but slightly overlapping subset of TsglOl UEV amides, consistent with the idea that PTAP and Ub bind to different sites (compare Figures 3a and 5a) Significant amide chemical shift changes (δ > 1 8) were observed for only 13 residues, suggesting that Ub does not contact a large surface area or cause large conformational changes upon binding (Fig 5a) Consistent with the weak affinity of TsglOl UEV for (unconjugated) ubiquitin, the complex was in fast exchange As shown in Figure 5a, single resonances were always observed for the perturbed amides and their chemical shift changes increased as the Ub protein ratio increased Residues undergoing the greatest chemical shift changes were located throughout the beta-tongue and at the vestigial active site loop, which flank a large hydrophobic patch on the protein surface that is formed by sidechains from strands 3 and 4 (Fig. 5b,c).
276. The importance of this region for Ub binding was tested by introducing a series of alanine point mutations and quantitating their effects on Ub, p6-Ub, and p6 binding (Fig. 4 and Table 4). Alanine substitutions of beta-tongue residues (Val43, Asn45, Asp46) and a hydrophobic sheet residue (Phe88) significantly reduced TsglOl UEV binding to both p6-Ub and Ub alone (>3-fold) without affecting p6 binding. Substitution of Tφ75, which is exposed on the hydrophobic surface, did not significantly affect the ubiquitin-binding activity of TsglOl UEV, although the indole amide of Tφ75 is significantly shifted during Ub titration. The mutagenesis and NMR chemical shift mapping experiments are generally in good agreement and define the location of the TsglOl UEV Ub-binding site. Interestingly, a Met85->Thr mutation known to block Ub binding and protein sorting by the yeast Vps23p protein (Katzmann et al, 2001), is also located in this region, suggesting that TsglOl and Vps23ρ use the same interface for interacting with Ub.
277. The complementary TsglOl UEV-interacting surface on ubiquitin was also mapped by chemical shift perturbation experiments. As expected, titration of unlabeled TsglOl UEV into 15N-labeled Ub shifted a small subset of Ub amides, and the complex was again in fast exchange (Fig. 5d). The greatest chemical shift changes (δ > 1.0) mapped to the two shortest strands (3 and 4) of the antiparallel β-sheet of Ub, and the N- terminal end of strand 5 (Fig. 5eJ). This region contains a number of polar and charged residues, which may form ionic and/or hydrogen bonding interactions with TsglOl UEV beta-tongue residues. The shifted ubiquitin residues include Lys48, which is used for the formation of polyubiquitin chains that target proteins for proteasomal degradation (Hershko and Ciechanover, 1998).
278. Previous biochemical and modeling studies have suggested that ubiquitin can bind to E2/UEV domains in two distinct modes. In contrast, disclosed herein, the data indicate that ubiquitin binds in yet a third way to the TsglOl UEV domain. As illustrated in Figure 6, both previously known modes of ubiquitin binding are utilized by the heterodimeric Ubcl3/Mms2 complex. This complex can assemble polymeric chains of Ub molecules by binding and catalyzing the linkage of "acceptor" and "donor" ubiquitin molecules. The most general mode of Ub binding is illustrated by the interaction between the donor ubiquitin and the catalytically active Ubcl 3 E2 domain. As in other E2 enzymes, the active site cysteine of Ubcl 3 forms a transient thioester bond with the C-terminus of Ub in the process of transferring Ub from an El enzyme onto the lysine side chain of a protein substrate (Lys63 of another Ub molecule in this case). This covalent chemistry implies that the C-terminal "tail" of Ub must bind near the active site cysteine residue, and there is direct evidence that tail residues form the major contacts when Ub binds to the Ubcl and HsUbc2b E2 enzymes (Hamilton et al, 2001 ; Miura et al, 1999).
279. In contrast, the catalytically inactive Mms2 UEV subunit of the Ubcl3/Mms2 complex binds Ub quite differently. The role of Mms2 is to position the acceptor Ub Lys-63 side chain to attack the C-terminus of the donor ubiquitin. Although two different models for the Mms2/Ub have been proposed (Moraes et al, 2001; VanDemark et al, 2001), mutagenesis studies are most consistent with Ub binding in a channel that straddles the Mms2/Ubcl3 interface (Chan and Hill, 2001; VanDemark et al, 2001), with the Mms2 binding surface defined by the C-terminal half of helix 1, the outer edge of strand 1, and the loop that connects strands 1 and 2. 280. In contrast, the chemical shift mapping and mutagenesis results disclosed herein indicate that ubiquitin binds to the concave "lower" half of the four-stranded sheet of TsglOl UEV. The most prominent feature of this binding site is the beta-tongue projection, and mutations of residues at the tip of the tongue reduce Ub binding. Although this site is distinct from both previously characterized Ub binding surfaces in E2/UEV proteins, it does roughly match the Mms2 binding site on the Ubcl 3 protein (Fig. 6a). Ub binds
TsglOl UEV using a convex surface that encompasses strands 3 and 4, and it is therefore proposed that shape complementarity may play an important role in recognition. The Lys48 residue at the N-terminal end of Ub strand 4 is likely to be sequestered at the TsglOl UEV/Ub interface, which likely precludes polyubiqutination via Lys48 linkages (the targeting signal for proteasomal degradation). 281. In summary, the Ub-binding surface of TsglOl differs from that used by other E2/UEV proteins, leading to the suφrising conclusion that although E2/UEV domains utilize a conserved three dimensional fold to bind ubiquitin, they have evolved at least three distinct surfaces to mediate these interactions. b) Experimental Methods
(1) TsglOl UEV domain 282. TsglOl UEV domain constructs were designed based on an alignment of TsglOl homologoues obtained from the NCBI protein database (A. thaliana, BAB03147; C. elegans, AAC25822; C. mydas, AAF87776; D. melanogaster, AAG29564; H. sapiens, AAC52083; M. musculus, AAH05424; and S. cerevisiae, AAB62820 all of which are incoφorated herein by reference for the protein sequences of the TSGIOI homologoues). Since canonical E2 enzymes are ~150 residues in length, gaps in the alignment near TsglOl residue 150 were inteφreted as potential domain boundaries. Based on the alignments, constructs spanning residues 1-145, 1-150, 1-157, and 1-161 of TsglOl were cloned and expressed from a pETl ld vector (Novagen). The three shortest constructs expressed soluble proteins at high levels in BL21(DE3) E. coli cells. To purify the proteins, cells were lysed using lysozyme and sonication, and insoluble material was removed from the lysate by centrifugation. TsglOl UEV was precipitated from the soluble fraction with ammonium sulfate at 28-55% saturation. The precipitate was redissolved in buffer containing 25 mM MOPS, pH 6.5, and fractionated on an SP-Sepharose column (Pharmacia). TsglOl UEV eluted at ~300 mM NaCl linear salt gradient (50 to 1000 mM NaCl over 400 mL). Fractions containing TsglOl were pooled, adjusted to 1 M ammonium sulfate, and re-fractionated on a Phenyl-Sepharose column (Pharmacia). Pure TsglOl UEV eluted near the beginning of a linear salt gradient (1 to 0 M ammonium sulfate over 200 mL), with typical yields of 15-20 mg of pure protein per liter of E. coli culture. N-terminal amino acid sequencing and mass spectrometry analyses showed that the N-terminal methionine was quantitatively removed during expression, and the masses of all purified proteins were within 1-3 Da of expected. The Η/15N-HSQC spectra of TsglOl . ^, TsglOl 1-150, and TsglOl ι_ι57 were completely superimposable (except for C-terminal residues), and amide protons beyond Phel42 displayed limited proton chemical shift dispersion and shaφ peaks with half-height linewidths of 14-19 Hz (versus 21-24 Hz for structured residues of the domain), indicating that they are disordered. In addition, all three UEV constructs bound with same affinities to p6, p6-Ub and Ub. TsglOl residues 1-145 therefore appear to encompass the entire ordered UEV domain. Hence, all reported structural and biochemical analyses were performed on this defined domain. Mutant TsglOl UEV constructs were cloned using the megaprimer PCR method (Picard et al, 1994), and purified as described for wildtype. (2) Other protein samples
283. GST-p6 constructs and the free p6 domain of the HIV-1 Gag protein were purified as described (Jenkins et al, 2001). The PTAP peptide (NH2-PEPTAPPEE-COOH) was obtained by solid-phase synthesis and purified using reverse phase HPLC. Bovine ubiquitin, which is identical in sequence to human ubiquitin, was purchased from Sigma and purified using size exclusion chromatography. 15N-labeled ubiquitin was purchased from VLI Research, Inc.
(3) NMR Spectroscopy
284. Samples for structure determination were approximately 1.5 mM TsglOl UEV in 20 mM sodium phosphate, 50 mM NaCl, pH 5.5 in 90%H2O/10%D2O. Spectra were recorded at 25 °C on a Varian Inova 600 MHz spectrometer equipped with a triple-resonance Η/1 C/I5N probe and z-axis pulsed field gradient capability. Backbone and sidechain assignments were made using the following NMR experiments: ' N/Η HSQC (Mori et al, 1995), HNCACB (Wittekind, 1993), and HNCO (Kay et al, 1994), , C/Η CT-HSQC (Santoro and King, 1992; Vuister, 1992), 3D 15N-edited TOCSY-HSQC (Zhang et al, 1994), H(CCO)NH, (H)C(CO)NH (Grzesiek et al, 1993) and 4D l3C/13C-edited HMQC-NOESY-HMQC (Vuister et al, 1993). The following NOE data were used to generate distance restraints: 3D 15N-edited NOESY-HSQC (Mori et al, 1995; Zhang et al, 1994), and 3D l 3C-edited NOESY-HSQC (Muhandiram et al, 1993; Pascal et al, 1994). NOESY mixing times were 80 ms. Three-bond coupling constants (VHN-HA) were obtained from a 3D HNHA experiment (Kuboniwa et al, 1994). Hydrogen-bonded amides were identified using deuterium exchange as previously described (Bai et al, 1997). All spectra were processed using FELIX (MSI). Structure coordinates and chemical shifts have been deposited (1KPP, CNS ensemble; 1KPQ, DYANA ensemble).
(4) Structure determination
285. Backbone and sidechain correlations were assigned and NOE intensities were integrated using the tools in SPARKY (T.D. Goddard and D.G. Kneller, University of California, San Francisco). Structures were calculated using the torsion angle dynamics approach in DYANA (Guntert et al, 1997). Initial structures were calculated from ~ 1,500 NOEs. Iterative rounds of structure calculation and NOE assignments led to 10 models that superimposed over secondary structure backbone atoms with an average rmsd of ~0.5 A. Hydrogen bonding restraints (two per hydrogen bond) and phi and psi dihedral angle restraints were then added. These restraints did not alter the structure, but improved convergence. To generate the reported structures, 200 structures were calculated using DYANA, and geometries of the 20 lowest-penalty structures were regularized using CNS (Brunger et al, 1998). The structures were analyzed using PROCHECK-NMR (Laskowski et al, 1996), MOLMOL (Koradi et al, 1996), and INSIGHT II (MSI) (Table 3). Structure figures were created with MOLSCRIPT (Kraulis, 1991), BOBSCRIPT (Esnouf, 1997), and GRASP (Nicholls et al, 1991).
(5) Chemical shift perturbation 286. Titration experiments were performed at 20 °C in 20 mM sodium phosphate, 50 mM NaCl, pH 6 in 90%H2O/10%D2O. To identify the PTAP and Ub binding sites on the UEV domain, unlabeled p6, PTAP peptide, or Ub were titrated into 0.5 mM 15N-labeled UEV domain. To identify the UEV binding site on Ub, unlabeled UEV domain was titrated into 0.2 mM l 5N-labeled Ub. Normalized chemical shift changes were calculated using the equation: δ = 25[(6HN)2 - (δ-VS)2]0'5 (Cheever et al, 2001). Amides displaying the greatest normalized chemical shift changes were displayed using cutoffs of δ > 1.8 (for TsglOl UEV amides) or 1.0 (for Ub amides). Amide chemical shift assignments for human Ub were obtained from the VLI Research, Inc. website.
(6) Binding experiments
287. Binding affinities of purified wildtype and mutant TsglOl UEV domains for immobilized GST- p6ι-27, GST-p6'.27-Ub, and GST-Ub were quantified using a Biacore biosensor as described (Garrus et al, 2001). Measurements were performed at 20 °C in 20 mM sodium phosphate, 150 mM NaCl, 0.05% BSA, 0.01 % P20, pH 7.2.
288. Table 5 sets forth coordinates and related information for the TSG I OI UEV.
289. Table 5
ATOM 1 N ALA 2 -22 .61 -3.413 -13.97 1 .00 0 .00
ATOM 2 CA ALA 2 -21 .71 -3.971 -14.96 1 .00 0 .00
ATOM 3 C ALA 2 -20 .83 -5.034 -14.31 1 .00 0 .00
ATOM 4 O ALA 2 -19 .72 -5.300 -14.77 1 .00 0 .00
ATOM 5 CB ALA 2 -20 .89 -2.845 -15.60 1 .00 0 .00
ATOM 6 N VAL 3 -21 .35 -5.611 -13.23 1 .00 0 .00
ATOM 7 CA VAL 3 -20 .62 -6.640 -12.51 1 .00 0 .00
ATOM 8 C VAL 3 -19. .19 -6.168 -12.27 1 .00 0 .00
ATOM 9 O VAL 3 -18, .93 -5.393 -11.34 1 .00 0, .00
ATOM 10 CB VAL 3 -20, .70 -7.967 -13.27 1. .00 0, .00
ATOM 11 CGI VAL 3 -19, .78 -9.013 -12.63 1 .00 0, .00
ATOM 12 CG2 VAL 3 -22, .14 -8.475 -13.35 1 .00 0, .00
ATOM 13 N SER 4 -18, .29 -6.655 -13.11 1, .00 0, .00
ATOM 14 CA SER 4 -16, .89 -6.293 -13.00 1 .00 0, .00
ATOM 15 c SER 4 -16, .46 -6.298 -11.53 1, .00 0, .00
ATOM 16 O SER 4 -16, .10 -7.342 -10.98 1 .00 0, .00
ATOM 17 CB SER 4 -16. .62 -4.922 -13.62 1, .00 0. .00
ATOM 18 OG SER 4 -17. .79 -4.115 -13.66 1, .00 0, .00
ATOM 19 N GLU 5 -16, .51 -5.119 -10.92 1, .00 0, .00
ATOM 20 CA GLU 5 -16, .13 -4.974 -9.533 1, .00 0, .00
ATOM 21 c GLU 5 -16. .72 -6.122 -8.705 1, .00 0, .00
ATOM 22 O GLU 5 -16, .04 -6.667 -7.833 1 .00 0. .00
ATOM 23 CB GLU 5 -16, .58 -3.619 -8.982 1, .00 0, .00
ATOM 24 CG GLU 5 -17, .94 -3.214 -9.560 1, .00 0, .00
ATOM 25 CD GLU 5 -18, .61 -2.144 -8.693 1, .00 0, .00
ATOM 26 OE1 GLU 5 -18, .38 -0.944 -8.903 1, .00 0, .00
ATOM 27 OE2 GLU 5 -19. ,39 -2.598 -7.773 1. .00 0. .00
ATOM 28 N SER 6 -17. ,96 -6.456 -9.008 1. .00 0. ,00
ATOM 29 CA SER 6 -18. .64 -7.531 -8.302 1. .00 0. .00
ATOM 30 c SER 6 -17. .91 -8.854 -8.539 1. .00 0. .00
ATOM 31 O SER 6 -17. ,84 -9.697 -7.645 1, .00 0. .00
ATOM 32 CB SER 6 -20. ,10 -7.642 -8.742 1. .00 0. ,00
ATOM 33 OG SER 6 -20. ,99 -7.770 -7.633 1. .00 0. .00
ATOM 34 N GLN 7 -17. ,39 -8.997 -9.748 1. .00 0. ,00
ATOM 35 CA GLN 7 -16. ,67 -10.20 -10.11 1. .00 0. ,00
ATOM 36 C GLN 7 -15. ,28 -10.20 -9.473 1. .00 0. ,00
ATOM 37 O GLN 7 -14. ,85 -11.21 -8.912 1. .00 0. ,00
ATOM 38 CB GLN 7 -16. 57 -10.34 -11.63 1. ,00 0. 00
ATOM 39 CG GLN 7 -16. 76 -11.79 -12.06 1. ,00 0. 00
ATOM 40 CD GLN 7 -15. 46 -12.37 -12.62 1. ,00 0. 00
ATOM 41 OE1 GLN 7 -14. ,72 -13.07 -11.95 1. ,00 0. .00
ATOM 42 NE2 GLN 7 -15. .23 -12.04 -13.89 1. ,00 0. ,00
ATOM 43 N LEU 8 -14. .61 -9.070 -9.580 1. .00 0. .00
ATOM 44 CA LEU 8 -13. ,28 -8.929 -9.019 1. ,00 0. .00
ATOM 45 C LEU 8 -13. ,24 -9.572 -7.630 1. ,00 0. ,00
ATOM 46 O LEU 8 -12. ,36 -10.37 -7.337 1. ,00 0. ,00 ATOM 47 CB LEU 8 ■12.84 -7.462 -9.027 1.00 0.00
ATOM 48 CG LEU 8 -12.65 -6.827 -10.40 1 .00 0 .00
ATOM 49 CD1 LEU 8 -11.55 -5.769 -10.37 1 .00 0 .00
ATOM 50 CD2 LEU 8 -12.40 -7.896 -11.47 1 .00 0 .00
ATOM 51 N LYS 9 -14.21 -9.191 -6.813 1 .00 0 .00
ATOM 52 CA LYS 9 -14.31 -9.719 -5.462 1 .00 0 .00
ATOM 53 C LYS 9 -14.27 -11.24 -5.514 1 .00 0 .00
ATOM 54 O LYS 9 -13.61 -11.87 -4.690 1 .00 0 .00
ATOM 55 CB LYS 9 -15.54 -9.158 -4.750 1 .00 0 .00
ATOM 56 CG LYS 9 -15.79 -9.895 -3.432 1 .00 0 .00
ATOM 57 CD LYS 9 -16.91 -9.219 -2.633 1 .00 0 .00
ATOM 58 CE LYS 9 -16.81 -9.571 -1.148 1 .00 0 .00
ATOM 59 NZ LYS 9 18.15 -9.878 -0.598 1 .00 0 .00
ATOM 60 N LYS 10 14.98 -11.78 -6.491 1 .00 0 .00
ATOM 61 CA LYS 10 -15.03 -13.22 -6.661 1 .00 0 .00
ATOM 62 C LYS 10 13.69 -13.72 -7.209 1 .00 0 .00
ATOM 63 O LYS 10 13.33 -14.88 -7.019 1 .00 0 .00
ATOM 64 CB LYS 10 16.23 -13.61 -7.525 1 .00 0 .00
ATOM 65 CG LYS 10 17.35 -14.21 -6.671 1 .00 0 .00
ATOM 66 CD LYS 10 18.56 -14.58 -7.531 1 00 0 .00
ATOM 67 CE LYS 10 19.63 -15.30 -6.700 1 .00 0 .00
ATOM 68 NZ LYS 10 19.30 -16.73 -6.556 1 .00 0 .00
ATOM 69 N MET 11 12.99 -12.82 -7.878 1 00 0 00
ATOM 70 CA MET 11 11.70 -13.15 -8.454 1 00 0 00
ATOM 71 C MET 11 10.60 -13.09 -7.396 1 00 0 00
ATOM 72 O MET 11 9.619 -13.82 -7.484 1 00 0 00
ATOM 73 CB MET 11 11.38 -12.17 -9.583 1 00 0 00
ATOM 74 CG MET 11 12.38 -12.30 -10.73 1 00 0 00
ATOM 75 SD MET 11 11.51 -12.50 -12.27 1 00 0 00
ATOM 76 CE MET 11 11.81 -10.91 -13.01 1 00 0 00
ATOM 77 N VAL 12 10.80 -12.22 -6.420 1 00 0 00
ATOM 78 CA VAL 12 9.846 -12.06 -5.346 1 00 0 00
ATOM 79 C VAL 12 10.27 -12.91 -4.151 1 00 0 00
ATOM 80 O VAL 12 9.824 -12.68 -3.028 1 00 0 00
ATOM 81 CB VAL 12 9.696 -10.58 -4.996 1 00 0 00
ATOM 82 CGI VAL 12 8.941 -9.837 -6.096 1 00 0 00
ATOM 83 CG2 VAL 12 11.05 -9.944 -4.733 1 00 0 00
ATOM 84 N SER 13 11.12 -13.88 -4.434 1 00 0 00
ATOM 85 CA SER 13 11.61 -14.77 -3.396 1 00 0 00
ATOM 86 C SER 13 10.43 -15.45 -2.695 1 00 0 00
ATOM 87 O SER 13 10.59 -16.03 -1.617 1 00 0 00
ATOM 88 CB SER 13 12.56 -15.82 -3.975 1 00 0 00
ATOM 89 OG SER 13 13.20 -16.58 -2.954 1 00 0 00
ATOM 90 N LYS 14 9.283 -15.37 -3.334 1 00 0 00
ATOM 91 CA LYS 14 8.081 -15.98 -2.785 1 00 0 00
ATOM 92 C LYS 14 7.390 -14.97 -1.861 1 00 0 00
ATOM 93 O LYS 14 7.025 -15.31 -0.735 1 00 0 00
ATOM 94 CB LYS 14 7.182 -16.50 -3.908 1 00 0 00
ATOM 95 CG LYS 14 6.910 -18.00 -3.742 1 00 0 00
ATOM 96 CD LYS 14 7.794 -18.82 -4.679 1. 00 0. 00
ATOM 97 CE LYS 14 7.319 -20.27 -4.740 1. 00 0 00
ATOM 98 NZ LYS 14 7.732 -21.01 -3.522 1. 00 0 00
ATOM 99 N TYR 15 7.231 -13.76 -2.370 1. 00 0. 00
ATOM 100 CA TYR 15 6.589 -12.71 -1.604 1. 00 0. 00
ATOM 101 C TYR 15 7.020 -12.76 -0.136 1. 00 0. 00
ATOM 102 O TYR 15 8.154 -12.41 0.195 1. 00 0. 00
ATOM 103 CB TYR 15 7.067 -11.39 -2.218 1. 00 0. 00
ATOM 104 CG TYR 15 6.149 -10.85 -3.314 1. 00 0. 00
ATOM 105 CD1 TYR 15 5.926 -11.58 -4.458 1. 00 0. 00
ATOM 106 CD2 TYR 15 5.544 -9.625 -3.158 1. 00 0. 00
ATOM 107 CE1 TYR 15 5.061 -11.08 -5.489 1. 00 0. 00
ATOM 108 CE2 TYR 15 4.679 -9.113 -4.189 1. 00 0. 00 ATOM 109 CZ TYR 15 -4.481 -9.866 -5.304 1.00 0.00
ATOM 110 OH TYR 15 -3.665 -9.382 -6 .278 1 .00 0 .00
ATOM 111 N LYS 16 -6.089 -13.18 0 .706 1 .00 0 .00
ATOM 112 CA LYS 16 -6.357 -13.28 2 .130 1 .00 0 .00
ATOM 113 C LYS 16 -7.073 -12.01 2 .599 1 .00 0 .00
ATOM 114 O LYS 16 8.131 -12.09 3 .222 1 .00 0 .00
ATOM 115 CB LYS 16 5.069 -13.58 2 .898 1 .00 0 .00
ATOM 116 CG LYS 16 5.330 -13.64 4 .405 1 .00 0 .00
ATOM 117 CD LYS 16 4.271 -12.85 5 .175 1 .00 0 .00
ATOM 118 CE LYS 16 3.300 -13.78 5 .895 1 .00 0 .00
ATOM 119 NZ LYS 16 2.596 -13.07 6 .981 1 .00 0 .00
ATOM 120 N TYR 17 6.466 -10.89 2 .283 1 .00 0 .00
ATOM 121 CA TYR 17 7.032 -9.608 2 .664 1 .00 0 .00
ATOM 122 C TYR 17 7.878 -9.024 1 .532 1 .00 0 .00
ATOM 123 O TYR 17 7.998 -7.806 1 .407 1 .00 0 .00
ATOM 124 CB TYR 17 5.841 -8.683 2 .925 1 .00 0 .00
ATOM 125 CG TYR 17 5.308 -8.744 4 .357 1 .00 0 .00
ATOM 126 CD1 TYR 17 6.187 -8.733 5 .422 1 .00 0 .00
ATOM 127 CD2 TYR 17 3.949 -8.809 4 586 1 .00 0 00
ATOM 128 CE1 TYR 17 5.685 -8.790 6 771 1 .00 0 00
ATOM 129 CE2 TYR 17 3.447 -8.866 5 .934 1 .00 0 00
ATOM 130 CZ TYR 17 4.340 -8.854 6 .960 1 .00 0 00
ATOM 131 OH TYR 17 3.866 -8.908 8 234 1 00 0 00
ATOM 132 N ARG 18 8.443 -9.919 0 734 1 00 0 00
ATOM 133 CA ARG 18 9.274 -9.507 -0 383 1 00 0 00
ATOM 134 C ARG 18 10.17 -8.339 0 025 1 00 0 00
ATOM 135 O ARG 18 10.24 -7.331 -0 676 1 00 0 00
ATOM 136 CB ARG 18 10.14 -10.66 -0 877 1 00 0 00
ATOM 137 CG ARG 18 11.05 -11.17 0 238 1 00 0 00
ATOM 138 CD ARG 18 11.68 -12.50 -0 143 1 00 0 00
ATOM 139 NE ARG 18 13.15 -12.45 0 062 1 00 0 00
ATOM 140 CZ ARG 18 13.75 -12.57 1 265 1 00 0 00
ATOM 141 NH1 ARG 18 15.06 -12.51 1 333 1 00 0 00
ATOM 142 NH2 ARG 18 13.01 -12.76 2 382 1 00 0 00
ATOM 143 N ASP 19 10.83 -8.512 1 160 1 00 0 00
ATOM 144 CA ASP 19 11.72 -7.485 1 671 1 00 0 00
ATOM 145 C ASP 19 10.99 -6.137 1 665 1 00 0 00
ATOM 146 O ASP 19 11.54 -5.137 1 198 1 00 0 00
ATOM 147 CB ASP 19 12.14 -7.787 3 110 1 00 0 00
ATOM 148 CG ASP 19 13.63 -8.090 3 297 1 00 0 00
ATOM 149 OD1 ASP 19 14.07 -9.237 3 141 1 00 0 00
ATOM 150 OD2 ASP 19 14.35 -7.074 3 622 1 00 0 00
ATOM 151 N LEU 20 9.783 -6.154 2 186 1 00 0 00
ATOM 152 CA LEU 20 8.978 -4.946 2 246 1 00 0 00
ATOM 153 C LEU 20 8.677 -4.468 0 825 1 00 0 00
ATOM 154 O LEU 20 9.072 -3.370 0 439 1 00 0 00
ATOM 155 CB LEU 20 7.726 -5.179 3 095 1 00 0 00
ATOM 156 CG LEU 20 7.816 -4.735 4 557 1 00 0 00
ATOM 157 CD1 LEU 20 7.065 -3.422 4. 778 1. 00 0. 00
ATOM 158 CD2 LEU 20 9.272 -4.648 5. 015 1. 00 0. 00
ATOM 159 N THR 21 7.979 -5.317 0. 085 1. 00 0 00
ATOM 160 CA THR 21 7.621 -4.995 -1. 286 1. 00 0. 00
ATOM 161 C THR 21 8.789 -4.310 -1. 996 1. 00 0. 00
ATOM 162 O THR 21 8.582 -3.447 -2. 848 1. 00 0. 00
ATOM 163 CB THR 21 7.166 -6.285 -1. 972 1. 00 0. 00
ATOM 164 OG1 THR 21 5.842 -6.489 -1. 485 1. 00 0. 00
ATOM 165 CG2 THR 21 6.985 -6.114 -3. 481 1. 00 0. 00
ATOM 166 N VAL 22 9.991 -4.719 -1. 620 1. 00 0. 00
ATOM 167 CA VAL 22 11.19 -4.155 -2. 209 1. 00 0. 00
ATOM 168 C VAL 22 11.46 -2.787 -1. 582 1. 00 0. 00
ATOM 169 O VAL 22 11.75 -1.822 -2. 290 1. 00 0. 00
ATOM 170 CB VAL 22 12.35 -5.132 -2. 053 1. 00 0. 00 ATOM 171 CGI VAL 22 13.68 -4.383 -1.946 1.00 0.00
ATOM 172 CG2 VAL 22 12.38 -6 .139 -3 .205 1 .00 0 .00
ATOM 173 N ARG 23 11.37 -2 .748 -0 .262 1 .00 0 .00
ATOM 174 CA ARG 23 11.61 -1 .514 0 .469 1 .00 0 .00
ATOM 175 C ARG 23 10.56 -0 .465 0 .094 1 .00 0 .00
ATOM 176 O ARG 23 10.89 0 .586 -0 .450 1 .00 0 .00
ATOM 177 CB ARG 23 11.56 -1 .751 1 .980 1 .00 0 .00
ATOM 178 CG ARG 23 12.97 -1 .969 2 .541 1 .00 0 .00
ATOM 179 CD ARG 23 13.11 -3 .362 3 .158 1 .00 0 .00
ATOM 180 NE ARG 23 14.32 -4 .031 2 .636 1 .00 0 .00
ATOM 181 CZ ARG 23 15.56 -3 .859 3 .146 1 .00 0 .00
ATOM 182 NH1 ARG 23 16.57 -4 .507 2 .600 1 .00 0 .00
ATOM 183 NH2 ARG 23 15.76 -3 .037 4 .197 1 .00 0 .00
ATOM 184 N GLU 24 9.317 -0 .787 0 .401 1 .00 0 .00
ATOM 185 CA GLU 24 8.217 0 .114 0 .104 1 .00 0 .00
ATOM 186 C GLU 24 8.351 0 .663 -1 .318 1 .00 0 .00
ATOM 187 O GLU 24 8.254 1 870 -1 533 1 .00 0 00
ATOM 188 CB GLU 24 6.869 -0 584 0 297 1 .00 0 00
ATOM 189 CG GLU 24 6.635 -0 924 1 771 1 .00 0 .00
ATOM 190 CD GLU 24 5.688 -2 117 1 915 1 .00 0 00
ATOM 191 OE1 GLU 24 5.927 -3 173 1 310 1 .00 0 00
ATOM 192 OE2 GLU 24 4.674 -1 919 2 686 1 .00 0 00
ATOM 193 N THR 25 8.571 -0 250 -2 253 1 00 0 00
ATOM 194 CA THR 25 8.719 0 128 -3 648 1 00 0 00
ATOM 195 C THR 25 9.949 1 020 -3 831 1 00 0 00
ATOM 196 O THR 25 9.866 2 076 -4 457 1 00 0 00
ATOM 197 CB THR 25 8.767 -1 154 -4 482 1 00 0 00
ATOM 198 OG1 THR 25 7.425 -1 631 -4 463 1 00 0 00
ATOM 199 CG2 THR 25 9.043 -0 879 -5 962 1 00 0 00
ATOM 200 N VAL 26 11.05 0 562 -3 274 1 00 0 00
ATOM 201 CA VAL 26 12.30 1 305 -3 369 1 00 0 00
ATOM 202 C VAL 26 12.04 2 768 -3 001 1 00 0 00
ATOM 203 O VAL 26 12.59 3 674 -3 629 1 00 0 00
ATOM 204 CB VAL 26 13.37 0 646 -2 496 1 00 0 00
ATOM 205 CGI VAL 26 14.36 1 684 -1 970 1 00 0 00
ATOM 206 CG2 VAL 26 14.09 -0 467 -3 260 1 00 0 00
ATOM 207 N ASN 27 11.21 2 953 -1 985 1 00 0 00
ATOM 208 CA ASN 27 10.88 4 290 -1 526 1 00 0 00
ATOM 209 C ASN 27 10.11 5 026 -2 625 1 00 0 00
ATOM 210 0 ASN 27 10.32 6 218 -2 844 1 00 0 00
ATOM 211 CB ASN 27 9.997 4 240 -0 281 1 00 0 00
ATOM 212 CG ASN 27 10.66 3 442 0 839 1 00 0 00
ATOM 213 OD1 ASN 27 11.86 3 486 1 033 1 00 0 00
ATOM 214 ND2 ASN 27 9.824 2 714 1 564 1 00 0 00
ATOM 215 N VAL 28 9.243 4 285 -3 289 1 00 0 00
ATOM 216 CA VAL 28 8.443 4 851 -4 360 1 00 0 00
ATOM 217 C VAL 28 9.360 5 253 -5 518 1 00 0 00
ATOM 218 O VAL 28 9.394 6 417 -5 912 1 00 0 00
ATOM 219 CB VAL 28 7.351 3 864 -4. 778 1 00 0 00
ATOM 220 CGI VAL 28 6.749 4 250 -6. 129 1 00 0. 00
ATOM 221 CG2 VAL 28 6.266 3 760 -3. 703 1 00 0. 00
ATOM 222 N ILE 29 10.07 4 265 -6. 032 1 00 0. 00
ATOM 223 CA ILE 29 10.98 4. 501 -7. 135 1 00 0. 00
ATOM 224 C ILE 29 12.06 5. 496 -6. 698 1. 00 0. 00
ATOM 225 O ILE 29 12.75 6. 076 -7. 534 1. 00 0. 00
ATOM 226 CB ILE 29 11.55 3. 177 -7. 659 1. 00 0. 00
ATOM 227 CGI ILE 29 11.62 2. 135 -6. 541 1. 00 0. 00
ATOM 228 CG2 ILE 29 10.74 2. 675 -8. 857 1 00 0. 00
ATOM 229 CD1 ILE 29 12.70 1. 090 -6. 837 1 00 0. 00
ATOM 230 N THR 30 12.17 5. 661 -5. 388 1. 00 0. 00
ATOM 231 CA THR 30 13.15 6. 575 -4. 828 1. 00 0. 00
ATOM 232 C THR 30 12.64 8. 014 -4. 889 1 00 0. 00 ATOM 233 O THR 30 -13.33 8.905 -5.379 1.00 0.00
ATOM 234 CB THR 30 -13.48 6.106 -3.410 1.00 0.00
ATOM 235 OG1 THR 30 -14.49 5.117 -3.595 1.00 0.00
ATOM 236 CG2 THR 30 -14.17 7.191 -2.580 1.00 0.00
ATOM 237 N LEU 31 -11.43 8.196 -4.383 1.00 0.00
ATOM 238 CA LEU 31 -10.81 9.511 -4.373 1.00 0.00
ATOM 239 C LEU 31 -10.39 9.885 -5.797 1.00 0.00
ATOM 240 O LEU 31 -10.38 11.061 -6.156 1.00 0.00
ATOM 241 CB LEU 31 -9.668 9.557 -3.364 1.00 0.00
ATOM 242 CG LEU 31 -9.245 10.949 -2.891 1.00 0.00
ATOM 243 CD1 LEU 31 -10.38 11.644 -2.142 1.00 0.00
ATOM 244 CD2 LEU 31 -7.968 10.878 -2.052 1.00 0.00
ATOM 245 N TYR 32 -10.06 8.861 -6.568 1.00 0.00
ATOM 246 CA TYR 32 -9.647 9.068 -7.945 1.00 0.00
ATOM 247 C TYR 32 -10.06 7.889 -8.827 1.00 0.00
ATOM 248 O TYR 32 -9.418 6.844 -8.819 1.00 0.00
ATOM 249 CB TYR 32 -8.119 9.150 -7.914 1.00 0.00
ATOM 250 CG TYR 32 -7.578 10.465 -7.349 1.00 0.00
ATOM 251 CD1 TYR 32 -7.383 11.547 -8.183 1.00 0.00
ATOM 252 CD2 TYR 32 -7.286 10.569 -6.004 1.00 0.00
ATOM 253 CE1 TYR 32 -6.874 12.784 -7.651 1.00 0.00
ATOM 254 CE2 TYR 32 -6.778 11.806 -5.471 1.00 0.00
ATOM 255 CZ TYR 32 -6.596 12.852 -6.321 1.00 0.00
ATOM 256 OH TYR 32 -6.115 14.022 -5.818 1.00 0.00
ATOM 257 N LYS 33 -11.13 8.098 -9.567 1.00 0.00
ATOM 258 CA LYS 33 -11.65 7.066 -10.45 1.00 0.00
ATOM 259 C LYS 33 -10.75 6.968 -11.68 1.00 0.00
ATOM 260 O LYS 33 -11.22 7.105 -12.81 1.00 0.00
ATOM 261 CB LYS 33 -13.12 7.325 -10.78 1.00 0.00
ATOM 262 CG LYS 33 -13.94 7.501 -9.506 1.00 0.00
ATOM 263 CD LYS 33 -15.23 8.288 -9.787 1.00 0.00
ATOM 264 CE LYS 33 -14.94 9.789 -9.870 1.00 0.00
ATOM 265 NZ LYS 33 -16.18 10.532 -10.19 1.00 0.00
ATOM 266 N ASP 34 -9.478 6.731 -11.43 1.00 0.00
ATOM 267 CA ASP 34 -8.509 6.613 -12.50 1.00 0.00
ATOM 268 C ASP 34 -7.854 5.232 -12.44 1.00 0.00
ATOM 269 O ASP 34 -7.599 4.617 -13.48 1.00 0.00
ATOM 270 CB ASP 34 -7.407 7.666 -12.37 1.00 0.00
ATOM 271 CG ASP 34 -6.722 7.716 -11.00 1.00 0.00
ATOM 272 OD1 ASP 34 -7.053 6.939 -10.09 1.00 0.00
ATOM 273 OD2 ASP 34 -5.800 8.611 -10.89 1.00 0.00
ATOM 274 N LEU 35 -7.599 4.785 -11.22 1.00 0.00
ATOM 275 CA LEU 35 -6.978 3.488 -11.01 1.00 0.00
ATOM 276 C LEU 35 -8.020 2.387 -11.23 1.00 0.00
ATOM 277 O LEU 35 -8.738 2.017 -10.30 1.00 0.00
ATOM 278 CB LEU 35 -6.299 3.431 -9.649 1.00 0.00
ATOM 279 CG LEU 35 -4.873 3.982 -9.585 1.00 0.00
ATOM 280 CD1 LEU 35 -3.998 3.368 -10.68 1.00 0.00
ATOM 281 CD2 LEU 35 -4.872 5.511 -9.640 1.00 0.00
ATOM 282 N LYS 36 -8.069 1.896 -12.46 1.00 0.00
ATOM 283 CA LYS 36 -9.011 0.846 -12.81 1.00 0.00
ATOM 284 C LYS 36 -8.482 -0.497 -12.30 1.00 0.00
ATOM 285 O LYS 36 -7.360 -0.887 -12.62 1.00 0.00
ATOM 286 CB LYS 36 -9.301 0.864 -14.31 1.00 0.00
ATOM 287 CG LYS 36 -10.75 0.505 -14.59 1.00 0.00
ATOM 288 CD LYS 36 -11.64 1.748 -14.53 1.00 0.00
ATOM 289 CE LYS 36 -12.80 1.544 -13.56 1.00 0.00
ATOM 290 NZ LYS 36 -14.06 2.081 -14.13 1.00 0.00
ATOM 291 N PRO 37 -9.339 -1.184 -11.50 1.00 0.00
ATOM 292 CA PRO 37 -8.970 -2.476 -10.94 1.00 0.00
ATOM 293 C PRO 37 -9.034 -3.570 -12.01 1.00 0.00
ATOM 294 O PRO 37 -10.10 -3.883 -12.52 1.00 0.00 ATOM 295 CB PRO 37 -9.943 -2.704 -9.803 1.00 0.00
ATOM 296 CG PRO 37 -11.10 -1.760 -10.05 1 .00 0 .00
ATOM 297 CD PRO 37 -10.67 -0.754 -11.10 1 .00 0 .00
ATOM 298 N VAL 38 -7 .870 -4.124 -12.32 1 .00 0 .00
ATOM 299 CA VAL 38 -7 .781 -5.176 -13.31 1 .00 0 .00
ATOM 300 C VAL 38 -7 .598 -6.523 -12.61 1 .00 0. .00
ATOM 301 O VAL 38 -7 .290 -6.570 -11.42 1 .00 0 .00
ATOM 302 CB VAL 38 -6 .659 -4.863 -14.31 1 .00 0 .00
ATOM 303 CGI VAL 38 -5 .392 -4.412 -13.58 1 .00 0 .00
ATOM 304 CG2 VAL 38 -6 .374 -6.065 -15.21 1 .00 0 .00
ATOM 305 N LEU 39 •7 .797 -7.586 -13.38 1 .00 0 .00
ATOM 306 CA LEU 39 ■7 .658 -8.930 -12.84 1 .00 0 .00
ATOM 307 C LEU 39 -6 .893 -9.796 -13.85 1 .00 0 .00
ATOM 308 O LEU 39 -7 .485 -10.35 -14.77 1 .00 0 .00
ATOM 309 CB LEU 39 -9 .026 -9.498 -12.46 1 .00 0 .00
ATOM 310 CG LEU 39 -9 .028 -10.54 -11.34 1 .00 0 .00
ATOM 311 CD1 LEU 39 -8 .425 -11.85 -11.83 1 .00 0. .00
ATOM 312 CD2 LEU 39 -8 .318 -10.02 -10.10 1 .00 0 .00
ATOM 313 N ASP 40 ■5 .588 -9.880 -13.63 1 .00 0, .00
ATOM 314 CA ASP 40 •4 .735 -10.66 -14.51 1 .00 0, .00
ATOM 315 C ASP 40 -4 .481 -12.02 -13.87 1 .00 0 .00
ATOM 316 O ASP 40 -4 .073 -12.10 -12.71 1 .00 0 .00
ATOM 317 CB ASP 40 •3 .382 -9.986 -14.72 1 .00 0. .00
ATOM 318 CG ASP 40 ■2 .840 -10.05 -16.15 1 .00 0, .00
ATOM 319 OD1 ASP 40 •2 .421 -11.12 -16.62 1 .00 0, .00
ATOM 320 OD2 ASP 40 ■2 .860 -8.937 -16.79 1 .00 0, .00
ATOM 321 N SER 41 •4, .734 -13.06 -14.65 1, .00 0. .00
ATOM 322 CA SER 41 ■4, .537 -14.42 -14.17 1, .00 0. .00
ATOM 323 C SER 41 •3, .108 -14.59 -13.65 1, .00 0. ,00
ATOM 324 O SER 41 ■2, .146 -14.34 -14.37 1, .00 0. .00
ATOM 325 CB SER 41 •4, .823 -15.44 -15.28 1, .00 0. ,00
ATOM 326 OG SER 41 •4. .742 -16.78 -14.80 1, .00 0. ,00
ATOM 327 N TYR 42 •3. .016 -15.02 -12.40 1. .00 0. .00
ATOM 328 CA TYR 42 ■1, .722 -15.23 -11.77 1, .00 0. ,00
ATOM 329 C TYR 42 0, .934 -16.32 -12.49 1, .00 0. ,00
ATOM 330 O TYR 42 •0. .948 -17.48 -12.07 1. .00 0. ,00
ATOM 331 CB TYR 42 •2. .013 -15.68 -10.34 1. .00 0. ,00
ATOM 332 CG TYR 42 ■0. .874 -15.40 -9.361 1, .00 0. .00
ATOM 333 CD1 TYR 42 0, .433 -15.64 -9.736 1, .00 0. .00
ATOM 334 CD2 TYR 42 ■1. .154 -14.92 -8.100 1. .00 0. ,00
ATOM 335 CE1 TYR 42 1. .506 -15.38 -8.810 1. .00 0. ,00
ATOM 336 CE2 TYR 42 •0. .082 -14.66 -7.174 1, .00 0. ,00
ATOM 337 CZ TYR 42 1, .195 -14.90 -7.575 1. .00 0. ,00
ATOM 338 OH TYR 42 2. ,208 -14.66 -6.700 1. .00 0. ,00
ATOM 339 N VAL 43 0. ,266 -15.92 -13.56 1. ,00 0. .00
ATOM 340 CA VAL 43 0. ,526 -16.86 -14.34 1. ,00 0. ,00
ATOM 341 C VAL 43 2. ,012 -16.56 -14.14 1. .00 0. ,00
ATOM 342 O VAL 43 2. ,422 -15.40 -14.15 1. ,00 0. ,00
ATOM 343 CB VAL 43 0. ,102 -16.80 -15.81 1. ,00 0. 00
ATOM 344 CGI VAL 43 0. ,288 -15.40 -16.38 1. ,00 0. 00
ATOM 345 CG2 VAL 43 0. ,865 -17.84 -16.64 1. .00 0. 00
ATOM 346 N PHE 44 2. ,778 -17.62 -13.96 1. ,00 0. 00
ATOM 347 CA PHE 44 4. 210 -17.49 -13.75 1. 00 0. 00
ATOM 348 C PHE 44 4. 978 -17.72 -15.05 1. 00 0. 00
ATOM 349 O PHE 44 4. 402 -17.66 -16.14 1. 00 0. 00
ATOM 350 CB PHE 44 4. 618 -18.56 -12.73 1. 00 0. 00
ATOM 351 CG PHE 44 3. 573 -18.81 -11.64 1. 00 0. 00
ATOM 352 CD1 PHE 44 2. 611 -19.75 -11.83 1. 00 0. 00
ATOM 353 CD2 PHE 44 3. 606 -18.09 -10.49 1. 00 0. 00
ATOM 354 CE1 PHE 44 1. 642 -19.98 -10.82 1. 00 0. 00
ATOM 355 CE2 PHE 44 2. 637 -18.32 -9.482 1. 00 0. 00
ATOM 356 CZ PHE 44 1. 674 -19.27 -9.668 1. 00 0. 00 ATOM 357 N ASN 45 6.266 -18.00 -14.90 1.00 0.00
ATOM 358 CA ASN 45 7 .118 -18 .24 -16.05 1 .00 0 .00
ATOM 359 C ASN 45 7 .172 -19 .75 -16.33 1 .00 0 .00
ATOM 360 O ASN 45 8 .171 -20 .25 -16.84 1 .00 0 .00
ATOM 361 CB ASN 45 8 .545 -17 .76 -15.79 1 .00 0 .00
ATOM 362 CG ASN 45 8 .745 -16 .33 -16.32 1 .00 0 .00
ATOM 363 OD1 ASN 45 9 .024 -16 .11 -17.49 1 .00 0 .00
ATOM 364 ND2 ASN 45 8 .589 -15 .39 -15.40 1 .00 0 .00
ATOM 365 N ASP 46 6 .084 -20 .42 -15.98 1 .00 0 00
ATOM 366 CA ASP 46 5 .996 -21 .85 -16.19 1 .00 0 .00
ATOM 367 C ASP 46 4 .917 -22 .15 -17.23 1 .00 0 .00
ATOM 368 O ASP 46 5 .045 -23 .09 -18.01 1 .00 0 .00
ATOM 369 CB ASP 46 5 .611 -22 .57 -14.89 1 .00 0 .00
ATOM 370 CG ASP 46 5 .697 -24 10 -14.95 1 .00 0 00
ATOM 371 OD1 ASP 46 4 .721 -24 .78 -15.29 1 .00 0 00
ATOM 372 OD2 ASP 46 6 .841 -24 .59 -14.62 1 .00 0 .00
ATOM 373 N GLY 47 3 .876 -21 .33 -17.21 1 .00 0 .00
ATOM 374 CA GLY 47 2 .776 -21 .49 -18.14 1 .00 0 .00
ATOM 375 C GLY 47 1 448 -21 66 -17.40 1 .00 0 00
ATOM 376 O GLY 47 0 .380 -21 48 -17.99 1 .00 0 00
ATOM 377 N SER 48 1 .557 -22 00 -16.13 1 .00 0 00
ATOM 378 CA SER 48 0 378 -22 19 -15.30 1 .00 0 00
ATOM 379 C SER 48 0 149 -20 84 -14.82 1 .00 0 00
ATOM 380 O SER 48 0 .627 -19 98 -14.41 1 .00 0 00
ATOM 381 CB SER 48 0 684 -23 10 -14.11 1 00 0 00
ATOM 382 OG SER 48 2 061 -23 46 -14.05 1 00 0 00
ATOM 383 N SER 49 1 465 -20 70 -14.88 1 00 0 00
ATOM 384 CA SER 49 2 105 -19 46 -14.45 1 00 0 00
ATOM 385 C SER 49 3 217 -19 77 -13.45 1 00 0 00
ATOM 386 O SER 49 3 760 -20 87 -13.44 1 00 0 00
ATOM 387 CB SER 49 2 669 -18 69 -15.65 1 00 0 00
ATOM 388 OG SER 49 3 908 -19 24 -16.10 1 00 0 00
ATOM 389 N ARG 50 3 522 -18 77 -12.63 1 00 0 00
ATOM 390 CA ARG 50 4 560 -18 92 -11.62 1 00 0 00
ATOM 391 C ARG 50 5 464 -17 69 -11.61 1 00 0 00
ATOM 392 O ARG 50 6 422 -17 61 -12.37 1 00 0 00
ATOM 393 CB ARG 50 3 953 -19 12 -10.23 1 00 0 00
ATOM 394 CG ARG 50 3 649 -20 60 -9.980 1 00 0 00
ATOM 395 CD ARG 50 3 099 -20 81 -8.567 1 00 0 00
ATOM 396 NE ARG 50 3 446 -22 16 -8.084 1 00 0 00
ATOM 397 CZ ARG 50 3 248 -22 59 -6.818 1 00 0 00
ATOM 398 NH1 ARG 50 3 596 -23 82 -6.495 1 00 0 00
ATOM 399 NH2 ARG 50 2 706 -21 77 -5.895 1 00 0 00
ATOM 400 N GLU 51 5 127 -16 76 -10.72 1 00 0 00
ATOM 401 CA GLU 51 5 897 -15 54 -10.59 1 00 0 00
ATOM 402 C GLU 51 5 158 -14 54 -9.706 1 00 0 00
ATOM 403 O GLU 51 4 845 -14 84 -8.556 1 00 0 00
ATOM 404 CB GLU 51 7 299 -15 82 -10.05 1 00 0 00
ATOM 405 CG GLU 51 7 229 -16 57 -8.725 1 00 0 00
ATOM 406 CD GLU 51 8 566 -17 24 -8.403 1 00 0 00
ATOM 407 OE1 GLU 51 8 872 -18 31 -8.953 1 00 0 00
ATOM 408 OE2 GLU 51 9 298 -16. 62 -7.546 1 00 0. 00
ATOM 409 N LEU 52 4 902 -13. 37 -10.27 1 00 0. 00
ATOM 410 CA LEU 52 4 206 -12. 32 -9.541 1. 00 0. 00
ATOM 411 C LEU 52 4 819 -10. 97 -9.893 1 00 0. 00
ATOM 412 O LEU 52 5 059 -10 68 -11.06 1 00 0. 00
ATOM 413 CB LEU 52 2. 700 -12. 40 -9.796 1. 00 0. 00
ATOM 414 CG LEU 52 1. 849 -11. 31 -9.134 1. 00 0. 00
ATOM 415 CD1 LEU 52 2. 019 -9.983 -9.848 1. 00 0. 00
ATOM 416 CD2 LEU 52 2 157 -11. 22 -7.639 1. 00 0. 00
ATOM 417 N MET 53 5 057 -10. 18 -8.858 1. 00 0. 00
ATOM 418 CA MET 53 5. 637 -8.864 -9.044 1. 00 0. 00 ATOM 419 C MET 53 -4.548 -7.792 -9.135 1.00 0.00
ATOM 420 O MET 53 -3.583 -7.817 -8.371 1.00 0.00
ATOM 421 CB MET 53 -6.570 -8.547 -7.873 1.00 0.00
ATOM 422 CG MET 53 -7.242 -7.185 -8.062 1.00 0.00
ATOM 423 SD MET 53 -8.014 -6.670 -6.536 1.00 0.00
ATOM 424 CE MET 53 -7.554 -4.945 -6.523 1.00 0.00
ATOM 425 N ASN 54 -4.740 -6.877 -10.07 1.00 0.00
ATOM 426 CA ASN 54 -3.785 -5.799 -10.27 1.00 0.00
ATOM 427 C ASN 54 -4.539 -4.473 -10.39 1.00 0.00
ATOM 428 O ASN 54 -5.767 -4.456 -10.45 1.00 0.00
ATOM 429 CB ASN 54 -2.981 -6.006 -11.55 1.00 0.00
ATOM 430 CG ASN 54 -3.462 -7.248 -12.31 1.00 0.00
ATOM 431 OD1 ASN 54 -4.451 -7.230 -13.02 1.00 0.00
ATOM 432 ND2 ASN 54 -2.706 -8.325 -12.11 1.00 0.00
ATOM 433 N LEU 55 -3.771 -3.394 -10.42 1.00 0.00
ATOM 434 CA LEU 55 -4.351 -2.066 -10.53 1.00 0.00
ATOM 435 C LEU 55 -3.835 -1.397 -11.81 1.00 0.00
ATOM 436 O LEU 55 -2.660 -1.041 -11.90 1.00 0.00
ATOM 437 CB LEU 55 -4.088 -1.256 -9.268 1.00 0.00
ATOM 438 CG LEU 55 -5.245 -1.174 -8.272 1.00 0.00
ATOM 439 CD1 LEU 55 -4.769 -1.475 -6.850 1.00 0.00
ATOM 440 CD2 LEU 55 -5.955 0.178 -8.364 1.00 0.00
ATOM 441 N THR 56 -4.738 -1.244 -12.77 1.00 0.00
ATOM 442 CA THR 56 -4.389 -0.624 -14.03 1.00 0.00
ATOM 443 C THR 56 -5.279 0.593 -14.30 1.00 0.00
ATOM 444 O THR 56 -6.491 0.456 -14.45 1.00 0.00
ATOM 445 CB THR 56 -4.481 -1.692 -15.12 1.00 0.00
ATOM 446 OG1 THR 56 -3.287 -2.453 -14.97 1.00 0.00
ATOM 447 CG2 THR 56 -4.368 -1.102 -16.53 1.00 0.00
ATOM 448 N GLY 57 -4.643 1.754 -14.33 1.00 0.00
ATOM 449 CA GLY 57 -5.363 2.993 -14.57 1.00 0.00
ATOM 450 C GLY 57 -4.411 4.099 -15.03 1.00 0.00
ATOM 451 O GLY 57 -3.474 3.843 -15.79 1.00 0.00
ATOM 452 N THR 58 -4.684 5.306 -14.56 1.00 0.00
ATOM 453 CA THR 58 -3.864 6.452 -14.91 1.00 0.00
ATOM 454 C THR 58 -3.705 7.385 -13.71 1.00 0.00
ATOM 455 0 THR 58 -4.508 7.347 -12.78 1.00 0.00
ATOM 456 CB THR 58 -4.498 7.130 -16.13 1.00 0.00
ATOM 457 OGl THR 58 -5.898 7.062 -15.87 1.00 0.00
ATOM 458 CG2 THR 58 -4.313 6.319 -17.41 1.00 0.00
ATOM 459 N ILE 59 -2.664 8.203 -13.77 1.00 0.00
ATOM 460 CA ILE 59 -2.390 9.144 -12.70 1.00 0.00
ATOM 461 C ILE 59 -2.101 10.522 -13.30 1.00 0.00
ATOM 462 O ILE 59 -1.425 10.630 -14.32 1.00 0.00
ATOM 463 CB ILE 59 -1.272 8.619 -11.80 1.00 0.00
ATOM 464 CGI ILE 59 -1.647 7.266 -11.19 1.00 0.00
ATOM 465 CG2 ILE 59 -0.903 9.646 -10.72 1.00 0.00
ATOM 466 CD1 ILE 59 -0.571 6.786 -10.21 1.00 0.00
ATOM 467 N PRO 60 -2.641 11.569 -12.62 1.00 0.00
ATOM 468 CA PRO 60 -2.448 12.936 -13.07 1.00 0.00
ATOM 469 C PRO 60 -1.031 13.421 -12.76 1.00 0.00
ATOM 470 O PRO 60 -0.450 13.044 -11.75 1.00 0.00
ATOM 471 CB PRO 60 -3.522 13.743 -12.36 1.00 0.00
ATOM 472 CG PRO 60 -3.975 12.889 -11.19 1.00 0.00
ATOM 473 CD PRO 60 -3.447 11.480 -11.40 1.00 0.00
ATOM 474 N VAL 61 -0.515 14.252 -13.66 1.00 0.00
ATOM 475 CA VAL 61 0.822 14.794 -13.49 1.00 0.00
ATOM 476 C VAL 61 0.775 16.315 -13.65 1.00 0.00
ATOM 477 O VAL 61 1.099 16.845 -14.71 1.00 0.00
ATOM 478 CB VAL 61 1.784 14.122 -14.47 1.00 0.00
ATOM 479 CGI VAL 61 2.981 15.027 -14.78 1.00 0.00
ATOM 480 CG2 VAL 61 2.245 12.761 -13.95 1.00 0.00 ATOM 481 N PRO 62 0.359 16.992 -12.54 1.00 0.00
ATOM 482 CA PRO 62 0.265 18.443 -12.55 1.00 0.00
ATOM 483 C PRO 62 1.653 19.082 -12.46 1.00 0.00
ATOM 484 O PRO 62 2.336 18.952 -11.44 1.00 0.00
ATOM 485 CB PRO 62 -0.622 18.782 -11.36 1.00 0.00
ATOM 486 CG PRO 62 -0.613 17.552 -10.47 1.00 0.00
ATOM 487 CD PRO 62 -0.033 16.399 -11.27 1.00 0.00
ATOM 488 N TYR 63 2.027 19.759 -13.53 1.00 0.00
ATOM 489 CA TYR 63 3.320 20.418 -13.59 1.00 0.00
ATOM 490 C TYR 63 3.158 21.939 -13.63 1.00 0.00
ATOM 491 O TYR 63 2.274 22.489 -12.97 1.00 0.00
ATOM 492 CB TYR 63 3.974 19.955 -14.89 1.00 0.00
ATOM 493 CG TYR 63 5.502 19.905 -14.84 1.00 0.00
ATOM 494 CD1 TYR 63 6.136 19.321 -13.76 1.00 0.00
ATOM 495 CD2 TYR 63 6.247 20.444 -15.87 1.00 0.00
ATOM 496 CE1 TYR 63 7.574 19.275 -13.71 1.00 0.00
ATOM 497 CE2 TYR 63 7.686 20.397 -15.82 1.00 0.00
ATOM 498 CZ TYR 63 8.279 19.815 -14.74 1.00 0.00
ATOM 499 OH TYR 63 9.636 19.771 -14.69 1.00 0.00
ATOM 500 N ARG 64 4.029 22.576 -14.40 1.00 0.00
ATOM 501 CA ARG 64 3.993 24.023 -14.53 1.00 0.00
ATOM 502 C ARG 64 2.549 24.526 -14.47 1.00 0.00
ATOM 503 O ARG 64 2.117 25.079 -13.46 1.00 0.00
ATOM 504 CB ARG 64 4.635 24.473 -15.84 1.00 0.00
ATOM 505 CG ARG 64 6.024 25.066 -15.60 1.00 0.00
ATOM 506 CD ARG 64 6.410 26.034 -16.72 1.00 0.00
ATOM 507 NE ARG 64 7.146 27.189 -16.16 1.00 0.00
ATOM 508 CZ ARG 64 7.821 28.090 -16.90 1.00 0.00
ATOM 509 NH1 ARG 64 8.445 29.083 -16.30 1.00 0.00
ATOM 510 NH2 ARG 64 7.857 27.977 -18.25 1.00 0.00
ATOM 511 N GLY 65 1.842 24.316 -15.57 1.00 0.00
ATOM 512 CA GLY 65 0.456 24.740 -15.67 1.00 0.00
ATOM 513 C GLY 65 -0.367 23.753 -16.50 1.00 0.00
ATOM 514 O GLY 65 -1.460 24.081 -16.96 1.00 0.00
ATOM 515 N ASN 66 0.190 22.562 -16.66 1.00 0.00
ATOM 516 CA ASN 66 -0.478 21.524 -17.43 1.00 0.00
ATOM 517 C ASN 66 -0.606 20.265 -16.57 1.00 0.00
ATOM 518 O ASN 66 -0.187 20.251 -15.42 1.00 0.00
ATOM 519 CB ASN 66 0.322 21.164 -18.68 1.00 0.00
ATOM 520 CG ASN 66 -0.364 21.691 -19.94 1.00 0.00
ATOM 521 OD1 ASN 66 -0.885 20.946 -20.76 1.00 0.00
ATOM 522 ND2 ASN 66 -0.336 23.016 -20.06 1.00 0.00
ATOM 523 N THR 67 -1.189 19.236 -17.17 1.00 0.00
ATOM 524 CA THR 67 -1.379 17.975 -16.48 1.00 0.00
ATOM 525 C THR 67 -1.394 16.814 -17.47 1.00 0.00
ATOM 526 O THR 67 -2.068" 16.881 -18.50 1.00 0.00
ATOM 527 CB THR 67 -2.659 18.080 -15.65 1.00 0.00
ATOM 528 OGl THR 67 -2.632 19.408 -15.13 1.00 0.00
ATOM 529 CG2 THR 67 -2.622 17.196 -14.40 1.00 0.00
ATOM 530 N TYR 68 -0.642 15.776 -17.13 1.00 0.00
ATOM 531 CA TYR 68 -0.562 14.601 -17.99 1.00 0.00
ATOM 532 C TYR 68 -1.026 13.350 -17.24 1.00 0.00
ATOM 533 O TYR 68 -0.680 13.151 -16.08 1.00 0.00
ATOM 534 CB TYR 68 0.917 14.445 -18.35 1.00 0.00
ATOM 535 CG TYR 68 1.519 15.666 -19.05 1.00 0.00
ATOM 536 CD1 TYR 68 0.855 16.251 -20.10 1.00 0.00
ATOM 537 CD2 TYR 68 2.724 16.182 -18.62 1.00 0.00
ATOM 538 CE1 TYR 68 1.422 17.400 -20.76 1.00 0.00
ATOM 539 CE2 TYR 68 3.291 17.331 -19.27 1.00 0.00
ATOM 540 CZ TYR 68 2.612 17.883 -20.32 1.00 0.00
ATOM 541 OH TYR 68 3.147 18.968 -20.94 1.00 0.00
ATOM 542 N ASN 69 -1.805 12.537 -17.94 1.00 0.00 ATOM 543 CA ASN 69 -2.321 11.310 -17.36 1.00 0.00
ATOM 544 C ASN 69 -1.492 10.125 -17.86 1.00 0.00
ATOM 545 O ASN 69 -1.675 9.668 -18.99 1.00 0.00
ATOM 546 CB ASN 69 -3.776 11.076 -17.77 1.00 0.00
ATOM 547 CG ASN 69 -4.475 12.399 -18.09 1.00 0.00
ATOM 548 OD1 ASN 69 -4.740 13.218 -17.22 1.00 0.00
ATOM 549 ND2 ASN 69 -4.758 12.561 -19.38 1.00 0.00
ATOM 550 N ILE 70 -0.600 9.662 -17.00 1.00 0.00
ATOM 551 CA ILE 70 0.257 8.539 -17.34 1.00 0.00
ATOM 552 C ILE 70 -0.362 7.248 -16.80 1.00 0.00
ATOM 553 O ILE 70 -0.563 7.108 -15.59 1.00 0.00
ATOM 554 CB ILE 70 1.686 8.787 -16.85 1.00 0.00
ATOM 555 CGI ILE 70 2.200 10.146 -17.33 1.00 0.00
ATOM 556 CG2 ILE 70 2.614 7.645 -17.27 1.00 0.00
ATOM 557 CD1 ILE 70 1.710 10.451 -18.74 1.00 0.00
ATOM 558 N PRO 71 -0.655 6.313 -17.74 1.00 0.00
ATOM 559 CA PRO 71 -1.247 5.038 -17.37 1.00 0.00
ATOM 560 C PRO 71 -0.208 4.116 -16.73 1.00 0.00
ATOM 561 O PRO 71 0.923 4.025 -17.21 1.00 0.00
ATOM 562 CB PRO 71 -1.817 4.481 -18.67 1.00 0.00
ATOM 563 CG PRO 71 -1.122 5.236 -19.79 1.00 0.00
ATOM 564 CD PRO 71 -0.430 6.444 -19.18 1.00 0.00
ATOM 565 N ILE 72 -0.630 3.455 -15.66 1.00 0.00
ATOM 566 CA ILE 72 0.251 2.544 -14.95 1.00 0.00
ATOM 567 C ILE 72 -0.459 1.201 -14.76 1.00 0.00
ATOM 568 O ILE 72 -1.673 1.107 -14.93 1.00 0.00
ATOM 569 CB ILE 72 0.732 3.175 -13.65 1.00 0.00
ATOM 570 CGI ILE 72 1.241 4.598 -13.88 1.00 0.00
ATOM 571 CG2 ILE 72 1.783 2.294 -12.96 1.00 0.00
ATOM 572 CD1 ILE 72 1.794 5.201 -12.59 1.00 0.00
ATOM 573 N CYS 73 0.330 0.195 -14.41 1.00 0.00
ATOM 574 CA CYS 73 -0.207 -1.137 -14.20 1.00 0.00
ATOM 575 C CYS 73 0.585 -1.799 -13.07 1.00 0.00
ATOM 576 O CYS 73 1.707 -2.256 -13.28 1.00 0.00
ATOM 577 CB CYS 73 -0.178 -1.972 -15.48 1.00 0.00
ATOM 578 SG CYS 73 -0.604 -0.924 -16.92 1.00 0.00
ATOM 579 N LEU 74 -0.031 -1.829 -11.90 1.00 0.00
ATOM 580 CA LEU 74 0.604 -2.427 -10.74 1.00 0.00
ATOM 581 C LEU 74 -0.062 -3.771 -10.43 1.00 0.00
ATOM 582 O LEU 74 -1.179 -4.029 -10.88 1.00 0.00
ATOM 583 CB LEU 74 0.586 -1.453 -9.559 1.00 0.00
ATOM 584 CG LEU 74 -0.174 -1.918 -8.316 1.00 0.00
ATOM 585 CD1 LEU 74 0.714 -2.785 -7.423 1.00 0.00
ATOM 586 CD2 LEU 74 -0.764 -0.728 -7.556 1.00 0.00
ATOM 587 N TRP 75 0.653 -4.591 -9.681 1.00 0.00
ATOM 588 CA TRP 75 0.147 -5.903 -9.313 1.00 0.00
ATOM 589 C TRP 75 0.214 -6.026 -7.790 1.00 0.00
ATOM 590 O TRP 75 1.231 -5.696 -7.181 1.00 0.00
ATOM 591 CB TRP 75 0.916 -7.010 -10.03 1.00 0.00
ATOM 592 CG TRP 75 0.752 -6.991 -11.55 1.00 0.00
ATOM 593 CD1 TRP 75 0.937 -5.960 -12.39 1.00 0.00
ATOM 594 CD2 TRP 75 0.359 -8.099 -12.39 1.00 0.00
ATOM 595 NE1 TRP 75 0.694 -6.321 -13.70 1.00 0.00
ATOM 596 CE2 TRP 75 0.331 -7.664 -13.70 1.00 0.00
ATOM 597 CE3 TRP 75 0.039 -9.426 -12.05 1.00 0.00
ATOM 598 CZ2 TRP 75 -0.012 -8.491 -14.77 1.00 0.00
ATOM 599 CZ3 TRP 75 -0.302 -10.24 -13.14 1.00 0.00
ATOM 600 CH2 TRP 75 -0.335 -9.817 -14.46 1.00 0.00
ATOM 601 N LEU 76 -0.883 -6.500 -7.217 1.00 0.00
ATOM 602 CA LEU 76 -0.961 -6.670 -5.776 1.00 0.00
ATOM 603 C LEU 76 -0.589 -8.110 -5.416 1.00 0.00
ATOM 604 0 LEU 76 -0.446 -8.957 -6.296 1.00 0.00 ATOM 605 CB LEU 76 -2.336 -6.243 -5.260 1.00 0.00
ATOM 606 CG LEU 76 -2 .641 -4.745 -5 .324 1 .00 0 .00
ATOM 607 CD1 LEU 76 -1 .494 -3.927 -4 .728 1 .00 0 .00
ATOM 608 CD2 LEU 76 -2 .972 -4.313 -6 .753 1 .00 0 .00
ATOM 609 N LEU 77 -0 .443 -8.343 -4 .120 1 .00 0 .00
ATOM 610 CA LEU 77 -0 .089 -9.665 -3 .632 1 .00 0 .00
ATOM 611 C LEU 77 -1 .340 -10.54 -3 .608 1 .00 0 .00
ATOM 612 O LEU 77 -2 .042 -10.66 -4 .613 1 .00 0 .00
ATOM 613 CB LEU 77 0 .618 -9.567 -2 .280 1 .00 0 .00
ATOM 614 CG LEU 77 -0 .012 -8.616 -1 .260 1 .00 0 .00
ATOM 615 CD1 LEU 77 0 .534 -7.196 -1 .425 1 .00 0 .00
ATOM 616 CD2 LEU 77 -1 .539 -8.655 -1 .345 1 .00 0 .00
ATOM 617 N ASP 78 -1 .582 -11.14 -2 .452 1 .00 0 .00
ATOM 618 CA ASP 78 -2. .736 -12.00 -2 .285 1 .00 0 .00
ATOM 619 C ASP 78 -2 .784 -12.51 -0 .842 1 .00 0 .00
ATOM 620 O ASP 78 -3 .858 -12.60 -0 .249 1 .00 0 .00
ATOM 621 CB ASP 78 -2. .649 -13.22 -3 .209 1 .00 0 .00
ATOM 622 CG ASP 78 -3. .903 -13.49 -4 .043 1 .00 0 .00
ATOM 623 OD1 ASP 78 -4 .948 -13.89 -3 .513 1 .00 0 .00
ATOM 624 OD2 ASP 78 -3 .776 -13.26 -5 .307 1 .00 0 .00
ATOM 625 N THR 79 ■1, .607 -12.81 -0 .317 1 .00 0 .00
ATOM 626 CA THR 79 -1 .502 -13.31 1 .046 1 .00 0 .00
ATOM 627 C THR 79 •0 .148 -12.92 1 .648 1 .00 0 .00
ATOM 628 O THR 79 0. .302 -13.54 2 .613 1 .00 0 .00
ATOM 629 CB THR 79 ■1, .751 -14.82 1 .024 1. .00 0 .00
ATOM 630 OGl THR 79 ■2. .013 -15.14 2. .386 1 .00 0 .00
ATOM 631 CG2 THR 79 -0, .490 -15.61 0 .684 1 .00 0 .00
ATOM 632 N TYR 80 0, .462 -11.91 1, .055 1 .00 0, .00
ATOM 633 CA TYR 80 1, .754 -11.44 1, .521 1, .00 0, .00
ATOM 634 C TYR 80 1. .706 -9.954 1, .846 1 .00 0 .00
ATOM 635 O TYR 80 2, .104 -9.124 1, .031 1 .00 0, .00
ATOM 636 CB TYR 80 2. .728 -11.66 0. .362 1. .00 0. .00
ATOM 637 CG TYR 80 3. .071 -13.13 0. .116 1, .00 0. .00
ATOM 638 CD1 TYR 80 4. .069 -13.74 0. .851 1, .00 0. .00
ATOM 639 CD2 TYR 80 2. .384 -13.85 -0. .840 1, .00 0. .00
ATOM 640 CE1 TYR 80 4. ,392 -15.12 0. .619 1. .00 0. ,00
ATOM 641 CE2 TYR 80 2. ,707 -15.23 -1. .072 1. .00 0. .00
ATOM 642 CZ TYR 80 3. ,695 -15.80 -0. .331 1. .00 0. .00
ATOM 643 OH TYR 80 4. .001 -17.11 -0. .549 1. .00 0. .00
ATOM 644 N PRO 81 1. ,203 -9.649 3. ,073 1. ,00 0. ,00
ATOM 645 CA PRO 81 1. .099 -8.270 3. .518 1. .00 0. ,00
ATOM 646 C PRO 81 2. ,471 -7.713 3. ,903 1. ,00 0. ,00
ATOM 647 O PRO 81 2. ,638 -7.161 4. ,990 1. .00 0. .00
ATOM 648 CB PRO 81 0. 124 -8.305 4. ,683 1. ,00 0. ,00
ATOM 649 CG PRO 81 0. 077 -9.753 5. ,144 1. ,00 0. .00
ATOM 650 CD PRO 81 0. ,724 -10.60 4. ,066 1. .00 0. ,00
ATOM 651 N TYR 82 3. ,418 -7.875 2. ,990 1. .00 0. ,00
ATOM 652 CA TYR 82 4. 769 -7.395 3. 221 1. ,00 0. 00
ATOM 653 C TYR 82 5. 554 -7.315 1. 910 1. ,00 0. 00
ATOM 654 O TYR 82 6. 275 -6.347 1. 673 1. ,00 0. 00
ATOM 655 CB TYR 82 5. 433 -8.426 4. 137 1. 00 0. 00
ATOM 656 CG TYR 82 4. 585 -8.819 5. 349 1. 00 0. 00
ATOM 657 CD1 TYR 82 3. 858 -9.991 5. 331 1. 00 0. 00
ATOM 658 CD2 TYR 82 4. 547 -7.999 6. 458 1. 00 0. 00
ATOM 659 CE1 TYR 82 3. 061 -10.36 6. 472 1. 00 0. 00
ATOM 660 CE2 TYR 82 3. 751 -8.369 7. 599 1. 00 0. 00
ATOM 661 CZ TYR 82 3. 046 -9.532 7. 549 1. 00 0. 00
ATOM 662 OH TYR 82 2. 293 -9.881 8. 627 1. 00 0. 00
ATOM 663 N ASN 83 5. 386 -8.345 1. 093 1. 00 0. 00
ATOM 664 CA ASN 83 6. 069 -8.403 -0. 188 1. 00 0. 00
ATOM 665 C ASN 83 5. 694 -7.174 -1. 018 1. 00 0. 00
ATOM 666 O ASN 83 4. 548 -6.729 -0. 991 1. 00 0. 00 ATOM 667 CB ASN 83 5.658 -9.649 -0.975 1.00 0.00
ATOM 668 CG ASN 83 6 .338 -9 .681 -2.345 1 .00 0 .00
ATOM 669 OD1 ASN 83 5 .899 -9 .060 -3.299 1 .00 0 .00
ATOM 670 ND2 ASN 83 7 .431 -10.43 -2.389 1 .00 0 .00
ATOM 671 N PRO 84 6 .707 -6 .647 -1.755 1 .00 0 .00
ATOM 672 CA PRO 84 6 .495 -5 .478 -2.593 1 .00 0 .00
ATOM 673 C PRO 84 5 .718 -5 .844 -3.858 1 .00 0 .00
ATOM 674 O PRO 84 5 .897 -6 .928 -4.409 1 .00 0 .00
ATOM 675 CB PRO 84 7 .888 -4 .945 -2.884 1 .00 0 .00
ATOM 676 CG PRO 84 8 .843 -6 .090 -2.591 1 .00 0 .00
ATOM 677 CD PRO 84 8 .078 -7 .148 -1.813 1 .00 0 .00
ATOM 678 N PRO 85 4 .848 -4 .893 -4.293 1 .00 0 .00
ATOM 679 CA PRO 85 4 .043 -5 .104 -5.484 1 .00 0 .00
ATOM 680 C PRO 85 4 .888 -4 .960 -6.751 1 .00 0 .00
ATOM 681 O PRO 85 6 .105 -4 .795 -6.673 1 .00 0 .00
ATOM 682 CB PRO 85 2 .928 -4 .076 -5.393 1 .00 0 .00
ATOM 683 CG PRO 85 3, .410 -3 .026 -4.404 1 .00 0, .00
ATOM 684 CD PRO 85 4, .609 -3. .597 -3.665 1 .00 0, .00
ATOM 685 N ILE 86 4 .210 -5 .027 -7.887 1. .00 0, .00
ATOM 686 CA ILE 86 4 .885 -4 .905 -9.169 1 .00 0, .00
ATOM 687 C ILE 86 4 .265 -3 .750 -9.958 1 .00 0, .00
ATOM 688 O ILE 86 3. .352 -3 .957 -10.75 1 .00 0, .00
ATOM 689 CB ILE 86 4, .862 -6. .241 -9.914 1, .00 0. .00
ATOM 690 CGI ILE 86 5, .241 -7, .395 -8.985 1, .00 0. .00
ATOM 691 CG2 ILE 86 5, .754 -6, .190 -11.15 1 .00 0. .00
ATOM 692 CD1 ILE 86 4, .097 -7, .720 -8.021 1 .00 0, .00
ATOM 693 N CYS 87 4, .789 -2, .558 -9.709 1. .00 0, .00
ATOM 694 CA CYS 87 4 .299 -1, .370 -10.38 1 .00 0, .00
ATOM 695 C CYS 87 5, .055 -1, .225 -11.70 1, .00 0. .00
ATOM 696 O CYS 87 6, .267 -1, .021 -11.71 1, .00 0. .00
ATOM 697 CB CYS 87 4, .436 -0, .123 -9.511 1 .00 0. .00
ATOM 698 SG CYS 87 3, .933 -0, .504 -7.793 1 .00 0, .00
ATOM 699 N PHE 88 4. .305 -1, .336 -12.79 1 .00 0. .00
ATOM 700 CA PHE 88 4, .889 -1, .219 -14.12 1 .00 0. .00
ATOM 701 C PHE 88 4. .143 -0. .180 -14.96 1, .00 0. ,00
ATOM 702 O PHE 88 3. .045 -0. .444 -15.44 1, .00 0. ,00
ATOM 703 CB PHE 88 4. .757 -2. ,588 -14.79 1, .00 0. ,00
ATOM 704 CG PHE 88 5. .511 -2. .710 -16.11 1, .00 0. ,00
ATOM 705 CD1 PHE 88 5. .027 -2. .099 -17.23 1, .00 0. ,00
ATOM 706 CD2 PHE 88 6. .664 -3. .427 -16.18 1, .00 0. ,00
ATOM 707 CE1 PHE 88 5. ,727 -2. ,211 -18.46 1. ,00 0. 00
ATOM 708 CE2 PHE 88 7. ,364 -3. ,539 -17.41 1. ,00 0. 00
ATOM 709 CZ PHE 88 6. ,880 -2. ,929 -18.52 1. .00 0. 00
ATOM 710 N VAL 89 4. ,767 0. ,980 -15.10 1. ,00 0. 00
ATOM 711 CA VAL 89 4. ,176 2. ,060 -15.87 1. .00 0. 00
ATOM 712 C VAL 89 4. ,172 1. ,679 -17.35 1. ,00 0. 00
ATOM 713 O VAL 89 5. 204 1. 297 -17.90 1. ,00 0. 00
ATOM 714 CB VAL 89 4. 916 3. 369 -15.59 1. ,00 0. 00
ATOM 715 CGI VAL 89 4. 341 4. 513 -16.43 1. ,00 0. 00
ATOM 716 CG2 VAL 89 4. ,883 3. 710 -14.10 1. ,00 0. 00
ATOM 717 N LYS 90 3. ,000 1. .798 -17.96 1. ,00 0. 00
ATOM 718 CA LYS 90 2. ,848 1. 472 -19.36 1. ,00 0. 00
ATOM 719 C LYS 90 2. 226 2. 663 -20.09 1. ,00 0. 00
ATOM 720 O LYS 90 1. 037 2. 936 -19.94 1. ,00 0. 00
ATOM 721 CB LYS 90 2. 063 0. 169 -19.53 1. ,00 0. 00
ATOM 722 CG LYS 90 2. 762 -0. 771 -20.51 1. ,00 0. 00
ATOM 723 CD LYS 90 1. 754 -1. 415 -21.47 1. ,00 0. 00
ATOM 724 CE LYS 90 2. 457 -1. 996 -22.69 1. ,00 0. 00
ATOM 725 NZ LYS 90 1. 881 -1. 433 -23.94 1. 00 0. 00
ATOM 726 N PRO 91 3. 080 3. 357 -20.89 1. 00 0. 00
ATOM 727 CA PRO 91 2. 627 4. 513 -21.65 1. 00 0. 00
ATOM 728 C PRO 91 1. 792 4. 085 -22.85 1. 00 0. 00 ATOM 729 O PRO 91 1.484 2.905 -23.01 1.00 0.00
ATOM 730 CB PRO 91 3.898 5 .251 -22 .04 1 .00 0.00
ATOM 731 CG PRO 91 5.027 4 .246 -21 .89 1 .00 0.00
ATOM 732 CD PRO 91 4.496 3 .061 -21 .10 1 .00 0.00
ATOM 733 N THR 92 1.448 5 .067 -23 .67 1 .00 0.00
ATOM 734 CA THR 92 0.654 4 .807 -24 .86 1 .00 0.00
ATOM 735 C THR 92 1.386 5 .302 -26 .11 1 .00 0.00
ATOM 736 O THR 92 1.415 4 .615 -27 .13 1 .00 0.00
ATOM 737 CB THR 92 -0.718 5 .455 -24 .67 1 .00 0.00
ATOM 738 OGl THR 92 -1.143 5 .777 -25 .99 1 .00 0.00
ATOM 739 CG2 THR 92 -0.630 6 .812 -23 .96 1 .00 0.00
ATOM 740 N SER 93 1.957 6 .491 -25 .99 1 .00 0.00
ATOM 741 CA SER 93 2.688 7 .085 -27 .10 1 .00 0.00
ATOM 742 C SER 93 2.922 8 .574 -26 .83 1 .00 0.00
ATOM 743 O SER 93 3.943 9 .127 -27 .24 1 .00 0.00
ATOM 744 CB SER 93 1.938 6 .895 -28 .42 1 .00 0.00
ATOM 745 OG SER 93 2.385 5 .742 -29 .13 1 .00 0.00
ATOM 746 N SER 94 1.961 9 .179 -26 .15 1 .00 0.00
ATOM 747 CA SER 94 2.051 10 .591 -25 .82 1 .00 0.00
ATOM 748 C SER 94 2.987 10 .794 -24 .63 1 .00 0.00
ATOM 749 O SER 94 3.184 11 .920 -24 .18 1 .00 0.00
ATOM 750 CB SER 94 0.670 11 .175 -25 .52 1 .00 0.00
ATOM 751 OG SER 94 0.081 11 .780 -26 .67 1 .00 0.00
ATOM 752 N MET 95 3.539 9, .687 -24 .16 1 .00 0.00
ATOM 753 CA MET 95 4.450 9, .730 -23, .02 1 .00 0.00
ATOM 754 C MET 95 5.897 9, .887 -23, .49 1, .00 0.00
ATOM 755 O MET 95 6.157 10, .023 -24, .69 1 .00 0.00
ATOM 756 CB MET 95 4.312 8, .442 -22, .21 1, .00 0.00
ATOM 757 CG MET 95 3.157 8, .544 -21, .21 1 .00 0.00
ATOM 758 SD MET 95 1.601 8. .596 -22. .08 1. .00 0.00
ATOM 759 CE MET 95 1.027 10. .215 -21. .60 1, .00 0.00
ATOM 760 N THR 96 6.803 9. .864 -22. .53 1. .00 0.00
ATOM 761 CA THR 96 8.219 10. .002 -22. .82 1. .00 0.00
ATOM 762 C THR 96 9.036 8. .994 -22. .01 1. .00 0.00
ATOM 763 O THR 96 9.938 8. .350 -22. .54 1. .00 0.00
ATOM 764 CB THR 96 8.616 11. .456 -22. .56 1. .00 0.00
ATOM 765 OGl THR 96 8.399 12. .105 -23. .81 1. .00 0.00
ATOM 766 CG2 THR 96 10.119 11. ,617 -22. .32 1, .00 0.00
ATOM 767 N ILE 97 8.688 8. .890 -20. .74 1, .00 0.00
ATOM 768 CA ILE 97 9.378 7. .972 -19. .85 1, .00 0.00
ATOM 769 C ILE 97 10.804 8. ,474 -19. ,61 1. ,00 0.00
ATOM 770 O ILE 97 11.602 8. ,557 -20. ,54 1. ,00 0.00
ATOM 771 CB ILE 97 9.313 6. ,544 -20. ,39 1. .00 0.00
ATOM 772 CGI ILE 97 8.684 5. ,594 -19. ,37 1. ,00 0.00
ATOM 773 CG2 ILE 97 10.694 6. ,067 -20. ,85 1. ,00 0.00
ATOM 774 CD1 ILE 97 8.650 4. 161 -19. 91 1. ,00 0.00
ATOM 775 N LYS 98 11.080 8. 796 -18. 35 1. ,00 0.00
ATOM 776 CA LYS 98 12.395 9. 287 -17. 98 1. 00 0.00
ATOM 777 C LYS 98 13.345 8. 102 -17. 79 1. 00 0.00
ATOM 778 O LYS 98 14.495 8. 150 -18. 23 1. 00 0.00
ATOM 779 CB LYS 98 12.299 10. 196 -16. 75 1. 00 0.00
ATOM 780 CG LYS 98 13.680 10. 710 -16. 34 1. 00 0.00
ATOM 781 CD LYS 98 13.567 11. 740 -15. 21 1. 00 0.00
ATOM 782 CE LYS 98 14.088 11. 168 -13. 89 1. 00 0.00
ATOM 783 NZ LYS 98 13.180 11. 525 -12. 78 1. 00 0.00
ATOM 784 N THR 99 12.827 7. 066 -17. 15 1. 00 0.00
ATOM 785 CA THR 99 13.614 5. 870 -16. 90 1. 00 0.00
ATOM 786 C THR 99 14.990 6. 243 -16. 35 1. 00 0.00
ATOM 787 0 THR 99 15.873 6. 661 -17. 09 1. 00 0.00
ATOM 788 CB THR 99 13.682 5. 070 -18. 21 1. 00 0.00
ATOM 789 OGl THR 99 13.958 6. 051 -19. 20 1. 00 0.00
ATOM 790 CG2 THR 99 12.322 4. 499 -18. 61 1. 00 0.00 ATOM 791 N GLY 100 15.129 6.078 -15.04 1.00 0.00
ATOM 792 CA GLY 100 16 .382 6 .393 -14.38 1 .00 0 .00
ATOM 793 C GLY 100 16 .275 6 .164 -12.87 1 .00 0 .00
ATOM 794 O GLY 100 17 .235 5 .732 -12.23 1 .00 0 .00
ATOM 795 N LYS 101 15 .098 6 .465 -12.34 1 .00 0 .00
ATOM 796 CA LYS 101 14 .852 6 .297 -10.91 1 .00 0 .00
ATOM 797 C LYS 101 13 .940 5 .088 -10.70 1 .00 0 .00
ATOM 798 O LYS 101 14 .418 3 .981 -10.45 1 .00 0 .00
ATOM 799 CB LYS 101 14 .311 7 .593 -10.31 1 .00 0 .00
ATOM 800 CG LYS 101 15 .391 8 .313 -9.502 1 .00 0 .00
ATOM 801 CD LYS 101 16 .096 9 .373 -10.35 1 .00 0 .00
ATOM 802 CE LYS 101 16 .511 10 .571 -9.494 1 .00 0 .00
ATOM 803 NZ LYS 101 17 .854 10 .353 -8.912 1 .00 0 .00
ATOM 804 N HIS 102 12 .642 5 .341 -10.79 1 .00 0 .00
ATOM 805 CA HIS 102 11 .659 4 .287 -10.61 1 .00 0 .00
ATOM 806 C HIS 102 11 .083 3 .882 -11.97 1 .00 0 .00
ATOM 807 O HIS 102 9 .895 4 .070 -12.22 1 .00 0 .00
ATOM 808 CB HIS 102 10 .581 4 .718 -9.618 1 .00 0 .00
ATOM 809 CG HIS 102 11 .015 5 .819 -8.681 1. .00 0 .00
ATOM 810 ND1 HIS 102 11 .339 5 .592 -7.355 1. .00 0 .00
ATOM 811 CD2 HIS 102 11 .175 7 .158 -8.892 1 .00 0 .00
ATOM 812 CE1 HIS 102 11 .678 6 .747 -6.803 1 .00 0 .00
ATOM 813 NE2 HIS 102 11, .575 7 .717 -7.757 1 .00 0 .00
ATOM 814 N VAL 103 11, .953 3. .333 -12.80 1 .00 0 .00
ATOM 815 CA VAL 103 11 .546 2 .899 -14.13 1 .00 0 .00
ATOM 816 C VAL 103 12 .690 2 .120 -14.78 1 .00 0 .00
ATOM 817 O VAL 103 12, .461 1, .108 -15.44 1 .00 0, .00
ATOM 818 CB VAL 103 11, .095 4, .104 -14.96 1 .00 0, .00
ATOM 819 CGI VAL 103 9, .577 4, .098 -15.15 1 .00 0, .00
ATOM 820 CG2 VAL 103 11, .561 5 .414 -14.32 1 .00 0 .00
ATOM 821 N ASP 104 13, .899 2, .622 -14.57 1. .00 0, .00
ATOM 822 CA ASP 104 15. .080 1, .985 -15.13 1. .00 0, .00
ATOM 823 C ASP 104 15. .108 2, .211 -16.64 1, .00 0, .00
ATOM 824 O ASP 104 15. .906 3. .004 -17.14 1, .00 0, .00
ATOM 825 CB ASP 104 15, ,064 0. .476 -14.88 1, .00 0, .00
ATOM 826 CG ASP 104 16. ,250 -0. ,057 -14.07 1. .00 0. .00
ATOM 827 OD1 ASP 104 17. ,417 0. ,153 -14.44 1. ,00 0. .00
ATOM 828 OD2 ASP 104 15. ,936 -0. ,724 -13.01 1. .00 0. ,00
ATOM 829 N ALA 105 14. ,228 1. ,500 -17.33 1. .00 0. ,00
ATOM 830 CA ALA 105 14. 142 1. ,613 -18.78 1. ,00 0. ,00
ATOM 831 C ALA 105 13. .172 0. ,557 -19.31 1. ,00 0. .00
ATOM 832 O ALA 105 13. ,421 -0. ,052 -20.35 1. ,00 0. ,00
ATOM 833 CB ALA 105 15. .541 1. ,480 -19.38 1. ,00 0. ,00
ATOM 834 N ASN 106 12. 087 0. 371 -18.58 1. 00 0. 00
ATOM 835 CA ASN 106 11. 078 -0. 601 -18.96 1. ,00 0. .00
ATOM 836 C ASN 106 9. 787 -0. 325 -18.19 1. ,00 0. ,00
ATOM 837 O ASN 106 9. 010 -1. 241 -17.92 1. ,00 0. .00
ATOM 838 CB ASN 106 11. 531 -2. 026 -18.63 1. 00 0. 00
ATOM 839 CG ASN 106 12. 557 -2. 025 -17.50 1. 00 0. 00
ATOM 840 OD1 ASN 106 13. 568 -1. 345 -17.54 1. 00 0. 00
ATOM 841 ND2 ASN 106 12. 240 -2. 825 -16.48 1. 00 0. 00
ATOM 842 N GLY 107 9. 599 0. 941 -17.84 1. 00 0. 00
ATOM 843 CA GLY 107 8. 416 1. 348 -17.11 1. 00 0. 00
ATOM 844 C GLY 107 8. 234 0. 497 -15.85 1. 00 0. 00
ATOM 845 O GLY 107 7. 108 0. 182 -15.47 1. 00 0. 00
ATOM 846 N LYS 108 9. 359 0. 149 -15.24 1. 00 0. 00
ATOM 847 CA LYS 108 9. 337 -0. 659 -14.03 1. 00 0. 00
ATOM 848 C LYS 108 9. 651 0. 226 -12.83 1. 00 0. 00
ATOM 849 O LYS 108 10. 805 0. 581 -12.59 1. 00 0. 00
ATOM 850 CB LYS 108 10. 276 -1. 859 -14.18 1. 00 0. 00
ATOM 851 CG LYS 108 9. 663 -3. 113 -13.55 1. 00 0. 00
ATOM 852 CD LYS 108 10. 522 -3. 620 -12.39 1. 00 0. 00
.1 — ATOM 853 CE LYS 108 9.707 -4.515 -11.45 1.00 0.00
ATOM 854 NZ LYS 108 10.595 -5.445 -10.72 1.00 0.00
ATOM 855 N ILE 109 8.602 0.558 -12.09 1.00 0.00
ATOM 856 CA ILE 109 8.751 1.395 -10.91 1.00 0.00
ATOM 857 C ILE 109 9.374 0.573 -9.785 1.00 0.00
ATOM 858 O ILE 109 8.681 0.162 -8.856 1.00 0.00
ATOM 859 CB ILE 109 7.414 037 -10.54 1.00 0.00
ATOM 860 CGI ILE 109 7.116 244 -11.43 1.00 0.00
ATOM 861 CG2 ILE 109 7.375 401 -9.055 1.00 0.00
ATOM 862 CD1 ILE 109 5.666 703 -11.27 1.00 0.00
ATOM 863 N TYR 110 10.676 357 -9.902 1.00 0.00
ATOM 864 CA TYR 110 11.401 0.409 -8.903 1.00 0.00
ATOM 865 C TYR 110 11.917 0.499 -7.785 1.00 0.00
ATOM 866 O TYR 110 12.832 1 294 -7.998 1.00 0.00
ATOM 867 CB TYR 110 12.594 -1 030 -9.631 1.00 0.00
ATOM 868 CG TYR 110 13.717 -0.039 -9.945 1.00 0.00
ATOM 869 CD1 TYR 110 14.778 0.100 -9.074 1.00 0.00
ATOM 870 CD2 TYR 110 13.667 0.716 -11.09 1.00 0.00
ATOM 871 CE1 TYR 110 15.834 .033 -9.371 1.00 0.00
ATOM 872 CE2 TYR 110 14.723 ,649 -11.39 1.00 0.00
ATOM 873 CZ TYR 110 15.755 762 -10.51 1.00 0.00
ATOM 874 OH TYR 110 16.752 643 -10.79 1.00 0.00
ATOM 875 N LEU 111 11.310 0.349 -6.617 1.00 0.00
ATOM 876 CA LEU Ml 11.696 1.146 -5. .465 1.00 0.00
ATOM 877 C LEU Ml 12.381 0.245 -4. .434 1.00 0.00
ATOM 878 O LEU Ml 11.789 -0.723 -3, .960 1.00 0.00
ATOM 879 CB LEU Ml 10.490 ,908 -4, .911 1.00 0.00
ATOM 880 CG LEU Ml 9.462 ,376 -5, .942 1.00 0.00
ATOM 881 CD1 LEU Ml 8.138 ,628 -5. .773 1.00 0.00
ATOM 882 CD2 LEU Ml 9.274 .893 -5. .880 1.00 0.00
ATOM 883 N PRO 112 13.652 0.607 -4, .110 1.00 0.00
ATOM 884 CA PRO 112 14.423 -0.157 -3 .143 1.00 0.00
ATOM 885 C PRO 112 13.942 0.117 -1, .717 1.00 0.00
ATOM 886 O PRO 112 14.216 -0.661 -0.806 1.00 0.00
ATOM 887 CB PRO 112 15.866 0.258 ,375 1.00 0.00
ATOM 888 CG PRO 112 15.804 1.573 ,136 1.00 0.00
ATOM 889 CD PRO 112 14.385 1.748 ,650 1.00 0.00
ATOM 890 N TYR 113 13.235 1.228 ,569 1.00 0.00
ATOM 891 CA TYR 113 12.714 1.616 -0.269 1.00 0.00
ATOM 892 C TYR 113 11.457 0.816 0.079 1.00 0.00
ATOM 893 O TYR 113 11.325 0.313 1.193 1.00 0.00
ATOM 894 CB TYR 113 12.347 095 -0.386 1.00 0.00
ATOM 895 CG TYR 113 12.678 920 0.859 1.00 0.00
ATOM 896 CD1 TYR 113 13.839 664 0.906 1.00 0.00
ATOM 897 CD2 TYR 113 11.815 919 1.937 1.00 0.00
ATOM 898 CE1 TYR 113 14.151 440 2.079 1.00 0.00
ATOM 899 CE2 TYR 113 12.127 694 3.109 1.00 0.00
ATOM 900 CZ TYR 113 13.279 417 3.122 1.00 0.00
ATOM 901 OH TYR 113 13.574 149 4.230 1.00 0.00
ATOM 902 N LEU 114 10.565 0.724 -0.897 1.00 0.00
ATOM 903 CA LEU 114 9.323 0.006 -0.708 1.00 0.00
ATOM 904 C LEU 114 9.608 1.508 -0.745 1.00 0.00
ATOM 905 O LEU 114 8.969 2.283 -0.034 1.00 0.00
ATOM 906 CB LEU 114 8.275 0.446 -1.728 1.00 0.00
ATOM 907 CG LEU 114 6.961 0.975 -1.150 1.00 0.00
ATOM 908 CD1 LEU 114 6.971 2.503 -1.072 1.00 0.00
ATOM 909 CD2 LEU 114 5.762 0.449 -1.942 1.00 0.00
ATOM 910 N HIS 115 10.570 -1.876 -1.579 1.00 0.00
ATOM 911 CA HIS 115 10.947 -3.272 -1.718 1.00 0.00
ATOM 912 C HIS 115 11.197 -3.876 -0.335 1.00 0.00
ATOM 913 O HIS 115 11.126 5.091 -0.162 1.00 0.00
ATOM 914 CB HIS 115 12.148 -3.418 2.655 1.00 0.00 ATOM 915 CG HIS 115 12.606 -4.845 -2.846 1.00 0.00
ATOM 916 ND1 HIS 115 12 .562 -5 .489 -4 .070 1 .00 0 .00
ATOM 917 CD2 HIS 115 13 .119 -5 .743 -1 .956 1 .00 0 .00
ATOM 918 CE1 HIS 115 13 .028 -6 .719 -3 .912 1 .00 0 .00
ATOM 919 NE2 HIS 115 13 .374 -6 .875 -2 .602 1 .00 0 .00
ATOM 920 N GLU 116 11 .484 -2 .998 0 .616 1 .00 0 .00
ATOM 921 CA GLU 116 11 .745 -3 .429 1 .978 1 .00 0 .00
ATOM 922 C GLU 116 10 .908 -2 .610 2 .963 1 .00 0 .00
ATOM 923 O GLU 116 11 .268 -2 .482 4 .133 1 .00 0 .00
ATOM 924 CB GLU 116 13 .235 -3 .330 2 .310 1 .00 0 .00
ATOM 925 CG GLU 116 14 .013 -4 .493 1 .693 1 .00 0 .00
ATOM 926 CD GLU 116 14 .830 -5 .231 2 .755 1 .00 0 .00
ATOM 927 OE1 GLU 116 16 .069 -5. .207 2 .712 1 .00 0 .00
ATOM 928 OE2 GLU 116 14 .132 -5 .845 3 .650 1 .00 0 .00
ATOM 929 N TRP 117 9 .806 -2 .078 2 .455 1 .00 0 .00
ATOM 930 CA TRP 117 8. .916 -1 .275 3 .276 1 .00 0 .00
ATOM 931 C TRP 117 8 .551 -2 .092 4 .517 1 .00 0 .00
ATOM 932 O TRP 117 8 .943 -1 .744 5 .630 1 .00 0 .00
ATOM 933 CB TRP 117 7 .692 -0 .824 2 .476 1 .00 0 .00
ATOM 934 CG TRP 117 6 .386 -1. .496 2 .907 1 .00 0 .00
ATOM 935 CD1 TRP 117 5 .625 -1 .214 3 .974 1 .00 0 .00
ATOM 936 CD2 TRP 117 5. .713 -2 .580 2 .232 1 .00 0 .00
ATOM 937 NE1 TRP 117 4 .517 -2 .032 4 .036 1 .00 0 .00
ATOM 938 CE2 TRP 117 4 .572 -2. .890 2 .943 1 .00 0 .00
ATOM 939 CE3 TRP 117 6 .058 -3. .275 1 .059 1 .00 0 .00
ATOM 940 CZ2 TRP 117 3, .683 -3 .902 2 .562 1. .00 0 .00
ATOM 941 CZ3 TRP 117 5, .159 -4. .283 0, .692 1. .00 0, .00
ATOM 942 CH2 TRP 117 4, .005 -4, .608 1. .397 1, .00 0, .00
ATOM 943 N LYS 118 7. .807 -3, .162 4, .284 1, .00 0, .00
ATOM 944 CA LYS 118 7. .385 -4, .031 5, .370 1, .00 0, .00
ATOM 945 C LYS 118 6. .654 -3, .201 6, .427 1, .00 0, .00
ATOM 946 O LYS 118 7. .283 -2, .466 7. .187 1, .00 0, .00
ATOM 947 CB LYS 118 8. .576 -4, .817 5. .920 1, .00 0, .00
ATOM 948 CG LYS 118 8. .659 -6, .206 5. .283 1, .00 0. .00
ATOM 949 CD LYS 118 9. ,516 -6. .179 4. ,017 1. .00 0. ,00
ATOM 950 CE LYS 118 10. ,713 -7. .124 4. ,145 1. ,00 0. .00
ATOM 951 NZ LYS 118 11. ,181 -7. .551 2. .807 1. ,00 0. ,00
ATOM 952 N HIS 119 5. ,338 -3. .347 6. .442 1. ,00 0. .00
ATOM 953 CA HIS 119 4. .514 -2. .620 7. .394 1. .00 0. .00
ATOM 954 C HIS 119 3. ,060 -2. .620 6. .919 1. .00 0. .00
ATOM 955 O HIS 119 2. .795 -2, .680 5. .719 1. .00 0. .00
ATOM 956 CB HIS 119 5. ,063 -1. .211 7. ,622 1. ,00 0. ,00
ATOM 957 CG HIS 119 5. ,787 -1. ,039 8. ,936 1. ,00 0. ,00
ATOM 958 ND1 HIS 119 6. ,655 0. ,011 9. ,182 1. ,00 0. ,00
ATOM 959 CD2 HIS 119 5. ,762 -1. ,793 10. ,072 1. ,00 0. ,00
ATOM 960 CE1 HIS 119 7. ,126 -0. .116 10. ,414 1. ,00 0. ,00
ATOM 961 NE2 HIS 119 6. ,572 -1. .234 10. ,964 1. ,00 0. ,00
ATOM 962 N PRO 120 2. ,132 -2. ,551 7. ,912 1. ,00 0. ,00
ATOM 963 CA PRO 120 0. 711 -2. 542 7. 607 1. 00 0. 00
ATOM 964 C PRO 120 0. 276 -1. 182 7. 059 1. 00 0. 00
ATOM 965 O PRO 120 -0. 900 -0. ,976 6. 761 1. 00 0. 00
ATOM 966 CB PRO 120 0. 027 -2. ,901 8. 916 1. 00 0. 00
ATOM 967 CG PRO 120 1. 052 -2. ,642 10. 008 1. 00 0. 00
ATOM 968 CD PRO 120 2. 410 -2. ,480 9. 342 1. 00 0. 00
ATOM 969 N GLN 121 1. 248 -0. .289 6. 941 1. 00 0. 00
ATOM 970 CA GLN 121 0. 980 1. 046 6. 434 1. 00 0. 00
ATOM 971 C GLN 121 0. 817 1. 013 4. 913 1. 00 0. 00
ATOM 972 O GLN 121 -0. 039 1. 704 4. 362 1. 00 0. 00
ATOM 973 CB GLN 121 2. 085 2. 021 6. 845 1. 00 0. 00
ATOM 974 CG GLN 121 1. 699 3. 462 6. 504 1. 00 0. 00
ATOM 975 CD GLN 121 1. 338 4. 245 7. 768 1. 00 0. 00
ATOM 976 OE1 GLN 121 0. 318 4. 911 7. 847 1. 00 0. 00 ATOM 977 NE2 GLN 121 2.229 4.130 8.750 1.00 0.00
ATOM 978 N SER 122 1.650 0.201 4.278 1.00 0.00
ATOM 979 CA SER 122 1.607 0.069 2.831 1.00 0.00
ATOM 980 C SER 122 0.211 -0.371 2.387 1.00 0.00
ATOM 981 O SER 122 -0.206 -1.495 2.660 1.00 0.00
ATOM 982 CB SER 122 2.660 -0.927 2.339 1.00 0.00
ATOM 983 OG SER 122 2.591 -1.122 0.929 1.00 0.00
ATOM 984 N ASP 123 -0.472 0.539 1.707 1.00 0.00
ATOM 985 CA ASP 123 -1.812 0.258 1.222 1.00 0.00
ATOM 986 C ASP 123 -1.996 0.900 -0.155 1.00 0.00
ATOM 987 O ASP 123 -1.099 1.579 -0.652 1.00 0.00
ATOM 988 CB ASP 123 -2.871 0.842 2.160 1.00 0.00
ATOM 989 CG ASP 123 -2.742 0.417 3.624 1.00 0.00
ATOM 990 OD1 ASP 123 -1.923 -0.448 3.968 1.00 0.00
ATOM 991 OD2 ASP 123 -3.538 1.023 4.439 1.00 0.00
ATOM 992 N LEU 124 -3.165 0.663 -0.733 1.00 0.00
ATOM 993 CA LEU 124 -3.477 1.209 -2.042 1.00 0.00
ATOM 994 C LEU 124 -3.578 2.733 -1.944 1.00 0.00
ATOM 995 O LEU 124 -2.904 3.452 -2.680 1.00 0.00
ATOM 996 CB LEU 124 -4.732 0.546 -2.614 1.00 0.00
ATOM 997 CG LEU 124 -4.601 -0.936 -2.974 1.00 0.00
ATOM 998 CDl LEU 124 -3.578 -1.141 -4.093 1.00 0.00
ATOM 999 CD2 LEU 124 -4.274 -1.774 -1.736 1.00 0.00
ATOM 1000 N LEU 125 -4.425 3.180 -1.028 1.00 0.00
ATOM 1001 CA LEU 125 -4.623 4.604 -0.823 1.00 0.00
ATOM 1002 C LEU 125 -3.299 5.243 -0.402 1.00 0.00
ATOM 1003 O LEU 125 -2.944 6.321 -0.880 1.00 0.00
ATOM 1004 CB LEU 125 -5.766 4.850 0.163 1.00 0.00
ATOM 1005 CG LEU 125 -6.576 6.130 -0.055 1.00 0.00
ATOM 1006 CDl LEU 125 -7.335 6.080 -1.383 1.00 0.00
ATOM 1007 CD2 LEU 125 -7.508 6.397 1.129 1.00 0.00
ATOM 1008 N GLY 126 -2.603 4.553 0.489 1.00 0.00
ATOM 1009 CA GLY 126 -1.325 5.040 0.981 1.00 0.00
ATOM 1010 C GLY 126 -0.223 4.835 -0.061 1.00 0.00
ATOM 1011 O GLY 126 0.876 5.371 0.079 1.00 0.00
ATOM 1012 N LEU 127 -0.554 4.058 -1.081 1.00 0.00
ATOM 1013 CA LEU 127 0.395 3.775 -2.146 1.00 0.00
ATOM 1014 C LEU 127 0.442 4.964 -3.108 1.00 0.00
ATOM 1015 O LEU 127 1.488 5.588 -3.278 1.00 0.00
ATOM 1016 CB LEU 127 0.057 2.447 -2.825 1.00 0.00
ATOM 1017 CG LEU 127 0.580 2.272 -4.252 1.00 0.00
ATOM 1018 CDl LEU 127 1.263 0.914 -4.423 1.00 0.00
ATOM 1019 CD2 LEU 127 -0.538 2.483 -5.275 1.00 0.00
ATOM 1020 N ILE 128 -0.703 5.242 -3.713 1.00 0.00
ATOM 1021 CA ILE 128 -0.805 6.343 -4.655 1.00 0.00
ATOM 1022 C ILE 128 -0.247 7.613 -4.008 1.00 0.00
ATOM 1023 O ILE 128 0.369 8.438 -4.683 1.00 0.00
ATOM 1024 CB ILE 128 -2.243 6.490 -5.155 1.00 0.00
ATOM 1025 CGI ILE 128 -2.617 5.339 -6.092 1.00 0.00
ATOM 1026 CG2 ILE 128 -2.460 7.856 -5.810 1.00 0.00
ATOM 1027 CDl ILE 128 -3.569 4.359 -5.402 1.00 0.00
ATOM 1028 N GLN 129 -0.482 7.730 -2.710 1.00 0.00
ATOM 1029 CA GLN 129 -0.009 8.885 -1.965 1.00 0.00
ATOM 1030 C GLN 129 1.466 9.147 -2.271 1.00 0.00
ATOM 1031 O GLN 129 1.883 10.298 -2.401 1.00 0.00
ATOM 1032 CB GLN 129 -0.234 8.698 -0.464 1.00 0.00
ATOM 1033 CG GLN 129 -1.342 9.624 0.045 1.00 0.00
ATOM 1034 CD GLN 129 -0.772 10.706 0.965 1.00 0.00
ATOM 1035 OEl GLN 129 -0.500 11.824 0.558 1.00 0.00
ATOM 1036 NE2 GLN 129 -0.609 10.314 2.226 1.00 0.00
ATOM 1037 N VAL 130 2.218 8.061 -2.376 1.00 0.00
ATOM 1038 CA VAL 130 3.639 8.159 -2.665 1.00 0.00 ATOM 1039 C VAL 130 3.832 8.761 -4.058 1.00 0.00
ATOM 1040 O VAL 130 4.836 9.422 -4.319 1.00 0.00
ATOM 1041 CB VAL 130 4.299 6.787 -2.509 1.00 0.00
ATOM 1042 CGI VAL 130 4.237 5.997 -3.817 1.00 0.00
ATOM 1043 CG2 VAL 130 5.742 6.928 -2.021 1.00 0.00
ATOM 1044 N MET 131 2.855 8.511 -4.917 1.00 0.00
ATOM 1045 CA MET 131 2.905 9.019 -6.276 1.00 0.00
ATOM 1046 C MET 131 2.299 10.422 -6.360 1.00 0.00
ATOM 1047 O MET 131 2.149 10.973 -7.449 1.00 0.00
ATOM 1048 CB MET 131 2.137 8.075 -7.204 1.00 0.00
ATOM 1049 CG MET 131 2.893 6.759 -7.395 1.00 0.00
ATOM 1050 SD MET 131 1.843 5.563 -8.203 1.00 0.00
ATOM 1051 CE MET 131 2.530 4.052 -7.545 1.00 0.00
ATOM 1052 N ILE 132 1.968 10.958 -5.195 1.00 0.00
ATOM 1053 CA ILE 132 1.381 12.285 -5.122 1.00 0.00
ATOM 1054 C ILE 132 2.450 13.287 -4.678 1.00 0.00
ATOM 1055 O ILE 132 2.196 14.489 -4.629 1.00 0.00
ATOM 1056 CB ILE 132 0.139 12.275 -4.228 1.00 0.00
ATOM 1057 CGI ILE 132 -1.031 12.990 -4.906 1.00 0.00
ATOM 1058 CG2 ILE 132 0.450 12.863 -2.851 1.00 0.00
ATOM 1059 CDl ILE 132 -2.317 12.832 -4.093 1.00 0.00
ATOM 1060 N VAL 133 3.621 12.753 -4.366 1.00 0.00
ATOM 1061 CA VAL 133 4.730 13.585 -3.928 1.00 0.00
ATOM 1062 C VAL 133 6.002 13.162 -4.666 1.00 0.00
ATOM 1063 O VAL 133 6.501 13.895 -5.518 1.00 0.00
ATOM 1064 CB VAL 133 4.869 13.511 -2.405 1.00 0.00
ATOM 1065 CGI VAL 133 6.112 14.266 -1.932 1.00 0.00
ATOM 1066 CG2 VAL 133 3.610 14.039 -1.713 1.00 0.00
ATOM 1067 N VAL 134 6.489 11.982 -4.311 1.00 0.00
ATOM 1068 CA VAL 134 7.693 11.454 -4.928 1.00 0.00
ATOM 1069 C VAL 134 7.543 11.500 -6.450 1.00 0.00
ATOM 1070 O VAL 134 8.521 11.705 -7.168 1.00 0.00
ATOM 1071 CB VAL 134 7.979 10.047 -4.398 1.00 0.00
ATOM 1072 CGI VAL 134 9.189 9.432 -5.104 1.00 0.00
ATOM 1073 CG2 VAL 134 8.177 10.063 -2.882 1.00 0.00
ATOM 1074 N PHE 135 6.310 11.308 -6.897 1.00 0.00
ATOM 1075 CA PHE 135 6.020 11.326 -8.321 1.00 0.00
ATOM 1076 C PHE 135 5.281 12.607 -8.714 1.00 0.00
ATOM 1077 O PHE 135 5.512 13.154 -9.791 1.00 0.00
ATOM 1078 CB PHE 135 5.119 10.123 -8.609 1.00 0.00
ATOM 1079 CG PHE 135 5.738 8.776 -8.225 1.00 0.00
ATOM 1080 CDl PHE 135 6.079 8.529 -6.931 1.00 0.00
ATOM 1081 CD2 PHE 135 5.945 7.828 -9.176 1.00 0.00
ATOM 1082 CE1 PHE 135 6.652 7.280 -6.576 1.00 0.00
ATOM 1083 CE2 PHE 135 6.518 6.578 -8.821 1.00 0.00
ATOM 1084 CZ PHE 135 6.860 6.330 -7.527 1.00 0.00
ATOM 1085 N GLY 136 4.410 13.047 -7.819 1.00 0.00
ATOM 1086 CA GLY 136 3.636 14.253 -8.059 1.00 0.00
ATOM 1087 C GLY 136 4.550 15.468 -8.226 1.00 0.00
ATOM 1088 O GLY 136 4.138 16.490 -8.770 1.00 0.00
ATOM 1089 N ASP 137 5.777 15.315 -7.747 1.00 0.00
ATOM 1090 CA ASP 137 6.754 16.387 -7.836 1.00 0.00
ATOM 1091 C ASP 137 7.837 16.001 -8.846 1.00 0.00
ATOM 1092 O ASP 137 8.523 16.867 -9.387 1.00 0.00
ATOM 1093 CB ASP 137 7.432 16.628 -6.485 1.00 0.00
ATOM 1094 CG ASP 137 7.699 18.096 -6.149 1.00 0.00
ATOM 1095 OD1 ASP 137 8.826 18.475 -5.796 1.00 0.00
ATOM 1096 OD2 ASP 137 6.678 18.877 -6.264 1.00 0.00
ATOM 1097 N GLU 138 7.956 14.700 -9.070 1.00 0.00
ATOM 1098 CA GLU 138 8.943 14.190 -10.00 1.00 0.00
ATOM 1099 C GLU 138 8.460 12.876 -10.62 1.00 0.00
ATOM 1100 O GLU 138 8.862 11.797 -10.18 1.00 0.00 ATOM 1101 CB GLU 138 10.301 14.010 -9.325 1.00 0.00
ATOM 1102 CG GLU 138 11.441 14.100 -10.34 1.00 0.00
ATOM 1103 CD GLU 138 12.759 13.618 -9.734 1.00 0.00
ATOM 1104 OEl GLU 138 13.202 12.495 -10.02 1.00 0.00
ATOM 1105 OE2 GLU 138 13.330 14.455 -8.935 1.00 0.00
ATOM 1106 N PRO 139 7.583 13.013 -11.65 1.00 0.00
ATOM 1107 CA PRO 139 7.041 11.849 -12.33 1.00 0.00
ATOM 1108 C PRO 139 8.084 11.221 -13.25 1.00 0.00
ATOM 1109 O PRO 139 9.152 11.791 -13.47 1.00 0.00
ATOM 1110 CB PRO 139 5.818 12.363 -13.07 1.00 0.00
ATOM Mil CG PRO 139 5.986 13.871 -13.16 1.00 0.00
ATOM 1112 CD PRO 139 7.086 14.274 -12.19 1.00 0.00
ATOM 1113 N PRO 140 7.728 10.023 -13.79 1.00 0.00
ATOM 1114 CA PRO 140 8.620 9.311 -14.69 1.00 0.00
ATOM 1115 C PRO 140 8.642 9.964 -16.07 1.00 0.00
ATOM 1116 O PRO 140 9.695 10.054 -16.71 1.00 0.00
ATOM 1117 CB PRO 140 8.098 7.884 -14.71 1.00 0.00
ATOM 1118 CG PRO 140 6.669 7.955 -14.20 1.00 0.00
ATOM 1119 CD PRO 140 6.471 9.318 -13.56 1.00 0.00
ATOM 1120 N VAL 141 7.468 10.403 -16.50 1.00 0.00
ATOM 1121 CA VAL 141 7.339 11.044 -17.80 1.00 0.00
ATOM 1122 C VAL 141 7.829 12.491 -17.70 1.00 0.00
ATOM 1123 O VAL 141 7.026 13.422 -17.69 1.00 0.00
ATOM 1124 CB VAL 141 5.897 10.935 -18.30 1.00 0.00
ATOM 1125 CGI VAL 141 5.740 11.581 -19.67 1.00 0.00
ATOM 1126 CG2 VAL 141 5.433 9.477 -18.32 1.00 0.00
ATOM 1127 N PHE 142 9.145 12.632 -17.63 1.00 0.00
ATOM 1128 CA PHE 142 9.751 13.949 -17.54 1.00 0.00
ATOM 1129 C PHE 142 10.740 14.185 -18.68 1.00 0.00
ATOM 1130 O PHE 142 10.547 15.084 -19.49 1.00 0.00
ATOM 1131 CB PHE 142 10.507 13.996 -16.21 1.00 0.00
ATOM 1132 CG PHE 142 10.849 15.410 -15.73 1.00 0.00
ATOM 1133 CDl PHE 142 10.311 15.891 -14.58 1.00 0.00
ATOM 1134 CD2 PHE 142 11.692 16.187 -16.47 1.00 0.00
ATOM 1135 CE1 PHE 142 10.628 17.203 -14.14 1.00 0.00
ATOM 1136 CE2 PHE 142 12.010 17.499 -16.03 1.00 0.00
ATOM 1137 CZ PHE 142 11.471 17.980 -14.87 1.00 0.00
ATOM 1138 N SER 143 11.777 13.361 -18.70 1.00 0.00
ATOM 1139 CA SER 143 12.796 13.469 -19.73 1.00 0.00
ATOM 1140 C SER 143 13.496 14.825 -19.63 1.00 0.00
ATOM 1141 O SER 143 13.086 15.786 -20.28 1.00 0.00
ATOM 1142 CB SER 143 12.193 13.279 -21.12 1.00 0.00
ATOM 1143 OG SER 143 12.858 14.070 -22.10 1.00 0.00
ATOM 1144 N ARG 144 14.539 14.861 -18.82 1.00- 0.00
ATOM 1145 CA ARG 144 15.300 16.086 -18.63 1.00 0.00
ATOM 1146 C ARG 144 16.283 16.283 -19.79 1.00 0.00
ATOM 1147 O ARG 144 17.078 15.396 -20.09 1.00 0.00
ATOM 1148 CB ARG 144 16.074 16.055 -17.31 1.00 0.00
ATOM 1149 CG ARG 144 15.208 16.560 -16.16 1.00 0.00
ATOM 1150 CD ARG 144 15.879 17.736 -15.44 1.00 0.00
ATOM 1151 NE ARG 144 15.708 18.973 -16.24 1.00 0.00
ATOM 1152 CZ ARG 144 16.541 20.035 -16.17 1.00 0.00
ATOM 1153 NH1 ARG 144 16.293 21.090 -16.92 1.00 0.00
ATOM 1154 NH2 ARG 144 17.609 20.017 -15.34 1.00 0.00
ATOM 1155 N PRO 145 16.192 17.484 -20.42 1.00 0.00
ATOM 1156 CA PRO 145 17.064 17.809 -21.53 1.00 0.00
ATOM 1157 C PRO 145 18.479 18.132 -21.05 1.00 0.00
ATOM 1158 O PRO 145 19.232 17.233 -20.68 1.00 0.00
ATOM 1159 CB PRO 145 16.392 18.983 -22.23 1.00 0.00
ATOM 1160 CG PRO 145 15.421 19.566 -21.22 1.00 0.00
ATOM 1161 CD PRO 145 15.262 18.559 -20.09 1.00 0.00
TER 290. Table 6 sets forth the coordinates of another set of coordinates and related information for the TSGIO I UEV.
291. Table 6
HEADER Structure from DYANA, f - = 4.01366E-01 ( 37-12 1
REMARK 1 DYANA 1.5, 07-12- 1
REMARK 1 Number of residues : 144
REMARK 1 Number of atoms : 2727
ATOM 1 N ALA 2 1 .325 0 .000 0 .000 1 .00 0 .00
ATOM 2 HN ALA 2 1 .884 0 .000 0 .829 1 .00 0 .00
ATOM 3 CA ALA 2 2 .073 0 .000 -1 .245 1 .00 o. .00
ATOM 4 HA ALA 2 1 .377 -0 .233 -2 .051 1 .00 0 .00
ATOM 5 QB ALA 2 2 .799 1 .723 -1 .547 1 .00 o. .00
ATOM 6 CB ALA 2 2 .660 1 .392 -1 .489 1 .00 0. .00
ATOM 7 1HB ALA 2 1 .940 2 .149 -1 .177 1 .00 0. .00
ATOM 8 2HB ALA 2 3 .578 1 .505 -0 .913 1 .00 o. .00
ATOM 9 3HB ALA 2 2 .878 1 .514 -2 .550 1 .00 0. .00
ATOM 10 C ALA 2 3, .151 -1 .085 -1, .188 1. .00 0. .00
ATOM 11 O ALA 2 4 .329 -0. .807 -1 .408 1. .00 0, .00
ATOM 12 N VAL 3 2 .709 -2 .298 -0 .891 1 .00 0, .00
ATOM 13 HN VAL 3 1 .749 -2 .515 -0 .714 1. .00 0, .00
ATOM 14 CA VAL 3 3 .621 -3, .426 -0 .802 1, .00 0, .00
ATOM 15 HA VAL 3 4 .346 -3 .201 -0 .020 1 .00 0, .00
ATOM 16 CB VAL 3 2 .856 -4 .686 -0 .392 1 .00 0, .00
ATOM 17 HB VAL 3 2, .008 -4, .798 -1, .068 1, .00 0, .00
ATOM 18 QG1 VAL 3 3, .944 -6, .226 -0 .564 1, .00 0, .00
ATOM 19 QG2 VAL 3 2, .179 -4 .526 1 .369 1, .00 0, .00
ATOM 20 CGI VAL 3 3, .735 -5 .930 -0. .531 1. .00 0, .00
ATOM 21 1HG1 VAL 3 3, .770 -6 .459 0, .422 1, .00 0, .00
ATOM 22 2HG1 VAL 3 3, .319 -6, .586 -1, .295 1 .00 0, .00
ATOM 23 3HG1 VAL 3 4, .744 -5 .632 -0. .817 1 .00 0, .00
ATOM 24 CG2 VAL 3 2, .309 -4, .557 1. .031 1, .00 0. .00
ATOM 25 1HG2 VAL 3 1. .975 -3, .533 1, .200 1, .00 0. .00
ATOM 26 2HG2 VAL 3 1, .468 -5, .239 1, .160 1, .00 0. .00
ATOM 27 3HG2 VAL 3 3, .093 -4, .806 1. .746 1, .00 0. .00
ATOM 28 QQG VAL 3 3. .062 -5, .376 0, .403 1, .00 0. .00
ATOM 29 C VAL 3 4, .363 -3, .582 -2, .131 1 .00 0. .00
ATOM 30 O VAL 3 5, .569 -3, .820 -2, .148 1, .00 0, .00
ATOM 31 N SER 4 3. .610 -3. .443 -3. .212 1, .00 0. ,00
ATOM 32 HN SER 4 2. ,629 -3. .249 -3. .190 1. .00 0. ,00
ATOM 33 CA SER 4 4. .181 -3. .566 -4. .543 1, .00 0. ,00
ATOM 34 HA SER 4 4. .519 -4. .599 -4. .617 1. .00 0. ,00
ATOM 35 CB SER 4 3. .130 -3. .295 -5. .621 1. ,00 0. ,00
ATOM 36 2HB SER 4 2. .134 -3. .411 -5. .193 1. .00 0. ,00
ATOM 37 1HB SER 4 3. .213 -2. ,262 -5. .957 1. .00 0. ,00
ATOM 38 QB SER 4 2. ,674 -2. ,836 -5. ,575 1. ,00 0. 00
ATOM 39 OG SER 4 3. ,272 -4. ,170 -6. ,736 1. ,00 0. 00
ATOM 40 HG SER 4 2. ,546 -3. ,996 -7. ,402 1. .00 0. 00
ATOM 41 C SER 4 5. .360 -2. .603 -4. ,697 1. .00 0. ,00
ATOM 42 O SER 4 6. .416 -2. .984 -5. .200 1. .00 0. ,00
ATOM 43 N GLU 5 5. .140 -1. ,373 -4. .255 1. ,00 0. ,00
ATOM 44 HN GLU 5 4. .278 -1. ,071 -3. .848 1. .00 0. ,00
ATOM 45 CA GLU 5 6. ,171 -0. ,353 -4. ,338 1. ,00 0. 00
ATOM 46 HA GLU 5 6. .554 -0. ,410 -5. ,357 1. ,00 0. ,00
ATOM 47 CB GLU 5 5. ,584 1. ,040 -4. ,101 1. .00 0. .00
ATOM 48 2HB GLU 5 4. ,759 0. ,975 -3. .392 1. .00 0. .00
ATOM 49 1HB GLU 5 6. ,340 1. ,685 -3. .652 1. .00 0. ,00
ATOM 50 QB GLU 5 5. ,549 1. ,330 -3. ,522 1. .00 0. 00
ATOM 51 CG GLU 5 5. ,091 1. ,658 -5. ,411 1. .00 0. 00
ATOM 52 2HG GLU 5 4. 952 2. 731 -5. 281 1. ,00 0. 00 ATOM 53 1HG GLU 5 5.846 1.527 -6.186 1.00 0.00
ATOM 54 QG GLU 5 5 .399 2 .129 -5 .733 1 .00 0 .00
ATOM 55 CD GLU 5 3 .776 1 .018 -5 .858 1 .00 0 .00
ATOM 56 OEl GLU 5 3 .776 0 .165 -6 .758 1 .00 0 .00
ATOM 57 OE2 GLU 5 2 .726 1 .434 -5 .234 1 .00 0 .00
ATOM 58 HE2 GLU 5 2 .360 2 .247 -5 .687 1 .00 0 .00
ATOM 59 C GLU 5 7 .295 -0 .651 -3 .343 1 .00 0 .00
ATOM 60 O GLU 5 8 .470 -0 .641 -3 .707 1 .00 0 .00
ATOM 61 N SER 6 6 .894 -0 .910 -2 .107 1 .00 0 .00
ATOM 62 HN SER 6 5 .936 -0 .917 -1 .820 1 .00 0 .00
ATOM 63 CA SER 6 7 .853 -1 .211 -1 .058 1 .00 0 .00
ATOM 64 HA SER 6 8 .500 -0 .337 -0 .999 1 .00 0 .00
ATOM 65 CB SER 6 7 .151 -1 .417 0 .286 1 .00 0 .00
ATOM 66 2HB SER 6 6 .077 -1 .277 0 .160 1 .00 0 .00
ATOM 67 1HB SER 6 7 .301 -2 .444 0 .620 1 .00 0 .00
ATOM 68 QB SER 6 6 .689 -1 .860 0 .390 1 .00 0 .00
ATOM 69 OG SER 6 7 .632 -0 .520 1 .283 1 .00 0 .00
ATOM 70 HG SER 6 7 .989 0 .310 0 .853 1 .00 0 .00
ATOM 71 C SER 6 8 .663 -2 .455 -1 .430 1 .00 0 .00
ATOM 72 O SER 6 9 .798 -2 .617 -0 .984 1 .00 0 .00
ATOM 73 N GLN 7 8 .048 -3 .301 -2 .243 1 .00 0. .00
ATOM 74 HN GLN 7 7 .125 -3. .162 -2 .601 1 .00 0. .00
ATOM 75 CA GLN 7 8. .698 -4 .525 -2 .679 1 .00 0. .00
ATOM 76 HA GLN 7 9 .357 -4 .812 -1 .860 1 .00 0. .00
ATOM 77 CB GLN 7 7 .673 -5. .638 -2 .911 1 .00 0. .00
ATOM 78 2HB GLN 7 6. .915 -5, .608 -2, .128 1, .00 0, .00
ATOM 79 1HB GLN 7 7. .159 -5, .473 -3, .858 1 .00 0, .00
ATOM 80 QB GLN 7 7, .037 -5, .540 -2, .993 1, .00 0, .00
ATOM 81 CG GLN 7 8, .348 -7, .011 -2, .923 1, .00 0, .00
ATOM 82 2HG GLN 7 7, .590 -7, .792 -2, .988 1, .00 0, .00
ATOM 83 1HG GLN 7 8. .977 -7. ,103 -3, .808 1, .00 0. .00
ATOM 84 QG GLN 7 8. .284 -7. .447 -3. .398 1. .00 0. .00
ATOM 85 CD GLN 7 9, .194 -7. .217 -1. .665 1, .00 0. .00
ATOM 86 OEl GLN 7 10, .409 -7. .109 -1. .679 1, .00 0. .00
ATOM 87 NE2 GLN 7 8. .486 -7. .518 -0. .580 1, .00 0. .00
ATOM 88 1HE2 GLN 7 7. .490 -7. ,591 -0. .637 1. .00 0. ,00
ATOM 89 2HE2 GLN 7 8. .950 -7. ,672 0. ,293 1. .00 0. ,00
ATOM 90 QE2 GLN 7 8, .220 -7. .632 -0. .172 1. .00 0. ,00
ATOM 91 C GLN 7 9, .522 -4. .267 -3. .943 1, .00 0. .00
ATOM 92 0 GLN 7 10. .630 -4. .782 -4. .081 1, .00 0. ,00
ATOM 93 N LEU 8 8. .948 -3. .470 -4. .832 1. ,00 0. ,00
ATOM 94 HN LEU 8 8. .046 -3. .056 -4. .712 1. .00 0. .00
ATOM 95 CA LEU 8 9. .615 -3. .138 -6. .079 1. .00 0. .00
ATOM 96 HA LEU 8 9. .704 -4. .057 -6. .657 1, .00 0. .00
ATOM 97 CB LEU 8 8. ,763 -2. ,168 -6. ,901 1. ,00 0. ,00
ATOM 98 2HB LEU 8 8. ,066 -1. ,668 -6. ,228 1. .00 0. ,00
ATOM 99 1HB LEU 8 9. ,418 -1. ,399 -7. ,311 1. .00 0. ,00
ATOM 100 QB LEU 8 8. ,742 -1. ,533 -6. ,769 1. ,00 0. ,00
ATOM 101 CG LEU 8 7. ,965 -2. ,785 -8. ,051 1. ,00 0. ,00
ATOM 102 HG LEU 8 7. 365 -3. 602 -7. 651 1. ,00 0. 00
ATOM 103 QD1 LEU 8 6. ,766 -1. 525 -8. 797 1. ,00 0. 00
ATOM 104 QD2 LEU 8 9. ,119 -3. 526 -9. ,357 1. ,00 0. 00
ATOM 105 CDl LEU 8 6. .996 -1. ,766 -8. ,654 1. ,00 0. 00
ATOM 106 1HD1 LEU 8 5. 997 -2. 200 -8. 702 1. 00 0. 00
ATOM 107 2HD1 LEU 8 6. 974 -0. 872 -8. 031 1. 00 0. 00
ATOM 108 3HD1 LEU 8 7. 326 -1. 502 -9. 659 1. 00 0. 00
ATOM 109 CD2 LEU 8 8. 897 -3. 383 -9. 106 1. 00 0. 00
ATOM 110 1HD2 LEU 8 9. 926 -3. 096 -8. 887 1. 00 0. 00
ATOM 111 2HD2 LEU 8 8. 813 -4. 470 -9. 091 1. 00 0. 00
ATOM 112 3HD2 LEU 8 8. 618 -3. 011 -10. 092 1. 00 0. 00
ATOM 113 QQD LEU 8 7. 942 -2. 525 -9. 077 1. 00 0. 00
ATOM 114 C LEU 8 11. 021 -2. 617 -5. 777 1. 00 0. 00 ATOM 115 O LEU 8 11.993 -3.047 -6.396 1.00 0.00
ATOM 116 N LYS 9 11 .085 -1 .698 -4 .824 1 .00 0 .00
ATOM 117 HN LYS 9 10 .290 -1 .354 -4 .325 1 .00 0 .00
ATOM 118 CA LYS 9 12 .357 -1 .114 -4 .432 1 .00 0 .00
ATOM 119 HA LYS 9 12 .746 -0 .570 -5 .293 1 .00 0 .00
ATOM 120 CB LYS 9 12 .154 -0 .095 -3 .308 1 .00 0 .00
ATOM 121 2HB LYS 9 11 .150 0 .324 -3 .369 1 .00 0 .00
ATOM 122 1HB LYS 9 12 .233 -0 .594 -2 .342 1 .00 0 .00
ATOM 123 QB LYS 9 11 .692 -0 .135 -2 .855 1 .00 0 .00
ATOM 124 CG LYS 9 13 .189 1 .029 -3 .394 1 .00 0 .00
ATOM 125 2HG LYS 9 14 .190 0 .618 -3 .261 1 .00 0 .00
ATOM 126 1HG LYS 9 13 .159 1 .480 -4 .386 1 .00 0 .00
ATOM 127 QG LYS 9 13 .674 1 .049 -3 .823 1 .00 0 .00
ATOM 128 CD LYS 9 12 .925 2 .098 -2 .332 1 .00 0, .00
ATOM 129 2HD LYS 9 12 .209 2 .826 -2 .714 1 .00 0, .00
ATOM 130 1HD LYS 9 12 .475 1. .639 -1. .452 1 .00 0, .00
ATOM 131 QD LYS 9 12 .342 2. .233 -2, .083 1, .00 0, .00
ATOM 132 CE LYS 9 14 .221 2 .810 -1 .937 1, .00 0, .00
ATOM 133 2HE LYS 9 14, .874 2, .898 -2, .806 1, .00 0. .00
ATOM 134 IHE LYS 9 13. .999 3, .822 -1, .601 1, .00 0. .00
ATOM 135 QE LYS 9 14 .437 3, .360 -2, .203 1, .00 0. .00
ATOM 136 NZ LYS 9 14 .914 2, .064 -0, .863 1, .00 0, .00
ATOM 137 1HZ LYS 9 14 .265 1 .553 -0, .276 1, .00 0. .00
ATOM 138 2HZ LYS 9 15 .572 1 .387 -1 .233 1, .00 0, .00
ATOM 139 QZ LYS 9 14. .918 1, .470 -0, .754 1, .00 0. .00
ATOM 140 C LYS 9 13 .340 -2, .232 -4, .080 1, .00 0, .00
ATOM 141 O LYS 9 14 .553 -2, .029 -4, .109 1, .00 0, .00
ATOM 142 N LYS 10 12 .780 -3, .387 -3, .754 1, .00 0, .00
ATOM 143 HN LYS 10 11 .792 -3, .544 -3. .732 1, .00 0, .00
ATOM 144 CA LYS 10 13, .592 -4, .538 -3. .396 1, .00 0. .00
ATOM 145 HA LYS 10 14, .534 -4, .161 -2, .996 1, .00 0. .00
ATOM 146 CB LYS 10 12, .919 -5, .344 -2. .283 1. .00 0. .00
ATOM 147 2HB LYS 10 11, .922 -4. .945 -2. .092 1. .00 0. .00
ATOM 148 1HB LYS 10 12, .792 -6, .378 -2. .604 1. .00 0. .00
ATOM 149 QB LYS 10 12. .357 -5. ,662 -2. ,348 1. ,00 0. ,00
ATOM 150 CG LYS 10 13. .746 -5. .300 -0. .997 1. .00 0. ,00
ATOM 151 2HG LYS 10 14. .577 -4. .606 -1. .118 1. ,00 0. ,00
ATOM 152 1HG LYS 10 13. .133 -4. .924 -0. ,178 1. ,00 0. ,00
ATOM 153 QG LYS 10 13. .855 -4, ,765 -0. ,648 1. .00 0. ,00
ATOM 154 CD LYS 10 14. .283 -6. .689 -0. .643 1. ,00 0. ,00
ATOM 155 2HD LYS 10 14. .387 -7. ,285 -1. ,550 1. 00 0. 00
ATOM 156 1HD LYS 10 15. .277 -6. ,598 -0. .206 1. 00 0. 00
ATOM 157 QD LYS 10 14. .832 -6. ,941 -0. .878 1. 00 0. 00
ATOM 158 CE LYS 10 13. ,352 -7. ,403 0. ,339 1. 00 0. 00
ATOM 159 2HE LYS 10 13. ,940 -7. ,980 1. ,053 1. 00 0. 00
ATOM 160 IHE LYS 10 12. ,786 -6. ,668 0. 912 1. 00 0. 00
ATOM 161 QE LYS 10 13. ,363 -7. .324 0. 982 1. 00 0. 00
ATOM 162 NZ LYS 10 12. ,423 -8. ,298 -0. 386 1. 00 0. 00
ATOM 163 1HZ LYS 10 12. ,908 -8. ,893 -1. ,049 1. 00 0. 00
ATOM 164 2HZ LYS 10 11. ,918 -8. ,912 0. .244 1. 00 0. 00
ATOM 165 QZ LYS 10 12. 413 -8. 903 -0. 403 1. 00 0. 00
ATOM 166 C LYS 10 13. .891 -5. 357 -4. 653 1. 00 0. 00
ATOM 167 O LYS 10 14. .903 -6. 053 -4. 719 1. 00 0. 00
ATOM 168 N MET 11 12. 993 -5. 246 • -5. 621 1. 00 0. 00
ATOM 169 HN MET 11 12. 172 -4. 677 -5. 559 1. 00 0. 00
ATOM 170 CA MET 11 13. 148 -5. 967 -6. 872 1. 00 0. 00
ATOM 171 HA MET 11 13. 515 -6. 956 -6. 597 1. 00 0. 00
ATOM 172 CB MET 11 11. 796 -6. 053 -7. 583 1. 00 0. 00
ATOM 173 2HB MET 11 11. 246 -5. 123 -7. 440 1. 00 0. 00
ATOM 174 1HB MET 11 11. 951 -6. 169 -8. 656 1. 00 0. 00
ATOM 175 QB MET 11 11. 599 -5. 646 -8. 048 1. 00 0. 00
ATOM 176 CG MET 11 10. 971 -7. 227 -7. 052 1. 00 0. 00 ATOM 177 2HG MET 11 10.767 -7.932 -7.857 1.00 0..00
ATOM 178 1HG MET 11 11 .537 -7 .765 -6 .292 1 .00 0. .00
ATOM 179 QG MET 11 11 .152 -7 .849 -7 .074 1 .00 0. .00
ATOM 180 SD MET 11 9 .436 -6 .631 -6 .361 1 .00 0. .00
ATOM 181 QE MET 11 8. .036 -7 .601 -7 .670 1 .00 0. .00
ATOM 182 CE MET 11 8 .273 -7 .437 -7 .449 1 .00 0. .00
ATOM 183 IHE MET 11 8 .222 -6 .895 -8 .393 1 .00 0 .00
ATOM 184 2HE MET 11 8, .599 -8 .461 -7 .635 1 .00 0 .00
ATOM 185 3HE MET 11 7 .288 -7 .448 -6 .983 1 .00 0, .00
ATOM 186 C MET 11 14 .161 -5 .272 -7 .784 1 .00 0. .00
ATOM 187 O MET 11 14 .631 -5 .859 -8 .757 1 .00 0. .00
ATOM 188 N VAL 12 14 .467 -4 .030 -7 .436 1 .00 0. .00
ATOM 189 HN VAL 12 14 .080 -3 .560 -6 .643 1 .00 0. .00
ATOM 190 CA VAL 12 15 .416 -3 .249 -8 .211 1 .00 0. .00
ATOM 191 HA VAL 12 15 .570 -3 .764 -9 .159 1 .00 0, .00
ATOM 192 CB VAL 12 14 .832 -1 .867 -8 .513 1 .00 0. .00
ATOM 193 HB VAL 12 15, .526 -1 .347 -9, .174 1 .00 0, .00
ATOM 194 QG1 VAL 12 13, .172 -2 .012 -9, .410 1 .00 0, .00
ATOM 195 QG2 VAL 12 14, .661 -0 .843 -6, .930 1. .00 0, .00
ATOM 196 CGI VAL 12 13, .490 -1 .985 -9, .238 1, .00 0, .00
ATOM 197 1HG1 VAL 12 12, .682 -1 .745 -8, .547 1 .00 0, .00
ATOM 198 2HG1 VAL 12 13, .469 -1 .290 -10, .078 1 .00 0, .00
ATOM 199 3HG1 VAL 12 13, .364 -3. .003 -9, .606 1, .00 0, .00
ATOM 200 CG2 VAL 12 14, .694 -1 .039 -7. .234 1, .00 0, .00
ATOM 201 1HG2 VAL 12 14. .141 -0, .125 -7. .450 1, .00 0. .00
ATOM 202 2HG2 VAL 12 14. .157 -1, .619 -6. .482 1. .00 0. .00
ATOM 203 3HG2 VAL 12 15. .684 -0, .784 -6. .856 1. .00 0. .00
ATOM 204 QQG VAL 12 13, .916 -1, .428 -8. .170 1. .00 0. ,00
ATOM 205 C VAL 12 16. .749 -3, .185 -7. .463 1. .00 0. .00
ATOM 206 O VAL 12 17. .572 -2, .310 -7. ,729 1. .00 0. .00
ATOM 207 N SER 13 16. .920 -4, .122 -6. .542 1, .00 0. .00
ATOM 208 HN SER 13 16. .245 -4, .829 -6. .332 1, .00 0, .00
ATOM 209 CA SER 13 18. .139 -4 .183 -5. .754 1, .00 0, .00
ATOM 210 HA SER 13 18. .134 -3, .279 -5. .145 1. .00 0. .00
ATOM 211 CB SER 13 18. .144 -5, .411 -4. .842 1. .00 0. .00
ATOM 212 2HB SER 13 17. .271 -6, .028 -5. ,059 1. .00 0. .00
ATOM 213 1HB SER 13 19. .024 -6, .018 -5. .055 1, .00 0. .00
ATOM 214 QB SER 13 18. .148 -6, .023 -5. .057 1, .00 0, .00
ATOM 215 OG SER 13 18. .138 -5, .052 -3. .463 1, .00 0, .00
ATOM 216 HG SER 13 18. .173 -5, .875 -2. ,895 1. .00 0. .00
ATOM 217 C SER 13 19. .359 -4, .202 -6. .677 1, .00 0. .00
ATOM 218 O SER 13 20. ,469 -3. ,888 -6. ,251 1. ,00 0. ,00
ATOM 219 N LYS 14 19. ,111 -4. .574 -7. ,924 1. .00 0. ,00
ATOM 220 HN LYS 14 18. ,205 -4. .828 -8. ,263 1. .00 0. ,00
ATOM 221 CA LYS 14 20. ,176 -4. ,639 -8. .911 1. ,00 0. ,00
ATOM 222 HA LYS 14 21. ,061 -5. .032 -8. 411 1. ,00 0. ,00
ATOM 223 CB LYS 14 19. ,813 -5. ,621 -10. 027 1. .00 0. ,00
ATOM 224 2HB LYS 14 19. ,713 -6. .625 -9. 615 1. ,00 0. ,00
ATOM 225 1HB LYS 14 18. .846 -5. .353 -10. 452 1. ,00 0. ,00
ATOM 226 QB LYS 14 19. .279 -5. ,989 -10. 033 1. ,00 0. ,00
ATOM 227 CG LYS 14 20. 878 -5. ,619 -11. 126 1. 00 0. 00
ATOM 228 2HG LYS 14 20. 414 -5. ,843 -12. 086 1. 00 0. 00
ATOM 229 1HG LYS 14 21. 318 -4. ,626 -11. 209 1. 00 0. 00
ATOM 230 QG LYS 14 20. 866 -5. ,234 -11. 647 1. ,00 0. 00
ATOM 231 CD LYS 14 21. 973 -6. ,646 -10. 830 1. ,00 0. 00
ATOM 232 2HD LYS 14 21. 584 -7. .415 -10. 163 1. .00 0. 00
ATOM 233 1HD LYS 14 22. 268 -7. .144 -11. 754 1. ,00 0. ,00
ATOM 234 QD LYS 14 21. 926 -7. .280 -10. 958 1. ,00 0. ,00
ATOM 235 CE LYS 14 23. 193 -5. ,978 -10. 192 1. 00 0. 00
ATOM 236 2HE LYS 14 24. 086 -6. ,208 -10. 773 1. 00 0. 00
ATOM 237 IHE LYS 14 23. 072 -4. ,895 -10. 209 1. 00 0. 00
ATOM 238 QE LYS 14 23. 579 -5. ,552 -10. 491 1. 00 0. 00 ATOM 239 NZ LYS 14 23.367 -6.442 -8.798 1.00 0.00
ATOM 240 1HZ LYS 14 24 .268 -6 .886 -8 .655 1 .00 0 .00
ATOM 241 2HZ LYS 14 23 .308 -5 .679 -8 .133 1 .00 0 .00
ATOM 242 QZ LYS 14 23 .788 -6 .283 -8 .394 1 .00 0 .00
ATOM 243 C LYS 14 20 .487 -3 .227 -9 .411 1 .00 0 .00
ATOM 244 O LYS 14 21 .650 -2 .830 -9 .475 1 .00 0 .00
ATOM 245 N TYR 15 19 .429 -2 .508 -9 .754 1 .00 0 .00
ATOM 246 HN TYR 15 18 .487 -2 .839 -9 .699 1 .00 0 .00
ATOM 247 CA TYR 15 19 .575 -1 .149 -10 .247 1 .00 0 .00
ATOM 248 HA TYR 15 20 .057 -1 .195 -11 .223 1 .00 0 .00
ATOM 249 CB TYR 15 18 .163 -0 .560 -10 .283 1 .00 0 .00
ATOM 250 2HB TYR 15 17 .668 -0 .770 -9 .335 1 .00 0 .00
ATOM 251 1HB TYR 15 18 .235 0 .524 -10 .372 1 .00 0 .00
ATOM 252 QB TYR 15 17 .952 -0 .123 -9 .854 1 .00 0 .00
ATOM 253 QD TYR 15 17 .213 -1 .144 -11 .533 1 .00 0 .00
ATOM 254 QE TYR 15 15 .771 -2 .031 -13 .430 1 .00 0 .00
ATOM 255 QR TYR 15 16 .492 -1, .588 -12 .481 1. .00 0. .00
ATOM 256 CG TYR 15 17 .296 -1 .093 -11 .425 1 .00 0. .00
ATOM 257 CDl TYR 15 17 .699 -2 .204 -12 .137 1 .00 0. .00
ATOM 258 HD1 TYR 15 18 .637 -2. .701 -11 .887 1 .00 o. .00
ATOM 259 CE1 TYR 15 16 .883 -2 .707 -13 .212 1 .00 0 .00
ATOM 260 HEI TYR 15 17 .190 -3 .583 -13 .782 1 .00 0 .00
ATOM 261 CZ TYR 15 15 .720 -2 .063 -13 .498 1 .00 0. .00
ATOM 262 CE2 TYR 15 15 .292 -0 .967 -12 .816 1 .00 0. .00
ATOM 263 HE2 TYR 15 14 .353 -0, .479 -13. .077 1 .00 0. .00
ATOM 264 CD2 TYR 15 16 .109 -0 .464 -11. .742 1 .00 0 .00
ATOM 265 HD2 TYR 15 15 .790 0 .413 -11 .179 1 .00 0 .00
ATOM 266 OH TYR 15 14 .948 -2, .538 -1 .513 1. .00 0. .00
ATOM 267 HH TYR 15 15, .368 -2, .318 -15, .393 1, .00 0, .00
ATOM 268 C TYR 15 20, .439 -0. .313 -9, .301 1, .00 0. .00
ATOM 269 O TYR 15 20, .238 -0. .335 -8, .088 1, .00 0. .00
ATOM 270 N LYS 16 21, .383 0, .405 -9, .893 1, .00 0. .00
ATOM 271 HN LYS 16 21. .540 0. .418 -10, .880 1, .00 0, .00
ATOM 272 CA LYS 16 22, .279 1, .247 -9, .118 1, .00 0. ,00
ATOM 273 HA LYS 16 22. .418 0. ,770 -8. .148 1, ,00 0. ,00
ATOM 274 CB LYS 16 23. .653 1. .325 -9. .786 1. .00 0. ,00
ATOM 275 2HB LYS 16 23. .677 0. .666 -10. ,655 1. ,00 0. ,00
ATOM 276 1HB LYS 16 23. .828 2. ,337 -10. .150 1. ,00 0. ,00
ATOM 277 QB LYS 16 23. .752 1. ,502 -10. .402 1. .00 0. ,00
ATOM 278 CG LYS 16 24. .761 0. ,928 -8. ,809 1, ,00 0. ,00
ATOM 279 2HG LYS 16 24. ,629 -0. ,110 -8. ,505 1. ,00 0. ,00
ATOM 280 1HG LYS 16 25. ,729 0. ,995 -9. ,305 1. .00 0. ,00
ATOM 281 QG LYS 16 25. ,179 0. ,442 -8. ,905 1. .00 0. ,00
ATOM 282 CD LYS 16 24. .751 1. ,831 -7. ,574 1. .00 0. .00
ATOM 283 2HD LYS 16 25. .426 2. ,673 -7. .729 1. .00 0. ,00
ATOM 284 1HD LYS 16 23. .753 2. ,246 -7. .429 1. .00 0. ,00
ATOM 285 QD LYS 16 24. ,590 2. 459 -7. ,579 1. ,00 0. .00
ATOM 286 CE LYS 16 25. ,173 1. 056 -6. ,324 1. ,00 0. ,00
ATOM 287 2HE LYS 16 24. ,295 0. 815 -5. ,724 1. ,00 0. ,00
ATOM 288 IHE LYS 16 25. ,630 0. 109 -6. ,613 1. ,00 0. ,00
ATOM 289 QE LYS 16 24. ,962 0. 462 -6. ,169 1. .00 0. ,00
ATOM 290 NZ LYS 16 26. ,129 1. 849 -5. .519 1. ,00 0. ,00
ATOM 291 1HZ LYS 16 26. 463 1. 335 -4. 712 1. ,00 0. 00
ATOM 292 2HZ LYS 16 26. 946 2. 117 -6. 056 1. .00 0. 00
ATOM 293 QZ LYS 16 26. 705 1. 726 -5. 384 1. .00 0. 00
ATOM 294 C LYS 16 21. 625 2. 613 -8. 897 1. .00 0. 00
ATOM 295 O LYS 16 22. 276 3. 550 -8. 440 1. ,00 0. 00
ATOM 296 N TYR 17 20. 345 2. 681 -9. 232 1. 00 0. 00
ATOM 297 HN TYR 17 19. 822 1. 914 -9. 604 1. 00 0. 00
ATOM 298 CA TYR 17 19. 595 3. 916 -9. 076 1. 00 0. 00
ATOM 299 HA TYR 17 20. 063 4. 495 -8. 280 1. 00 0. 00
ATOM 300 CB TYR 17 19. 628 4. 605 -10. 442 1. 00 0. 00 ATOM 301 2HB TYR 17 19.245 3.916 -11.195 1.00 0.00
ATOM 302 1HB TYR 17 18 .954 5 .461 -10 .422 1 .00 0 .00
ATOM 303 QB TYR 17 19 .100 4 .688 -10 .808 1 .00 0 .00
ATOM 304 QD TYR 17 21 .152 5 .124 -10 .907 1 .00 0 .00
ATOM 305 QE TYR 17 23 .464 5 .912 -11 .612 1 .00 0 .00
ATOM 306 QR TYR 17 22 .308 5 .518 -11 .259 1 .00 0 .00
ATOM 307 CG TYR 17 21 .020 5 .079 -10 .866 1 .00 0 .00
ATOM 308 CDl TYR 17 21 .978 4 .159 -11 .240 1 .00 0 .00
ATOM 309 HD1 TYR 17 21 .744 3 .094 -11 .232 1 .00 0 .00
ATOM 310 CE1 TYR 17 23 .288 4 .605 -11 .639 1 .00 0 .00
ATOM 311 HEI TYR 17 24 .054 3 .889 -11 .937 1 .00 0 .00
ATOM 312 CZ TYR 17 23 .547 5 .940 -11 .637 1 .00 0 .00
ATOM 313 CE2 TYR 17 22 .626 6 .873 -11 .275 1 .00 0. .00
ATOM 314 HE2 TYR 17 22 .874 7 .934 -11 .287 1 .00 0 .00
ATOM 315 CD2 TYR 17 21 .316 6 .427 -10 .876 1. .00 0 .00
ATOM 316 HD2 TYR 17 20 .560 7 .153 -10 .581 1 .00 0 .00
ATOM 317 OH TYR 17 24 .784 6 .361 -12 .014 1, .00 0, .00
ATOM 318 HH TYR 17 25 .071 7 .132 -11 .445 1 .00 0, .00
ATOM 319 C TYR 17 18 .141 3, .631 -8 .697 1, .00 0, .00
ATOM 320 O TYR 17 17, .219 4. .171 -9, .308 1, .00 0. .00
ATOM 321 N ARG 18 17, .980 2, .782 -7, .693 1. .00 0. ,00
ATOM 322 HN ARG 18 18, .735 2, .347 -7, .202 1. .00 0. .00
ATOM 323 CA ARG 18 16, .653 2, .419 -7, .225 1. .00 0. .00
ATOM 324 HA ARG 18 16, .207 1. .868 -8, .054 1. .00 0. .00
ATOM 325 CB ARG 18 16, .731 1. .532 -5, .980 1, .00 0. .00
ATOM 326 2HB ARG 18 17 .019 2, .134 -5 .119 1, .00 0, .00
ATOM 327 1HB ARG 18 15, .748 1. ,116 -5, .764 1. ,00 0. .00
ATOM 328 QB ARG 18 16, .383 1. .625 -5, .441 1. .00 0. .00
ATOM 329 CG ARG 18 17, .740 0. .399 -6, .177 1. .00 0, .00
ATOM 330 2HG ARG 18 17, .658 0. .007 -7, .191 1. .00 0, ,00
ATOM 331 1HG ARG 18 18, .753 0. .785 -6, .065 1, .00 0. .00
ATOM 332 QG ARG 18 18, .206 0. .396 -6, .628 1. .00 0. .00
ATOM 333 CD ARG 18 17, .502 -0. .727 -5, .169 1. .00 0, .00
ATOM 334 2HD ARG 18 16. .718 -0. ,440 -4. .468 1. ,00 0, .00
ATOM 335 1HD ARG 18 17, .156 -1. ,622 -5, .685 1. .00 0. .00
ATOM 336 QD ARG 18 16. .937 -1. .031 -5. .077 1. .00 0. .00
ATOM 337 NE ARG 18 18. .753 -1. .021 -4, .434 1. ,00 0. ,00
ATOM 338 HE ARG 18 19. .597 -0. ,590 -4, .754 1. ,00 0. .00
ATOM 339 CZ ARG 18 18. .827 -1. ,834 -3, .359 1. .00 0. .00
ATOM 340 NH1 ARG 18 19. .997 -2. .025 -2. .780 1. ,00 0. ,00
ATOM 341 HH1 ARG 18 20. .137 -2. .610 -1. .981 1. ,00 0. ,00
ATOM 342 NH2 ARG 18 17. ,719 -2. ,442 -2. ,883 1. ,00 0. 00
ATOM 343 1HH2 ARG 18 17. ,782 -3. ,043 -2. ,087 1. ,00 0. 00
ATOM 344 2HH2 ARG 18 16. ,836 -2. .292 -3. ,328 1. 00 0. 00
ATOM 345 QH2 ARG 18 17. .309 -2. .668 -2. ,707 1. 00 0. 00
ATOM 346 C ARG 18 15. ,843 3. .675 -6. ,898 1. 00 0. 00
ATOM 347 O ARG 18 14. ,619 3. .678 -7. ,023 1. 00 0. 00
ATOM 348 N ASP 19 16. ,558 4. .711 -6. ,486 1. ,00 0. 00
ATOM 349 HN ASP 19 17. ,553 4. 700 -6. ,387 1. 00 0. 00
ATOM 350 CA ASP 19 15. ,920 5. 970 -6. ,140 1. 00 0. 00
ATOM 351 HA ASP 19 15. ,108 5. 704 -5. ,464 1. 00 0. 00
ATOM 352 CB ASP 19 16. ,907 6. 917 -5. ,454 1. 00 0. 00
ATOM 353 2HB ASP 19 17. ,852 6. 392 -5. ,313 1. 00 0. 00
ATOM 354 1HB ASP 19 17. ,105 7. 756 -6. ,121 1. .00 0. 00
ATOM 355 QB ASP 19 17. ,479 7. .074 -5. ,717 1. 00 0. 00
ATOM 356 CG ASP 19 16. 444 7. 464 -4. 102 1. 00 0. 00
ATOM 357 OD1 ASP 19 15. 241 7. 501 -3. 806 1. 00 0. 00
ATOM 358 OD2 ASP 19 17. ,391 7. 870 -3. 326 1. 00 0. 00
ATOM 359 HD2 ASP 19 17. .385 7. 344 -2. ,475 1. 00 0. 00
ATOM 360 C ASP 19 15. ,421 6. 651 -7. ,416 1. 00 0. 00
ATOM 361 0 ASP 19 14. 224 6. 888 -7. .570 1. 00 0. 00
ATOM 362 N LEU 20 16. .364 6. 947 -8. .299 1. 00 0. 00 ATOM 363 HN LEU 20 17.336 6.751 -8.166 1.00 0.00
ATOM 364 CA LEU 20 16 .035 7 .596 -9 .556 1 .00 0 .00
ATOM 365 HA LEU 20 15 .646 8 .587 -9 .320 1 .00 0 .00
ATOM 366 CB LEU 20 17 .294 7 .794 -10 .403 1 .00 0 .00
ATOM 367 2HB LEU 20 18 .104 7 .219 -9 .953 1 .00 0 .00
ATOM 368 1HB LEU 20 17 .113 7 .372 -11 .391 1 .00 0 .00
ATOM 369 QB LEU 20 17 .609 7 .296 -10 .672 1 .00 0 .00
ATOM 370 CG LEU 20 17 .766 9 .239 -10 .575 1 .00 0 .00
ATOM 371 HG LEU 20 18 .716 9. .227 -11 .109 1 .00 0 .00
ATOM 372 QD1 LEU 20 16 .545 10 .231 -11 .629 1 .00 0 .00
ATOM 373 QD2 LEU 20 18 .079 10 .056 -8 .896 1 .00 0 .00
ATOM 374 CDl LEU 20 16 .780 10 .041 -11 .427 1 .00 0 .00
ATOM 375 1HD1 LEU 20 16 .055 10 .533 -10 .778 1 .00 0 .00
ATOM 376 2HD1 LEU 20 17 .322 10 .792 -12 .001 1 .00 0 .00
ATOM 377 3HD1 LEU 20 16 .259 9 .368 -12 .108 1 .00 0 .00
ATOM 378 CD2 LEU 20 18 .019 9 .899 -9 .218 1 .00 0 .00
ATOM 379 1HD2 LEU 20 19 .054 10 .237 -9 .165 1 .00 0 .00
ATOM 380 2HD2 LEU 20 17 .352 10 .753 -9 .099 1 .00 0 .00
ATOM 381 3HD2 LEU 20 17 .831 9 .178 -8 .423 1 .00 0 .00
ATOM 382 QQD LEU 20 17 .312 10 .143 -10 .262 1 .00 0 .00
ATOM 383 C LEU 20 14 .937 6 .800 -10 .264 1 .00 0 .00
ATOM 384 O LEU 20 13 .988 7 .378 -10 .792 1 .00 0 .00
ATOM 385 N THR 21 15 .102 5, .486 -10 .252 1 .00 0 .00
ATOM 386 HN THR 21 15 .876 5 .023 -9 .820 1 .00 0 .00
ATOM 387 CA THR 21 14 .136 4, .604 -10, .886 1, .00 0, .00
ATOM 388 HA THR 21 14 .034 4, .901 -11, .930 1. .00 0, .00
ATOM 389 CB THR 21 14 .680 3, .176 -10, .812 1, .00 0, .00
ATOM 390 HB THR 21 15 .416 3, .080 -10, .014 1, .00 0, .00
ATOM 391 QG2 THR 21 13 .306 1, .887 -10, .625 1, .00 0, .00
ATOM 392 OGl THR 21 15, .205 2. .937 -12. ,115 1. .00 0. .00
ATOM 393 HG1 THR 21 16, .198 2. .825 -12. .068 1. .00 0. .00
ATOM 394 CG2 THR 21 13, .570 2. .134 -10. .661 1, .00 0. ,00
ATOM 395 1HG2 THR 21 14, .014 1. .152 -10. .495 1. .00 0, ,00
ATOM 396 2HG2 THR 21 12, .939 2. .396 -9. .811 1. .00 0. .00
ATOM 397 3HG2 THR 21 12. .967 2. .111 -11. .568 1. .00 0. ,00
ATOM 398 C THR 21 12. .760 4. .765 -10. .237 1. ,00 0. ,00
ATOM 399 O THR 21 11, .755 4, ,909 -10. .931 1. ,00 0. ,00
ATOM 400 N VAL 22 12, .760 4. ,735 -8. ,912 1. .00 0. ,00
ATOM 401 HN VAL 22 13, .582 4. ,618 -8. .355 1. .00 0. .00
ATOM 402 CA VAL 22 11. .524 4. .876 -8. .161 1, .00 0, .00
ATOM 403 HA VAL 22 10. .820 4. .137 -8. .544 1. .00 0. ,00
ATOM 404 CB VAL 22 11. .772 4. ,572 -6. .683 1. ,00 0. .00
ATOM 405 HB VAL 22 12. .687 5. .084 -6. ,384 1. .00 0. .00
ATOM 406 QG1 VAL 22 10. .359 5. .230 -5. .608 1. .00 0. .00
ATOM 407 QG2 VAL 22 12. .028 2. .717 -6. .405 1. .00 0. ,00
ATOM 408 CGI VAL 22 10. ,630 5. ,104 -5. ,814 1. ,00 0. .00
ATOM 409 1HG1 VAL 22 10. ,581 4. ,531 -4. ,888 1. ,00 0. .00
ATOM 410 2HG1 VAL 22 10. ,809 6. ,154 -5. ,582 1. ,00 0. ,00
ATOM 411 3HG1 VAL 22 9. ,688 5. .005 -6. .353 1. ,00 0. ,00
ATOM 412 CG2 VAL 22 11. ,979 3. ,073 -6. ,458 1. ,00 0. ,00
ATOM 413 1HG2 VAL 22 11. 059 2. 632 -6. 073 1. 00 0. 00
ATOM 414 2HG2 VAL 22 12. 242 2. 597 -7. 403 1. 00 0. 00
ATOM 415 3HG2 VAL 22 12. 784 2. 920 -5. 739 1. 00 0. 00
ATOM 416 QQG VAL 22 11. .194 3. 973 -6. 006 1. 00 0. 00
ATOM 417 C VAL 22 10. .946 6. 273 -8. 395 1. 00 0. 00
ATOM 418 O VAL 22 9. .778 6. 413 -8. 757 1. 00 0. 00
ATOM 419 N ARG 23 11. 790 7. 271 -8. 180 1. 00 0. 00
ATOM 420 HN ARG 23 12. 738 7. 149 -7. 886 1. 00 0. 00
ATOM 421 CA ARG 23 11. 378 8. 653 -8. 363 1. 00 0. 00
ATOM 422 HA ARG 23 10. 574 8. 802 -7. 642 1. 00 0. 00
ATOM 423 CB ARG 23 12. 533 9. 615 -8. 078 1. 00 0. 00
ATOM 424 2HB ARG 23 13. 482 9. 090 -8. 185 1. 00 0. 00 ATOM 425 1HB ARG 23 12.529 10.421 -8.811 1.00 0.00
ATOM 426 QB ARG 23 13 .006 9 .756 -8 .498 1 .00 0 .00
ATOM 427 CG ARG 23 12 .424 10 .199 -6 .668 1 .00 0 .00
ATOM 428 2HG ARG 23 12 .242 11 .272 -6 .729 1 .00 0 .00
ATOM 429 1HG ARG 23 11 .569 9 .760 -6 .153 1 .00 0 .00
ATOM 430 QG ARG 23 11 .906 10 .516 -6 .441 1 .00 0 .00
ATOM 431 CD ARG 23 13 .700 9 .937 -5 .865 1 .00 o . .00
ATOM 432 2HD ARG 23 13 .589 9 .025 -5 .278 1 .00 0. .00
ATOM 433 1HD ARG 23 14 .539 9 .780 -6 .542 1 .00 0. .00
ATOM 434 QD ARG 23 14 .064 9 .403 -5 .910 1 .00 0. .00
ATOM 435 NE ARG 23 13 .979 11 .083 -4 .971 1 .00 0 .00
ATOM 436 HE ARG 23 14, .776 11 .652 -5 .174 1 .00 0, .00
ATOM 437 CZ ARG 23 13, .227 11, .407 -3 .899 1. .00 0, .00
ATOM 438 NH1 ARG 23 13, .569 12, .452 -3 .169 1, .00 0, .00
ATOM 439 HH1 ARG 23 13, .066 12, .759 -2 .361 1, .00 0, .00
ATOM 440 NH2 ARG 23 12, .140 10, .674 -3 .577 1, .00 0, .00
ATOM 441 1HH2 ARG 23 11, .587 10, .921 -2 .781 1, .00 0, .00
ATOM 442 2HH2 ARG 23 11, .887 9, .884 -4 .135 1, .00 0, .00
ATOM 443 QH2 ARG 23 11, .737 10, .402 -3 .458 1, .00 0, .00
ATOM 444 C ARG 23 10, .881 8, .873 -9 .793 1, .00 0, .00
ATOM 445 O ARG 23 9, .773 9, .366 -10 .000 1 .00 0, .00
ATOM 446 N GLU 24 11, .724 8, .497 -10, .743 1, .00 0, .00
ATOM 447 HN GLU 24 12, .624 8, .097 -10, .566 1, .00 0, .00
ATOM 448 CA GLU 24 11, .385 8, .648 -12, .148 1, .00 0, .00
ATOM 449 HA GLU 24 11, .223 9, .716 -12, .294 1, .00 0, .00
ATOM 450 CB GLU 24 12, .538 8, .189 -13 .043 1, .00 0, .00
ATOM 451 2HB GLU 24 12, .906 7, .222 -12, .700 1, .00 0, .00
ATOM 452 1HB GLU 24 12, .178 8, .049 -14, .063 1, .00 0, .00
ATOM 453 QB GLU 24 12. .542 7, .635 -13 .381 1, .00 0, .00
ATOM 454 CG GLU 24 13, .679 9, .208 -13 .034 1, .00 0, .00
ATOM 455 2HG GLU 24 14, .021 9, .366 -12. .011 1, .00 0, .00
ATOM 456 1HG GLU 24 14, .526 8, .816 -13 .597 1, .00 0, .00
ATOM 457 QG GLU 24 14. .274 9. .091 -12, .804 1. .00 0. .00
ATOM 458 CD GLU 24 13. .229 10. .540 -13, .639 1. .00 0. ,00
ATOM 459 OEl GLU 24 12. .278 10. .570 -14, .434 1. ,00 0. ,00
ATOM 460 OE2 GLU 24 13. .906 11. .569 -13. .256 1. ,00 0. ,00
ATOM 461 HE2 GLU 24 13. .394 12. .406 -13. .450 1. ,00 0. ,00
ATOM 462 C GLU 24 10. ,102 7. .879 -12. .469 1. ,00 0. ,00
ATOM 463 O GLU 24 9. .187 8. ,422 -13. .087 1. ,00 0. .00
ATOM 464 N THR 25 10. .075 6. ,627 -12. .036 1. ,00 0. .00
ATOM 465 HN THR 25 10. .824 6. .193 -11. .534 1. ,00 0. ,00
ATOM 466 CA THR 25 8. .919 5. ,779 -12. .270 1. ,00 0. ,00
ATOM 467 HA THR 25 8. ,782 5. ,674 -13. ,346 1. ,00 0. ,00
ATOM 468 CB THR 25 9. ,208 4. ,407 -11. ,656 1. ,00 0. .00
ATOM 469 HB THR 25 9. ,615 4. ,509 -10. .650 1. ,00 0. .00
ATOM 470 QG2 THR 25 7. ,689 3. .277 -11. .661 1. ,00 0. ,00
ATOM 471 OGl THR 25 10. .100 3. .793 -12. .582 1. ,00 0. ,00
ATOM 472 HG1 THR 25 10. ,988 4. ,253 -12. ,559 1. ,00 0. ,00
ATOM 473 CG2 THR 25 7. ,980 3. .494 -11. ,660 1. ,00 0. ,00
ATOM 474 1HG2 THR 25 7. .423 3. .630 -10. .733 1. .00 0. ,00
ATOM 475 2HG2 THR 25 7. ,343 3. ,746 -12. .507 1. ,00 0. ,00
ATOM 476 3HG2 THR 25 8. ,301 2. ,455 -11. ,742 1. ,00 0. ,00
ATOM 477 C THR 25 7. .654 6. .437 -11. ,717 1. .00 0. .00
ATOM 478 O THR 25 6. ,704 6. ,684 -12. ,458 1. .00 0. ,00
ATOM 479 N VAL 26 7. ,682 6. ,703 -10. ,419 1. .00 0. 00
ATOM 480 HN VAL 26 8. .458 6. ,499 -9. ,823 1. .00 0. 00
ATOM 481 CA VAL 26 6. .549 7. ,328 -9. ,759 1. .00 0. 00
ATOM 482 HA VAL 26 5. ,738 6. ,600 -9. ,736 1. ,00 0. ,00
ATOM 483 CB VAL 26 6. ,913 7. ,678 -8. ,314 1. ,00 0. .00
ATOM 484 HB VAL 26 7. ,802 8. .307 -8. ,336 1. ,00 0. 00
ATOM 485 QG1 VAL 26 5. ,524 8. .662 -7. ,484 1. ,00 0. ,00
ATOM 486 QG2 VAL 26 7. ,327 6. ,119 -7. ,323 1. ,00 0. 00 ATOM 487 CGI VAL 26 5.790 8.473 -7.643 1.00 0.00
ATOM 488 1HG1 VAL 26 5 .173 7 .799 -7 .050 1 .00 0 .00
ATOM 489 2HG1 VAL 26 6 .223 9 .235 -6 .995 1 .00 0 .00
ATOM 490 3HG1 VAL 26 5 .177 8 .950 -8 .407 1 .00 0 .00
ATOM 491 CG2 VAL 26 7 .247 6 .419 -7 .513 1 .00 0 .00
ATOM 492 1HG2 VAL 26 7 .147 5 .543 -8 .154 1 .00 0 .00
ATOM 493 2HG2 VAL 26 8 .271 6 .484 -7 .144 1 .00 0 .00
ATOM 494 3HG2 VAL 26 6 .562 6 .332 -6 .670 1 .00 0 .00
ATOM 495 QQG VAL 26 6 .425 7 .390 -7 .403 1 .00 0 .00
ATOM 496 C VAL 26 6 .096 8 .543 -10 .572 1 .00 0 .00
ATOM 497 O VAL 26 4 .962 8 .589 -11 .045 1 .00 0 .00
ATOM 498 N ASN 27 7 .006 9 .495 -10 .709 1 .00 0 .00
ATOM 499 HN ASN 27 7 .927 9 .450 -10 .321 1 .00 0 .00
ATOM 500 CA ASN 27 6. .715 10 .707 -11 .457 1 .00 0 .00
ATOM 501 HA ASN 27 5 .978 11 .242 -10 .859 1 .00 0 .00
ATOM 502 CB ASN 27 7 .975 11 .553 -11 .648 1 .00 0 .00
ATOM 503 2HB ASN 27 8, .848 10. .992 -11 .313 1 .00 0 .00
ATOM 504 1HB ASN 27 8. .120 11, .762 -12 .708 1 .00 0 .00
ATOM 505 QB ASN 27 8 .484 11 .377 -12 .010 1 .00 0 .00
ATOM 506 CG ASN 27 7. .877 12 .867 -10 .872 1 .00 0 .00
ATOM 507 OD1 ASN 27 6 .803 13 .343 -10 .540 1 .00 o. .00
ATOM 508 ND2 ASN 27 9, .053 13, .425 -10, .601 1 .00 0. .00
ATOM 509 1HD2 ASN 27 9, .897 12, .983 -10, .903 1 .00 0. .00
ATOM 510 2HD2 ASN 27 9, .093 14. .288 -10. .097 1, .00 0, .00
ATOM 511 QD2 ASN 27 9. .495 13. .635 -10. .500 1, .00 0, .00
ATOM 512 C ASN 27 6, .184 10, .331 -12. .842 1 .00 0, .00
ATOM 513 O ASN 27 5, .226 10, .931 -13, .327 1 .00 0, .00
ATOM 514 N VAL 28 6, .829 9, .339 -13. .439 1 .00 0, .00
ATOM 515 HN VAL 28 7. ,607 8. .857 -13. .037 1, .00 0. .00
ATOM 516 CA VAL 28 6. .433 8. .876 -14. .758 1, .00 0, .00
ATOM 517 HA VAL 28 6. .467 9. .733 -15. .431 1, .00 0, .00
ATOM 518 CB VAL 28 7. .430 7. .833 -15. .267 1, .00 0, .00
ATOM 519 HB VAL 28 7. .714 7. .202 -14. .425 1 .00 0, .00
ATOM 520 QG1 VAL 28 6, .639 6, .725 -16. .583 1 .00 0. .00
ATOM 521 QG2 VAL 28 8. ,999 8. .660 -15. .930 1, .00 0, .00
ATOM 522 CGI VAL 28 6. .791 6. .937 -16. .331 1, .00 0, .00
ATOM 523 1HG1 VAL 28 6. .299 7. .558 -17. ,080 1, .00 0, .00
ATOM 524 2HG1 VAL 28 7. .562 6. .334 -16. .809 1. .00 0, .00
ATOM 525 3HG1 VAL 28 6. .056 6. .283 -15. .861 1, .00 0. .00
ATOM 526 CG2 VAL 28 8. .698 8. ,501 -15. .802 1, .00 0, .00
ATOM 527 1HG2 VAL 28 9. ,571 8. ,064 -15. ,318 1. .00 0. .00
ATOM 528 2HG2 VAL 28 8. ,763 8. ,346 -16. ,879 1. .00 0. ,00
ATOM 529 3HG2 VAL 28 8. ,662 9. ,570 -15. ,591 1. ,00 0. ,00
ATOM 530 QQG VAL 28 7. .819 7. ,692 -16. ,256 1. .00 0. ,00
ATOM 531 C VAL 28 4. .997 8. ,352 -14. ,700 1. .00 0. ,00
ATOM 532 O VAL 28 4. .084 8. ,972 -15. ,245 1. .00 0. ,00
ATOM 533 N ILE 29 4. 841 7. 217 -14. 036 1. ,00 0. 00
ATOM 534 HN ILE 29 5. 589 6. 719 -13. 596 1. ,00 0. 00
ATOM 535 CA ILE 29 3. 531 6. 603 -13. 900 1. ,00 0. 00
ATOM 536 HA ILE 29 3. 205 6. 305 -14. 896 1. ,00 0. 00
ATOM 537 CB ILE 29 3. 621 5. 330 -13. 055 1. ,00 0. 00
ATOM 538 HB ILE 29 2. 635 4. 866 -13. 031 1. ,00 0. 00
ATOM 539 QG2 ILE 29 4. 810 4. 080 -13. 835 1. 00 0. 00
ATOM 540 CG2 ILE 29 4. 582 4. 320 -13. 685 1. 00 0. 00
ATOM 541 1HG2 ILE 29 4. 497 4. 367 -14. 771 1. 00 0. 00
ATOM 542 2HG2 ILE 29 5. 604 4. 557 -13. 390 1. .00 0. 00
ATOM 543 3HG2 ILE 29 4. 329 3. 316 -13. 344 1. .00 0. 00
ATOM 544 CGI ILE 29 4. 001 5. 657 -11. 609 1. .00 0. 00
ATOM 545 2HG1 ILE 29 5. 081 5. 580 -11. 487 1. 00 0. 00
ATOM 546 1HG1 ILE 29 3. 727 6. 688 -11. 382 1. 00 0. 00
ATOM 547 QG1 ILE 29 4. 404 6. 134 -11. 435 1. 00 0. 00
ATOM 548 QD1 ILE 29 3. 137 4. 485 -10. 399 1. 00 0. 00 ATOM 549 CDl ILE 29 3.303 4.710 -10.631 1.00 0.00
ATOM 550 1HD1 ILE 29 3 .513 3 .678 -10 .912 1 .00 0.00
ATOM 551 2HD1 ILE 29 3 .671 4 .895 -9 .622 1 .00 0.00
ATOM 552 3HD1 ILE 29 2 .227 4 .884 -10 .663 1 .00 0.00
ATOM 553 C ILE 29 2 .543 7 .635 -13 .353 1 .00 0.00
ATOM 554 O ILE 29 1 .334 7 .497 -13 .531 1 .00 0.00
ATOM 555 N THR 30 3 .094 8 .647 -12 .699 1 .00 0.00
ATOM 556 HN THR 30 4 .079 8 .752 -12 .559 1 .00 0.00
ATOM 557 CA THR 30 2 .277 9 .702 -12 .126 1 .00 0.00
ATOM 558 HA THR 30 1 .410 9 .244 -11 .649 1 .00 0.00
ATOM 559 CB THR 30 3 .114 10 .430 -11 .072 1 .00 0.00
ATOM 560 HB THR 30 4 .121 10 .625 -11 .442 1 .00 0.00
ATOM 561 QG2 THR 30 2, .293 12 .026 -10 .470 1 .00 0.00
ATOM 562 OGl THR 30 3 .071 9 .568 -9 .939 1 .00 0.00
ATOM 563 HG1 THR 30 3 .580 8 .728 -10 .128 1 .00 0.00
ATOM 564 CG2 THR 30 2 .451 11 .719 -10. .585 1 .00 0.00
ATOM 565 1HG2 THR 30 1 .639 11 .988 -11 .261 1 .00 0.00
ATOM 566 2HG2 THR 30 2 .053 11 .567 -9 .582 1 .00 0.00
ATOM 567 3HG2 THR 30 3. .188 12 .522 -10 .566 1. .00 0.00
ATOM 568 C THR 30 1 .749 10 .625 -13 .226 1 .00 0.00
ATOM 569 O THR 30 0 .554 10 .913 -13 .279 1 .00 0.00
ATOM 570 N LEU 31 2. .665 11 .062 -14, .077 1 .00 0.00
ATOM 571 HN LEU 31 3, .634 10 .823 -14, .027 1 .00 0.00
ATOM 572 CA LEU 31 2, .306 11. .947 -15, .173 1. .00 0.00
ATOM 573 HA LEU 31 1, .722 12 .766 -14, .754 1. .00 0.00
ATOM 574 CB LEU 31 3, .561 12. .560 -15, .799 1 .00 0.00
ATOM 575 2HB LEU 31 4. .407 11 .907 -15, .583 1 .00 0.00
ATOM 576 1HB LEU 31 3, .434 12, .570 -16, .882 1, .00 0.00
ATOM 577 QB LEU 31 3, .920 12, .239 -16, .232 1. .00 0.00
ATOM 578 CG LEU 31 3, .915 13, .976 -15, .342 1, .00 0.00
ATOM 579 HG LEU 31 3, .715 14, .050 -14. .273 1, .00 0.00
ATOM 580 QD1 LEU 31 5, .758 14, .328 -15. .591 1, .00 0.00
ATOM 581 QD2 LEU 31 2. .824 15. .261 -16. .205 1. ,00 0.00
ATOM 582 CDl LEU 31 5. .405 14. ,261 -15. .543 1. ,00 0.00
ATOM 583 1HD1 LEU 31 5. .947 13. ,319 -15. ,623 1. ,00 0.00
ATOM 584 2HD1 LEU 31 5. .544 14. ,839 -16. .456 1. .00 0.00
ATOM 585 3HD1 LEU 31 5. ,784 14. ,827 -14. ,692 1. ,00 0.00
ATOM 586 CD2 LEU 31 3. ,034 15. ,014 -16. ,039 1. .00 0.00
ATOM 587 1HD2 LEU 31 3. .393 15. .172 -17. ,056 1. .00 0.00
ATOM 588 2HD2 LEU 31 2. .005 14. .656 -16. ,069 1. .00 0.00
ATOM 589 3HD2 LEU 31 3. ,075 15. .955 -15. .489 1. ,00 0.00
ATOM 590 QQD LEU 31 4. ,291 14. .794 -15. .898 1. ,00 0.00
ATOM 591 C LEU 31 1. ,430 11. ,186 -16. .171 1. ,00 0.00
ATOM 592 O LEU 31 0. ,690 11. ,795 -16. ,942 1. ,00 0.00
ATOM 593 N TYR 32 1. ,543 9. ,867 -16. ,123 1. ,00 0.00
ATOM 594 HN TYR 32 2. ,147 9. ,380 -15. ,493 1. ,00 0.00
ATOM 595 CA TYR 32 0. ,770 9. ,018 -17. ,013 1. ,00 0.00
ATOM 596 HA TYR 32 0. ,100 9. ,583 -17. ,347 1. ,00 0.00
ATOM 597 CB TYR 32 1. ,719 8. ,620 -18. .146 1. ,00 0.00
ATOM 598 2HB TYR 32 2. ,561 8. .070 -17. 724 1. ,00 0.00
ATOM 599 1HB TYR 32 1. .199 7. ,938 -18. ,819 1. ,00 0.00
ATOM 600 QB TYR 32 1. .880 8. .004 -18. 272 1. ,00 0.00
ATOM 601 QD TYR 32 2. .305 9. .915 -19. 031 1. ,00 0.00
ATOM 602 QE TYR 32 3. 193 11. 882 -20. 374 1. 00 0.00
ATOM 603 QR TYR 32 2. 749 10. 899 -19. 702 1. 00 0.00
ATOM 604 CG TYR 32 2. 254 9. 803 -18. 954 1. 00 0.00
ATOM 605 CDl TYR 32 1. 459 10. 400 -19. 912 1. 00 0.00
ATOM 606 HD1 TYR 32 0. 450 10. 028 -20. 092 1. 00 0.00
ATOM 607 CE1 TYR 32 1. 963 11. 514 -20. 673 1. 00 0.00
ATOM 608 HEI TYR 32 1. 346 11. 995 -21. 432 1. 00 0.00
ATOM 609 CZ TYR 32 3. 225 11. 953 -20. 423 1. 00 0.00
ATOM 610 CE2 TYR 32 4. 034 11. 388 -19. 487 1. 00 0.00 ATOM 611 HE2 TYR 32 5.041 11.770 -19.316 1.00 0.00
ATOM 612 CD2 TYR 32 3.531 10.274 -18. 726 1.00 0.00
ATOM 613 HD2 TYR 32 4.158 9 9..880033 --1177..9 96699 1.00 0.00
ATOM 614 OH TYR 32 3.701 1 133..000055 --2211..1 14411 1.00 0.00
ATOM 615 HH TYR 32 4.546 1 133 3...333444666 - -2200. . 773300 1.00 0.00
ATOM 616 C TYR 32 0.298 7 7 7...777555444 - -1166. . 229922 1.00 0.00
ATOM 617 O TYR 32 1.063 6 6..880044 - -1166. . 113300 1.00 0.00
ATOM 618 N LYS 33 0.960 7 7..778822 - -1155. . 887788 1.00 0.00
ATOM 619 HN LYS 33 1.576 8 8..555588 - -1166. . 001133 1.00 0.00
ATOM 620 CA LYS 33 1.543 6 6..665511 - -1155. . 117777 1.00 0.00
ATOM 621 HA LYS 33 0.784 6 6..225588 - -1144. . 550022 1.00 0.00
ATOM 622 CB LYS 33 2.724 7 7..110044 - -1144. . 331155 1.00 0.00
ATOM 623 2HB LYS 33 335 7 7 7...888111444 - -1144. . 887733 1.00 0.00
ATOM 624 1HB LYS 33 359 6 6 6...222555000 - -1144. . 008844 1.00 0.00
ATOM 625 QB LYS 33 347 7 7 7...000333222 - -1144. . 447799 1.00 0.00
ATOM 626 CG LYS 33 238 7 7..775522 - -1133. . 001177 1.00 0.00
ATOM 627 2HG LYS 33 148 7 7..772299 - -1122. . 998811 1.00 0.00
ATOM 628 1HG LYS 33 535 8 8 8...888000000 - -1122. . 999966 1.00 0.00
ATOM 629 QG LYS 33 842 8 8 8...222666444 - -1122. . 998888 1.00 0.00
ATOM 630 CD LYS 33 809 7 7 7...002288 - -1111., . 779966 1.00 0.00
ATOM 631 2HD LYS 33 637 7 7 7...660044 - -1111., . 338822 1.00 0.00
ATOM 632 1HD LYS 33 213 6 6..000666222 - -1122., . 009988 1.00 0.00
ATOM 633 QD LYS 33 425 6 6..888333333 - -1111., . 774400 1.00 0.00
ATOM 634 CE LYS 33 735 6 6..888222666 - -1100., . 772266 1.00 0.00
ATOM 635 2HE LYS 33 780 6 6..559977 - -1111. . 119999 1.00 0.00
ATOM 636 IHE LYS 33 597 7 7..774499 - -1100. . 116622 1.00 0.00
ATOM 637 QE LYS 33 189 7 7..117733 - -1100., . 668800 1.00 0.00
ATOM 638 NZ LYS 33 -2.117 5 5..773300 - -99., . 880088 1.00 0.00
ATOM 639 1HZ LYS 33 -2 .003 4 4..88 8111888 - -1100., . 223377 1.00 0.00
ATOM 640 2HZ LYS 33 -1 .556 5 5..777222999 - -88., . 996633 1.00 0.00
ATOM 641 QZ LYS 33 -1 .780 5 5..222777333 - -99. . 660000 1.00 0.00
ATOM 642 C LYS 33 -1 .904 5 5..556611 - -1166., . 118899 1.00 0.00
ATOM 643 O LYS 33 -3. .080 5 5..226688 - -1166., . 339999 1.00 0.00
ATOM 644 N ASP 34 -0. ,870 4 4..999900 - -1166.. . 778899 1.00 0.00
ATOM 645 HN ASP 34 0.084 5 5..22 2333444 - -1166.. . 661122 1.00 0.00
ATOM 646 CA ASP 34 -1.063 3 3..999333999 - -1177.. . 777733 1.00 0.00
ATOM 647 HA ASP 34 -1.994 3 3..444444999 - -1177.. . 449911 1.00 0.00
ATOM 648 CB ASP 34 -1.162 4 4..555111999 - -1199.. . 118866 1.00 0.00
ATOM 649 2HB ASP 34 -0.213 4 4..999933 - -1199.. , 443355 1.00 0.00
ATOM 650 1HB ASP 34 -1.303 3 3..669988 - -1199.. . 889900 1.00 0.00
ATOM 651 QB ASP 34 -0.758 4 4..334466 - -1199.. . 666633 1.00 0.00
ATOM 652 CG ASP 34 -2.287 5 5..553366 - -1199.. , 338899 1.00 0.00
ATOM 653 OD1 ASP 34 -3.445 5 5..11 1666888 - -1199.. , 663366 1.00 0.00
ATOM 654 OD2 ASP 34 -1.930 6 6..777777111 - -1199.. , 228833 1.00 0.00
ATOM 655 HD2 ASP 34 -1.013 6 6..888999666 - -1199.. , 666633 1.00 0.00
ATOM 656 C ASP 34 0.134 2 2..999888666 - -1177.. , 773377 1.00 0.00
ATOM 657 O ASP 34 -0.036 1 1..777777555 - -1177.. . 660033 1.00 0.00
ATOM 658 N LEU 35 1.318 3 33...555666999 - -1177.. , 885599 1.00 0.00
ATOM 659 HN LEU 35 .447 4 44...555555444 - -1177.. , 996688 1.00 0.00
ATOM 660 CA LEU 35 .542 2 2..777888666 - -1177.. , 884411 1.00 0.00
ATOM 661 HA LEU 35 .448 2 2..000111666 - -1188.. , 660077 1.00 0.00
ATOM 662 CB LEU 35 .740 3 3..666555888 - -1188.. , 222222 1.00 0.00
ATOM 663 2HB LEU 35 .381 4 4..666688 - -1188.. , 442211 1.00 0.00
ATOM 664 1HB LEU 35 .407 3 3..772211 - -1177.. , 336622 1.00 0.00
ATOM 665 QB LEU 35 .894 4 4..119944 - -1177.. . 889911 1.00 0.00
ATOM 666 CG LEU 35 .554 3 3..119900 - -1199.. 4 43300 1.00 0.00
ATOM 667 HG LEU 35 .859 2 2..115577 - -1199.. 2 25577 1.00 0.00
ATOM 668 QD1 LEU 35 .502 3 3..220066 - -2211.. 0 00044 1.00 0.00
ATOM 669 QD2 LEU 35 6.134 4 4..221144 - -1199.. 6 62233 1.00 0.00
ATOM 670 CDl LEU 35 3.704 3 3..220033 - -2200.. 7 70022 1.00 0.00
ATOM 671 1HD1 LEU 35 4.354 3 3..113344 - -2211.. 5 57744 1.00 0.00
ATOM 672 2HD1 LEU 35 3.021 2 2..335533 - -2200.. , 669911 1.00 0.00 ATOM 673 3HD1 LEU 35 3.132 4.129 -20.747 1.00 0.00
ATOM 674 CD2 LEU 35 5 .831 4 .018 -19 .586 1 .00 0 .00
ATOM 675 1HD2 LEU 35 6 .392 4 .000 -18 .651 1 .00 0 .00
ATOM 676 2HD2 LEU 35 6 .442 3 .597 -20 .384 1 .00 0 .00
ATOM 677 3HD2 LEU 35 5 .569 5 .047 -19 .833 1 .00 0 .00
ATOM 678 QQD LEU 35 4 .818 3 .710 -20 .313 1 .00 0 .00
ATOM 679 C LEU 35 2 .686 2 .103 -16 .480 1 .00 0 .00
ATOM 680 O LEU 35 3 .381 2 .608 -15 .599 1 .00 0 .00
ATOM 681 N LYS 36 2 .019 0 .966 -16 .351 1 .00 0 .00
ATOM 682 HN LYS 36 1 .457 0 .562 -17 .072 1 .00 0 .00
ATOM 683 CA LYS 36 2 .065 0 .208 -15 .112 1 .00 0 .00
ATOM 684 HA LYS 36 2 .023 0 .923 -14 .290 1 .00 0 .00
ATOM 685 CB LYS 36 0 .835 -0 .693 -14 .989 1 .00 0 .00
ATOM 686 2HB LYS 36 0 .466 -0 .949 -15 .983 1 .00 0 .00
ATOM 687 1HB LYS 36 1 .112 -1 .628 -14 .503 1 .00 0 .00
ATOM 688 QB LYS 36 0. .789 -1 .289 -15 .243 1 .00 0 .00
ATOM 689 CG LYS 36 ■0. .273 -0 .004 -14 .190 1 .00 0 .00
ATOM 690 2HG LYS 36 •0. .199 1 .076 -14 .315 1 .00 0 .00
ATOM 691 1HG LYS 36 ■1, .246 -0. .304 -14 .578 1 .00 0. .00
ATOM 692 QG LYS 36 ■0, .722 0. .386 -14 .446 1 .00 0, .00
ATOM 693 CD LYS 36 ■0, .178 -0. .359 -12 .704 1 .00 0 .00
ATOM 694 2HD LYS 36 ■0, .783 -1 .242 -12 .499 1 .00 0, .00
ATOM 695 1HD LYS 36 0. .851 -0 .611 -12 .452 1 .00 0. .00
ATOM 696 QD LYS 36 0 .034 -0 .927 -12 .475 1. .00 0. .00
ATOM 697 CE LYS 36 •0, .653 0 .805 -11, .832 1, .00 0, .00
ATOM 698 2HE LYS 36 0, .190 1, .222 -11, .282 1, .00 0, .00
ATOM 699 IHE LYS 36 •1, .048 1, .602 -12, .462 1, .00 0, .00
ATOM 700 QE LYS 36 ■0, .429 1. .412 -11, .872 1, .00 0, .00
ATOM 701 NZ LYS 36 •1, .695 0, .351 -10, .885 1, .00 0, .00
ATOM 702 1HZ LYS 36 2. .016 -0. .588 -11. .094 1. ,00 0. .00
ATOM 703 2HZ LYS 36 1. ,360 0. .340 -9. .928 1. ,00 0. .00
ATOM 704 QZ LYS 36 1. ,688 -0, .124 -10. .511 1. .00 0. .00
ATOM 705 C LYS 36 3. ,392 -0. .548 -15. ,030 1, .00 0, .00
ATOM 706 O LYS 36 3. .750 -1, .283 -15. .948 1, .00 0, .00
ATOM 707 N PRO 37 4. ,105 -0. .335 -13. .891 1. ,00 0. .00
ATOM 708 CD PRO 37 3. ,713 0, .529 -12. .782 1. .00 0. .00
ATOM 709 CA PRO 37 5. .386 -0, ,989 -13. .677 1. .00 0. .00
ATOM 710 HA PRO 37 5. .926 -0, .976 -14. .518 1, .00 0, .00
ATOM 711 CB PRO 37 6. .052 -0, .193 -12. ,567 1, .00 0, ,00
ATOM 712 2HB PRO 37 6, ,557 -0, .854 -11. .862 1, .00 0. .00
ATOM 713 1HB PRO 37 6. ,808 0. ,481 -12. .969 1. .00 0. ,00
ATOM 714 QB PRO 37 6. ,683 -0. ,186 -12. ,415 1. ,00 0. ,00
ATOM 715 CG PRO 37 4. ,938 0. .583 -11. .883 1. ,00 0. ,00
ATOM 716 2HG PRO 37 4. ,715 0. .152 -10. ,907 1. .00 0. ,00
ATOM 717 1HG PRO 37 5. ,241 1. .616 -11. ,713 1. .00 0. ,00
ATOM 718 QG PRO 37 4. 978 0. ,884 -11. ,310 1. ,00 0. 00
ATOM 719 2HD PRO 37 2. ,851 0. ,125 -12. ,251 1. ,00 0. ,00
ATOM 720 1HD PRO 37 3. .435 1. ,522 -13. ,133 1. ,00 0. .00
ATOM 721 QD PRO 37 3. 143 0. ,824 -12. .692 1. ,00 0. 00
ATOM 722 C PRO 37 5. .196 -2. ,465 -13. ,324 1. ,00 0. .00
ATOM 723 O PRO 37 4. 571 -2. 790 -12. 315 1. 00 0. 00
ATOM 724 N VAL 38 5. 745 -3. 320 -14. 174 1. 00 0. 00
ATOM 725 HN VAL 38 6. 251 -3. 047 -14. 992 1. 00 0. 00
ATOM 726 CA VAL 38 5. 644 -4. ,754 -13. 964 1. 00 0. 00
ATOM 727 HA VAL 38 5. 063 -4. .913 -13. 057 1. 00 0. 00
ATOM 728 CB VAL 38 4. 892 -5. .401 -15. 129 1. 00 0. 00
ATOM 729 HB VAL 38 3. 925 -4. 907 -15. 219 1. 00 0. 00
ATOM 730 QG1 VAL 38 5. 824 -5. 156 -16. 759 1. 00 0. 00
ATOM 731 QG2 VAL 38 4. 578 -7. 238 -14. 796 1. 00 0. 00
ATOM 732 CGI VAL 38 5. 645 -5. .203 -16. 446 1. 00 0. 00
ATOM 733 1HG1 VAL 38 5. 068 -4. .550 -17. 100 1. 00 0. 00
ATOM 734 2HG1 VAL 38 6. 616 -4. 750 -16. 245 1. 00 0. 00 ATOM 735 3HG1 VAL 38 5.788 -6.169 -16.931 1.00 0.00
ATOM 736 CG2 VAL 38 4 .638 -6 .886 -14 .860 1 .00 0 .00
ATOM 737 1HG2 VAL 38 4 .372 -7 .025 -13 .812 1 .00 0 .00
ATOM 738 2HG2 VAL 38 3 .822 -7 .235 -15 .492 1 .00 0 .00
ATOM 739 3HG2 VAL 38 5 .540 -7 .455 -15 .084 1 .00 0 .00
ATOM 740 QQG VAL 38 5 .201 -6 .197 -15 .777 1 .00 0 .00
ATOM 741 C VAL 38 7 .045 -5 .335 -13 .761 1 .00 0 .00
ATOM 742 O VAL 38 8 .006 -4 .879 -14 .378 1 .00 0 .00
ATOM 743 N LEU 39 7 .116 -6 .333 -12 .892 1 .00 0 .00
ATOM 744 HN LEU 39 6 .329 -6 .698 -12 .394 1 .00 0 .00
ATOM 745 CA LEU 39 8 .383 -6 .981 -12 .599 1 .00 0 .00
ATOM 746 HA LEU 39 9 .171 -6 .373 -13 .043 1 .00 0 .00
ATOM 747 CB LEU 39 8 .632 -7 .014 -11 .090 1 .00 0 .00
ATOM 748 2HB LEU 39 8. .291 -6 .070 -10 .665 1 .00 0. .00
ATOM 749 1HB LEU 39 8. .014 -7 .800 -10 .657 1 .00 0. .00
ATOM 750 QB LEU 39 8. .152 -6 .935 -10 .661 1 .00 0. .00
ATOM 751 CG LEU 39 10. .080 -7 .244 -10 .654 1 .00 0, .00
ATOM 752 HG LEU 39 10, .174 -6 .947 -9. .609 1 .00 0, .00
ATOM 753 QD1 LEU 39 10, .537 -9 .078 -10 .756 1 .00 0, .00
ATOM 754 QD2 LEU 39 11 .269 -6 .160 -11 .652 1 .00 0, .00
ATOM 755 CDl LEU 39 10 .449 -8 .726 -10. .737 1 .00 0 .00
ATOM 756 1HD1 LEU 39 10 .967 -9 .023 -9 .825 1 .00 0 .00
ATOM 757 2HD1 LEU 39 9, .542 -9 .320 -10. .850 1 .00 0, .00
ATOM 758 3HD1 LEU 39 11, .101 -8 .891 -11, .595 1 .00 0, .00
ATOM 759 CD2 LEU 39 11, .041 -6 .368 -11 .460 1. .00 0, .00
ATOM 760 1HD2 LEU 39 11, .987 -6 .278 -10, .925 1 .00 0, .00
ATOM 761 2HD2 LEU 39 11, .217 -6 .823 -12, .435 1. .00 0, .00
ATOM 762 3HD2 LEU 39 10, .605 -5 .378 -11 .595 1. .00 0, .00
ATOM 763 QQD LEU 39 10. .903 -7. .619 -11. .204 1. .00 0. ,00
ATOM 764 C LEU 39 8. .408 -8, .363 -13. .256 1, .00 0. .00
ATOM 765 O LEU 39 7. ,787 -9, .301 -12, .760 1, .00 0. .00
ATOM 766 N ASP 40 9. .132 -8, .443 -14. .363 1, .00 0. .00
ATOM 767 HN ASP 40 9. ,634 -7, .675 -14. .760 1, ,00 0, .00
ATOM 768 CA ASP 40 9. .246 -9. .694 -15. .093 1, .00 0. ,00
ATOM 769 HA ASP 40 8. ,495 -10. ,351 -14. .656 1. ,00 0. ,00
ATOM 770 CB ASP 40 8. ,982 -9. ,486 -16. ,586 1. ,00 0. ,00
ATOM 771 2HB ASP 40 8. .284 -8. .657 -16. .704 1. .00 0. ,00
ATOM 772 1HB ASP 40 9. ,914 -9. .189 -17. .067 1. .00 0. ,00
ATOM 773 QB ASP 40 9. ,099 -8. ,923 -16. .886 1. .00 0. ,00
ATOM 774 CG ASP 40 8. ,420 -10. ,706 -17. ,319 1. ,00 0. ,00
ATOM 775 OD1 ASP 40 7. ,204 -10. ,949 -17. ,317 1. ,00 0. 00
ATOM 776 OD2 ASP 40 9. ,300 -11. ,435 -17. ,918 1. ,00 0. 00
ATOM 777 HD2 ASP 40 9. .103 -12. ,404 -17. ,765 1. ,00 0. 00
ATOM 778 C ASP 40 10. .666 -10. ,243 -14. ,937 1. ,00 0. 00
ATOM 779 O ASP 40 11. .609 -9. ,483 -14. ,724 1. ,00 0. .00
ATOM 780 N SER 41 10. ,773 -11. ,559 -15. .048 1. ,00 0. 00
ATOM 781 HN SER 41 10. 000 -12. 170 -15. 221 1. 00 0. 00
ATOM 782 CA SER 41 12. 061 -12. 219 -14. 922 1. 00 0. 00
ATOM 783 HA SER 41 12. 527 -11. .775 -14. 042 1. ,00 0. 00
ATOM 784 CB SER 41 11. 890 -13. .723 -14. 703 1. ,00 0. 00
ATOM 785 2HB SER 41 11. 469 -13. ,901 -13. 714 1. ,00 0. 00
ATOM 786 1HB SER 41 11. 177 -14. .116 -15. 428 1. .00 0. 00
ATOM 787 QB SER 41 11. 323 -14. 009 -14. 571 1. 00 0. 00
ATOM 788 OG SER 41 13. 125 -14. 424 -14. 825 1. 00 0. 00
ATOM 789 HG SER 41 13. 888 -13. 779 -14. 803 1. 00 0. 00
ATOM 790 C SER 41 12. 908 -11. 956 -16. 169 1. 00 0. 00
ATOM 791 O SER 41 12. 381 -11. 889 -17. 278 1. 00 0. 00
ATOM 792 N TYR 42 14. 206 -11. 815 -15. 944 1. 00 0. 00
ATOM 793 HN TYR 42 14. 626 -11. 872 -15. 039 1. 00 0. 00
ATOM 794 CA TYR 42 15. 131 -11. 562 -17. 036 1. 00 0. 00
ATOM 795 HA TYR 42 14. 553 -11. 494 -17. 957 1. 00 0. 00
ATOM 796 CB TYR 42 15. 867 -10. 271 -16. 673 1. 00 0. 00 ATOM 797 2HB TYR 42 15.235 -9.420 -16.927 1.00 0.00
ATOM 798 1HB TYR 42 16 .021 -10 .243 -15 .594 1 .00 0 .00
ATOM 799 QB TYR 42 15 .628 -9 .831 -16 .260 1 .00 o . .00
ATOM 800 QD TYR 42 17 .347 -10 .093 -17 .437 1 .00 0 .00
ATOM 801 QE TYR 42 19 .594 -9 .823 -18 .597 1 .00 0 .00
ATOM 802 QR TYR 42 18 .470 -9 .958 -18 .017 1 .00 0 .00
ATOM 803 CG TYR 42 17 .219 -10 .108 -17 .371 1 .00 0 .00
ATOM 804 CDl TYR 42 17 .409 -10 .627 -18 .636 1 .00 0 .00
ATOM 805 HD1 TYR 42 16 .597 -11 .152 -19 .137 1 .00 0 .00
ATOM 806 CE1 TYR 42 18 .682 -10 .474 -19 .293 1 .00 0 .00
ATOM 807 HEI TYR 42 18 .846 -10 .879 -20 .291 1 .00 0 .00
ATOM 808 CZ TYR 42 19 .674 -9 .813 -18 .639 1 .00 0. .00
ATOM 809 CE2 TYR 42 19 .520 -9 .290 -17 .393 1 .00 0 .00
ATOM 810 HE2 TYR 42 20 .341 -8 .767 -16 .903 1 .00 0 .00
ATOM 811 CD2 TYR 42 18 .248 -9 .443 -16 .736 1 .00 0 .00
ATOM 812 HD2 TYR 42 18 .098 -9 .033 -15 .737 1 .00 0 .00
ATOM 813 OH TYR 42 20 .876 -9 .669 -19 .259 1 .00 0 .00
ATOM 814 HH TYR 42 21 .433 -8 .995 -18 .774 1, .00 0 .00
ATOM 815 C TYR 42 16 .149 -12 .696 -17 .166 1 .00 0 .00
ATOM 816 O TYR 42 17 .016 -12 .859 -16 .308 1 .00 0 .00
ATOM 817 N VAL 43 16 .011 -13 .451 -18. .246 1, .00 0 .00
ATOM 818 HN VAL 43 15, .304 -13, .312 -18. .939 1. .00 0, .00
ATOM 819 CA VAL 43 16, .908 -14, .565 -18. ,500 1. .00 0, .00
ATOM 820 HA VAL 43 17, .341 -14, .864 -17, ,545 1. .00 0, .00
ATOM 821 CB VAL 43 16, .122 -15, .754 -19. .056 1, .00 0, .00
ATOM 822 HB VAL 43 15, .603 -16. .231 -18, .225 1, .00 0, .00
ATOM 823 QG1 VAL 43 14, .818 -15, .181 -20. .304 1, .00 0, .00
ATOM 824 QG2 VAL 43 17, .283 -17 .035 -19, .828 1, .00 0, .00
ATOM 825 CGI VAL 43 15, .068 -15, .291 -20, .064 1, .00 0, .00
ATOM 826 1HG1 VAL 43 14, .202 -14. .900 -19, .531 1, .00 0, .00
ATOM 827 2HG1 VAL 43 15 .489 -14 .509 -20, .696 1, .00 0, .00
ATOM 828 3HG1 VAL 43 14. .763 -16 .134 -20, .684 1, .00 0, .00
ATOM 829 CG2 VAL 43 17. .061 -16, .789 -19. ,680 1. ,00 0. .00
ATOM 830 1HG2 VAL 43 16. .789 -17, .784 -19. ,328 1. .00 0. .00
ATOM 831 2HG2 VAL 43 16, .973 -16, .751 -20. ,766 1. .00 0, .00
ATOM 832 3HG2 VAL 43 18. .088 -16, .569 -19. .391 1. ,00 0, .00
ATOM 833 QQG VAL 43 16. .051 -16, .108 -20. .066 1. ,00 0, .00
ATOM 834 C VAL 43 18. .035 -14, .107 -19. ,429 1. ,00 0. .00
ATOM 835 O VAL 43 17, .798 -13, .354 -20. .373 1. .00 0, ,00
ATOM 836 N PHE 44 19. .235 -14, .579 -19. .128 1. ,00 0, .00
ATOM 837 HN PHE 44 19. .419 -15. .190 -18. .358 1. ,00 0. .00
ATOM 838 CA PHE 44 20, ,399 -14. .226 -19. ,924 1. .00 0, .00
ATOM 839 HA PHE 44 20. ,200 -13. ,254 -20. ,376 1. ,00 0. ,00
ATOM 840 CB PHE 44 21. ,601 -14. ,216 -18. ,978 1. ,00 0. ,00
ATOM 841 2HB PHE 44 21. ,468 -14. ,996 -18. ,229 1. ,00 0. ,00
ATOM 842 1HB PHE 44 22. ,498 -14. ,468 -19. ,545 1. ,00 0. ,00
ATOM 843 QB PHE 44 21. ,983 -14. ,732 -18. ,887 1. ,00 0. .00
ATOM 844 QD PHE 44 21. ,843 -12. ,761 -18. ,205 1. ,00 0. .00
ATOM 845 QE PHE 44 22. ,207 -10. ,568 -17. ,040 1. 00 0. ,00
ATOM 846 QR PHE 44 22. ,025 -11. ,665 -17. .623 1. 00 0. 00
ATOM 847 CG PHE 44 21. ,823 -12. ,879 -18. ,268 1. .00 0. .00
ATOM 848 CDl PHE 44 22. ,701 -11. ,975 -18. .780 1. 00 0. 00
ATOM 849 HD1 PHE 44 23. ,246 -12. ,202 -19. ,696 1. 00 0. .00
ATOM 850 CE1 PHE 44 22. 907 -10. 734 -18. 120 1. 00 0. 00
ATOM 851 HEI PHE 44 23. 610 -10. 009 -18. 530 1. 00 0. 00
ATOM 852 CZ PHE 44 22. 227 -10. ,450 -16. 977 1. 00 0. 00
ATOM 853 HZ PHE 44 22. 385 -9. ,498 -16. 471 1. 00 0. 00
ATOM 854 CE2 PHE 44 21. 349 -11. ,355 -16. 466 1. 00 0. 00
ATOM 855 HE2 PHE 44 20. 804 -11. .127 -15. 550 1. 00 0. 00
ATOM 856 CD2 PHE 44 21. 143 -12. 595 -17. 125 1. 00 0. 00
ATOM 857 HD2 PHE 44 20. 440 -13. 320 -16. 715 1. 00 0. 00
ATOM 858 C PHE 44 20. 641 -15. 258 -21. 027 1. 00 0. 00 ATOM 859 O PHE 44 19.808 -16.134 -21.257 1.00 0.00
ATOM 860 N ASN 45 21 .786 -15 .121 -21 .680 1 .00 0 .00
ATOM 861 HN ASN 45 22 .458 -14 .406 -21 .487 1 .00 0 .00
ATOM 862 CA ASN 45 22 .149 -16 .031 -22 .754 1 .00 0 .00
ATOM 863 HA ASN 45 21 .233 -16 .178 -23 .326 1 .00 0 .00
ATOM 864 CB ASN 45 23 .247 -15 .432 -23 .636 1 .00 0 .00
ATOM 865 2HB ASN 45 24 .077 -15 .100 -23 .013 1 .00 0 .00
ATOM 866 1HB ASN 45 23 .637 -16 .198 -24 .306 1 .00 0 .00
ATOM 867 QB ASN 45 23 .857 -15 .649 -23 .659 1 .00 0 .00
ATOM 868 CG ASN 45 22 .712 -14 .255 -24 .454 1 .00 0 .00
ATOM 869 OD1 ASN 45 22 .324 -14 .389 -25 .603 1 .00 0 .00
ATOM 870 ND2 ASN 45 22 .713 -13 .097 -23 .800 1 .00 0 .00
ATOM 871 1HD2 ASN 45 23 .045 -13 .055 -22 .857 1 .00 0 .00
ATOM 872 2HD2 ASN 45 22 .382 -12 .268 -24 .251 1 .00 0 .00
ATOM 873 QD2 ASN 45 22 .714 -12, .662 -23 .554 1 .00 0 .00
ATOM 874 C ASN 45 22 .681 -17 .334 -22 .155 1 .00 0 .00
ATOM 875 O ASN 45 22 .863 -18 .320 -22 .867 1 .00 0 .00
ATOM 876 N ASP 46 22, .917 -17 .295 -20 .851 1 .00 0 .00
ATOM 877 HN ASP 46 22 .767 -16 .489 -20 .279 1 .00 0 .00
ATOM 878 CA ASP 46 23 .425 -18 .461 -20 .148 1 .00 0 .00
ATOM 879 HA ASP 46 24 .095 -18. .951 -20 .854 1 .00 0. .00
ATOM 880 CB ASP 46 24, .178 -18, .054 -18 .880 1 .00 0, .00
ATOM 881 2HB ASP 46 23, .571 -17, .334 -18 .330 1 .00 0. .00
ATOM 882 1HB ASP 46 24. .286 -18, .932 -18 .242 1 .00 0, .00
ATOM 883 QB ASP 46 23, .928 -18, .133 -18, .286 1 .00 0, .00
ATOM 884 CG ASP 46 25. .562 -17. .448 -19, .116 1. .00 0, .00
ATOM 885 OD1 ASP 46 26, .567 -18. .168 -19, .209 1 .00 0, .00
ATOM 886 OD2 ASP 46 25, .586 -16, .161 -19, .205 1 .00 0, .00
ATOM 887 HD2 ASP 46 26. .076 -15. ,884 -20, .032 1, .00 0. .00
ATOM 888 C ASP 46 22. ,253 -19. .354 -19. .737 1, .00 0. .00
ATOM 889 O ASP 46 22. .456 -20. .443 -19. .201 1, .00 0. .00
ATOM 890 N GLY 47 21. .052 -18. .860 -20, .002 1. .00 0. .00
ATOM 891 HN GLY 47 20. .896 -17. ,974 -20. .438 1, .00 0. ,00
ATOM 892 CA GLY 47 19. ,848 -19. ,600 -19. .666 1. .00 0. ,00
ATOM 893 2HA GLY 47 19. .085 -19. ,425 -20. .425 1. .00 0. .00
ATOM 894 1HA GLY 47 20. ,061 -20. ,669 -19. .669 1. .00 0. ,00
ATOM 895 QA GLY 47 19. .573 -20. ,047 -20. ,047 1. .00 0. ,00
ATOM 896 C GLY 47 19. .314 -19. ,184 -18. ,294 1. .00 0. ,00
ATOM 897 O GLY 47 18. .117 -19. .289 -18. .032 1, .00 0. .00
ATOM 898 N SER 48 20. ,229 -18. ,722 -17. .454 1. .00 0. ,00
ATOM 899 HN SER 48 21. .201 -18. ,640 -17. .675 1. .00 0. ,00
ATOM 900 CA SER 48 19. .865 -18. .290 -16. .115 1, .00 0. ,00
ATOM 901 HA SER 48 19. .616 -19. 204 -15. ,575 1. ,00 0. ,00
ATOM 902 CB SER 48 21. ,039 -17. .594 -15. ,423 1. .00 0. ,00
ATOM 903 2HB SER 48 20. ,679 -17. .074 -14. .535 1. .00 0. ,00
ATOM 904 1HB SER 48 21. ,756 -18. .342 -15. .085 1, .00 0. ,00
ATOM 905 QB SER 48 21. 218 -17. 708 -14. ,810 1. ,00 0. 00
ATOM 906 OG SER 48 21. 692 -16. 666 -16. ,285 1. ,00 0. 00
ATOM 907 HG SER 48 22. 665 -16. 884 -16. ,348 1. .00 0. 00
ATOM 908 C SER 48 18. 655 -17. 356 -16. 177 1. ,00 0. 00
ATOM 909 O SER 48 18. 363 -16. 781 -17. 225 1. .00 0. 00
ATOM 910 N SER 49 17. 984 -17. 233 -15. ,041 1. .00 0. 00
ATOM 911 HN SER 49 18. 228 -17. 704 -14. .194 1. .00 0. 00
ATOM 912 CA SER 49 16. 812 -16. 378 -14. 953 1. 00 0. 00
ATOM 913 HA SER 49 16. 769 -15. 850 -15. 906 1. 00 0. 00
ATOM 914 CB SER 49 15. 539 -17. 206 -14. 771 1. 00 0. 00
ATOM 915 2HB SER 49 14. 668 -16. 580 -14. 968 1. 00 0. 00
ATOM 916 1HB SER 49 15. 523 -18. 013 -15. 504 1. 00 0. 00
ATOM 917 QB SER 49 15. 096 -17. 296 -15. 236 1. 00 0. 00
ATOM 918 OG SER 49 15. 441 -17. 754 -13. 460 1. 00 0. 00
ATOM 919 HG SER 49 15. 497 -18. 752 -13. 501 1. 00 0. 00
ATOM 920 C SER 49 16. 972 -15. 389 -13. 797 1. 00 0. 00 ATOM 921 O SER 49 17.112 -15.793 -12.644 1.00 0.00
ATOM 922 N ARG 50 16 .946 -14 .111 -14 .146 1 .00 0 .00
ATOM 923 HN ARG 50 16 .832 -13 .790 -15 .086 1 .00 0 .00
ATOM 924 CA ARG 50 17 .086 -13 .060 -13 .152 1 .00 0 .00
ATOM 925 HA ARG 50 17 .326 -13 .583 -12 .226 1 .00 0 .00
ATOM 926 CB ARG 50 18 .214 -12 .096 -13 .524 1 .00 0 .00
ATOM 927 2HB ARG 50 18 .927 -12 .600 -14 .178 1 .00 0 .00
ATOM 928 1HB ARG 50 17 .808 -11 .254 -14 .084 1 .00 0 .00
ATOM 929 QB ARG 50 18 .367 -11 .927 -14 .131 1 .00 0 .00
ATOM 930 CG ARG 50 18 .934 -11 .585 -12 .274 1 .00 0 .00
ATOM 931 2HG ARG 50 18 .297 -11 .726 -11 .401 1 .00 0 .00
ATOM 932 1HG ARG 50 19 .839 -12 .168 -12 .107 1 .00 0 .00
ATOM 933 QG ARG 50 19 .068 -11 .947 -11 .754 1 .00 0 .00
ATOM 934 CD ARG 50 19 .293 -10 .104 -12 .416 1 .00 0 .00
ATOM 935 2HD ARG 50 20 .376 -9 .981 -12 .401 1 .00 o . .00
ATOM 936 1HD ARG 50 18 .943 -9 .727 -13 .376 1 .00 0. .00
ATOM 937 QD ARG 50 19 .659 -9 .854 -12 .889 1 .00 0 .00
ATOM 938 NE ARG 50 18. .681 -9. .328 -11. .315 1 .00 0 .00
ATOM 939 HE ARG 50 17, .862 -8, .792 -11 .518 1 .00 0 .00
ATOM 940 CZ ARG 50 19 .161 -9 .297 -10 .053 1 .00 0 .00
ATOM 941 NH1 ARG 50 18 .534 -8 .569 -9 .148 1 .00 0 .00
ATOM 942 HHl ARG 50 18, .823 -8, .492 -8, .194 1, .00 0, .00
ATOM 943 NH2 ARG 50 20, .264 -10, .001 -9 .722 1 .00 0 .00
ATOM 944 1HH2 ARG 50 20 .612 -9 .973 -8 .785 1 .00 0 .00
ATOM 945 2HH2 ARG 50 20. .733 -10, .551 -10 .413 1 .00 0 .00
ATOM 946 QH2 ARG 50 20, .673 -10, .262 -9 .599 1 .00 0 .00
ATOM 947 C ARG 50 15, .779 -12, .277 -13 .019 1 .00 0 .00
ATOM 948 O ARG 50 14, .698 -12, .825 -13 .234 1. .00 0 .00
ATOM 949 N GLU 51 15, .919 -11. .008 -12, .665 1 .00 0, .00
ATOM 950 HN GLU 51 16, .802 -10. .570 -12, .493 1 .00 0 .00
ATOM 951 CA GLU 51 14, .762 -10, .145 -12, .501 1 .00 0 .00
ATOM 952 HA GLU 51 13, .957 -10, .631 -13, .052 1, .00 0 .00
ATOM 953 CB GLU 51 14. ,366 -10. .034 -11. .028 1, .00 0, .00
ATOM 954 2HB GLU 51 13. .516 -9. ,359 -10. .926 1, .00 0, .00
ATOM 955 1HB GLU 51 14. .045 -11. ,008 -10, .659 1, .00 0, .00
ATOM 956 QB GLU 51 13. ,780 -10. ,183 -10. ,793 1. .00 0. .00
ATOM 957 CG GLU 51 15. .534 -9. .522 -10. .182 1. .00 0. .00
ATOM 958 2HG GLU 51 16. .413 -10. .142 -10. .358 1. .00 0. .00
ATOM 959 1HG GLU 51 15. .792 -8. ,509 -10. ,488 1. .00 0. .00
ATOM 960 QG GLU 51 16. ,103 -9. ,326 -10. ,423 1. .00 0. .00
ATOM 961 CD GLU 51 15. ,181 -9. ,538 -8. .693 1. .00 0. ,00
ATOM 962 OEl GLU 51 14. ,244 -8. ,844 -8. ,271 1. .00 0. ,00
ATOM 963 OE2 GLU 51 15. 920 -10. 306 -7. .966 1. ,00 0. .00
ATOM 964 HE2 GLU 51 16. .863 -10. 285 -8. .296 1. ,00 0. ,00
ATOM 965 C GLU 51 15. ,042 -8. ,764 -13. ,099 1. ,00 0. ,00
ATOM 966 O GLU 51 16. ,127 -8. ,214 -12. ,920 1. .00 0. ,00
ATOM 967 N LEU 52 14. 043 -8. 244 -13. ,797 1. ,00 0. ,00
ATOM 968 HN LEU 52 13. .163 -8. 698 -13. ,938 1. ,00 0. ,00
ATOM 969 CA LEU 52 14. ,167 -6. ,938 -14. ,423 1. ,00 0. ,00
ATOM 970 HA LEU 52 14. 890 -6. 366 -13. .842 1. ,00 0. ,00
ATOM 971 CB LEU 52 14. 730 -7. 074 -15. .839 1. ,00 0. 00
ATOM 972 2HB LEU 52 15. 552 -7. 790 -15. .815 1. ,00 0. .00
ATOM 973 1HB LEU 52 13. 955 -7. 500 -16. ,477 1. ,00 0. ,00
ATOM 974 QB LEU 52 14. 754 -7. 645 -16. 146 1. 00 0. 00
ATOM 975 CG LEU 52 15. 233 -5. 783 -16. 488 1. 00 0. 00
ATOM 976 HG LEU 52 15. 613 -6. 025 -17. 480 1. ,00 0. 00
ATOM 977 QD1 LEU 52 13. 820 -4. 544 -16. 717 1. 00 0. 00
ATOM 978 QD2 LEU 52 16. 671 -5. 045 -15. 502 1. 00 0. 00
ATOM 979 CDl LEU 52 14. 091 -4. 782 -16. 673 1. 00 0. 00
ATOM 980 1HD1 LEU 52 13. 139 -5. 311 -16. 664 1. 00 0. 00
ATOM 981 2HD1 LEU 52 14. 110 -4. 054 -15. 861 1. 00 0. 00
ATOM 982 3HD1 LEU 52 14. 212 -4. 266 -17. 626 1. 00 0. 00 ATOM 983 CD2 LEU 52 16.395 -5.186 -15.691 1.00 0.00
ATOM 984 1HD2 LEU 52 16 .597 -5 .810 -14 .821 1 .00 0 .00
ATOM 985 2HD2 LEU 52 17 .283 -5 .144 -16 .322 1 .00 0 .00
ATOM 986 3HD2 LEU 52 16 .133 -4 .180 -15 .364 1 .00 0 .00
ATOM 987 QQD LEU 52 15 .246 -4 .794 -16 .110 1 .00 0 .00
ATOM 988 C LEU 52 12 .818 -6 .219 -14 .363 1 .00 0 .00
ATOM 989 O LEU 52 11 .773 -6 .833 -14 .572 1 .00 0 .00
ATOM 990 N MET 53 12 .885 -4 .927 -14 .077 1 .00 0 .00
ATOM 991 HN MET 53 13 .739 -4 .435 -13 .909 1 .00 0 .00
ATOM 992 CA MET 53 11 .682 -4 .117 -13 .988 1 .00 0 .00
ATOM 993 HA MET 53 10 .879 -4 .812 -13 .746 1 .00 0 .00
ATOM 994 CB MET 53 11 .856 -3 .063 -12 .892 1 .00 0 .00
ATOM 995 2HB MET 53 12 .183 -3. .544 -11 .969 1 .00 0 .00
ATOM 996 1HB MET 53 12 .638 -2 .360 -13 .179 1 .00 0 .00
ATOM 997 QB MET 53 12 .410 -2 .952 -12 .574 1 .00 0 .00
ATOM 998 CG MET 53 10 .549 -2 .308 -12 .645 1 .00 0 .00
ATOM 999 2HG MET 53 9. .963 -2 .269 -13 .563 1 .00 0 .00
ATOM 1000 1HG MET 53 9 .948 -2 .837 -11 .905 1 .00 0. .00
ATOM 1001 QG MET 53 9 .955 -2. .553 -12. .734 1 .00 0 .00
ATOM 1002 SD MET 53 10 .898 -0 .653 -12 .074 1 .00 0 .00
ATOM 1003 QE MET 53 9 .077 -0, .232 -11. .015 1 .00 0, .00
ATOM 1004 CE MET 53 9 .385 -0, .303 -11 .194 1 .00 0, .00
ATOM 1005 IHE MET 53 9, .621 0, .137 -10 .226 1 .00 0, .00
ATOM 1006 2HE MET 53 8, .781 0, .396 -11, ,773 1, .00 0, .00
ATOM 1007 3HE MET 53 8, .828 -1, .228 -11. .047 1, .00 0. .00
ATOM 1008 C MET 53 11. .387 -3, .424 -15. .320 1, .00 0, .00
ATOM 1009 O MET 53 12, .266 -2, .790 -15, .902 1, .00 0, .00
ATOM 1010 N ASN 54 10, .147 -3. .569 -15, .763 1. .00 0. ,00
ATOM 1011 HN ASN 54 9, .438 -4. ,086 -15, .283 1, .00 0. .00
ATOM 1012 CA ASN 54 9, .725 -2. .965 -17. .016 1, .00 0. .00
ATOM 1013 HA ASN 54 10, .551 -2. .319 -17, .315 1, .00 0. .00
ATOM 1014 CB ASN 54 9, .459 -4. .032 -18, .079 1, .00 0. ,00
ATOM 1015 2HB ASN 54 8, .624 -3. ,723 -18, .708 1, .00 0. ,00
ATOM 1016 1HB ASN 54 10, .328 -4. .128 -18, .729 1, .00 0. .00
ATOM 1017 QB ASN 54 9, .476 -3. .925 -18, .719 1, .00 0. .00
ATOM 1018 CG ASN 54 9. .145 -5. .383 -17, .434 1, .00 0, .00
ATOM 1019 OD1 ASN 54 9, .936 -5. ,945 -16. .694 1, .00 0, ,00
ATOM 1020 ND2 ASN 54 7, .951 -5. .872 -17, .754 1, .00 0, .00
ATOM 1021 1HD2 ASN 54 7, .349 -5. .360 -18. .368 1, .00 0, .00
ATOM 1022 2HD2 ASN 54 7. .654 -6. ,751 -17. .382 1. .00 0, ,00
ATOM 1023 QD2 ASN 54 7. .501 -6, ,055 -17. ,875 1. ,00 0. ,00
ATOM 1024 C ASN 54 8. .427 -2. .187 -16. .790 1. ,00 0. ,00
ATOM 1025 O ASN 54 7. .932 -2. .111 -15. .667 1. .00 0, ,00
ATOM 1026 N LEU 55 7. ,912 -1. ,630 -17. ,876 1. ,00 0. 00
ATOM 1027 HN LEU 55 8. ,321 -1. ,696 -18. ,786 1. .00 0. 00
ATOM 1028 CA LEU 55 6. ,681 -0. ,861 -17. ,811 1. .00 0. 00
ATOM 1029 HA LEU 55 6. .183 -1. ,120 -16. ,877 1. ,00 0. 00
ATOM 1030 CB LEU 55 6. ,986 0. 637 -17. 760 1. ,00 0. 00
ATOM 1031 2HB LEU 55 7. ,660 0. 879 -18. 583 1. ,00 0. 00
ATOM 1032 1HB LEU 55 6. ,060 1. 183 -17. .937 1. .00 0. 00
ATOM 1033 QB LEU 55 6. 860 1. 031 -18. 260 1. 00 0. 00
ATOM 1034 CG LEU 55 7. 609 1. 151 -16. 460 1. 00 0. 00
ATOM 1035 HG LEU 55 7. 547 0. 358 -15. 715 1. 00 0. 00
ATOM 1036 QD1 LEU 55 9. ,444 1. 551 -16. 699 1. 00 0. 00
ATOM 1037 QD2 LEU 55 6. 642 2. 632 -15. 784 1. 00 0. 00
ATOM 1038 CDl LEU 55 9. 092 1. 474 -16. 653 1. 00 0. 00
ATOM 1039 1HD1 LEU 55 9. ,665 1. 062 -15. 822 1. 00 0. 00
ATOM 1040 2HD1 LEU 55 9. .441 1. 036 -17. 588 1. 00 0. 00
ATOM 1041 3HD1 LEU 55 9. 227 2. 556 -16. 686 1. 00 0. 00
ATOM 1042 CD2 LEU 55 6. 828 2. 348 -15. 914 1. 00 0. 00
ATOM 1043 1HD2 LEU 55 7. 322 3. 272 -16. 214 1. 00 0. 00
ATOM 1044 2HD2 LEU 55 5. 814 2. 332 -16. 313 1. 00 0. 00 ATOM 1045 3HD2 LEU 55 6.791 2.292 -14.826 1.00 0.00
ATOM 1046 QQD LEU 55 8 .043 2 .091 -16 .241 1 .00 0 .00
ATOM 1047 C LEU 55 5 .771 -1 .264 -18 .973 1 .00 0 .00
ATOM 1048 O LEU 55 6 .012 -0 .880 -20 .117 1 .00 0 .00
ATOM 1049 N THR 56 4 .744 -2 .032 -18 .640 1 .00 0 .00
ATOM 1050 HN THR 56 4 .555 -2 .340 -17 .708 1 .00 0 .00
ATOM 1051 CA THR 56 3 .797 -2 .491 -19 .642 1 .00 0 .00
ATOM 1052 HA THR 56 4 .154 -2 .177 -20 .622 1 .00 0 .00
ATOM 1053 CB THR 56 3 .749 -4 .019 -19 .582 1 .00 0 .00
ATOM 1054 HB THR 56 3 .642 -4 .365 -18 .554 1 .00 0 .00
ATOM 1055 QG2 THR 56 2 .391 -4 .745 -20 .684 1 .00 0 .00
ATOM 1056 OGl THR 56 4 .961 -4 .430 -20 .208 1 .00 0 .00
ATOM 1057 HG1 THR 56 5 .352 -5 .209 -19 .719 1 .00 0 .00
ATOM 1058 CG2 THR 56 2 .651 -4 .606 -20 .472 1 .00 0 .00
ATOM 1059 1HG2 THR 56 2 .576 -4 .021 -21 .389 1 .00 0 .00
ATOM 1060 2HG2 THR 56 2 .898 -5 .639 -20 .720 1 .00 0 .00
ATOM 1061 3HG2 THR 56 1 .699 -4 .576 -19 .943 1 .00 0 .00
ATOM 1062 C THR 56 2 .433 -1 .831 -19 .428 1 .00 0, .00
ATOM 1063 O THR 56 1 .636 -2 .295 -18 .614 1 .00 0 .00
ATOM 1064 N GLY 57 2 .207 -0 .760 -20 .174 1 .00 0. .00
ATOM 1065 HN GLY 57 2 .861 -0 .390 -20 .834 1 .00 0 .00
ATOM 1066 CA GLY 57 0 .953 -0 .032 -20 .077 1 .00 0, .00
ATOM 1067 2HA GLY 57 0 .177 -0 .688 -19 .683 1 .00 0. .00
ATOM 1068 1HA GLY 57 1 .062 0 .793 -19 .372 1 .00 0 .00
ATOM 1069 QA GLY 57 0. .619 0. .053 -19, .528 1 .00 0, .00
ATOM 1070 C GLY 57 0. .526 0 .510 -21, .443 1 .00 0. .00
ATOM 1071 O GLY 57 0, .720 -0 .149 -22, .463 1. .00 0, .00
ATOM 1072 N THR 58 ■0 .047 1 .704 -21, .417 1 .00 0. .00
ATOM 1073 HN THR 58 -0. .202 2, .232 -20. .583 1, .00 0. .00
ATOM 1074 CA THR 58 •0, .504 2. .341 -22, .641 1, .00 0. .00
ATOM 1075 HA THR 58 0, .037 1, .901 -23. .479 1, .00 0, .00
ATOM 1076 CB THR 58 ■2, .000 2. .057 -22. .792 1, .00 0. ,00
ATOM 1077 HB THR 58 ■2. .402 2. .553 -23. .675 1, .00 0. ,00
ATOM 1078 QG2 THR 58 ■2. ,387 0. .204 -22. ,821 1, .00 0. .00
ATOM 1079 OGl THR 58 •2. .565 2. .511 -21. .565 1, .00 0. ,00
ATOM 1080 HG1 THR 58 ■2. ,479 3. ,505 -21. ,496 1. .00 0. ,00
ATOM 1081 CG2 THR 58 •2. ,312 0. ,560 -22. ,815 1. ,00 0. ,00
ATOM 1082 1HG2 THR 58 ■1. ,998 0. .108 -21. ,875 1. ,00 0. ,00
ATOM 1083 2HG2 THR 58 ■3. .385 0. .415 -22. ,947 1. .00 0. ,00
ATOM 1084 3HG2 THR 58 •1. ,778 0. ,090 -23. ,641 1. ,00 0. 00
ATOM 1085 C THR 58 ■0. .167 3. .833 -22. ,623 1. .00 0. ,00
ATOM 1086 O THR 58 •0. .064 4. ,437 -21. .556 1. .00 0. ,00
ATOM 1087 N ILE 59 0. ,004 4. ,385 -23. 816 1. ,00 0. 00
ATOM 1088 HN ILE 59 ■0. ,089 3. ,887 -24. .679 1. ,00 0. 00
ATOM 1089 CA ILE 59 0. ,319 5. ,795 -23. .951 1. ,00 0. 00
ATOM 1090 HA ILE 59 0, .417 6. ,205 -22. .946 1. .00 0. 00
ATOM 1091 CB ILE 59 1. .671 5. ,971 -24. 645 1. ,00 0. 00
ATOM 1092 HB ILE 59 1. .698 5. ,311 -25. 512 1. ,00 0. 00
ATOM 1093 QG2 ILE 59 1. .882 7. ,741 -25. 283 1. ,00 0. 00
ATOM 1094 CG2 ILE 59 1. 841 7. 401 -25. 160 1. 00 0. 00
ATOM 1095 1HG2 ILE 59 2. 810 7. 788 -24. 845 1. 00 0. 00
ATOM 1096 2HG2 ILE 59 1. 786 7. 405 -26. 249 1. 00 0. 00
ATOM 1097 3HG2 ILE 59 1. 049 8. 030 -24. 754 1. 00 0. 00
ATOM 1098 CGI ILE 59 2. 819 5. 553 -23. 724 1. 00 0. 00
ATOM 1099 2HG1 ILE 59 2. 672 4. 524 -23. 398 1. 00 0. 00
ATOM 1100 1HG1 ILE 59 3. 760 5. 583 -24. 273 1. 00 0. 00
ATOM 1101 QG1 ILE 59 3. 216 5. 053 -23. 835 1. 00 0. 00
ATOM 1102 QD1 ILE 59 2. 926 6. 691 -22. 214 1. 00 0. 00
ATOM 1103 CDl ILE 59 2. 905 6. 473 -22. 504 1. 00 0. 00
ATOM 1104 1HD1 ILE 59 2. 509 7. 455 -22. 760 1. 00 0. 00
ATOM 1105 2HD1 ILE 59 2. 322 6. 048 -21. 687 1. 00 0. 00
ATOM 1106 3HD1 ILE 59 3. 946 6. 570 -22. 195 1. 00 0. 00 ATOM 1107 C ILE 59 0.833 6.513 -24.658 1.00 0.00
ATOM 1108 O ILE 59 -1 .302 6 .062 -25 .702 1 .00 0 .00
ATOM 1109 N PRO 60 -1 .266 7 .646 -24 .044 1 .00 0 .00
ATOM 1110 CD PRO 60 0 .734 8 .210 -22 .807 1 .00 0 .00
ATOM Mil CA PRO 60 2 .354 8 .431 -24 .603 1 .00 0 .00
ATOM 1112 HA PRO 60 3 .082 7 .829 -24 .933 1 .00 0 .00
ATOM 1113 CB PRO 60 2 .829 9 .315 -23 .462 1 .00 0 .00
ATOM 1114 2HB PRO 60 3 .051 10 .322 -23 .814 1 .00 0 .00
ATOM 1115 1HB PRO 60 3 .744 8 .923 -23 .019 1 .00 0 .00
ATOM 1116 QB PRO 60 3 .397 9 .623 -23 .417 1 .00 0 .00
ATOM 1117 CG PRO 60 1 .696 9 .330 -22 .448 1 .00 0 .00
ATOM 1118 2HG PRO 60 1 .184 10 .292 -22 .462 1 .00 0 .00
ATOM 1119 1HG PRO 60 2 .085 9 .191 -21 .439 1 .00 0 .00
ATOM 1120 QG PRO 60 1 .635 9 .742 -21 .950 1 .00 0 .00
ATOM 1121 2HD PRO 60 0 279 8 587 -22 .947 1 .00 0 .00
ATOM 1122 1HD PRO 60 0 688 7 .459 -22 .018 1 .00 0 .00
ATOM 1123 QD PRO 60 0 204 8 .023 -22 .483 1 .00 0 .00
ATOM 1124 C PRO 60 1 885 9 228 -25 822 1 00 0 00
ATOM 1125 O PRO 60 1 183 10 228 -25 682 1 00 0 00
ATOM 1126 N VAL 61 2 293 8 755 -26 991 1 00 0 00
ATOM 1127 HN VAL 61 2 864 7 941 -27 097 1 00 0 00
ATOM 1128 CA VAL 61 1 923 9 411 -28 234 1 00 0 00
ATOM 1129 HA VAL 61 1 181 10 173 -27 995 1 00 0 00
ATOM 1130 CB VAL 61 1 278 8 403 -29 186 1 00 0 00
ATOM 1131 HB VAL 61 2 003 7 613 -29 379 1 00 0 00
ATOM 1132 QG1 VAL 61 0 846 9 214 -30 842 1 00 0 00
ATOM 1133 QG2 VAL 61 0 251 7 609 -28 400 1 00 0 00
ATOM 1134 CGI VAL 61 0 928 9 058 -30 524 1 00 0 00
ATOM 1135 1HG1 VAL 61 1 668 9 825 -30 757 1 00 0 00
ATOM 1136 2HG1 VAL 61 0 059 9 514 -30 458 1 00 0 00
ATOM 1137 3HG1 VAL 61 0 929 8 303 -31 310 1 00 0 00
ATOM 1138 CG2 VAL 61 0 042 7 761 -28 551 1 00 0 00
ATOM 1139 1HG2 VAL 61 0 768 8 490 -28 516 1 00 0 00
ATOM 1140 2HG2 VAL 61 0 282 7 437 -27 538 1 00 0 00
ATOM 1141 3HG2 VAL 61 0 267 6 901 -29 145 1 00 0 00
ATOM 1142 QQG VAL 61 0 297 8 411 -29 621 1 00 0 00
ATOM 1143 C VAL 61 3 155 10 094 -28 831 1 00 0 00
ATOM 1144 O VAL 61 3 994 9 439 -29 448 1 00 0 00
ATOM 1145 N PRO 62 3 228 11 435 -28 621 1 00 0 00
ATOM 1146 CD PRO 62 2 253 12 244 -27 895 1 00 0 00
ATOM 1147 CA PRO 62 4 343 12 214 -29 132 1 00 0 00
ATOM 1148 HA PRO 62 5 203 11 722 -28 992 1 00 0 00
ATOM 1149 CB PRO 62 4 306 13 516 -28 348 1 00 0 00
ATOM 1150 2HB PRO 62 4 517 14 367 -28 996 1 00 0 00
ATOM 1151 1HB PRO 62 5 060 13 519 -27 561 1 00 0 00
ATOM 1152 QB PRO 62 4 788 13 943 -28 278 1 00 0 00
ATOM 1153 CG PRO 62 2 906 13 610 -27 763 1 00 0. 00
ATOM 1154 2HG PRO 62 2 323 14 365 -28 290 1 00 0. 00
ATOM 1155 1HG PRO 62 2 949 13 913 -26 717 1 00 0 00
ATOM 1156 QG PRO 62 2 636 14 139 -27 504 1 00 0 00
ATOM 1157 2HD PRO 62 1 309 12 307 -28 437 1 00 0. 00
ATOM 1158 1HD PRO 62 2 032 11 815 -26 918 1 00 0. 00
ATOM 1159 QD PRO 62 1 670 12 061 -27 677 1 00 0 00
ATOM 1160 C PRO 62 4 221 12 421 -30 643 1 00 0. 00
ATOM 1161 O PRO 62 3 150 12 766 -31 141 1 00 0. 00
ATOM 1162 N TYR 63 5 333 12 203 -31 330 1 00 0. 00
ATOM 1163 HN TYR 63 6 199 11 923 -30 917 1 00 0. 00
ATOM 1164 CA TYR 63 5. 363 12. 362 -32. 774 1. 00 0. 00
ATOM 1165 HA TYR 63 4. 334 12. 406 -33 129 1. 00 0. 00
ATOM 1166 CB TYR 63 6 153 11 168 -33 313 1 00 0. 00
ATOM 1167 2HB TYR 63 6 533 10 588 -32 472 1 00 0. 00
ATOM 1168 1HB TYR 63 7. 018 11. 536 -33. 864 1. 00 0. 00 ATOM 1169 QB TYR 63 -6.776 11.062 -33.168 1.00 0.00
ATOM 1170 QD TYR 63 -5 .264 10 .158 -34 .311 1 .00 0 .00
ATOM 1171 QE TYR 63 -3 .914 8 .625 -35 .825 1 .00 0 .00
ATOM 1172 QR TYR 63 -4 .589 9 .392 -35 .068 1 .00 0 .00
ATOM 1173 CG TYR 63 -5 .341 10 .245 -34 .224 1 .00 0 .00
ATOM 1174 CDl TYR 63 -5 .244 8 .899 -33 .935 1 .00 0 .00
ATOM 1175 HD1 TYR 63 -5 .746 8 .494 -33 .056 1 .00 0 .00
ATOM 1176 CE1 TYR 63 -4 .480 8 .031 -34 .792 1 .00 0 .00
ATOM 1177 HEI TYR 63 -4 .395 6 .967 -34 .575 1 .00 0 .00
ATOM 1178 CZ TYR 63 -3 .866 8 .570 -35 .880 1 .00 0 00
ATOM 1179 CE2 TYR 63 -3 .941 9 .891 -36 .194 1 .00 0 .00
ATOM 1180 HE2 TYR 63 -3 .433 10 .284 -37 .075 1 .00 0 .00
ATOM 1181 CD2 TYR 63 -4 .705 10 .759 -35 .336 1 .00 0 .00
ATOM 1182 HD2 TYR 63 -4 781 11 .822 -35 565 1 .00 0 00
ATOM 1183 OH TYR 63 -3 144 7 .750 -36 .690 1 .00 0 00
ATOM 1184 HH TYR 63 -2 690 8 .286 -37 .402 1 .00 0 00
ATOM 1185 C TYR 63 -6 .083 13 .654 -33 .168 1 .00 0 00
ATOM 1186 O TYR 63 -5 .451 14 .608 -33 .618 1 .00 0 .00
ATOM 1187 N ARG 64 -7 395 13 642 -32 985 1 00 0 00
ATOM 1188 HN ARG 64 -7 902 12 861 -32 619 1 00 0 00
ATOM 1189 CA ARG 64 -8 207 14 800 -33 316 1 .00 0 00
ATOM 1190 HA ARG 64 -7 521 15 .492 -33 805 1 .00 0 00
ATOM 1191 CB ARG 64 -9 345 14 422 -34 267 1 00 0 00
ATOM 1192 2HB ARG 64 10 260 14 934 -33 967 1 00 0 00
ATOM 1193 1HB ARG 64 -9 108 14 758 -35 276 1 00 0 00
ATOM 1194 QB ARG 64 -9 684 14 846 -34 622 1 00 0 00
ATOM 1195 CG ARG 64 -9 578 12 909 -34 268 1 00 0 00
ATOM 1196 2HG ARG 64 -8 678 12 400 -34 612 1 00 0 00
ATOM 1197 1HG ARG 64 -9 770 12 566 -33 252 1 00 0 00
ATOM 1198 QG ARG 64 -9 224 12 483 -33 932 1 00 0 00
ATOM 1199 CD ARG 64 10 757 12 537 -35 169 1 00 0 00
ATOM 1200 2HD ARG 64 10 646 13 014 -36 143 1 00 0 00
ATOM 1201 1HD ARG 64 10 770 11 461 -35 340 1 00 0 00
ATOM 1202 QD ARG 64 10 708 12 237 -35 742 1 00 0 00
ATOM 1203 NE ARG 64 12 028 12 963 -34 541 1 00 0 00
ATOM 1204 HE ARG 64 12 003 13 257 -33 586 1 00 0 00
ATOM 1205 CZ ARG 64 13 218 12 980 -35 178 1 00 0 00
ATOM 1206 NH1 ARG 64 14 291 13 380 -34 519 1 00 0 00
ATOM 1207 HH1 ARG 64 15 207 13 422 -34 916 1 00 0 00
ATOM 1208 NH2 ARG 64 13 311 12 594 -36 468 1 00 0 00
ATOM 1209 1HH2 ARG 64 14 197 12 610 -36 932 1 00 0 00
ATOM 1210 2HH2 ARG 64 12 494 12 293 -36 960 1 00 0 00
ATOM 1211 QH2 ARG 64 13 345 12 451 -36 946 1 00 0 00
ATOM 1212 C ARG 64 -8 797 15 415 -32 046 1 00 0 00
ATOM 1213 O ARG 64 -8 344 16 465 -31 592 1 00 0 00
ATOM 1214 N GLY 65 -9 799 14 736 -31 507 1 00 0 00
ATOM 1215 HN GLY 65 10 162 13 883 -31 882 1 00 0 00
ATOM 1216 CA GLY 65 10 455 15 203 -30 298 1 00 0 00
ATOM 1217 2HA GLY 65 10 026 16 157 -29 992 1 00 0. 00
ATOM 1218 1HA GLY 65 11 512 15 378 -30. 498 1 00 0. 00
ATOM 1219 QA GLY 65 10 769 15 767 -30 245 1 00 0. 00
ATOM 1220 C GLY 65 10 307 14 184 -29 166 1 00 0. 00
ATOM 1221 O GLY 65 10. 180 14. 559 -28. 001 1. 00 0. 00
ATOM 1222 N ASN 66 10. 329 12. 916 -29. 547 1. 00 0. 00
ATOM 1223 HN ASN 66 10 432 12 619 -30. 497 1. 00 0. 00
ATOM 1224 CA ASN 66 10 198 11 840 -28. 579 1. 00 0. 00
ATOM 1225 HA ASN 66 10 510 12 272 -27. 628 1 00 0. 00
ATOM 1226 CB ASN 66 11. 088 10. 653 -28. 951 1. 00 0. 00
ATOM 1227 2HB ASN 66 11 176 9 978 -28. 099 1. 00 0. 00
ATOM 1228 1HB ASN 66 12 093 11 005 -29. 184 1 00 0. 00
ATOM 1229 QB ASN 66 11 634 10 492 -28 641 1 00 0. 00
ATOM 1230 CG ASN 66 10. 516 9. 895 -30. 152 1. 00 0. 00 ATOM 1231 OD1 ASN 66 -9.565 9.138 -30.045 1.00 0.00
ATOM 1232 ND2 ASN 66 -11 .148 10 .140 -31 .296 1 .00 0 .00
ATOM 1233 1HD2 ASN 66 -11 .922 10 .772 -31 .314 1 .00 0 .00
ATOM 1234 2HD2 ASN 66 -10 .848 9 .692 -32 .138 1 .00 0 .00
ATOM 1235 QD2 ASN 66 -11 .386 10 .232 -31 .726 1 .00 0 .00
ATOM 1236 C ASN 66 -8 .747 11 .355 -28 .554 1 .00 0 .00
ATOM 1237 O ASN 66 -7 .977 11 .643 -29 .468 1 .00 0 .00
ATOM 1238 N THR 67 -8 .418 10 .627 -27 .497 1 .00 0 .00
ATOM 1239 HN THR 67 -9. .051 10 .397 -26 .758 1 .00 0 .00
ATOM 1240 CA THR 67 -7 .074 10 .099 -27 .341 1 .00 0 .00
ATOM 1241 HA THR 67 -6 .485 10 .395 -28 .210 1 .00 0 .00
ATOM 1242 CB THR 67 -6, .467 10 .715 -26 .079 1 .00 0 .00
ATOM 1243 HB THR 67 -7 .117 10 .556 -25 .218 1 .00 0 .00
ATOM 1244 QG2 THR 67 -4 .717 10 .081 -25 .732 1 .00 0 .00
ATOM 1245 OGl THR 67 -6, .279 12, .086 -26, .417 1. .00 0, .00
ATOM 1246 HG1 THR 67 -6, .801 12 .667 -25. .793 1 .00 0, .00
ATOM 1247 CG2 THR 67 -5, .053 10 .203 -25 .799 1 .00 0 .00
ATOM 1248 1HG2 THR 67 -4, .357 11, .042 -25, .795 1, .00 0, .00
ATOM 1249 2HG2 THR 67 -5, .031 9 .709 -24 .827 1 .00 0, .00
ATOM 1250 3HG2 THR 67 -4, .763 9. .494 -26 .574 1 .00 0 .00
ATOM 1251 C THR 67 -7, .101 8, .569 -27, .318 1, .00 0, .00
ATOM 1252 O THR 67 -7, .875 7 .970 -26 .575 1 .00 0, .00
ATOM 1253 N TYR 68 -6 .245 7 .982 -28 .142 1 .00 0 .00
ATOM 1254 HN TYR 68 -5, .618 8, .477 -28, .744 1, .00 0, .00
ATOM 1255 CA TYR 68 -6, .161 6, .534 -28, .226 1, .00 0, .00
ATOM 1256 HA TYR 68 -7, .161 6, .129 -28 .071 1 .00 0, .00
ATOM 1257 CB TYR 68 -5. .577 6, .224 -29, .606 1, .00 0, .00
ATOM 1258 2HB TYR 68 -4, .686 6, .835 -29, .757 1, .00 0, .00
ATOM 1259 1HB TYR 68 -5, .256 5, .183 -29, .628 1, .00 0, .00
ATOM 1260 QB TYR 68 -4. .971 6, .009 -29. .693 1. .00 0. .00
ATOM 1261 QD TYR 68 -6. ,640 6, .493 -30. .872 1, .00 0. .00
ATOM 1262 QE TYR 68 -8. ,254 6, .899 -32. .793 1, .00 0. .00
ATOM 1263 QR TYR 68 -7. ,447 6. .696 -31. .832 1*. ,00 0. .00
ATOM 1264 CG TYR 68 -6. .548 6. ,469 -30. ,762 1. ,00 0. ,00
ATOM 1265 CDl TYR 68 -6. ,897 5. .431 -31. ,602 1. .00 0. ,00
ATOM 1266 HD1 TYR 68 -6. ,481 4. .437 -31. ,441 1. ,00 0. ,00
ATOM 1267 CE1 TYR 68 -7. ,812 5. ,662 -32. .690 1. ,00 0. ,00
ATOM 1268 HEI TYR 68 -8. .096 4. .850 -33. .361 1. ,00 0. .00
ATOM 1269 CZ TYR 68 -8. ,313 6. .914 -32. ,862 1. ,00 0. ,00
ATOM 1270 CE2 TYR 68 -7. ,990 7. .959 -32. ,054 1. .00 0. ,00
ATOM 1271 HE2 TYR 68 -8. .414 8. .948 -32. .226 1. ,00 0. ,00
ATOM 1272 CD2 TYR 68 -7. ,075 7. ,728 -30. ,965 1. ,00 0. ,00
ATOM 1273 HD2 TYR 68 -6. ,800 8. ,548 -30. ,302 1. .00 0. ,00
ATOM 1274 OH TYR 68 -9. ,176 7. .132 -33. .890 1. .00 0. ,00
ATOM 1275 HH TYR 68 -9. ,861 6. ,404 -33. ,921 1. .00 0. ,00
ATOM 1276 C TYR 68 -5. ,225 5. .976 -27. ,152 1. ,00 0. ,00
ATOM 1277 0 TYR 68 -4. ,373 6. ,695 -26. ,632 1. ,00 0. ,00
ATOM 1278 N ASN 69 -5. 414 4. ,699 -26. ,852 1. ,00 0. 00
ATOM 1279 HN ASN 69 -6. ,110 4. ,122 -27. .280 1. ,00 0. ,00
ATOM 1280 CA ASN 69 -4. .598 4. ,037 -25. .850 1. ,00 0. ,00
ATOM 1281 HA ASN 69 -4. 033 4. ,835 -25. 367 1. 00 0. 00
ATOM 1282 CB ASN 69 -5. 467 3. ,297 -24. 832 1. ,00 0. 00
ATOM 1283 2HB ASN 69 -4. 839 2. ,675 -24. 194 1. ,00 0. 00
ATOM 1284 1HB ASN 69 -5. 967 4. 016 -24. 183 1. ,00 0. ,00
ATOM 1285 QB ASN 69 -5. 403 3. ,346 -24. 188 1. 00 0. 00
ATOM 1286 CG ASN 69 -6. 511 2. ,425 -25. 533 1. 00 0. 00
ATOM 1287 OD1 ASN 69 -6. 608 2. ,384 -26. 749 1. ,00 0. 00
ATOM 1288 ND2 ASN 69 -7. 284 1. 731 -24. 702 1. 00 0. 00
ATOM 1289 1HD2 ASN 69 -7. 152 1. 810 -23. 714 1. 00 0. 00
ATOM 1290 2HD2 ASN 69 -7. 997 1. .131 -25. 065 1. 00 0. 00
ATOM 1291 QD2 ASN 69 -7. 574 1. 471 -24. 390 1. 00 0. 00
ATOM 1292 C ASN 69 -3. 692 3. 010 -26. 533 1. 00 0. 00 ATOM 1293 O ASN 69 -4.102 1.875 -26.769 1.00 0.00
ATOM 1294 N ILE 70 -2 .477 3 .446 -26 .832 1 .00 0 .00
ATOM 1295 HN ILE 70 -2 .151 4 .371 -26 .637 1 .00 0 .00
ATOM 1296 CA ILE 70 -1 .510 2 .579 -27 .484 1 .00 0 .00
ATOM 1297 HA ILE 70 -2 .069 1 .815 -28 .024 1 .00 0 .00
ATOM 1298 CB ILE 70 -0 .699 3 .363 -28 .517 1 .00 0 .00
ATOM 1299 HB ILE 70 0 .018 3 .989 -27 .985 1 .00 0 .00
ATOM 1300 QG2 ILE 70 0 .294 2 .195 -29 .628 1 .00 0 .00
ATOM 1301 CG2 ILE 70 0 .104 2 .419 -29 .415 1 .00 0 .00
ATOM 1302 1HG2 ILE 70 1 .162 2 .672 -29 .354 1 .00 0 .00
ATOM 1303 2HG2 ILE 70 -0 .043 1 .391 -29 .084 1 .00 0 .00
ATOM 1304 3HG2 ILE 70 -0 .236 2 .522 -30 .445 1 .00 0 .00
ATOM 1305 CGI ILE 70 -1 .600 4 .298 -29 .327 1 .00 0 .00
ATOM 1306 2HG1 ILE 70 -2 .070 5 .022 -28 .663 1 .00 0 .00
ATOM 1307 1HG1 ILE 70 ■0 .997 4 .862 -30 .039 1 .00 0 .00
ATOM 1308 QG1 ILE 70 ■1 .534 4 .942 -29 .351 1 .00 0 .00
ATOM 1309 QD1 ILE 70 ■2 .932 3 .321 -30 .253 1 .00 0. .00
ATOM 1310 CDl ILE 70 ■2 .676 3 .509 -30, .075 1 .00 0, .00
ATOM 1311 1HD1 ILE 70 ■2. .992 4 .069 -30 .955 1 .00 0, .00
ATOM 1312 2HD1 ILE 70 ■2 .272 2 .545 -30 .384 1 .00 0, .00
ATOM 1313 3HD1 ILE 70 ■3 .532 3 .350 -29 .419 1 .00 0, .00
ATOM 1314 C ILE 70 ■0, .651 1 .891 -26, .421 1, .00 0. .00
ATOM 1315 O ILE 70 0, .016 2 .557 -25, .631 1, .00 0. ,00
ATOM 1316 N PRO 71 ■0, .698 0 .532 -26, .436 1 .00 0. .00
ATOM 1317 CD PRO 71 ■1, .477 -0 .290 -27, .357 1. .00 0. .00
ATOM 1318 CA PRO 71 0, .068 -0. .254 -25, .484 1, .00 0. ,00
ATOM 1319 HA PRO 71 0, .015 0, .157 -24, .573 1, .00 0. ,00
ATOM 1320 CB PRO 71 ■0, .563 -1 .636 -25, .516 1 .00 0. .00
ATOM 1321 2HB PRO 71 0. .199 -2, .414 -25, .481 1, .00 0. .00
ATOM 1322 1HB PRO 71 •1. .214 -1 .789 -24, .656 1 .00 0. ,00
ATOM 1323 QB PRO 71 •0, .507 -2 .102 -25, .068 1, .00 0. .00
ATOM 1324 CG PRO 71 ■1, .351 -1 .704 -26, .814 1, .00 0. .00
ATOM 1325 2HG PRO 71 0. .845 -2, .346 -27. .535 1, .00 0. ,00
ATOM 1326 1HG PRO 71 ■2. .337 -2, .135 -26. .640 1, .00 0. .00
ATOM 1327 QG PRO 71 •1. .591 -2, .240 -27, .088 1, .00 0. .00
ATOM 1328 2HD PRO 71 1. .091 -0, .220 -28. .374 1. .00 0. .00
ATOM 1329 1HD PRO 71 2. .518 0. .031 -27. .390 1, .00 0. ,00
ATOM 1330 QD PRO 71 1. .805 -0. .095 -27. .882 1, .00 0. ,00
ATOM 1331 C PRO 71 1, .553 -0, .266 -25. .851 1, .00 0. .00
ATOM 1332 O PRO 71 1. .917 -0. .625 -26. ,970 1. .00 0. ,00
ATOM 1333 N ILE 72 2. .372 0. ,132 -24. .888 1. .00 0. ,00
ATOM 1334 HN ILE 72 2. ,068 0. .422 -23. ,980 1. .00 0. .00
ATOM 1335 CA ILE 72 3. ,809 0. ,171 -25. ,096 1. ,00 0. 00
ATOM 1336 HA ILE 72 4. ,019 -0. ,358 -26. ,025 1. ,00 0. 00
ATOM 1337 CB ILE 72 4. ,284 1. .614 -25. ,280 1. ,00 0. 00
ATOM 1338 HB ILE 72 3. ,835 2. ,224 -24. ,497 1. ,00 0. 00
ATOM 1339 QG2 ILE 72 6. 163 1. ,740 -25. 078 1. 00 0. 00
ATOM 1340 CG2 ILE 72 5. ,802 1. ,716 -25. 117 1. 00 0. 00
ATOM 1341 1HG2 ILE 72 6. ,095 2. ,766 -25. ,087 1. ,00 0. 00
ATOM 1342 2HG2 ILE 72 6. 102 1. 229 -24. 189 1. 00 0. 00
ATOM 1343 3HG2 ILE 72 6. 292 1. ,226 -25. 959 1. 00 0. 00
ATOM 1344 CGI ILE 72 3. 812 2. ,180 -26. 621 1. 00 0. 00
ATOM 1345 2HG1 ILE 72 4. ,518 1. ,904 -27. 404 1. ,00 0. 00
ATOM 1346 1HG1 ILE 72 2. 852 1. 739 -26. 888 1. 00 0. 00
ATOM 1347 QG1 ILE 72 3. 685 1. ,822 -27. 146 1. 00 0. 00
ATOM 1348 QD1 ILE 72 3. 650 4. ,065 -26. 542 1. 00 0. 00
ATOM 1349 CDl ILE 72 3. 681 3. 703 -26. 557 1. 00 0. 00
ATOM 1350 1HD1 ILE 72 2. 786 4. 013 -27. 096 1. 00 0. 00
ATOM 1351 2HD1 ILE 72 3. 607 4. 018 -25. 517 1. 00 0. 00
ATOM 1352 3HD1 ILE 72 4. 558 4. 162 -27. 014 1. 00 0. 00
ATOM 1353 C ILE 72 4. 506 -0. 565 -23. 950 1. 00 0. 00
ATOM 1354 O ILE 72 4. 071 -0. 488 -22. 802 1. 00 0. 00 ATOM 1355 N CYS 73 5.578 -1.260 -24.301 1.00 0.00
ATOM 1356 HN CYS 73 5 .926 -1 .317 -25 .237 1 .00 0 .00
ATOM 1357 CA CYS 73 6 .340 -2 .009 -23 .316 1 .00 0 .00
ATOM 1358 HA CYS 73 5 .870 -1 .825 -22 .350 1 .00 0 .00
ATOM 1359 CB CYS 73 6 .273 -3 .516 -23 .575 1 .00 0 .00
ATOM 1360 2HB CYS 73 6 .492 -3 .723 -24 .622 1 .00 0 .00
ATOM 1361 1HB CYS 73 7 .030 -4 .029 -22 .983 1 .00 0 .00
ATOM 1362 QB CYS 73 6 .761 -3 .876 -23 .803 1 .00 0 .00
ATOM 1363 SG CYS 73 4 .610 -4 .151 -23 .148 1 .00 0 .00
ATOM 1364 HG CYS 73 4 .768 -5 .344 -23 .713 1 .00 0 .00
ATOM 1365 C CYS 73 7 .779 -1 .492 -23 .328 1 .00 0. .00
ATOM 1366 O CYS 73 8 .445 -1 .520 -24 .362 1 .00 o . .00
ATOM 1367 N LEU 74 8 .218 -1 .031 -22 .165 1 .00 0 .00
ATOM 1368 HN LEU 74 7 .670 -1 .011 -21 .329 1 .00 0 .00
ATOM 1369 CA LEU 74 9 .567 -0 .508 -22 .029 1 .00 0 .00
ATOM 1370 HA LEU 74 10 .137 -0 .844 -22 .895 1 .00 0. .00
ATOM 1371 CB LEU 74 9 .554 1 .022 -22 .061 1 .00 0 .00
ATOM 1372 2HB LEU 74 9 .576 1 .344 -23 .102 1 .00 0 .00
ATOM 1373 1HB LEU 74 8. .609 1 .366 -21 .641 1 .00 0, .00
ATOM 1374 QB LEU 74 9 .093 1 .355 -22 .372 1 .00 0. .00
ATOM 1375 CG LEU 74 10 .695 1 .718 -21 .317 1 .00 0 .00
ATOM 1376 HG LEU 74 11 .559 1. .053 -21, .316 1 .00 0 .00
ATOM 1377 QD1 LEU 74 11 .214 3 .308 -22, .204 1 .00 0 .00
ATOM 1378 QD2 LEU 74 10 .232 2 .034 -19, .508 1 .00 0, .00
ATOM 1379 CDl LEU 74 11 .114 3. .003 -22, .034 1 .00 0. .00
ATOM 1380 1HD1 LEU 74 12, .063 2, .840 -22. .545 1, .00 0, .00
ATOM 1381 2HD1 LEU 74 10, .351 3, .278 -22, .762 1 .00 0, .00
ATOM 1382 3HD1 LEU 74 11. .227 3, .805 -21, .305 1, .00 0, .00
ATOM 1383 CD2 LEU 74 10, .321 1. .973 -19. ,855 1, .00 0, .00
ATOM 1384 1HD2 LEU 74 10, .870 2, .840 -19. ,486 1, .00 0. .00
ATOM 1385 2HD2 LEU 74 9, .250 2, .163 -19. .782 1, .00 0. .00
ATOM 1386 3HD2 LEU 74 10, .577 1, .099 -19. .257 1, .00 0, .00
ATOM 1387 QQD LEU 74 10. .723 2. .671 -20. ,856 1. .00 0. .00
ATOM 1388 C LEU 74 10. .210 -1. .091 -20. ,769 1. .00 0. .00
ATOM 1389 O LEU 74 9, .604 -1, .086 -19. ,699 1, .00 0. .00
ATOM 1390 N TRP 75 11. .430 -1. ,580 -20. ,938 1. .00 0. .00
ATOM 1391 HN TRP 75 11. .916 -1. .580 -21. ,812 1. .00 0. .00
ATOM 1392 CA TRP 75 12, .162 -2. .165 -19. .828 1. .00 0. .00
ATOM 1393 HA TRP 75 11, .434 -2, .508 -19. .093 1, .00 0, .00
ATOM 1394 CB TRP 75 12. .952 -3. ,395 -20. ,280 1. ,00 0. ,00
ATOM 1395 2HB TRP 75 13. .722 -3. ,081 -20. ,985 1. .00 0. .00
ATOM 1396 1HB TRP 75 13, .465 -3. .822 -19. .418 1, .00 0. .00
ATOM 1397 QB TRP 75 13. ,593 -3. .451 -20. ,202 1. ,00 0. ,00
ATOM 1398 CG TRP 75 12. ,094 -4. ,480 -20. ,934 1. .00 0. ,00
ATOM 1399 CDl TRP 75 11. .385 -4. .400 -22. ,068 1. .00 0. ,00
ATOM 1400 CD2 TRP 75 11. .883 -5. .821 -20. ,443 1. .00 0. ,00
ATOM 1401 CE3 TRP 75 12. ,381 -6. ,458 -19. 294 1. ,00 0. 00
ATOM 1402 CE2 TRP 75 11. ,047 -6. ,477 -21. ,324 1. .00 0. ,00
ATOM 1403 NE1 TRP 75 10. ,735 -5. ,585 -22. ,343 1. .00 0. ,00
ATOM 1404 HD1 TRP 75 11. ,329 -3. .509 -22. 694 1. ,00 0. 00
ATOM 1405 HE3 TRP 75 13. ,043 -5. .962 -18. 583 1. ,00 0. 00
ATOM 1406 CZ3 TRP 75 11. .962 -7. ,784 -19. 131 1. .00 0. 00
ATOM 1407 CZ2 TRP 75 10. .636 -7. ,804 -21. 147 1. ,00 0. 00
ATOM 1408 HEI TRP 75 10. 094 -5. 786 -23. 202 1. 00 0. 00
ATOM 1409 HZ3 TRP 75 12. 319 -8. 325 -18. 255 1. 00 0. 00
ATOM 1410 CH2 TRP 75 11. ,121 -8. 459 -20. 008 1. 00 0. 00
ATOM 1411 HZ2 TRP 75 9. 975 -8. 300 -21. 857 1. 00 0. 00
ATOM 1412 HH2 TRP 75 10. 839 -9. 493 -19. 811 1. 00 0. 00
ATOM 1413 C TRP 75 13. 048 -1. 077 -19. 219 1. 00 0. 00
ATOM 1414 O TRP 75 13. .417 -0. 120 -19. 898 1. 00 0. 00
ATOM 1415 N LEU 76 13. 362 -1. 259 -17. 945 1. 00 0. 00
ATOM 1416 HN LEU 76 13. 058 -2. 039 -17. 400 1. 00 0. 00 ATOM 1417 CA LEU 76 14.198 -0.304 -17.237 1.00 0.00
ATOM 1418 HA LEU 76 14 .163 0 .634 -17 .791 1 .00 0 .00
ATOM 1419 CB LEU 76 13 .631 -0 .027 -15 .843 1 .00 0 .00
ATOM 1420 2HB LEU 76 12 .695 -0 .575 -15 .737 1 .00 0 .00
ATOM 1421 1HB LEU 76 14 .323 -0 .431 -15 .104 1 .00 0 .00
ATOM 1422 QB LEU 76 13 .509 -0 .503 -15 .420 1 .00 0 .00
ATOM 1423 CG LEU 76 13 .370 1 .442 -15 .505 1 .00 0 .00
ATOM 1424 HG LEU 76 14 .318 1 .978 -15 .553 1 .00 0 .00
ATOM 1425 QD1 LEU 76 12 .214 2 .236 -16 .777 1 .00 0 .00
ATOM 1426 QD2 LEU 76 12 .713 1 .626 -13 .738 1 .00 0 .00
ATOM 1427 CDl LEU 76 12 .436 2 .084 -16 .533 1 .00 0 .00
ATOM 1428 1HD1 LEU 76 11 .554 1 .457 -16 .664 1 .00 0 .00
ATOM 1429 2HD1 LEU 76 12 .132 3 .070 -16 .182 1 .00 0 .00
ATOM 1430 3HD1 LEU 76 12 .957 2 .182 -17 .485 1 .00 0 .00
ATOM 1431 CD2 LEU 76 12 .839 1 .591 -14 .077 1 .00 0 .00
ATOM 1432 1HD2 LEU 76 12 .255 0 .709 -13 .814 1 .00 0 .00
ATOM 1433 2HD2 LEU 76 13 .676 1. .692 -13 .387 1 .00 0 .00
ATOM 1434 3HD2 LEU 76 12 .207 2 .477 -14 .015 1 .00 0 .00
ATOM 1435 QQD LEU 76 12 .464 1 .931 -15 .258 1 .00 0 .00
ATOM 1436 C LEU 76 15 .642 -0, .807 -17 .224 1 .00 0, .00
ATOM 1437 O LEU 76 15 .914 -1 .936 -17 .631 1 .00 0 .00
ATOM 1438 N LEU 77 16 .532 0 .055 -16 .753 1 .00 0 .00
ATOM 1439 HN LEU 77 16 .303 0, .971 -16 .424 1 .00 0 .00
ATOM 1440 CA LEU 77 17 .942 -0 .288 -16 .683 1 .00 0 .00
ATOM 1441 HA LEU 77 18 .067 -1 .256 -17 .168 1. .00 0 .00
ATOM 1442 CB LEU 77 18 .779 0. .723 -17 .467 1 .00 0. .00
ATOM 1443 2HB LEU 77 19 .817 0, .635 -17. .144 1 .00 0, .00
ATOM 1444 1HB LEU 77 18 .750 0, .450 -18 .522 1 .00 0, .00
ATOM 1445 QB LEU 77 19 .283 0, .542 -17 .833 1 .00 0, .00
ATOM 1446 CG LEU 77 18, .357 2, .188 -17, .337 1, .00 0, .00
ATOM 1447 HG LEU 77 17, .275 2, .244 -17, .461 1, .00 0, .00
ATOM 1448 QD1 LEU 77 18, .757 2. .859 -15. .613 1, .00 0, .00
ATOM 1449 QD2 LEU 77 19. .132 3. .242 -18. .706 1, .00 0. ,00
ATOM 1450 CDl LEU 77 18, .680 2. .731 -15, .943 1, .00 0. .00
ATOM 1451 1HD1 LEU 77 17, .895 2. .435 -15, .248 1. .00 0. .00
ATOM 1452 2HD1 LEU 77 19. ,634 2. ,325 -15. .608 1. .00 0. ,00
ATOM 1453 3HD1 LEU 77 18. .741 3. .818 -15. .982 1. .00 0. ,00
ATOM 1454 CD2 LEU 77 18. .983 3. ,040 -18. .443 1. ,00 0. ,00
ATOM 1455 1HD2 LEU 77 19. .264 4. .012 -18. .038 1. .00 0. .00
ATOM 1456 2HD2 LEU 77 19. .870 2. ,538 -18. .830 1. ,00 0. ,00
ATOM 1457 3HD2 LEU 77 18. ,262 3. ,177 -19. .249 1. ,00 0. ,00
ATOM 1458 QQD LEU 77 18. ,944 3. ,051 -17. ,159 1. ,00 0. .00
ATOM 1459 C LEU 77 18. ,356 -0. 424 -15. ,216 1. ,00 0. 00
ATOM 1460 O LEU 77 17. ,513 -0. ,373 -14. ,322 1. .00 0. 00
ATOM 1461 N ASP 78 19. ,655 -0. ,596 -15. ,015 1. ,00 0. 00
ATOM 1462 HN ASP 78 20. 334 -0. 636 -15. 748 1. 00 0. 00
ATOM 1463 CA ASP 78 20. 191 -0. 739 -13. 672 1. 00 0. 00
ATOM 1464 HA ASP 78 19. ,349 -0. 553 -13. 006 1. ,00 0. 00
ATOM 1465 CB ASP 78 20. 756 -2. 144 -13. 452 1. 00 0. 00
ATOM 1466 2HB ASP 78 21. 257 -2. 171 -12. 485 1. 00 0. 00
ATOM 1467 1HB ASP 78 19. 926 -2. 849 -13. 400 1. 00 0. 00
ATOM 1468 QB ASP 78 20. 592 -2. 510 -12. 942 1. 00 0. 00
ATOM 1469 CG ASP 78 21. 737 -2. 622 -14. 525 1. 00 0. 00
ATOM 1470 OD1 ASP 78 21. 365 -2. 807 -15. 693 1. 00 0. 00
ATOM 1471 OD2 ASP 78 22. 945 -2. 810 -14. 114 1. 00 0. 00
ATOM 1472 HD2 ASP 78 22. 941 -3. 082 -13. 152 1. 00 0. 00
ATOM 1473 C ASP 78 21. 329 0. 264 -13. 472 1. 00 0. 00
ATOM 1474 O ASP 78 21. 367 0. 972 -12. 467 1. 00 0. 00
ATOM 1475 N THR 79 22. 228 0. 293 -14. 445 1. 00 0. 00
ATOM 1476 HN THR 79 22. 189 -0. 287 -15. 259 1. 00 0. 00
ATOM 1477 CA THR 79 23. 363 1. 198 -14. 388 1. 00 0. 00
ATOM 1478 HA THR 79 23. 785 1. 157 -13. 384 1. 00 0. 00 ATOM 1479 CB THR 79 24.404 0.714 -15.400 1.00 0.00
ATOM 1480 HB THR 79 24 .952 -0 .146 -15 .014 1 .00 0 .00
ATOM 1481 QG2 THR 79 23 .646 0 .329 -17 .092 1 .00 0 .00
ATOM 1482 OGl THR 79 25 .217 1 .860 -15 .637 1 .00 0 .00
ATOM 1483 HG1 THR 79 26 .020 1 .838 -15 .042 1 .00 o. .00
ATOM 1484 CG2 THR 79 23 .791 0 .403 -16 .767 1 .00 0 .00
ATOM 1485 1HG2 THR 79 22 .860 0 .957 -16 .882 1 .00 0 .00
ATOM 1486 2HG2 THR 79 24 .488 0 .696 -17 .553 1 .00 0 .00
ATOM 1487 3HG2 THR 79 23 .590 -0 .666 -16 .840 1 .00 0 .00
ATOM 1488 C THR 79 22 .909 2 .639 -14 .626 1. .00 0. .00
ATOM 1489 O THR 79 23 .437 3 .568 -14 .017 1 .00 0. .00
ATOM 1490 N TYR 80 21 .934 2 .780 -15 .512 1 .00 0 .00
ATOM 1491 HN TYR 80 21 .510 2 .019 -16 .002 1. .00 0. .00
ATOM 1492 CA TYR 80 21 .402 4 .093 -15 .837 1 .00 0. .00
ATOM 1493 HA TYR 80 20 .633 3 .965 -16 .598 1 .00 0 .00
ATOM 1494 CB TYR 80 20 .879 4 .673 -14 .522 1 .00 0 .00
ATOM 1495 2HB TYR 80 20 .563 3. .855 -13 .875 1 .00 0, .00
ATOM 1496 1HB TYR 80 21 .695 5 .185 -14 .012 1. .00 0, .00
ATOM 1497 QB TYR 80 21 .129 4 .520 -13 .944 1 .00 0, .00
ATOM 1498 QD TYR 80 19, .602 5. .741 -14. .709 1. .00 0, .00
ATOM 1499 QE TYR 80 17, .663 7 .361 -14. .993 1, .00 0, .00
ATOM 1500 QR TYR 80 18 .633 6 .551 -14, .851 1, .00 0, .00
ATOM 1501 CG TYR 80 19, .712 5, .649 -14, .693 1. .00 0. .00
ATOM 1502 CDl TYR 80 18, .467 5, .330 -14, .189 1. .00 0. .00
ATOM 1503 HD1 TYR 80 18, .315 4, .384 -13, .670 1. .00 0. .00
ATOM 1504 CE1 TYR 80 17, .369 6, .248 -14, .350 1, .00 0. .00
ATOM 1505 HEI TYR 80 16. .381 6, .009 -13. .958 1. ,00 0. .00
ATOM 1506 CZ TYR 80 17, .593 7, .419 -15. .004 1. .00 0. .00
ATOM 1507 CE2 TYR 80 18, .807 7, .764 -15, .512 1. .00 0. ,00
ATOM 1508 HE2 TYR 80 18. .945 8. .713 -16. .029 1. .00 0. .00
ATOM 1509 CD2 TYR 80 19. .905 6, .846 -15. .351 1. .00 0. .00
ATOM 1510 HD2 TYR 80 20. .888 7, .098 -15, .748 1. .00 0. .00
ATOM 1511 OH TYR 80 16. .556 8. .286 -15. .156 1. .00 0. .00
ATOM 1512 HH TYR 80 16, .398 8, .782 -14. .302 1. .00 0. .00
ATOM 1513 C TYR 80 22, .499 5, .008 -16. .384 1. .00 0. .00
ATOM 1514 O TYR 80 22. ,913 5. .955 -15. .717 1. ,00 0. ,00
ATOM 1515 N PRO 81 22. ,951 4, .685 -17. .626 1. .00 0. .00
ATOM 1516 CD PRO 81 22. .484 3, .571 -18. .446 1. .00 0. .00
ATOM 1517 CA PRO 81 23. .992 5, .467 -18. ,271 1. .00 0. .00
ATOM 1518 HA PRO 81 24. ,708 5. .702 -17. ,613 1. ,00 0. ,00
ATOM 1519 CB PRO 81 24. .520 4. ,578 -19. ,385 1. .00 0. ,00
ATOM 1520 2HB PRO 81 24. .705 5. .155 -20. .290 1. .00 0. ,00
ATOM 1521 1HB PRO 81 25. ,466 4. ,117 -19. ,101 1. ,00 0. 00
ATOM 1522 QB PRO 81 25. ,085 4. ,636 -19. ,696 1. ,00 0. 00
ATOM 1523 CG PRO 81 23. ,449 3. ,525 -19. ,619 1. ,00 0. ,00
ATOM 1524 2HG PRO 81 22. .923 3. ,717 -20. 554 1. .00 0. 00
ATOM 1525 1HG PRO 81 23. ,899 2. ,536 -19. ,705 1. .00 0. 00
ATOM 1526 QG PRO 81 23. ,411 3. ,126 -20. ,130 1. .00 0. 00
ATOM 1527 2HD PRO 81 21. 459 3. 728 -18. 781 1. 00 0. 00
ATOM 1528 1HD PRO 81 22. 497 2. ,635 -17. 886 1. 00 0. 00
ATOM 1529 QD PRO 81 21. ,978 3. ,182 -18. 334 1. 00 0. 00
ATOM 1530 C PRO 81 23. .440 6. ,800 -18. ,780 1. 00 0. 00
ATOM 1531 O PRO 81 23. 704 7. 850 -18. 196 1. 00 0. 00
ATOM 1532 N TYR 82 22. ,683 6. ,715 -19. 865 1. 00 0. 00
ATOM 1533 HN TYR 82 22. .473 5. ,857 -20. ,334 1. 00 0. 00
ATOM 1534 CA TYR 82 22. 091 7. 901 -20. 460 1. 00 0. 00
ATOM 1535 HA TYR 82 22. 794 8. 725 -20. 338 1. 00 0. 00
ATOM 1536 CB TYR 82 21. .807 7. ,543 -21. .920 1. 00 0. 00
ATOM 1537 2HB TYR 82 21. 207 6. 634 -21. 950 1. 00 0. 00
ATOM 1538 1HB TYR 82 21. 207 8. 336 -22. 367 1. 00 0. 00
ATOM 1539 QB TYR 82 21. 207 7. .485 -22. 159 1. 00 0. 00
ATOM 1540 QD TYR 82 23. 184 7. 316 -22. 846 1. 00 0. 00 ATOM 1541 QE TYR 82 25.274 6.971 -24.252 1.00 0.00
ATOM 1542 QR TYR 82 24 .229 7 .143 -23 .549 1 .00 0 .00
ATOM 1543 CG TYR 82 23 .065 7 .335 -22 .766 1 .00 0 .00
ATOM 1544 CDl TYR 82 23 .568 6 .064 -22 .954 1 .00 0 .00
ATOM 1545 HDl TYR 82 23 .069 5 .208 -22 .499 1 .00 0 .00
ATOM 1546 CE1 TYR 82 24 .752 5 .869 -23 .750 1 .00 0 .00
ATOM 1547 HEI TYR 82 25 .160 4 .870 -23 .906 1 .00 0 .00
ATOM 1548 CZ TYR 82 25 .349 6 .958 -24 .303 1 .00 0 .00
ATOM 1549 CE2 TYR 82 24 .880 8 .224 -24 .137 1 .00 0 .00
ATOM 1550 HE2 TYR 82 25 .388 9 .071 -24 .598 1 .00 0 .00
ATOM 1551 CD2 TYR 82 23 .696 8 .419 -23. .341 1 .00 0 .00
ATOM 1552 HD2 TYR 82 23 .299 9 .423 -23 .193 1 .00 0 .00
ATOM 1553 OH TYR 82 26 .467 6 .774 -25 .055 1 .00 o . .00
ATOM 1554 HH TYR 82 27 .230 6 .495 -24 .471 1 .00 o . .00
ATOM 1555 C TYR 82 20 .774 8 .262 -19. .770 1 .00 0 .00
ATOM 1556 O TYR 82 20 .649 9 .338 -19 .187 1 .00 0 .00
ATOM 1557 N ASN 83 19 .825 7 .341 -19 .858 1 .00 0 .00
ATOM 1558 HN ASN 83 19 .935 6 .468 -20 .333 1 .00 0 .00
ATOM 1559 CA ASN 83 18 .522 7 .549 -19 .249 1 .00 0 .00
ATOM 1560 HA ASN 83 18 .674 7 .381 -18 .183 1 .00 0 .00
ATOM 1561 CB ASN 83 18 .014 8. .969 -19 .507 1 .00 0. .00
ATOM 1562 2HB ASN 83 18 .704 9, .491 -20, .169 1 .00 0. .00
ATOM 1563 1HB ASN 83 17 .052 8. .927 -20 .017 1 .00 0 .00
ATOM 1564 QB ASN 83 17 .878 9, .209 -20 .093 1 .00 0 .00
ATOM 1565 CG ASN 83 17 .870 9, .745 -18 .197 1 .00 0. .00
ATOM 1566 OD1 ASN 83 18, .596 10, .685 -17, .919 1. .00 0. .00
ATOM 1567 ND2 ASN 83 16, .894 9, .301 -17, .409 1 .00 0, .00
ATOM 1568 1HD2 ASN 83 16, .334 8, .525 -17, .697 1 .00 0, .00
ATOM 1569 2HD2 ASN 83 16. .721 9. .745 -16, .530 1, .00 0. .00
ATOM 1570 QD2 ASN 83 16. .527 9. .135 -17, .113 1. .00 0. .00
ATOM 1571 C ASN 83 17. .518 6. .569 -19, .859 1. .00 0. .00
ATOM 1572 O ASN 83 16. .834 5. .845 -19, .137 1, .00 0, .00
ATOM 1573 N PRO 84 17. .458 6. ,578 -21. ,218 1. .00 0. .00
ATOM 1574 CD PRO 84 18. ,252 7. ,422 -22. .106 1. .00 0. .00
ATOM 1575 CA PRO 84 16. .548 5. .700 -21. .933 1. .00 0. .00
ATOM 1576 HA PRO 84 15. .659 5. ,673 -21. ,475 1. ,00 0. ,00
ATOM 1577 CB PRO 84 16. .445 6. ,292 -23. ,329 1. .00 0. ,00
ATOM 1578 2HB PRO 84 16. .447 5. .508 -24. .087 1. .00 0. ,00
ATOM 1579 1HB PRO 84 15. .516 6. .849 -23. .450 1, .00 0. .00
ATOM 1580 QB PRO 84 15. .982 6. ,179 -23. ,768 1. .00 0. ,00
ATOM 1581 CG PRO 84 17. .652 7. ,203 -23. ,485 1, .00 0. ,00
ATOM 1582 2HG PRO 84 18, .386 6. ,754 -24. ,154 1, .00 0. .00
ATOM 1583 1HG PRO 84 17. ,357 8. ,154 -23. ,929 1. .00 0. ,00
ATOM 1584 QG PRO 84 17. .871 7. ,454 -24. ,041 1. .00 0. ,00
ATOM 1585 2HD PRO 84 19. .305 7. ,141 -22. .083 1. .00 0. ,00
ATOM 1586 1HD PRO 84 18. .195 8. ,470 -21. ,811 1. .00 0. ,00
ATOM 1587 QD PRO 84 18. ,750 7. .806 -21. ,947 1. .00 0. .00
ATOM 1588 C PRO 84 17. ,062 4. .259 -21. ,931 1. ,00 0. ,00
ATOM 1589 O PRO 84 18. ,088 3. .961 -22. ,541 1. ,00 0. .00
ATOM 1590 N PRO 85 16. ,307 3. 380 -21. 219 1. ,00 0. 00
ATOM 1591 CD PRO 85 15. ,087 3. 697 -20. 483 1. ,00 0. 00
ATOM 1592 CA PRO 85 16. ,676 1. 977 -21. 129 1. ,00 0. 00
ATOM 1593 HA PRO 85 17. ,663 1. 886 -20. 995 1. ,00 0. 00
ATOM 1594 CB PRO 85 15. 893 1. 440 -19. 942 1. 00 0. 00
ATOM 1595 2HB PRO 85 15. 498 0. 446 -20. 153 1. .00 0. 00
ATOM 1596 1HB PRO 85 16. ,531 1. 349 -19. 063 1. .00 0. 00
ATOM 1597 QB PRO 85 16. 014 0. 898 -19. 608 1. 00 0. 00
ATOM 1598 CG PRO 85 14. 769 2. 434 -19. 700 1. 00 0. 00
ATOM 1599 2HG PRO 85 13. 815 2. 016 -20. 020 1. 00 0. 00
ATOM 1600 1HG PRO 85 14. 679 2. 656 -18. 637 1. .00 0. 00
ATOM 1601 QG PRO 85 14. 247 2. 336 -19. 328 1. 00 0. 00
ATOM 1602 2HD PRO 85 14. 273 3. 958 -21. 160 1. 00 0. 00 ATOM 1603 1HD PRO 85 15.235 4.548 -19.819 1.00 0.00
ATOM 1604 QD PRO 85 14 .754 4 .253 -20 .489 1 .00 0 .00
ATOM 1605 C PRO 85 16 .362 1 .243 -22 .434 1 .00 0 .00
ATOM 1606 O PRO 85 17 .195 1 .193 -23 .338 1 .00 0 .00
ATOM 1607 N ILE 86 15 .158 0 .693 -22 .492 1 .00 0 .00
ATOM 1608 HN ILE 86 14 .487 0 .739 -21 .752 1 .00 0 .00
ATOM 1609 CA ILE 86 14 .724 -0 .036 -23 .671 1 .00 0 .00
ATOM 1610 HA ILE 86 15 .361 0 .273 -24 .499 1 .00 0 .00
ATOM 1611 CB ILE 86 14 .930 -1 .540 -23 .478 1 .00 0 .00
ATOM 1612 HB ILE 86 14 .521 -1 .819 -22 .507 1 .00 0 .00
ATOM 1613 QG2 ILE 86 13 .986 -2 .528 -24 .788 1 .00 0 .00
ATOM 1614 CG2 ILE 86 14 .167 -2 .339 -24 .536 1 .00 0 .00
ATOM 1615 1HG2 ILE 86 14 .147 -1 .777 -25 .471 1 .00 0 .00
ATOM 1616 2HG2 ILE 86 14 .664 -3 .295 -24 .698 1 .00 0 .00
ATOM 1617 3HG2 ILE 86 13 .147 -2 .512 -2 .195 1 .00 0 .00
ATOM 1618 CGI ILE 86 16 .420 -1 .890 -23 .458 1 .00 0 .00
ATOM 1619 2HG1 ILE 86 16 .657 -2 .531 -24 .308 1 .00 0 .00
ATOM 1620 1HG1 ILE 86 17. .012 -0, .982 -23, .568 1 .00 0, .00
ATOM 1621 QG1 ILE 86 16, .835 -1, .756 -23, .938 1 .00 0, .00
ATOM 1622 QD1 ILE 86 16 .889 -2 .768 -21, .848 1 .00 0 .00
ATOM 1623 CDl ILE 86 16 .799 -2 .599 -22 .157 1 .00 0, .00
ATOM 1624 1HD1 ILE 86 16, .152 -3, .464 -22, .012 1 .00 0, .00
ATOM 1625 2HD1 ILE 86 17, .837 -2, .927 -22, .211 1 .00 0, .00
ATOM 1626 3HD1 ILE 86 16 .678 -1 .911 -21, .320 1 .00 0 .00
ATOM 1627 C ILE 86 13 .280 0 .349 -24 .000 1 .00 0 .00
ATOM 1628 0 ILE 86 12, .389 0, .202 -23, .165 1. .00 0, .00
ATOM 1629 N CYS 87 13, .094 0, .834 -25, .219 1 .00 0, .00
ATOM 1630 HN CYS 87 13 .824 0 .950 -25, .892 1 .00 0, .00
ATOM 1631 CA CYS 87 11, .774 1, .241 -25, .669 1, .00 0, .00
ATOM 1632 HA CYS 87 11, .135 1, .263 -24, .786 1, .00 0, .00
ATOM 1633 CB CYS 87 11, .787 2, .653 -26, .257 1 .00 0. .00
ATOM 1634 2HB CYS 87 10, .818 2, .881 -26, .701 1 .00 0, .00
ATOM 1635 1HB CYS 87 11. ,955 3. .384 -25. .466 1, .00 0. ,00
ATOM 1636 QB CYS 87 11. .386 3. .132 -26. .084 1, .00 0. ,00
ATOM 1637 SG CYS 87 13. .101 2, .791 -27. .524 1, .00 0. .00
ATOM 1638 HG CYS 87 13. ,720 3. .830 -26. .970 1. .00 0. ,00
ATOM 1639 C CYS 87 11. ,270 0. ,207 -26. .678 1. .00 0. .00
ATOM 1640 O CYS 87 11. .987 -0. ,158 -27. ,609 1. .00 0. .00
ATOM 1641 N PHE 88 10. .040 -0. .236 -26. ,459 1. .00 0. .00
ATOM 1642 HN PHE 88 9. ,464 0. ,066 -25. .700 1. .00 0. ,00
ATOM 1643 CA PHE 88 9. ,432 -1. ,221 -27. ,338 1. ,00 0. ,00
ATOM 1644 HA PHE 88 9. ,856 -1. ,073 -28. ,331 1. .00 0. ,00
ATOM 1645 CB PHE 88 9. 744 -2. 598 -26. 749 1. ,00 0. 00
ATOM 1646 2HB PHE 88 10. 607 -2. 513 -26. 088 1. ,00 0. 00
ATOM 1647 1HB PHE 88 8. ,902 -2. ,918 -26. .134 1. ,00 0. ,00
ATOM 1648 QB PHE 88 9. ,755 -2. ,716 -26. ,111 1. ,00 0. .00
ATOM 1649 QD PHE 88 10. 052 -3. 769 -27. 892 1. ,00 0. 00
ATOM 1650 QE PHE 88 10. ,517 -5. 534 -29. ,614 1. ,00 0. 00
ATOM 1651 QR PHE 88 10. ,285 -4. 652 -28. .753 1. ,00 0. .00
ATOM 1652 CG PHE 88 10. 027 -3. 674 -27. 799 1. ,00 0. 00
ATOM 1653 CDl PHE 88 8. 997 -4. 351 -28. 374 1. ,00 0. 00
ATOM 1654 HDl PHE 88 7. 970 -4. 126 -28. 087 1. ,00 0. 00
ATOM 1655 CE1 PHE 88 9. 260 -5. 349 -29. 349 1. ,00 0. 00
ATOM 1656 HEI PHE 88 8. 435 -5. 892 -29. 810 1. 00 0. 00
ATOM 1657 CZ PHE 88 10. 542 -5. 629 -29. 707 1. 00 0. 00
ATOM 1658 HZ PHE 88 10. 744 -6. 396 -30. 455 1. ,00 0. 00
ATOM 1659 CE2 PHE 88 11. 572 -4. 953 -29. 131 1. 00 0. 00
ATOM 1660 HE2 PHE 88 12. 599 -5. 177 -29. 418 1. 00 0. 00
ATOM 1661 CD2 PHE 88 11. 309 -3. 954 -28. 157 1. 00 0. 00
ATOM 1662 HD2 PHE 88 12. 134 -3. 412 -27. 696 1. 00 0. 00
ATOM 1663 C PHE 88 7. 915 -1. 037 -27. 400 1. 00 0. 00
ATOM 1664 O PHE 88 7. 247 -1. 003 -26. 368 1. 00 0. 00 ATOM 1665 N VAL 89 7.414 -0.923 -28.622 1.00 0.00
ATOM 1666 HN VAL 89 7 .964 -0 .952 -29 .456 1 .00 0 .00
ATOM 1667 CA VAL 89 5 .988 -0 .744 -28 .832 1 .00 0 .00
ATOM 1668 HA VAL 89 5 .595 -0 .196 -27 .976 1 .00 0 .00
ATOM 1669 CB VAL 89 5 .746 0 .099 -30 .086 1 .00 0 .00
ATOM 1670 HB VAL 89 6 .366 0 .992 -30 .014 1 .00 0 .00
ATOM 1671 QG1 VAL 89 6 .262 -0 .842 -31 .646 1 .00 0 .00
ATOM 1672 QG2 VAL 89 3 .939 0 .652 -30 .194 1 .00 0 .00
ATOM 1673 CGI VAL 89 6 .163 -0 .662 -31 .347 1 .00 0 .00
ATOM 1674 1HG1 VAL 89 6 .114 -1 .734 -31 .157 1 .00 0 .00
ATOM 1675 2HG1 VAL 89 5 .489 -0 .407 -32 .164 1 .00 0 .00
ATOM 1676 3HG1 VAL 89 7 .182 -0 .387 -31 .617 1 .00 0 .00
ATOM 1677 CG2 VAL 89 4 .285 0 .546 -30 .173 1 .00 0 .00
ATOM 1678 1HG2 VAL 89 3 .993 0 .632 -31 .219 1 .00 0 .00
ATOM 1679 2HG2 VAL 89 3 .651 -0 .189 -29 .678 1 .00 0 .00
ATOM 1680 3HG2 VAL 89 4 .172 1 .513 -29 .683 1 .00 0 .00
ATOM 1681 QQG VAL 89 5 .100 -0 .095 -30 .920 1 .00 0 .00
ATOM 1682 C VAL 89 5 .309 -2 .114 -28 .893 1 .00 0 .00
ATOM 1683 O VAL 89 5 .875 -3 .068 -29 .426 1 .00 0 .00
ATOM 1684 N LYS 90 4 .107 -2 .168 -28 .338 1 .00 0. .00
ATOM 1685 HN LYS 90 3 .655 -1 .388 -27 .907 1 .00 0. .00
ATOM 1686 CA LYS 90 3 .346 -3 .406 -28 .323 1 .00 0 .00
ATOM 1687 HA LYS 90 3. .951 -4, .168 -28, .812 1. .00 0, .00
ATOM 1688 CB LYS 90 3, .109 -3, .871 -26, .884 1. .00 0, .00
ATOM 1689 2HB LYS 90 3, .725 -3, .285 -26, .202 1 .00 0, .00
ATOM 1690 1HB LYS 90 2, .070 -3, .693 -26, .607 1 .00 0, .00
ATOM 1691 QB LYS 90 2, .897 -3. .489 -26, .405 1, .00 0. .00
ATOM 1692 CG LYS 90 3, .437 -5, .357 -26. .728 1, .00 0. .00
ATOM 1693 2HG LYS 90 4, .143 -5, .661 -27. .500 1, .00 0. .00
ATOM 1694 1HG LYS 90 3, .923 -5, .526 -25, .767 1, .00 0, .00
ATOM 1695 QG LYS 90 4, .033 -5, .593 -26, .633 1, .00 0, .00
ATOM 1696 CD LYS 90 2, .171 -6. .211 -26, .822 1, .00 0. .00
ATOM 1697 2HD LYS 90 1, .292 -5, .566 -26, .827 1, .00 0. .00
ATOM 1698 1HD LYS 90 2, .168 -6, .760 -27, .764 1, .00 0, .00
ATOM 1699 QD LYS 90 1, .730 -6, .163 -27, .295 1, .00 0, .00
ATOM 1700 CE LYS 90 2. .083 -7. .193 -25. .652 1, .00 0. ,00
ATOM 1701 2HE LYS 90 3. .054 -7. .659 -25. .488 1. .00 0. .00
ATOM 1702 IHE LYS 90 1. .828 -6. .656 -24. .738 1. .00 0. .00
ATOM 1703 QE LYS 90 2. .441 -7. .158 -25. .113 1, .00 0. .00
ATOM 1704 NZ LYS 90 1. .066 -8. .233 -25. ,924 1. ,00 0. ,00
ATOM 1705 1HZ LYS 90 1. ,141 -9. .014 -25. .282 1. .00 0. ,00
ATOM 1706 2HZ LYS 90 0. .122 -7. .872 -25. .839 1. .00 0. ,00
ATOM 1707 QZ LYS 90 0. .631 -8. ,443 -25. ,560 1. ,00 0. ,00
ATOM 1708 C LYS 90 2. ,059 -3. ,218 -29. ,128 1. ,00 0. 00
ATOM 1709 O LYS 90 1. ,056 -2. ,739 -28. ,600 1. ,00 0. 00
ATOM 1710 N PRO 91 2. ,130 -3. ,615 -30. ,427 1. ,00 0. 00
ATOM 1711 CD PRO 91 3. ,301 -4. ,187 -31. ,086 1. ,00 0. 00
ATOM 1712 CA PRO 91 0. ,983 -3. ,495 -31. .310 1. ,00 0. 00
ATOM 1713 HA PRO - 91 0. 523 -2. 619 -31. 166 1. 00 0. 00
ATOM 1714 CB PRO 91 1. 554 -3. 606 -32. 714 1. 00 0. 00
ATOM 1715 2HB PRO 91 0. ,910 -4. 213 -33. 351 1. 00 0. 00
ATOM 1716 1HB PRO 91 1. ,633 -2. ,625 -33. 183 1. .00 0. 00
ATOM 1717 QB PRO 91 1. 272 -3. 419 -33. 267 1. 00 0. 00
ATOM 1718 CG PRO 91 2. 924 -4. 246 -32. 558 1. 00 0. 00
ATOM 1719 2HG PRO 91 2. 905 -5. 279 -32. 905 1. 00 0. 00
ATOM 1720 1HG PRO 91 3. 663 -3. 720 -33. 162 1. 00 0. 00
ATOM 1721 QG PRO 91 3. 284 -4. 500 -33. 034 1. 00 0. 00
ATOM 1722 2HD PRO 91 3. 530 -5. 178 -30. 696 1. 00 0. 00
ATOM 1723 1HD PRO 91 4. 185 -3. 569 -30. 928 1. 00 0. 00
ATOM 1724 QD PRO 91 3. 858 -4. 374 -30. 812 1. 00 0. 00
ATOM 1725 C PRO 91 0. 061 -4. 571 -31. 003 1. 00 0. 00
ATOM 1726 O PRO 91 0. 208 -5. 503 -30. 247 1. 00 0. 00 ATOM 1727 N THR 92 -1.230 -4.405 -31.605 1.00 0.00
ATOM 1728 HN THR 92 -1 .440 -3 .644 -32 .218 1 .00 0 .00
ATOM 1729 CA THR 92 2 .315 -5 .351 -31 .405 1 .00 0 .00
ATOM 1730 HA THR 92 1 .982 -6 .111 -30 .698 1 .00 0 .00
ATOM 1731 CB THR 92 3 .502 -4 .589 -30 .813 1 .00 0 .00
ATOM 1732 HB THR 92 4 .372 -5 .239 -30 .715 1 .00 0 .00
ATOM 1733 QG2 THR 92 3 .084 -3 .763 -29 .161 1 .00 0 .00
ATOM 1734 OGl THR 92 3 .695 -3 .496 -31 .708 1 .00 0 .00
ATOM 1735 HG1 THR 92 4 .031 -3 .830 -32 .588 1 .00 0 00
ATOM 1736 CG2 THR 92 3 .164 -3 .922 -29 .478 1 .00 0 .00
ATOM 1737 1HG2 THR 92 3 .977 -4 .089 -28 .772 1 .00 0 .00
ATOM 1738 2HG2 THR 92 2 244 -4 .350 -29 .081 1 .00 0 00
ATOM 1739 3HG2 THR 92 3 030 -2 .851 -29 .631 1 .00 0 00
ATOM 1740 C THR 92 2 .645 -6 .069 -32 .715 1 .00 0 00
ATOM 1741 O THR 92 1 894 -5 975 -33 685 1 .00 0 00
ATOM 1742 N SER 93 3 769 -6 .769 -32 .701 1 .00 0 00
ATOM 1743 HN SER 93 4 374 -6 .841 -31 .908 1 .00 0 00
ATOM 1744 CA SER 93 4 208 -7 503 -33 .876 1 .00 0 00
ATOM 1745 HA SER 93 3 298 -7 902 -34 .324 1 .00 0 00
ATOM 1746 CB SER 93 5 135 -8 .658 -33 .490 1 .00 0 00
ATOM 1747 2HB SER 93 5 219 -9 350 -34 328 1 00 0 00
ATOM 1748 1HB SER 93 4 697 -9 212 -32 660 1 .00 0 00
ATOM 1749 QB SER 93 4 958 -9 281 -33 .494 1 .00 0 00
ATOM 1750 OG SER 93 6 433 -8 200 -33 122 1 00 0 00
ATOM 1751 HG SER 93 6 378 -7 269 -32 760 1 00 0 00
ATOM 1752 C SER 93 4 915 -6 558 -34 849 1 00 0 00
ATOM 1753 O SER 93 4 946 -6 810 -36 053 1 00 0 00
ATOM 1754 N SER 94 5 466 -5 489 -34 292 1 00 0 00
ATOM 1755 HN SER 94 5 436 -5 291 -33 312 1 00 0 00
ATOM 1756 CA SER 94 6 170 -4 505 -35 095 1 00 0 00
ATOM 1757 HA SER 94 6 883 -5 075 -35 691 1 00 0 00
ATOM 1758 CB SER 94 6 926 -3 511 -34 211 1 00 0 00
ATOM 1759 2HB SER 94 6 257 -3 132 -33 438 1 00 0 00
ATOM 1760 1HB SER 94 7 236 -2 655 -34 811 1 00 0 00
ATOM 1761 QB SER 94 6 747 -2 894 -34 124 1 00 0 00
ATOM 1762 OG SER 94 8 070 -4 101 -33 601 1 00 0 00
ATOM 1763 HG SER 94 7 791 -4 864 -33 018 1 00 0 00
ATOM 1764 C SER 94 5 183 -3 766 -36 001 1 00 0 00
ATOM 1765 O SER 94 5 244 -3 891 -37 224 1 00 0 00
ATOM 1766 N MET 95 4 298 -3 011 -35 367 1 00 0 00
ATOM 1767 HN MET 95 4 256 -2 915 -34 373 1 00 0 00
ATOM 1768 CA MET 95 3 300 -2 252 -36 101 1 00 0 00
ATOM 1769 HA MET 95 3 654 -2 222 -37 131 1 00 0 00
ATOM 1770 CB MET 95 3 190 -0 846 -35 508 1 00 0 00
ATOM 1771 2HB MET 95 2 362 -0 313 -35 976 1 00 0 00
ATOM 1772 1HB MET 95 4 097 -0 282 -35 730 1 00 0 00
ATOM 1773 QB MET 95 3 229 -0 298 -35 853 1 00 0 00
ATOM 1774 CG MET 95 2 977 -0 904 -33 994 1 00 0 00
ATOM 1775 2HG MET 95 2 578 -1 878 -33 712 1 00 0 00
ATOM 1776 1HG MET 95 2 239 -0 159 -33 694 1 00 0 00
ATOM 1777 QG MET 95 2 409 -1 019 -33 703 1 00 0 00
ATOM 1778 SD MET 95 4 520 -0 609 -33 148 1 00 0. 00
ATOM 1779 QE MET 95 3 785 0 239 -31 316 1 00 0. 00
ATOM 1780 CE MET 95 3 909 0 095 -31 626 1 00 0. 00
ATOM 1781 IHE MET 95 3. 972 -0 648 -30. 831 1. 00 0. 00
ATOM 1782 2HE MET 95 2 871 0 401 -31. 757 1. 00 0. 00
ATOM 1783 3HE MET 95 4 512 0 964 -31. 359 1. 00 0. 00
ATOM 1784 C MET 95 1. 934 -2. 939 -36. 040 1. 00 0. 00
ATOM 1785 O MET 95 1. 538 -3. 449 -34. 993 1. 00 0. 00
ATOM 1786 N THR 96 1. 252 -2. 931 -37. 176 1. 00 0. 00
ATOM 1787 HN THR 96 1. 581 -2. 514 -38. 023 1. 00 0. 00
ATOM 1788 CA THR 96 0. 061 -3. 547 -37. 265 1. 00 0. 00 ATOM 1789 HA THR 96 0.166 -4.254 -36.441 1.00 0.00
ATOM 1790 CB THR 96 0 .141 -4 .299 -38 .595 1 .00 0 .00
ATOM 1791 HB THR 96 0 .452 -3 .633 -39 .400 1 .00 0 .00
ATOM 1792 QG2 THR 96 1 .266 -5 .819 -38 .502 1 .00 0 .00
ATOM 1793 OGl THR 96 -1 .164 -4 .843 -38 .766 1 .00 0 .00
ATOM 1794 HG1 THR 96 -1 .378 -4 .922 -39 .740 1 .00 0 .00
ATOM 1795 CG2 THR 96 1 .050 -5 .527 -38 .520 1 .00 0 .00
ATOM 1796 1HG2 THR 96 1 .992 -5 .314 -39 .027 1 .00 0 .00
ATOM 1797 2HG2 THR 96 1 .247 -5 .770 -37 .476 1 .00 0 .00
ATOM 1798 3HG2 THR 96 0 .561 -6 .372 -39 .004 1 .00 o . .00
ATOM 1799 C THR 96 1 .157 -2 .494 -37 .095 1 .00 0. .00
ATOM 1800 O THR 96 0 .873 -1 .298 -37 .050 1 .00 0 .00
ATOM 1801 N ILE 97 2 .388 -2. .976 -37 .005 1 .00 0 .00
ATOM 1802 HN ILE 97 2. .611 -3, .950 -37 .042 1 .00 0 .00
ATOM 1803 CA ILE 97 3. .529 -2 .091 -36 .841 1 .00 0 .00
ATOM 1804 HA ILE 97 3 .221 -1 .282 -36 .178 1 .00 0. .00
ATOM 1805 CB ILE 97 4, .682 -2, .825 -36 .153 1. .00 0. .00
ATOM 1806 HB ILE 97 4 .269 -3, .673 -35 .607 1. .00 0, .00
ATOM 1807 QG2 ILE 97 5 .900 -3 .518 -37. .426 1. .00 0, .00
ATOM 1808 CG2 ILE 97 5, .666 -3, .385 -37, .182 1, .00 0, .00
ATOM 1809 1HG2 ILE 97 5, .123 -3, .689 -38, .076 1, .00 0, .00
ATOM 1810 2HG2 ILE 97 6, .395 -2, .617 -37, .443 1, .00 0, .00
ATOM 1811 3HG2 ILE 97 6, .183 -4, .246 -36, .759 1, .00 0. .00
ATOM 1812 CGI ILE 97 5, .374 -1, .922 -35, .130 1, .00 0, .00
ATOM 1813 2HG1 ILE 97 5, .909 -1, .125 -35 .646 1, .00 0, .00
ATOM 1814 1HG1 ILE 97 4, .626 -1, .446 -34, .496 1, .00 0, .00
ATOM 1815 QG1 ILE 97 5, .267 -1, .285 -35, .071 1, .00 0, .00
ATOM 1816 QD1 ILE 97 6, .581 -2, .912 -34, .059 1, .00 0, .00
ATOM 1817 CDl ILE 97 6, .350 -2, .722 -34 .264 1, .00 0, .00
ATOM 1818 1HD1 ILE 97 6, .226 -2. .438 -33, .220 1. .00 0. .00
ATOM 1819 2HD1 ILE 97 6, .147 -3, .787 -34, .378 1, .00 0, .00
ATOM 1820 3HD1 ILE 97 7, .371 -2, .511 -34, .580 1, .00 0, .00
ATOM 1821 C ILE 97 3. .903 -1. .492 -38, .198 1. .00 0. ,00
ATOM 1822 O ILE 97 3. .477 -1. .989 -39, .239 1. .00 0. .00
ATOM 1823 N LYS 98 4, .696 -0. .432 -38, .142 1. .00 0. .00
ATOM 1824 HN LYS 98 5. .038 -0. .033 -37. .291 1. ,00 0. .00
ATOM 1825 CA LYS 98 5. .132 0. .241 -39. .354 1. ,00 0. .00
ATOM 1826 HA LYS 98 4. .812 -0. .368 -40. ,199 1. .00 0. .00
ATOM 1827 CB LYS 98 4. .444 1. .601 -39. .490 1. .00 0. .00
ATOM 1828 2HB LYS 98 3. .722 1. ,729 -38. .684 1. ,00 0. ,00
ATOM 1829 1HB LYS 98 5. .181 2. ,397 -39. ,387 1. ,00 0. ,00
ATOM 1830 QB LYS 98 4. ,452 2. .063 -39. .035 1. .00 0. ,00
ATOM 1831 CG LYS 98 3. ,737 1. ,725 -40. ,841 1. ,00 0. 00
ATOM 1832 2HG LYS 98 3. ,467 2. ,766 -41. .020 1. ,00 0. 00
ATOM 1833 1HG LYS 98 4. ,417 1. ,429 -41. .640 1. ,00 0. .00
ATOM 1834 QG LYS 98 3. ,942 2. ,097 -41. ,330 1. 00 0. 00
ATOM 1835 CD LYS 98 2. ,481 0. ,852 -40. ,884 1. ,00 0. 00
ATOM 1836 2HD LYS 98 2. ,718 -0. ,152 -40. ,532 1. ,00 0. 00
ATOM 1837 1HD LYS 98 1. 729 1. 258 -40. ,207 1. 00 0. 00
ATOM 1838 QD LYS 98 2. ,223 0. ,553 -40. ,370 1. ,00 0. 00
ATOM 1839 CE LYS 98 1. ,912 0. ,780 -42. ,303 1. ,00 0. 00
ATOM 1840 2HE LYS 98 0. ,931 0. ,305 -42. .284 1. .00 0. .00
ATOM 1841 IHE LYS 98 1. .771 1. ,786 -42. .696 1. ,00 0. 00
ATOM 1842 QE LYS 98 1. ,351 1. ,046 -42. .490 1. ,00 0. 00
ATOM 1843 NZ LYS 98 2. ,822 0. ,018 -43. ,187 1. ,00 0. 00
ATOM 1844 1HZ LYS 98 3. 215 0. 599 -43. .919 1. 00 0. 00
ATOM 1845 2HZ LYS 98 3. 603 -0. 380 -42. .677 1. ,00 0. 00
ATOM 1846 QZ LYS 98 3. 409 0. 109 -43. .298 1. 00 0. 00
ATOM 1847 C LYS 98 6. 660 0. 321 -39. 365 1. 00 0. 00
ATOM 1848 O LYS 98 7. 324 -0. 293 -38. 531 1. 00 0. 00
ATOM 1849 N THR 99 7. 174 1. 083 -40. .320 1. 00 0. 00
ATOM 1850 HN THR 99 6. 627 1. 579 -40. 994 1. 00 0. 00 ATOM 1851 CA THR 99 8.611 1.251 -40.451 1.00 0.00
ATOM 1852 HA THR 99 9 .063 1 .123 -39 .468 1 .00 0 .00
ATOM 1853 CB THR 99 9 .130 0 .166 -41 .397 1 .00 0 .00
ATOM 1854 HB THR 99 10 .177 0 .337 -41 .648 1 .00 0 .00
ATOM 1855 QG2 THR 99 8 .876 -1 .579 -40 .706 1 .00 0 .00
ATOM 1856 OGl THR 99 8 .248 0 .229 -42 .514 1 .00 0 .00
ATOM 1857 HG1 THR 99 8 .660 0 .771 -43 .246 1 .00 0 .00
ATOM 1858 CG2 THR 99 8 .925 -1 .244 -40 .839 1 .00 0 .00
ATOM 1859 1HG2 THR 99 9 .209 -1 .978 -41 .593 1 .00 0 .00
ATOM 1860 2HG2 THR 99 9 .543 -1 .377 -39 .951 1 .00 0 .00
ATOM 1861 3HG2 THR 99 7 .876 -1 .381 -40 .575 1 .00 0 .00
ATOM 1862 C THR 99 8 .942 2 .671 -40 .916 1 .00 0 .00
ATOM 1863 O THR 99 8 .259 3 .220 -41 .778 1 .00 0 .00
ATOM 1864 N GLY 100 9 .990 3 .224 -40 .323 1 .00 0 .00
ATOM 1865 HN GLY 100 10 .540 2 .770 -39 .622 1 .00 0 .00
ATOM 1866 CA GLY 100 10 .419 4 .569 -40 .665 1 .00 0 .00
ATOM 1867 2HA GLY 100 10 .226 4 .759 -41 .721 1 .00 0 .00
ATOM 1868 1HA GLY 100 9 .837 5 .296 -40 .099 1 .00 0 .00
ATOM 1869 QA GLY 100 10 .031 5 .027 -40, .910 1 .00 0. .00
ATOM 1870 C GLY 100 11 .908 4 .761 -40, .371 1 .00 0. .00
ATOM 1871 O GLY 100 12 .728 3. .914 -40, .723 1 .00 0 .00
ATOM 1872 N LYS 101 12 .213 5 .879 -39 .728 1 .00 0 .00
ATOM 1873 HN LYS 101 11, .540 6, .562 -39. .446 1 .00 0, .00
ATOM 1874 CA LYS 101 13, .589 6, .192 -39. .383 1 .00 0, .00
ATOM 1875 HA LYS 101 14, .228 5, .723 -40, .131 1 .00 0, .00
ATOM 1876 CB LYS 101 13, .831 7, .701 -39, .463 1, .00 0, .00
ATOM 1877 2HB LYS 101 13, .214 8. .131 -40. .252 1, .00 0, .00
ATOM 1878 1HB LYS 101 13, .526 8. .172 -38. .528 1, .00 0, .00
ATOM 1879 QB LYS 101 13, .370 8. .151 -39. .390 1, .00 0, .00
ATOM 1880 CG LYS 101 15. .305 8. .006 -39. .737 1, .00 0, .00
ATOM 1881 2HG LYS 101 15, .652 8, .782 -39. .055 1, .00 0, .00
ATOM 1882 1HG LYS 101 15. .906 7. .118 -39. .541 1. .00 0. .00
ATOM 1883 QG LYS 101 15. .779 7. .950 -39. .298 1, .00 0. .00
ATOM 1884 CD LYS 101 15. .512 8. ,460 -41. .183 1, .00 0, .00
ATOM 1885 2HD LYS 101 14. .569 8. .395 -41. .726 1, .00 0, .00
ATOM 1886 1HD LYS 101 15. .817 9. ,507 -41. ,199 1. .00 0. .00
ATOM 1887 QD LYS 101 15. .193 8. .951 -41. ,463 1. .00 0. .00
ATOM 1888 CE LYS 101 16. .570 7. .604 -41. ,881 1, .00 0, .00
ATOM 1889 2HE LYS 101 17. .566 7. .955 -41. ,611 1, .00 0, .00
ATOM 1890 IHE LYS 101 16. ,493 6. ,572 -41. ,541 1. .00 0. .00
ATOM 1891 QE LYS 101 17. ,030 7. ,263 -41. ,576 1. .00 0. ,00
ATOM 1892 NZ LYS 101 16. .398 7. ,663 -43. ,350 1. ,00 0. .00
ATOM 1893 1HZ LYS 101 15. ,948 8. ,522 -43. ,646 1. ,00 0. .00
ATOM 1894 2HZ LYS 101 17. ,285 7. 612 -43. 839 1. ,00 0. ,00
ATOM 1895 QZ LYS 101 16. ,617 8. ,067 -43. 742 1. ,00 0. ,00
ATOM 1896 C LYS 101 13. ,917 5. ,588 -38. 016 1. ,00 0. ,00
ATOM 1897 O LYS 101 14. ,872 4. ,824 -37. 885 1. ,00 0. ,00
ATOM 1898 N HIS 102 13. ,107 5. .953 -37. 033 1. ,00 0. ,00
ATOM 1899 HN HIS 102 12. 333 6. 575 -37. 149 1. 00 0. 00
ATOM 1900 CA HIS 102 13. 300 5. 457 -35. 681 1. 00 0. 00
ATOM 1901 HA HIS 102 14. 203 4. 847 -35. 698 1. 00 0. 00
ATOM 1902 CB HIS 102 13. 534 6. 613 -34. 707 1. 00 0. 00
ATOM 1903 2HB HIS 102 13. 494 6. 229 -33. 687 1. 00 0. 00
ATOM 1904 1HB HIS 102 14. 540 7. 005 -34. 859 1. 00 0. 00
ATOM 1905 QB HIS 102 14. 017 6. 617 -34. 273 1. 00 0. 00
ATOM 1906 CG HIS 102 12. 542 7. 743 -34. 844 1. 00 0. 00
ATOM 1907 ND1 HIS 102 11. 265 7. 688 -34. 312 1. 00 0. 00
ATOM 1908 CD2 HIS 102 12. 653 8. 957 -35. 456 1. 00 0. 00
ATOM 1909 HDl HIS 102 10. 878 6. 922 -33. 800 1. 00 0. 00
ATOM 1910 CE1 HIS 102 10. 644 8. 823 -34. 599 1. 00 0. 00
ATOM 1911 NE2 HIS 102 11. 506 9. 607 -35. 308 1. 00 0. 00
ATOM 1912 HD2 HIS 102 13. 534 9. 329 -35. 978 1. 00 0. 00 ATOM 1913 HEI HIS 102 9.624 9.083 -34.317 1.00 0.00
ATOM 1914 C HIS 102 12 .113 4 .577 -35 .284 1 .00 0 .00
ATOM 1915 O HIS 102 11 .547 4 .743 -34 .204 1 .00 0 .00
ATOM 1916 N VAL 103 11 .771 3 .661 -36 .177 1 .00 0 .00
ATOM 1917 HN VAL 103 12 .237 3 .533 -37 .053 1 .00 0 .00
ATOM 1918 CA VAL 103 10 .662 2 .755 -35 .933 1 .00 0 .00
ATOM 1919 HA VAL 103 10 .432 2 .795 -34 .868 1 .00 0 .00
ATOM 1920 CB VAL 103 9 .425 3 .223 -36 .702 1 .00 0 .00
ATOM 1921 HB VAL 103 9 .705 3 .339 -37 .749 1 .00 0 .00
ATOM 1922 QG1 VAL 103 8 .040 1 .935 -36 .611 1 .00 0 .00
ATOM 1923 QG2 VAL 103 8 .829 4 .905 -36 .070 1 .00 0 .00
ATOM 1924 CGI VAL 103 8 .306 2 .182 -36 .628 1 .00 0 .00
ATOM 1925 1HG1 VAL 103 7 .359 2 .646 -36 .904 1 .00 0 .00
ATOM 1926 2HG1 VAL 103 8 .524 1. .365 -37, .315 1 .00 0 .00
ATOM 1927 3HG1 VAL 103 8 .238 1 .794 -35 .612 1 .00 0 .00
ATOM 1928 CG2 VAL 103 8 .943 4 .583 -36 .191 1 .00 0 .00
ATOM 1929 1HG2 VAL 103 8 .549 4 .472 -35 .181 1 .00 0 .00
ATOM 1930 2HG2 VAL 103 9 .778 5. .283 -36 .181 1 .00 0 .00
ATOM 1931 3HG2 VAL 103 8 .159 4 .961 -36 .847 1 .00 0 .00
ATOM 1932 QQG VAL 103 8 .435 3, .420 -36 .340 1 .00 0 .00
ATOM 1933 C VAL 103 11 .085 1 .329 -36 .293 1 .00 0 .00
ATOM 1934 O VAL 103 10 .838 0. .394 -35 .532 1 .00 0 .00
ATOM 1935 N ASP 104 11 .715 1, .207 -37, .452 1 .00 0 .00
ATOM 1936 HN ASP 104 11 .912 1, .973 -38, .064 1 .00 0 .00
ATOM 1937 CA ASP 104 12 .174 -0 .089 -37 .921 1 .00 0 .00
ATOM 1938 HA ASP 104 12. .523 0, .083 -38, .939 1 .00 0 .00
ATOM 1939 CB ASP 104 13, .308 -0, .622 -37, .043 1, .00 0 .00
ATOM 1940 2HB ASP 104 13, .067 -1, .642 -36, .745 1, .00 0, .00
ATOM 1941 1HB ASP 104 14, .218 -0, .671 -37, .641 1, .00 0 .00
ATOM 1942 QB ASP 104 13. .643 -1. .157 -37. .193 1. .00 0, .00
ATOM 1943 CG ASP 104 13. .594 0. ,201 -35. .785 1. .00 0. .00
ATOM 1944 OD1 ASP 104 13, .721 1. .433 -35. .843 1, .00 0, .00
ATOM 1945 OD2 ASP 104 13. .687 -0. ,483 -34. .696 1. .00 0, .00
ATOM 1946 HD2 ASP 104 12. .968 -1. ,178 -34. .666 1. ,00 0. .00
ATOM 1947 C ASP 104 11. ,018 -1. .088 -37. ,859 1. .00 0. .00
ATOM 1948 0 ASP 104 9. ,877 -0. ,708 -37. ,598 1. ,00 0. ,00
ATOM 1949 N ALA 105 11. ,352 -2. ,347 -38. .102 1. ,00 0. .00
ATOM 1950 HN ALA 105 12. .282 -2. ,648 -38. ,313 1. ,00 0. ,00
ATOM 1951 CA ALA 105 10. .356 -3. .404 -38. .077 1. .00 0. .00
ATOM 1952 HA ALA 105 9. ,381 -2. ,945 -38. ,241 1. ,00 0. .00
ATOM 1953 QB ALA 105 10. ,697 -4. ,629 -39. .480 1. ,00 0. ,00
ATOM 1954 CB ALA 105 10. .632 -4. ,394 -39. ,211 1. ,00 0. ,00
ATOM 1955 1HB ALA 105 9. ,697 -4. 859 -39. ,523 1. ,00 0. .00
ATOM 1956 2HB ALA 105 11. ,074 -3. 865 -40. ,055 1. ,00 0. .00
ATOM 1957 3HB ALA 105 11. ,321 -5. ,163 -38. ,862 1. .00 0. .00
ATOM 1958 C ALA 105 10. ,365 -4. 076 -36. .702 1. ,00 0. ,00
ATOM 1959 O ALA 105 9. ,738 -5. 116 -36. .511 1. ,00 0. ,00
ATOM 1960 N ASN 106 11. ,084 -3. 452 -35. ,780 1. ,00 0. ,00
ATOM 1961 HN ASN 106 11. 591 -2. 606 -35. 943 1. 00 0. 00
ATOM 1962 CA ASN 106 11. 184 -3. 976 -34. 428 1. 00 0. 00
ATOM 1963 HA ASN 106 10. 829 -5. 005 -34. 493 1. 00 0. 00
ATOM 1964 CB ASN 106 12. ,628 -3. 932 -33. 925 1. 00 0. 00
ATOM 1965 2HB ASN 106 13. 281 -3. 566 -34. 717 1. 00 0. 00
ATOM 1966 1HB ASN 106 12. 706 -3. 228 -33. 096 1. 00 0. 00
ATOM 1967 QB ASN 106 12. 994 -3. 397 -33. 907 1. 00 0. 00
ATOM 1968 CG ASN 106 13. 093 -5. 317 -33. 471 1. 00 0. 00
ATOM 1969 OD1 ASN 106 13. 234 -5. 597 -32. 292 1. 00 0. 00
ATOM 1970 ND2 ASN 106 13. 324 -6. 164 -34. 469 1. 00 0. 00
ATOM 1971 1HD2 ASN 106 13. 189 -5. 870 -35. 416 1. 00 0. 00
ATOM 1972 2HD2 ASN 106 13. 632 -7. 095 -34. 274 1. 00 0. 00
ATOM 1973 QD2 ASN 106 13. 411 -6. 483 -34. 845 1. 00 0. 00
ATOM 1974 C ASN 106 10. 329 -3. 121 -33. 490 1. 00 0. 00 ATOM 1975 O ASN 106 9.998 -3.548 -32.385 1.00 0.00
ATOM 1976 N GLY 107 9 .998 -1 .930 -33 .965 1 .00 0 .00
ATOM 1977 HN GLY 107 10 .272 -1 .590 -34 .865 1 .00 0 .00
ATOM 1978 CA GLY 107 9 .189 -1 .011 -33 .182 1 .00 0 .00
ATOM 1979 2HA GLY 107 8 .839 -0 .197 -33 .818 1 .00 0 .00
ATOM 1980 1HA GLY 107 8 .305 -1 .527 -32 .809 1 .00 0 .00
ATOM 1981 QA GLY 107 8 .572 -0 .862 -33 .313 1 .00 0 .00
ATOM 1982 C GLY 107 9 .987 -0 .441 -32 .008 1 .00 0 .00
ATOM 1983 O GLY 107 9 .415 0 .144 -31 .089 1 .00 0 .00
ATOM 1984 N LYS 108 11 .297 -0 .630 -32 .077 1 .00 0 .00
ATOM 1985 HN LYS 108 11 .754 -1 .106 -32 .828 1 .00 0 .00
ATOM 1986 CA LYS 108 12 .180 -0 .142 -31 .031 1 .00 0 .00
ATOM 1987 HA LYS 108 11 .567 0 .054 -30 .151 1 .00 0 .00
ATOM 1988 CB LYS 108 13 .197 -1 .217 -30 .644 1 .00 0 .00
ATOM 1989 2HB LYS 108 12 .680 -2 .073 -30. .209 1 .00 0 .00
ATOM 1990 1HB LYS 108 13 .710 -1 .576 -31 .536 1 .00 0 .00
ATOM 1991 QB LYS 108 13 .195 -1 .824 -30 .872 1 .00 0 .00
ATOM 1992 CG LYS 108 14. .219 -0 .670 -29, .645 1. .00 0 .00
ATOM 1993 2HG LYS 108 14 .351 0 .400 -29. .803 1 .00 0. .00
ATOM 1994 1HG LYS 108 13 .845 -0 .799 -28, .629 1 .00 0. .00
ATOM 1995 QG LYS 108 14 .098 -0 .200 -29 .216 1 .00 o . .00
ATOM 1996 CD LYS 108 15, .565 -1. .382 -29, .793 1 .00 0, .00
ATOM 1997 2HD LYS 108 15, .401 -2 .440 -30, .001 1, .00 0, .00
ATOM 1998 1HD LYS 108 16, .107 -0 .971 -30, .645 1 .00 0 .00
ATOM 1999 QD LYS 108 15 .754 -1 .705 -30, .323 1. .00 o . .00
ATOM 2000 CE LYS 108 16, .408 -1, .231 -28, .525 1, .00 0, .00
ATOM 2001 2HE LYS 108 16, .854 -0, .237 -28, .494 1 .00 0, .00
ATOM 2002 IHE LYS 108 15, .771 -1, .322 -27, .645 1 .00 0. .00
ATOM 2003 QE LYS 108 16, .312 -0, .780 -28, .070 1 .00 0, .00
ATOM 2004 NZ LYS 108 17, .471 -2, .260 -28, .484 1 .00 0, .00
ATOM 2005 1HZ LYS 108 18, .258 -2, .017 -29, .075 1. .00 0, .00
ATOM 2006 2HZ LYS 108 17, .837 -2, .391 -27, .547 1. .00 0, .00
ATOM 2007 QZ LYS 108 18. .047 -2, .204 -28, .311 1, .00 0, .00
ATOM 2008 C LYS 108 12. .817 1, .174 -31. .481 1. .00 0, .00
ATOM 2009 O LYS 108 13. .787 1. .171 -32. .239 1, .00 0, .00
ATOM 2010 N ILE 109 12. .248 2. .267 -30. ,996 1. .00 0, .00
ATOM 2011 HN ILE 109 11. ,460 2. ,261 -30. ,380 1, .00 0, .00
ATOM 2012 CA ILE 109 12. .748 3. .587 -31. .338 1. .00 0, .00
ATOM 2013 HA ILE 109 12. .413 3. .811 -32. ,351 1. .00 0, .00
ATOM 2014 CB ILE 109 12. ,141 4. ,647 -30. ,417 1. .00 0. .00
ATOM 2015 HB ILE 109 12. ,527 4. .486 -29. ,410 1. .00 0. .00
ATOM 2016 QG2 ILE 109 12. .665 6. .387 -30. ,946 1. .00 0. .00
ATOM 2017 CG2 ILE 109 12. 564 6. 053 -30. 844 1. ,00 0. ,00
ATOM 2018 1HG2 ILE 109 13. 585 6. ,025 -31. 227 1. ,00 0. ,00
ATOM 2019 2HG2 ILE 109 11. ,894 6. ,414 -31. 624 1. ,00 0. ,00
ATOM 2020 3HG2 ILE 109 12. 516 6. ,724 -29. 986 1. ,00 0. ,00
ATOM 2021 CGI ILE 109 10. 619 4. 503 -30. 345 1. ,00 0. 00
ATOM 2022 2HG1 ILE 109 10. 149 5. 463 -30. 562 1. ,00 0. 00
ATOM 2023 1HG1 ILE 109 10. 280 3. 802 -31. 107 1. ,00 0. 00
ATOM 2024 QG1 ILE 109 10. 215 4. 632 -30. 835 1. 00 0. 00
ATOM 2025 QD1 ILE 109 10. 075 3. 899 -28. 635 1. ,00 0. 00
ATOM 2026 CDl ILE 109 10. 179 4. 015 -28. 963 1. ,00 0. 00
ATOM 2027 1HD1 ILE 109 9. 092 4. 054 -28. 893 1. ,00 0. 00
ATOM 2028 2HD1 ILE 109 10. 516 2. 988 -28. 817 1. 00 0. 00
ATOM 2029 3HD1 ILE 109 10. 617 4. 653 -28. 196 1. 00 0. 00
ATOM 2030 C ILE 109 14. 278 3. 567 -31. 327 1. 00 0. 00
ATOM 2031 0 ILE 109 14. 896 3. 668 -30. 268 1. 00 0. 00
ATOM 2032 N TYR 110 14. 845 3. 435 -32. 517 1. 00 0. 00
ATOM 2033 HN TYR 110 14. 335 3. 353 -33. 374 1. 00 0. 00
ATOM 2034 CA TYR 110 16. 291 3. 399 -32. 658 1. 00 0. 00
ATOM 2035 HA TYR 110 16. 712 3. 054 -31. 713 1. 00 0. 00
ATOM 2036 CB TYR 110 16. 578 2. 469 -33. 838 1. 00 0. 00 ATOM 2037 2HB TYR 110 15.634 2.195 -34.309 1.00 0.00
ATOM 2038 1HB TYR 110 17 .160 3 .012 -34 .582 1 .00 0 .00
ATOM 2039 QB TYR 110 16 .397 2 .603 -34 .446 1 .00 0 .00
ATOM 2040 QD TYR 110 17 .400 1 .071 -33 .419 1 .00 0 .00
ATOM 2041 QE TYR 110 18 .649 -1 .050 -32 .784 1 .00 0 .00
ATOM 2042 QR TYR 110 18 .025 0 .011 -33 .102 1 .00 0 .00
ATOM 2043 CG TYR 110 17 .329 1 .192 -33 .456 1 .00 0 .00
ATOM 2044 CDl TYR 110 16 .772 -0 .042 -33 .721 1 .00 0 .00
ATOM 2045 HDl TYR 110 15 .797 -0 .108 -34 .204 1 .00 0 .00
ATOM 2046 CE1 TYR 110 17 .479 -1 .244 -33 .362 1 .00 0 .00
ATOM 2047 HEI TYR 110 17 .051 -2 .225 -33 .566 1 .00 0 .00
ATOM 2048 CZ TYR 110 18 .694 -1 .127 -32 .761 1 .00 o . .00
ATOM 2049 CE2 TYR 110 19 .271 0 .073 -32 .485 1 .00 0 .00
ATOM 2050 HE2 TYR 110 20 .247 0 .125 -32 .002 1 .00 0 .00
ATOM 2051 CD2 TYR 110 18 .564 1 .275 -32 .845 1 .00 0 .00
ATOM 2052 HD2 TYR 110 19 .004 2 .250 -32 .635 1 .00 0 .00
ATOM 2053 OH TYR 110 19 .362 -2 .262 -32 .421 1 .00 0 .00
ATOM 2054 HH TYR 110 18 .712 -3 .000 -32 .243 1 .00 0 .00
ATOM 2055 C TYR 110 16 .845 4 .790 -32 .974 1 .00 0, .00
ATOM 2056 O TYR 110 16 .771 5 .248 -34 .113 1 .00 0. .00
ATOM 2057 N LEU 111 17 .388 5 .423 -31 .944 1 .00 0. .00
ATOM 2058 HN LEU 111 17, .445 5, .044 -31, .021 1, .00 0, .00
ATOM 2059 CA LEU 111 17, .955 6, .753 -32 .098 1 .00 0, .00
ATOM 2060 HA LEU 111 17, .929 6 .998 -33. .160 1, .00 0, .00
ATOM 2061 CB LEU 111 17, .094 7 .789 -31. .373 1 .00 0 .00
ATOM 2062 2HB LEU 111 17. .087 7, .546 -30, .310 1. .00 0, .00
ATOM 2063 1HB LEU 111 17, .572 8, .764 -31, .474 1, .00 0, .00
ATOM 2064 QB LEU 111 17, .330 8, .155 -30, .892 1. .00 0. .00
ATOM 2065 CG LEU 111 15. .646 7. .910 -31. .850 1. .00 0. .00
ATOM 2066 HG LEU 111 15. .286 6. ,914 -32. .106 1. .00 0. ,00
ATOM 2067 QD1 LEU 111 14. .530 8. ,570 -30, .470 1, .00 0. .00
ATOM 2068 QD2 LEU 111 15. .534 8, .965 -33, .418 1, .00 0. .00
ATOM 2069 CDl LEU 111 14. .744 8. ,443 -30. .734 1. .00 0. .00
ATOM 2070 1HD1 LEU 111 14. .842 7. ,808 -29. .854 1. .00 0. .00
ATOM 2071 2HD1 LEU 111 15. .040 9. ,461 -30, .483 1. .00 0. ,00
ATOM 2072 3HD1 LEU 111 13. .708 8. .439 -31. .072 1. .00 0. .00
ATOM 2073 CD2 LEU 111 15. .555 8. .763 -33. .117 1. .00 0. ,00
ATOM 2074 1HD2 LEU 111 16. ,156 8. .308 -33. .904 1. .00 0. ,00
ATOM 2075 2HD2 LEU 111 14. .516 8. .823 -33, .441 1, .00 0. ,00
ATOM 2076 3HD2 LEU 111 15. .929 9. ,765 -32. .907 1. .00 0. .00
ATOM 2077 QQD LEU 111 15. ,032 8. ,767 -31. .943 1, .00 0. ,00
ATOM 2078 C LEU 111 19. ,415 6. .736 -31. .640 1. .00 0. ,00
ATOM 2079 O LEU 111 19. ,700 6. .910 -30. ,456 1. ,00 0. ,00
ATOM 2080 N PRO 112 20. ,325 6. ,520 -32. ,628 1. ,00 0. ,00
ATOM 2081 CD PRO 112 20. ,024 6. ,310 -34. ,041 1. ,00 0. ,00
ATOM 2082 CA PRO 112 21. ,748 6. ,479 -32. .338 1. ,00 0. ,00
ATOM 2083 HA PRO 112 21. 916 5. 968 -31. ,495 1. ,00 0. 00
ATOM 2084 CB PRO 112 22. ,375 5. 799 -33. ,544 1. ,00 0. 00
ATOM 2085 2HB PRO 112 23. ,310 6. 285 -33. ,824 1. ,00 0. 00
ATOM 2086 1HB PRO 112 22. 611 4. 757 -33. 326 1. 00 0. 00
ATOM 2087 QB PRO 112 22. 960 5. 521 -33. 575 1. 00 0. 00
ATOM 2088 CG PRO 112 21. 350 5. 903 -34. 661 1. 00 0. 00
ATOM 2089 2HG PRO 112 21. 666 6. 638 -35. 402 1. 00 0. 00
ATOM 2090 1HG PRO 112 21. 252 4. 950 -35. 180 1. 00 0. 00
ATOM 2091 QG PRO 112 21. 459 5. 794 -35. 291 1. 00 0. 00
ATOM 2092 2HD PRO 112 19. 633 7. 218 -34. 501 1. 00 0. 00
ATOM 2093 1HD PRO 112 19. 269 5. 535 -34. 174 1. 00 0. 00
ATOM 2094 QD PRO 112 19. 451 6. 376 -34. 338 1. 00 0. 00
ATOM 2095 C PRO 112 22. 298 7. 885 -32. 091 1. 00 0. 00
ATOM 2096 O PRO 112 23. 362 8. 043 -31. 494 1. 00 0. 00
ATOM 2097 N TYR 113 21. 549 8. 870 -32. 563 1. 00 0. 00
ATOM 2098 HN TYR 113 20. 685 8. 733 -33. 048 1. 00 0. 00 ATOM 2099 CA TYR 113 21.948 10.258 -32.401 1.00 0.00
ATOM 2100 HA TYR 113 23 .037 10 .300 -32 .432 1 .00 0 .00
ATOM 2101 CB TYR 113 21 .268 11 .028 -33 .535 1 .00 0 .00
ATOM 2102 2HB TYR 113 20 .893 10 .316 -34 .270 1 .00 0 .00
ATOM 2103 1HB TYR 113 20 .404 11 .557 -33 .134 1 .00 0 .00
ATOM 2104 QB TYR 113 20 .648 10 .936 -33 .702 1 .00 0 .00
ATOM 2105 QD TYR 113 22 .268 12 .128 -34 .307 1 .00 0 .00
ATOM 2106 QE TYR 113 23 .785 13 .797 -35 .479 1 .00 0 .00
ATOM 2107 QR TYR 113 23 .027 12 .962 -34 .893 1 .00 0 .00
ATOM 2108 CG TYR 113 22 .181 12 .032 -34 .240 1 .00 0 .00
ATOM 2109 CDl TYR 113 22 .451 13 .251 -33 .652 1 .00 0 .00
ATOM 2110 HDl TYR 113 22 .013 13 .498 -32 .685 1 .00 0 .00
ATOM 2111 CE1 TYR 113 23 .310 1 .197 -34 .316 1 .00 0. .00
ATOM 2112 HEI TYR 113 23 .531 15 .163 -33 .862 1 .00 0 .00
ATOM 2113 CZ TYR 113 23 .840 13 .857 -35 .521 1 .00 0. .00
ATOM 2114 CE2 TYR 113 23 .595 12 .665 -36 .129 1 .00 0. .00
ATOM 2115 HE2 TYR 113 24, .040 12, .431 -37, .096 1 .00 0, .00
ATOM 2116 CD2 TYR 113 22, .736 11 .720 -35, .465 1 .00 0, .00
ATOM 2117 HD2 TYR 113 22, .523 10 .757 -35 .929 1 .00 0, .00
ATOM 2118 OH TYR 113 24 .652 14 .750 -36 .148 1 .00 0 .00
ATOM 2119 HH TYR 113 25, .510 14, .846 -35, .643 1 .00 0, .00
ATOM 2120 C TYR 113 21, .465 10 .815 -31, .061 1 .00 0, .00
ATOM 2121 O TYR 113 22, .154 11 .616 -30. .432 1 .00 0, .00
ATOM 2122 N LEU 114 20, .283 10, .368 -30. .662 1, .00 0, .00
ATOM 2123 HN LEU 114 19, .728 9, .716 -31, .179 1 .00 0, .00
ATOM 2124 CA LEU 114 19, .699 10 .811 -29, .408 1 .00 0, .00
ATOM 2125 HA LEU 114 19. .930 11 .871 -29, .297 1 .00 0, .00
ATOM 2126 CB LEU 114 18. .175 10, .683 -29, .451 1, .00 0, .00
ATOM 2127 2HB LEU 114 17. .846 10, .838 -30, .479 1, .00 0, .00
ATOM 2128 1HB LEU 114 17. .909 9, .660 -29. .182 1, .00 0, .00
ATOM 2129 QB LEU 114 17. .877 10, .249 -29, .831 1, .00 0, .00
ATOM 2130 CG LEU 114 17. ,395 11. .638 -28. ,546 1, .00 0. .00
ATOM 2131 HG LEU 114 18. .075 12. .017 -27. .783 1, .00 0. .00
ATOM 2132 QD1 LEU 114 16. ,761 13. .131 -29. .521 1, .00 0. .00
ATOM 2133 QD2 LEU 114 15. ,997 10. .732 -27. .647 1, .00 0. .00
ATOM 2134 CDl LEU 114 16. ,883 12. ,845 -29. ,334 1. ,00 0. ,00
ATOM 2135 1HD1 LEU 114 16. ,410 12. ,503 -30. ,255 1. .00 0. ,00
ATOM 2136 2HD1 LEU 114 16. ,154 13. .389 -28. ,733 1. ,00 0. ,00
ATOM 2137 3HD1 LEU 114 17. ,718 13. .502 -29. ,576 1. ,00 0. .00
ATOM 2138 CD2 LEU 114 16. ,265 10. ,905 -27. ,820 1. ,00 0. ,00
ATOM 2139 1HD2 LEU 114 15. ,333 11. ,041 -28. ,368 1. ,00 0. ,00
ATOM 2140 2HD2 LEU 114 16. ,500 9. ,843 -27. ,760 1. ,00 0. ,00
ATOM 2141 3HD2 LEU 114 16. ,157 11. ,311 -26. .814 1. ,00 0. ,00
ATOM 2142 QQD LEU 114 16. 379 11. ,931 -28. 584 1. 00 0. 00
ATOM 2143 C LEU 114 20. 348 10. ,049 -28. 251 1. ,00 0. 00
ATOM 2144 O LEU 114 20. ,256 10. ,469 -27. 098 1. ,00 0. .00
ATOM 2145 N HIS 115 20. .989 8. ,943 -28. .598 1. ,00 0. .00
ATOM 2146 HN HIS 115 21. 059 8. .609 -29. 538 1. 00 0. 00
ATOM 2147 CA HIS 115 21. 653 8. ,119 -27. 603 1. 00 0. 00
ATOM 2148 HA HIS 115 20. 931 7. ,952 -26. 803 1. ,00 0. .00
ATOM 2149 CB HIS 115 22. 025 6. 755 -28. 187 1. 00 0. 00
ATOM 2150 2HB HIS 115 21. 142 6. 116 -28. 181 1. 00 0. 00
ATOM 2151 1HB HIS 115 22. 317 6. 885 -29. 229 1. 00 0. 00
ATOM 2152 QB HIS 115 21. 730 6. 500 -28. 705 1. 00 0. 00
ATOM 2153 CG HIS 115 23. 141 6. 055 -27. 450 1. 00 0. 00
ATOM 2154 ND1 HIS 115 22. 935 4. 930 -26. 670 1. 00 0. 00
ATOM 2155 CD2 HIS 115 24. 475 6. 330 -27. 382 1. 00 0. 00
ATOM 2156 HDl HIS 115 22. 056 4. 477 -26. 518 1. 00 0. 00
ATOM 2157 CE1 HIS 115 24. 099 4. 555 -26. 160 1. 00 0. 00
ATOM 2158 NE2 HIS 115 25. 052 5. 424 -26. 602 1. 00 0. 00
ATOM 2159 HD2 HIS 115 24. 981 7. 155 -27. 883 1. 00 0. 00
ATOM 2160 HEI HIS 115 24. 265 3. 701 -25. 503 1. 00 0. 00 ATOM 2161 C HIS 115 22 . 859 8 . 870 -27 . 036 1 . 00 0 . 00
ATOM 2162 O HIS 115 23 .098 8 .848 -25 .830 1 .00 0 .00
ATOM 2163 N GLU 116 23 .588 9 .517 -27 .934 1 .00 0 .00
ATOM 2164 HN GLU 116 23 .386 9 .530 -28 .913 1 .00 0 .00
ATOM 2165 CA GLU 116 24 .764 10 .274 -27 .539 1 .00 0 .00
ATOM 2166 HA GLU 116 25 .194 9 .724 -26 .702 1 .00 0 .00
ATOM 2167 CB GLU 116 25 .784 10 .335 -28 .677 1 .00 0 .00
ATOM 2168 2HB GLU 116 26 .681 10 .854 -28 .338 1 .00 0 .00
ATOM 2169 1HB GLU 116 26 .086 9 .325 -28 .954 1 .00 0 .00
ATOM 2170 QB GLU 116 26 .384 10 .090 -28 .646 1 .00 0 .00
ATOM 2171 CG GLU 116 25 .203 11 .053 -29 .897 1 .00 0 .00
ATOM 2172 2HG GLU 116 24 .385 10 .465 -30 .313 1 .00 0 .00
ATOM 2173 1HG GLU 116 24 .784 12 .012 -29 .593 1 .00 0 .00
ATOM 2174 QG GLU 116 24 .584 11 .239 -29 .953 1 .00 0 .00
ATOM 2175 CD GLU 116 26 .275 11 .273 -30 .966 1 .00 0 .00
ATOM 2176 OEl GLU 116 26 .656 12 .422 -31 .234 1 .00 0 .00
ATOM 2177 OE2 GLU 116 26 .716 10, .198 -31 .525 1 .00 0 .00
ATOM 2178 HE2 GLU 116 26 .123 9 .941 -32 .287 1 .00 0 .00
ATOM 2179 C GLU 116 24 .363 11 .680 -27 .086 1 .00 0 .00
ATOM 2180 O GLU 116 25, .218 12 .544 -26 .903 1 .00 0 .00
ATOM 2181 N TRP 117 23, .061 11, .864 -26 .918 1 .00 0 .00
ATOM 2182 HN TRP 117 22, .372 11 .155 -27 .069 1 .00 0 .00
ATOM 2183 CA TRP 117 22, .537 13, .150 -26, .489 1 .00 0, .00
ATOM 2184 HA TRP 117 23, .156 13, .928 -26, .936 1 .00 0, .00
ATOM 2185 CB TRP 117 21, .113 13, .361 -27, .008 1, .00 0, .00
ATOM 2186 2HB TRP 117 21. .091 14. .262 -27. .622 1, .00 0. .00
ATOM 2187 1HB TRP 117 20. .846 12. .527 -27. .658 1, .00 0, .00
ATOM 2188 QB TRP 117 20, .969 13, .395 -27, .640 1, .00 0, .00
ATOM 2189 CG TRP 117 20, .061 13, .487 -25, .905 1 .00 0, .00
ATOM 2190 CDl TRP 117 19. .947 12. .758 -24. .786 1, .00 0, .00
ATOM 2191 CD2 TRP 117 18. .971 14, .432 -25, .859 1, .00 0, .00
ATOM 2192 CE3 TRP 117 18, .602 15, .439 -26, .768 1 .00 0, .00
ATOM 2193 CE2 TRP 117 18. ,257 14. .213 -24. .700 1, .00 0. .00
ATOM 2194 NE1 TRP 117 18. ,869 13. .162 -24. .026 1, .00 0, .00
ATOM 2195 HDl TRP 117 20. .622 11. .947 -24. .511 1, .00 0, .00
ATOM 2196 HE3 TRP 117 19. ,150 15. ,632 -27. ,690 1. .00 0. .00
ATOM 2197 CZ3 TRP 117 17. ,473 16. .178 -26. .396 1, .00 0. .00
ATOM 2198 CZ2 TRP 117 17. ,128 14. .961 -24. .341 1, .00 0. ,00
ATOM 2199 HEI TRP 117 18. ,555 12. ,736 -23. ,073 1, .00 0. ,00
ATOM 2200 HZ3 TRP 117 17. ,143 16. ,972 -27. ,066 1. .00 0. ,00
ATOM 2201 CH2 TRP 117 16. ,742 15. ,969 -25. .232 1. .00 0. ,00
ATOM 2202 HZ2 TRP 117 16. ,580 14. ,768 -23. ,419 1. .00 0. .00
ATOM 2203 HH2 TRP 117 15. 872 16. 589 -25. ,013 1. .00 0. ,00
ATOM 2204 C TRP 117 22. 633 13. 215 -24. ,964 1. .00 0. ,00
ATOM 2205 O TRP 117 22. 114 14. 143 -24. ,345 1. ,00 0. 00
ATOM 2206 N LYS 118 23. 301 12. 218 -24. 402 1. 00 0. 00
ATOM 2207 HN LYS 118 23. 720 11. 468 -24. 912 1. ,00 0. 00
ATOM 2208 CA LYS 118 23. 472 12. 151 -22. 960 1. ,00 0. 00
ATOM 2209 HA LYS 118 22. 598 11. 644 -22. 551 1. 00 0. 00
ATOM 2210 CB LYS 118 24. 695 11. 303 -22. 605 1. 00 0. 00
ATOM 2211 2HB LYS 118 24. 896 10. 594 -23. 407 1. 00 0. 00
ATOM 2212 1HB LYS 118 25. 573 11. 943 -22. 518 1. 00 0. 00
ATOM 2213 QB LYS 118 25. 235 11. 269 -22. 963 1. 00 0. 00
ATOM 2214 CG LYS 118 24. 476 10. 548 -21. 292 1. 00 0. 00
ATOM 2215 2HG LYS 118 23. 447 10. 683 -20. 959 1. 00 0. 00
ATOM 2216 1HG LYS 118 24. 621 9. 480 -21. 454 1. 00 0. 00
ATOM 2217 QG LYS 118 24. 034 10. 081 -21. 207 1. 00 0. 00
ATOM 2218 CD LYS 118 25. 437 11. 040 -20. 209 1. 00 0. 00
ATOM 2219 2HD LYS 118 25. 499 12. 128 -20. 240 1. 00 0. 00
ATOM 2220 1HD LYS 118 25. 052 10. 771 -19. 226 1. 00 0. 00
ATOM 2221 QD LYS 118 25. 276 11. 450 -19. 733 1. 00 0. 00
ATOM 2222 CE LYS 118 26. 831 10. 439 -20. 399 1. 00 0. 00 ATOM 2223 2HE LYS 118 26.909 9.991 -21.390 1.00 0.00
ATOM 2224 IHE LYS 118 27 .584 11 .226 -20 .346 1 .00 0 .00
ATOM 2225 QE LYS 118 27 .246 10 .609 -20 .868 1 .00 0 .00
ATOM 2226 NZ LYS 118 27 .100 9 .417 -19 .363 1 .00 0 .00
ATOM 2227 1HZ LYS 118 26 .327 8 .769 -19 .260 1 .00 0 .00
ATOM 2228 2HZ LYS 118 27 .921 8 .862 -19 .581 1 .00 0 .00
ATOM 2229 QZ LYS 118 27 .124 8 .815 -19 .420 1 .00 0 .00
ATOM 2230 C LYS 118 23 .520 13 .570 -22 .390 1 .00 0 .00
ATOM 2231 O LYS 118 24 .277 14 .411 -22 .873 1 .00 0 .00
ATOM 2232 N HIS 119 22 .704 13 .792 -21 .371 1 .00 0 .00
ATOM 2233 HN HIS 119 22 .092 13 .102 -20 .984 1. .00 0, .00
ATOM 2234 CA HIS 119 22 .644 15 .095 -20 .730 1 .00 0 .00
ATOM 2235 HA HIS 119 23. .668 15. .365 -20 .474 1. .00 0 .00
ATOM 2236 CB HIS 119 22 .111 16 .153 -21 .698 1 .00 0 .00
ATOM 2237 2HB HIS 119 21 .884 15 .676 -22 .652 1 .00 o . .00
ATOM 2238 1HB HIS 119 21 .172 16 .547 -21 .308 1 .00 0 .00
ATOM 2239 QB HIS 119 21, .528 16 .112 -21 .980 1 .00 0 .00
ATOM 2240 CG HIS 119 23 .062 17 .301 -21 .937 1 .00 0 .00
ATOM 2241 ND1 HIS 119 22 .641 18 .543 -22 .378 1 .00 0 .00
ATOM 2242 CD2 HIS 119 24, .416 17 .381 -21 .793 1 .00 0 .00
ATOM 2243 HDl HIS 119 21, .696 18 .804 -22 .577 1 .00 0, .00
ATOM 2244 CE1 HIS 119 23 .702 19 .329 -22 .491 1 .00 0 .00
ATOM 2245 NE2 HIS 119 24, .801 18, .606 -22 .128 1 .00 0, .00
ATOM 2246 HD2 HIS 119 25, .070 16, .576 -21, .459 1, .00 0, .00
ATOM 2247 HEI HIS 119 23, .698 20, .369 -22 .816 1, .00 0, .00
ATOM 2248 C HIS 119 21. .819 14, .997 -19. .445 1 .00 0 .00
ATOM 2249 O HIS 119 21, .305 13, .930 -19, .113 1, .00 0, .00
ATOM 2250 N PRO 120 21, .716 16, .155 -18, .739 1, .00 0, .00
ATOM 2251 CD PRO 120 22, .311 17, .437 -19, .102 1, .00 0, .00
ATOM 2252 CA PRO 120 20. .962 16. .210 -17, .498 1. .00 0. .00
ATOM 2253 HA PRO 120 21. .144 15. .397 -16. .944 1. .00 0. .00
ATOM 2254 CB PRO 120 21. .433 17. .479 -16. .807 1. .00 0. .00
ATOM 2255 2HB PRO 120 20. .597 18. ,007 -16. .348 1. ,00 0. ,00
ATOM 2256 1HB PRO 120 22. .142 17. ,251 -16. .011 1. ,00 0. .00
ATOM 2257 QB PRO 120 21. .369 17. ,629 -16. .180 1. ,00 0. .00
ATOM 2258 CG PRO 120 22. ,084 18. ,325 -17. .890 1. .00 0. ,00
ATOM 2259 2HG PRO 120 21. .446 19. .170 -18. .149 1, ,00 0. .00
ATOM 2260 1HG PRO 120 23. .029 18. .737 -17. .535 1. ,00 0. .00
ATOM 2261 QG PRO 120 22. .237 18. .954 -17. .842 1. ,00 0. .00
ATOM 2262 2HD PRO 120 21. ,841 17. ,854 -19. .992 1. .00 0. .00
ATOM 2263 1HD PRO 120 23. .374 17. .332 -19. .322 1. .00 0. ,00
ATOM 2264 QD PRO 120 22. .607 17. .593 -19. .657 1. .00 0. ,00
ATOM 2265 C PRO 120 19. ,456 16. ,201 -17. ,770 1. ,00 0. ,00
ATOM 2266 O PRO 120 18. ,672 15. ,764 -16. ,929 1. .00 0. ,00
ATOM 2267 N GLN 121 19. .097 16. ,689 -18. .948 1. .00 0. .00
ATOM 2268 HN GLN 121 19. ,741 17. ,042 -19. ,627 1. ,00 0. ,00
ATOM 2269 CA GLN 121 17. ,700 16. ,743 -19. ,342 1. ,00 0. .00
ATOM 2270 HA GLN 121 17. ,141 16. ,861 -18. ,413 1. ,00 0. .00
ATOM 2271 CB GLN 121 17. 430 17. 948 -20. ,245 1. .00 0. 00
ATOM 2272 2HB GLN 121 16. 360 18. ,037 -20. ,429 1. 00 0. 00
ATOM 2273 1HB GLN 121 17. ,744 18. ,862 -19. ,741 1. ,00 0. ,00
ATOM 2274 QB GLN 121 17. .052 18. .449 -20. .085 1. ,00 0. .00
ATOM 2275 CG GLN 121 18. 173 17. 812 -21. 576 1. 00 0. 00
ATOM 2276 2HG GLN 121 19. 133 18. 324 -21. 515 1. 00 0. 00
ATOM 2277 1HG GLN 121 18. 384 16. 761 -21. 773 1. 00 0. 00
ATOM 2278 QG GLN 121 18. 758 17. 542 -21. 644 1. 00 0. 00
ATOM 2279 CD GLN 121 17. 349 18. 397 -22. 725 1. 00 0. 00
ATOM 2280 OEl GLN 121 16. 201 18. 046 -22. 942 1. 00 0. 00
ATOM 2281 NE2 GLN 121 17. 997 19. 306 -23. 448 1. 00 0. 00
ATOM 2282 1HE2 GLN 121 18. 940 19. 549 -23. 216 1. 00 0. 00
ATOM 2283 2HE2 GLN 121 17. 543 19. 746 -24. 222 1. 00 0. 00
ATOM 2284 QE2 GLN 121 18. 241 19. 648 -23. 719 1. 00 0. 00 ATOM 2285 C GLN 121 17.292 15.439 -20.031 1.00 0.00
ATOM 2286 O GLN 121 16 .181 15 .326 -20 .547 1 .00 0 .00
ATOM 2287 N SER 122 18 .212 14 .486 -20 .017 1 .00 0 .00
ATOM 2288 HN SER 122 19 .113 14 .585 -19 .595 1 .00 0 .00
ATOM 2289 CA SER 122 17 .962 13 .195 -20 .634 1 .00 0 .00
ATOM 2290 HA SER 122 17 .506 13 .419 -21 .598 1 .00 0 .00
ATOM 2291 CB SER 122 19 .268 12 .427 -20 .854 1 .00 0 .00
ATOM 2292 2HB SER 122 19 .102 11 .631 -21 .579 1 .00 0 .00
ATOM 2293 1HB SER 122 20 .014 13 .097 -21 .280 1 .00 0 .00
ATOM 2294 QB SER 122 19 .558 12 .364 -21 .430 1 .00 0 .00
ATOM 2295 OG SER 122 19 .769 11 .869 -19 .642 1 .00 0 .00
ATOM 2296 HG SER 122 20 .721 11 .586 -19 .764 1 .00 0 .00
ATOM 2297 C SER 122 17 .005 12 .376 -19 .765 1 .00 0 .00
ATOM 2298 O SER 122 16 .639 11 .258 -20 .123 1 .00 0 .00
ATOM 2299 N ASP 123 16 .628 12 .965 -18 .639 1 .00 0 .00
ATOM 2300 HN ASP 123 16 .931 13 .875 -18 .356 1 .00 0 .00
ATOM 2301 CA ASP 123 15 .721 12 .304 -17, .717 1 .00 0 .00
ATOM 2302 HA ASP 123 16 .306 11 .503 -17, .265 1 .00 0 .00
ATOM 2303 CB ASP 123 15 .218 13 .276 -16, .648 1 .00 0, .00
ATOM 2304 2HB ASP 123 14, .439 12, .782 -16, .067 1, .00 0, .00
ATOM 2305 1HB ASP 123 16 .036 13, .495 -15, .963 1 .00 0, .00
ATOM 2306 QB ASP 123 15 .238 13 .139 -16, .015 1 .00 0, .00
ATOM 2307 CG ASP 123 14, .663 14, .597 -17. .185 1, .00 0, .00
ATOM 2308 OD1 ASP 123 13, .763 14, .612 -18, .038 1, .00 0, .00
ATOM 2309 OD2 ASP 123 15 .202 15, .658 -16, .686 1 .00 0, .00
ATOM 2310 HD2 ASP 123 16, .171 15, .695 -16. .927 1, .00 0, .00
ATOM 2311 C ASP 123 14, .508 11, .780 -18, .488 1 .00 0, .00
ATOM 2312 O ASP 123 14, .414 11, .960 -19, .701 1 .00 0, .00
ATOM 2313 N LEU 124 13, .610 11, .142 -17, .752 1 .00 0 .00
ATOM 2314 HN LEU 124 13, .693 10. .999 -16. .766 1, .00 0, .00
ATOM 2315 CA LEU 124 12, .407 10, .590 -18. .352 1, .00 0, .00
ATOM 2316 HA LEU 124 12, .677 10, .214 -19, .339 1, .00 0, .00
ATOM 2317 CB LEU 124 11. .899 9. ,399 -17. .537 1, .00 0, .00
ATOM 2318 2HB LEU 124 12. .279 9. .492 -16. .520 1, .00 0, ,00
ATOM 2319 1HB LEU 124 10. .812 9. .461 -17. .479 1, .00 0. .00
ATOM 2320 QB LEU 124 11. .545 9. ,477 -16. ,999 1. .00 0. .00
ATOM 2321 CG LEU 124 12. ,275 8. .014 -18. ,067 1. .00 0. .00
ATOM 2322 HG LEU 124 12. .650 8. .128 -19. ,084 1. ,00 0. .00
ATOM 2323 QD1 LEU 124 13. ,669 7. ,250 -17. ,039 1. ,00 0. ,00
ATOM 2324 QD2 LEU 124 10. ,757 6. ,886 -18. ,154 1. ,00 0. ,00
ATOM 2325 CDl LEU 124 13. ,402 7. ,397 -17. ,237 1. .00 0. ,00
ATOM 2326 1HD1 LEU 124 13. ,018 6. ,538 -16. ,686 1. ,00 0. ,00
ATOM 2327 2HD1 LEU 124 14. ,206 7. 074 -17. 898 1. ,00 0. 00
ATOM 2328 3HD1 LEU 124 13. .784 8. 138 -16. 535 1. ,00 0. 00
ATOM 2329 CD2 LEU 124 11. ,049 7. 102 -18. 137 1. ,00 0. .00
ATOM 2330 1HD2 LEU 124 11. 295 6. 205 -18. 705 1. 00 0. 00
ATOM 2331 2HD2 LEU 124 10. ,746 6. 823 -17. 128 1. ,00 0. 00
ATOM 2332 3HD2 LEU 124 10. ,231 7. 630 -18. 629 1. ,00 0. ,00
ATOM 2333 QQD LEU 124 12. 213 7. 068 -17. 597 1. 00 0. 00
ATOM 2334 C LEU 124 11. 371 11. 704 -18. 525 1. ,00 0. 00
ATOM 2335 O LEU 124 10. 401 11. 545 -19. 263 1. ,00 0. 00
ATOM 2336 N LEU 125 11. 614 12. 806 -17. 831 1. ,00 0. 00
ATOM 2337 HN LEU 125 12. 406 12. 927 -17. 232 1. 00 0. 00
ATOM 2338 CA LEU 125 10. 715 13. 945 -17. 898 1. 00 0. 00
ATOM 2339 HA LEU 125 9. 701 13. 570 -17. 759 1. 00 0. 00
ATOM 2340 CB LEU 125 10. 997 14. 919 -16. 752 1. 00 0. 00
ATOM 2341 2HB LEU 125 11. 977 15. 368 -16. 916 1. 00 0. 00
ATOM 2342 1HB LEU 125 10. 265 15. 725 -16. 797 1. 00 0. 00
ATOM 2343 QB LEU 125 11. 121 15. 547 -16. 856 1. 00 0. 00
ATOM 2344 CG LEU 125 10. 970 14. 322 -15. 343 1. 00 0. 00
ATOM 2345 HG LEU 125 11. 552 13. 401 -15. 351 1. 00 0. 00
ATOM 2346 QD1 LEU 125 11. 788 15. 489 -14. 096 1. 00 0. 00 ATOM 2347 QD2 LEU 125 9.205 13.865 -14.834 1.00 0.00
ATOM 2348 CDl LEU 125 11 .631 15 .265 -14 .335 1 .00 0 .00
ATOM 2349 1HD1 LEU 125 11 .203 15 .099 -13 .347 1 .00 0 .00
ATOM 2350 2HD1 LEU 125 12 .703 15 .070 -14 .304 1 .00 0 .00
ATOM 2351 3HD1 LEU 125 11 .458 16 .298 -14 .637 1 .00 0 .00
ATOM 2352 CD2 LEU 125 9 .544 13 .952 -14 .931 1 .00 0 .00
ATOM 2353 1HD2 LEU 125 9 .541 13 .612 -13 .896 1 .00 0 .00
ATOM 2354 2HD2 LEU 125 8 .899 14 .826 -15 .028 1 .00 0 .00
ATOM 2355 3HD2 LEU 125 9 .174 13 .156 -15 .577 1 .00 0 .00
ATOM 2356 QQD LEU 125 10 .496 14 .677 -14 .465 1 .00 0 .00
ATOM 2357 C LEU 125 10 .810 14 .584 -19 .285 1 .00 0 .00
ATOM 2358 O LEU 125 10 .027 15 .471 -19 .619 1 .00 0 .00
ATOM 2359 N GLY 126 11 .777 14 .108 -20 .055 1 .00 0 .00
ATOM 2360 HN GLY 126 12 .410 13 .386 -19 .776 1 .00 0 .00
ATOM 2361 CA GLY 126 11 .985 14 .621 -21 .398 1 .00 0 .00
ATOM 2362 2HA GLY 126 11 .145 15 .254 -21 .684 1 .00 0 .00
ATOM 2363 1HA GLY 126 12 .877 15 .247 -21 .418 1 .00 0 .00
ATOM 2364 QA GLY 126 12 .011 15. .251 -21 .551 1 .00 0 .00
ATOM 2365 C GLY 126 12 .135 13 .479 -22 .405 1 .00 0 .00
ATOM 2366 O GLY 126 12 .645 13 .679 -23 .506 1 .00 0 .00
ATOM 2367 N LEU 127 11 .681 12 .305 -21 .991 1 .00 0 .00
ATOM 2368 HN LEU 127 11 .267 12, .150 -21 .094 1 .00 0 .00
ATOM 2369 CA LEU 127 11 .757 11, .130 -22, .843 1. .00 0 .00
ATOM 2370 HA LEU 127 12 .356 11, .397 -23, .714 1 .00 0 .00
ATOM 2371 CB LEU 127 12 .486 9, .993 -22, .124 1 .00 0 .00
ATOM 2372 2HB LEU 127 13. .153 10. .429 -21, .379 1, .00 0, .00
ATOM 2373 1HB LEU 127 11. .749 9, .400 -21, .582 1, .00 0, .00
ATOM 2374 QB LEU 127 12, .451 9, .915 -21, .481 1, .00 0. .00
ATOM 2375 CG LEU 127 13. .304 9. .053 -23. .012 1. .00 0, .00
ATOM 2376 HG LEU 127 13, .690 8. .246 -22. .390 1, .00 0, .00
ATOM 2377 QD1 LEU 127 12, .216 8. .261 -24. .343 1, .00 0, .00
ATOM 2378 QD2 LEU 127 14, .797 9, .949 -23, .755 1, .00 0, .00
ATOM 2379 CDl LEU 127 12, .425 8. .413 -24. .088 1, .00 0, .00
ATOM 2380 1HD1 LEU 127 11, .448 8. .176 -23, .666 1, .00 0, .00
ATOM 2381 2HD1 LEU 127 12, .303 9. .109 -24, .918 1, .00 0, .00
ATOM 2382 3HD1 LEU 127 12. .898 7. .499 -24. .447 1, .00 0. .00
ATOM 2383 CD2 LEU 127 14. .510 9. .777 -23. .613 1, .00 0, .00
ATOM 2384 1HD2 LEU 127 15. .406 9. .522 -23. .047 1. .00 0, .00
ATOM 2385 2HD2 LEU 127 14, .637 9. .472 -24. .651 1, .00 0, .00
ATOM 2386 3HD2 LEU 127 14. .347 10. ,854 -23. ,568 1. .00 0. .00
ATOM 2387 QQD LEU 127 13. .506 9. .105 -24. .049 1. .00 0. .00
ATOM 2388 C LEU 127 10. .351 10. .756 -23. .317 1. .00 0, ,00
ATOM 2389 O LEU 127 10. ,195 10. ,041 -24. ,305 1. ,00 0, ,00
ATOM 2390 N ILE 128 9. ,364 11. .257 -22. ,589 1. ,00 0, ,00
ATOM 2391 HN ILE 128 9. ,499 11. .838 -21. ,787 1. .00 0. ,00
ATOM 2392 CA ILE 128 7. ,976 10. .985 -22. ,923 1. .00 0. ,00
ATOM 2393 HA ILE 128 7. 970 10. 205 -23. 685 1. ,00 0. 00
ATOM 2394 CB ILE 128 7. 231 10. 433 -21. 706 1. ,00 0. 00
ATOM 2395 HB ILE 128 7. ,371 11. 127 -20. 876 1. ,00 0. 00
ATOM 2396 QG2 ILE 128 5. 370 10. 329 -22. 039 1. 00 0. 00
ATOM 2397 CG2 ILE 128 5. 727 10. 349 -21. 975 1. 00 0. 00
ATOM 2398 1HG2 ILE 128 5. 552 10. 320 -23. 051 1. 00 0. 00
ATOM 2399 2HG2 ILE 128 5. 326 9. 444 -21. 518 1. ,00 0. 00
ATOM 2400 3HG2 ILE 128 5. 232 11. 221 -21. 549 1. 00 0. 00
ATOM 2401 CGI ILE 128 7. 812 9. 086 -21. 271 1. 00 0. 00
ATOM 2402 2HG1 ILE 128 7. 490 8. 307 -21. 963 1. 00 0. 00
ATOM 2403 1HG1 ILE 128 8. 900 9. 124 -21. 317 1. 00 0. 00
ATOM 2404 QG1 ILE 128 8. 195 8. 715 -21. 640 1. 00 0. 00
ATOM 2405 QD1 ILE 128 7. 262 8. 645 -19. 514 1. 00 0. 00
ATOM 2406 CDl ILE 128 7. 368 8. 730 -19. 851 1. ,00 0. 00
ATOM 2407 1HD1 ILE 128 7. 783 7. 761 -19. 572 1. 00 0. 00
ATOM 2408 2HD1 ILE 128 7. 724 9. 491 -19. 157 1. 00 0. 00 ATOM 2409 3HD1 ILE 128 6.279 8.683 -19.812 1.00 0.00
ATOM 2410 C ILE 128 7 .341 12 .245 -23 .513 1 .00 0 .00
ATOM 2411 O ILE 128 6 .247 12 .189 -24 .073 1 .00 0 .00
ATOM 2412 N GLN 129 8 .054 13 .352 -23 .368 1 .00 0 .00
ATOM 2413 HN GLN 129 8 .943 13 .389 -22 .911 1 .00 0 .00
ATOM 2414 CA GLN 129 7 .574 14 .624 -23 .880 1 .00 0 .00
ATOM 2415 HA GLN 129 6 .516 14 .660 -23 .620 1 .00 0 .00
ATOM 2416 CB GLN 129 8 .296 15 .794 -23 .207 1 .00 0 .00
ATOM 2417 2HB GLN 129 7 .978 15 .872 -22 .168 1 .00 0 .00
ATOM 2418 1HB GLN 129 9 .370 15 .607 -23 .199 1 .00 0 .00
ATOM 2419 QB GLN 129 8 .674 15 .740 -22 .683 1 .00 0 .00
ATOM 2420 CG GLN 129 8 .007 17 .108 -23 .936 1 .00 0 .00
ATOM 2421 2HG GLN 129 8 .222 16 .994 -24 .998 1 .00 0 .00
ATOM 2422 1HG GLN 129 6 .948 17 .351 -23 .848 1 .00 0 .00
ATOM 2423 QG GLN 129 7 .585 17 .173 -24 .423 1. .00 0 .00
ATOM 2424 CD GLN 129 8 .847 18 .250 -23 .360 1 .00 0 .00
ATOM 2425 OEl GLN 129 8 .565 18 .791 -22 .304 1 .00 0 .00
ATOM 2426 NE2 GLN 129 9 .893 18 .584 -24 .111 1 .00 0 .00
ATOM 2427 1HE2 GLN 129 10 .068 18 .099 -24 .967 1 .00 0, .00
ATOM 2428 2HE2 GLN 129 10 .503 19 .320 -23 .818 1. .00 0 .00
ATOM 2429 QE2 GLN 129 10 .286 18 .710 -24 .393 1 .00 0 .00
ATOM 2430 C GLN 129 7 .738 14 .680 -25 .400 1 .00 0 .00
ATOM 2431 0 GLN 129 6, .805 15 .041 -26, .116 1 .00 0, .00
ATOM 2432 N VAL 130 8, .931 14 .318 -25 .849 1 .00 0, .00
ATOM 2433 HN VAL 130 9 .685 14 .026 -25 .260 1 .00 0, .00
ATOM 2434 CA VAL 130 9 .229 14 .323 -27 .271 1 .00 0, .00
ATOM 2435 HA VAL 130 8, .963 15. .306 -27, .659 1, .00 0, .00
ATOM 2436 CB VAL 130 10, .729 14, .116 -27, .492 1, .00 0, .00
ATOM 2437 HB VAL 130 11, .259 14, .624 -26. .687 1, .00 0, .00
ATOM 2438 QG1 VAL 130 11, .178 12, .278 -27, .416 1, .00 0, .00
ATOM 2439 QG2 VAL 130 11, .286 14, .883 -29, .131 1, .00 0, .00
ATOM 2440 CGI VAL 130 11. .092 12. .631 -27. .431 1. .00 0. .00
ATOM 2441 1HG1 VAL 130 10. .838 12. .235 -26. .447 1. .00 0. .00
ATOM 2442 2HG1 VAL 130 10. .535 12. .089 -28. .195 1. ,00 0. .00
ATOM 2443 3HG1 VAL 130 12. .161 12. .510 -27. .606 1. ,00 0. .00
ATOM 2444 CG2 VAL 130 11. .179 14. ,736 -28. ,816 1. ,00 0. ,00
ATOM 2445 1HG2 VAL 130 11. ,718 13. ,991 -29. ,401 1. ,00 0. ,00
ATOM 2446 2HG2 VAL 130 10. ,305 15. ,074 -29. ,374 1. ,00 0. ,00
ATOM 2447 3HG2 VAL 130 11. .833 15. .585 -28. .616 1. ,00 0. ,00
ATOM 2448 QQG VAL 130 11. ,232 13. ,581 -28. ,273 1. ,00 0. ,00
ATOM 2449 C VAL 130 8. ,370 13. ,268 -27. ,971 1. ,00 0. .00
ATOM 2450 O VAL 130 8. ,043 13. ,410 -29. ,148 1. ,00 0. ,00
ATOM 2451 N MET 131 8. ,029 12. ,233 -27. ,217 1. .00 0. ,00
ATOM 2452 HN MET 131 8. 300 12. 125 -26. 260 1. ,00 0. 00
ATOM 2453 CA MET 131 7. 215 11. 154 -27. ,751 1. ,00 0. 00
ATOM 2454 HA MET 131 7. ,501 11. ,062 -28. ,798 1. ,00 0. ,00
ATOM 2455 CB MET 131 7. .504 9. ,866 -26. ,978 1. ,00 0. ,00
ATOM 2456 2HB MET 131 8. .151 10. .084 -26. ,129 1. ,00 0. ,00
ATOM 2457 1HB MET 131 6. 575 9. 462 -26. 576 1. 00 0. 00
ATOM 2458 QB MET 131 7. 363 9. 773 -26. 352 1. 00 0. 00
ATOM 2459 CG MET 131 8. 172 8. 825 -27. 880 1. 00 0. 00
ATOM 2460 2HG MET 131 8. 144 7. 846 -27. 401 1. 00 0. 00
ATOM 2461 1HG MET 131 7. 622 8. 737 -28. 817 1. 00 0. 00
ATOM 2462 QG MET 131 7. 883 8. 291 -28. 109 1. 00 0. 00
ATOM 2463 SD MET 131 9. 862 9. 295 -28. 207 1. 00 0. 00
ATOM 2464 QE MET 131 10. 884 7. 566 -27. 445 1. 00 0. 00
ATOM 2465 CE MET 131 10. 712 7. 858 -27. 574 1. 00 0. 00
ATOM 2466 IHE MET 131 11. 601 8. 173 -27. 029 1. 00 0. 00
ATOM 2467 2HE MET 131 10. 049 7. 311 -26. 903 1. 00 0. 00
ATOM 2468 3HE MET 131 11. 002 7. 213 -28. 403 1. 00 0. 00
ATOM 2469 C MET 131 5. 725 11. 489 -27. 646 1. 00 0. 00
ATOM 2470 O MET 131 4. 876 10. 670 -27. 995 1. 00 0. 00 ATOM 2471 N ILE 132 5.454 12.693 -27.164 1.00 0.00
ATOM 2472 HN ILE 132 6 .151 13 .352 -26 .883 1 .00 0 .00
ATOM 2473 CA ILE 132 4 .082 13 .146 -27 .009 1 .00 0 .00
ATOM 2474 HA ILE 132 3 .444 12 .262 -27 .017 1 .00 0 .00
ATOM 2475 CB ILE 132 3 .893 13 .828 -25 .653 1 .00 0 .00
ATOM 2476 HB ILE 132 4 .638 13 .430 -24 .963 1 .00 0 .00
ATOM 2477 QG2 ILE 132 4 .194 15 .693 -25 .784 1 .00 0 .00
ATOM 2478 CG2 ILE 132 4 .136 15 .335 -25 .759 1 .00 0 .00
ATOM 2479 1HG2 ILE 132 4 .721 15 .547 -26 .654 1 .00 0 .00
ATOM 2480 2HG2 ILE 132 3 .179 15 .854 -25 .820 1 .00 0 .00
ATOM 2481 3HG2 ILE 132 4 .680 15 .679 -24 .879 1 .00 0 .00
ATOM 2482 CGI ILE 132 2 .517 13 .509 -25 .065 1 .00 0 .00
ATOM 2483 2HG1 ILE 132 1 .750 14 .061 -25. .608 1. .00 0 .00
ATOM 2484 1HG1 ILE 132 2 .300 12 .449 -25. .195 1 .00 0, .00
ATOM 2485 QG1 ILE 132 2 .025 13 .255 -25. .401 1. .00 0. .00
ATOM 2486 QD1 ILE 132 2 .445 13 .955 -23 .227 1. .00 0. .00
ATOM 2487 CDl ILE 132 2 .458 13, .870 -23, .579 1, .00 0, .00
ATOM 2488 1HD1 ILE 132 3, .461 14, .107 -23, .223 1, .00 0, .00
ATOM 2489 2HD1 ILE 132 1, .810 14, .734 -23, .441 1, .00 0. .00
ATOM 2490 3HD1 ILE 132 2, .063 13, .024 -23, .016 1. .00 0. .00
ATOM 2491 C ILE 132 3, .703 14, .028 -28, .200 1, .00 0, .00
ATOM 2492 O ILE 132 2, .533 14, .359 -28, .384 1, .00 0, .00
ATOM 2493 N VAL 133 4, .715 14, .384 -28, .978 1. .00 0, .00
ATOM 2494 HN VAL 133 5, .664 14, .110 -28, .821 1, .00 0, .00
ATOM 2495 CA VAL 133 4, .503 15, .221 -30, .146 1, .00 0, .00
ATOM 2496 HA VAL 133 3, .427 15, .317 -30, .291 1, .00 0, .00
ATOM 2497 CB VAL 133 5, .073 16, .619 -29, .898 1, .00 0, .00
ATOM 2498 HB VAL 133 6 .102 16, .506 -29, .555 1, .00 0, .00
ATOM 2499 QG1 VAL 133 5. .101 17 .634 -31, .496 1, .00 0, .00
ATOM 2500 QG2 VAL 133 4 .104 17 .517 -28, .541 1, .00 0, .00
ATOM 2501 CGI VAL 133 5, .095 17. .439 -31. .189 1. .00 0, .00
ATOM 2502 1HG1 VAL 133 4, .663 16. .853 -32, .000 1. .00 0. .00
ATOM 2503 2HG1 VAL 133 4, .515 18, .351 -31. .051 1. .00 0. .00
ATOM 2504 3HG1 VAL 133 6, .125 17. .698 -31. .438 1. .00 0. .00
ATOM 2505 CG2 VAL 133 4. .290 17. .344 -28. .801 1. .00 0. .00
ATOM 2506 1HG2 VAL 133 4, .794 17. .209 -27. .845 1. ,00 0. .00
ATOM 2507 2HG2 VAL 133 4, .236 18. .408 -29. .036 1. .00 0. .00
ATOM 2508 3HG2 VAL 133 3, .282 16. ,934 -28. ,743 1. .00 0. ,00
ATOM 2509 QQG VAL 133 4, .602 17. ,575 -30. .019 1. .00 0. .00
ATOM 2510 C VAL 133 5, .107 14, ,539 -31. ,374 1. .00 0. .00
ATOM 2511 O VAL 133 4, .383 13. .980 -32. .197 1. .00 0. ,00
ATOM 2512 N VAL 134 6. .428 14. .606 -31. .460 1. .00 0. ,00
ATOM 2513 HN VAL 134 7. .009 15. .062 -30. ,786 1. .00 0. ,00
ATOM 2514 CA VAL 134 7. .137 14. ,001 -32. ,574 1. .00 0. ,00
ATOM 2515 HA VAL 134 7. ,031 14. ,665 -33. ,431 1. ,00 0. 00
ATOM 2516 CB VAL 134 8. ,627 13. 887 -32. 245 1. ,00 0. 00
ATOM 2517 HB VAL 134 8. .720 13. ,400 -31. 274 1. ,00 0. 00
ATOM 2518 QG1 VAL 134 9. .523 12. .813 -33. 521 1. ,00 0. 00
ATOM 2519 QG2 VAL 134 9. .427 15. 598 -32. 117 1. ,00 0. 00
ATOM 2520 CGI VAL 134 9. ,351 13. .019 -33. ,276 1. ,00 0. 00
ATOM 2521 1HG1 VAL 134 8. ,832 12. 066 -33. .378 1. ,00 0. 00
ATOM 2522 2HG1 VAL 134 9. ,363 13. .531 -34. .239 1. ,00 0. 00
ATOM 2523 3HG1 VAL 134 0. .375 12. ,841 -32. ,947 1. ,00 0. 00
ATOM 2524 CG2 VAL 134 9. ,274 15. ,269 -32. ,142 1. ,00 0. 00
ATOM 2525 1HG2 VAL 134 0. ,297 15. 166 -31. ,780 1. ,00 0. 00
ATOM 2526 2HG2 VAL 134 9. .282 15. ,741 -33. ,124 1. ,00 0. 00
ATOM 2527 3HG2 VAL 134 8. ,703 15. ,886 -31. ,447 1. ,00 0. 00
ATOM 2528 QQG VAL 134 9. ,475 14. ,205 -32. ,819 1. ,00 0. 00
ATOM 2529 C VAL 134 6. 495 12. 654 -32. 912 1. 00 0. 00
ATOM 2530 0 VAL 134 6. 172 12. 389 -34. 069 1. 00 0. 00
ATOM 2531 N PHE 135 6. 328 11. 839 -31. 881 1. 00 0. 00
ATOM 2532 HN PHE 135 6. 593 12. 062 -30. 943 1. 00 0. 00 ATOM 2533 CA PHE 135 5.730 10.526 -32.054 1.00 0.00
ATOM 2534 HA PHE 135 5 .964 10 .194 -33 .065 1 .00 0 .00
ATOM 2535 CB PHE 135 6 .318 9 .620 -30 .970 1 .00 0 .00
ATOM 2536 2HB PHE 135 6 .145 10 .076 -29 .996 1 .00 0 .00
ATOM 2537 1HB PHE 135 5 .785 8 .669 -30 .977 1 .00 0 .00
ATOM 2538 QB PHE 135 5 .965 9 .373 -30 .486 1 .00 0 .00
ATOM 2539 QD PHE 135 7 .948 9 .325 -31 .146 1 .00 0 .00
ATOM 2540 QE PHE 135 10 .404 8 .881 -31 .410 1 .00 0 .00
ATOM 2541 QR PHE 135 9 .176 9 .103 -31 .278 1 .00 0 .00
ATOM 2542 CG PHE 135 7 .815 9 .349 -31 .132 1 .00 0 .00
ATOM 2543 CDl PHE 135 8 .715 10 .340 -30 .892 1 .00 0 .00
ATOM 2544 HDl PHE 135 8 .370 11 .328 -30 .585 1 .00 0 .00
ATOM 2545 CE1 PHE 135 10 .105 10 .089 -31 .041 1 .00 0 .00
ATOM 2546 HEI PHE 135 10 .826 10 .883 -30 .849 1 .00 0 .00
ATOM 2547 CZ PHE 135 10 .536 8 .857 -31 .424 1 .00 0 .00
ATOM 2548 HZ PHE 135 11 .603 8 .664 -31 .539 1 .00 0 .00
ATOM 2549 CE2 PHE 135 9 .636 7 .866 -31 .664 1 .00 0 .00
ATOM 2550 HE2 PHE 135 9 .981 6 .879 -31 .971 1 .00 0 .00
ATOM 2551 CD2 PHE 135 8 .246 8 .117 -31 .515 1 .00 0 .00
ATOM 2552 HD2 PHE 135 7 .525 7 .323 -31 .707 1 .00 0 .00
ATOM 2553 C PHE 135 4, .211 10, .589 -31 .880 1 .00 0 .00
ATOM 2554 O PHE 135 3 .490 9 .723 -32 .373 1 .00 0. .00
ATOM 2555 N GLY 136 3 .770 11, .622 -31 .177 1 .00 0 .00
ATOM 2556 HN GLY 136 4, .363 12, .322 -30 .780 1 .00 0 .00
ATOM 2557 CA GLY 136 2, .350 11, .809 -30 .932 1 .00 0 .00
ATOM 2558 2HA GLY 136 1, .937 10, .915 -30 .464 1 .00 0 .00
ATOM 2559 1HA GLY 136 2. .203 12. .632 -30, .233 1, .00 0, .00
ATOM 2560 QA GLY 136 2. .070 11. .773 -30, .348 1, .00 0, .00
ATOM 2561 C GLY 136 1. .602 12. .099 -32, .235 1, .00 0, .00
ATOM 2562 O GLY 136 0. .384 11. .941 -32, .305 1, .00 0. .00
ATOM 2563 N ASP 137 2, .363 12. .519 -33, .235 1, .00 0, .00
ATOM 2564 HN ASP 137 3. .353 12. .645 -33, .171 1, .00 0, .00
ATOM 2565 CA ASP 137 1. .788 12. .833 -34, .532 1, .00 0, .00
ATOM 2566 HA ASP 137 0. .711 12. ,730 -34. .400 1. ,00 0. .00
ATOM 2567 CB ASP 137 2. ,146 14. ,256 -34. .964 1. .00 0. .00
ATOM 2568 2HB ASP 137 3. ,098 14. ,529 -34. .507 1. .00 0. .00
ATOM 2569 1HB ASP 137 2. .296 14. .266 -36. .043 1, .00 0. .00
ATOM 2570 QB ASP 137 2. .697 14. .398 -35, .275 1, .00 0. .00
ATOM 2571 CG ASP 137 1. .108 15, .322 -34, .604 1. .00 0, .00
ATOM 2572 OD1 ASP 137 0, .102 15. .035 -33. .938 1, .00 0, .00
ATOM 2573 OD2 ASP 137 1. .368 16. ,506 -35. .044 1, .00 0, .00
ATOM 2574 HD2 ASP 137 0. ,582 17. ,106 -34. ,896 1. .00 0. .00
ATOM 2575 C ASP 137 2. ,345 11. ,867 -35. ,580 1. .00 0. ,00
ATOM 2576 O ASP 137 1. ,875 11. ,840 -36. ,716 1. .00 0. ,00
ATOM 2577 N GLU 138 3. ,338 11. ,097 -35. ,160 1. ,00 0. ,00
ATOM 2578 HN GLU 138 3. ,714 11. ,126 -34. ,234 1. .00 0. ,00
ATOM 2579 CA GLU 138 3. ,964 10. ,133 -36. ,048 1. .00 0. ,00
ATOM 2580 HA GLU 138 3. ,173 9. ,805 -36. ,723 1. .00 0. ,00
ATOM 2581 CB GLU 138 5. 082 10. 784 -36. 864 1. 00 0. 00
ATOM 2582 2HB GLU 138 4. 773 11. 779 -37. 182 1. 00 0. 00
ATOM 2583 1HB GLU 138 5. 967 10. 909 -36. 241 1. 00 0. 00
ATOM 2584 QB GLU 138 5. 370 11. 344 -36. 712 1. 00 0. 00
ATOM 2585 CG GLU 138 5. 431 9. 936 -38. 090 1. 00 0. 00
ATOM 2586 2HG GLU 138 6. 354 9. 387 -37. 905 1. 00 0. 00
ATOM 2587 1HG GLU 138 4. 648 9. 197 -38. 260 1. 00 0. 00
ATOM 2588 QG GLU 138 5. 501 9. 292 -38. 083 1. 00 0. 00
ATOM 2589 CD GLU 138 5. 592 10. 812 -39. 334 1. 00 0. 00
ATOM 2590 OEl GLU 138 4. 705 10. 828 -40. 200 1. 00 0. 00
ATOM 2591 OE2 GLU 138 6. 686 11. 494 -39. 382 1. 00 0. 00
ATOM 2592 HE2 GLU 138 6. 570 12. 361 -38. 898 1. 00 0. 00
ATOM 2593 C GLU 138 4. 492 8. 940 -35. 248 1. 00 0. 00
ATOM 2594 O GLU 138 5. 702 8. 764 -35. 115 1. 00 0. 00 ATOM 2595 N PRO 139 3.534 8.130 -34.723 1.00 0.00
ATOM 2596 CD PRO 139 2 .091 8 .308 -34 .860 1 .00 0 .00
ATOM 2597 CA PRO 139 3 .890 6 .959 -33 .940 1 .00 0 .00
ATOM 2598 HA PRO 139 4 .644 7 .174 -33 .318 1 .00 0 .00
ATOM 2599 CB PRO 139 2 .624 6 .591 -33 .184 1 .00 0 .00
ATOM 2600 2HB PRO 139 2 .480 5 .511 -33 .165 1 .00 0 .00
ATOM 2601 1HB PRO 139 2 .677 6 .924 -32 .147 1 .00 0 .00
ATOM 2602 QB PRO 139 2 .578 6 .218 -32 .656 1 .00 0 .00
ATOM 2603 CG PRO 139 1 .485 7 .280 -33 .919 1 .00 0 .00
ATOM 2604 2HG PRO 139 0 .896 6 .552 -34 .477 1 .00 0 .00
ATOM 2605 1HG PRO 139 0 .809 7 .761 -33 .211 1 .00 0 .00
ATOM 2606 QG PRO 139 0 .852 7 .156 -33 .844 1 .00 0 .00
ATOM 2607 2HD PRO 139 1 .768 8 .143 -35 .888 1 .00 0 .00
ATOM 2608 1HD PRO 139 1 .789 9 .319 -34 .589 1 .00 0 .00
ATOM 2609 QD PRO 139 1 .778 8 .731 -35 .238 1 .00 0 .00
ATOM 2610 C PRO 139 4 .398 5 .832 -34 .840 1 .00 0 .00
ATOM 2611 O PRO 139 4 .279 5, .906 -36, .062 1 .00 0, .00
ATOM 2612 N PRO 140 4 .969 4 .786 -34, .185 1, .00 0, .00
ATOM 2613 CD PRO 140 5 .127 4, .663 -32, .738 1 .00 0, .00
ATOM 2614 CA PRO 140 5 .495 3, .644 -34 .912 1 .00 0, .00
ATOM 2615 HA PRO 140 5 .991 3, .949 -35, .725 1, .00 0, .00
ATOM 2616 CB PRO 140 6 .410 2, .936 -33, .926 1 .00 0, .00
ATOM 2617 2HB PRO 140 6 .299 1, .854 -33, .997 1 .00 0, .00
ATOM 2618 1HB PRO 140 7 .456 3 .164 -34 .132 1 .00 0 .00
ATOM 2619 QB PRO 140 6 .878 2 .509 -34, .065 1 .00 0 .00
ATOM 2620 CG PRO 140 6, .005 3, .437 -32, .549 1, .00 0, .00
ATOM 2621 2HG PRO 140 5 .466 2, .661 -32, .005 1, .00 0, .00
ATOM 2622 1HG PRO 140 6 .887 3, .686 -31, .959 1, .00 0, .00
ATOM 2623 QG PRO 140 6 .177 3, .174 -31, .982 1 .00 0, .00
ATOM 2624 2HD PRO 140 4 .164 4, .540 -32, .244 1, .00 0, .00
ATOM 2625 1HD PRO 140 5, .592 5. .553 -32. .314 1, .00 0. ,00
ATOM 2626 QD PRO 140 4, .878 5. .046 -32. .279 1, .00 0. ,00
ATOM 2627 C PRO 140 4, .363 2. .750 -35. .424 1, .00 0. .00
ATOM 2628 O PRO 140 4, .276 2. ,477 -36. .620 1. .00 0. .00
ATOM 2629 N VAL 141 3, .525 2. ,320 -34. ,493 1. .00 0. .00
ATOM 2630 HN VAL 141 3. .603 2. ,547 -33. ,522 1. ,00 0. ,00
ATOM 2631 CA VAL 141 2. .402 1. ,463 -34. ,834 1. .00 0. ,00
ATOM 2632 HA VAL 141 2. .773 0. .686 -35. ,502 1. .00 0. ,00
ATOM 2633 CB VAL 141 1. .858 0. .786 -33. ,575 1. .00 0. ,00
ATOM 2634 HB VAL 141 2. .620 0. ,099 -33. 208 1. ,00 0. 00
ATOM 2635 QG1 VAL 141 1. .519 2. ,058 -32. 214 1. ,00 0. 00
ATOM 2636 QG2 VAL 141 0, ,304 -0. ,222 -33. 964 1. ,00 0. 00
ATOM 2637 CGI VAL 141 1. ,584 1. ,814 -32. 475 1. ,00 0. 00
ATOM 2638 1HG1 VAL 141 1. ,396 2. ,788 -32. ,927 1. .00 0. ,00
ATOM 2639 2HG1 VAL 141 0. ,712 1. 506 -31. 899 1. ,00 0. 00
ATOM 2640 3HG1 VAL 141 2. ,450 1. 881 -31. 816 1. ,00 0. 00
ATOM 2641 CG2 VAL 141 0. ,602 -0. ,028 -33. 889 1. ,00 0. 00
ATOM 2642 1HG2 VAL 141 0. ,738 -0. ,556 -34. 834 1. ,00 0. ,00
ATOM 2643 2HG2 VAL 141 0. ,428 -o, ,751 -33. ,092 1. ,00 0. ,00
ATOM 2644 3HG2 VAL 141 0. 255 0. 640 -33. 967 1. 00 0. 00
ATOM 2645 QQG VAL 141 0. ,911 0. 918 -33. 089 1. ,00 0. 00
ATOM 2646 C VAL 141 1. ,346 2. 286 -35. 575 1. .00 0. 00
ATOM 2647 O VAL 141 0. .248 2. 498 -35. 062 1. 00 0. 00
ATOM 2648 N PHE 142 1. 714 2. 726 -36. 769 1. 00 0. 00
ATOM 2649 HN PHE 142 2. 609 2. 548 -37. 179 1. 00 0. 00
ATOM 2650 CA PHE 142 0. 812 3. 520 -37. 585 1. 00 0. 00
ATOM 2651 HA PHE 142 0. 125 4. 027 -36. 908 1. 00 0. 00
ATOM 2652 CB PHE 142 1. 677 4. 484 -38. 400 1. 00 0. 00
ATOM 2653 2HB PHE 142 2. 620 4. 640 -37. 876 1. 00 0. 00
ATOM 2654 1HB PHE 142 1. 916 4. 021 -39. 357 1. 00 0. 00
ATOM 2655 QB PHE 142 2. 268 4. 331 -38. 617 1. 00 0. 00
ATOM 2656 QD PHE 142 0. 963 5. 962 -38. 680 1. 00 0. 00
Figure imgf000131_0001
ATOM 2657 QE PHE 142 -0 .112 8 .190 -39 .101 1 .00 0 .00
ATOM 2658 QR PHE 142 0 .425 7 .076 -38 .891 1 .00 0 .00
ATOM 2659 CG PHE 142 1 .021 5 .842 -38 .657 1 .00 0 .00
ATOM 2660 CDl PHE 142 0 .785 6 .253 -39 .932 1 .00 0 .00
ATOM 2661 HDl PHE 142 1 .064 5 .615 -40 .770 1 .00 0 .00
ATOM 2662 CE1 PHE 142 0 .177 7 .514 -40 .171 1 .00 0 .00
ATOM 2663 HEI PHE 142 -0 .012 7 .843 -41 .192 1 .00 0 .00
ATOM 2664 CZ PHE 142 -0 .170 8 .310 -39 .124 1 .00 0 .00
ATOM 2665 HZ PHE 142 -0 .637 9 .278 -39 .307 1 .00 0 .00
ATOM 2666 CE2 PHE 142 0 .065 7 .899 -37 .849 1 .00 0 .00
ATOM 2667 HE2 PHE 142 -0 .213 8 .538 -37 .011 1 .00 0 .00
ATOM 2668 CD2 PHE 142 0 .674 6 .639 -37 .611 1 .00 0 .00
ATOM 2669 HD2 PHE 142 0 .863 6 .309 -36 .589 1 .00 0. .00
ATOM 2670 C PHE 142 0 .016 2 .632 -38 .545 1. .00 0. .00
ATOM 2671 O PHE 142 0 .188 1 .415 -38 .557 1. .00 0. .00
ATOM 2672 N SER 143 -0 .838 3 .278 -39, .326 1 .00 0 .00
ATOM 2673 HN SER 143 -0 .972 4 .268 -39, .310 1. .00 0. .00
ATOM 2674 CA SER 143 -1 .661 2 .562 -40 .287 1. .00 0. .00
ATOM 2675 HA SER 143 -2 .116 3 .334 -40 .907 1. .00 0 .00
ATOM 2676 CB SER 143 -0, .809 1, .641 -41, .163 1, .00 0, .00
ATOM 2677 2HB SER 143 0, .094 2, .168 -41, .473 1. .00 0, .00
ATOM 2678 1HB SER 143 -0, .490 0, .778 -40. .579 1. .00 0, .00
ATOM 2679 QB SER 143 -0, .198 1, .473 -41. .026 1. .00 0, .00
ATOM 2680 OG SER 143 -1, .518 1, .197 -42. .317 1, .00 0, .00
ATOM 2681 HG SER 143 -2, .450 1, .559 -42. .306 1. .00 0, .00
ATOM 2682 C SER 143 -2, .736 1, .755 -39. .557 1, .00 0, .00
ATOM 2683 O SER 143 -2. .895 0, .561 -39. .803 1. .00 0. .00
ATOM 2684 N ARG 144 -3. .446 2, .440 -38. .672 1. .00 0. .00
ATOM 2685 HN ARG 144 -3, .310 3, .412 -38. .478 1, .00 0. .00
ATOM 2686 CA ARG 144 -4, .502 1, .802 -37. .905 1, .00 0. .00
ATOM 2687 HA ARG 144 -4, .094 0, .832 -37. .622 1. .00 0, .00
ATOM 2688 CB ARG 144 -4, .845 2, .617 -36, .656 1. .00 0, .00
ATOM 2689 2HB ARG 144 -5, .467 3, .468 -36. .933 1. .00 0, .00
ATOM 2690 1HB ARG 144 -5. .428 2. .006 -35. .967 1. ,00 0. ,00
ATOM 2691 QB ARG 144 -5. .448 2. .737 -36. .450 1. .00 0. .00
ATOM 2692 CG ARG 144 -3. .576 3, .112 -35. ,959 1. .00 0. .00
ATOM 2693 2HG ARG 144 -3. .623 2. .871 -34. .897 1. .00 0. .00
ATOM 2694 1HG ARG 144 -2. .708 2. .594 -36. ,366 1. ,00 0. .00
ATOM 2695 QG ARG 144 -3. .165 2. .733 -35. ,631 1. .00 0. .00
ATOM 2696 CD ARG 144 -3. .406 4. .622 -36. ,138 1. .00 0. .00
ATOM 2697 2HD ARG 144 -3. ,120 4. .845 -37. .166 1, .00 0. .00
ATOM 2698 1HD ARG 144 -4. ,353 5. ,128 -35. ,953 1. .00 0. ,00
ATOM 2699 QD ARG 144 -3. ,737 4. ,987 -36. .559 1. .00 0. ,00
ATOM 2700 NE ARG 144 -2. ,373 5. ,129 -35. 206 1. ,00 0. ,00
ATOM 2701 HE ARG 144 -1. ,463 5. ,320 -35. .574 1. .00 0. ,00
ATOM 2702 CZ ARG 144 -2. ,583 5. ,349 -33. 891 1. ,00 0. ,00
ATOM 2703 NH1 ARG 144 -1. ,588 5. ,803 -33. 151 1. ,00 0. 00
ATOM 2704 HH1 ARG 144 -1. ,661 5. ,993 -32. 172 1. ,00 0. 00
ATOM 2705 NH2 ARG 144 -3. 792 5. 109 -33. 340 1. 00 0. 00
ATOM 2706 1HH2 ARG 144 -3. 939 5. 275 -32. 365 1. 00 0. 00
ATOM 2707 2HH2 ARG 144 -4. 540 4. 765 -33. 907 1. .00 0. 00
ATOM 2708 QH2 ARG 144 -4. ,240 5. 020 -33. 136 1. .00 0. 00
ATOM 2709 C ARG 144 -5. ,759 1. ,642 -38. 762 1. ,00 0. 00
ATOM 2710 O ARG 144 -6. ,406 0. ,597 -38. 732 1. ,00 0. 00
ATOM 2711 N PRO 145 -6. ,075 2. ,722 -39. 526 1. ,00 0. ,00
ATOM 2712 CD PRO 145 -5. 332 3. 977 -39. 587 1. 00 0. 00
ATOM 2713 CA PRO 145 -7. 243 2. 711 -40. 390 1. 00 0. 00
ATOM 2714 HA PRO 145 -8. 019 2. 290 -39. 920 1. .00 0. 00
ATOM 2715 CB PRO 145 -7. 507 4. 173 -40. 713 1. 00 0. 00
ATOM 2716 2HB PRO 145 -7. 786 4. 298 -41. 759 1. .00 0. 00
ATOM 2717 1HB PRO 145 -8. 331 4. 562 -40. 115 1. .00 0. 00
ATOM 2718 QB PRO 145 -8. 059 4. 430 -40. 937 1. ,00 0. 00 ATOM 2719 CG PRO 145 6 214 4 909 -40 403 1 00 0 00
ATOM 2720 2HG PRO 145 5 710 5 201 -41 324 1 00 0 00
ATOM 2721 1HG PRO 145 6 419 5 824 -39 847 1 00 0 00
ATOM 2722 QG PRO 145 6 065 5 512 -40 586 1 00 0 00
ATOM 2723 2HD PRO 145 4 359 3 839 -40 058 1 00 0 00
ATOM 2724 1HD PRO 145 5 149 4 378 -38 590 1 00 0 00
ATOM 2725 QD PRO 145 4 754 4 108 -39 324 1 00 0 00
ATOM 2726 C PRO 145 6 996 1 859 -41 636 1 00 0 00
ATOM 2727 0 PRO 145 5 931 1 261 -41 782 1 00 0 00
TER 2728 PRO 145
END
292. Table 7: List of Files on CD-R
Volume in drive D is 2M010024U3
Volume Serial Number is 04EF-61DD
Filename File Size Date Created
TABLE- -08 TXT 372 477 09-19-02 7 :13p
TABLE- -09 TXT 372 477 09-19-02 7 :14p
TABLE- -10 TXT 372 472 09-19-02 7 :16p
TABLE- -11 TXT 372 473 09-19-02 7 :16p
TABLE- -12 TXT 372, 479 09-19-02 7 :17p
TABLE- -13 TXT 372, 480 09-19-02 7 :18p
TABLE- -14 TXT 558, 716 09-19-02 7 :18p
TABLE- -15 TXT 371, 352 09-19-02 7 :19p
TABLE- -16 TXT 371, 354 09-19-02 7 :19p
TABLE- -17 TXT 371, 356 09-19-02 7 :20p
TABLE- -18 TXT 371, 913 09-19-02 7 :21p
TABLE- -19 TXT 371, 356 09-19-02 7 •21p
TABLE- -20 TXT 371, 352 09-19-02 7 *22p
TABLE- -21 TXT 371, 356 09-19-02 7 23p
TABLE- -22 TXT 371, 356 09-19-02 7 23p
TABLE- -23 TXT 371, 356 09-19-02 7 23p
TABLE- -24 TXT 371, 354 09-19-02 7 24p
TABLE- -25 TXT 371, 354 09-19-02 7 25p
TABLE- -26 TXT 557, 031 09-19-02 7 25p
TABLE- -27 TXT 388, 747 09-17-02 4 12p
TABLE- -28 TXT 386, 351 09-17-02 4 16p
TABLE- -29 TXT 386, 352 09-18-02 5 Olp
TABLE- -30 TXT 386, 352 09-17-02 4 23p
TABLE- -31 TXT 386, 352 09-17-02 4 28p
TABLE- -32 TXT 386, 352 09-18-02 5 03p
TABLE- -33 TXT 386, 352 09-17-02 4 35p
TABLE- -34 TXT 386, 352 09-17-02 4 38p
TABLE- -35 TXT 386, 352 09-17-02 4 42p
TABLE- -36 TXT 386, 354 09-17-02 5 37p
TABLE- -37 TXT 391, 170 09-18-02 5 08p
TABLE- -38 TXT 391, 166 09-18-02 5 49p
TABLE- -39 TXT 391, 168 09-18-02 5 04p
TABLE- -40 TXT 391, 168 09-17-02 6 08p
TABLE- -41 TXT 391, 170 09-19-02 3 44p
TABLE- -42 TXT 391, 170 09-17-02 6 15p
TABLE- -43 TXT 391, 168 09-18-02 11 03a
TABLE- -44 TXT 391, 168 09-18-02 1 52p
TABLE- -45 TXT 391, 168 09-18-02 4 59p
TABLE- -46 TXT 391, 170 09-18-02 2 02p
39 fil e(s) 15,213,666 byt :es
293. Tables 08-26 are tables providing coordinate data for minimal energy structures without being complexed to PTAP and table 27-46 provide coordinate data for minimal energy structures complexed with PTAP. All of the material in tables 27-46 and contained on the two CD-ROMs filed herewith are incorporated-by-reference in their entireties. The file names, size inn bytes and date created are also set forth herein.
2. Example Structure of the TsglOl UEV domain in complex with a HIV-1 PTAP "late domain" peptide
294. HIV and Ebola usurp human TsglOl and other components of the vacuolarprotein sorting machinery to facilitate virus budding (Garrus, J. E. et al. Cell 107, 55-65 (2001); Martin-Serrano, et al, Nat Med 7, 1313-9 (2001 ); and Demirov, D. G, et al, Proc Natl Acad Sci U S A 99, 955-60 (2002)). This cellular machinery is recruited by a direct interaction between the TsglOl UEV (Ubiquitin E2 Enzyme Variant) domain and a conserved PTAP motif in the viral structural proteins (the "late domain"). Disclosed is the solution structure of the TsglOl UEV domain in complex with a PTAP peptide that spans the late domain of HIV-1 p6Gag (5PEPTAPPEE13). TsglOl UEV resembles ubiquitin E2 conjugating enzymes (Pornillos, O. et al, EMBO J 2 , 2397-406 (2002); VanDemark, A. P., et al. Cell 105, 71 1-20 (2001); and Moraes, T. F. et al., Nat Struct Biol 8, 669-73 (2001)) and the PTAP peptide binds in a bifurcated groove above the vestigial enzyme active site. Each PTAP residue makes important contacts, and the 9Ala-ProlO dipeptide binds in a deep pocket that resembles the X-Pro binding pockets of SH3 and WW domains (Zarrinpar, A. & Lim, W. A. Converging on proline: the mechanism of WW domain peptide recognition. Nat Struct Biol 7, 61 1 -3 (2000)). The structure reveals the molecular basis of PTAP late domain function.
295. The PTAP peptide used in these studies was selected because it binds TsglOl UEV with the same affinity as the intact pόGag protein (KD = 3 μM under the NMR solution conditions), and because the
TsglOl UEV-PTAP peptide complex is in slow exchange (Pornillos, O. et al, EMBO J 21, 2397-406 (2002)) and gives high quality NMR spectra (Fig. 7a & 10a). The structure of the complex was calculated using 1,955 NOE restraints (including 82 intermolecular NOEs), 90 hydrogen bonding restraints, and 85 dihedral angle restraints. The entire structure is well ordered, and the 20 lowest-penalty structures superimpose over the mean coordinate positions with rmsd's of 0.75 A (backbone atoms) and 1.04 A (all heavy atoms) (Table 47 & Figures 10 b,c).
296. TsglOl UEV adopts the α/β/loop/α fold characteristic of ubiquitin E2 ligases (Pickart, C. M., Annu Rev Biochem 70, 503-33 (2001)), but like other UEV domains lacks the two C-terminal helices found in the E2 enzymes (Pornillos, O. et al, EMBO J2X, 2397-406 (2002); Cell 105, 71 1-20 (2001); and Moraes, T. F. et al, Nat Struct Biol 8, 669-73 (2001 ). The PTAP peptide binds in a groove between the strand S2/S3 hairpin, the N-terminal third of the vestigial active site loop, and the C-terminal residues of TsglOl UEV (Figs. 7, 8). The analogous site is occupied by the C-terminal helix in E2 enzymes, and divergence from the canonical E2 fold therefore allows Tsgl Ol UEV to use this site to mediate intermolecular interactions. 297. When the PTAP peptide binds, the TsglOl UEV groove closes significantly to envelop the central PTAP motif (Fig. 7b). Most significantly, the flexible C-terminal residues of TsglOl UEV become well ordered and wrap around one side of the PTAP motif. Other changes in TsglOl UEV that accompany peptide binding include: 1) The final turn of helix H4 rotates toward the peptide, facilitated by backbone torsion angle changes at Phel 5 and Gly 136. 2) The strand S2/S3 hairpin shifts and twists to orient S3 perpendicular to the peptide. This allows Tyr68 and Asn69 to interact with the peptide from opposite sides of this strand. 3) The N-terminal third of the vestigial active site loop reorients and increases in order, as judged by a 30% increase in observable intramolecular NOEs in this region. 298. The central 9Ala-Pron tripeptide of the bound PTAP peptide forms one turn of a left-handed type
II polyproline helix, and the flanking N- and C-termini adopt extended conformations. Peptide binding is mediated primarily by extensive intermolecular contacts with the four central 7PTAP10 residues (discussed below), hydrogen bonds to the Pro5 and Glu6 mainchain carbonyl oxygens, and modest contacts with the Pro5, Prol 1 and Glu 12 sidechains (Fig. 8). Thus, the overall structure is consistent with the fact that single point mutations in any of the four conserved PTAP residues can block TsglOl UEV binding and viral budding, whereas mutations in the less conserved flanking residues have only modest effects on both processes (Garrus, J. E. et al. Cell 107, 55-65 (2001) and Huang, M, et al, J Virol 69, 6810-8 (1995)).
299. Sequence-specific recognition of the 7PTAP10 motif is achieved primarily within two distinct pockets along the peptide binding groove (Figs. 8c, 9). Pro7 is cradled in a shallow pocket, which is lined by Tsg 101 residues Pro71 (bottom), and methyl groups from Thr58, Thr92, and Met95 (sides) (Fig. 9a). The 9Ala-Proιodipeptide binds in a deeper pocket, with Ala9 contacting TsglOl methyl and methylene groups from Ile70, Met95, Vall41, and Serl43. The 7PTAPιo ProlO ring wedges between the aromatic rings of Tyr63 and Tyr68, and is buttressed on one side by Prol39 and Vall41 (Figs. 9b,c).
300. Understanding how proteins recognize proline-rich binding sites is related because these are the most frequently occurring motifs in metazoan proteomes (Zarrinpar, A. & Lim, W. A., Nat Struct Biol 7,
61 1 -3 (2000) and Kay, B. K, et al, Faseb J 14, 231-41 (2000)). In the case of TsglOl UEV, the 9 Ala-Pro 10 binding pocket appears to be the most important recognition element and is reminiscent of the "X-Pro" pockets used by WW and SH3 domains for recognizing their proline-rich ligands. In WW and SH3 domains, the "key" prolines of peptide ligands also bind X-Pro pockets as type II polyproline helices, and are also wedged between two orthogonal aromatic ringss. As shown in Figure 9, the relative positions of the key prolines and the two aromatic rings are highly conserved across the TsglOl UEV-PTAP, Dystrophin WW- PPXY12, and Grb2 SH3-PXXP 13 complexes, revealing that all three domains have converged upon the same strategy for recognizing proline, despite having very different protein folds.
301. The conserved p6 7PTAP10 Thr8 residue traverses a ridge that separates the Pro7 and 9Ala- Pro 10 binding pockets and thereby links the two recognition elements. Unlike linker residues in SH3 and WW domain ligands, however, Thr8 contacts the UEV 4 domain and is essential for binding (Garrus, J. E. et al. Cell 107, 55-65 (2001)). The Thr8 hydroxyl proton is protected from solvent exchange, indicating a hydrogen bonding interaction. The data herein suggest that Thr80ydonates a hydrogen bond to the backbone carbonyl of Arg 144 (observed in 5/20 structures), and accepts one from Serl430γ, although these assignments are not definitive because the Serl43 and Argl44 positions are not well defined by the ΝOE data The methyl group of Thr8 does not make significant contacts, consistent with the fact that Thr and Ser are found at this position in natural HIV-1 isolates and with the disclosed observation that both PSAP and PTAP sequences bind TsglOl UEV equally well. 302. The structure of the TsglOl UEV-PTAP peptide complex agrees well with mutational analyses of the HIV-1 p6 requirements for TsglOl UEV binding and viral budding (Garrus, J. E. et al. Cell 107, 55-65 (2001) and Pornillos, O. et al. Structure and functional interactions of the TsglOl UEV domain. EMBO J 21 , 2397-406 (2002)). In particular, alanine/glycine mutations at each of the final three p6 7PTAPιo residues reduce TsglOl UEV binding affinity at least 35-fold (Garrus, J. E. et al. Cell 107, 55-65 (2001)), and all of these mutations remove atoms that make important contacts in the complex. The Pro7 position appears less critical, and a ρ6 Pro7>Ala mutation reduces TsglOl UEV binding only 3-fold, consistent with the fact that the Pro7 gamma and delta atoms make only modest intermolecular contacts. However, a Leu substitution at position Pro7 cannot be accommodated without distortions, and this mutation reduces TsglOl UEV binding 70-fold and blocks virus budding (Garrus, J. E. et al. Cell 107, 55-65 (2001) and Huang, M., et al, J Virol 69, 6810-8 (1995)).
303. The TsglOl UEV-PTAP peptide structure is also generally consistent with mutational analyses of the TsglOl UEV domain. Alanine substitutions of TsglOl UEV residues Tyr63 and Met95 reduce p6 binding by 13- and 52-fold, respectively (Pornillos, O. et al, EMBO J 21, 2397-406 (2002)), and are readily explained because Met95 makes extensive intermolecular hydrophobic contacts with Pro7 and Ala9, while Tyr63 forms one side of the ProlO binding slot (Figs. 8, 9). The Y63A and M95A TsglOl mutations also inhibit HIV-1 budding and infectivity, underscoring the importance of the TsglOl-PTAP complex in HIV 5 replication. Similarly, mutation of the TsglOl UEV 67TYN69 tripepeptide to 67 AAA69 diminishes the p6/Tsg 101 interaction in a yeast two hybrid system (VerPlank, L. et al., Proc Natl Acad Sci USA 98, 7724-9 (2001 )). Both Tyr68 and Asn69 contact the PTAP peptide. In contrast, other TsglOl UEV mutations reported to reduce p6 binding (e.g., Yl 10W, Yl 13V, WI 17A, and Kl 18A) (VerPlank, L. et al., Proc Natl Acad Sci USA 98, 7724-9 (2001)) are well removed from the PTAP binding site and their effects probably reflect indirect structural perturbations.
304. It is, of course, likely that the PTAP binding groove evolved to mediate TsglOl interactions with other cellular proteins and that the viruses are simply mimicking a natural TsglOl interaction. Potential
TsglOl UEV binding P(S/T)AP motifs are located downstream in TsglOl itself and within Hrs, a protein that may recruit TsglOl to the endosomal membrane during vacuolar protein sorting (Raiborg, C, et al, Biochem Soc Trans 29, 472-5 (2001) and Bishop, N., et al., J Cell Biol 157, 91-102 (2002)). TsglOl UEV can also bind P(S/T)AP-containing peptides derived from TsglOl and Hrs, although the biological relevance of these interactions remains to be established.
305. TsglOl and its yeast ortholog, Vps23p, also bind ubiquitin (Ub) (Garrus, J. E. et al. Cell 107, 55- 65 (2001); Pornillos, O. et al, EMBOJ 2 , 2397-406 (2002); Raiborg, C, et al, Biochem Soc Trans 29, 472-5 (2001 ); and Bishop, N, et al, J Cell Biol 157, 91 - 102 (2002)), which serves as a protein targeting signal in the vacuolar protein sorting pathway (Raiborg, C, et al, Biochem Soc Trans 29, 472-5 (2001); and Bishop, N, et al, J Cell Biol 157, 91- 102 (2002)). Ub binding maps to the concave TsglOl β-sheet (Fig. 7b, 8b) (Pornillos, O. et al, EMBOJ2X, 2397-406 (2002) and Bishop, N, et al, J Cell Biol 157, 91-102 (2002) An extended groove on TsglOl UEV connects the N-terminal end of the PTAP peptide binding site to this Ub binding surface, and this groove could create a continuous polypeptide recognition surface upon ubiquitination of upstream lysine residues (see Fig. 8b). This model is consistent with the fact that several potential TsglOl UEV-binding partners are monoubiquitinated (Bishop, N, et al, J Cell Biol 157, 91-102 (2002); Katzmann, D.J. et al., Cell 106, 145-55 (2001 ); Strack, B, et al, Proc Natl Acad Sci USA 97, 13063-8 (2000); and Polo, S. et al. Nature 416, 451-5 (2002). and with the emerging role of ubiquitin in enhancing proteinprotein interactions and stimulating productive complex formation and biological activity (Pickart, C. M, Mol Cell 8, 499-504 (2001 )).
306. The TsglOl-PTAP interaction is essential for HIV replication, making the TsglOl UEV PTAP binding site a potentially attractive target for novel inhibitors of viral replication (although the importance of this binding site for normal TsglOl functions and cell viability remains to be tested). Similarities between proline recognition by the TsglOl UEV domain and SH3 domains suggest that proline peptidomimetic strategies developed for SH3 domains may also apply to TsglOl inhibitor development. For example, Lim and co-workers have shown that Ν-substituted amino acids can replace the key prolines recognized by X-Pro pockets (Nguyen, j. T., et al., Science 282, 2088-92 (1998)). These "peptoids" have been used as a basis for designing or screening small molecule ligands with enhanced affinity for specific SH3 domains over natural peptide ligands (Nguyen, J. T. et al, Chem Biol 7, 463-73 (2000)). a) Methods
(1) Protein and peptide samples
307. TsglOl UEV domain (residues 2-145) was purified as described (Pornillos, O. et al, EMBO J 21, 2397-406 (2002)). PTAP peptides (HIV- I N -3 p6 residues 5-13: HN-PEPTAPPEE-COOH) were synthesized (unlabeled peptide) or expressed for isotopic labeling as Tφ.LE peptide fusions, purified from inclusion bodies, released with CNBr and purified by reversed-phase HPLC (Dadlez, M. & Kim, P. S. Biochemistry 35, 16153-64 ( 1996)).
(2) NMR spectroscopy
308. NMR samples were 1 :1 UEV domain and PTAP peptide, at ~1.5 mM in 20 mM sodium phosphate, pH 5.5, 10 mM NaCl, 10% 2H2O. Spectra were recorded at 18 °C on a Varian INOVA 600 MHz spectrometer. Backbone and sidechain resonance assignments were obtained using standard triple-resonance NMR experiments (Ferentz, A. E. & Wagner, G., Q Rev Biophys 33, 29-65 (2000)) on mixed samples in which only one component was uC/isN-labeled. Inter- and intramolecular NOEs were similarly identified using X-edited/filtered spectra (X = 13C/15N) on mixed samples (Ogura, K., et al, JMagn Reson B 112, 63-8 (1996); Ikura, M. & Bax, J. Am. Chem. Soc. 114, 2433-2440 (1992); and Zwahlen, C. et al. J. Am. Chem. Soc. 1 19, 671 1-6721 (1997). Spectra were processed using FELIX97 (MSI) 7 and analyzed using SPARKY (T.D. Goddard and D.G. Kneller, University of California, San Francisco, which is publically available).
(3) Structure determination 309. Structures were calculated using DYANA (Guntert, P, et al, j Mol Biol 273, 283-98 (1997)) and CNS (Brunger, A. T. et al, Acta Crystallogr D Biol Crystallogr 54, 905- 21 (1998)) as described for the uncomplexed TsglOl UEV domain (Pornillos, O. et al, EMBO J 21, 2397-406 (2002)). Structures were analyzed using PROCHECK-NMR (Laskowski, R. A, et al, j Biomol NMR 8, 477-86 (1996)), MOLMOL (Koradi, R, Billeter, M. & Wϋthrich, K, J. Mol. Graphics 14, 51-55 (1996)), and INSIGHT II (MSI) (Table 1), and displayed using MOLSCRIPT (Kraulis, P. J, J Applied Cryst 24, 946-50 (1991)), LIGPLOT (Wallace, A. C, Laskowski, R. A. & Thornton, J. M, Protein Eng 8, 127-34 (1995)), and PYMOL (DeLano Scientific). Figures were made using the lowest penalty structure. The coordinates, chemical shifts and NOE restraints have been deposited in theProtein Data Bank (lm4q, CNS ensemble; lm4p, DYANA ensemble) and are therefore obtainable and considered part of this application, and are specifically incoφorated by reference herein.
Table 47 Structure statistics for the Tsg101 UEV-PTAP peptide complex.
<TAD>1 <CNS>1
NOE distance restraints^ (A) 1955 1955
IntraUEV 1765 1765
Sequential (|/'-y|=1 ) 594 594
Medium range (2<|/-/'|<5) 319 319
Long range (|.-/|>5) 479 479
Intrapeptide 108 108
Intermolecular3 82 82
Hydrogen bond distance restraints4 (A) 90 90
Dihedral angle restraints (°) 85 85
HNHA coupling constants 0 96
DYANA Target function (A2) 1.39±0.08 n/a
CNS energy ~10000±20005 213±15
Residual distance restraint violations
Number of violations ≥ 0.4 A 0 0
Sum of violations (A or kcal/mol)6 1.8±0.4 21±3
Maximum violation (A) 0.34
Residual dihedral angle restraint violations
Number of violations ≥ 3° 1 0
Sum of violations (° or kcal/mol)6 0.02+0.01 0.20+0.07
Maximum violation (°) 3.15°
Van der Waals violations
Number ≥ 0.6 A 0 0
Sum of violations (A or kcal/mol)6 5.2±0.3 71±6
Maximum violation (A) 0.58
Ramachandran statistics7
Favored 66.1 % 74.1%
Allowed 26.3% 22.2%
Generously allowed 4.5% 2.4%
Disallowed 3.1% 1.2%
RMS deviations to the average coordinates8 (A)
Tsg101 UEV residues 4-143
Backbone 0.75±0.37 OJO±O.35
Heavy atoms 1.07±0.56 1.01±0.52
Tsg101 UEV secondary structures9
Backbone 0.61±0.27 0.56±0.25
Heavy atoms 0.91 ±0.44 0.85±0.39
PTAP peptide residues 5-13
Backbone 0.60+0.31 0.66+0.28
Heavy atom 0J5±0.51 0.83+0.51
<TAD> is the ensemble of 20 lowest-penalty structures (from 200 total) calculated using the program
DYANA1. <CNS> is the same ensemble after 2000 steps (15 psec each) of simulated annealing at 300
K, 2000 slow-cooling steps to 0 K, and 2000 steps of restrained Powell minimization in Cartesian space
(anneal. inp protocol)2.
Only meaningful and non-redundant restraints as determined by the DYANA CALIBA function.
More than 75% of the 82 intermolecular NOEs are to the 7PTAP10 motif, emphasizing the extensive contacts between Tsg101 UEV and this conserved tetrapeptide. 4 Two upper-limit distance restraints were used to define each hydrogen bond.
5 Energies for structures input into CNS (from DYANA) were estimated within the generate_easy.inp program after the first regularization without restraints.
6 Violation energies from DYANA have units of A or °, while energies from CNS are in kcal/mol. 7 Determined using PROCHECK-NMR3.
8 Superposition and overall r.m.s.d.s for the ensemble were calculated using MOLMOL4.
9 Helices: H1 , residues 4-13; H2, 18-31 ; H3, 112-115; H4, 124-138. Strands: S1 , 36-44; S2, 48-63; S3, 66-76; S4, 86-90 (See Fig. 8) 310. A representative set of coordinates for the complexed structure are set forth in Table 27 below.
COMPL -22.TXT
TABLE 27 part A
ATOM 1 N ALA 2 1.325 0.000 0.000 1.00 0.00
ATOM 2 HN ALA 2 1.884 0.000 0.829 1.00 0.00
ATOM 3 CA ALA 2 2.073 0.000 -1.245 1.00 0.00
ATOM 4 HA ALA 2 1.451 -0.471 -2.006 1.00 0.00
ATOM 5 QB ALA 2 2.430 1.784 -1.768 1.00 0.00
ATOM 6 CB ALA 2 2.362 1.442 -1.668 1.00 0.00
ATOM 7 1 HB ALA 2 1.642 2.1 10 - 1.195 1.00 0.00
ATOM 8 2HB ALA 2 3.370 1.716 - 1.359 1.00 0.00
ATOM 9 3HB ALA 2 2.278 1.527 -2.752 1.00 0.00
ATOM 10 C ALA 2 3.351 -0.822 -1.067 1.00 0.00
ATOM 1 1 O ALA 2 4.446 -0.266 -0.993 1.00 0.00
ATOM 12 N VAL 3 3.170 -2.133 -1.005 1.00 0.00
ATOM 13 HN VAL 3 2.276 -2.577 - 1.066 1.00 0.00
ATOM 14 CA VAL 3 4.295 -3.037 -0.837 1.00 0.00
ATOM 15 HA VAL 3 5.1 18 -2.463 -0.41 1 1.00 0.00
ATOM 16 CB VAL 3 3.931 -4.147 0.151 1.00 0.00
ATOM 17 HB VAL 3 3.595 -3.676 1.075 1.00 0.00
ATOM 18 QG1 VAL 3 2.511 -5.208 -0.513 1.00 0.00
ATOM 19 QG2 VAL 3 5.441 -5.214 0.559 1.00 0.00
ATOM 20 CG I VAL 3 2.783 -5.004 -0.385 1.00 0.00
ATOM 21 1 HG 1 VAL 3 1.838 -4.483 -0.232 1.00 0.00
ATOM 22 2HG 1 VAL 3 2.931 -5.184 -1.450 1.00 0.00
ATOM 23 3HG 1 VAL 3 2.763 -5.957 0.144 1.00 0.00
ATOM 24 CG2 VAL 3 5.152 -5.009 0.481 1.00 0.00
ATOM 25 1 HG2 VAL 3 5.888 -4.408 1.015 1.00 0.00
ATOM 26 2HG2 VAL 3 4.846 -5.848 1.106 1.00 0.00
ATOM 27 3HG2 VAL 3 5.591 -5.385 -0.443 1.00 0.00
ATOM 28 QQG VAL 3 3.976 -5.21 1 0.023 1.00 0.00
ATOM 29 C VAL 3 4.723 -3.571 -2.205 1.00 0.00
ATOM 30 O VAL 3 5.862 -4.001 -2.379 1.00 0.00
ATOM 31 N SER 4 3.786 -3.527 -3.141 1.00 0.00
ATOM 32 HN SER 4 2.862 -3.176 -2.992 1.00 0.00
ATOM 33 CA SER 4 4.052 -4.001 -4.489 1.00 0.00
ATOM 34 HA SER 4 4.516 -4.980 -4.364 1.00 0.00
ATOM 35 CB SER 4 2.755 -4.151 -5.286 1.00 0.00
ATOM 36 2HB SER 4 1.906 -4.130 -4.603 1.00 0.00
ATOM 37 1 HB SER 4 2.643 -3.302 -5.960 1.00 0.00
ATOM 38 QB SER 4 2.275 -3.716 -5.281 1.00 0.00
ATOM 39 OG SER 4 2.728 -5.360 -6.039 1.00 0.00
ATOM 40 HG SER 4 3.563 -5.443 -6.584 1.00 0.00
ATOM 41 C SER ■ 4 5.006 -3.042 -5.203 1.00 0.00
ATOM 42 O SER 4 5.758 -3.451 -6.086 1.00 0.00
ATOM 43 N GLU 5 4.945 - 1.783 -4.793 1.00 0.00
ATOM 44 HN GLU 5 4.331 -1.459 -4.073 1.00 0.00 ATOM 45 CA GLU 5 5.794 -0.762 -5.382 1.00 0.00
ATOM 46 HA GLU 5 5.335 -0.521 -6.341 1.00 0.00
ATOM 47 CB GLU 5 5.825 0.495 -4.511 1.00 0.00
ATOM 48 2HB GLU 5 4.819 0.907 -4.425 1.00 0.00 ATOM 49 1HB GLU 5 6.150 0.237 -3.503 1.00 0.00
ATOM 50 QB GLU 5 5.484 0.572 -3.964 1.00 0.00
ATOM 51 CG GLU 5 6.764 1.549 -5.101 1.00 0.00
ATOM 52 2HG GLU 5 6.717 1.515 -6.190 1.00 0.00
ATOM 53 1HG GLU 5 6.437 2.543 -4.799 1.00 0.00 ATOM 54 QG GLU 5 6.577 2.029 -5.494 1.00 0.00
ATOM 55 CD GLU 5 8.205 1.318 -4.641 1.00 0.00
ATOM 56 OEl GLU 5 8.531 1.574 -3.472 1.00 0.00
ATOM 57 0E2 GLU 5 8.999 0.853 -5.545 1.00 0.00
ATOM 58 HE2 GLU 5 9.815 1.427 -5.612 1.00 0.00 ATOM 59 C GLU 5 7.206 -1.309 -5.605 1.00 0.00
ATOM 60 O GLU 5 7.819 -1.052 -6.640 1.00 0.00
ATOM 61 N SER 6 7.680 -2.053 -4.616 1.00 0.00
ATOM 62 HN SER 6 7.175 -2.257 -3.778 1.00 0.00
ATOM 63 CA SER 6 9.008 -2.638 -4.691 1.00 0.00 ATOM 64 HA SER 6 9.683 -1.801 -4.869 1.00 0.00
ATOM 65 CB SER 6 9.383 -3.324 -3.376 1.00 0.00
ATOM 66 2HB SER 6 9.271 -2.618 -2.554 1.00 0.00
ATOM 67 1HB SER 6 8.692 -4.146 -3.186 1.00 0.00
ATOM 68 QB SER 6 8.982 -3.382 -2.870 1.00 0.00 ATOM 69 OG SER 6 10.718 -3.823 -3.395 1.00 0.00
ATOM 70 HG SER 6 10.864 -4.377 -4.215 1.00 0.00
ATOM 71 C SER 6 9.075 -3.636 -5.849 1.00 0.00
ATOM 72 O SER 6 10.035 -3.636 -6.619 1.00 0.00
ATOM 73 N GLN 7 8.044 -4.463 -5.936 1.00 0.00 ATOM 74 HN GLN 7 7.267 -4.457 -5.306 1.00 0.00
ATOM 75 CA GLN 7 7.974 -5.465 -6.986 1.00 0.00
ATOM 76 HA GLN 7 8.963 -5.922 -7.018 1.00 0.00
ATOM 77 CB GLN 7 6.936 -6.538 -6.653 1.00 0.00
ATOM 78 2HB GLN 7 6.606 -6.421 -5.620 1.00 0.00 ATOM 79 1HB GLN 7 6.057 -6.409 -7.285 1.00 0.00
ATOM 80 QB GLN 7 6.332 -6.415 -6.452 1.00 0.00
ATOM 81 CG GLN 7 7.513 -7.940 -6.854 1.00 0.00
ATOM 82 2HG GLN 7 6.702 -8.661 -6.953 1.00 0.00
ATOM 83 1HG GLN 7 8.083 -7.973 -7.782 1.00 0.00 ATOM 84 QG GLN 7 7.392 -8.317 -7.367 1.00 0.00
ATOM 85 CD GLN 7 8.414 -8.336 -5.682 1.00 0.00
ATOM 86 OEl GLN 7 9.501 -7.814 -5.497 1.00 0.00
ATOM 87 NE2 GLN 7 7.903 -9.285 -4.903 1.00 0.00
ATOM 88 1HE2 GLN 7 7.004 -9.672 -5.110 1.00 0.00 ATOM 89 2HE2 GLN 7 8.417 -9.612 -4.1 10 1.00 0.00
ATOM 90 QE2 GLN 7 7.711 -9.642 -4.610 1.00 0.00
ATOM 91 C GLN 7 7.665 -4.803 -8.331 1.00 0.00
ATOM 92 O GLN 7 7.955 -5.366 -9.385 1.00 0.00
ATOM 93 N LEU 8 7.081 -3.616 -8.250 1.00 0.00 ATOM 94 HN LEU 8 6.849 -3.165 -7.388 1.00 0.00
ATOM 95 CA LEU 8 6.730 -2.871 -9.447 1.00 0.00
ATOM 96 HA LEU 8 6.084 -3.509 -10.051 1.00 0.00
ATOM 97 CB LEU 8 5.922 -1.624 -9.084 1.00 0.00
ATOM 98 2HB LEU 8 4.863 -1.883 -9.100 1.00 0.00 ATOM 99 1HB LEU 8 6.165 -1.343 -8.059 1.00 0.00
ATOM 100 QB LEU 8 5.514 -1.613 -8.580 1.00 0.00
ATOM 101 CG LEU 8 6.133 -0.403 -9.982 1.00 0.00
ATOM 102 HG LEU 8 7.189 -0.134 -9.950 1.00 0.00
ATOM 103 QD1 LEU 8 5.713 -0.805 -1 1.784 1.00 0.00 ATOM 104 QD2 LEU 5.156 1.087 -9.342 1.000.00 ATOM 105 CDl LEU 5.794 -0.728-11.438 1.000.00 ATOM 106 1HD1 LEU 4.765 -0.434-11.646 1.000.00 ATOM 107 2HD1 LEU 6.468 -0.183-12.098 1.000.00 ATOM 108 3HD1 LEU 5.907 -1.799-11.607 1.000.00 ATOM 109 CD2 LEU 5.344 0.801 -9.465 1.000.00 ATOM 1 10 1HD2 LEU 6.029 1.625 -9.263 1.000.00 ATOM 1 1 1 2HD2 LEU 4.616 1.109-10.216 1.000.00 ATOM 1 12 3HD2 LEU 4.824 0.528 -8.546 1.000.00 ATOM 113 QQD LEU 5.435 0.141-10.563 1.000.00 ATOM 1 14 C LEU 7.999 -2.571-10.246 1.000.00 ATOM 1 15 O LEU 8.144 -3.022-11.381 1.000.00 ATOM 1 16 N LYS 9 8.887 -1.810 -9.622 1.000.00 ATOM 1 17 HN LYS 9 8.761 -1.447 -8.699 1.000.00 ATOM 1 18 CA LYS 9 10.139 -1.444-10.261 1.000.00 ATOM 1 19 HA LYS 9 9.903 -0.758-11.074 1.000.00 ATOM 120 CB LYS 9 11.041 -0.691 -9.281 1.000.00 ATOM 121 2HB LYS 9 10.547 0.226 -8.957 1.000.00 ATOM 122 1 HB LYS 9 11.201 -1.297 -8.389 1.000.00 ATOM 123 QB LYS 9 10.874 -0.536 -8.673 1.000.00 ATOM 124 CG LYS 9 12.387 -0.352 -9.924 1.000.00 ATOM 125 2HG LYS 9 12.386 -0.667-10.967 1.000.00 ATOM 126 1 HG LYS 9 12.536 0.728 -9.917 1.000.00 ATOM 127 QG LYS 9 12.461 0.030-10.442 1.000.00 ATOM 128 CD LYS 9 13.537 -1.035 -9.180 1.000.00 ATOM 129 2HD LYS 9 13.139 -1.793 -8.506 1.000.00 ATOM 130 1HD LYS 9 14.181 -1.549 -9.894 1.000.00 ATOM 131 QD LYS 9 13.660 -1.671 -9.200 1.000.00 ATOM 132 CE LYS 9 14.357 -0.017 -8.386 1.000.00 ATOM 133 2HE LYS 9 14.830 0.690 -9.068 1.000.00 ATOM 134 IHE LYS 9 13.701 0.559 -7.734 1.000.00 ATOM 135 QE LYS 9 14.265 0.625 -8.401 1.000.00 ATOM 136 NZ LYS 9 15.391 -0.702 -7.578 1.000.00 ATOM 137 1 HZ LYS 9 15.127 -0.769 -6.601 1.000.00 ATOM 138 2HZ LYS 9 15.562 -1.648 -7.902 1.000.00 ATOM 139 QZ LYS 9 15.344 -1.209 -7.252 1.000.00 ATOM 140 C LYS 9 10.788 -2.695-10.856 1.000.00 ATOM 141 O LYS 9 11.578 -2.603-11.794 1.000.00 ATOM 142 N LYS 10 10.431 -3.836-10.286 1.000.00 ATOM 143 HN LYS 10 9.788 -3.903 -9.523 1.000.00 ATOM 144 CA LYS 10 10.968 -5.105-10.748 1.000.00 ATOM 145 HA LYS 10 11.991 -4.925-11.079 1.000.00 ATOM 146 CB LYS 10 11.036 -6.110 -9.596 1.000.00 ATOM 147 2HB LYS 10 10.535 -5.699 -8.720 1.000.00 ATOM 148 1 HB LYS 10 10.501 -7.019 -9.871 1.000.00 ATOM 149 QB LYS 10 10.518 -6.359 -9.295 1.000.00 ATOM 150 CG LYS 10 12.487 -6.449 -9.249 1.000.00 ATOM 151 2HG LYS 10 13.127 -6.248-10.108 1.000.00 ATOM 152 1 HG LYS 10 12.830 -5.807 -8.438 1.000.00 ATOM 153 QG LYS 10 12.978 -6.028 -9.273 1.000.00 ATOM 154 CD LYS 10 12.623 -7.917 -8.838 1.000.00 ATOM 155 2HD LYS 10 12.188 -8.063 -7.849 1.000.00 ATOM 156 1 HD LYS 10 12.062 -8.546 -9.529 1.000.00 ATOM 157 QD LYS 10 12.125 -8.304 -8.689 1.000.00 ATOM 158 CE LYS 10 14.091 -8.348 -8.824 1.000.00 ATOM 159 2HE LYS 10 14.437 -8.512 -9.845 1.000.00 ATOM 160 I HE LYS 10 14.706 -7.553 -8.403 1.000.00 ATOM 161 QE LYS 10 14.572 -8.033 -9.124 1.000.00 ATOM 162 NZ LYS 10 14.260 -9.587 -8.032 1.000.00 ATOM 1631 HZ LYS 10 15.141 -9.599 -7.530 1.000.00
ATOM 1642HZ LYS 10 13.526 -9.698 -7.340 1.000.00
ATOM 165 QZ LYS 10 14.333 -9.649 -7.435 1.000.00
ATOM 166 C LYS 10 10.151 -5.595-11.945 1.000.00
ATOM 167 O LYS 10 10.700 -6.171 -12.882 1.000.00
ATOM 168 N MET 11 8.851 -5.348-11.873 1.000.00
ATOM 169 HN MET 11 8.412 -4.879-11.107 1.000.00
ATOM 170 CA MET 11 7.952 -5.757-12.939 1.000.00
ATOM 171 HA MET 11 8.118 -6.826-13.068 1.000.00
ATOM 172 CB MET 11 6.507 -5.462-12.530 1.000.00
ATOM 1732HB MET 11 6.462 -4.507-12.006 1.000.00
ATOM 1741HB MET 11 5.886 -5.367-13.420 1.000.00
ATOM 175 QB MET 11 6.174 -4.937-12.713 1.000.00
ATOM 176 CG MET 11 5.955 -6.571 -11.632 1.000.00
ATOM 1772HG MET 11 5.327 -7.244-12.215 1.000.00
ATOM 1781HG MET 11 6.775 -7.167-11.230 1.000.00
ATOM 179 QG MET 11 6.051 -7.205-11.723 1.000.00
ATOM 180 SD MET 11 5.009 -5.859-10.296 1.000.00
ATOM 181 QE MET 11 3.319 -5.112-11.392 1.000.00
ATOM 182 CE MET 11 3.605 -5.238-11.207 1.000.00
ATOM 183 IHE MET 11 3.125 -4.443-10.636 1.000.00
ATOM 1842HE MET 11 3.940 -4.845-12.167 1.000.00
ATOM 1853HE MET 11 2.893 -6.047-11.373 1.000.00
ATOM 186 C MET 11 8.274 -5.020-14.241 1.000.00
ATOM 187 O MET 11 7.749 -5.363-15.299 1.000.00
ATOM 188 N VAL 12 9.137 -4.022-14.121 1.000.00
ATOM 189 HN VAL 12 9.560 -3.749-13.256 1.000.00
ATOM 190 CA VAL 12 9.536 -3.234-15.275 1.000.00
ATOM 191 HA VAL 12 9.005 -3.629-16.141 1.000.00
ATOM 192 CB VAL 12 9.113 -1.776-15.084 1.000.00
ATOM 193 HB VAL 12 9.875 -1.144-15.541 1.000.00
ATOM 194 QG1 VAL 12 7.469 -1.427-15.954 1.000.00
ATOM 195 QG2VAL 12 9.016 -1.332-13.246 1.000.00
ATOM 196 CGI VAL 12 7.784 -1.494 -15.787 1.000.00
ATOM 1971HG1 VAL 12 7.519 -2.343-16.418 1.000.00
ATOM 1982HG1 VAL 12 7.004 -1.338-15.042 1.000.00
ATOM 1993HG1 VAL 12 7.882 -0.600-16.403 1.000.00
ATOM 200 CG2 VAL 12 9.035 -1.417-13.599 1.000.00
ATOM 2011HG2VAL 12 9.073 -0.334-13.484 1.000.00
ATOM 2022HG2 VAL 12 8.100 -1.794-13.183 1.000.00
ATOM 2033HG2 VAL 12 9.875 -1.869-13.071 1.000.00
ATOM 204 QQG VAL 12 8.242 -1.379-14.600 1.000.00
ATOM 205 C VAL 12 11.040 -3.396-15.502 1.000.00
ATOM 206 O VAL 12 11.466 -4.249-16.279 1.000.00
ATOM 207 N SER 1 13 11.804 -2.563-14.810 1.000.00
ATOM 208 HN SER 13 11.450 -1.872-14.181 1.000.00
ATOM 209 CA SER 13 13.251 -2.603-14.927 1.000.00
ATOM 210 HA SER 13 13.604 -1.684-14.459 1.000.00
ATOM 211 CB SER 13 13.831 -3.808-14.184 1.000.00
ATOM 2122HB SER 13 13.530 -3.767-13.137 1.000.00
ATOM 2131HB SER 13 13.414 -4.725-14.599 1.000.00
ATOM 214 QB SER 13 13.472 -4.246-13.868 1.000.00
ATOM 215 OG SER 13 15.253 -3.854-14.267 1.000.00
ATOM 216 HG SER 13 15.549 -3.608-15.190 1.000.00
ATOM 217 C SER 1 3 13.657 -2.644-16.402 1.000.00
ATOM 218 O SER 1 13 14.691 -3.211 -16.750 1.000.00
ATOM 219 N LYS S 14 12.820 -2.036-17.230 1.000.00
ATOM 220 HN LYS 14 11.980 -1.577-16.939 1.000.00
ATOM 221 CA LYS 14 13.078 -1.996-18.659 1.000.00 ATOM 222 HA LYS 14 14.102 -2.333-18.816 1.000.00
ATOM 223 CB LYS 14 12.162 -2.975-19.396 1.000.00
ATOM 2242HB LYS 14 11.175 -2.974-18.934 1.000.00
ATOM 2251HB LYS 14 12.030 -2.648-20.428 1.000.00
ATOM 226 QB LYS 14 11.602 -2.811-19.681 1.000.00
ATOM 227 CG LYS 14 12.741 -4.391 -19.374 1.000.00
ATOM 2282HG LYS 14 13.821 -4.343-19.236 1.000.00
ATOM 2291HG LYS 14 12.335 -4.940-18.525 1.000.00
ATOM 230 QG LYS 14 13.078 -4.642-18.880 1.000.00
ATOM 231 CD LYS 14 12.419 -5.135-20.671 1.000.00
ATOM 2322HD LYS 14 11.577 -5.808-20.510 1.000.00
ATOM 2331HD LYS 14 12.116 -4.423-21.438 1.000.00
ATOM 234 QD LYS 14 11.846 -5.115-20.974 1.000.00
ATOM 235 CE LYS 14 13.630 -5.933-21.160 1.000.00
ATOM 2362HE LYS 14 14.482 -5.750-20.506 1.000.00
ATOM 237 IHE LYS 14 13.414 -7.001 -21.110 1.000.00
ATOM 238 QE LYS 14 13.948 -6.375-20.808 1.000.00
ATOM 239 NZ LYS 14 13.973 -5.556-22.549 1.000.00
ATOM 2401HZ LYS 14 14.157 -4.563-22.639 1.000.00
ATOM 2412HZ LYS 14 14.801 -6.039-22.881 1.000.00
ATOM 242 QZ LYS 14 14.479 -5.301 -22.760 1.000.00
ATOM 243 C LYS 14 12.961 -0.553-19.154 1.000.00
ATOM 2440 LYS 14 13.812 -0.080-19.905 1.000.00
ATOM 245 N TYR 15 11.900 0.106-18.712 1.000.00
ATOM 246 HN TYR 15 11.212 -0.286-18.101 1.000.00
ATOM 247 CA TYR 15 11.661 1.486-19.101 1.000.00
ATOM 248 HA TYR 15 11.205 1.482-20.091 1.000.00
ATOM 249 CB TYR 15 10.766 2.082-18.012 1.000.00
ATOM 2502HB TYR 15 11.038 1.642-17.052 1.000.00
ATOM 251 1HB TYR 15 10.963 3.151 -17.939 1.000.00
ATOM 252 QB TYR 15 11.000 2.397-17.496 1.000.00
ATOM 253 QD TYR 15 9.128 1.848-18.272 1.000.00
ATOM 254 QE TYR 15 6.642 1.492-18.667 1.000.00
ATOM 255 QR TYR 15 7.885 1.670-18.470 1.000.00
ATOM 256 CG TYR 15 9.270 1.868-18.250 1.000.00
ATOM 257 CDl TYR 15 8.443 1.543-17.193 1.000.00
ATOM 258 HDl TYR 15 8.856 1.438-16.190 1.000.00
ATOM 259 CE1 TYR 15 7.035 1.341 -17.417 1.000.00
ATOM 260 HEI TYR 15 6.371 1.084-16.592 1.000.00
ATOM 261 CZ TYR 15 6.552 1.479-18.681 1.000.00
ATOM 262 CE2TYR 15 7.339 1.798-19.744 1.000.00
ATOM 263 HE2TYR 15 6.913 1.900-20.742 1.000.00
ATOM 264 CD2 TYR 15 8.747 2.000-19.520 1.000.00
ATOM 265 HD2TYR 15 9.400 2.257-20.354 1.000.00
ATOM 266 OH TYR 15 5.222 1.289-18.892 1.000.00
ATOM 267 HH TYR 15 4.787 2.156-19.135 1.000.00
ATOM 268 C TYR 15 12.970 2.275-19.156 1.000.00
ATOM 2690 TYR 15 13.936 1.930-18.477 1.000.00
ATOM 270 N LYS 16 12.961 3.318-19.973 1.000.00
ATOM 271 HN LYS 16 12.172 3.592-20.522 1.000.00
ATOM 272 CA LYS 16 14.137 4.159-20.126 1.000.00
ATOM 273 HA LYS 16 14.922 3.545-20.567 1.000.00
ATOM 274 CB LYS 16 13.854 5.303-21.102 1.000.00
ATOM 2752HB LYS 16 13.154 4.968-21.868 1.000.00
ATOM 2761HB LYS 16 13.375 6.127-20.573 1.000.00
ATOM 277 QB LYS 16 13.265 5.548-21.220 1.000.00
ATOM 278 CG LYS 16 15.144 5.793-21.761 1.000.00
ATOM 2792HG LYS 16 15.125 6.880-21.844 1.000.00
ATOM 2801HG LYS 16 15.998 5.537-21.133 1.000.00 ATOM 281 QG LYS 16 15.561 6.208-21.489 1.000.00
ATOM 282 CD LYS 16 15.321 5.173-23.149 1.000.00
ATOM 2832HD LYS 16 14.442 4.579-23.400 1.000.00
ATOM 2841HD LYS 16 15.396 5.963-23.897 1.000.00
ATOM 285 QD LYS 16 14.919 5.271 -23.648 1.000.00
ATOM 286 CE LYS 16 16.571 4.293-23.201 1.000.00
ATOM 2872HE LYS 16 17.210 4.507-22.344 1.000.00
ATOM 288 IHE LYS 16 16.286 3.243-23.131 1.000.00
ATOM 289 QE LYS 16 16.748 3.875-22.738 1.000.00
ATOM 290 NZ LYS 16 17.318 4.528-24.456 1.000.00
ATOM 2911 HZ LYS 16 18.118 5.135-24.314 1.000.00
ATOM 2922HZ LYS 16 17.672 3.665-24.855 1.000.00
ATOM 293 QZ LYS 16 17.895 4.400-24.585 1.000.00
ATOM 294 C LYS 16 14.606 4.629-18.747 1.000.00
ATOM 295 O LYS 16 15.796 4.580-18.443 1.000.00
ATOM 296 N TYR 17 13.645 5.073-17.950 1.000.00
ATOM 297 HN TYR 17 12.679 5.109-18.206 1.000.00
ATOM 298 CA TYR 17 13.945 5.551 -16.611 1.000.00
ATOM 299 HA TYR 17 14.969 5.264-16.373 1.000.00
ATOM 300 CB TYR 17 13.718 7.064-16.643 1.000.00
ATOM 3012HB TYR 17 12.647 7.261 -16.616 1.000.00
ATOM 3021HB TYR 17 14.146 7.504-15.742 1.000.00
ATOM 303 QB TYR 17 13.396 7.382-16.179 1.000.00
ATOM 304 QD TYR 17 14.376 7.823-17.983 1.000.00
ATOM 305 QE TYR 17 15.374 8.976-20.018 1.000.00
ATOM 306 QR TYR 17 14.875 8.399-19.001 1.000.00
ATOM 307 CG TYR 17 14.319 7.757-17.867 1.000.00
ATOM 308 CDl TYR 17 15.689 7.876-17.991 1.000.00
ATOM 309 HDl TYR 17 16.342 7.475-17.215 1.000.00
ATOM 310 CE1TYR 17 16.254 8.528-19.143 1.000.00
ATOM 311 HEI TYR 17 17.334 8.629-19.253 1.000.00
ATOM 312 CZ TYR 17 15.410 9.017-20.091 1.000.00
ATOM 313 CE2TYR 17 14.057 8.917-20.001 1.000.00
ATOM 314 HE2TYR 17 13.415 9.322-20.783 1.000.00
ATOM 315 CD2TYR 17 13.492 8.264-18.848 1.000.00
ATOM 316 HD2TYR 17 12.410 8.171 -18.751 1.000.00
ATOM 317 OH TYR 17 15.944 9.633-21.179 1.000.00
ATOM 318 HH TYR 17 16.655 10.277-20.894 1.000.00
ATOM 319 C TYR 17 13.000 4.927-15.582 1.000.00
ATOM 320 O TYR 17 12.121 5.604-15.050 1.000.00
ATOM 321 N ARG 18 13.212 3.644-15.332 1.000.00
ATOM 322 HN ARG 18 13.929 3.100-15.769 1.000.00
ATOM 323 CA ARG 18 12.390 2.921 -14.376 1.000.00
ATOM 324 HA ARG 18 11.432 2.787-14.878 1.000.00
ATOM 325 CB ARG 18 13.006 1.562-14.037 1.000.00
ATOM 3262HB ARG 18 13.915 1.707-13.452 1.000.00
ATOM 3271HB ARG 18 12.315 0.991 -13.417 1.000.00
ATOM 328 QB ARG 18 13.115 1.349-13.434 1.000.00
ATOM 329 CG ARG 18 13.331 0.774-15.308 1.000.00
ATOM 3302HG ARG 18 12.699 -0.112-15.361 1.000.00
ATOM 3311HG ARG 18 13.104 1.381 -16.184 1.000.00
ATOM 332 QG ARG 18 12.901 0.635-15.773 1.000.00
ATOM 333 CD ARG 18 14.803 0.360-15.335 1.000.00
ATOM 3342HD ARG 18 15.178 0.251-14.317 1.000.00
ATOM 3351HD ARG 18 14.908 -0.611 -15.819 1.000.00
ATOM 336 QD ARG 18 15.043 -0.180-15.068 1.000.00
ATOM 337 NE ARG 18 15.601 1.374-16.060 1.000.00
ATOM 338 HE ARG 18 15.131 1.949-16.731 1.000.00
ATOM 339 CZ ARG 18 16.923 1.572-15.874 1.000.00 ATOM 340 NH1 ARG 18 17.536 2.507-16.577 1.000.00
ATOM 341 HH1 ARG 18 18.510 2.716-16.499 1.000.00
ATOM 342 NH2ARG 18 17.609 0.826-14.982 1.000.00
ATOM 3431HH2ARG 18 18.588 0.979-14.850 1.000.00 ATOM 3442HH2ARG 18 17.137 0.120-14.454 1.000.00
ATOM 345 QH2ARG 18 17.863 0.550-14.652 1.000.00
ATOM 346 C ARG 18 12.230 3.736 -13.092 1.000.00
ATOM 347 O ARG 18 11.111 3.988-12.648 1.000.00
ATOM 348 N ASP 19 13.365 4.126-12.530 1.000.00 ATOM 349 HN ASP 19 14.271 3.917-12.898 1.000.00
ATOM 350 CA ASP 19 13.365 4.907-11.305 1.000.00
ATOM 351 HA ASP 19 12.944 4.248-10.546 1.000.00
ATOM 352 CB ASP 19 14.783 5.336-10.925 1.000.00
ATOM 3532HB ASP 19 15.350 4.449-10.639 1.000.00 ATOM 3541HB ASP 19 15.269 5.754 -11.806 1.000.00
ATOM 355 QB ASP 19 15.309 5.102-11.223 1.000.00
ATOM 356 CG ASP 19 14.867 6.357 -9.788 1.000.00
ATOM 357 OD1 ASP 19 14.032 6.363 -8.872 1.000.00
ATOM 358 OD2ASP 19 15.855 7.183 -9.870 1.000.00 ATOM 359 HD2 ASP 19 16.407 7.139 -9.037 1.000.00
ATOM 360 C ASP 19 12.528 6.171 -11.512 1.000.00
ATOM 361 O ASP 19 11.582 6.423-10.767 1.000.00
ATOM 362 N LEU 20 2.907 6.934-12.527 1.000.00
ATOM 363 HN LEU 20 13.678 6.722-13.128 1.000.00 ATOM 364 CA LEU 20 1 122..220044 8.166-12.841 1.000.00
ATOM 365 HA LEU 20 1122..333344 8.841-11.995 1.000.00
ATOM 366 CB LEU 20 1122..883311 8.844-14.061 1.000.00
ATOM 3672HB LEU 20 1133..889988 : 8.623-14.067 1.000.00
ATOM 3681HB LEU 20 1122..440077 ' 8.395-14.959 1.000.00 ATOM 369 QB LEU 20 1133..115533 8.509-14.513 1.000.00
ATOM 370 CG LEU 20 1122..665522 10.361 -14.150 1.000.00
ATOM 371 HG LEU 20 1111..990033 10.661 -13.418 1.000.00
ATOM 372 QD1 LEU 20 1144..225588 \ 11.261 -13.706 1.000.00
ATOM 373 QD2 LEU 20 12.003 10.869-15.855 1.000.00 ATOM 374 CDl LEU 20 13.950 11.088-13.792 1.000.00
ATOM 3751 HDl LEU 20 13.779 12.165-13.805 1.000.00
ATOM 3762HD1 LEU 20 14.273 10.784-12.796 1.000.00
ATOM 3773HD1LEU 20 14.722 10.833-14.518 1.000.00
ATOM 378 CD2 LEU 20 12.128 10.772-15.528 1.000.00 ATOM 3791HD2LEU 20 12.965 11.057-16.165 1.000.00
ATOM 3802HD2 LEU 20 11.597 9.933-15.979 1.000.00
ATOM 3813HD2LEU 20 11.448 11.617-15.421 1.000.00
ATOM 382 QQD LEU 20 13.131 11.065-14.781 1.000.00
ATOM 383 C LEU 20 10.712 7.869-13.002 1.000.00 ATOM 384 O LEU 20 9.870 8.677-12.612 1.000.00
ATOM 385 N THR 21 10.430 6.709-13.575 1.000.00
ATOM 386 HN THR 21 11.121 6.058-13.889 1.000.00
ATOM 387 CA THR 21 9.054 6.296-13.792 1.000.00
ATOM 388 HA THR 21 8.510 7.131 -14.233 1.000.00 ATOM 389 CB THR 21 9.061 5.118 -14.768 1.000.00
ATOM 390 HB THR 21 9.612 4.274-14.355 1.000.00
ATOM 391 QG2THR 21 7.317 4.599-15.291 1.000.00
ATOM 392 OGl THR 21 9.634 5.657-15.957 1.000.00
ATOM 393 HG1 THR 21 10.547 6.016-15.765 1.000.00 ATOM 394 CG2 THR 21 7.652 4.698-15.191 1.000.00
ATOM 3951HG2THR 21 7.011 4.641 -14.311 1.000.00
ATOM 3962HG2THR 21 7.247 5.432-15.887 1.000.00
ATOM 3973HG2THR 21 7.693 3.722-15.674 1.000.00 ATOM 398 C THR 21 8.377 5.974 -12.458 1.000.00 ATOM 399 O THR 21 7.363 6.578 -12.1 10 1.00 0.00
ATOM 400 N VAL 22 8.966 5.024 -1 1.746 1.00 0.00
ATOM 401 HN VAL 22 9.791 4.539 -12.036 1.00 0.00
ATOM 402 CA VAL 22 8.433 4.615 -10.458 1.00 0.00
ATOM 403 HA VAL 22 7.471 4.135 -10.637 1.00 0.00
ATOM 404 CB VAL 22 9.362 3.586 -9.810 1.00 0.00
ATOM 405 HB VAL 22 10.381 3.968 -9.874 1.00 0.00
ATOM 406 QG1 VAL 22 8.942 3.352 -7.979 1.00 0.00
ATOM 407 QG2 VAL 22 9.299 1.937 -10.737 1.00 0.00
ATOM 408 CGI VAL 22 9.023 3.397 -8.330 1.00 0.00
ATOM 409 1 HG1 VAL 22 9.732 2.701 -7.881 1.00 0.00
ATOM 410 2HG1 VAL 22 9.082 4.357 -7.818 1.00 0.00
ATOM 41 1 3HG1 VAL 22 8.013 2.997 -8.237 1.00 0.00
ATOM 412 CG2 VAL 22 9.31 1 2.254 -10.559 1.00 0.00
ATOM 413 1 HG2 VAL 22 8.955 2.422 -1 1.576 1.00 0.00
ATOM 414 2HG2 VAL 22 10.310 1.817 -10.592 1.00 0.00
ATOM 415 3HG2 VAL 22 8.634 1.573 -10.045 1.00 0.00
ATOM 416 QQG VAL 22 9.121 2.644 -9.358 1.00 0.00
ATOM 417 C VAL 22 8.21 1 5.853 -9.586 1.00 0.00
ATOM 418 O VAL 22 7.271 5.898 -8.794 1.00 0.00
ATOM 419 N ARG 23 9.092 6.827 -9.762 1.00 0.00
ATOM 420 HN ARG 23 9.854 6.782 -10.408 1.00 0.00
ATOM 421 CA ARG 23 9.005 8.062 -9.001 1.00 0.00
ATOM 422 HA ARG 23 8.878 7.743 -7.966 1.00 0.00
ATOM 423 CB ARG 23 10.282 8.891 -9.149 1.00 0.00
ATOM 424 2HB ARG 23 1 1.152 8.236 -9.11 1 1.00 0.00
ATOM 425 1HB ARG 23 10.292 9.379 -10.123 1.00 0.00
ATOM 426 QB ARG 23 10.722 8.808 -9.617 1.00 0.00
ATOM 427 CG ARG 23 10.382 9.945 -8.044 1.00 0.00
ATOM 428 2HG ARG 23 9.640 10.726 -8.212 1.00 0.00
ATOM 429 1HG ARG 23 10.152 9.490 -7.080 1.00 0.00
ATOM 430 QG ARG 23 9.896 10.108 -7.646 1.00 0.00
ATOM 431 CD ARG 23 1 1.780 10.564 -8.001 1.00 0.00
ATOM 432 2HD ARG 23 12.433 9.964 -7.366 1.00 0.00
ATOM 433 1 HD ARG 23 12.218 10.563 -8.999 1.00 0.00
ATOM 434 QD ARG 23 12.325 10.263 -8.183 1.00 0.00
ATOM 435 NE ARG 23 1 1.706 1 1.948 -7.484 1.00 0.00
ATOM 436 HE ARG 23 10.818 12.407 -7.499 1.00 0.00
ATOM 437 CZ ARG 23 12.762 12.630 -6.992 1.00 0.00
ATOM 438 NH1 ARG 23 12.581 13.863 -6.556 1.00 0.00
ATOM 439 HH1 ARG 23 13.309 14.435 -6.178 1.00 0.00
ATOM 440 NH2 ARG 23 13.985 12.060 -6.947 1.00 0.00
ATOM 441 1 HH2 ARG 23 14.762 12.572 -6.581 1.00 0.00
ATOM 442 2HH2 ARG 23 14.1 14 1 1.126 -7.279 1.00 0.00
ATOM 443 QH2 ARG 23 14.438 1 1.849 -6.930 1.00 0.00
ATOM 444 C ARG : 23 7.808 8.891 -9.472 1.00 0.00
ATOM 445 O ARG 23 7.164 9.568 -8.672 1.00 0.00
ATOM 446 N GLU : 24 7.548 8.812 -10.769 1.00 0.00
ATOM 447 HN GLU 24 8.077 8.259 -1 1.413 1.00 0.00
ATOM 448 CA GLU 24 6.440 9.547 -11.355 1.00 0.00
ATOM 449 HA GLU 24 6.497 10.548 -10.927 1.00 0.00
ATOM 450 CB GLU 24 6.590 9.644 -12.875 1.00 0.00
ATOM 451 2HB GLU 24 7.324 8.915 -13.219 1.00 0.00
ATOM 452 1HB GLU 24 5.644 9.393 -13.354 1.00 0.00
ATOM 453 QB GLU 24 6.484 9.154 -13.286 1.00 0.00
ATOM 454 CG GLU 24 7.024 1 1.050 -13.295 1.00 0.00
ATOM 455 2HG GLU 24 7.982 11.292 - 12.834 1.00 0.00
ATOM 456 1 HG GLU 24 7.172 1 1.081 -14.374 1.00 0.00
ATOM 457 QG GLU 24 7.577 1 1.186 -13.604 1.00 0.00 ATOM 458 CD GLU 24 5.979 12.091 -12.887 1.00 0.00 ATOM 459 OEl GLU 24 4.996 1 1.751 -12.212 1.00 0.00 ATOM 460 OE2 GLU 24 6.216 13.290 -13.297 1.00 0.00 ATOM 461 HE2 GLU 24 6.940 13.703 - 12.745 1.00 0.00 ATOM 462 C GLU 24 5.109 8.894 -10.976 1.00 0.00 ATOM 463 O GLU 24 4.120 9.585 -10.740 1.00 0.00 ATOM 464 N THR 25 5.128 7.570 -10.931 1.00 0.00 ATOM 465 HN THR 25 5.937 7.015 -1 1.125 1.00 0.00 ATOM 466 CA THR 25 3.935 6.816 -10.584 1.00 0.00 ATOM 467 HA THR 25 3.101 7.206 -1 1.168 1.00 0.00 ATOM 468 CB THR 25 4.178 5.352 -10.955 1.00 0.00 ATOM 469 HB THR 25 5.129 5.001 -10.555 1.00 0.00 ATOM 470 QG2 THR 25 2.757 4.223 -10.413 1.00 0.00 ATOM 471 OGl THR 25 4.108 5.338 -12.378 1.00 0.00 ATOM 472 HG1 THR 25 4.996 5.085 -12.762 1.00 0.00 ATOM 473 CG2 THR 25 3.030 4.439 -10.517 1.00 0.00 ATOM 474 1HG2 THR 25 2.938 3.609 -1 1.218 1.00 0.00 ATOM 475 2HG2 THR 25 3.235 4.051 -9.519 1.00 0.00 ATOM 4763HG2 THR 25 2.100 5.007 -10.503 1.00 0.00 ATOM 477 C THR 25 3.586 7.019 -9.109 1.00 0.00 ATOM 478 O THR 25 2.471 7.423 -8.782 1.00 0.00 ATOM 479 N VAL 26 4.559 6.731 -8.258 1.00 0.00 ATOM 480 HN VAL 26 5.463 6.403 -8.532 1.00 0.00 ATOM 481 CA VAL 26 4.368 6.877 -6.825 1.00 0.00 ATOM 482 HA VAL 26 3.61 1 6.154 -6.519 1.00 0.00 ATOM 483 CB VAL 26 5.666 6.544 -6.087 1.00 0.00 ATOM 484 HB VAL 26 5.529 6.797 -5.036 1.00 0.00 ATOM 485 QG1 VAL 26 6.053 4.694 -6.195 1.00 0.00 ATOM 486 QG2 VAL 26 7.107 7.578 -6.750 1.00 0.00 ATOM 487 CGI VAL 26 5.979 5.049 -6.174 1.00 0.00 ATOM 488 1HG1 VAL 26 6.303 4.688 -5.198 1.00 0.00 ATOM 489 2HG1 VAL 26 5.084 4.508 -6.483 1.00 0.00 ATOM 490 3HG1 VAL 26 6.772 4.885 -6.903 1.00 0.00 ATOM 491 CG2 VAL 26 6.831 7.380 -6.623 1.00 0.00 ATOM 492 1HG2 VAL 26 6.605 7.708 -7.637 1.00 0.00 ATOM 493 2HG2 VAL 26 6.977 8.250 -5.983 1.00 0.00 ATOM 4943HG2 VAL 26 7.738 6.776 -6.629 1.00 0.00 ATOM 495 QQG VAL 26 6.580 6.136 -6.472 1.00 0.00 ATOM 496 C VAL : 26 3.854 8.286 -6.524 1.00 0.00 ATOM 497 O VAL 26 2.955 8.461 -5.703 1.00 0.00 ATOM 498 N ASN : 27 4.446 9.255 -7.206 1.00 0.00 ATOM 499 HN ASN 27 5.176 9.105 -7.872 1.00 0.00 ATOM 500 CA ASN 27 4.059 10.644 -7.022 1.00 0.00 ATOM 501 HA ASN 27 4.356 10.892 -6.004 1.00 0.00 ATOM 502 CB ASN 27 4.769 1 1.551 -8.029 1.00 0.00 ATOM 503 2HB ASN 27 4.918 1 1.014 -8.966 1.00 0.00 ATOM 504 1HB ASN 27 4.140 12.414 -8.253 1.00 0.00 ATOM 505 QB ASN 27 4.529 11.714 -8.610 1.00 0.00 ATOM 506 CG ASN 27 6.1 18 12.024 -7.486 1.00 0.00 ATOM 507 OD1 ASN 27 6.809 1 1.318 -6.769 1.00 0.00 ATOM 508 ND2 ASN 27 6.454 13.253 -7.865 1.00 0.00 ATOM 509 1 HD2 ASN 27 5.841 13.779 -8.455 1.00 0.00 ATOM 510 2HD2 ASN 27 7.319 13.652 -7.561 1.00 0.00 ATOM 51 1 QD2 ASN 27 6.580 13.716 -8.008 1.00 0.00 ATOM 512 C ASN : 27 2.551 10.782 -7.242 1.00 0.00 ATOM 513 O ASN : 27 1.859 1 1.410 -6.443 1.00 0.00 ATOM 514 N VAL : 28 2.087 10.185 -8.330 1.00 0.00 ATOM 515 HN VAL 28 2.657 9.676 -8.975 1.00 0.00 ATOM 516 CA VAL 28 0.674 10.233 -8.665 1.00 0.00 ATOM 517 HA VAL 28 0.406 1 1.280 -8.812 1.00 0.00
ATOM 518 CB VAL 28 0.422 9.491 -9.979 1.00 0.00
ATOM 519 HB VAL 28 0.905 8.517 -9.912 1.00 0.00
ATOM 520 QG1 VAL 28 -1.430 9.205 -10.253 1.00 0.00 ATOM 521 QG2 VAL 28 1.188 10.420 -1 1.441 1.00 0.00
ATOM 522 CGI VAL 28 -1.074 9.260 -10.200 1.00 0.00
ATOM 523 1 HG1 VAL 28 -1.433 8.506 -9.499 1.00 0.00
ATOM 524 2HG 1 VAL 28 -1.614 10.193 -10.038 1.00 0.00
ATOM 525 3HG 1 VAL 28 -1.242 8.916 -1 1.221 1.00 0.00 ATOM 526 CG2 VAL 28 1.041 10.242 -1 1.160 1.00 0.00
ATOM 527 1HG2 VAL 28 1.952 10.744 -10.834 1.00 0.00
ATOM 528 2HG2 VAL 28 1.281 9.534 -1 1.954 1.00 0.00
ATOM 529 3HG2 VAL 28 0.332 10.980 -1 1.534 1.00 0.00
ATOM 530 QQG VAL 28 -0.121 9.812 -10.847 1.00 0.00 ATOM 531 C VAL 28 -0.142 9.676 -7.498 1.00 0.00
ATOM 532 O VAL 28 -0.879 10.412 -6.843 1.00 0.00
ATOM 533 N ILE 29 0.016 8.379 -7.273 1.00 0.00
ATOM 534 HN ILE 29 0.617 7.788 -7.810 1.00 0.00
ATOM 535 CA ILE 29 -0.697 7.714 -6.195 1.00 0.00 ATOM 536 HA ILE 29 -1.762 7.786 -6.416 1.00 0.00
ATOM 537 CB ILE 29 -0.342 6.227 -6.156 1.00 0.00
ATOM 538 HB ILE 29 -0.803 5.789 -5.271 1.00 0.00
ATOM 539 QG2 ILE 29 -1.049 5.320 -7.661 1.00 0.00
ATOM 540 CG2 ILE 29 -0.913 5.494 -7.372 1.00 0.00 ATOM 541 1 HG2 ILE 29 -1.791 6.028 -7.738 1.00 0.00
ATOM 542 2HG2 ILE 29 -0.160 5.452 -8.158 1.00 0.00
ATOM 543 3HG2 ILE 29 -1.197 4.482 -7.086 1.00 0.00
ATOM 544 CGI ILE 29 1.169 6.027 -6.025 1.00 0.00
ATOM 545 2HG 1 ILE 29 1.666 6.382 -6.927 1.00 0.00 ATOM 546 1 HG 1 ILE 29 1.548 6.625 -5.196 1.00 0.00
ATOM 547 QG1 ILE 29 1.607 6.503 -6.062 1.00 0.00
ATOM 548 QD1 ILE 29 1.590 4.203 -5.741 1.00 0.00
ATOM 549 CDl ILE 29 1.510 4.553 -5.795 1.00 0.00
ATOM 550 1 HD1 ILE 29 2.097 4.181 -6.635 1.00 0.00 ATOM 551 2HD1 ILE 29 2.086 4.452 -4.875 1.00 0.00
ATOM 552 3HD1 ILE 29 0.588 3.976 -5.712 1.00 0.00
ATOM 553 C ILE 29 - 0.423 .447 -4.880 1.00 0.00
ATOM 554 O ILE 29 • 1.220 1.371 -3.946 1.00 0.00
ATOM 555 N THR 30 0.706 9.139 -4.849 1.00 0.00 ATOM 556 HN THR 30 1.348 9.196 -5.613 1.00 0.00
ATOM 557 CA THR 30 1.094 9.885 -3.664 1.000.00
ATOM 558 HA THR 30 0.849 9.287 -2.786 1.000.00
ATOM 559 CB THR 30 2.606 10.1 1 1 -3.722 1.000.00
ATOM 560 HB THR 30 2.914 10.433 -4.717 1.000.00 ATOM 561 QG2 THR 30 3.209 1 1.326 -2.401 1.000.00
ATOM 562 OGl THR 30 3.160 8.860 -3.321 1.000.00
ATOM 563 HG1 THR 30 3.785 8.522 -4.025 1.000.00
ATOM 564 CG2 THR 30 3.093 1 1.093 -2.655 1.000.00
ATOM 565 1 HG2 THR 30 2.460 1 1.981 -2.662 1.000.00 ATOM 566 2HG2 THR 30 3.042 10.619 -1.675 1.000.00
ATOM 567 3HG2 THR 30 4.123 11.379 -2.867 1.000.00
ATOM 568 C THR 30 0.289 11.182 -3.562 1.000.00
ATOM 569 O THR 30 0.190 11.772 -2.488 1.000.00
ATOM 570 N LEU 31 -0.264 11.588 -4.696 1.000.00 ATOM 571 HN LEU 31 -0.178 11.102 -5.565 1.000.00
ATOM 572 CA LEU 31 -1.057 12.804 -4.748 1.000.00
ATOM 573 HA LEU 31 -0.750 13.430 -3.910 1.00 0.00
ATOM 574 CB LEU 31 -0.758 13.585 -6.029 1.00 0.00
ATOM 575 2HB LEU 31 0.316 13.768 -6.077 1.00 0.00 ATOM 576 1HB LEU 31 - 1.012 12.955 -6.882 1.00 0.00
ATOM 577 QB LEU 31 -0.348 13.361 -6.480 1.00 0.00
ATOM 578 CG LEU 31 -1.482 14.923 -6.184 1.00 0.00
ATOM 579 HG LEU 31 -2.261 14.980 -5.424 1.00 0.00
ATOM 580 QD1 LEU 31 -0.302 16.373 -5.885 1.00 0.00
ATOM 581 QD2 LEU 31 -2.337 15.040 -7.869 1.00 0.00
ATOM 582 CDl LEU 31 -0.528 16.094 -5.943 1.00 0.00
ATOM 583 1HD1 LEU 31 0.391 15.726 -5.487 1.00 0.00
ATOM 584 2HD1 LEU 31 -0.296 16.576 -6.893 1.00 0.00
ATOM 585 3HD1 LEU 31 -1.001 16.816 -5.276 1.00 0.00
ATOM 586 CD2 LEU 31 -2.173 15.018 -7.546 1.00 0.00
ATOM 587 1HD2 LEU 31 -2.102 16.039 -7.919 1.00 0.00
ATOM 588 2HD2 LEU 31 -1.688 14.340 -8.248 1.00 0.00
ATOM 589 3HD2 LEU 31 -3.223 14.742 -7.441 1.00 0.00
ATOM 590 QQD LEU 31 -1.320 15.706 -6.877 1.00 0.00
ATOM 591 C LEU : 31 -2.535 12.452 -4.573 1.00 0.00
ATOM 592 O LEU 31 -3.279 13.185 -3.923 1.00 0.00
ATOM 593 N TYR 32 -2.917 1 1.330 -5.165 1.00 0.00
ATOM 594 HN TYR 32 -2.306 10.740 -5.692 1.00 0.00
ATOM 595 CA TYR 32 -4.294 10.872 -5.084 1.00 0.00
ATOM 596 HA TYR 32 -4.924 1 1.736 -4.873 1.00 0.00
ATOM 597 CB TYR 32 -4.595 10.201 -6.425 1.00 0.00
ATOM 598 2HB TYR 32 -3.930 9.346 -6.550 1.00 0.00
ATOM 599 1HB TYR 32 -5.613 9.812 -6.405 1.00 0.00
ATOM 600 QB TYR 32 -4.772 9.579 -6.477 1.00 0.00
ATOM 601 QD TYR 32 -4.428 1 1.216 -7.747 1.00 0.00
ATOM 602 QE TYR 32 -4.175 12.756 -9.754 1.00 0.00
ATOM 603 QR TYR 32 -4.302 1 1.986 -8.750 1.00 0.00
ATOM 604 CG TYR 32 -4.443 1 1.128 -7.633 1.00 0.00
ATOM 605 CDl TYR 32 -3.882 10.653 -8.801 1.00 0.00
ATOM 606 HDl TYR 32 -3.548 9.617 -8.863 1.00 0.00
ATOM 607 CE1 TYR 32 -3.739 1 1.525 -9.938 1.00 0.00
ATOM 608 HEI TYR 32 -3.298 1 1.163 -10.866 1.00 0.00
ATOM 609 CZ TYR 32 -4.166 12.812 -9.826 1.00 0.00
ATOM 610 CE2 TYR 32 -4.722 13.312 -8.690 1.00 0.00
ATOM 61 1 HE2 TYR 32 -5.052 14.349 -8.641 1.00 0.00
ATOM 612 CD2 TYR 32 -4.866 12.439 -7.554 1.00 0.00
ATOM 613 HD2 TYR 32 -5.308 12.814 -6.631 1.00 0.00
ATOM 614 OH TYR 32 -4.030 13.636 -10.899 1.00 0.00
ATOM 615 HH TYR 32 -4.320 14.562 -10.658 1.00 0.00
ATOM 616 C TYR 32 -4.464 9.844 -3.963 1.00 0.00
ATOM 617 O TYR 32 -5.253 10.049 -3.042 1.00 0.00
ATOM 618 N LYS : 33 -3.711 8.760 -4.079 1.00 0.00
ATOM 619 HN LYS 33 -3.071 8.601 -4.831 1.00 0.00
ATOM 620 CA LYS 33 -3.768 7.699 -3.087 1.00 0.00
ATOM 621 HA LYS 33 -2.855 7.1 1 1 -3.185 1.00 0.00
ATOM 622 CB LYS 33 -3.779 8.287 -1.675 1.00 0.00
ATOM 623 2HB LYS 33 -3.606 9.362 -1.722 1.00 0.00
ATOM 624 1HB LYS 33 -4.761 8.142 -1.224 1.00 0.00
ATOM 625 QB LYS 33 -4.184 8.752 -1.473 1.00 0.00
ATOM 626 CG LYS 33 -2.709 7.631 -0.799 1.00 0.00
ATOM 627 2HG LYS 33 -2.493 6.629 -1.172 1.00 0.00
ATOM 628 1HG LYS 33 -1.783 8.201 -0.863 1.00 0.00
ATOM 629 QG LYS 33 -2.138 7.415 -1.017 1.00 0.00
ATOM 630 CD LYS 33 -3.167 7.550 0.658 1.00 0.00
ATOM 631 2HD LYS 33 -4.252 7.460 0.698 1.00 0.00
ATOM 632 1HD LYS 33 -2.755 6.655 1.124 1.00 0.00
ATOM 633 QD LYS 33 -3.504 7.057 0.91 1 1.00 0.00
ATOM 634 CE LYS 33 -2.724 8.788 1.441 1.00 0.00 ATOM 635 2HE LYS 33 -2.162 9.457 0.788 1.00 0.00
ATOM 636 I HE LYS 33 -3.599 9.340 1.785 1.00 0.00
ATOM 637 QE LYS 33 -2.881 9.398 1.287 1.00 0.00
ATOM 638 NZ LYS 33 -1.889 8.399 2.599 1.00 0.00
ATOM 639 1 HZ LYS 33 -1.423 7.51 1 2.449 1.00 0.00
ATOM 640 2HZ LYS 33 - 1.165 9.082 2.793 1.00 0.00
ATOM 641 QZ LYS 33 -1.294 8.296 2.621 1.00 0.00
ATOM 642 C LYS 33 -4.964 6.792 -3.386 1.00 0.00
ATOM 643 O LYS 33 -5.219 5.836 -2.656 1.00 0.00
ATOM 644 N ASP 34 -5.665 7.125 -4.460 1.00 0.00
ATOM 645 HN ASP 34 -5.450 7.904 -5.048 1.00 0.00
ATOM 646 CA ASP 34 -6.827 6.352 -4.863 1.00 0.00
ATOM 647 HA ASP 34 -7.074 5.734 -4.000 1.00 0.00
ATOM 648 CB ASP 34 -7.998 7.267 -5.227 1.00 0.00
ATOM 649 2HB ASP 34 -7.763 7.779 -6.160 1.00 0.00
ATOM 650 1HB ASP 34 -8.877 6.651 -5.413 1.00 0.00
ATOM 651 QB ASP 34 -8.320 7.215 -5.787 1.00 0.00
ATOM 652 CG ASP 34 -8.351 8.316 -4.170 1.00 0.00
ATOM 653 OD1 ASP 34 -7.551 9.216 -3.871 1.00 0.00
ATOM 654 OD2 ASP 34 -9.518 8.181 -3.637 1.00 0.00
ATOM 655 HD2 ASP 34 -9.723 7.212 -3.502 1.00 0.00
ATOM 656 C ASP 34 -6.477 5.520 -6.098 1.00 0.00
ATOM 657 O ASP 34 -7.109 4.498 -6.362 1.00 0.00
ATOM 658 N LEU 35 -5.471 5.988 -6.822 1.00 0.00
ATOM 659 HN LEU 35 -4.962 6.820 -6.601 1.00 0.00
ATOM 660 CA LEU 35 -5.029 5.299 -8.023 1.00 0.00
ATOM 661 HA LEU 35 -5.913 4.877 -8.501 1.00 0.00
ATOM 662 CB LEU 35 -4.411 6.290 -9.012 1.00 0.00
ATOM 663 2HB LEU 35 -4.508 7.294 -8.599 1.00 0.00
ATOM 664 1 HB LEU 35 -3.344 6.079 -9.088 1.00 0.00
ATOM 665 QB LEU 35 -3.926 6.686 -8.843 1.00 0.00
ATOM 666 CG LEU 35 -5.004 6.289 -10.422 1.00 0.00
ATOM 667 HG LEU 35 -4.998 5.265 -10.795 1.00 0.00
ATOM 668 QD1 LEU 35 -6.807 6.865 -10.400 1.00 0.00
ATOM 669 QD2 LEU 35 -3.944 7.320 -1 1.605 1.00 0.00
ATOM 670 CDl LEU 35 -6.461 6.755 -10.404 1.00 0.00
ATOM 671 1 HD1 LEU 35 -6.614 7.500 -1 1.185 1.00 0.00
ATOM 672 2HD1 LEU 35 -7.117 5.903 -10.582 1.00 0.00
ATOM 673 3HD1 LEU 35 -6.691 7.193 -9.433 1.00 0.00
ATOM 674 CD2 LEU 35 -4.148 7.122 -1 1.378 1.00 0.00
ATOM 675 1 HD2 LEU 35 -4.325 6.796 -12.403 1.00 0.00
ATOM 676 2HD2 LEU 35 -4.414 8.175 - 1 1.281 1.00 0.00
ATOM 677 3HD2 LEU 35 -3.094 6.989 -1 1.131 1.00 0.00
ATOM 678 QQD LEU 35 -5.376 7.093 -1 1.003 1.00 0.00
ATOM 679 C LEU 35 -4.093 4.154 -7.634 1.00 0.00
ATOM 680 0 LEU 35 -3.587 4.1 14 -6.514 1.00 0.00
ATOM 681 N LYS 36 -3.891 3.249 -8.581 1.00 0.00
ATOM 682 HN LYS 36 -4.307 3.289 -9.490 1.00 0.00
ATOM 683 CA LYS 36 -3.025 2.106 -8.351 1.00 0.00
ATOM 684 HA LYS 36 -2.222 2.432 -7.690 1.00 0.00
ATOM 685 CB LYS 36 -3.785 0.995 -7.624 1.00 0.00
ATOM 686 2HB LYS 36 -4.799 1.328 -7.402 1.00 0.00
ATOM 687 1HB LYS 36 -3.872 0.123 -8.273 1.00 0.00
ATOM 688 QB LYS 36 -4.335 0.725 -7.838 1.00 0.00
ATOM 689 CG LYS 36 -3.076 0.603 -6.327 1.00 0.00
ATOM 690 2HG LYS 36 -2.232 -0.049 -6.552 1.00 0.00
ATOM 691 1 HG LYS 36 -2.671 1.493 -5.846 1.00 0.00
ATOM 692 QG LYS 36 -2.451 0.722 -6.199 1.00 0.00
ATOM 693 CD LYS 36 -4.035 -0.108 -5.370 1.00 0.00 ATOM 694 2HD LYS 36 -4.419 0.603 -4.639 1.00 0.00
ATOM 695 1 HD LYS 36 -4.893 -0.488 -5.925 1.00 0.00
ATOM 696 QD LYS 36 -4.656 0.058 -5.282 1.00 0.00
ATOM 697 CE LYS 36 -3.336 -1.262 -4.649 1.00 0.00
ATOM 698 2HE LYS 36 -2.882 -1.933 -5.378 1.00 0.00
ATOM 699 I HE LYS 36 -2.529 -0.874 -4.027 1.00 0.00
ATOM 700 QE LYS 36 -2.706 -1.403 -4.703 1.00 0.00
ATOM 701 NZ LYS 36 -4.300 -2.010 -3.81 1 1.00 0.00
ATOM 702 1 HZ LYS 36 -3.839 -2.524 -3.068 1.00 0.00
ATOM 703 2HZ LYS 36 -4.974 -1.396 -3.368 1.00 0.00
ATOM 704 QZ LYS 36 -4.407 -1.960 -3.218 1.00 0.00
ATOM 705 C LYS 36 -2.409 1.662 -9.680 1.00 0.00
ATOM 706 O LYS 36 -3.120 1.480 - 10.667 1.00 0.00
ATOM 707 N PRO 37 -1.060 1.496 -9.661 1.00 0.00
ATOM 708 CD PRO 37 -0.186 1.702 -8.510 1.00 0.00
ATOM 709 CA PRO 37 -0.341 1.077 -10.852 1.00 0.00
ATOM 710 HA PRO 37 -0.692 1.556 -1 1.657 1.00 0.00
ATOM 711 CB PRO 37 1.1 13 1.428 -10.578 1.00 0.00
ATOM 712 2HB PRO 37 1.778 0.639 -10.931 1.00 0.00
ATOM 713 1HB PRO 37 1.398 2.342 - 1 1.098 1.00 0.00
ATOM 714 QB PRO 37 1.588 1.491 -1 1.015 1.00 0.00
ATOM 715 CG PRO 37 1.223 1.600 -9.072 1.00 0.00
ATOM 716 2HG PRO 37 1.750 0.755 -8.629 1.00 0.00
ATOM 717 1 HG PRO 37 1.796 2.495 -8.831 1.00 0.00
ATOM 718 QG PRO 37 1.773 1.625 -8.730 1.00 0.00
ATOM 719 2HD PRO 37 -0.361 0.950 -7.741 1.00 0.00
ATOM 720 1HD PRO 37 -0.359 2.675 -8.050 1.00 0.00
ATOM 721 QD PRO 37 -0.360 1.812 -7.895 1.00 0.00
ATOM 722 C PRO 37 -0.555 -l 3.413 -1 1.126 1.00 0.00
ATOM 723 O PRO 37 -0.310 - 1.249 -10.258 1.00 0.00
ATOM 724 N VAL 38 - 1.010 - 0.700 - 12.338 1.00 0.00
ATOM 725 HN VAL 38 -1.206 -0.014 -13.038 1.00 0.00
ATOM 726 CA VAL 38 -1.260 -2.074 -12.737 1.00 0.00
ATOM 727 HA VAL 38 -1.127 -2.702 - 1 1.856 1.00 0.00
ATOM 728 CB VAL 38 -2.706 -2.226 -13.213 1.00 0.00
ATOM 729 HB VAL 38 -3.323 -2.449 - 12.343 1.00 0.00
ATOM 730 QG 1 VAL 38 -3.340 -0.615 -13.979 1.00 0.00
ATOM 731 QG2 VAL 38 -2.872 -3.667 -14.429 1.00 0.00
ATOM 732 CG I VAL 38 -3.219 -0.924 -13.832 1.00 0.00
ATOM 733 1 HG1 VAL 38 -3.267 ' -0.151 -13.065 1.00 0.00
ATOM 734 2HG 1 VAL 38 -2.541 -0.607 -14.625 1.00 0.00
ATOM 735 3HG 1 VAL 38 -4.213 i -1.087 -14.248 1.00 0.00
ATOM 736 CG2 VAL 38 -2.840 -3.391 -14.196 1.00 0.00
ATOM 737 1 HG2 VAL 38 -2.43C I -4.295 -13.745 1.00 0.00
ATOM 738 2HG2 VAL 38 -3.893 ■ -3.547 -14.432 1.00 0.00
ATOM 739 3HG2 VAL 38 -2.293 ■ -3.160 -15.1 10 1.00 0.00
ATOM 740 QQG VAL 38 -3.106 i -2.141 - 14.204 1.00 0.00
ATOM 741 C VAL 38 -0.235 -: 2.487 -13.796 1.00 0.00
ATOM 742 O VAL 38 0.338 - 1.637 -14.475 1.00 0.00
ATOM 743 N LEU : 39 -0.036 -: 3.793 -13.903 1.00 0.00
ATOM 744 HN LEU 39 -0.507 -4.478 -13.346 1.00 0.00
ATOM 745 CA LEU 39 0.909 • -4.329 -14.867 1.00 0.00
ATOM 746 HA LEU 39 1.405 -3.484 -15.343 1.00 0.00
ATOM 747 CB LEU 39 1.991 - -5.148 -14.159 1.00 0.00
ATOM 748 2HB LEU 39 2.053 -4.812 - 13.124 1.00 0.00
ATOM 749 1 HB LEU 39 1.673 -6.190 -14.138 1.00 0.00
ATOM 750 QB LEU 39 1.863 ■ -5.501 -13.631 1.00 0.00
ATOM 751 CG LEU 39 3.391 ■ -5.082 -14.772 1.00 0.00
ATOM 752 HG LEU 39 4.053 -5.715 -14.181 1.00 0.00 ATOM 753 QDl LEU 39 3.391 -5.767-16.537 1.000.00
ATOM 754 QD2 LEU 39 4.084 -3.322-14.694 1.000.00
ATOM 755 CDl LEU 39 3.391 -5.635-16.199 1.000.00
ATOM 7561 HDl LEU 39 4.295 -6.223-16.360 1.000.00
ATOM 7572HD1 LEU 39 2.515 -6.268-16.343 1.000.00
ATOM 7583HD1 LEU 39 3.364 -4.809-16.909 1.000.00
ATOM 759 CD2 LEU 39 3.951 -3.659-14.709 1.000.00
ATOM 7601HD2LEU 39 4.827 -3.642-14.061 1.000.00
ATOM 7612HD2LEU 39 4.233 -3.335-15.711 1.000.00
ATOM 7623HD2 LEU 39 3.191 -2.987-14.310 1.000.00
ATOM 763 QQD LEU 39 3.737 -4.544-15.616 1.000.00
ATOM 764 C LEU 39 0.148 -5.112-15.939 1.000.00
ATOM 765 O LEU 39 -0.846 -5.773 -15.642 1.000.00
ATOM 766 N ASP 40 0.645 -5.012-17.163 1.000.00
ATOM 767 HN ASP 40 1.454 -4.473-17.396 1.000.00
ATOM 768 CA ASP 40 0.025 -5.703-18.281 1.000.00
ATOM 769 HA ASP 40 -0.564 -6.503-17.833 1.000.00
ATOM 770 CB ASP 40 -0.870 -4.757-19.085 1.000.00
ATOM 7712HB ASP 40 -1.576 -5.353-19.664 1.000.00
ATOM 7721HB ASP 40 -1.457 -4.157-18.389 1.000.00
ATOM 773 QB ASP 40 -1.516 -4.755-19.027 1.000.00
ATOM 774 CG ASP 40 -0.128 -3.816-20.036 1.000.00
ATOM 775 OD1 ASP 40 -0.102 -2.593-19.833 1.000.00
ATOM 776 OD2 ASP 40 0.449 -4.395-21.035 1.000.00
ATOM 777 HD2 ASP 40 -0.093 -5.180-21.335 1.000.00
ATOM 778 C ASP 40 1.114 -6.231-19.217 1.000.00
ATOM 779 O ASP 40 2.158 -5.602-19.377 1.000.00
ATOM 780 N SER 41 0.833 -7.383 -19.809 1.000.00
ATOM 781 HN SER 41 -0.019 -7.888-19.673 1.000.00
ATOM 782 CA SER 41 1.776 -8.003-20.724 1.000.00
ATOM 783 HA SER 41 2.579 -7.276-20.848 1.000.00
ATOM 784 CB SER 41 2.345 -9.296-20.136 1.000.00
ATOM 7852HB SER 41 3.199 -9.060-19.502 1.000.00
ATOM 7861HB SER 41 1.595 -9.765-19.499 1.000.00
ATOM 787 QB SER 41 2.397 -9.412-19.500 1.000.00
ATOM 788 OG SER 41 2.747-10.212-21.150 1.000.00
ATOM 789 HG SER 41 2.527-11.147-20.873 1.000.00
ATOM 790 C SER 41 1.095 -8.285-22.065 1.000.00
ATOM 791 O SER 41 0.280 -9.199-22.172 1.000.00
ATOM 792 N TYR 42 1.456 -7.481 -23.056 1.000.00
ATOM 793 HN TYR 42 2.120 -6.740-22.961 1.000.00
ATOM 794 CA TYR 42 0.890 -7.633-24.386 1.000.00
ATOM 795 HA TYR 42 0.289 -8.542-24.394 1.000.00
ATOM 796 CB TYR 42 0.086 -6.359-24.649 1.000.00
ATOM 7972HB TYR 42 -0.192 -5.913-23.694 1.000.00
ATOM 7981HB TYR 42 0.722 -5.639-25.164 1.000.00
ATOM 799 QB TYR 42 0.265 -5.776-24.429 1.000.00
ATOM 800 QD TYR 42 -1.301 -6.604-25.557 1.000.00
ATOM 801 QE TYR 42 -3.404 -6.976-26.935 1.000.00
ATOM 802 QR TYR 42 -2.352 -6.790-26.246 1.000.00
ATOM 803 CG TYR 42 -1.181 -6.583-25.478 1.000.00
ATOM 804 CDl TYR 42 -2.405 -6.697-24.851 1.000.00
ATOM 805 HDl TYR 42 -2.470 -6.627 -23.765 1.000.00
ATOM 806 CE1 TYR 42 -3.597 -6.908-25.632 1.000.00
ATOM 807 HEI TYR 42 -4.570 -6.999-25.150 1.000.00
ATOM 808 CZ TYR 42 -3.480 -6.990-26.984 1.000.00
ATOM 809 CE2 TYR 42 -2.290 -6.882-27.633 1.000.00
ATOM 810 HE2TYR 42 -2.239 -6.953-28.720 1.000.00
ATOM 811 CD2TYR 42 -1.098 -6.671 -26.853 1.000.00 ATOM 812 HD2TYR 42 -0.132 -6.581 -27.348 1.000.00
ATOM 813 OH TYR 42 -4.606 -7.189-27.722 1.000.00
ATOM 814 HH TYR 42 -4.487 -6.804-28.637 1.000.00
ATOM 815 C TYR 42 1.993 -7.753-25.440 1.000.00
ATOM 816 O TYR 42 3.162 -7.503-25.151 1.000.00
ATOM 817 N VAL 43 1.581 -8.135-26.640 1.000.00
ATOM 818 HN VAL 43 0.628 -8.336-26.866 1.000.00
ATOM 819 CA VAL 43 2.519 -8.291 -27.738 1.000.00
ATOM 820 HA VAL 43 3.487 -8.548-27.310 1.00 0.00
ATOM 821 CB VAL 43 2.079 -9.444-28.642 1.000.00
ATOM 822 HB VAL 43 2.874 -9.624-29.366 1.000.00
ATOM 823 QG1 VAL 43 1.833-11.033-27.642 1.000.00
ATOM 824 QG2 VAL 43 0.509 -8.995-29.600 1.000.00
ATOM 825 CGI VAL 43 1.880-10.728-27.834 1.000.00
ATOM 8261HG1 VAL , 43 0.832-10.818-27.547 1.000.00
ATOM 8272HG1 VAL , 43 2.165-11.588-28.441 1.000.00
ATOM 8283HG1 VAL , 43 2.501-10.694-26.939 1.000.00
ATOM 829 CG2 VAL 43 0.810 -9.081-29.417 1.00 0.00
ATOM 8301HG2VAL , 43 0.729 -9.717-30.299 1.000.00
ATOM 8312HG2VAL , 43 -0.060 -9.232-28.778 1.000.00
ATOM 8323HG2 VAL . 43 0.859 -8.037-29.724 1.000.00
ATOM 833 QQG VAL 43 1.171-10.014-28.621 1.000.00
ATOM 834 C VAL 43 2.648 -6.962-28.486 1.000.00
ATOM 835 O VAL 43 1.703 -6.176-28.530 1.000.00
ATOM 836 N PHE 44 3.826 -6.751 -29.055 1.000.00
ATOM 837 HN PHE 44 4.589 -7.396-29.014 1.000.00
ATOM 838 CA PHE 44 4.091 -5.531-29.798 1.000.00
ATOM 839 HA PHE 44 3.163 -5.248-30.296 1.000.00
ATOM 840 CB PHE 44 4.575 -4.489-28.788 1.000.00
ATOM 8412HB PHE 44 5.303 -4.953-28.123 1.000.00
ATOM 8421HB PHE 44 5.095 -3.694-29.323 1.000.00
ATOM 843 QB PHE 44 5.199 -4.324-28.723 1.000.00
ATOM 844 QD PHE 44 3.359 -3.817-27.871 1.000.00
ATOM 845 QE PHE 44 1.525 -2.804-26.489 1.000.00
ATOM 846 QR PHE 44 2.442 -3.311-27.180 1.000.00
ATOM 847 CG PHE 44 3.457 -3.872-27.946 1.000.00
ATOM 848 CDl PHE 44 2.701 -2.862-28.454 1.000.00
ATOM 849 HDl PHE 44 2.892 -2.493-29.462 1.000.00
ATOM 850 CE1 PHE 44 1.664 -2.289-27.672 1.000.00
ATOM 851 HEI PHE 44 1.058 -1.479-28.080 1.000.00
ATOM 852 CZ PHE 44 1.426 -2.749-26.415 1.000.00
ATOM 853 HZ PHE 44 0.629 -2.309-25.815 1.000.00
ATOM 854 CE2 PHE 44 2.182 -3.759-25.907 1.000.00
ATOM 855 HE2PHE 44 1.991 -4.128-24.899 1.000.00
ATOM 856 CD2 PHE 44 3.220 -4.332-26.688 1.000.00
ATOM 857 HD2PHE 44 3.826 -5.141 -26.281 1.000.00
ATOM 858 C PHE ' U 5.182 -5.754-30.847 1.000.00
ATOM 859 O PHE ■ 44 4.917 -5.694-32.046 1.000.00
ATOM 860 N ASN 45 6.387 -6.007-30.356 1.000.00
ATOM 861 HN ASN 45 6.594 -6.054-29.379 1.000.00
ATOM 862 CA ASN 45 7.519 -6.239-31.236 1.000.00
ATOM 863 HA ASN 45 7.725 -5.274-31.699 1.000.00
ATOM 864 CB ASN 45 8.735 -6.733-30.450 1.000.00
ATOM 8652HB ASN 45 8.434 -7.002-29.438 1.000.00
ATOM 8661HB ASN 45 9.132 -7.635-30.916 1.000.00
ATOM 867 QB ASN 45 8.783 -7.319-30.177 1.000.00
ATOM 868 CG ASN 45 9.825 -5.660-30.395 1.000.00
ATOM 869 OD1 ASN 45 10.127 -4.994-31.371 1.000.00
ATOM 870 ND2 ASN 45 10.397 -5.531 ■29.201 1.000.00 ATOM 8711HD2ASN 45 10.102 -6.109-28.440 1.000.00
ATOM 8722HD2ASN 45 11.121 -4.855-29.0641.000.00
ATOM 873 QD2ASN 45 10.612 -5.482-28.752 1.000.00
ATOM 874 C ASN 45 7.151 -7.313-32.262 1.000.00 ATOM 8750 ASN 45 7.299 -8.505-31.997 1.000.00
ATOM 876 N ASP 46 6.679 -6.852-33.410 1.000.00
ATOM 877 HN ASP 46 6.562 -5.881 -33.618 1.000.00
ATOM 878 CA ASP 46 6.288 -7.759-34.477 1.000.00
ATOM 879 HA ASP 46 5.703 -7.153-35.168 1.000.00 ATOM 880 CB ASP 46 7.515 -8.347-35.177 1.000.00
ATOM 8812HB ASP 46 8.275 -7.570-35.259 1.000.00
ATOM 8821HB ASP 46 7.931 -9.134-34.548 1.000.00
ATOM 883 QB ASP 46 8.103 -8.352-34.903 1.000.00
ATOM 884 CG ASP 46 7.251 -8.922-36.570 1.000.00 ATOM 885 OD1 ASP 46 6.124 -8.862-37.082 1.000.00
ATOM 8860D2ASP 46 8.276 -9.458-37.141 1.000.00
ATOM 887 HD2ASP 46 8.053-10.383-37.447 1.000.00
ATOM 888 C ASP 46 5.481 -8.916-33.886 1.000.00
ATOM 889 O ASP 46 5.470-10.016-34.438 1.000.00 ATOM 890 N GLY 47 4.825 -8.630-32.771 1.000.00
ATOM 891 HN GLY 47 4.839 -7.733-32.329 1.000.00
ATOM 892 CA GLY 47 4.017 -9.634-32.100 1.000.00
ATOM 8932HA GLY 47 3.167 -9.155-31.614 1.000.00
ATOM 8941HA GLY 47 3.613-10.331-32.833 1.000.00 ATOM 895 QA GLY 47 3.390 -9.743 -32.224 1.000.00
ATOM 896 C GLY 47 4.842-10.397-31.062 1.000.00
ATOM 897 O GLY 47 4.886-11.626-31.081 1.000.00
ATOM 898 N SER 48 5.474 -9.637-30.180 1.000.00
ATOM 899 HN SER 48 5.433 -8.638-30.172 1.000.00 ATOM 900 C A SER 48 6.295-10.226-29.136 1.000.00
ATOM 901 HA SER 48 6.097-11.297-29.183 1.000.00
ATOM 902 CB SER 48 7.782 -9.973-29.395 1.000.00
ATOM 9032HB SER 48 7.981-10.045-30.465 1.000.00
ATOM 9041HB SER 48 8.035 -8.957-29.092 1.000.00 ATOM 905 QB SER 48 8.008 -9.501-29.778 1.000.00
ATOM 906 OG SER 48 8.611-10.897-28.696 1.000.00
ATOM 907 HG SER 48 8.427-10.846-27.714 1.000.00
ATOM 908 C SER 48 5.891 -9.663-27.772 1.000.00
ATOM 909 O SER 48 5.906 -8.451-27.568 1.000.00 ATOM 910 N SER 49 5.540-10.572-26.874 1.000.00
ATOM 911 HN SER 49 5.530-11.556-27.048 1.000.00
ATOM 912 CA SER 49 5.132-10.181-25.535 1.000.00
ATOM 913 HA SER 49 4.119 -9.792-25.643 1.000.00
ATOM 914 CB SER 49 5.116-11.385-24.591 1.000.00 ATOM 9152HB SER 49 4.323-11.257-23.854 1.000.00
ATOM 9161HB SER 49 4.883-12.287-25.157 1.000.00
ATOM 917 QB SER 49 4.603-11.772-24.505 1.000.00
ATOM 918 OG SER 49 6.362-11.554-23.921 1.000.00
ATOM 919 HG SER 49 6.374-12.429-23.436 1.000.00 ATOM 920 C SER 49 6.069 -9.097-24.998 1.000.00
ATOM 921 O SER 49 7.285 -9.191-25.1521.000.00
ATOM 922 N ARG 50 5.466 -8.093-24.378 1.000.00
ATOM 923 HN ARG 50 4.476 -8.024-24.256 1.000.00
ATOM 924 CA ARG 50 6.232 -6.993-23.817 1.000.00 ATOM 925 HA ARG 50 7.194 -7.430-23.549 1.000.00
ATOM 926 CB ARG 50 6.424 -5.876-24.844 1.000.00
ATOM 9272HB ARG 50 7.223 -6.146-25.535 1.000.00
ATOM 9281HB ARG 50 5.516 -5.761-25.436 1.000.00
ATOM 929 QB ARG 50 6.370 -5.953-25.486 1.000.00 ATOM 930 CG ARG 50 6.763 -4.551-24.157 1.000.00
ATOM 9312HG ARG 50 7.153 -4.745-23.158 1.000.00
ATOM 9321HG ARG 50 7.550 -4.040-24.713 1.000.00
ATOM 933 QG ARG 50 7.351 -4.393-23.935 1.000.00
ATOM 934 CD ARG 50 5.530 -3.651 -24.063 1.000.00
ATOM 9352HD ARG 50 4.857 -3.855-24.896 1.000.00
ATOM 9361HD ARG 50 4.979 -3.868-23.148 1.000.00
ATOM 937 QD ARG 50 4.918 -3.861 -24.022 1.000.00
ATOM 938 NE ARG 50 5.939 -2.229-24.081 1.000.00
ATOM 939 HE ARG 50 6.088 - 1.773 -23.203 1.000.00
ATOM 940 CZ ARG 50 6.124 -1.508-25.208 1.000.00
ATOM 941 NH1 ARG 50 6.490 -0.244-25.106 1.000.00
ATOM 942 HH1 ARG 50 6.648 0.357-25.889 1.000.00
ATOM 943 NH2 ARG 50 5.938 -2.072-26.420 1.000.00
ATOM 9441HH2ARG 50 6.077 -1.532-27.250 1.000.00
ATOM 9452HH2 ARG 50 5.660 -3.031 -26.488 1.000.00
ATOM 946 QH2 ARG 50 5.869 -2.281-26.869 1.000.00
ATOM 947 C ARG 50 5.523 -6.427-22.585 1.000.00
ATOM 948 O ARG 50 4.305 -6.251 -22.591 1.000.00
ATOM 949 N GLU 51 6.315 -6.157-21.558 1.000.00
ATOM 950 HN GLU 51 7.304 -6.303-21.561 1.000.00
ATOM 951 CA GLU 51 5.778 -5.614-20.321 1.000.00
ATOM 952 HA GLU 51 4.908 -6.228-20.089 1.000.00
ATOM 953 CB GLU 51 6.794 -5.734-19.183 1.000.00
ATOM 9542HB GLU 51 7.780 -5.954-19.593 1.000.00
ATOM 9551HB GLU 51 6.872 -4.782-18.659 1.000.00
ATOM 956 QB GLU 51 7.326 -5.368-19.126 1.000.00
ATOM 957 CG GLU 51 6.388 -6.833-18.199 1.000.00
ATOM 9582HG GLU 51 6.437 -6.449-17.180 1.000.00
ATOM 9591HG GLU 51 5.354 -7.125-18.381 1.000.00
ATOM 960 QG GLU 51 5.896 -6.787-17.780 1.000.00
ATOM 961 CD GLU 51 7.300 -8.054-18.334 1.000.00
ATOM 962 OEl GLU 51 7.796 -8.339-19.435 1.000.00
ATOM 963 OE2GLU 51 7.488 -8.717-17.244 1.000.00
ATOM 964 HE2GLU 51 8.329 -9.254-17.311 1.000.00
ATOM 965 C GLU : 51 5.349 -4.160-20.522 1.000.00
ATOM 966 O GLU 51 6.099 -3.359-21.078 1.000.00
ATOM 967 N LEU ; 52 4.144 -3.862-20.058 1.000.00
ATOM 968 HN LEU 52 3.540 -4.520-19.607 1.000.00
ATOM 969 CA LEU 52 3.606 -2.518-20.180 1.000.00
ATOM 970 HA LEU 52 4.450 -1.837-20.293 1.000.00
ATOM 971 CB LEU 52 2.754 -2.395-21.445 1.000.00
ATOM 9722HB LEU 52 2.958 -3.255-22.082 1.000.00
ATOM 9731HB LEU 52 1.704 -2.453-21.159 1.000.00
ATOM 974 QB LEU 52 2.331 -2.854-21.621 1.000.00
ATOM 975 CG LEU 52 2.959 -1.123-22.271 1.000.00
ATOM 976 HG LEU 52 4.030 -0.973-22.407 1.000.00
ATOM 977 QDl LEU 52 2.196 -1.303-23.994 1.000.00
ATOM 978 QD2 LEU 52 2.294 0.395-21.355 1.000.00
ATOM 979 CDl LEU 52 2.343 -1.268-23.663 1.000.00
ATOM 9801HD1 LEU 52 1.686 -2.138-23.681 1.000.00
ATOM 9812HD1 LEU 52 1.767 -0.374-23.901 1.000.00
ATOM 9823HD1 LEU 52 3.136 -1.396-24.400 1.000.00
ATOM 983 CD2 LEU 52 2.422 0.104-21.531 1.000.00
ATOM 9841HD2LEU 52 2.326 0.936-22.229 1.000.00
ATOM 9852HD2 LEU 52 1.445 -0.128-21.105 1.000.00
ATOM 9863HD2 LEU 52 3.111 0.377 -20.732 1.000.00
ATOM 987 QQD LEU 52 2.245 -0.454-22.675 1.000.00
ATOM 988 C LEU 52 2.857 -2.155-18.896 1.000.00 ATOM 989 O LEU 52 2.047 -2.938-18.403 1.000.00
ATOM 990 N MET 53 3.154 -0.966-18.392 1.000.00
ATOM 991 HN MET 53 3.814 -0.335-18.800 1.000.00
ATOM 992 CA MET 53 2.519 -0.490-17.175 1.000.00 ATOM 993 HA MET 53 2.219 -1.385-16.631 1.000.00
ATOM 994 CB MET 53 3.519 0.343-16.370 1.000.00
ATOM 9952HB MET 53 4.526 0.179-16.753 1.000.00
ATOM 9961HB MET 53 3.299 1.403-16.494 1.000.00
ATOM 997 QB MET 53 3.913 0.791 -16.624 1.000.00 ATOM 998 CG MET 53 3.467 -0.024-14.885 1.000.00
ATOM 9992HG MET 53 2.111 -0.853-14.731 1.000.00
ATOM 10001HG MET 53 4.449 -0.360-14.551 1.000.00
ATOM 1001 QG MET 53 3.613 -0.607-14.641 1.000.00
ATOM 1002 SD MET 53 2.948 1.388-13.925 1.000.00 ATOM 1003 QE MET 53 4.536 2.759-14.388 1.000.00
ATOM 1004 CE MET 53 4.268 2.527-14.310 1.000.00
ATOM 1005 IHE MET 53 5.038 2.010-14.882 1.000.00
ATOM 10062HE MET 53 3.873 3.355 -14.898 1.000.00
ATOM 10073HE MET 53 4.698 2.911 -13.385 1.000.00 ATOM 1008 C MET 53 1.288 0.361 17.496 1.000.00
ATOM 1009 O MET 53 1.067 0.729 18.648 1.000.00
ATOM 1010 N ASN 54 0.519 0.647-16.456 1.000.00
ATOM 1011 HN ASN 54 0.706 0.343-15.521 1.000.00
ATOM 1012 CA ASN 54 -0.683 1.447-16.612 1.000.00 ATOM 1013 HA ASN 54 -0.367 2.336-17.157 1.000.00
ATOM 1014 CB ASN 54 -1.754 0.684-17.395 1.000.00
ATOM 10152HB ASN 54 -2.718 1.179-17.276 1.000.00
ATOM 10161HB ASN 54 -1.515 0.703-18.458 1.000.00
ATOM 1017 QB ASN 54 -2.116 0.941 -17.867 1.000.00 ATOM 1018 CG ASN 54 -1.857 -0.765-16.914 1.000.00
ATOM 1019 OD1 ASN 54 -0.868 -1.434-16.665 1.000.00
ATOM 1020 ND2 ASN 54 -3.105 -1.210-16.800 1.000.00
ATOM 10211HD2 ASN 54 -3.872 -0.608-17.021 1.000.00
ATOM 10222HD2 ASN 54 -3.276 -2.146-16.492 1.000.00 ATOM 1023 QD2 ASN 54 -3.574 -1.377-16.757 1.000.00
ATOM 1024 C ASN 54 -1.253 1.779 -15.231 1.000.00
ATOM 1025 O ASN 54 -1.089 1.008-14.287 1.000.00
ATOM 1026 N LEU 55 -1.911 2.926-15.158 .000.00
ATOM 1027 HN LEU 55 -2.040 3.547-15.931 1.000.00 ATOM 1028 CA LEU 55 -2.506 3.369 13.909 1.000.00
ATOM 1029 HA LEU 55 -2.049 2.791 13.106 1.000.00
ATOM 1030 CB LEU 55 -2.177 4.841 ■ 13.651 1.000.00
ATOM 10312HB LEU 55 -2.502 5.422 -14.513 1.000.00
ATOM 10321HB LEU 55 -2.765 5.180 -12.798 1.000.00 ATOM 1033 QB LEU 55 -2.634 5.301 13.656 1.000.00
ATOM 1034 CG LEU 55 -0.706 5.161 13.379 1.000.00
ATOM 1035 HG LEU 55 -0.468 6.110-13.861 1.000.00
ATOM 1036 QDl LEU 55 -0.390 5.381 -11.526 1.000.00
ATOM 1037 QD2 LEU 55 0.426 3.849 - 14.141 1.000.00 ATOM 1038 CDl LEU 55 -0.450 5.339- 11.881 1.000.00
ATOM 10391HD1 LEU 55 -1.142 6.080 -11.480 1.000.00
ATOM 10402HD1 LEU 55 -0.601 4.387 -11.372 1.000.00
ATOM 10413HD1 LEU 55 0.574 5.676 -11.725 1.000.00
ATOM 1042 CD2 LEU 55 0.209 4.101 - 13.995 1.000.00 ATOM 10431HD2 LEU 55 1.246 4.326 -13.745 1.000.00
ATOM 10442HD2 LEU 55 -0.055 3.120 -13.601 1.000.00
ATOM 10453HD2 LEU 55 0.088 4.102 -15.078 1.000.00
ATOM 1046 QQD LEU 55 0.018 4.615 -12.833 1.000.00 ATOM 1047 C LEU 55 -4.006 3.069 13.929 1.000.00 ATOM 1048 O LEU 55 -4.648 : 3.162 -114.974 1.00 0.00
ATOM 1049 N THR 56 -4.522 2.715 -: 12.761 1.00 0.00
ATOM 1050 HN THR 56 -3.994 2.642 -1 1.915 1.00 0.00
ATOM 1051 CA THR 56 -5.935 2.401 ■ -12.631 1.00 0.00 ATOM 1052 HA THR 56 -6.494 3.048 -13.306 1.00 0.00
ATOM 1053 CB THR 56 -6.134 0.941 - ■13.041 1.00 0.00
ATOM 1054 HB THR 56 -5.577 0.712 - - 13.950 1.00 0.00
ATOM 1055 QG2 THR 56 -5.689 -0.269 -1 1.653 ; 1.00 0.00
ATOM 1056 OGl THR 56 -7.546 0.808 -13.178 1.00 0.00 ATOM 1057 HG1 THR 56 -8.000 1.092 -12.333 1.00 0.00
ATOM 1058 CG2 THR 56 -5.775 -0.037 - 1 1.920 ι 1.00 0.00
ATOM 1059 1 HG2 THR 56 -6.681 -0.332 - 1 1.391 1.00 0.00
ATOM 1060 2HG2 THR 56 -5.299 » -0.920 -12.346 1.00 0.00
ATOM 1061 3HG2 THR 56 -5.089 » 0.446 i -1 1.223 1.00 0.00 ATOM 1062 C THR 56 -6.421 : 2.706 - 1 1 1.212 i 1.00 0.00
ATOM 1063 O THR 56 -5.639 : 2.671 -1 10.264 1.00 0.00
ATOM 1064 N GLY 57 -7.709 2.998 - 1 1.1 13 1.00 0.00
ATOM 1065 HN GLY 57 -8.339 3.024 -1 1.889 1.00 0.00
ATOM 1066 CA GLY 57 -8.309 3.308 -9.826 1.00 0.00 ATOM 1067 2HA GLY 57 -8.756 2.409 -9.403 1.00 0.00
ATOM 1068 1 HA GLY 57 -7.537 3.637 -9.131 1.00 0.00
ATOM 1069 QA GLY 57 -8.146 3.023 -9.267 1.00 0.00
ATOM 1070 C GLY 57 -9.375 - 1397 - 9.966 1.00 0.00
ATOM 1071 O GLY 57 -9.508 5.007 -; 1 1.026 1.00 0.00 ATOM 1072 N THR 58 -10.106 4.607 -i 8 3..888822 11.000.00
ATOM 1073 HN THR 58 -9.991 4.107 -- 88..002244 1.000.00
ATOM 1074 CA THR 58 -11.156 5.612 •- -88..887700 1.000.00
ATOM 1075 HA THR 58 -11.420 5.844 -9.902 1.000.00
ATOM 1076 CB THR 58 -12.370 5.018 - •8.154 1.000.00 ATOM 1077 HB THR 58 -13.207 5.717 ■ -8.162 1.000.00
ATOM 1078 QG2 THR 58 -12.883 3.340 -8.865 1.000.00
ATOM 1079 OG l THR 58 -11.887 4.709 -6.849 1.000.00
ATOM 1080 HG 1 THR 58 -11.713 5.552 -6.340 1.000.00
ATOM 1081 CG2 THR 58 -12.785 3.662 -8.729 1.000.00 ATOM 1082 1 HG2 THR 58 -11.953 3 2.963 -8.646 1.000.00
ATOM 1083 2HG2 THR 58 -13.639 ? 3.278 -8.172 1.000.00
ATOM 1084 3HG2 THR 58 -13.057 7 3.780 -9.777 1.000.00
ATOM 1085 C THR 58 -10.648 6.907 -8.234 11.000.00
ATOM 1086 O THR 58 -10.362 6.945 -' 7.038 11.000.00 ATOM 1087 N ILE 59 -10.551 7.937 -9.062 1.000.00
ATOM 1088 HN ILE 59 -10.786 7.898-10.033 1.000.00
ATOM 1089 CA ILE 59 -10.082 9.231 -8.595 1.000.00
ATOM 1090 HA ILE 59 -9.305 9.048 -7.852 1.000.00
ATOM 1091 CB ILE 59 -9.438 10.013 -9.741 1.000.00 ATOM 1092 HB ILE 59 -10.167 10.101-10.547 1.000.00
ATOM 1093 QG2 ILE 59 -8.992 11.770 -9.197 1.000.00
ATOM 1094 CG2 ILE 59 -9.077 11.433 -9.301 1.000.00
ATOM 1095 1 HG2 ILE 59 -9.858 11.820 -8.646 1.000.00
ATOM 1096 2HG2 ILE 59 -8.128 11.417 -8.766 1.000.00 ATOM 1097 3HG2 ILE 59 -8.989 12.074-10.179 1.000.00
ATOM 1098 CG I ILE 59 -8.229 9.263-10.305 1.000.00
ATOM 1099 2HG 1 ILE 59 -7.497 9.100 -9.515 1.000.00
ATOM 1 100 1 HG 1 ILE 59 -8.540 8.280-10.660 1.000.00
ATOM 1 101 QG 1 ILE 59 -8.018 8.690-10.087 1.000.00 ATOM 1 102 QDl ILE 59 -7.432 10.230-11.724 1.000.00
ATOM 1 103 CDl ILE 59 -7.585 10.045-11.452 1.000.00
ATOM 1 104 1 HDl ILE 59 -8.277 10.810-11.804 1.000.00
ATOM 1 105 2HD1 ILE 59 -6.669 10.518-11.099 1.000.00
ATOM 1 106 3HD1 1LE 59 -7.351 9.363-12.270 1.000.00 ATOM 1107 C ILE 59 11.236 9.972 -7.917 1.00 0.00
ATOM 1 108 O ILE 59 12.379 9.893 -8.366 1.000.00
ATOM 1 109 N PRO 60 -10.889 10.694 -6.818 1.000.00
ATOM 1 110 CD PRO 60 -9.546 10.811 -6.257 1.000.00
ATOM 1 111 CA PRO 60 -11.883 11.449 -6.074 1.000.00
ATOM 1 112 HA PRO 60 -12.722 10.915 -5.975 1.000.00
ATOM 1 113 CB PRO 60 -11.234 11.734.4.729 1.000.00
ATOM 1 1142HB PRO 60 -11.451 12.749 -4.398 1.000.00
ATOM 1 1151HB PRO 60 -11.616 11.060 -3.961 1.000.00
ATOM 1 116 QB PRO 60 -11.534 11.904 -4.179 1.000.00
ATOM 1 117 CG PRO 60 -9.742 1.535 -4.935 1.000.00
ATOM 1 I182HG PRO 60 -9.227 12.496 -4.946 1.000.00
ATOM 1 1191HG PRO 60 -9.317 10.955 -4.116 1.000.00
ATOM 1 120 QG PRO 60 -9.272 11.726 4.531 1.000.00
ATOM 1 1212HD PRO 60 -8.887 11.370 -6.921 1.000.00
ATOM 1! 1221HD PRO 60 -9.093 9.831 -6.109 1.000.00
ATOM ι: 123 QD PRO 60 -8.990 10.600 -6.515 1.000.00
ATOM 1 124 C PRO 60 -12.282 12.720 -6.826 1.000.00
ATOM 1 125 O PRO 60 -11.658 13.767 -6.658 1.000.00
ATOM li 126 N VAL 61 -13.319 12.587 -7.639 1.000.00
ATOM 1 : 127 HN VAL 61 -13.821 11.732 -7.770 1.000.00
ATOM li 128 CA VAL 61 -13.809 13.712 -8.418 1.000.00
ATOM li 129 HA VAL 61 -12.945 14.300 -8.726 1.000.00
ATOM li 130 CB VAL 61 -14.514 13.209 -9.679 1.000.00
ATOM 11 131 HB VAL 61 -15.023 12.278 -9.429 1.000.00
ATOM 11 132 QG1 VAL 61 -15.821 14.446-10.266 1.000.00
ATOM 11 133 QG2VAL 61 -13.264 12.839-11.052 1.000.00
ATOM 11 134 CGI VAL 61 -15.570 14.209-10.153 1.000.00
ATOM 11 1351HG1 VAL 61 -15.755 14.065-11.218 1.000.00
ATOM 11 I362HG1 VAL 61 -16.495 14.051 -9.599 1.000.00
ATOM 11 I373HG1 VAL 61 -15.212 15.224 -9.981 1.000.00
ATOM 11 138 CG2VAL 61 -13.504 12.910-10.789 1.000.00
ATOM 11 1391HG2VAL 61 -12.996 11.969-10.574 1.000.00
ATOM 11 I402HG2VAL 61 -14.025 12.832-11.743 1.000.00
ATOM 11 1413HG2VAL 61 -12.771 13.715-10.840 1.000.00
ATOM 11 142 QQG VAL 61 -14.542 13.643-10.659 1.000.00
ATOM 11 143 C VAL 61 -14.708 14.583 -7.538 1.000.00
ATOM 11 144 O VAL 61 -15.773 14.144 -7.106 1.000.00
ATOM 11 145 N PRO 62 -14.234 15.834 -7.291 1.000.00
ATOM 11 146 CD PRO 62 -12.978 16.388 -7.786 1.000.00
ATOM 11 147 CA PRO 62 -14.984 16.770 -6.471 1.000.00
ATOM 11 48 HA PRO 62 -15.367 16.303 -5.673 1.000.00
ATOM 11 49 CB PRO 62 -13.976 17.835 -6.070 1.000.00
ATOM 11 502HB PRO 62 -14.421 18.829 -6.113 1.000.00
ATOM 11 1511HB PRO 62 -13.634 17.683 -5.046 1.000.00
ATOM 11 152 QB PRO 62 -14.028 18.256 -5.579 1.000.00
ATOM 11 53 CG PRO 62 -12.824 17.711 -7.054 1.000.00
ATOM 11 542HG PRO 62 -12.834 18.541 -7.759 1.000.00
ATOM 11 551HG PRO 62 -11.869 17.749 -6.530 1.000.00
ATOM 11 56 QG PRO 62 -12.352 18.145 -7.145 1.000.00
ATOM 11 572HD PRO 62 -13.007 16.534 -8.866 1.000.00
ATOM 11 581HD PRO 62 -12.141 15.721 -7.577 1.000.00
ATOM 11 59 QD PRO 62 -12.574 16.127 -8.222 1.000.00
ATOM 11 60 C PRO i S2 -16.180 17.336 -7.238 1.000.00
ATOM 11 61 O PRO 62 -16.204 17.305 -8.468 1.000.00
ATOM 11 62 N TYR 63 -17.143 17.841 -6.481 1.000.00
ATOM 11 63 HN TYR 63 -17.115 17.863 -5.482 1.000.00
ATOM 11 64 CA TYR 63 -18.339 18.414 -7.075 1.000.00
ATOM 11 65 HA TYR 63 -18.170 18.509 -8.147 1.000.00 ATOM 1 166 CB TYR 63 -19.485 17.468 -6.71 1 1.00 0.00
ATOM 1 167 2HB TYR 63 -19.066 16.536 -6.330 1.00 0.00
ATOM 1 168 1 HB TYR 63 -20.066 17.91 1 -5.903 1.00 0.00
ATOM 1 169 QB TYR 63 -19.566 17.224 -6.1 16 1.00 0.00
ATOM 1 170 QD TYR 63 -20.51 1 17.1 18 -7.988 1.00 0.00
ATOM 1 171 QE TYR 63 -22.068 16.588 -9.927 1.00 0.00
ATOM 1 172 QR TYR 63 -21.289 16.853 -8.958 1.00 0.00
ATOM 1 173 CG TYR 63 -20.422 17.149 -7.878 1.00 0.00
ATOM 1 174 CDl TYR 63 -19.971 16.386 -8.936 1.00 0.00
ATOM 1 175 HDl TYR 63 -18.948 16.01 1 -8.941 1.00 0.00
ATOM 1 176 CE1 TYR 63 -20.853 16.085 -10.034 1.00 0.00
ATOM 1 177 HEI TYR 63 -20.510 15.484 -10.876 1.00 0.00
ATOM 1 178 CZ TYR 63 -22.123 16.569 -9.997 1.00 0.00
ATOM 1 179 CE2 TYR 63 -22.599 17.323 -8.970 1.00 0.00
ATOM 1 180 HE2 TYR 63 -23.625 17.692 -8.978 1.00 0.00
ATOM 1 181 CD2 TYR 63 -21.717 17.623 -7.872 1.00 0.00
ATOM 1 182 HD2 TYR 63 -22.073 18.226 -7.036 1.00 0.00
ATOM 1 183 OH TYR 63 -22.956 16.285 -1 1.034 1.00 0.00
ATOM 1 184 HH TYR 63 -23.083 17.097 -1 1.603 1.00 0.00
ATOM 1 185 C TYR 63 -18.632 19.798 -6.491 1.00 0.00
ATOM 1 186 O TYR 63 -17.758 20.419 -5.889 1.00 0.00
ATOM 1 187 N ARG 64 -19.865 20.240 -6.690 1.00 0.00
ATOM 1 188 HN ARG 64 -20.570 19.728 -7.181 1.00 0.00
ATOM 1 189 CA ARG 64 -20.284 21.539 -6.191 1.00 0.00
ATOM 1 190 HA ARG 64 -19.517 22.231 -6.537 1.00 0.00
ATOM 1 191 CB ARG 64 -21.649 21.932 -6.758 1.00 0.00
ATOM 1 192 2HB ARG 64 -22.042 21.1 18 -7.367 1.00 0.00
ATOM 1 193 1 HB ARG 64 -22.355 22.089 -5.942 1.00 0.00
ATOM 1 194 QB ARG 64 -22.199 21.603 -6.655 1.00 0.00
ATOM 1 195 CG ARG 64 -21.546 23.204 -7.602 1.00 0.00
ATOM 1 196 2HG ARG 64 -20.522 23.332 -7.951 1.00 0.00
ATOM 1 197 1 HG ARG 64 -22.175 23.1 10 -8.487 1.00 0.00
ATOM 1 198 QG ARG 64 -21.349 23.221 -8.219 1.00 0.00
ATOM 1 199 CD ARG 64 -21.973 24.433 -6.796 1.00 0.00
ATOM 1200 2HD ARG 64 -22.235 24.138 -5.780 1.00 0.00
ATOM 1201 1 HD ARG 64 -21.142 25.134 -6.720 1.00 0.00
ATOM 1202 QD ARG 64 -21.688 24.636 -6.250 1.00 0.00
ATOM 1203 NE ARG 64 -23.129 25.089 -7.446 1.00 0.00
ATOM 1204 HE ARG 64 -23.379 24.792 -8.368 1.00 0.00
ATOM 1205 CZ ARG 64 -23.868 26.062 -6.873 1.00 0.00
ATOM 1206 NH 1 ARG 64 -24.881 26.577 -7.545 1.00 0.00
ATOM 1207 HH1 ARG 64 -25.476 27.300 -7.193 1.00 0.00
ATOM 1208 NH2 ARG 64 -23.577 26.501 -5.630 1.00 0.00
ATOM 1209 1 HH2 ARG 64 -24.129 27.223 -5.212 1.00 0.00
ATOM 1210 2HH2 ARG 64 -22.808 26.106 -5.127 1.00 0.00
ATOM 121 1 QH2 ARG 64 -23.469 26.664 -5.170 1.00 0.00
ATOM 1212 C ARG 64 -20.360 21.521 -4.663 1.00 0.00
ATOM 1213 O ARG 64 -20.492 22.569 -4.032 1.00 0.00
ATOM 1214 N GLY 65 -20.274 20.319 -4.1 12 1.00 0.00
ATOM 1215 HN GLY 65 -20.167 19.472 -4.632 1.00 0.00
ATOM 1216 CA GLY 65 -20.331 20.151 -2.670 1.00 0.00
ATOM 1217 2HA GLY 65 - 19.522 20.712 -2.202 1.00 0.00
ATOM 1218 1 HA GLY 65 -21.266 20.563 -2.289 1.00 0.00
ATOM 1219 QA GLY 65 -20.394 20.637 -2.246 1.00 0.00
ATOM 1220 C GLY 65 -20.225 18.674 -2.285 1.00 0.00
ATOM 1221 O GLY 65 -20.864 18.229 -1.333 1.00 0.00
ATOM 1222 N ASN 66 -19.412 17.955 -3.045 1.00 0.00
ATOM 1223 HN ASN 66 -18.896 18.324 -3.818 1.00 0.00
ATOM 1224 CA ASN 66 -19.213 16.537 -2.796 1.00 0.00 ATOM 1225 HA ASN 66 -19.1 19 16.447 -1.714 1.00 0.00
ATOM 1226 CB ASN 66 -20.399 15.717 -3.306 1.00 0.00
ATOM 1227 2HB ASN 66 -20.337 15.615 -4.390 1.00 0.00
ATOM 1228 1 HB ASN 66 -20.357 14.710 -2.889 1.00 0.00
ATOM 1229 QB ASN 66 -20.347 15.163 -3.640 1.00 0.00
ATOM 1230 CG ASN 66 -21.727 16.376 -2.926 1.00 0.00
ATOM 1231 OD1 ASN 66 -22.31 1 16.103 -1.891 1.00 0.00
ATOM 1232 ND2 ASN 66 -22.168 17.258 -3.819 1.00 0.00
ATOM 1233 1 HD2 ASN 66 -21.639 17.436 -4.649 1.00 0.00
ATOM 1234 2HD2 ASN 66 -23.028 17.742 -3.661 1.00 0.00
ATOM 1235 QD2 ASN 66 -22.334 17.589 -4.155 1.00 0.00
ATOM 1236 C ASN 66 -17.959 16.065 -3.534 1.00 0.00
ATOM 1237 O ASN 66 -17.266 16.864 -4.161 1.00 0.00
ATOM 1238 N THR 67 -17.705 14.768 -3.433 1.00 0.00
ATOM 1239 HN THR 67 -18.274 14.125 -2.920 1.00 0.00
ATOM 1240 CA THR 67 -16.546 14.180 -4.083 1.00 0.00
ATOM 1241 HA THR 67 -16.437 14.635 -5.068 1.00 0.00
ATOM 1242 CB THR 67 - 15.315 14.499 -3.233 1.00 0.00
ATOM 1243 HB THR 67 -15.347 13.962 -2.285 1.00 0.00
ATOM 1244 QG2 THR 67 - 13.694 14.157 -4.150 1.00 0.00
ATOM 1245 OGl THR 67 -15.345 15.917 -3.097 1.00 0.00
ATOM 1246 HG 1 THR 67 -15.680 16.166 -2.189 1.00 0.00
ATOM 1247 CG2 THR 67 -14.005 14.223 -3.974 1.00 0.00
ATOM 1248 1 HG2 THR 67 -13.452 13.440 -3.455 1.00 0.00
ATOM 1249 2HG2 THR 67 -14.224 13.900 -4.991 1.00 0.00
ATOM 1250 3HG2 THR 67 -13.405 15.133 -4.003 1.00 0.00
ATOM 1251 C THR 67 -16.762 12.681 -4.303 1.00 0.00
ATOM 1252 O THR 67 - 16.684 1 1.895 -3.360 1.00 0.00
ATOM 1253 N TYR 68 - 17.028 12.331 -5.553 1.00 0.00
ATOM 1254 HN TYR 68 -17.089 12.977 -6.313 1.00 0.00
ATOM 1255 CA TYR 68 -17.255 10.941 -5.908 1.00 0.00
ATOM 1256 HA TYR 68 -17.625 10.423 -5.023 1.00 0.00
ATOM 1257 CB TYR 68 -18.247 10.959 -7.072 1.00 0.00
ATOM 1258 2HB TYR 68 -18.103 1 1.875 -7.645 1.00 0.00
ATOM 1259 1 HB TYR 68 -18.025 10.127 -7.740 1.00 0.00
ATOM 1260 QB TYR 68 -18.064 1 1.002 -7.692 1.00 0.00
ATOM 1261 QD TYR 68 -19.852 10.862 -6.600 1.00 0.00
ATOM 1262 QE TYR 68 -22.287 10.715 -5.885 1.00 0.00
ATOM 1263 QR TYR 68 -21.069 10.788 -6.243 1.00 0.00
ATOM 1264 CG TYR 68 -19.713 10.871 -6.641 1.00 0.00
ATOM 1265 CD l TYR 68 -20.436 9.722 -6.888 1.00 0.00
ATOM 1266 HDl TYR 68 - 19.964 8.877 -7.391 1.00 0.00
ATOM 1267 CE 1 TYR 68 -21.816 9.638 -6.483 1.00 0.00
ATOM 1268 HEI TYR 68 -22.398 8.736 -6.672 1.00 0.00
ATOM 1269 CZ TYR 68 -22.375 10.709 -5.859 1.00 0.00
ATOM 1270 CE2 TYR 68 -21.691 1 1.856 -5.600 1.00 0.00
ATOM 1271 HE2 TYR 68 -22.175 12.692 -5.097 1.00 0.00
ATOM 1272 CD2 TYR 68 -20.31 1 1 1.939 -6.005 1.00 0.00
ATOM 1273 HD2 TYR 68 -19.740 12.847 -5.810 1.00 0.00
ATOM 1274 OH TYR 68 -23.677 10.630 -5.476 1.00 0.00
ATOM 1275 HH TYR 68 -24.204 10.122 -6.158 1.00 0.00
ATOM 1276 C TYR i 68 -15.957 10.274 -6.371 1.00 0.00
ATOM 1277 O TYR 68 - 14.888 10.878 -6.306 1.00 0.00
ATOM 1278 N ASN 69 -16.095 9.038 -6.827 1.00 0.00
ATOM 1279 HN ASN 69 -16.969 8.554 -6.877 1.00 0.00
ATOM 1280 CA ASN 69 -14.947 8.283 -7.301 1.00 0.00
ATOM 1281 HA ASN 69 - 14.105 8.972 -7.237 1.00 0.00
ATOM 1282 CB ASN 69 - 14.704 7.048 -6.431 1.00 0.00
ATOM 1283 2HB ASN 69 - 15.173 6.178 -6.889 1.00 0.00 ATOM 12841HB ASN 6699 -13.635 6.842 -6.377 1.000.00
ATOM 1285 QB ASN 6 699 -14.404 6.510 -6.633 1.000.00
ATOM 1286 CG ASN 6 699 -15.261 7.252 -5.021 1.000.00
ATOM 1287 OD1 ASN 66S9 -14.746 8.022 -4.227 1.000.00
ATOM 1288 ND2ASN 66S9 -16.340 6.521 -4.754 1.000.00
ATOM 12891HD2 ASN f & 69 -16.713 5.908 -5.451 1.000.00
ATOM 12902HD2 ASN \ 669 -16.778 6.585 -3.858 1.000.00
ATOM 1291 QD2ASN 6 699 -16.745 6.246 -4.654 1.000.00
ATOM 1292 C ASN 6699 -15.209 7.809 -8.732 1.000.00
ATOM 1293 O ASN 6699 -16.132 7.033 -8.973 1.000.00
ATOM 1294 N ILE " 7 '00 - 14.380 8.296 -9.643 1.000.00
ATOM 1295 HN ILE 7700 -13.632 8.927 -9.438 1.000.00
ATOM 1296 CA ILE 7700 -14.510 7.932-11.044 1.000.00
ATOM 1297 HA ILE 7700 -15.414 7.331-11.142 1.000.00
ATOM 1298 CB ILE 7700 -14.701 9.181-11.907 1.000.00
ATOM 1299 HB ILE 7700 -15.012 10.000-11.258 1.000.00
ATOM 1300 QG2ILE 7 700 -13.072 9.699-12.719 1.000.00
ATOM 1301 CG2ILE 7 700 -13.384 9.600-12.563 1.000.00
ATOM 13021HG2 ILE 7 700 -13.117 8.877-13.335 1.000.00
ATOM 13032HG2 ILE 7 700 -13.500 10.586-13.014 1.000.00
ATOM 13043HG2 ILE 7 700 -12.597 9.635-11.810 1.00 0.00
ATOM 1305 CGI ILE 7 700 -15.814 8.972-12.936 1.000.00
ATOM 13062HG1 ILE 7 700 -15.408 9.077-13.942 1.000.00
ATOM 13071HG1 ILE 7 700 -16.203 7.957-12.854 1.000.00
ATOM 1308 QG1 ILE 7 700 -15.806 8.517-13.398 1.000.00
ATOM 1309 QDl ILE 7 700 -17.217 10.216-12.680 1.000.00
ATOM 1310 CDl ILE 7 700 -16.948 9.977-12.729 1.000.00
ATOM 13111HD1 ILE 7 700 -17.675 9.876-13.535 1.000.00
ATOM 13122HD1 ILE 7 700 -17.436 9.784-11.773 1.000.00
ATOM 13133HD1 ILE 7 700 -16.54 10.989-12.731 1.000.00
ATOM 1314 C ILE 70 13.311 7.076-11.457 1.000.00
ATOM 1315 0 ILE 70 12.165 7.451-11.218 1.000.00
ATOM 1316 N PRO 71 -13.626 5.912-12.087 1.000.00
ATOM 1317 CD PRO 71 -14.973 5.435-12.386 1.000.00
ATOM 1318 CA PRO 71 -12.588 5.000-12.536 1.000.00
ATOM 1319 HA PRO 71 -11.872 4.920-11.842 1.000.00
ATOM 1320 CB PRO 71 -13.300 3.676-12.765 1.000.00
ATOM 13212HB PRO 71 -12.936 3.189-13.670 1.000.00
ATOM 13221HB PRO 71 -13.121 2.989-11.939 1.000.00
ATOM 1323 QB PRO 71 -13.028 3.089-12.804 1.000.00
ATOM 1324 CG PRO 71 -14.777 4.013-12.885 1.000.00
ATOM 13252HG PRO 71 -15.107 3.923-13.920 1.000.00
ATOM 13261HG PRO 71 -15.376 3.317-12.298 1.000.00
ATOM 1327 QG PRO 71 -15.241 3.620-13.109 1.000.00
ATOM 13282HD PRO 71 -15.454 6.057-13.142 1.000.00
ATOM 13291HD PRO 71 -15.608 5.461 -11.501 1.000.00
ATOM 1330 QD PRO 71 -15.531 5.759-12.321 1.000.00
ATOM 1331 C PRO 71 -11.896 5.532-13.792 1.000.00
ATOM 1332 O PRO 71 -12.530 6.169-14.632 1.000.00
ATOM 1333 N ILE 72 10.604 5.252-13.881 1.000.00
ATOM 1334 HN ILE 72 -10.096 4.733-13.194 1.000.00
ATOM 1335 CA ILE 72 -9.819 5.695-15.021 1.000.00
ATOM 1336 HA ILE 72 -10.462 5.646-15.899 1.000.00
ATOM 1337 CB ILE 72 -9.400 7.156-14.847 1.000.00
ATOM 1338 HB ILE 72 -8.894 7.255-13.887 1.000.00
ATOM 1339 QG2 ILE 72 -8.165 7.671 -16.186 1.000.00
ATOM 1340 CG2 ILE 72 -8.402 7.572-15.930 1.000.00
ATOM 13411HG2ILE 72 -7.853 8.454-15.598 1.000.00
ATOM 13422HG2 ILE 72 -7.702 6.756-16.112 1.000.00 ATOM 13433HG2 ILE 72 -8.939 7.803-16.850 1.000.00
ATOM 1344 CGI ILE 72 -10.622 8.076-14.810 1.000.00
ATOM 13452HG1 ILE 72 -11.342 7.760-15.565 1.000.00
ATOM 13461HG1 ILE 72 -11.116 7.991 -13.843 1.000.00
ATOM 1347 QGl ILE 72 -11.229 7.876-14.704 1.000.00
ATOM 1348 QDl ILE 72 -10.125 9.877-15.117 1.000.00
ATOM 1349 CDl ILE 72 -10.220 9.531-15.058 1.000.00
ATOM 13501HD1 ILE 72 -9.191 9.684-14.736 1.000.00
ATOM 13512HD1 ILE 72 -10.305 9.756-16.121 1.000.00
ATOM 13523HD1 ILE 72 -10.879 10.191 -14.494 1.000.00
ATOM 1353 C ILE 72 -8.643 4.738-15.227 1.000.00
ATOM 1354 O ILE 72 -8.067 4.240-14.261 1.000.00
ATOM 1355 N CYS 73 -8.321 4.511 -16.492 1.000.00
ATOM 1356 HN CYS 73 -8.795 4.920-17.272 1.000.00
ATOM 1357 CA CYS 73 -7.224 3.623-16.837 1.000.00
ATOM 1358 HA CYS 73 -6.558 3.599-15.975 1.000.00
ATOM 1359 CB CYS 73 -7.709 2.192-17.079 1.000.00
ATOM 13602HB CYS 73 -8.379 1.886-16.276 1.000.00
ATOM 13611HB CYS 73 -8.280 2.144-18.006 1.000.00
ATOM 1362 QB CYS 73 -8.330 2.015-17.141 1.000.00
ATOM 1363 SG CYS 73 -6.279 1.053-17.166 1.000.00
ATOM 1364 HG CYS 73 -6.882 0.130-17.910 1.000.00
ATOM 1365 C CYS 73 -6.508 4.197-18.061 1.000.00
ATOM 13660 CYS 73 -7.151 4.586-19.035 1.000.00
ATOM 1367 N LEU 74 -5.187 4.233-17.971 1.000.00
ATOM 1368 HN LEU 74 -4.671 3.915-17.176 1.000.00
ATOM 1369 CA LEU 74 -4.376 4.753-19.059 1.000.00
ATOM 1370 HA LEU 74 -4.942 4.618-19.981 1.000.00
ATOM 1371 CB LEU 74 -4.147 6.256-18.886 1.000.00
ATOM 13722HB LEU 74 -3.673 6.638-19.790 1.000.00
ATOM 13731HB LEU 74 -5.118 6.744-18.804 1.000.00
ATOM 1374 QB LEU 74 -4.396 6.691 -19.297 1.000.00
ATOM 1375 CG LEU 74 -3.296 6.670-17.683 1.000.00
ATOM 1376 HG LEU 74 -3.259 7.759-17.650 1.000.00
ATOM 1377 QDl LEU 74 -4.083 6.087-16.063 1.000.00
ATOM 1378 QD2LEU 74 -1.515 6.055-17.868 1.000.00
ATOM 1379 CDl LEU 74 -3.932 6.199-16.374 1.000.00
ATOM 13801HD1 LEU 74 -5.018 6.220-16.469 1.000.00
ATOM 13812HD1 LEU 74 -3.606 5.182-16.156 1.000.00
ATOM 13823HD1 LEU 74 -3.626 6.860-15.563 1.000.00
ATOM 1383 CD2LEU 74 -1.857 6.173-17.833 1.000.00
ATOM 13841HD2LEU 74 -1.705 5.303-17.194 1.000.00
ATOM 13852HD2 LEU 74 -1.674 5.897-18.871 1.000.00
ATOM 13863HD2 LEU 74 -1.167 6.964-17.540 1.000.00
ATOM 1387 QQD LEU 74 -2.799 6.071-16.965 1.000.00
ATOM 1388 C LEU 74 -3.083 3.941 -19.160 1.000.00
ATOM 1389 O LEU 74 -2.534 3.514-18.146 1.000.00
ATOM 1390 N TRP ' 75 -2.635 3.754-20.393 1.000.00
ATOM 1391 HN TRP 75 -3.087 4.105-21.212 1.000.00
ATOM 1392 CA TRP 75 -1.416 3.001-20.639 1.000.00
ATOM 1393 HA TRP 75 -1.342 2.227-19.875 1.000.00
ATOM 1394 CB TRP 75 -1.477 2.287-21.991 1.000.00
ATOM 13952HB TRP 75 -1.732 3.014-22.763 1.000.00
ATOM 13961HB TRP 75 -0.486 1.902-22.231 1.000.00
ATOM 1397 QB TRP 75 -1.109 2.458-22.497 1.000.00
ATOM 1398 CG TRP 75 -2.483 1.136-22.042 1.000.00
ATOM 1399 CDl TRP 75 -3.814 1.196-21.898 1.000.00
ATOM 1400 CD2TRP 75 -2.183 -0.259-22.261 1.000.00
ATOM 1401 CE3TRP 75 -0.951 -0.902-22.473 1.000.00 ATOM 1402 CE2 TRP 75 -3.368 -0.966-22.234 1.000.00
ATOM 1403 NE1 TRP 75 -4.391 -0.053-22.006 1.000.00
ATOM 1404 HDl TRP 75 -4.370 2.116-21.717 1.000.00
ATOM 1405 HE3TRP 75 -0.002 -0.367-22.499 1.000.00
ATOM 1406 CZ3TRP 75 -1.038 -2.288-22.651 1.000.00
ATOM 1407 CZ2 TRP 75 -3.438 -2.352-22.413 1.000.00
ATOM 1408 HEI TRP 75 -5.454 -0.281 -21.928 1.000.00
ATOM 1409 HZ3 TRP 75 -0.111 -2.836-22.819 1.000.00
ATOM 1410 CH2TRP 75 -2.223 -3.014-22.627 1.000.00
ATOM 1411 HZ2TRP 75 -4.387 -2.888-22.388 1.000.00
ATOM 1412 HH2TRP 75 -2.206 -4.094-22.773 1.000.00
ATOM 1413 C TRP ' 75 -0.234 3.965-20.524 1.000.00
ATOM 1414 O TRP ' 75 -0.265 5.060-21.082 1.000.00
ATOM 1415 N LEU 76 0.781 3.522-19.796 1.000.00
ATOM 1416 HN LEU 76 0.798 2.629-19.346 1.000.00
ATOM 1417 CA LEU 76 1.972 4.331 -19.601 1.000.00
ATOM 1418 HA LEU 76 1.709 5.361-19.841 1.000.00
ATOM 1419 CB LEU 76 2.403 4.305-18.133 1.000.00
ATOM 14202HB LEU 76 1.595 3.869-17.546 1.000.00
ATOM 14211HB LEU 76 3.261 3.639-18.039 1.000.00
ATOM 1422 QB LEU 76 2.428 3.754-17.792 1.000.00
ATOM 1423 CG LEU 76 2.772 5.656-17.518 1.000.00
ATOM 1424 HG LEU 76 3.264 6.257-18.283 1.000.00
ATOM 1425 QDl LEU 76 1.223 6.601 -16.977 1.000.00
ATOM 1426 QD2 LEU 76 4.005 5.441 -16.098 1.000.00
ATOM 1427 CDl LEU 76 1.520 6.420-17.081 1.000.00
ATOM 14281HD1 LEU 76 1.210 6.073-16.095 1.000.00
ATOM 14292HD1 LEU 76 1.741 7.486-17.038 1.000.00
ATOM 14303HD1 LEU 76 0.718 6.243-17.797 1.000.00
ATOM 1431 CD2 LEU 76 3.768 5.483-16.370 1.000.00
ATOM 14321HD2 LEU 76 3.235 5.510-15.420 1.000.00
ATOM 14332HD2 LEU 76 4.278 4.525-16.473 1.000.00
ATOM 14343HD2 LEU 76 4.501 6.289-16.399 1.000.00
ATOM 1435 QQD LEU 76 2.614 6.021 -16.537 1.000.00
ATOM 1436 C LEU ' 76 3.062 3.870-20.571 1.000.00
ATOM 1437 0 LEU ' 76 3.581 2.762-20.444 1.000.00
ATOM 1438 N LEU ' 77 3.376 4.742-21.517 1.000.00
ATOM 1439 HN LEU 77 2.949 5.641 -21.612 1.000.00
ATOM 1440 CA LEU 77 4.395 4.438-22.507 1.000.00
ATOM 1441 HA LEU 77 4.158 3.462-22.930 1.000.00
ATOM 1442 CB LEU 77 4.348 5.451-23.653 1.000.00
ATOM 14432HB LEU 77 3.807 6.333-23.309 1.000.00
ATOM 14441HB LEU 77 5.367 5.768-23.873 1.000.00
ATOM 1445 QB LEU 77 4.587 6.050-23.591 1.000.00
ATOM 1446 CG LEU 77 3.702 4.965-24.952 1.000.00
ATOM 1447 HG LEU 77 2.711 4.576-24.716 1.000.00
ATOM 1448 QDl LEU 77 3.466 6.395-26.169 1.000.00
ATOM 1449 QD2 LEU 77 4.694 3.543-25.712 1.000.00
ATOM 1450 CDl LEU 77 3.511 6.121 -25.935 1.000.00
ATOM 1451 1HD1 LEU 77 3.337 7.044-25.382 1.000.00
ATOM 14522HD1 LEU 77 4.406 6.228-26.548 1.000.00
ATOM 14533HD1 LEU 77 2.654 5.915-26.577 1.000.00
ATOM 1454 CD2 LEU 77 4.504 3.816-25.566 1.000.00
ATOM 14551HD2 LEU 77 4.102 2.865-25.217 1.000.00
ATOM 14562HD2 LEU 77 4.433 3.863-26.653 1.000.00
ATOM 14573HD2 LEU 77 5.548 3.901 -25.266 1.000.00
ATOM 1458 QQD LEU 77 4.080 4.969-25.940 1.000.00
ATOM 1459 C LEU 77 5.759 4.351 -21.819 1.000.00
ATOM 1460 0 LEU ' 77 5.845 4.409-20.593 1.000.00 ATOM 1461 N ASP 78 6.791 4.212-22.638 1.000.00
ATOM 1462 HN ASP 78 6.712 4.165-23.634 1.000.00
ATOM 1463 CA ASP 78 8.146 4.116-22.124 1.000.00
ATOM 1464 HA ASP 78 8.081 3.444-21.268 1.000.00
ATOM 1465 CB ASP 78 9.098 3.554-23.182 1.000.00
ATOM 14662HB ASP 78 10.123 3.769-22.878 1.000.00
ATOM 14671HB ASP 78 8.994 2.469-23.204 1.000.00
ATOM 1468 QB ASP 78 9.558 3.119-23.041 1.000.00
ATOM 1469 CG ASP 78 8.884 4.095-24.597 1.000.00
ATOM 1470 OD1 ASP 78 7.746 4.178-25.083 1.000.00
ATOM 1471 OD2ASP 78 9.960 4.444-25.216 1.000.00
ATOM 1472 HD2ASP 78 9.767 5.202-25.838 1.000.00
ATOM 1473 C ASP 78 8.640 5.511 -21.736 1.000.00
ATOM 1474 O ASP 78 8.988 5.752-20.581 1.000.00
ATOM 1475 N THR 79 8.656 6.394-22.724 1.000.00
ATOM 1476 HN THR 79 8.371 6.190-23.661 1.000.00
ATOM 1477 CA THR 79 9.101 7.759-22.501 1.000.00
ATOM 1478 HA THR 79 8.415 8.234-21.800 1.000.00
ATOM 1479 CB THR 79 10.501 7.705-21.887 1.000.00
ATOM 1480 HB THR 79 10.467 7.300-20.875 1.000.00
ATOM 1481 QG2THR 79 11.727 6.739-22.960 1.000.00
ATOM 1482 OGl THR 79 10.964 9.050-21.957 1.000.00
ATOM 1483 HG1 THR 79 10.552 9.593-21.225 1.000.00
ATOM 1484 CG2 THR 79 11.491 6.924-22.754 1.000.00
ATOM 14851HG2THR . 79 12.508 7.237-22.515 1.000.00
ATOM 14862HG2 THR . 79 11.384 5.857-22.558 1.000.00
ATOM 14873HG2 THR 79 11.288 7.123-23.806 1.000.00
ATOM 1488 C THR 79 9.039 8.560-23.803 1.000.00
ATOM 1489 O THR 79 9.924 9.368-24.081 1.000.00
ATOM 1490 N TYR 80 7.986 8.307-24.566 1.000.00
ATOM 1491 HN TYR 80 7.271 7.649-24.332 1.000.00
ATOM 1492 CA TYR 80 7.797 8.995-25.832 1.000.00
ATOM 1493 HA TYR 80 8.119 10.028-25.705 1.000.00
ATOM 1494 CB TYR 80 8.617 8.215-26.862 1.000.00
ATOM 14952HB TYR 80 9.675 8.429-26.707 1.000.00
ATOM 14961HB TYR 80 8.479 7.148-26.688 1.000.00
ATOM 1497 QB TYR 80 9.077 7.788-26.697 1.000.00
ATOM 1498 QD TYR 80 8.221 8.561 -28.452 1.000.00
ATOM 1499 QE TYR 80 7.620 9.087-30.865 1.000.00
ATOM 1500 QR TYR 80 7.920 8.824-29.659 1.000.00
ATOM 1501 CG TYR 80 8.255 8.531-28.314 1.000.00
ATOM 1502 CDl TYR 80 9.061 9.369-29.059 1.000.00
ATOM 1503 HDl TYR 80 9.955 9.804-28.613 1.000.00
ATOM 1504 CE1 TYR 80 8.720 9.667-30.426 1.000.00
ATOM 1505 HEI TYR 80 9.348 10.326-31.026 1.000.00
ATOM 1506 CZ TYR 80 7.598 9.106-30.952 1.000.00
ATOM 1507 CE2TYR 80 6.783 8.278-30.246 1.000.00
ATOM 1508 HE2TYR 80 5.892 7.848-30.705 1.000.00
ATOM 1509 CD2TYR 80 7.124 7.980-28.879 1.000.00
ATOM 1510 HD2TYR 80 6.488 7.318-28.291 1.000.00
ATOM 1511 OH TYR 80 7.277 9.388-32.244 1.000.00
ATOM 1512 HH TYR 80 6.304 9.215-32.399 1.000.00
ATOM 1513 C TYR 80 6.326 8.978-26.251 1.000.00
ATOM 1514 O TYR 80 5.594 8.045-25.924 1.000.00
ATOM 1515 N PRO 81 5.926 10.049-26.987 1.000.00
ATOM 1516 CD PRO 81 4.582 10.277-27.510 1.000.00
ATOM 1517 CA PRO 81 6.856 11.111 -27.330 1.000.00
ATOM 1518 HA PRO 81 7.739 10.726-27.598 1.000.00
ATOM 1519 CB PRO 81 6.196 11.857-28.478 1.000.00 ATOM 15202HB PRO 81 6.327 12.934-28.371 1.000.00
ATOM 15211HB PRO 81 6.639 11.576-29.433 1.000.00
ATOM 1522 QB PRO 81 6.483 12.255-28.902 1.000.00
ATOM 1523 CG PRO 81 4.724 11.480-28.428 1.000.00
ATOM 15242HG PRO 81 4.128 12.315-28.058 1.000.00
ATOM 15251HG PRO 81 4.356 11.244-29.427 1.000.00
ATOM 1526 QG PRO 81 4.242 11.780-28.743 1.000.00
ATOM 15272HD PRO 81 3.872 10.474-26.706 1.000.00
ATOM 15281HD PRO 81 4.215 9.406-28.053 1.000.00
ATOM 1529 QD PRO 81 4.044 9.940-27.380 1.000.00
ATOM 1530 C PRO 81 7.139 12.004-26.121 1.000.00
ATOM 1531 O PRO 81 8.154 12.698-26.081 1.000.00
ATOM 1532 N TYR 82 6.224 11.958-25.164 1.000.00
ATOM 1533 HN TYR 82 5.401 11.391-25.204 1.000.00
ATOM 1534 CA TYR 82 6.362 12.754-23.956 1.000.00
ATOM 1535 HA TYR 82 7.397 12.681-23.621 1.000.00
ATOM 1536 CB TYR 82 5.936 14.174-24.336 1.000.00
ATOM 15372HB TYR 82 4.947 14.136-24.793 1.000.00
ATOM 15381HB TYR 82 5.846 14.771 -23.429 1.000.00
ATOM 1539 QB TYR 82 5.396 14.453-24.111 1.000.00
ATOM 1540 QD TYR 82 6.989 14.943-25.388 1.000.00
ATOM 1541 QE TYR 82 8.588 16.109-26.985 1.000.00
ATOM 1542 QR TYR 82 7.789 15.526-26.186 1.000.00
ATOM 1543 CG TYR 82 6.898 14.876-25.297 1.000.00
ATOM 1544 CDl TYR 82 8.224 15.038-24.950 1.000.00
ATOM 1545 HDl TYR 82 8.586 14.666-23.992 1.000.00
ATOM 1546 CE1 TYR 82 9.130 15.699-25.854 1.000.00
ATOM 1547 HEI TYR 82 10.179 15.833-25.593 1.000.00
ATOM 1548 CZ TYR 82 8.645 16.151-27.042 1.000.00
ATOM 1549 CE2TYR 82 7.345 16.008-27.415 1.000.00
ATOM 1550 HE2TYR 82 6.997 16.385-28.376 1.000.00
ATOM 1551 CD2TYR 82 6.440 15.347-26.511 1.000.00
ATOM 1552 HD2TYR 82 5.393 15.219-26.785 1.000.00
ATOM 1553 OH TYR 82 9.500 16.775-27.896 1.000.00
ATOM 1554 HH TYR 82 8.985 17.286-28.584 1.000.00
ATOM 1555 C TYR 82 5.440 12.237-22.850 1.000.00
ATOM 1556 O TYR 82 5.839 12.164-21.689 1.000.00
ATOM 1557 N ASN 83 4.225 11.892-23.249 1.000.00
ATOM 1558 HN ASN 83 3.909 11.954-24.196 1.000.00
ATOM 1559 CA ASN 83 3.244 11.384-22.306 1.000.00
ATOM 1560 HA ASN 83 3.825 10.969-21.483 1.000.00
ATOM 1561 CB ASN 83 2.326 12.503-21.810 1.000.00
ATOM 15622HB ASN 83 2.196 13.247-22.596 1.000.00
ATOM 15631HB ASN 83 1.338 12.097-21.590 1.000.00
ATOM 1564 QB ASN 83 1.767 12.672-22.093 1.000.00
ATOM 1565 CG ASN 83 2.900 13.170-20.559 1.000.00
ATOM 1566 OD1 ASN 83 3.921 13.836-20.593 1.000.00
ATOM 1567 ND2ASN 83 2.189 12.953-19.456 1.000.00
ATOM 15681HD2ASN 83 1.360 12.396-19.497 1.000.00
ATOM 15692HD2 ASN 83 2.484 13.348-18.586 1.000.00
ATOM 1570 QD2ASN 83 1.922 12.872-19.041 1.000.00
ATOM 1571 C ASN 83 2.375 10.331-22.998 1.000.00
ATOM 1572 O ASN 83 2.357 10.245-24.225 1.000.00
ATOM 1573 N PRO 84 1.658 9.536-22.159 1.000.00
ATOM 1574 CD PRO 84 1.655 9.609-20.701 1.000.00
ATOM 1575 CA PRO 84 0.790 8.493-22.677 1.000.00
ATOM 1576 HA PRO 84 1.237 8.010-23.430 1.000.00
ATOM 1577 CB PRO 84 0.530 7.574-21.495 1.000.00
ATOM 15782HB PRO 84 -0.511 7.252-21.472 1.000.00 ATOM 15791HB PRO 84 1.141 6.674-21.558 1.000.00
ATOM 1580 QB PRO 84 0.315 6.963-21.515 1.000.00
ATOM 1581 CG PRO 84 0.877 8.382-20.255 1.000.00
ATOM 15822HG PRO 84 -0.029 8.676-19.725 1.000.00
ATOM 15831HG PRO 84 1.471 7.784-19.563 1.000.00
ATOM 1584 QG PRO 84 0.721 8.230-19.644 1.000.00
ATOM 15852HD PRO 84 1.182 10.527-20.352 1.000.00
ATOM 15861HD PRO 84 2.669 9.602-20.302 1.000.00
ATOM 1587 QD PRO 84 1.926 10.065-20.327 1.000.00
ATOM 1588 C PRO 84 -0.492 9.088-23.265 1.000.00
ATOM 1589 O PRO 84 -1.307 9.655-22.539 1.000.00
ATOM 1590 N PRO 85 -0.633 8.933-24.609 1.000.00
ATOM 1591 CD PRO 85 0.311 8.266-25.500 1.000.00
ATOM 1592 CA PRO 85 -1.802 9.448-25.302 1.000.00
ATOM 1593 HA PRO 85 -2.037 10.357-24.958 1.000.00
ATOM 1594 CB PRO 85 -1.404 9.485-26.769 1.000.00
ATOM 15952HB PRO 85 -2.225 9.153-27.404 1.000.00
ATOM 15961HB PRO 85 -1.151 10.499-27.079 1.000.00
ATOM 1597 QB PRO 85 -1.688 9.826-27.242 1.000.00
ATOM 1598 CG PRO 85 -0.205 8.560-26.899 1.000.00
ATOM 15992HG PRO 85 -0.489 7.636-27.403 1.000.00
ATOM 16001HG PRO 85 0.573 9.027-27.503 1.000.00
ATOM 1601 QG PRO 85 0.042 8.331 -27.453 1.000.00
ATOM 16022HD PRO 85 0.347 7.194-25.308 1.000.00
ATOM 16031HD PRO 85 1.323 8.649-25.363 1.000.00
ATOM 1604 QD PRO 85 0.835 7.921 -25.335 1.000.00
ATOM 1605 C PRO 85 -3.027 8.571 -25.037 1.000.00
ATOM 1606 O PRO 85 -4.160 9.000-25.254 1.000.00
ATOM 1607 N ILE 86 -2.759 7.360-24.572 1.000.00
ATOM 1608 HN ILE 86 -1.835 7.020-24.398 1.000.00
ATOM 1609 CA ILE 86 -3.826 6.419-24.275 1.000.00
ATOM 1610 HA ILE 86 -4.640 6.618-24.972 1.000.00
ATOM 1611 CB ILE 86 -3.359 4.984-24.523 1.000.00
ATOM 1612 HB ILE 86 -2.479 4.800-23.907 1.000.00
ATOM 1613 QG2ILE 86 -4.683 3.738-23.992 1.000.00
ATOM 1614 CG2 ILE 86 -4.429 3.977-24.094 1.000.00
ATOM 16151HG2ILE 86 -5.411 4.338-24.401 1.000.00
ATOM 16162HG2 ILE 86 -4.232 3.015-24.566 1.000.00
ATOM 16173HG2 ILE 86 -4.406 3.863-23.011 1.000.00
ATOM 1618 CGI ILE 86 -2.939 4.788-25.981 1.000.00
ATOM 16192HG1 ILE 86 -3.821 4.603-26.595 1.000.00
ATOM 16201HG1 ILE 86 -2.476 5.700-26.356 1.000.00
ATOM 1621 QGl ILE 86 -3.148 5.152-26.475 1.000.00
ATOM 1622 QDl ILE 86 -1.729 3.342-26.150 1.000.00
ATOM 1623 CDl ILE 86 -1.961 3.619-26.118 1.000.00
ATOM 16241HD1 ILE 86 -2.418 2.831 -26.715 1.000.00
ATOM 16252HD1 ILE 86 -1.050 3.964-26.607 1.000.00
ATOM 16263HD1 ILE 86 -1.718 3.231 -25.128 1.000.00
ATOM 1627 C ILE 86 - -4.335 6.664-22.853 1.000.00
ATOM 1628 O ILE 86 -3.827 6.077-21.899 1.000.00
ATOM 1629 N CYS 87 -5.331 7.532-22.756 1.000.00
ATOM 1630 HN CYS 87 -5.739 8.005-23.537 1.000.00
ATOM 1631 CA CYS 87 -5.914 7.861 -21.466 1.000.00
ATOM 1632 HA CYS 87 -5.592 7.086-20.770 1.000.00
ATOM 1633 CB CYS 87 -5.392 9.197-20.934 1.000.00
ATOM 16342HB CYS 87 -5.778 10.016-21.542 1.000.00
ATOM 16351HB CYS 87 -5.751 9.359-19.918 1.000.00
ATOM 1636 QB CYS 87 -5.765 9.687-20.730 1.000.00
ATOM 1637 SG CYS 87 -3.563 9.210-20.960 1.000.00 ATOM 1638 HG CYS 87 -3.438 8.785-22.214 1.000.00
ATOM 1639 C CYS 87 -7.437 7.860-21.613 1.000.00
ATOM 16400 CYS 87 -8.021 8.845-22.063 1.000.00
ATOM 1641 N PHE 88 -8.036 6.745-21.225 1.000.00 ATOM 1642 HN PHE 88 -7.554 5.948-20.860 1.000.00
ATOM 1643 CA PHE 88 -9.480 6.603-21.307 1.000.00
ATOM 1644 HA PHE 88 -9.886 7.579-21.573 1.000.00
ATOM 1645 CB PHE 88 -9.765 5.526-22.356 1.000.00
ATOM 16462HB PHE 88 -10.829 5.293-22.343 1.000.00 ATOM 16471HB PHE 88 -9.538 5.927-23.344 1.000.00
ATOM 1648 QB PHE 88 -10.184 5.610-22.844 1.000.00
ATOM 1649 QD PHE 88 -8.901 4.120-22.135 1.000.00
ATOM 1650 QE PHE 88 -7.600 2.000-21.800 1.000.00
ATOM 1651 QR PHE 88 -8.251 3.060-21.968 1.000.00 ATOM 1652 CG PHE 88 -8.971 4.234-22.153 1.000.00
ATOM 1653 CDl PHE 88 -9.347 3.350-21.190 1.000.00
ATOM 1654 HDl PHE 88 -10.214 3.562-20.564 1.000.00
ATOM 1655 CE1 PHE 88 -8.611 2.150-21.001 1.000.00
ATOM 1656 HEI PHE 88 -8.912 1.442-20.230 1.000.00 ATOM 1657 CZ PHE 88 -7.530 1.886-21.782 1.000.00
ATOM 1658 HZ PHE 88 -6.965 0.965-21.637 1.000.00
ATOM 1659 CE2 PHE 88 -7.154 2.770-22.745 1.000.00
ATOM 1660 HE2 PHE 88 -6.287 2.558-23.371 1.000.00
ATOM 1661 CD2PHE 88 -7.890 3.969-22.934 1.000.00 ATOM 1662 HD2 PHE 88 -7.589 4.678-23.705 1.000.00
ATOM 1663 C PHE 88 -10.065 6.158-19.965 1.000.00
ATOM 16640 PHE 88 -9.364 5.570-19.143 1.000.00
ATOM 1665 N VAL 89 -11.344 6.455-19.786 1.000.00
ATOM 1666 HN VAL 89 -11.907 6.933-20.460 1.000.00 ATOM 1667 CA VAL 89 -12.031 6.093-18.558 1.000.00
ATOM 1668 HA VAL 89 -11.306 6.149-17.746 1.000.00
ATOM 1669 CB VAL 89 -13.146 7.099-18.266 1.000.00
ATOM 1670 HB VAL 89 -12.694 8.088-18.191 1.000.00
ATOM 1671 QGl VAL 89 -14.408 7.142-19.677 1.000.00 ATOM 1672 QG2 VAL 89 -13.989 6.718-16.614 1.000.00
ATOM 1673 CGI VAL 89 -14.166 7.134-19.407 1.000.00
ATOM 16741HG1 VAL 89 -14.244 6.143-19.854 1.000.00
ATOM 16752HG1 VAL 89 -15.138 7.434-19.016 1.000.00
ATOM 16763HG1 VAL 89 -13.841 7.849-20.162 1.000.00 ATOM 1677 CG2 VAL 89 -13.827 6.791-16.931 1.000.00
ATOM 16781HG2 VAL 89 -13.543 5.792-16.600 1.000.00
ATOM 16792HG2 VAL 89 -13.514 7.523-16.1861.000.00
ATOM 16803HG2 VAL 89 -14.909 6.839-17.055 1.000.00
ATOM 1681 QQG VAL 89 -14.198 6.930-18.146 1.000.00 ATOM 1682 C VAL 89 -12.538 4.654-18.668 1.000.00
ATOM 1683 O VAL 89 -12.930 4.210-19.746 1.000.00
ATOM 1684 N LYS 90 -12.514 3.964-17.537 1.000.00
ATOM 1685 HN LYS 90 -12.193 4.332-16.664 1.000.00
ATOM 1686 CA LYS 90 -12.966 2.584-17.492 1.000.00 ATOM 1687 HA LYS 90 -13.319 2.323-18.490 1.000.00
ATOM 1688 CB LYS 90 -11.800 1.648-17.167 1.000.00
ATOM 16892HB LYS 90 -12.161 0.622-17.094 1.000.00
ATOM 16901HB LYS 90 -11.072 1.672-17.978 1.000.00
ATOM 1691 QB LYS 90 -11.617 1.147-17.536 1.000.00 ATOM 1692 CG LYS 90 -11.124 2.051-15.855 1.000.00
ATOM 16932HG LYS 90 -10.260 2.682-16.066 1.000.00
ATOM 16941HG LYS 90 -11.812 2.644-15.254 1.000.00
ATOM 1695 QG LYS 90 -11.036 2.663-15.660 1.000.00
ATOM 1696 CD LYS 90 -10.680 0.817-15.065 1.000.00 ATOM 16972HD LYS 90 -10.752 -0.068-15.697 1.000.00
ATOM 16981HD LYS 90 -9.633 0.921 -14.780 1.000.00
ATOM 1699 QD LYS 90 -10.193 0.426-15.238 1.000.00
ATOM 1700 CE LYS 90 -11.540 0.629-13.814 1.000.00
ATOM 17012HE LYS 90 -12.468 1.192-13.915 1.000.00
ATOM 1702 IHE LYS 90 -11.813 -0.421 -13.708 1.000.00
ATOM 1703 QE LYS 90 -12.141 0.385-13.812 1.000.00
ATOM 1704 NZ LYS 90 -10.808 1.081 -12.610 1.000.00
ATOM 17051HZ LYS 90 -9.897 0.642-12.531 1.000.00
ATOM 17062HZ LYS 90 -10.652 2.083-12.614 1.000.00
ATOM 1707 QZ LYS 90 -10.274 1.363-12.573 1.000.00
ATOM 1708 C LYS 90 -14.139 2.467-16.517 1.000.00
ATOM 1709 O LYS 90 -13.964 2.034-15.379 1.000.00
ATOM 1710 N PRO 91 -15.340 2.871 -17.011 1.000.00
ATOM 1711 CD PRO 91 -15.585 3.389-18.354 1.000.00
ATOM 1712 CA PRO 91 -16.541 2.816-16.196 1.000.00
ATOM 1713 HA PRO 91 -16.345 3.129-15.266 1.000.00
ATOM 1714 CB PRO 91 -17.535 3.727-16.898 1.000.00
ATOM 17152HB PRO 91 -18.535 3.292-16.893 1.000.00
ATOM 17161HB PRO 91 -17.605 4.691 -16.394 1.000.00
ATOM 1717 QB PRO 91 -18.070 3.992-16.644 1.000.00
ATOM 1718 CG PRO 91 -17.019 3.890-18.318 1.000.00
ATOM 17192HG PRO 91 -17.638 3.327-19.017 1.000.00
ATOM 17201HG PRO 91 -17.066 4.936-18.623 1.000.00
ATOM 1721 QG PRO 91 -17.352 4.131 -18.820 1.000.00
ATOM 17222HD PRO 91 -15.455 2.612-19.108 1.000.00
ATOM 17231HD PRO 91 -14.890 4.192-18.601 1.000.00
ATOM 1724 QD PRO 91 -15.173 3.402-18.854 1.000.00
ATOM 1725 C PRO 91 -17.044 1.378-16.056 1.000.00
ATOM 1726 O PRO 91 -16.632 0.497-16.809 1.000.00
ATOM 1727 N THR 92 -17.927 1.185-15.087 1.000.00
ATOM 1728 HN THR 92 -18.256 1.907-14.479 1.000.00
ATOM 1729 CA THR 92 -18.490 -0.131 -14.839 1.000.00
ATOM 1730 HA THR 92 -17.719 -0.877-15.033 1.000.00
ATOM 1731 CB THR 92 -18.906 -0.198-13.368 1.000.00
ATOM 1732 HB THR 92 -19.212 -1.208-13.096 1.000.00
ATOM 1733 QG2THR 92 -17.556 0.438-12.203 1.000.00
ATOM 1734 OGl THR 92 -19.945 0.771 -13.258 1.000.00
ATOM 1735 HG1 THR 92 -20.441 0.645-12.398 1.000.00
ATOM 1736 CG2THR 92 -17.815 0.316-12.427 1.000.00
ATOM 17371HG2 THR 92 -17.503 1.311 -12.742 1.000.00
ATOM 17382HG2 THR 92 -18.205 0.363-11.410 1.000.00
ATOM 17393HG2 THR 92 -16.961 -0.360-12.458 1.000.00
ATOM 1740 C THR 92 -19.639 -0.412-15.809 1.000.00
ATOM 1741 O THR 92 -19.642 0.088-16.934 1.000.00
ATOM 1742 N SER 93 -20.587 -1.209-15.339 1.000.00
ATOM 1743 HN SER 93 -20.576 -1.611 -14.424 1.000.00
ATOM 1744 CA SER 93 -21.739 -1.561 -16.152 1.000.00
ATOM 1745 HA SER 93 -21.535 -1.145-17.138 1.000.00
ATOM 1746 CB SER 93 -21.891 -3.080-16.262 1.000.00
ATOM 17472HB SER 93 -21.351 -3.559-15.445 1.000.00
ATOM 17481HB SER 93 -22.942 -3.348-16.149 1.000.00
ATOM 1749 QB SER 93 -22.147 -3.453-15.797 1.000.00
ATOM 1750 OG SER 93 -21.406 -3.576-17.506 1.000.00
ATOM 1751 HG SER 93 -21.632 -2.937-18.241 1.000.00
ATOM 1752 C SER 93 ■ -23.006 -0.942-15.558 1.000.00
ATOM 1753 O SER 93 -24.032 -0.856-16.231 1.000.00
ATOM 1754 N SER 94 -22.893 -0.528-14.305 1.000.00
ATOM 1755 HN SER 94 -22.055 -0.602-13.765 1.000.00 ATOM 1756 CA SER 94 -24.017 0.080-13.614 1.000.00
ATOM 1757 HA SER 94 -24.906 -0.314-14.105 1.000.00
ATOM 1758 CB SER 94 -24.035 -0.315-12.136 1.000.00
ATOM 17592HB SER 94 -23.514 -1.264-12.009 1.000.00
ATOM 17601HB SER 94 -23.488 0.428-11.556 1.000.00
ATOM 1761 QB SER 94 -23.501 -0.418-11.782 1.000.00
ATOM 1762 OG SER 94 -25.362 -0.430-11.630 1.000.00
ATOM 1763 HG SER 94 -25.592 0.378-11.088 1.000.00
ATOM 1764 C SER 94 -23.957 1.603-13.755 1.000.00
ATOM 1765 O SER 94 -24.757 2.318-13.155 1.000.00
ATOM 1766 N MET 95 -23.000 2.053-14.553 1.000.00
ATOM 1767 HN MET 95 -22.353 1.465-15.038 1.000.00
ATOM 1768 CA MET 95 -22.825 3.478-14.781 1.000.00
ATOM 1769 HA MET 95 -23.269 3.969-13.916 1.000.00
ATOM 1770 CB MET 95 -21.333 3.796-14.898 1.000.00
ATOM 17712HB MET 95 -20.758 2.871 -14.886 1.000.00
ATOM 17721HB MET 95 -21.135 4.282-15.854 1.000.00
ATOM 1773 QB MET 95 -20.946 3.576-15.370 1.000.00
ATOM 1774 CG MET 95 -20.875 4.703-13.754 1.000.00
ATOM 17752HG MET 95 -21.409 5.652-13.795 1.000.00
ATOM 17761HG MET 95 -21.115 4.243-12.796 1.000.00
ATOM 1777 QG MET 95 -21.262 4.948-13.296 1.000.00
ATOM 1778 SD MET 95 -19.116 4.989-13.869 1.000.00
ATOM 1779 QE MET 95 -18.493 4.252-11.949 1.000.00
ATOM 1780 CE MET 95 -18.599 4.377-12.274 1.000.00
ATOM 1781 IHE MET 95 -18.144 5.187-11.704 1.000.00
ATOM 17822HE MET 95 -19.464 3.993-11.734 1.000.00
ATOM 17833HE MET 95 -17.871 3.576-12.411 1.000.00
ATOM 1784 C MET 95 -23.543 3.921 -16.057 1.000.00
ATOM 1785 O MET 95 -24.320 3.161-16.633 1.000.00
ATOM 1786 N THR 96 -23.258 5.150-16.462 1.000.00
ATOM 1787 HN THR 96 -22.625 5.762-15.988 1.000.00
ATOM 1788 CA THR 96 -23.868 5.704-17.659 1.000.00
ATOM 1789 HA THR 96 -24.017 4.895-18.374 1.000.00
ATOM 1790 CB THR 96 -25.223 6.297-17.269 1.000.00
ATOM 1791 HB THR 96 -25.095 7.213-16.691 1.000.00
ATOM 1792 QG2THR 96 -26.343 6.594-18.766 1.000.00
ATOM 1793 OGl THR 96 -25.869 5.247-16.555 1.000.00
ATOM 1794 HG1 THR 96 -25.657 5.316-15.580 1.000.00
ATOM 1795 CG2THR 96 -26.128 6.537-18.479 1.000.00
ATOM 17961HG2 THR 96 -25.559 7.033-19.265 1.000.00
ATOM 17972HG2 THR 96 -26.502 5.582-18.848 1.000.00
ATOM 17983HG2 THR 96 -26.968 7.167-18.186 1.000.00
ATOM 1799 C THR 96 -22.928 6.717-18.316 1.000.00
ATOM 1800 O THR 96 -22.902 7.885-17.932 1.000.00
ATOM 1801 N ILE 97 - 22.179 6.231 -19.296 1.000.00
ATOM 1802 HN ILE 97 -22.207 5.280-19.602 1.000.00
ATOM 1803 CA ILE 97 -21.240 7.079-20.010 1.000.00
ATOM 1804 HA ILE 97 -20.590 7.545-19.269 1.000.00
ATOM 1805 CB ILE 97 -20.350 6.239-20.928 1.000.00
ATOM 1806 HB ILE 97 -20.392 5.204-20.590 1.000.00
ATOM 1807 QG2ILE 97 -20.990 6.271-22.709 1.000.00
ATOM 1808 CG2ILE 97 -20.867 6.265-22.368 1.000.00
ATOM 18091HG2 ILE 97 -21.953 6.176-22.365 1.000.00
ATOM 18102HG2 ILE 97 -20.580 7.205-22.840 1.000.00
ATOM 18113HG2 ILE 97 -20.436 5.433-22.924 1.000.00
ATOM 1812 CGI ILE 97 -18.890 6.686-20.835 1.000.00
ATOM 18132HG1 ILE 97 -18.706 7.491 -21.547 1.000.00
ATOM 18141HG1 ILE 97 -18.691 7.088-19.842 1.000.00 ATOM 1815 QGl ILE 97 -18.699 7.289-20.694 1.000.00
ATOM 1816 QDl ILE 97 -17.715 5.243-21.186 1.000.00
ATOM 1817 CDl ILE 97 -17.940 5.520-21.119 1.000.00
ATOM 18181HD1 ILE 97 -18.329 4.614-20.655 1.000.00
ATOM 18192HD1 ILE 97 -17.859 5.372-22.196 1.000.00
ATOM 18203HD1 ILE 97 -16.956 5.745-20.708 1.000.00
ATOM 1821 C ILE 97 - 22.009 8.182-20.741 1.000.00
ATOM 1822 O ILE 97 - 23.076 7.933-21.301 1.000.00
ATOM 1823 N LYS 98 -21.438 9.377-20.711 1.000.00
ATOM 1824 HN LYS 98 -20.570 9.571 -20.254 1.000.00
ATOM 1825 CA LYS 98 -22.056 10.519-21.364 1.000.00
ATOM 1826 HA LYS 98 -23.026 10.193-21.741 1.000.00
ATOM 1827 CB LYS 98 -22.316 11.637-20.353 1.000.00
ATOM 18282HB LYS 98 -23.144 11.359-19.701 1.000.00
ATOM 18291HB LYS 98 -21.441 11.769-19.717 1.000.00
ATOM 1830 QB LYS 98 -22.292 11.564-19.709 1.000.00
ATOM 1831 CG LYS 98 -22.639 12.954-21.064 1.000.00
ATOM 18322HG LYS 98 -23.060 12.746-22.047 1.000.00
ATOM 18331HG LYS 98 -23.398 13.498-20.501 1.000.00
ATOM 1834 QG LYS 98 -23.229 13.122-21.274 1.000.00
ATOM 1835 CD LYS 98 -21.386 13.819-21.211 1.000.00
ATOM 18362HD LYS 98 -20.942 13.991-20.231 1.000.00
ATOM 18371HD LYS 98 -20.644 13.291 -21.810 1.000.00
ATOM 1838 QD LYS 98 -20.793 13.641 -21.020 1.000.00
ATOM 1839 CE LYS 98 -21.720 15.160-21.868 1.000.00
ATOM 18402HE LYS 98 -20.836 15.558-22.366 1.000.00
ATOM 1841 IHE LYS 98 -22.481 15.016-22.636 1.000.00
ATOM 1842 QE LYS 98 -21.659 15.287-22.501 1.000.00
ATOM 1843 NZ LYS 98 -22.205 16.126-20.858 1.000.00
ATOM 18441HZ LYS 98 -22.053 15.795-19.911 1.000.00
ATOM 18452HZ LYS 98 -21.736 17.022-20.934 1.000.00
ATOM 1846 QZ LYS 98 -21.895 16.409-20.423 1.000.00
ATOM 1847 C LYS 98 -21.194 10.951 -22.552 1.000.00
ATOM 1848 O LYS 98 -20.011 11.247-22.389 1.000.00
ATOM 1849 N THR 99 -21.819 10.973-23.719 1.000.00
ATOM 1850 HN THR 99 -22.781 10.731 -23.843 1.000.00
ATOM 1851 CA THR 99 -21.124 11.364-24.934 1.000.00
ATOM 1852 HA THR 99 -20.125 10.927-24.914 1.000.00
ATOM 1853 CB THR 99 -21.903 10.805-26.126 1.000.00
ATOM 1854 HB THR 99 -21.417 11.067-27.066 1.000.00
ATOM 1855 QG2THR 99 -22.172 8.935-26.002 1.000.00
ATOM 1856 OGl THR 99 -23.209 11.354-25.975 1.000.00
ATOM 1857 HG1 THR 99 -23.707 11.293-26.840 1.000.00
ATOM 1858 CG2THR 99 -22.120 9.294-26.026 1.000.00
ATOM 18591HG2THR 99 -23.067 9.095-25.524 1.000.00
ATOM 18602HG2THR 99 -22.142 8.863-27.027 1.000.00
ATOM 18613HG2THR 99 -21.306 8.846-25.456 1.000.00
ATOM 1862 C THR 99 -20.948 12.883-24.982 1.000.00
ATOM 1863 O THR 99 -21.851 13.629-24.606 1.000.00
ATOM 1864 N GLY 100 -19.778 13.297-25.447 1.000.00
ATOM 1865 HN GLY 100 -19.049 12.684-25.751 1.000.00
ATOM 1866 CA GLY 100 -19.472 14.714-25.550 1.000.00
ATOM 18672HA GLY 100 -20.333 15.247-25.951 1.000.00
ATOM 18681HA GLY 100 -19.280 15.120-24.557 1.000.00
ATOM 1869 QA GLY 100 -19.806 15.184-25.254 1.000.00
ATOM 1870 C GLY 100 -18.256 14.948-26.447 1.000.00
ATOM 1871 O GLY 100 -17.943 14.122-27.304 1.000.00
ATOM 1872 N LYS 1 101 -17.602 16.079-26.221 1.000.00
ATOM 1873 HN LYS 101 -17.863 16.745-25.523 1.000.00 ATOM 1874 CA LYS 101 -16.427 16.432-26.999 1.000.00
ATOM 1875 HA LYS 101 -16.575 16.047-28.007 1.000.00
ATOM 1876 CB LYS 101 -16.297 17.953-27.111 1.000.00
ATOM 18772HB LYS 101 -15.515 18.203-27.828 1.000.00
ATOM 18781HB LYS 101 -17.226 18.374-27.493 1.000.00
ATOM 1879 QB LYS 101 -16.370 18.288-27.661 1.000.00
ATOM 1880 CG LYS 101 -15.969 18.576-25.752 1.000.00
ATOM 18812HG LYS 101 -16.294 17.909-24.954 1.000.00
ATOM 18821HG LYS 101 -14.889 18.691 -25.652 1.000.00
ATOM 1883 QG LYS 101 -15.592 18.300-25.303 1.000.00
ATOM 1884 CD LYS 101 -16.649 19.938-25.596 1.000.00
ATOM 18852HD LYS 101 -16.63720.466-26.549 1.000.00
ATOM 18861HD LYS 101 -17.694 19.797-25.322 1.000.00
ATOM 1887 QD LYS 101 -17.16620.132-25.936 1.000.00
ATOM 1888 CE LYS 101 -15.946 20.782-24.530 1.000.00
ATOM 18892HE LYS 101 -16.497 20.725-23.591 1.000.00
ATOM 1890 IHE LYS 101 -14.95020.383-24.340 1.000.00
ATOM 1891 QE LYS 101 -15.723 20.554-23.966 1.000.00
ATOM 1892 NZ LYS 101 -15.847 22.192-24.969 1.000.00
ATOM 18931HZ LYS 101 -14.902 22.440-25.240 1.000.00
ATOM 18942HZ LYS 101 -16.442 22.384-25.768 1.000.00
ATOM 1895 QZ LYS 101 -15.672 22.412-25.504 1.000.00
ATOM 1896 C LYS i 101 -15.197 15.752-26.394 1.000.00
ATOM 1897 O LYS 101 -14.182 15.583-27.069 1.000.00
ATOM 1898 N HIS 102 - 15.328 15.380-25.129 1.000.00
ATOM 1899 HN HIS 102 -16.157 15.521-24.588 1.000.00
ATOM 1900 CA HIS 102 -14.240 14.722-24.427 1.000.00
ATOM 1901 HA HIS 102 -13.321 15.000-24.943 1.000.00
ATOM 1902 CB HIS 102 -14.137 15.230-22.987 1.000.00
ATOM 19032HB HIS 102 -15.142 15.359-22.585 1.000.00
ATOM 19041HB HIS 102 -13.646 14.471 -22.379 1.000.00
ATOM 1905 QB HIS 102 -14.394 14.915-22.482 1.000.00
ATOM 1906 CG HIS 102 -13.384 16.531-22.847 1.000.00
ATOM 1907 ND1 HIS 102 -12.115 16.608-22.300 1.000.00
ATOM 1908 CD2 HIS 102 -13.733 17.805-23.189 1.000.00
ATOM 1909 HDl HIS 102 -11.580 15.838-21.952 1.000.00
ATOM 1910 CE1HIS 102 -11.728 17.875-22.317 1.000.00
ATOM 1911 NE2HIS 102 -12.733 18.615-22.867 1.000.00
ATOM 1912 HD2HIS 102 -14.675 18.105-23.648 1.000.00
ATOM 1913 HEI HIS 102 -10.774 18.259-21.954 1.000.00
ATOM 1914 C HIS 102 - 14.419 13.205-24.509 1.000.00
ATOM 1915 O HIS 102 - 13.444 12.468-24.650 1.000.00
ATOM 1916 N VAL 103 -15.671 12.783-24.416 1.000.00
ATOM 1917 HN VAL 103 -16.458 13.389-24.301 1.000.00
ATOM 1918 CA VAL 103 -15.991 11.367-24.478 1.000.00
ATOM 1919 HA VAL 103 -15.057 10.826-24.631 1.000.00
ATOM 1920 CB VAL 103 -16.592 10.908-23.148 1.000.00
ATOM 1921 HB VAL 103 -17.538 11.430-23.010 1.000.00
ATOM 1922 QGl VAL 103 -16.952 9.049-23.172 1.000.00
ATOM 1923 QG2VAL 103 -15.460 11.361 -21.699 1.000.00
ATOM 1924 CGI VAL 103 -16.883 9.406-23.168 1.000.00
ATOM 19251HG1 VAL . 103 -16.879 9.022-22.148 1.000.00
ATOM 19262HG1 VAL . 103 -17.860 9.231 -23.618 1.000.00
ATOM 19273 HG1 VAL . 103 -16.117 8.895-23.751 1.000.00
ATOM 1928 CG2 VAL 103 -15.677 11.274-21.977 1.000.00
ATOM 19291HG2 VAL . 103 -14.686 10.852-22.145 1.000.00
ATOM 19302HG2 VAL . 103 -15.602 12.359-21.901 1.000.00
ATOM 19313HG2 VAL . 103 -16.092 10.872-21.053 1.000.00
ATOM 1932 QQG VAL , 103 -16.206 10.205-22.436 1.000.00 ATOM 1933 C VAL 103 -16.912 11.108-25.672 1.000.00
ATOM 19340 VAL 103 -17.716 11.965-26.037 1.000.00
ATOM 1935 N ASP 104 -16.764 9.924-26.246 1.000.00
ATOM 1936 HN ASP 104 -16.108 9.233-25.943 1.000.00 ATOM 1937 CA ASP 104 -17.573 9.542-27.391 1.000.00
ATOM 1938 HA ASP 104 -17.997 10.473-27.766 1.000.00
ATOM 1939 CB ASP 104 -16.721 8.863-28.466 1.000.00
ATOM 19402HB ASP 104 -15.675 9.117-28.292 1.000.00
ATOM 19411HB ASP 104 -16.810 7.783-28.351 1.000.00 ATOM 1942 QB ASP 104 -16.243 8.450-28.322 1.000.00
ATOM 1943 CG ASP 104 -17.081 9.234-29.906 1.000.00
ATOM 1944 OD1 ASP 104 -18.185 9.728-30.181 1.000.00
ATOM 1945 OD2 ASP 104 -16.161 8.992-30.778 1.000.00
ATOM 1946 HD2 ASP 104 -16.499 8.344-31.460 1.000.00 ATOM 1947 C ASP 104 -18.647 8.548-26.943 1.000.00
ATOM 1948 O ASP 104 -19.835 8.764-27.178 1.000.00
ATOM 1949 N ALA 105 -18.190 7.480-26.305 1.000.00
ATOM 1950 HN ALA 105 -17.223 7.312-26.118 1.000.00
ATOM 1951 CA ALA 105 -19.097 6.453-25.822 1.000.00 ATOM 1952 HA ALA 105 -19.754 6.911-25.083 1.000.00
ATOM 1953 QB ALA 105 -20.149 5.811-27.259 1.000.00
ATOM 1954 CB ALA 105 -19.947 5.934-26.983 1.000.00
ATOM 19551HB ALA 105 -19.710 6.496-27.887 1.000.00
ATOM 19562HB ALA 105 -19.734 4.878-27.146 1.000.00 ATOM 19573HB ALA 105 -21.003 6.059-26.745 1.000.00
ATOM 1958 C ALA 105 -18.289 5.341-25.149 1.000.00
ATOM 19590 ALA 105 -18.712 4.788-24.135 1.000.00
ATOM 1960 N ASN 106 -17.141 5.047-25.741 1.000.00
ATOM 1961 HN ASN 106 -16.804 5.501-26.565 1.000.00 ATOM 1962 C A ASN 106 -16.270 4.011-25.211 1.000.00
ATOM 1963 HA ASN 106 -16.927 3.172-24.987 1.000.00
ATOM 1964 CB ASN 106 -15.207 3.608-26.236 1.000.00
ATOM 19652HB ASN 106 -15.107 4.391-26.988 1.000.00
ATOM 19661HB ASN 106 -14.240 3.513-25.743 1.000.00 ATOM 1967 QB ASN 106 -14.673 3.952-26.365 1.000.00
ATOM 1968 CG ASN 106 -15.573 2.286-26.914 1.000.00
ATOM 1969 OD1 ASN 106 -16.572 2.168-27.604 1.000.00
ATOM 1970 ND2 ASN 106 -14.711 1.301-26.679 1.000.00
ATOM 19711HD2 ASN 106 -13.910 1.465-26.102 1.000.00 ATOM 19722HD2 ASN 106 -14.863 0.397-27.079 1.000.00
ATOM 1973 QD2 ASN 106 -14.386 0.931-26.590 1.000.00
ATOM 1974 C ASN 106 -15.551 4.541-23.969 1.000.00
ATOM 19750 ASN 106 -14.871 3.789-23.273 1.000.00
ATOM 1976 N GLY 107 -15.728 5.832-23.728 1.000.00 ATOM 1977 HN GLY 107 -16.283 6.437-24.299 1.000.00
ATOM 1978 CA GLY 107 -15.105 6.471-22.581 1.000.00
ATOM 19792H A GLY 107 -15.679 7.352-22.295 1.000.00
ATOM 19801 HA GLY 107 -15.118 5.791-21.730 1.000.00
ATOM 1981 QA GLY 107 -15.399 6.572-22.012 1.000.00 ATOM 1982 C GLY 107 -13.663 6.876-22.895 1.000.00
ATOM 19830 GLY 107 -12.847 7.035-21.988 1.000.00
ATOM 1984 N LYS 108 -13.392 7.029-24.183 1.000.00
ATOM 1985 HN LYS 108 -14.061 6.898-24.915 1.000.00
ATOM 1986 CA LYS 108 -12.063 7.412-24.628 1.000.00 ATOM 1987 HA LYS 108 -11.354 7.058-23.880 1.000.00
ATOM 1988 CB LYS 108 -11.717 6.714-25.945 1.000.00
ATOM 19892HB LYS 108 -10.743 7.054-26.296 1.000.00
ATOM 19901HB LYS 108 -11.639 5.639-25.781 1.000.00
ATOM 1991 QB LYS 108 -11.191 6.346-26.039 1.000.00 ATOM 1992 CG LYS 108 -12.777 6.998-27.011 1.000.00
ATOM 19932HG LYS 108 -13.330 6.085-27.231 1.000.00
ATOM 19941HG LYS 108 -13.497 7.722-26.630 1.000.00
ATOM 1995 QG LYS 108 -13.414 6.904-26.930 1.000.00
ATOM 1996 CD LYS 108 -12.136 7.533-28.293 1.000.00
ATOM 19972HD LYS 108 -12.108 8.623-28.262 1.000.00
ATOM 19981HD LYS 108 -11.104 7.190-28.359 1.000.00
ATOM 1999 QD LYS 108 -11.606 7.906-28.310 1.000.00
ATOM 2000 CE LYS 108 -12.913 7.073-29.528 1.000.00
ATOM 20012HE LYS 108 -13.948 6.866-29.258 1.000.00
ATOM 2002 IHE LYS 108 -12.930 7.870-30.272 1.000.00
ATOM 2003 QE LYS 108 -13.439 7.368-29.765 1.000.00
ATOM 2004 NZ LYS 108 -12.293 5.860-30.107 1.000.00
ATOM 20051HZ LYS 108 -12.152 5.946-31.107 1.00 0.00
ATOM 20062HZ LYS 108 -11.386 5.664-29.698 1.000.00
ATOM 2007 QZ LYS 108 -11.769 5.805-30.403 1.000.00
ATOM 2008 C LYS i 108 -11.973 8.938-24.699 1.000.00
ATOM 2009 O LYS 108 -12.745 9.576-25.413 1.000.00
ATOM 2010 N ILE 109 - ■11.024 9.478-23.948 1.000.00
ATOM 2011 HN ILE 109 -10.401 8.952-23.371 1.000.00
ATOM 2012 CA ILE 109 -10.823 10.917-23.917 1.000.00
ATOM 2013 HA ILE 109 -11.764 11.371 -23.608 1.000.00
ATOM 2014 CB ILE 109 -9.775 11.289-22.867 1.000.00
ATOM 2015 HB ILE 109 -8.883 10.689-23.047 1.000.00
ATOM 2016 QG2 ILE 109 -9.268 13.106-23.028 1.000.00
ATOM 2017 CG2ILE 109 -9.365 12.757-22.997 1.000.00
ATOM 20181HG2ILE 109 -8.286 12.822-23.136 1.000.00
ATOM 20192HG2 ILE 109 -9.870 13.201 -23.855 1.000.00
ATOM 20203HG2 ILE 109 -9.648 13.295 -22.092 1.000.00
ATOM 2021 CGI ILE 109 -10.268 10.954-21.457 1.000.00
ATOM 20222HG1 ILE 109 -11.250 11.398-21.297 1.000.00
ATOM 20231HG1 ILE 109 -10.386 9.875-21.357 1.000.00
ATOM 2024 QGl ILE 109 -10.818 10.636-21.327 1.000.00
ATOM 2025 QDl ILE 109 -9.058 11.589-20.147 1.000.00
ATOM 2026 CDl ILE 109 -9.290 11.467-20.398 1.000.00
ATOM 20271HD1 ILE 109 -9.767 12.254-19.814 1.000.00
ATOM 20282HD1 ILE 109 -9.005 10.647-19.739 1.000.00
ATOM 20293HD1 ILE 109 -8.401 11.865-20.887 1.000.00
ATOM 2030 C ILE 109 - 10.485 11.411 -25.325 1.000.00
ATOM 2031 O ILE 109 -9.616 10.851 -25.992 1.000.00
ATOM 2032 N TYR 110 -11.190 12.455-25.736 1.000.00
ATOM 2033 HN TYR 110 -11.895 12.905-25.188 1.00 0.00
ATOM 2034 CA TYR 110 -10.975 13.031 -27.053 1.000.00
ATOM 2035 HA TYR 110 -10.646 12.234-27.719 1.000.00
ATOM 2036 CB TYR 110 -12.308 13.663-27.459 1.000.00
ATOM 20372HB TYR 110 -13.021 13.540-26.643 1.000.00
ATOM 20381HB TYR 110 -12.163 14.735-27.596 1.000.00
ATOM 2039 QB TYR 110 -12.592 14.137-27.119 1.000.00
ATOM 2040 QD TYR 110 -12.968 13.022-28.858 1.000.00
ATOM 2041 QE TYR 110 -13.970 12.048-30.982 1.000.00
ATOM 2042 QR TYR 110 -13.469 12.535-29.920 1.000.00
ATOM 2043 CG TYR 110 -12.911 13.077-28.737 1.000.00
ATOM 2044 CDl TYR 110 -12.750 13.734-29.940 1.000.00
ATOM 2045 HDl TYR 110 -12.194 14.671 -29.979 1.000.00
ATOM 2046 CE1 TYR 110 -13.318 13.183-31.143 1.000.00
ATOM 2047 HEI TYR 110 -13.199 13.692-32.100 1.000.00
ATOM 2048 CZ TYR 110 -14.006 12.013-31.059 1.000.00
ATOM 2049 CE2 TYR 110 -14.183 11.340-29.890 1.000.00
ATOM 2050 HE2TYR 110 -14.742 10.405-29.865 1.000.00 ATOM 2051 CD2TYR 110 -13.615 11.892-28.687 1.000.00
ATOM 2052 HD2TYR 110 -13.742 11.373-27.737 1.000.00
ATOM 2053 OH TYR 110 -14.542 11.492-32.195 1.000.00
ATOM 2054 HH TYR 110 -14.371 12.105-32.9661.000.00 ATOM 2055 C TYR 110 -9.901 14.120-27.007 1.000.00
ATOM 2056 O TYR 110 -9.120 14.187-26.059 1.000.00
ATOM 2057 N LEU 111 -9.896 14.946-28.043 1.000.00
ATOM 2058 HN LEU 111 -10.535 14.885-28.809 1.000.00
ATOM 2059 CA LEU 111 -8.931 16.028-28.132 1.000.00 ATOM 2060 HA LEU 111 -9.188 16.624-29.008 1.000.00
ATOM 2061 CB LEU 111 -9.041 16.946-26.913 1.000.00
ATOM 20622HB LEU 111 -8.390 16.556-26.130 1.000.00
ATOM 20631HB LEU 111 -8.656 17.929-27.187 1.000.00
ATOM 2064 QB LEU 111 -8.523 17.243 -26.659 1.000.00 ATOM 2065 CG LEU 111 -10.444 17.123-26.331 1.000.00
ATOM 2066 HG LEU 111 -10.841 16.137-26.090 1.000.00
ATOM 2067 QDl LEU 111 -10.390 18.113-24.718 1.000.00
ATOM 2068 QD2LEU 111 -11.613 17.901 -27.601 1.000.00
ATOM 2069 CDl LEU 111 -10.400 17.923-25.027 1.000.00 ATOM 20701 HDl LEU 111 -11.282 18.561 -24.963 1.000.00
ATOM 20712HD1 LEU 111 -10.385 17.238-24.1801.000.00
ATOM 20723HD1 LEU 111 -9.502 18.541 -25.011 1.000.00
ATOM 2073 CD2LEU 111 -11.389 17.752-27.358 1.000.00
ATOM 20741HD2LEU 111 -11.965 16.968-27.848 1.000.00 ATOM 20752HD2 LEU 111 -12.067 18.440-26.854 1.000.00
ATOM 20763HD2 LEU 111 -10.806 18.295-28.102 1.000.00
ATOM 2077 QQD LEU 111 -11.001 18.007-26.160 1.000.00
ATOM 2078 C LEU 111 -7.532 15.443-28.337 1.000.00
ATOM 2079 O LEU 111 -7.297 14.272-28.044 1.000.00 ATOM 2080 N PRO 112 -6.617 16.307-28.853 1.000.00
ATOM 2081 CD PRO 112 -6.861 17.701-29.211 1.000.00
ATOM 2082 CA PRO 112 -5.248 15.888-29.100 1.000.00
ATOM 2083 HA PRO 112 -5.233 14.973-29.504 1.000.00
ATOM 2084 CB PRO 112 -4.683 16.931 -30.050 1.000.00 ATOM 20852HB PRO 112 -3.658 17.188-29.782 1.000.00
ATOM 20861HB PRO 112 -4.660 16.557-31.073 1.000.00
ATOM 2087 QB PRO 112 -4.159 16.873-30.427 1.000.00
ATOM 2088 CG PRO 112 -5.597 18.140-29.932 1.000.00
ATOM 20892HG PRO 112 -5.102 18.940-29.381 1.000.00 ATOM 20901HG PRO 112 -5.837 18.535-30.919 1.000.00
ATOM 2091 QG PRO 112 -5.469 18.738-30.150 1.000.00
ATOM 20922HD PRO 112 -7.045 18.311 -28.327 1.000.00
ATOM 20931HD PRO 112 -7.736 17.798-29.853 1.000.00
ATOM 2094 QD PRO 112 -7.391 18.054-29.0901.000.00 ATOM 2095 C PRO 112 -4.462 15.781 -27.792 1.000.00
ATOM 2096 O PRO 112 -3.748 14.804-27.571 1.000.00
ATOM 2097 N TYR 113 -4.621 16.799-26.959 1.000.00
ATOM 2098 HN TYR 113 -5.203 17.590-27.147 1.000.00
ATOM 2099 CA TYR 113 -3.935 16.832-25.679 1.000.00 ATOM 2100 HA TYR 113 -4.207 17.760-25.175 1.000.00
ATOM 2101 CB TYR 113 -4.375 15.572-24.931 1.000.00
ATOM 21022HB TYR 113 -4.797 14.866-25.647 1.000.00
ATOM 21031HB TYR 113 -3.498 15.096-24.494 1.000.00
ATOM 2104 QB TYR 113 -4.147 14.981 -25.070 1.000.00 ATOM 2105 QD TYR 113 -5.50015.855-23.722 1.000.00
ATOM 2106 QE TYR 113 -7.206 16.284-21.887 1.000.00
ATOM 2107 QR TYR 113 -6.353 16.070-22.805 1.000.00
ATOM 2108 CG TYR 113 -5.402 15.830-23.827 1.000.00
ATOM 2109 CDl TYR 113 -5.228 15.269-22.578 1.000.00 ATOM 2110 HDl TYR 113 -4.360 14.642-22.379 1.000.00 ATOM 2111 CE1TYR 113 -6.195 15.513-21.539 1.000.00 ATOM 2112 HEI TYR 113 -6.070 15.076-20.548 1.000.00 ATOM 2113 CZ TYR 113 -7.267 16.300-21.821 1.000.00 ATOM 2114 CE2TYR 113 -7.469 16.868-23.040 1.000.00 ATOM 2115 HE2TYR 113 -8.342 17.493-23.226 1.000.00 ATOM 2116 CD2TYR 113 -6.502 16.625-24.080 1.000.00 ATOM 2117 HD2TYR 113 -6.639 17.068-25.066 1.000.00 ATOM 2118 OH TYR 113 -8.180 16.530-20.839 1.000.00 ATOM 2119 HH TYR 113 -8.29017.514-20.699 1.000.00 ATOM 2120 C TYR 113 -2.417 16.793-25.869 1.000.00 ATOM 2121 O TYR 113 -1.748 17.820-25.762 1.000.00 ATOM 2122 N LEU 114 -1.918 15.598-26.147 1.000.00 ATOM 2123 HN LEU 114 -2.46914.768-26.231 1.000.00 ATOM 2124 CA LEU 114 -0.491 15.412-26.352 1.000.00 ATOM 2125 HA LEU 114 0.012 15.703-25.431 1.000.00 ATOM 2126 CB LEU 114 -0.173 13.935-26.594 1.000.00 ATOM 21272HB LEU 114 -0.538 13.361 -25.743 1.000.00 ATOM 21281HB LEU 114 -0.733 13.601 -27.467 1.000.00 ATOM 2129 QB LEU 114 -0.63613.481 -26.605 1.000.00 ATOM 2130 CG LEU 114 1.303 13.593-26.808 1.000.00 ATOM 2131 HG LEU 114 1.836 14.515-27.043 1.000.00 ATOM 2132 QDl LEU 114 2.072 12.889-25.229 1.000.00 ATOM 2133 QD2LEU 114 1.522 12.429-28.285 1.000.00 ATOM 2134 CDl LEU 114 1.925 13.024-25.532 1.000.00 ATOM 21351HD1 LEU 114 1.213 13.112-24.711 1.000.00 ATOM 21362HD1 LEU 114 2.174 11.974-25.686 1.000.00 ATOM 21373HD1 LEU 114 2.830 13.580-25.289 1.000.00 ATOM 2138 CD2LEU 114 1.480 12.652-28.002 1.000.00 ATOM 21391HD2 LEU 114 0.510 12.253-28.297 1.000.00 ATOM 21402HD2 LEU 114 1.916 13.202-28.836 1.000.00 ATOM 21413HD2 LEU 114 2.141 11.832-27.722 1.000.00 ATOM 2142 QQD LEU 114 1.797 12.659-26.757 1.000.00 ATOM 2143 C LEU 114 -0.018 16.335-27.477 1.000.00 ATOM 2144 O LEU 114 1.107 16.830-27.446 1.000.00 ATOM 2145 N HIS 115 -0.901 16.539-28.443 1.000.00 ATOM 2146 HN HIS 115 -1.81416.132-28.461 1.000.00 ATOM 2147 CA HIS 115 -0.588 17.394-29.576 1.000.00 ATOM 2148 HA HIS 115 0.498 17.478-29.612 1.000.00 ATOM 2149 CB HIS 115 -1.05016.752-30.885 1.000.00 ATOM 21502HB HIS 115 -0.93415.671 -30.809 1.000.00 ATOM 21511HB HIS 115 -2.113 16.949-31.019 1.000.00 ATOM 2152 QB HIS 115 -1.523 16.310-30.914 1.000.00 ATOM 2153 CG HIS 115 -0.30417.239-32.105 1.000.00 ATOM 2154 ND1 HIS 115 -0.679 16.907-33.395 1.000.00 ATOM 2155 CD2HIS 115 0.79618.038-32.217 1.000.00 ATOM 2156 HDl HIS 115 -1.455 16.329-33.648 1.000.00 ATOM 2157 CE1 HIS 115 0.16617.484-34.237 1.000.00 ATOM 2158 NE2HIS 115 1.079 18.184-33.505 1.000.00 ATOM 2159 HD2HIS 115 1.34918.481 -31.388 1.000.00 ATOM 2160 HEI HIS 115 0.136 17.412-35.324 1.000.00 ATOM 2161 C HIS 115 -1.18818.783-29.352 1.000.00 ATOM 2162 O HIS 115 -1.432 19.519-30.306 1.000.00 ATOM 2163 N GLU 116 -1.41019.099-28.084 1.000.00 ATOM 2164 HN GLU 116 -1.210 18.494-27.314 1.000.00 ATOM 2165 CA GLU 116 -1.97820.387-27.723 1.000.00 ATOM 2166 HA GLU 116 -2.07320.935-28.660 1.000.00 ATOM 2167 CB GLU 116 -3.36420.219-27.097 1.000.00 ATOM 21682HB GLU 116 -3.873 19.370-27.555 1.000.00 ATOM 21691HB GLU 116 -3.263 19.995-26.035 1.000.00
ATOM 2170 QB GLU 116 -3.568 19.682-26.795 1.000.00
ATOM 2171 CG GLU 116 -4.20521.484-27.279 1.000.00
ATOM 21722HG GLU 116 -3.59222.363-27.081 1.000.00
ATOM 21731HG GLU 116 -4.541 21.556-28.314 1.000.00
ATOM 2174 QG GLU 116 -4.06721.960-27.698 1.000.00
ATOM 2175 CD GLU 116 -5.41521.477-26.343 1.000.00
ATOM 2176 OEl GLU 116 -5.25721.641 -25.124 1.000.00
ATOM 2177 OE2GLU 116 -6.55321.295-26.924 1.000.00
ATOM 2178 HE2GLU 116 -7.12422.109-26.820 1.000.00
ATOM 2179 C GLU 116 -1.03721.135-26.777 1.000.00
ATOM 2180 O GLU 116 -0.40822.117-27.169 1.000.00
ATOM 2181 N TRP 1 117 -0.96920.642-25.549 1.000.00
ATOM 2182 HN TRP 117 -1.483 19.843-25.238 1.000.00
ATOM 2183 CA TRP 117 -0.11521.252-24.544 1.000.00
ATOM 2184 HA TRP 117 -0.32522.322-24.533 1.000.00
ATOM 2185 CB TRP 117 -0.44320.719-23.148 1.000.00
ATOM 21862HB TRP 117 -1.52620.710-23.0191.000.00
ATOM 21871HB TRP 117 -0.105 19.685-23.076 1.000.00
ATOM 2188 QB TRP 117 -0.81520.197-23.048 1.000.00
ATOM 2189 CG TRP 117 0.18521.526-22.0101.000.00
ATOM 2190 CDl TRP 117 1.061 21.106-21.087 1.000.00
ATOM 2191 CD2TRP 117 -0.05322.917-21.709 1.000.00
ATOM 2192 CE3TRP 117 -0.88223.857-22.347 1.000.00
ATOM 2193 CE2TRP 117 0.70523.257-20.608 1.000.00
ATOM 2194 NE1 TRP 117 1.40522.121 -20.217 1.000.00
ATOM 2195 HDl TRP 117 1.45420.091-21.031 1.000.00
ATOM 2196 HE3TRP 117 -1.49023.613-23.218 1.000.00
ATOM 2197 CZ3TRP 117 -0.86525.135-21.775 1.000.00
ATOM 2198 CZ2TRP 117 0.711 24.540-20.048 1.000.00
ATOM 2199 HEI TRP 117 2.09722.046-19.379 1.000.00
ATOM 2200 HZ3 TRP 117 -1.491 25.902-22.231 1.000.00
ATOM 2201 CH2TRP 117 -0.10725.493-20.666 1.000.00
ATOM 2202 HZ2 TRP 117 1.31924.784-19.177 1.000.00
ATOM 2203 HH2TRP 117 -0.15026.512-20.280 1.000.00
ATOM 2204 C TRP 1 17 1.341 21.009-24.949 1.000.00
ATOM 2205 O TRP 1 117 1.98221.884-25.528 1.000.00
ATOM 2206 N LYS 118 1.819 19.815-24.6301.000.00
ATOM 2207 HN LYS 118 1.29019.109-24.160 1.000.00
ATOM 2208 CA LYS 118 3.18619.446-24.954 1.000.00
ATOM 2209 HA LYS 118 3.47018.629-24.290 1.000.00
ATOM 2210 CB LYS 118 3.273 18.916-26.387 1.000.00
ATOM 22112HB LYS 118 4.308 18.671 -26.626 1.000.00
ATOM 22121HB LYS 118 2.70017.993-26.472 1.000.00
ATOM 2213 QB LYS 118 3.50418.332-26.549 1.000.00
ATOM 2214 CG LYS 118 2.743 19.947-27.385 1.000.00
ATOM 22152HG LYS 118 1.66820.067-27.253 1.000.00
ATOM 22161HG LYS 118 3.19920.917-27.188 1.000.00
ATOM 2217 QG LYS 118 2.43420.492-27.221 1.000.00
ATOM 2218 CD LYS 118 3.041 19.520-28.824 1.000.00
ATOM 22192HD LYS 118 3.03418.432-28.893 1.000.00
ATOM 22201HD LYS 118 2.25619.886-29.486 1.000.00
ATOM 2221 QD LYS 118 2.645 19.159-29.189 1.000.00
ATOM 2222 CE LYS 118 4.39720.058-29.286 1.000.00
ATOM 22232HE LYS 118 4.32320.412-30.315 1.000.00
ATOM 2224 IHE LYS 118 4.68320.913-28.675 1.000.00
ATOM 2225 QE LYS 118 4.50320.662-29.495 1.000.00
ATOM 2226 NZ LYS 118 5.432 19.004-29.191 1.000.00
ATOM 22271HZ LYS 118 5.831 18.947-28.261 1.000.00 ATOM 22282HZ LYS 118 5.061 18.086-29.409 1.000.00
ATOM 2229 QZ LYS 118 5.446 18.516-28.835 1.000.00
ATOM 2230 C LYS 118 4.11020.635-24.681 1.000.00
ATOM 2231 O LYS 118 5.011 20.919-25.468 1.000.00 ATOM 2232 N HIS 119 3.85321.298-23.563 1.000.00
ATOM 2233 HN HIS 119 3.11721.060-22.928 1.000.00
ATOM 2234 CA HIS 119 4.65022.450-23.176 1.000.00
ATOM 2235 HA HIS 119 4.46823.221-23.924 1.000.00
ATOM 2236 CB HIS 119 4.19322.996-21.822 1.000.00 ATOM 22372HB HIS 119 3.29522.463-21.510 1.000.00
ATOM 22381HB HIS 119 4.96322.786-21.079 1.000.00
ATOM 2239 QB HIS 119 4.12922.624-21.294 1.000.00
ATOM 2240 CG HIS 119 3.90624.479-21.823 1.000.00
ATOM 2241 ND1 HIS 119 4.88725.433-21.617 1.000.00 ATOM 2242 CD2 HIS 119 2.73925.160-22.007 1.000.00
ATOM 2243 HDl HIS 119 5.85625.249-21.452 1.000.00
ATOM 2244 CE1 HIS 119 4.32526.631-21.677 1.000.00
ATOM 2245 NE2 HIS 119 2.99326.460-21.918 1.000.00
ATOM 2246 HD2 HIS 119 1.76324.713-22.196 1.000.00 ATOM 2247 HEI HIS 119 4.83627.585-21.554 1.000.00
ATOM 2248 C HIS 119 6.13322.077-23.1961.000.00
ATOM 2249 O HIS 119 6.95822.823-23.722 1.000.00
ATOM 2250 N PRO 120 6.43620.893-22.600 1.000.00
ATOM 2251 CD PRO 120 7.76920.308-22.482 1.000.00 ATOM 2252 CA PRO 120 5.40020.070-22.000 1.000.00
ATOM 2253 HA PRO 120 4.591 20.048-22.587 1.000.00
ATOM 2254 CB PRO 120 6.027 18.693-21.852 1.000.00
ATOM 22552HB PRO 120 5.753 18.239-20.900 1.000.00
ATOM 22561HB PRO 120 5.681 18.020-22.637 1.000.00 ATOM 2257 QB PRO 120 5.717 18.130-21.769 1.000.00
ATOM 2258 CG PRO 120 7.529 18.907-21.942 1.000.00
ATOM 22592HG PRO 120 7.990 18.792-20.961 1.000.00
ATOM 22601HG PRO 120 7.982 18.163-22.596 1.000.00
ATOM 2261 QG PRO 120 7.986 18.478-21.778 1.000.00 ATOM 22622HD PRO 120 8.39820.890-21.808 1.000.00
ATOM 22631HD PRO 120 8.27520.279-23.446 1.000.00
ATOM 2264 QD PRO 120 8.33720.584-22.627 1.000.00
ATOM 2265 C PRO 120 4.93320.660-20.668 1.000.00
ATOM 22660 PRO 120 3.73420.805-20.435 1.000.00 ATOM 2267 N GLN 121 5.90620.985-19.828 1.000.00
ATOM 2268 HN GLN 121 6.87820.864-20.026 1.000.00
ATOM 2269 CA GLN 121 5.61021.557-18.526 1.000.00
ATOM 2270 HA GLN 121 6.57921.745-18.064 1.000.00
ATOM 2271 CB GLN 121 4.85722.881 -18.666 1.000.00 ATOM 22722HB GLN 121 5.41623.555-19.315 1.000.00
ATOM 22731HB GLN 121 3.89222.707-19.144 1.000.00
ATOM 2274 QB GLN 121 4.65423.131 -19.229 1.000.00
ATOM 2275 CG GLN 121 4.64423.539-17.301 1.000.00
ATOM 22762HG GLN 121 5.58323.545-16.746 1.000.00 ATOM 22771HG GLN 121 4.34724.579-17.436 1.000.00
ATOM 2278 QG GLN 121 4.96524.062-17.091 1.000.00
ATOM 2279 CD GLN 121 3.57522.798-16.496 1.000.00
ATOM 2280 OEl GLN 121 3.82822.249-15.4361.000.00
ATOM 2281 NE2GLN 121 2.36922.812-17.057 1.000.00 ATOM 22821HE2 GLN 121 2.22923.280-17.9291.000.00
ATOM 22832HE2 GLN 121 1.60322.354-16.606 1.000.00
ATOM 2284 QE2 GLN 121 1.91622.817-17.268 1.000.00
ATOM 2285 C GLN 121 4.81520.562-17.677 1.000.00
ATOM 2286 O GLN 121 5.281 20.126-16.626 1.000.00 ATOM 2287 N SER 122 3.62920.231 -18.166 1.000.00
ATOM 2288 HN SER 122 3.25720.590-19.023 1.000.00
ATOM 2289 CA SER 122 2.765 19.295-17.467 1.000.00
ATOM 2290 HA SER 122 2.480 19.801 -16.544 1.000.00
ATOM 2291 CB SER 122 1.511 18.985-18.286 1.000.00
ATOM 22922HB SER 122 1.231 19.864-18.866 1.000.00
ATOM 22931HB SER 122 1.731 18.190-18.998 1.000.00
ATOM 2294 QB SER 122 1.481 19.027-18.932 1.000.00
ATOM 2295 OG SER 122 0.418 18.594-17.460 1.000.00
ATOM 2296 HG SER 122 -0.062 17.819-17.872 1.000.00
ATOM 2297 C SER 122 3.531 18.007-17.159 1.000.00
ATOM 2298 O SER 122 4.560 17.730-17.773 1.000.00
ATOM 2299 N ASP 123 2.998 17.252-16.209 1.000.00
ATOM 2300 HN ASP 123 2.160 17.485-15.714 1.000.00
ATOM 2301 CA ASP 123 3.618 16.000-15.812 1.000.00
ATOM 2302 HA ASP 123 4.353 15.786-16.588 1.000.00
ATOM 2303 CB ASP 123 4.295 16.128-14.446 1.000.00
ATOM 23042HB ASP 123 3.542 16.409-13.709 1.000.00
ATOM 23051HB ASP 123 4.677 15.150-14.153 1.000.00
ATOM 2306 QB ASP 123 4.110 15.779-13.931 1.000.00
ATOM 2307 CG ASP 123 5.440 17.140-14.384 1.000.00
ATOM 2308 OD1 ASP 123 6.394 17.074-15.173 1.000.00
ATOM 2309 OD2 ASP 123 5.325 18.039-13.466 1.000.00
ATOM 2310 HD2ASP 123 5.759 17.723-12.622 1.000.00
ATOM 2311 C ASP 123 2.544 14.915-15.708 1.000.00
ATOM 2312 O ASP 123 1.351 15.212-15.742 1.000.00
ATOM 2313 N LEU 124 3.006 13.680-15.582 1.000.00
ATOM 2314 HN LEU 124 3.978 13.446-15.554 1.000.00
ATOM 2315 CA LEU 124 2.100 12.549-15.472 1.00 0.00
ATOM 2316 HA LEU 124 1.711 12.344-16.470 1.000.00
ATOM 2317 CB LEU 124 2.856 11.299-15.016 1.000.00
ATOM 23182HB LEU 124 3.923 11.470-15.161 1.000.00
ATOM 23191HB LEU 124 2.696 11.173-13.945 1.000.00
ATOM 2320 QB LEU 124 3.309 11.322-14.553 1.000.00
ATOM 2321 CG LEU 124 2.477 9.993-15.718 1.000.00
ATOM 2322 HG LEU 124 2.973 9.171-15.200 1.000.00
ATOM 2323 QDl LEU 124 0.613 9.680-15.609 1.000.00
ATOM 2324 QD2 LEU 124 3.095 9.980-17.507 1.000.00
ATOM 2325 CDl LEU 124 0.971 9.740-15.630 1.000.00
ATOM 23261HD1 LEU 124 0.671 9.053-16.421 1.000.00
ATOM 23272HD1 LEU 124 0.732 9.304-14.660 1.000.00
ATOM 23283HD1 LEU 124 0.437 10.683 -15.745 1.000.00
ATOM 2329 CD2LEU 124 2.977 9.983-17.164 1.000.00
ATOM 23301HD2 LEU 124 4.028 9.693-17.183 1.000.00
ATOM 23312HD2 LEU 124 2.393 9.269-17.745 1.000.00
ATOM 23323HD2 LEU 124 2.866 10.978-17.593 1.000.00
ATOM 2333 QQD LEU 124 1.854 9.830-16.558 1.000.00
ATOM 2334 C LEU 124 0.929 12.926-14.563 1.000.00
ATOM 2335 O LEU 124 -0.220 12.598-14.856 1.000.00
ATOM 2336 N LEU 125 1.261 13.609-13.477 1.000.00
ATOM 2337 HN LEU 125 2.198 13.871 -13.246 1.000.00
ATOM 2338 CA LEU 125 0.251 14.034-12.523 1.000.00
ATOM 2339 HA LEU 125 -0.352 13.160-12.274 1.000.00
ATOM 2340 CB LEU 125 0.907 14.515-11.227 1.000.00
ATOM 23412HB LEU 125 1.639 15.282-11.477 1.000.00
ATOM 23421HB LEU 125 0.143 14.991 -10.612 1.000.00
ATOM 2343 QB LEU 125 0.891 15.137-11.044 1.000.00
ATOM 2344 CG LEU 125 1.601 13.441 -10.387 1.000.00
ATOM 2345 HG LEU 125 0.934 12.582-10.313 1.000.00 ATOM 2346 QDl LEU 125 33..118899 12.844 -1 1.228 1.00 0.00
ATOM 2347 QD2 LEU 125 1 1..991199 14.056 -8.626 1.00 0.00
ATOM 2348 CDl LEU 125 2 2..888844 12.959 -11.067 1.00 0.00
ATOM 2349 1HD1 LEU 125 3 3..44555^ 13.819 -11.418 1.00 0.00
ATOM 2350 2HD1 LEU 125 3 3..44883: 12.393 -10.353 1.00 0.00
ATOM 2351 3HD1 LEU 125 2 2..66330( 12.321 -11.913 1.00 0.00
ATOM 2352 CD2 LEU 125 1 1..885588 13.938 -8.964 1.00 0.00
ATOM 2353 1HD2 LEU 125 1 1..44118$ 13.242 -8.250 1.00 0.00
ATOM 2354 2HD2 LEU 125 2 2..99332: 14.005 -8.791 1.00 0.00
ATOM 2355 3HD2 LEU 125 1 1..44008? 14.923 -8.836 1.00 0.00
ATOM 2356 QQD LEU 125 2 2..55554 13.450 -9.927 1.00 0.00
ATOM 2357 C LEU 125 - -00..665566 15.078 -13.177 1.00 0.00
ATOM 2358 O LEU 125 - -11..888800 14.977 -13.101 1.00 0.00
ATOM 2359 N GLY 126 - -00..002211 16.056 -13.806 1.00 0.00
ATOM 2360 HN GLY 126 00..997755 16.130 -13.863 1.00 0.00
ATOM 2361 CA GLY 126 --00..775555 17.1 18 -14.473 1.00 0.00
ATOM 2362 2HA GLY 126 --11..331123 17.697 -13.738 1.00 0.00
ATOM 2363 1HA GLY 126 --00..00556. 17.802 -14.954 1.00 0.00
ATOM 2364 QA GLY 126 --00..668855 17.749 -14.346 1.00 0.00
ATOM 2365 C GLY 126 --11..771177 16.546 -15.517 1.00 0.00
ATOM 2366 O GLY 126 --22..881188 17.064 -15.701 1.00 0.00
ATOM 2367 N LEU 127 --11..226677 15.487 -16.173 1.00 0.00
ATOM 2368 HN LEU 127 --00..337711 15.072 -16.017 1.00 0.00
ATOM 2369 CA LEU 127 - -22..007744 14.840 -17.193 1.00 0.00
ATOM 2370 HA LEU 127 --22..229922 15.585 -17.958 1.00 0.00
ATOM 2371 CB LEU 127 --11..228855 13.716 -17.867 1.00 0.00
ATOM 2372 2HB LEU 127 --00..440099 14.151 -18.348 1.00 0.00
ATOM 2373 1HB LEU 127 --00..992211 13.040 -17.094 1.00 0.00
ATOM 2374 QB LEU 127 --00..666655 13.595 -17.721 1.00 0.00
ATOM 2375 CG LEU 127 --22..004477 12.892 -18.908 1.00 0.00
ATOM 2376 HG LEU 127 --22..888877 13.488 -19.267 1.00 0.00
ATOM 2377 QDl LEU 127 --00..995522 12.510 -20.405 1.00 0.00
ATOM 2378 QD2 LEU 127 --22..776666 1 1.320 -18.135 1.00 0.00
ATOM 2379 CDl LEU 127 --11..116622 12.584 -20.117 1.00 0.00
ATOM 2380 1HD1 LEU 127 --11..7799(0 12.400 -20.989 1.00 0.00
ATOM 2381 2HD1 LEU 127 --00..5500(6 13.432 -20.314 1.00 0.00
ATOM 2382 3HD1 LEU 127 --00..5566(0 1 1.699 -19.91 1 1.00 0.00
ATOM 2383 CD2 LEU 127 --22..662288 1 1.622 -18.284 1.00 0.00
ATOM 2384 1HD2 LEU 127 --11..9955:2 10.786 -18.465 1.00 0.00
ATOM 2385 2HD2 LEU 127 --22..7744:7 11.767 -17.210 1.00 0.00
ATOM 2386 3HD2 LEU 127 --33..5599.9 1 1.408 -18.731 1.00 0.00
ATOM 2387 QQD LEU 127 --11..88559, 1 1.915 -19.270 1.00 0.00
ATOM 2388 C LEU 127 --33..339966 114.379 -16.575 1.00 0.00
ATOM 2389 O LEU 127 --44..446699 14.773 -17.030 1.00 0.00
ATOM 2390 N ILE 128 - • 33..227755 l1i3.550-15.548 1.000.00
ATOM 2391 HN ILE 128 --22..339988 13.235-15.185 1.000.00
ATOM 2392 CA ILE 128 -4.447 13.031 -14.864 1.000.00
ATOM 2393 HA ILE 128 -5.107 12.609-15.621 1.000.00
ATOM 2394 CB ILE 128 -4.055 1 11.892-13.920 1.000.00
ATOM 2395 HB ILE 128 -3.206 12.222-13.321 1.000.00
ATOM 2396 QG2 ILE 128 -5.463 11.491-12.720 1.000.00
ATOM 2397 CG2 ILE 128 -5.193 11.568- 12.950 1.000.00
ATOM 2398 1HG2 ILE 128 -6.1 13 11.405 -13.511 1.000.00
ATOM 2399 2HG2 ILE 128 -4.946 10.667 -12.388 1.000.00
ATOM 2400 3HG2 ILE 128 -5.331 12.401 -12.260 1.000.00
ATOM 2401 CGI ILE 128 -3.602 10.660- 14.705 1.000.00
ATOM 2402 2HG1 ILE 128 -4.108 9.774 - 14.321 1.000.00
ATOM 2403 1 HG1 ILE 128 -3.892 10.764-15.751 1.000.00
ATOM 2404 QGl ILE 128 -4.000 10.269-15.036 1.000.00 ATOM 2405 QDl ILE 128 -1.727 10.428 -14.582 1.00 0.00
ATOM 2406 CDl ILE 128 -2.087 10.472 -14.606 1.00 0.00
ATOM 2407 1HD1 ILE 128 -1.849 9.409 -14.641 1.00 0.00
ATOM 2408 2HD1 ILE 128 -1.603 10.981 -15.440 1.00 0.00 ATOM 2409 3HD1 ILE 128 -1.730 10.894 -13.666 1.00 0.00
ATOM 2410 C ILE 128 -5.178 14.182 -14.169 1.00 0.00
ATOM 241 1 O ILE 128 -6.335 14.040 -13.777 1.00 0.00
ATOM 2412 N GLN 129 -4.472 15.295 -14.038 1.00 0.00
ATOM 2413 HN GLN 129 -3.531 15.402 -14.360 1.00 0.00 ATOM 2414 CA GLN 129 -5.039 16.470 -13.398 1.00 0.00
ATOM 2415 HA GLN 129 -5.616 16.090 -12.554 1.00 0.00
ATOM 2416 CB GLN 129 -3.938 17.395 - 12.875 1.00 0.00
ATOM 2417 2HB GLN 129 -2.969 16.906 -12.976 1.00 0.00
ATOM 2418 1HB GLN 129 -3.902 18.301 -13.481 1.00 0.00 ATOM 2419 QB GLN 129 -3.436 17.604 -13.228 1.00 0.00
ATOM 2420 CG GLN 129 -4.181 17.764 -1 1.410 1.00 0.00
ATOM 2421 2HG GLN 129 -4.763 18.684 -1 1.355 1.00 0.00
ATOM 2422 1HG GLN 129 -4.770 16.984 -10.928 1.00 0.00
ATOM 2423 QG GLN 129 -4.767 17.834 -1 1.142 1.00 0.00 ATOM 2424 CD GLN 129 -2.857 17.945 -10.664 1.00 0.00
ATOM 2425 OEl GLN 129 -1.833 17.385 -1 1.019 1.00 0.00
ATOM 2426 NE2 GLN 129 -2.935 18.758 -9.615 1.00 0.00
ATOM 2427 1HE2 GLN 129 -3.807 19.187 -9.378 1.00 0.00
ATOM 2428 2HE2 GLN 129 -2.122 18.941 -9.062 1.00 0.00 ATOM 2429 QE2 GLN 129 -2.964 19.064 -9.220 1.00 0.00
ATOM 2430 C GLN 129 -5.963 17.209 -14.368 1.00 0.00
ATOM 2431 O GLN 129 -7.029 17.683 -13.976 1.00 0.00
ATOM 2432 N VAL 130 -5.520 17.285 -15.614 1.00 0.00
ATOM 2433 HN VAL 130 -4.652 16.898 -15.924 1.00 0.00 ATOM 2434 CA VAL 130 -6.294 17.959 -16.643 1.00 0.00
ATOM 2435 HA VAL 130 -6.473 18.980 -16.304 1.00 0.00
ATOM 2436 CB VAL 130 -5.490 18.026 -17.943 1.00 0.00
ATOM 2437 HB VAL 130 -5.040 17.047 -18.109 1.00 0.00
ATOM 2438 QGl VAL 130 -6.614 18.407 -19.418 1.00 0.00 ATOM 2439 QG2 VAL 130 -4.091 19.295 -17.81 1 1.00 0.00
ATOM 2440 CG I VAL 130 -6.399 18.334 -19.135 1.00 0.00
ATOM 2441 1HG 1 VAL 130 -7.383 18.633 -18.773 1.00 0.00
ATOM 2442 2HG1 VAL 130 -5.966 19.144 -19.722 1.00 0.00
ATOM 2443 3HG1 VAL 130 -6.495 17.445 -19.758 1.00 0.00 ATOM 2444 CG2 VAL 130 -4.359 19.051 -17.836 1.00 0.00
ATOM 2445 1HG2 VAL 130 -3.657 18.904 -18.657 1.00 0.00
ATOM 2446 2HG2 VAL 130 -4.775 20.057 -17.890 1.00 0.00
ATOM 2447 3HG2 VAL 130 -3.840 18.922 -16.886 1.00 0.00
ATOM 2448 QQG VAL 130 -5.353 18.851 -18.614 1.00 0.00 ATOM 2449 C VAL 130 -7.640 17.251 -16.808 1.00 0.00
ATOM 2450 O VAL 130 -8.686 17.898 -16.839 1.00 0.00
ATOM 2451 N MET 131 -7.570 15.932 -16.91 1 1.00 0.00
ATOM 2452 HN MET 131 -6.716 15.414 -16.885 1.00 0.00
ATOM 2453 CA MET 131 -8.771 15.129 -17.072 1.00 0.00 ATOM 2454 HA MET 131 -9.271 15.525 -17.956 1.00 0.00
ATOM 2455 CB MET 131 -8.382 13.662 -17.262 1.00 0.00
ATOM 2456 2HB MET 131 -9.277 13.064 -17.431 1.00 0.00
ATOM 2457 1 HB MET 131 -7.757 13.559 -18.150 1.00 0.00
ATOM 2458 QB MET 131 -8.517 13.31 1 -17.791 1.00 0.00 ATOM 2459 CG MET 131 -7.631 13.131 -16.039 1.00 0.00
ATOM 2460 2HG MET 131 -6.699 13.681 -15.907 1.00 0.00
ATOM 2461 1 HG MET 131 -8.226 13.290 -15.140 1.00 0.00
ATOM 2462 QG MET 131 -7.462 13.486 -15.523 1.00 0.00
ATOM 2463 SD MET 131 -7.287 1 1.391 -16.242 1.00 0.00 ATOM 2464 QE MET 131 -6.526 11.393-18.251 1.000.00
ATOM 2465 CE MET 131 -6.655 11.392-17.911 1.000.00
ATOM 2466 IHE MET 131 -6.156 12.341 -18.110 1.000.00
ATOM 24672HE MET 131 -5.943 10.575-18.030 1.000.00
ATOM 24683HE MET 131 -7.479 11.262-18.612 1.000.00
ATOM 2469 C MET 131 -9.687 15.262-15.854 1.000.00
ATOM 2470 O MET 131 -10.909 15.261 -15.989 1.000.00
ATOM 2471 N ILE 132 -9.060 15.372-14.692 1.000.00
ATOM 2472 HN ILE 132 -8.065 15.372-14.591 1.000.00
ATOM 2473 CA ILE 132 -9.804 15.505-13.451 1.000.00
ATOM 2474 HA ILE 132 -10.534 14.696-13.419 1.000.00
ATOM 2475 CB ILE 132 -8.876 15.324-12.248 1.000.00
ATOM 2476 HB ILE 132 -7.935 15.832-12.463 1.000.00
ATOM 2477 QG2ILE 132 -9.605 16.134-10.700 1.000.00
ATOM 2478 CG2ILE 132 -9.465 15.979-10.997 1.000.00
ATOM 24791HG2 ILE 132 -9.321 17.058-11.049 1.000.00
ATOM 24802HG2 ILE 132 -10.531 15.757-10.939 1.000.00
ATOM 24813HG2 ILE 132 -8.964 15.587-10.112 1.000.00
ATOM 2482 CGI ILE 132 -8.551 13.846-12.023 1.000.00
ATOM 24832HG1 ILE 132 -9.437 13.327-11.657 1.000.00
ATOM 24841HG1 ILE 132 -8.278 13.382-12.970 1.000.00
ATOM 2485 QGl ILE 132 -8.858 13.355-12.314 1.000.00
ATOM 2486 QDl ILE 132 -7.135 13.644-10.783 1.000.00
ATOM 2487 CDl ILE 132 -7.406 13.683-11.021 1.000.00
ATOM 24881HD1 ILE 132 -6.957 12.697-11.140 1.000.00
ATOM 24892HD1 ILE 132 -6.653 14.450-11.201 1.000.00
ATOM 24903HD1 ILE 132 -7.794 13.785-10.007 1.000.00
ATOM 2491 C ILE 132 - 10.557 16.837-13.452 1.000.00
ATOM 2492 O ILE 132 - 11.640 16.942-12.880 1.000.00
ATOM 2493 N VAL 133 -9.952 17.821-14.101 1.000.00
ATOM 2494 HN VAL 133 -9.071 17.727-14.564 1.000.00
ATOM 2495 CA VAL 133 -10.552 19.142-14.185 1.000.00
ATOM 2496 HA VAL 133 -10.879 19.418-13.182 1.000.00
ATOM 2497 CB VAL 133 -9.507 20.163-14.640 1.000.00
ATOM 2498 HB VAL 133 -8.980 19.744-15.497 1.000.00
ATOM 2499 QGl VAL 133 -10.331 21.775-15.195 1.000.00
ATOM 2500 QG2VAL 133 -8.23420.486-13.276 1.000.00
ATOM 2501 CGI VAL 133 -10.173 21.466-15.088 1.000.00
ATOM 25021HG1 VAL 133 -10.963 21.242-15.805 1.000.00
ATOM 25032HG1 VAL 133 -10.60021.972-14.223 1.000.00
ATOM 25043HG1 VAL 133 -9.429 22.111 -15.556 1.000.00
ATOM 2505 CG2VAL 133 -8.47920.424-13.537 1.000.00
ATOM 25061HG2 VAL 133 -7.65421.011 -13.941 1.000.00
ATOM 25072HG2 VAL 133 -8.951 20.973-12.723 1.000.00
ATOM 25083HG2 VAL 133 -8.098 19.474-13.163 1.000.00
ATOM 2509 QQG VAL 133 -9.282 21.131 -14.235 1.000.00
ATOM 2510 C VAL 133 -11.773 19.086-15.104 1.000.00
ATOM 2511 0 VAL 133 -12.766 19.771 -14.865 1.000.00
ATOM 2512 N VAL 134 -11.659 18.263-16.137 1.000.00
ATOM 2513 HN VAL 134 -10.848 17.709-16.324 1.000.00
ATOM 2514 CA VAL 134 -12.742 18.109-17.093 1.000.00
ATOM 2515 HA VAL 134 -13.210 19.085-17.220 1.000.00
ATOM 2516 CB VAL 134 -12.184 17.671 -18.449 1.000.00
ATOM 2517 HB VAL 134 -11.472 16.864-18.274 1.000.00
ATOM 2518 QGl VAL 134 -13.559 17.001 -19.564 1.000.00
ATOM 2519 QG2VAL 134 -11.258 19.091 -19.292 1.000.00
ATOM 2520 CGI VAL 134 -13.296 17.130-19.350 1.000.00
ATOM 25211HG1 VAL 134 -14.262 17.476-18.983 1.000.00
ATOM 25222HG1 VAL 134 -13.144 17.488-20.369 1.000.00 ATOM 2523 3HG1 VAI - 134 -13.273 16.040-19.342 1.000.00 ATOM 2524 CG2 VAL 134 -11.435 18.818-19.130 1.000.00 ATOM 2525 1HG2 VAL 134 -11.702 19.761-18.652 1.000.00 ATOM 2526 2HG2 VAL 134 -10.361 18.656-19.038 1.000.00 ATOM 2527 3HG2 VAL 134 -11.709 18.855-20.184 1.000.00 ATOM 2528 QQG VAL 134 -12.408 18.046-19.428 1.00 0.00 ATOM 2529 C VAL 134 13.779 17.134-16.530 1.000.00 ATOM 2530 O VAL 134 ■14.981 17.357-16.663 1.000.00 ATOM 2531 N PHE 135 13.275 16.075-15.914 1.000.00 ATOM 2532 HN PHE 135 -12.296 15.902-15.810 1.000.00 ATOM 2533 CA PHE 135 -14.143 15.066-15.331 1.000.00 ATOM 2534 HA PHE 135 -14.915 14.840-16.065 1.000.00 ATOM 2535 CB PHE 135 -13.262 13.861 -14.992 1.000.00 ATOM 2536 2HB PHE 135 -12.306 14.219-14.610 1.000.00 ATOM 2537 1HB PHE 135 -13.734 13.294-14.189 1.000.00 ATOM 2538 QB PHE 135 -13.020 13.757-14.399 1.000.00 ATOM 2539 QD PHE 135 -12.983 12.843-16.279 1.000.00 ATOM 2540 QE PHE 135 -12.562 11.308-18.220 1.000.00 ATOM 2541 QR PHE 135 -12.772 12.076-17.249 1.000.00 ATOM 2542 CG PHE 135 -13.006 12.926-16.175 1.000.00 ATOM 2543 CDl PHE 135 -12.748 11.608-15.956 1.000.00 ATOM 2544 HDl PHE 135 -12.725 11.219-14.938 1.000.00 ATOM 2545 CE1 PHE 135 -12.510 10.740-17.054 1.000.00 ATOM 2546 HEI PHE 135 -12.304 9.684-16.879 1.000.00 ATOM 2547 CZ PHE 135 -12.539 11.225-18.324 1.000.00 ATOM 2548 HZ PHE 135 -12.356 10.559-19.167 1.000.00 ATOM 2549 CE2 PHE 135 -12.797 12.543-18.542 1.000.00 ATOM 2550 HE2 PHE 135 -12.820 12.932-19.560 1.000.00 ATOM 2551 CD2 PHE 135 -13.035 13.411 -17.445 1.000.00 ATOM 2552 HD2 PHE 135 -13.241 14.467-17.620 1.000.00 ATOM 2553 C PHE i 135 14.797 15.581-14.047 1.000.00 ATOM 2554 O PHE 135 15.679 14.928-13.491 1.000.00 ATOM 2555 N GLY 136 -14.341 16.748-13.615 1.000.00 ATOM 2556 HN GLY 136 -13.624 17.272-14.074 1.000.00 ATOM 2557 CA GLY 136 -14.872 17.358-12.408 1.000.00 ATOM 2558 2HA GLY 136 -15.294 16.588-11.763 1.000.00 ATOM 2559 1HA GLY 136 -14.064 17.833-11.851 1.000.00 ATOM 2560 QA GLY 136 -14.679 17.211-11.807 1.000.00 ATOM 2561 C GLY 136 -15.946 18.395-12.744 1.000.00 ATOM 2562 0 GLY 136 -16.885 18.592-11.976 1.000.00 ATOM 2563 N ASP 1 137 --15.770 19.031-13.894 1.000.00 ATOM 2564 HN ASP 137 -15.003 18.864-14.513 1.000.00 ATOM 2565 CA ASP 137 -16.71220.042-14.341 1.000.00 ATOM 2566 HA ASP 137 -16.93020.641-13.457 1.000.00 ATOM 2567 CB ASP 137 -16.10520.910-15.446 1.000.00 ATOM 2568 2HB ASP 137 -15.642 20.257-16.186 1.000.00 ATOM 2569 1HB ASP 137 -16.91021.444-15.951 1.000.00 ATOM 2570 QB ASP 137 -16.27620.851 -16.069 1.000.00 ATOM 2571 CG ASP 137 -15.065 21.927-14.972 1.000.00 ATOM 2572 OD1 ASP 137 -15.10022.386-13.821 1.000.00 ATOM 2573 OD2 ASP 137 -14.17922.250-15.852 1.000.00 ATOM 2574 HD2 ASP 137 -13.915 21.446-16.383 1.000.00 ATOM 2575 C ASP 1 37 --17.958 19.358-14.907 1.000.00 ATOM 2576 O ASP 137 -19.074 19.635-14.473 1.000.00 ATOM 2577 N GLU 138 -17.724 18.477-15.869 1.000.00 ATOM 2578 HN GLU 138 -16.813 18.257-16.217 1.000.00 ATOM 2579 CA GLU 138 -18.814 17.751-16.500 1.000.00 ATOM 2580 HA GLU 138 -19.726 18.209-16.117 1.000.00 ATOM 2581 CB GLU 138 -18.772 17.912-18.021 1.000.00 ATOM 25822HB GLU 138 -19.658 17.457-18.462 1.000.00
ATOM 25831HB GLU 138 -18.794 18.970-18.279 1.000.00
ATOM 2584 QB GLU 138 -19.226 18.214-18.371 1.000.00
ATOM 2585 CG GLU 138 -17.515 17.265-18.606 1.000.00
ATOM 25862HG GLU 138 -16.654 17.912-18.432 1.000.00
ATOM 25871HG GLU 138 -17.314 16.323-18.095 1.000.00
ATOM 2588 QG GLU 138 -16.984 17.118-18.263 1.000.00
ATOM 2589 CD GLU 138 -17.675 17.013-20.106 1.000.00
ATOM 2590 OEl GLU 138 -17.965 15.880-20.517 1.000.00
ATOM 2591 OE2GLU 138 -17.489 18.047-20.856 1.000.00
ATOM 2592 HE2GLU 138 -18.352 18.323-21.278 1.000.00
ATOM 2593 C GLU 138 -18.767 16.274-16.103 1.000.00
ATOM 2594 O GLU 138 -17.704 15.749-15.775 1.000.00
ATOM 2595 N PRO 139 -19.964 15.630-16.146 1.000.00
ATOM 2596 CD PRO 139 -21.243 16.220-16.528 1.000.00
ATOM 2597 CA PRO 139 -20.070 14.224-15.794 1.000.00
ATOM 2598 HA PRO 139 -19.517 14.026-14.985 1.000.00
ATOM 2599 CB PRO 139 -21.550 13.993-15.535 1.000.00
ATOM 26002HB PRO 139 -21.875 13.040-15.952 1.000.00
ATOM 26011HB PRO 139 -21.759 13.962-14.466 1.000.00
ATOM 2602 QB PRO 139 -21.817 13.501 -15.209 1.000.00
ATOM 2603 CG PRO 139 -22.275 15.153-16.199 1.000.00
ATOM 26042HG PRO 139 -22.781 14.819-17.104 1.000.00
ATOM 26051HG PRO 139 -23.040 15.554-15.535 1.000.00
ATOM 2606 QG PRO 139 -22.911 15.187-16.320 1.000.00
ATOM 26072HD PRO 139 -21.261 16.474-17.588 1.000.00
ATOM 26081HD PRO 139 -21.436 17.140-15.977 1.000.00
ATOM 2609 QD PRO 139 -21.348 16.807-16.783 1.000.00
ATOM 2610 C PRO 139 -19.513 13.337-16.910 1.000.00
ATOM 2611 O PRO 139 -20.075 13.279-18.002 1.000.00
ATOM 2612 N PRO 140 -18.385 12.649-16.587 1.000.00
ATOM 2613 CD PRO 140 -17.691 12.692-15.303 1.000.00
ATOM 2614 CA PRO 140 -17.745 11.767-17.549 1.000.00
ATOM 2615 HA PRO 140 -17.732 12.192-18.454 1.000.00
ATOM 2616 CB PRO 140 -16.341 11.548-17.009 1.000.00
ATOM 26172HB PRO 140 -16.034 10.509-17.130 1.000.00
ATOM 26181HB PRO 140 -15.616 12.159-17.546 1.000.00
ATOM 2619 QB PRO 140 -15.825 11.334-17.338 1.000.00
ATOM 2620 CG PRO 140 -16.395 11.932-15.539 1.000.00
ATOM 26212HG PRO 140 -16.355 11.043-14.910 1.000.00
ATOM 26221HG PRO 140 -15.537 12.549-15.274 1.000.00
ATOM 2623 QG PRO 140 -15.946 11.796-15.092 1.000.00
ATOM 26242HD PRO 140 -18.285 12.227-14.516 1.000.00
ATOM 26251HD PRO 140 -17.496 13.718-14.993 1.000.00
ATOM 2626 QD PRO 140 -17.891 12.973-14.755 1.000.00
ATOM 2627 C PRO 140 -18.534 10.466-17.709 1.000.00
ATOM 2628 O PRO 140 -18.492 9.836-18.765 1.000.00
ATOM 2629 N VAL 141 -19.236 10.102-16.646 1.000.00
ATOM 2630 HN VAL 141 -19.265 10.620-15.791 1.000.00
ATOM 2631 CA VAL 141 -20.033 8.888-16.656 1.000.00
ATOM 2632 HA VAL 141 -20.699 8.938-17.517 1.000.00
ATOM 2633 CB VAL 141 -19.126 7.667-16.828 1.000.00
ATOM 2634 HB VAL 141 -18.559 7.800-17.750 1.000.00
ATOM 2635 QGl VAL 141 -17.892 7.532-15.399 1.000.00
ATOM 2636 QG2 VAL 141 -20.147 6.082-16.997 1.000.00
ATOM 2637 CGI VAL 141 -18.129 7.558-15.673 1.000.00
ATOM 26381HG1 VAL 141 -17.475 6.702-15.839 1.000.00
ATOM 26392HG1 VAL 141 -17.531 8.467-15.622 1.000.00
ATOM 26403HG1 VAL 141 -18.670 7.426-14.737 1.000.00 ATOM 2641 CG2VAL 141 -19.951 6.386-16.964 1.000.00
ATOM 26421HG2 VAL 141 -19.960 6.069-18.007 1.000.00
ATOM 26432HG2 VAL 141 -19.508 5.602-16.350 1.000.00
ATOM 26443HG2 VAL 141 -20.972 6.574-16.633 1.000.00 ATOM 2645 QQG VAL 141 -19.019 6.807-16.198 1.000.00
ATOM 2646 C VAL 141 -20.879 8.828-15.382 1.000.00
ATOM 26470 VAL 141 -20.820 7.850-14.638 1.000.00
ATOM 2648 N PHE 142 -21.647 9.887-15.170 1.000.00
ATOM 2649 HN PHE 142 -21.689 10.678-15.779 1.000.00 ATOM 2650 CA PHE 142 -22.503 9.967-13.999 1.000.00
ATOM 2651 HA PHE 142 -21.854 10.007-13.125 1.000.00
ATOM 2652 CB PHE 142 -23.370 11.218-14.164 1.000.00
ATOM 26532HB PHE 142 -23.847 11.445-13.210 1.000.00
ATOM 26541HB PHE 142 -22.726 12.063-14.408 1.000.00 ATOM 2655 QB PHE 142 -23.286 11.754-13.809 1.000.00
ATOM 2656 QD PHE 142 -24.545 11.078 -15.335 1.000.00
ATOM 2657 QE PHE 142 -26.316 10.867-17.100 1.000.00
ATOM 2658 QR PHE 142 -25.431 10.973-16.218 1.000.00
ATOM 2659 CG PHE 142 -24.44911.089-15.240 1.000.00 ATOM 2660 CDl PHE 142 -25.719 10.747-14.892 1.000.00
ATOM 2661 HDl PHE 142 -25.967 10.564-13.846 1.000.00 -
ATOM 2662 CE1 PHE 142 -26.721 10.628-15.891 1.000.00
ATOM 2663 HEI PHE 142 -27.739 10.353-15.612 1.000.00
ATOM 2664 CZ PHE 142 -26.412 10.856-17.195 1.000.00 ATOM 2665 HZ PHE 142 -27.181 10.764-17.962 1.000.00
ATOM 2666 CE2 PHE 142 -25.142 11.198-17.543 1.000.00
ATOM 2667 HE2 PHE 142 -24.894 11.381-18.589 1.000.00
ATOM 2668 CD2 PHE 142 -24.140 11.317-16.544 1.000.00
ATOM 2669 HD2 PHE 142 -23.123 11.592-16.823 1.000.00 ATOM 2670 C PHE 142 -23.413 8.741 -13.900 1.000.00
ATOM 2671 O PHE 142 -24.073 8.373-14.870 1.000.00
ATOM 2672 N SER 143 -23.418 8.142-12.718 1.000.00
ATOM 2673 HN SER 143 -22.879 8.448-11.933 1.000.00
ATOM 2674 CA SER 143 -24.236 6.965-12.479 1.000.00 ATOM 2675 HA SER 143 -24.223 6.410-13.417 1.000.00
ATOM 2676 CB SER 143 -23.642 6.098-11.367 1.000.00
ATOM 26772HB SER 143 -23.017 5.321-11.807 1.000.00
ATOM 26781HB SER 143 -22.995 6.709-10.738 1.000.00
ATOM 2679 QB SER 143 -23.006 6.015-11.272 1.000.00 ATOM 2680 OG SER 143 -24.653 5.496-10.563 1.000.00
ATOM 2681 HG SER 143 -24.321 4.629-10.189 1.000.00
ATOM 2682 C SER 143 -25.664 7.383-12.122 1.000.00
ATOM 2683 O SER 143 -25.944 8.569-11.956 1.000.00
ATOM 2684 N ARG 144 -26.529 6.385-12.013 1.000.00 ATOM 2685 HN ARG 144 -26.292 5.423-12.150 1.000.00
ATOM 2686 CA ARG 144 -27.920 6.634-11.679 1.000.00
ATOM 2687 HA ARG 144 -28.035 7.716-11.753 1.000.00
ATOM 2688 CB ARG 144 -28.858 5.932-12.663 1.000.00
ATOM 26892HB ARG 144 -28.300 5.193-13.238 1.000.00 ATOM 26901HB ARG 144 -29.629 5.392-12.114 1.000.00
ATOM 2691 QB ARG 144 -28.965 5.293-12.676 1.000.00
ATOM 2692 CG ARG 144 -29.510 6.939-13.613 1.000.00
ATOM 26932HG ARG 144 -29.643 7.893-13.101 1.000.00
ATOM 26941HG ARG 144 -28.851 7.123-14.462 1.000.00 ATOM 2695 QG ARG 144 -29.247 7.508-13.782 1.000.00
ATOM 2696 CD ARG 144 -30.863 6.427-14.110 1.000.00
ATOM 26972HD ARG 144 -30.856 6.355-15.198 1.000.00
ATOM 26981HD ARG 144 -31.045 5.424-13.725 1.000.00
ATOM 2699 QD ARG 144 -30.951 5.890-14.462 1.000.00 ATOM 2700 NE ARG 144 -31.942 7.341 -13.672 1.00 0.00
ATOM 2701 HE ARG 144 -32.542 7.036 -12.933 1.00 0.00
ATOM 2702 CZ ARG 144 -32.166 8.559 -14.208 1.00 0.00
ATOM 2703 NH1 ARG 144 -33.159 9.292 -13.739 1.00 0.00
ATOM 2704 HH1 ARG 144 -33.391 10.203 -14.080 1.00 0.00
ATOM 2705 NH2 ARG 144 -31.386 9.022 -15.208 1.00 0.00
ATOM 2706 1 HH2 ARG 144 -31.559 9.926 -15.599 1.00 0.00
ATOM 2707 2HH2 ARG 144 -30.636 8.461 -15.558 1.00 0.00
ATOM 2708 QH2 ARG 144 -31.097 9.194 -15.579 1.00 0.00
ATOM 2709 C ARG 144 -28.221 6.144 -10.261 1.00 0.00
ATOM 2710 O ARG 144 -27.514 5.287 -9.733 1.00 0.00
ATOM 271 1 N PRO 145 -29.300 6.724 -9.669 1.00 0.00
ATOM 2712 CD PRO 145 -30.161 7.742 -10.264 1.00 0.00
ATOM 2713 CA PRO 145 -29.703 6.355 -8.323 1.00 0.00
ATOM 2714 HA PRO 145 -28.901 6.264 -7.733 1.00 0.00
ATOM 2715 CB PRO 145 -30.615 7.481 -7.863 1.00 0.00
ATOM 2716 2HB PRO 145 -31.472 7.090 -7.314 1.00 0.00
ATOM 2717 1 HB PRO 145 -30.090 8.160 -7.192 1.00 0.00
ATOM 2718 QB PRO 145 -30.781 7.625 -7.253 1.00 0.00
ATOM 2719 CG PRO 145 -31.060 8.199 -9.127 1.00 0.00
ATOM 2720 2HG PRO 145 -32.102 7.971 -9.349 1.00 0.00
ATOM 2721 1 HG PRO 145 -30.991 9.279 -8.996 1.00 0.00
ATOM 2722 QG PRO 145 -31.547 8.625 -9.172 1.00 0.00
ATOM 2723 2HD PRO 145 -30.743 7.335 -1 1.090 1.00 0.00
ATOM 2724 1HD PRO 145 -29.576 8.571 -10.664 1.00 0.00
ATOM 2725 QD PRO 145 -30.160 7.953 -10.877 1.00 0.00
ATOM 2726 C PRO 145 -30.389 4.988 -8.31 1 1.00 0.00
ATOM 2727 O PRO 145 -31.612 4.903 -8.222 1.00 0.00
TER
ATOM 3079 N PRO 205 -1 1.989 2.640 -3.240 1.00 0.00
ATOM 3080 CD PRO 205 -11.152 3.836 -3.249 1.00 0.00
ATOM 3081 CA PRO 205 -13.407 2.939 -3.128 1.00 0.00
ATOM 3082 HA PRO 205 -13.847 2.304 -2.493 1.00 0.00
ATOM 3083 CB PRO 205 -13.467 4.372 -2.624 1.00 0.00
ATOM 3084 2HB PRO 205 -14.256 4.930 -3.128 1.00 0.00
ATOM 3085 1 HB PRO 205 -13.688 4.402 -1.557 1.00 0.00
ATOM 3086 QB PRO 205 -13.972 4.666 -2.342 1.00 0.00
ATOM 3087 CG PRO 205 -12.102 4.975 -2.914 1.00 0.00
ATOM 3088 2HG PRO 205 -12.164 5.677 -3.745 1.00 0.00
ATOM 3089 1 HG PRO 205 -1 1.740 5.533 -2.051 1.00 0.00
ATOM 3090 QG PRO 205 -1 1.952 5.605 -2.898 1.00 0.00
ATOM 3091 2HD PRO 205 -10.685 3.985 -4.223 1.00 0.00
ATOM 3092 1 HD PRO 205 -10.348 3.763 -2.517 1.00 0.00
ATOM 3093 QD PRO 205 -10.516 3.874 -3.370 1.00 0.00
ATOM 3094 C PRO 205 -14.1 15 2.748 -4.470 1.00 0.00
ATOM 3095 O PRO 205 - 13.590 3.132 -5.514 1.00 0.00
ATOM 3096 N GLU 206 -15.297 2.153 -4.400 1.00 0.00
ATOM 3097 HN GLU 206 -15.717 1.844 -3.547 1.00 0.00
ATOM 3098 CA GLU 206 -16.083 1.906 -5.597 1.00 0.00
ATOM 3099 HA GLU 206 -15.519 1.167 -6.166 1.00 0.00
ATOM 3100 CB GLU 206 -17.454 1.326 -5.242 1.00 0.00
ATOM 3101 2HB GLU 206 -17.822 0.721 -6.071 1.00 0.00
ATOM 3102 1 HB GLU 206 -17.361 0.664 -4.381 1.00 0.00
ATOM 3103 QB GLU 206 -17.592 0.693 -5.226 1.00 0.00
ATOM 3104 CG GLU 206 -18.456 2.439 -4.931 1.00 0.00
ATOM 3105 2HG GLU 206 -17.932 3.299 -4.514 1.00 0.00
ATOM 3106 1HG GLU 206 -18.933 2.772 -5.853 1.00 0.00
ATOM 3107 QG GLU 206 -18.433 3.036 -5.183 1.00 0.00
ATOM 3108 CD GLU 206 -19.522 1.957 -3.944 1.00 0.00 ATOM 3109 OEl GLU 206 -20.550 1.405 -4.364 1.00 0.00
ATOM 3110 OE2 GLU 206 -19.252 2.172 -2.702 1.00 0.00
ATOM 31 1 1 HE2 GLU 206 -19.877 1.651 -2.121 1.00 0.00
ATOM 31 12 C GLU 206 -16.226 3.192 -6.413 1.00 0.00
ATOM 31 13 O GLU 206 -16.250 4.287 -5.854 1.00 0.00
ATOM 31 14 N PRO 207 -16.321 3.012 -7.758 1.00 0.00
ATOM 31 15 CD PRO 207 -16.297 1.729 -8.455 1.00 0.00
ATOM 31 16 CA PRO 207 -16.461 4.144 -8.657 1.00 0.00
ATOM 31 17 HA PRO 207 - 15.854 4.888 -8.376 1.00 0.00
ATOM 31 18 CB PRO 207 -16.094 3.605 -10.029 1.00 0.00
ATOM 3119 2HB PRO 207 -16.762 3.999 -10.795 1.00 0.00
ATOM 3120 1HB PRO 207 - 15.082 3.900 - 10.307 1.00 0.00
ATOM 3121 QB PRO 207 -15.922 3.949 - 10.551 1.00 0.00
ATOM 3122 CG PRO 207 -16.213 2.093 -9.929 1.00 0.00
ATOM 3123 2HG PRO 207 -17.099 1.743 -10.459 1.00 0.00
ATOM 3124 1HG PRO 207 -15.352 1.611 -10.392 1.00 0.00
ATOM 3125 QG PRO 207 -16.226 1.677 -10.426 1.00 0.00
ATOM 3126 2HD PRO 207 -17.192 1.146 -8.242 1.00 0.00
ATOM 3127 1HD PRO 207 -15.443 1.127 -8.147 1.00 0.00
ATOM 3128 QD PRO 207 -16.318 1.136 -8.194 1.00 0.00
ATOM 3129 C PRO 207 -17.879 4.718 -8.599 1.00 0.00
ATOM 3130 O PRO 207 -18.159 5.610 -7.800 1.00 0.00
ATOM 3131 N THR 208 -18.735 4.182 -9.456 1.00 0.00
ATOM 3132 HN THR 208 -18.499 3.456 -10.102 1.00 0.00
ATOM 3133 CA THR 208 -20.1 16 4.629 -9.513 1.00 0.00
ATOM 3134 HA THR 208 -20.699 3.877 -10.044 1.00 0.00
ATOM 3135 CB THR 208 -20.632 4.755 -8.078 1.00 0.00
ATOM 3136 HB THR 208 -19.928 4.315 -7.371 1.00 0.00
ATOM 3137 QG2 THR 208 -21.034 6.544 -7.607 1.00 0.00
ATOM 3138 OG l THR 208 -21.902 4.109 -8.107 1.00 0.00
ATOM 3139 HG1 THR 208 -22.274 4.044 -7.181 1.00 0.00
ATOM 3140 CG2 THR 208 -20.957 6.200 -7.697 1.00 0.00
ATOM 3141 1HG2 THR 208 -20.032 6.770 -7.609 1.00 0.00
ATOM 3142 2HG2 THR 208 -21.586 6.646 -8.468 1.00 0.00
ATOM 3143 3HG2 THR 208 -21.485 6.215 -6.743 1.00 0.00
ATOM 3144 C THR 208 -20.224 5.928 -10.313 1.00 0.00
ATOM 3145 O THR 208 -20.993 6.01 1 -1 1.269 1.00 0.00
ATOM 3146 N ALA 209 -19.441 6.91 1 -9.892 1.00 0.00
ATOM 3147 HN ALA 209 -18.818 6.836 -9.1 14 1.00 0.00
ATOM 3148 CA ALA 209 -19.439 8.203 -10.558 1.00 0.00
ATOM 3149 HA ALA 209 -18.478 8.678 -10.357 1.00 0.00
ATOM 3150 QB ALA 209 -19.615 7.951 -12.426 1.00 0.00
ATOM 3151 CB ALA 209 -19.581 7.999 -12.068 1.00 0.00
ATOM 3152 1HB ALA 209 -19.047 7.097 -12.365 1.00 0.00
ATOM 3153 2HB ALA 209 -20.636 7.897 -12.322 1.00 0.00
ATOM 3154 3HB ALA 209 - 19.163 8.859 - 12.591 1.00 0.00
ATOM 3155 C ALA 209 -20.556 9.072 -9.979 1.00 0.00
ATOM 3156 O ALA 209 -21.577 8.557 -9.526 1.00 0.00
ATOM 3157 N PRO 210 -20.318 10.41 1 -10.012 1.00 0.00
ATOM 3158 CD PRO 210 - 19.120 1 1.057 - 10.540 1.00 0.00
ATOM 3159 CA PRO 210 -21.292 11.357 -9.495 1.00 0.00
ATOM 3160 HA PRO 210 -21.680 1 1.022 -8.637 1.00 0.00
ATOM 3161 CB PRO 210 -20.518 12.650 -9.298 1.00 0.00
ATOM 3162 2HB PRO 210 -21.109 13.51 1 -9.61 1 1.00 0.00
ATOM 3163 1HB PRO 210 -20.269 12.800 -8.247 1.00 0.00
ATOM 3164 QB PRO 210 -20.689 13.156 -8.929 1.00 0.00
ATOM 3165 CG PRO 210 -19.261 12.517 -10.142 1.00 0.00
ATOM 3166 2HG PRO 210 -19.327 13.149 -1 1.027 1.00 0.00
ATOM 3167 1HG PRO 210 -18.387 12.846 -9.579 1.00 0.00 ATOM 3168 QG PRO 210 -18.857 12.998-10.303 1.000.00
ATOM 31692HD PRO 210 -19.055 10.946-11.622 1.000.00
ATOM 31701HD PRO 210 -18.215 10.618-10.119 1.000.00
ATOM 3171 QD PRO 210 -18.635 10.782-10.871 1.000.00
ATOM 3172 C PRO i 210 -22.473 11.508-10.457 1.000.00
ATOM 3173 O PRO 210 -22.285 11.582-11.670 1.000.00
ATOM 3174 N PRO : 211 -23.696 11.551 -9.863 1.000.00
ATOM 3175 CD PRO 211 -23.957 11.467 -8.429 1.000.00
ATOM 3176 CA PRO 211 -24.907 11.692-10.653 1.000.00
ATOM 3177 HA PRO 211 -24.858 11.116-11.469 1.000.00
ATOM 3178 CB PRO 211 -26.033 11.262 -9.727 1.000.00
ATOM 31792HB PRO 211 -26.900 11.914 -9.837 1.000.00
ATOM 31801HB PRO 211 -26.364 10.250 -9.958 1.000.00
ATOM 3181 QB PRO 211 -26.632 11.082 -9.898 1.000.00
ATOM 3182 CG PRO 211 -25.467 11.342 -8.318 1.000.00
ATOM 31832HG PRO 211 -25.883 12.198 -7.788 1.000.00
ATOM 31841HG PRO 211 -25.736 10.453 -7.748 1.000.00
ATOM 3185 QG PRO 211 -25.810 11.326 -7.768 1.000.00
ATOM 31862HD PRO 211 -23.593 12.352 -7.908 1.000.00
ATOM 31871HD PRO 211 -23.455 10.607 -7.985 1.000.00
ATOM 3188 QD PRO 211 -23.524 11.480 -7.946 1.000.00
ATOM 3189 C PRO : 211 -25.066 13.126-11.162 1.000.00
ATOM 3190 o PRO : 211 -24.303 14.012-10.780 1.000.00
ATOM 3191 N GLU 212 -26.061 13.310-12.017 1.000.00
ATOM 3192 HN GLU 212 -26.677 12.583-12.323 1.000.00
ATOM 3193 CA GLU 212 -26.329 14.621 -12.583 1.000.00
ATOM 3194 HA GLU 212 -25.382 15.157-12.533 1.000.00
ATOM 3195 CB GLU 212 -26.766 14.509-14.045 1.000.00
ATOM 31962HB GLU 212 -26.774 13.461 -14.346 1.000.00
ATOM 31971HB GLU 212 -27.785 14.879-14.154 1.000.00
ATOM 3198 QB GLU 212 -27.280 14.170-14.250 1.000.00
ATOM 3199 CG GLU 212 -25.829 15.300-14.959 1.000.00
ATOM 32002HG GLU 212 -24.856 15.411 -14.481 1.000.00
ATOM 32011HG GLU 212 -25.667 14.749-15.886 1.000.00
ATOM 3202 QG GLU 212 -25.262 15.080-15.183 1.000.00
ATOM 3203 CD GLU 212 -26.409 16.681 -15.275 1.000.00
ATOM 3204 OEl GLU 212 -25.870 17.699-14.817 1.000.00
ATOM 3205 OE2GLU 212 -27.457 16.673-16.027 1.000.00
ATOM 3206 HE2 GLU 212 -27.242 16.254-16.909 1.000.00
ATOM 3207 C GLU i 212 -27.385 15.352-11.750 1.000.00
ATOM 3208 O GLU : 212 -28.096 14.733-10.961 1.000.00
ATOM 3209 N GLU i 213 -27.452 16.659-11.955 1.000.00
ATOM 3210 HN GLU 213 -26.869 17.155-12.598 1.000.00
ATOM 3211 CA GLU 213 -28.408 17.481 -11.233 1.000.00
ATOM 3212 HA GLU 213 -27.995 18.490-11.250 1.000.00
ATOM 3213 CB GLU 213 -29.768 17.485-11.934 1.000.00
ATOM 32142HB GLU 213 -30.434 18.191-11.439 1.000.00
ATOM 32151HB GLU 213 -29.649 17.826-12.963 1.000.00
ATOM 3216 QB GLU 213 -30.042 18.009-12.201 1.000.00
ATOM 3217 CG GLU 213 -30.395 16.090-11.923 1.000.00
ATOM 32182HG GLU 213 -29.985 15.496-12.740 1.000.00
ATOM 32191HG GLU 213 -30.135 15.578-10.996 1.000.00
ATOM 3220 QG GLU 213 -30.060 15.537-11.868 1.000.00
ATOM 3221 CD GLU 213 -31.917 16.171 -12.057 1.000.00
ATOM 3222 OEl GLU 213 -32.601 16.589-11.111 1.000.00
ATOM 3223 OE2GLU 213 -32.385 15.782-13.194 1.000.00
ATOM 3224 HE2 GLU 213 -31.766 16.055-13.931 1.000.00
ATOM 3225 C GLU : 213 -28.539 16.998 -9.787 1.000.00
ATOM 3226 O GLU : 213 -27.545 16.644 -9.155 1.000.00 TER 3227 GLU 213 END
COMPLEXCNS02.TXT Table 27 PART B
ATOM 1 CA ALA 2 12.540 -7.888 17.145 1.000.00 ATOM 2 HA ALA 2 11.603 -7.708 17.652 1.000.00 ATOM 3 CB ALA 2 12.695 -6.840 16.053 1.000.00 ATOM 4 HB1 ALA 2 12.440 -5.868 16.448 1.000.00 ATOM 5 HB2 ALA 2 12.036 -7.077 15.230 1.000.00 ATOM 6 HB3 ALA 2 13.717 -6.831 15.705 1.000.00 ATOM 7 C ALA : 12.509 -9.285 16.535 1.000.00 ATOM 8 O ALA 13.548 -9.842 16.182 1.000.00 ATOM 9 N ALA 13.640 -7.763 18.137 1.000.00 ATOM 10 HT1 ALA 2 13.448 -6.923 18.718 1.000.00 ATOM 1 1 HT2 ALA 2 14.531 -7.661 17.610 1.000.00 ATOM 12 HT3 ALA 2 13.643 -8.626 18.717 1.000.00 ATOM 13 N VAL 3 11.310 -9.846 16.415 1.000.00 ATOM 14 HN VAL 3 10.519 -9.351 16.715 1.000.00 ATOM 15 CA VAL 3 11.144-11.178 15.848 1.000.00 ATOM 16 HA VAL 3 12.093-11.690 15.914 1.000.00 ATOM 17 CB VAL 3 10.098-11.995 16.630 1.000.00 ATOM 18 HB VAL 3 9.124-11.568 16.443 1.000.00 ATOM 19 CGI VAL 3 10.082-13.439 16.154 1.000.00 ATOM 20 HG1 1 VAL 3 9.669-14.069 16.928 1.000.00 ATOM 21 HG12 VAL 3 11.090-13.757 15.932 1.000.00 ATOM 22 HG 13 VAL 3 9.476-13.518 15.263 1.000.00 ATOM 23 CG2 VAL 10.372-11.922 18.124 1.000.00 ATOM 24 HG21 VAL 11.404-12.176 18.314 1.000.00 ATOM 25 HG22 VAL 9.729-12.618 18.643 1.000.00 ATOM 26 HG23 VAL 10.177-10.920 18.477 1.000.00 ATOM 27 C VAL 3 10.722-11.104 14.384 1.000.00 ATOM 28 O VAL 3 11.282-11.792 13.531 1.000.00 ATOM 29 N SER 4 9.731 -10.264 14.101 1.000.00 ATOM 30 HN SER 4 9.325 -9.743 14.825 1.000.00 ATOM 31 CA SER 4 9.234-10.100 12.741 1.000.00 ATOM 32 HA SER 4 9.203-11.075 12.279 1.000.00 ATOM 33 CB SER 4 7.822 -9.514 12.759 1.000.00 ATOM 34 HB1 SER 4 7.161 -10.192 13.276 1.000.00 ATOM 35 HB2 SER 4 7.477 -9.379 11.745 1.000.00 ATOM 36 OG SER 4 7.798 -8.260 13.419 1.000.00 ATOM 37 HG SER 4 7.815 -7.555 12.767 1.000.00 ATOM 38 C SER 4 10.159 -9.201 11.927 1.000.00 ATOM 39 O SER 4 10.564 -9.552 10.819 1.000.00 ATOM 40 N GLU 5 10.489 -8.039 12.484 1.000.00 ATOM 41 HN GLU 5 10.133 -7.816 13.369 1.000.00 ATOM 42 CA GLU 5 11.367 -7.088 11.809 1.000.00 ATOM 43 HA GLU 5 10.853 -6.732 10.928 1.000.00 ATOM 44 CB GLU 5 11.664 -5.898 12.726 1.000.00 ATOM 45 HB1 GLU 5 12.723 -5.877 12.941 1.000.00 ATOM 46 HB2 GLU 5 11.121 -6.027 13.650 1.000.00 ATOM 47 CG GLU 5 11.273 -4.557 12.128 1.000.00 ATOM 48 HG1 GLU 5 10.294 -4.648 11.681 1.000.00 ATOM 49 HG2 GLU 5 11.992 -4.293 11.366 1.000.00 ATOM 50 CD GLU 5 11.234 -3.448 13.160 1.000.00 ATOM 51 OEl GLU 5 11.819 -2.375 12.902 1.000.00 ATOM 52 OE2 GLU 5 10.618 -3.652 14.228 1.000.00 ATOM 53 C GLU 5 12.669 -7.758 11.380 1.000.00
ATOM 54 O GLU 5 13.123 -7.591 10.248 1.000.00
ATOM 55 N SER 6 13.263 -8.522 12.292 1.000.00
ATOM 56 HN SER 6 12.850 -8.619 13.175 1.000.00
ATOM 57 CA SER 6 14.509 -9.224 12.008 1.000.00
ATOM 58 HA SER 6 15.252 -8.487 11.743 1.000.00
ATOM 59 CB SER 6 14.983 -9.988 13.245 1.000.00
ATOM 60 HB1 SER 6 14.555-10.980 13.238 1.000.00
ATOM 61 HB2SER 6 14.663 -9.465 14.134 1.000.00
ATOM 62 OG SER 6 16.395-10.100 13.266 1.000.00
ATOM 63 HG SER 6 16.696-10.514 12.454 1.000.00
ATOM 64 C SER 6 14.330-10.186 10.838 1.000.00
ATOM 65 O SER 6 15.154-10.231 9.925 1.000.00
ATOM 66 N GLN 7 13.244-10.951 10.875 1.000.00
ATOM 67 HN GLN 7 12.625-10.866 11.630 1.000.00
ATOM 68 CA GLN 7 12.948-11.913 9.820 1.000.00
ATOM 69 HA GLN 7 13.840-12.494 9.640 1.000.00
ATOM 70 CB GLN 7 11.823-12.851 10.262 1.000.00
ATOM 71 HB1 GLN 7 10.898-12.525 9.810 1.000.00
ATOM 72 HB2 GLN 7 11.726-12.796 11.336 1.000.00
ATOM 73 CG GLN 7 12.056-14.304 9.879 1.000.00
ATOM 74 HG1 GLN 7 13.102-14.535 10.015 1.000.00
ATOM 75 HG2GLN 7 11.791-14.435 8.840 1.000.00
ATOM 76 CD GLN 7 11.233-15.266 10.714 1.000.00
ATOM 77 OEl GLN 7 10.035-15.066 10.912 1.000.00
ATOM 78 NE2GLN 7 11.875-16.318 11.208 1.000.00
ATOM 79HE21 GLN 7 12.830-16.413 11.010 1.000.00
ATOM 80 HE22 GLN 7 11.368-16.956 11.752 1.000.00
ATOM 81 C GLN 7 12.555-11.200 8.530 1.000.00
ATOM 82 O GLN 7 12.770-11.716 7.434 1.000.00
ATOM 83 N LEU 8 11.977-10.012 8.671 1.000.00
ATOM 84 HN LEU 8 11.832 -9.652 9.570 1.000.00
ATOM 85 CA LEU 8 11.553 -9.226 7.521 1.000.00
ATOM 86 HA LEU 8 10.844 -9.816 6.961 1.000.00
ATOM 87 CB LEU 8 10.862 -7.940 7.995 1.000.00
ATOM 88 HB1 LEU 8 11.301 -7.652 8.939 1.000.00
ATOM 89 HB2 LEU 8 9.817 -8.161 8.158 1.000.00
ATOM 90 CG LEU 8 10.955 -6.746 7.043 1.000.00
ATOM 91 HG LEU 8 11.979 -6.407 7.010 1.000.00
ATOM 92 CDl LEU 8 10.543 -7.145 5.632 1.000.00
ATOM 93 HDl 1 LEU 8 10.345 -8.207 5.600 1.000.00
ATOM 94 HDl 2 LEU 8 11.341 -6.908 4.944 1.000.00
ATOM 95 HDl 3 LEU 8 9.652 -6.604 5.349 1.000.00
ATOM 96 CD2 LEU 8 10.094 -5.597 7.548 1.000.00
ATOM 97HD21 LEU 8 10.266 -5.455 8.604 1.000.00
ATOM 98 HD22 LEU 8 9.052 -5.828 7.381 1.000.00
ATOM 99 HD23 LEU 8 10.352 -4.693 7.016 1.000.00
ATOM 100 C LEU 8 12.744 -8.903 6.618 1.000.00
ATOM 101 O LEU 8 12.667 -9.047 5.399 1.000.00
ATOM 102 N LYS 9 13.841 -8.466 7.227 1.000.00
ATOM 103 HN LYS 9 13.841 -8.372 8.202 1.000.00
ATOM 104 CA LYS 9 15.048 -8.123 6.480 1.000.00
ATOM 105 HA LYS 9 14.809 -7.292 5.833 1.000.00
ATOM 106 CB LYS 9 16.162 -7.699 7.440 1.000.00
ATOM 107 HB1 LYS 9 16.904 -8.483 7.483 1.000.00
ATOM 108 HB2LYS 9 15.740 -7.561 8.424 1.000.00
ATOM 109 CG LYS 9 16.856 -6.409 7.034 1.000.00
ATOM 110 HG1 LYS 9 16.175 -5.817 6.440 1.000.00
ATOM 111 HG2LYS 9 17.731 -6.650 6.448 1.000.00 ATOM 112 CD LYS 9 17.284 -5.598 8.248 1.000.00
ATOM 113 HDl LYS 9 16.787 -5.989 9.124 1.000.00
ATOM 114 HD2 LYS 9 16.998 -4.568 8.100 1.000.00
ATOM 115 CE LYS 9 18.788 -5.665 8.463 1.000.00
ATOM 116 HEI LYS 9 19.139 -4.688 8.761 1.000.00
ATOM 117 HE2LYS 9 19.259 -5.948 7.533 1.000.00
ATOM 118 NZ LYS 9 19.157 -6.654 9.513 1.000.00
ATOM 119 HZ1 LYS 9 20.100 -7.046 9.319 1.000.00
ATOM 120 HZ2LYS 9 18.467 -7.432 9.529 1.000.00
ATOM 121 HZ3LYS 9 19.168 -6.196 10.447 1.000.00
ATOM 122 C LYS 9 15.517 -9.294 5.619 1.000.00
ATOM 123 O LYS 9 15.952 -9.107 4.484 1.000.00
ATOM 124 N LYS 10 15.430-10.500 6.167 1.000.00
ATOM 125 HN LYS 10 15.078-10.587 7.078 1.000.00
ATOM 126 CA LYS 10 15.850-11.699 5.449 1.000.00
ATOM 127 HA LYS 10 16.824-11.505 5.026 1.000.00
ATOM 128 CB LYS 10 15.957-12.882 6.413 1.000.00
ATOM 129 HB1 LYS 10 15.806-13.797 5.860 1.000.00
ATOM 130 HB2LYS 10 15.184-12.793 7.162 1.00 0.00
ATOM 131 CG LYS 10 17.299-12.971 7.122 1.000.00
ATOM 132 HG1 LYS 10 17.435-12.085 7.726 1.000.00
ATOM 133 HG2LYS 10 18.083-13.029 6.383 1.000.00
ATOM 134 CD LYS 10 17.375-14.197 8.018 1.000.00
ATOM 135 HDl LYS 10 16.378-14.455 8.343 1.000.00
ATOM 136 HD2LYS 10 17.987-13.966 8.877 1.000.00
ATOM 137 CE LYS 10 17.981-15.384 7.287 1.000.00
ATOM 138 HEI LYS 10 19.019-15.474 7.572 1.000.00
ATOM 139 HE2LYS 10 17.914-15.209 6.224 1.000.00
ATOM 140 NZ LYS 10 17.276-16.655 7.613 1.000.00
ATOM 141 HZ1 LYS 10 16.790-16.570 8.529 1.000.00
ATOM 142 HZ2LYS 10 17.958-17.438 7.668 1.000.00
ATOM 143 HZ3 LYS 10 16.574-16.873 6.878 1.000.00
ATOM 144 C LYS 10 14.882-12.040 4.318 1.000.00
ATOM 145 O LYS 10 15.243-12.741 3.372 1.000.00
ATOM 146 N MET 11 13.652-11.547 4.420 1.000.00
ATOM 147 HN MET 11 13.421 -10.995 5.194 1.000.00
ATOM 148 CA MET 11 12.637-11.809 3.404 1.000.00
ATOM 149 HA MET 11 12.564-12.878 3.287 1.000.00
ATOM 150 CB MET 11 11.277-11.270 3.853 1.000.00
ATOM 151 HB1 MET 11 10.561 -11.425 3.060 1.000.00
ATOM 152 HB2MET 11 11.365-10.212 4.046 1.000.00
ATOM 153 CG MET 11 10.748-11.944 5.110 1.000.00
ATOM 154 HG1 MET 11 11.104-11.398 5.970 1.000.00
ATOM 155 HG2MET 11 11.130-12.953 5.146 1.000.00
ATOM 156 SD MET 11 8.946-12.012 5.173 1.000.00
ATOM 157 CE MET 11 8.509-10.423 4.470 1.000.00
ATOM 158 HEI MET 11 8.937-10.336 3.483 1.000.00
ATOM 159 HE2MET 11 8.892 -9.633 5.099 1.000.00
ATOM 160 HE3 MET 11 7.434-10.342 4.405 1.000.00
ATOM 161 C MET 11 13.031-11.204 2.061 1.000.00
ATOM 1620 MET 11 12.557-11.639 1.011 1.000.00
ATOM 163 N VAL 12 13.911-10.211 2.098 1.000.00
ATOM 164 HN VAL 12 14.263 -9.918 2.963 1.000.00
ATOM 165 CA VAL 12 14.379 -9.563 0.878 1.000.00
ATOM 166 HA VAL 12 13.696 -9.835 0.084 1.000.00
ATOM 167 CB VAL 12 14.395 -8.016 0.991 1.000.00
ATOM 168 HB VAL 12 15.276 -7.650 0.484 1.000.00
ATOM 169 CGI VAL 12 13.177 -7.422 0.301 1.000.00
ATOM 170HG11 VAL 12 12.921 -8.023 -0.558 1.000.00 ATOM 171HG12VAL 12 13.400 -6.415 -0.017 1.000.00
ATOM 172 HG 13 VAL 12 12.346 -7.406 0.991 1.000.00
ATOM 173 CG2VAL 12 14.457 -7.559 2.443 1.000.00
ATOM 174HG21VAL 12 15.432 -7.778 2.849 1.000.00 ATOM 175HG22VAL 12 13.702 -8.074 3.017 1.000.00
ATOM 176HG23VAL 12 14.280 -6.494 2.491 1.000.00
ATOM 177 C VAL 12 15.771-10.069 0.511 1.000.00
ATOM 1780 VAL 12 15.906-11.014 -0.266 1.000.00
ATOM 179 N SER 13 16.803 -9.455 1.087 1.000.00 ATOM 180 HN SER 13 16.632 -8.720 1.714 1.000.00
ATOM 181 CA SER 13 18.187 -9.863 0.834 1.000.00
ATOM 182 HA SER 13 18.819 -9.289 1.4941.000.00
ATOM 183 CB SER 13 18.367-11.349 1.159 1.000.00
ATOM 184 HB1 SER 13 18.987-11.809 0.404 1.000.00 ATOM 185 HB2SER 13 17.402-11.832 1.175 1.000.00
ATOM 186 OG SER 13 18.983-11.523 2.4241.000.00
ATOM 187 HG SER 13 19.899-11.781 2.301 1.000.00
ATOM 188 C SER 13 18.622 -9.592 -0.6101.000.00
ATOM 189 O SER 13 19.639 -8.939 -0.843 1.000.00 ATOM 190 N LYS 14 17.866-10.112 -1.574 1.000.00
ATOM 191 HN LYS 14 17.079-10.639 -1.335 1.000.00
ATOM 192 CA LYS 14 18.201 -9.938 -2.985 1.000.00
ATOM 193 HA LYS 14 19.268-10.061 -3.085 1.000.00
ATOM 194 CB LYS 14 17.505-11.011 -3.826 1.000.00 ATOM 195 HB1 LYS 14 16.675-10.561 -4.351 1.000.00
ATOM 196 HB2LYS 14 17.128-11.779 -3.167 1.000.00
ATOM 197 CG LYS 14 18.417-11.667 -4.849 1.000.00
ATOM 198 HG1 LYS 14 18.800-12.589 -4.436 1.000.00
ATOM 199 HG2LYS 14 19.238-11.000 -5.066 1.000.00 ATOM 200 CD LYS 14 17.678-11.973 -6.142 1.000.00
ATOM 201 HDl LYS 14 16.832-11.308 -6.227 1.000.00
ATOM 202 HD2LYS 14 17.333-12.996 -6.114 1.000.00
ATOM 203 CE LYS 14 18.576-11.790 -7.354 1.000.00
ATOM 204 HEI LYS 14 19.581 -12.085 -7.090 1.000.00 ATOM 205 HE2LYS 14 18.571-10.747 -7.635 1.000.00
ATOM 206 NZ LYS 14 18.120-12.605 -8.513 1.000.00
ATOM 207 HZ1 LYS 14 18.667-12.358 -9.362 1.000.00
ATOM 208 HZ2LYS 14 17.112-12.428 -8.700 1.000.00
ATOM 209 HZ3LYS 14 18.251-13.617 -8.312 1.000.00 ATOM 210 C LYS 14 17.822 -8.549 -3.501 1.000.00
ATOM 211 O LYS 14 18.051 -8.236 -4.669 1.000.00
ATOM 212 N TYR 15 17.255 -7.712 -2.636 1.000.00
ATOM 213 HN TYR 15 17.098 -8.000 -1.713 1.000.00
ATOM 214 CA TYR 15 16.871 -6.364 -3.034 1.000.00 ATOM 215 HA TYR 15 16.290 -6.433 -3.943 1.000.00
ATOM 216 CB TYR 15 16.024 -5.709 -1.941 1.000.00
ATOM 217 HB1TYR 15 16.266 -4.657 -1.889 1.000.00
ATOM 218 HB2TYR 15 16.254 -6.171 -0.993 1.000.00
ATOM 219 CG TYR 15 14.533 -5.831 -2.163 1.000.00 ATOM 220 CDl TYR 15 13.682 -4.773 -1.871 1.000.00
ATOM 221 HDl TYR 15 14.099 -3.854 -1.485 1.000.00
ATOM 222 CD2TYR 15 13.977 -7.004 -2.659 1.000.00
ATOM 223 HD2TYR 15 14.625 -7.836 -2.890 1.000.00
ATOM 224 CE1 TYR 15 12.318 -4.879 -2.067 1.000.00 ATOM 225 HEI TYR 15 11.673 -4.045 -1.835 1.000.00
ATOM 226 CE2TYR 15 12.614 -7.117 -2.858 1.000.00
ATOM 227 HE2TYR 15 12.199 -8.036 -3.245 1.000.00
ATOM 228 CZ TYR 15 11.790 -6.052 -2.560 1.000.00
ATOM 229 OH TYR 15 10.433 -6.161 -2.755 1.000.00 ATOM 230 HH TYR 15 9.972 -5.871 - 1.964 1.00 0.00
ATOM 231 C TYR 15 18.1 13 - 5.520 - 3.299 1.00 0.00
ATOM 232 O TYR 15 19.105 - 5.622 - •2.577 1.00 0.00
ATOM 233 N LYS 16 18.057 - 4.679 - 4.328 1.00 0.00
ATOM 234 HN LYS 16 17.240 -4.631 -4.867 1.00 0.00
ATOM 235 CA LYS 16 19.187 -3.818 -4.660 1.00 0.00
ATOM 236 HA LYS 16 20.036 -4.449 -4.877 1.00 0.00
ATOM 237 CB LYS 16 18.867 -2.963 -5.888 1.00 0.00
ATOM 238 HB 1 LYS 16 18.212 -2.158 -5.591 1.00 0.00
ATOM 239 HB2 LYS 16 18.360 -3.578 -6.618 1.00 0.00
ATOM 240 CG LYS 16 20.097 -2.359 -6.546 1.00 0.00
ATOM 241 HG 1 LYS 16 20.712 -3.157 -6.937 1.00 0.00
ATOM 242 HG2 LYS 16 20.653 -1.803 -5.807 1.00 0.00
ATOM 243 CD LYS 16 19.718 -1.424 -7.684 1.00 0.00
ATOM 244 HDl LYS 16 18.943 -0.754 -7.342 1.00 0.00
ATOM 245 HD2 LYS 16 19.349 -2.01 1 -8.512 1.00 0.00
ATOM 246 CE LYS 16 20.910 ■ -0.606 -8.153 1.00 0.00
ATOM 247 HEI LYS 16 21.817 -1.1 13 -7.859 1.00 0.00
ATOM 248 HE2 LYS 16 20.872 0.365 -7.682 1.00 0.00
ATOM 249 NZ LYS 16 20.913 -0.425 -9.631 1.00 0.00
ATOM 250 HZ1 LYS 16 20.985 -1.349 - 10.104 1.00 0.00
ATOM 251 HZ2 LYS 16 21.721 0.163 -9.918 1.00 0.00
ATOM 252 HZ3 LYS 16 20.034 0.041 -9.936 1.00 0.00
ATOM 253 C LYS 16 19.524 -: 2.924 -i 3.473 1.00 0.00
ATOM 254 O LYS 16 20.678 -: 2.548 - 3.266 1.00 0.00
ATOM 255 N TYR 17 18.501 - 2.604 - 2.689 1.00 0.00
ATOM 256 HN TYR 17 17.611 -2.949 -2.907 1.00 0.00
ATOM 257 CA TYR 17 18.662 -1.774 -1.505 1.00 0.00
ATOM 258 HA TYR 17 19.698 -1.820 -1.203 1.00 0.00
ATOM 259 CB TYR 17 18.291 -0.322 -1.816 1.00 0.00
ATOM 260 HB 1 TYR 17 18.428 0.275 -0.927 1.00 0.00
ATOM 261 HB2 TYR 17 17.255 -0.280 -2.1 16 1.00 0.00
ATOM 262 CG TYR 17 19.1 19 0.292 -2.922 1.00 0.00
ATOM 263 CD l TYR 17 18.619 0.396 -4.214 1.00 0.00
ATOM 264 HDl TYR 17 17.625 0.031 -4.424 1.00 0.00
ATOM 265 CD2 TYR 17 20.401 0.767 -2.674 1.00 0.00
ATOM 266 HD2 TYR 17 20.804 0.693 -1.675 1.00 0.00
ATOM 267 CE1 TYR 17 19.373 0.956 -5.228 1.00 0.00
ATOM 268 HE I TYR 17 18.967 1.028 -6.226 1.00 0.00
ATOM 269 CE2 TYR 17 21.161 1.329 -3.683 1.00 0.00
ATOM 270 HE2 TYR 17 22.155 1.693 -3.470 1.00 0.00
ATOM 271 CZ TYR 17 20.643 1.421 • -4.957 1.00 0.00
ATOM 272 OH TYR 17 21.397 1.980 -5.964 1.00 0.00
ATOM 273 HH TYR 17 20.925 2.726 -6.341 1.00 0.00
ATOM 274 C TYR 17 17.791 -: 2.310 - 0.374 1.00 0.00
ATOM 275 O TYR 17 17.032 - 1.566 i 0.247 1.00 0.00
ATOM 276 N ARG 18 17.899 - 3.615 - ■0.120 1.00 0.00
ATOM 277 HN ARG 18 18.515 -4.155 -0.656 1.00 0.00
ATOM 278 CA ARG 18 17.1 14 -4.264 0.928 1.00 0.00
ATOM 279 HA ARG 18 16.095 -4.332 0.575 1.00 0.00
ATOM 280 CB ARG 18 17.636 -5.682 1.191 1.00 0.00
ATOM 281 HB 1 ARG 18 17.801 -6.172 0.242 1.00 0.00
ATOM 282 HB2 ARG 18 16.888 -6.231 1.742 1.00 0.00
ATOM 283 CG ARG 18 18.935 -5.730 1.981 1.00 0.00
ATOM 284 HG1 ARG 18 18.703 -5.840 3.030 1.00 0.00
ATOM 285 HG2 ARG 18 19.472 -4.810 1.824 1.00 0.00
ATOM 286 CD ARG 18 19.813 -6.891 1.544 1.00 0.00
ATOM 287 HD l ARG 18 19.476 -7.238 0.578 1.00 0.00
ATOM 288 HD2 ARG 18 19.719 -7.688 2.265 1.00 0.00 ATOM 289 NE ARG 18 21.219 -6.505 1.444 1.00 0.00
ATOM 290 HE ARG 18 21.826 -6.824 2.144 1.00 0.00
ATOM 291 CZ ARG 18 21.713 -5.750 0.466 1.00 0.00
ATOM 292 NH1 ARG 18 20.922 -5.303 -0.501 1.00 0.00
ATOM 293 HH1 1 ARG I 18 19.949 -5.532 -0.498 1.00 0.00
ATOM 294 HH 12 ARG 1 18 21.299 -4.736 -1.233 1.00 0.00
ATOM 295 NH2 ARG 18 23.003 -5.442 0.453 1.00 0.00
ATOM 296 HH21 ARG ! 18 23.604 -5.776 1.179 1.00 0.00
ATOM 297 HH22 ARG 1 18 23.374 -4.874 -0.282 1.00 0.00
ATOM 298 C ARG 18 17.131 -3.442 2.216 1.00 0.00
ATOM 299 O ARG 18 16.128 -3.355 2.922 1.00 0.00
ATOM 300 N ASP 19 18.276 -2.835 2.510 1.00 0.00
ATOM 301 HN ASP 19 19.040 -2.935 1.904 1.00 0.00
ATOM 302 CA ASP 19 18.421 -2.014 3.706 1.00 0.00
ATOM 303 HA ASP 19 18.201 -2.633 4.562 1.00 0.00
ATOM 304 CB ASP 19 19.855 -1.493 3.823 1.00 0.00
ATOM 305 HB 1 ASP 19 19.843 -0.531 4.312 1.00 0.00
ATOM 306 HB2 ASP 19 20.273 -1.384 2.833 1.00 0.00
ATOM 307 CG ASP 19 20.746 -2.427 4.619 1.00 0.00
ATOM 308 OD 1 ASP 19 20.565 -3.657 4.510 1.00 0.00
ATOM 309 OD2 ASP 19 21.625 -1.926 5.351 1.00 0.00
ATOM 310 C ASP i 19 17.443 -0.843 3.680 1.00 0.00
ATOM 31 1 O ASP 19 16.623 -0.685 4.584 1.00 0.00
ATOM 312 N LEU 20 17.541 -0.024 2.637 1.00 0.00
ATOM 313 HN LEU 20 18.217 -0.204 1.951 1.00 0.00
ATOM 314 CA LEU 20 16.670 1.136 2.488 1.00 0.00
ATOM 315 HA LEU 20 16.744 1.723 3.391 1.00 0.00
ATOM 316 CB LEU 20 17.125 1.991 1.303 1.00 0.00
ATOM 317 HB1 LEU 20 16.251 2.427 0.842 1.00 0.00
ATOM 318 HB2 LEU 20 17.606 1.344 0.583 1.00 0.00
ATOM 319 CG LEU 20 18.093 3.122 1.655 1.00 0.00
ATOM 320 HG LEU 20 18.375 3.640 0.750 1.00 0.00
ATOM 321 CDl LEU 20 17.426 4.126 2.582 1.00 0.00
ATOM 322 HDl 1 LEU 20 17.984 5.051 2.572 1.00 0.00
ATOM 323 HDl 2 LEU 20 17.405 3.729 3.586 1.00 0.00
ATOM 324 HDl 3 LEU 20 16.416 4.310 2.247 1.00 0.00
ATOM 325 CD2 LEU 20 19.356 2.562 2.292 1.00 0.00
ATOM 326 HD21 LEU 20 19.973 3.375 2.644 1.00 0.00
ATOM 327 HD22 LEU 20 19.903 1.985 1.560 1.00 0.00
ATOM 328 HD23 LEU 20 19.088 1.927 3.123 1.00 0.00
ATOM 329 C LEU : 20 15.216 0.714 2.296 1.00 0.00
ATOM 330 O LEU : 20 14.295 1.455 2.640 1.00 0.00
ATOM 331 N THR 21 15.014 -0.480 1.746 1.00 0.00
ATOM 332 HN THR 21 15.786 -1.029 1.494 1.00 0.00
ATOM 333 CA THR 21 13.669 -0.993 1.514 1.00 0.00
ATOM 334 HA THR 21 13.065 -0.181 1.138 1.00 0.00
ATOM 335 CB THR 21 13.696 -2.1 16 0.477 1.00 0.00
ATOM 336 HB THR 21 14.239 -2.956 0.885 1.00 0.00
ATOM 337 OG l THR 21 14.353 -1.692 -0.704 1.00 0.00
ATOM 338 HG1 THR 21 15.166 -1.237 -0.473 1.00 0.00
ATOM 339 CG2 THR 21 12.317 -2.601 0.088 1.00 0.00
ATOM 340 HG21 THR 21 1 1.586 -2.199 0.774 1.00 0.00
ATOM 341 HG22 THR 21 12.290 -3.680 0.126 1.00 0.00
ATOM 342 HG23 THR 21 12.088 -2.270 -0.915 1.00 0.00
ATOM 343 C THR : 21 13.058 -1.500 2.814 1.00 0.00
ATOM 344 O THR : 21 1 1.931 -1.149 3.162 1.00 0.00
ATOM 345 N VAL 22 13.815 -2.322 3.531 1.00 0.00
ATOM 346 HN VAL 22 14.706 -2.559 3.202 1.00 0.00
ATOM 347 CA VAL 22 13.357 -2.874 4.798 1.00 0.00 ATOM 348 HA VAL 22 12.457 -3.442 4.609 1.00 0.00
ATOM 349 CB VAL 22 14.411 -3.820 5.409 1.00 ( 3.00
ATOM 350 HB VAL 22 15.339 -3.275 5.504 1.00 1 D.00
ATOM 351 CG I VAL 22 13.987 -4.288 6.795 1.00 0.00 ATOM 352 HG 1 1 VAL 22 14.439 -3.653 3 7.543 1.00 0.00
ATOM 353 HG 12 VAL 22 14.310 -5.307 7 6.946 1.00 0.00
ATOM 354 HG 13 VAL 22 12.912 -4.235 5 6.880 1.00 0.00
ATOM 355 CG2 VAL 22 14.650 -5.009 4.492 1.00 0.00
ATOM 356 HG21 VAL 22 14.443 -4.724 1 3.471 1.00 0.00 ATOM 357 HG22 VAL 22 13.999 -5.821 l 4.778 1.00 0.00
ATOM 358 HG23 VAL 22 15.679 -5.327 7 4.575 1.00 0.00
ATOM 359 C VAL 22 13.039 -1.756 5.786 1.00 0.00
ATOM 360 O VAL 22 11.995 -1.770 6.437 1.00 0.00
ATOM 361 N ARG 23 13.942 0.784 5.884 1.000.00 ATOM 362 HN ARG 23 14.751 -0.825 5.333 1.000.00
ATOM 363 CA ARG 23 13.751 0.347 6.785 1.00 0.00
ATOM 364 HA ARG 23 13.658 -0.039 7.789 1.00 0.00
ATOM 365 CB ARG 23 14.955 1.289 6.721 1.00 0.00
ATOM 366 HB 1 ARG 23 14.799 2.000 5.922 1.00 0.00 ATOM 367 HB2 ARG 23 15.841 0.709 6.508 1.00 0.00
ATOM 368 CG ARG 23 15.191 2.064 8.008 1.00 0.00
ATOM 369 HG 1 ARG 23 14.246 2.451 8.361 1.00 0.00
ATOM 370 HG2 ARG 23 15.865 2.882 7.806 1.00 0.00
ATOM 371 CD ARG 23 15.798 1.182 9.088 1.00 0.00 ATOM 372 HD l ARG 23 16.819 1.491 9.255 1.00 0.00
ATOM 373 HD2 ARG 23 15.784 0.156 8.750 1.00 0.00
ATOM 374 NE ARG 23 15.063 1.274 10.347 1.00 0.00
ATOM 375 HE ARG 23 14.445 0.546 10.565 1.00 0.00
ATOM 376 CZ ARG 23 15.187 2.284 1 1.205 1.00 0.00 ATOM- 377 NH 1 ARG 23 16.014 3.289 10.944 .00 0.00
ATOM 378 HH 1 1 ARG 23 16.549 3.291 10.100 1.00 0.00
ATOM 379 HH 12 ARG 23 16.102 4.045 1 1.593 1.00 0.00
ATOM 380 NH2 ARG 23 14.481 2.291 12.328 .00 0.00
ATOM 381 HH21 ARG 23 13.855 1.537 12.529 1.00 0.00 ATOM 382 HH22 ARG 23 14.573 3.049 12.973 1.00 0.00
ATOM 383 C ARG 23 12.477 1.103 6.428 1.00 0.00
ATOM 384 O ARG 23 11.681 1.448 7.302 1.00 0.00
ATOM 385 N GLU 24 12.285 1.348 5.137 i 1.00 I o.oo
ATOM 386 HN GLU 24 12.951 1.041 4.486 1.00 0.00 ATOM 387 CA GLU 24 1 1.099 2.050 4.666 1.00 0.00
ATOM 388 HA GLU 24 1 1.038 2.992 5.191 1.00 0.00
ATOM 389 CB GLU 24 1 1.198 2.319 3.163 1.00 0.00
ATOM 390 HB 1 GLU 24 10.222 2.595 2.793 1.00 0.00
ATOM 391 HB2 GLU 24 1 1.518 1.414 2.668 1.00 0.00 ATOM 392 CG GLU 24 12.175 3.427 2.807 1.00 0.00
ATOM 393 HG 1 GLU 24 13.077 3.294 3.385 1.00 i 0.00
ATOM 394 HG2 GLU 24 1 1.726 4.378 3.054 1.00 i 0.00
ATOM 395 CD GLU 24 12.538 3.432 1.335 1.00 0.00
ATOM 396 OEl GLU 24 12.438 2.364 0.695 1.00 0.00 ATOM 397 OE2 GLU 24 12.922 4.504 0.822 1.00 0.00
ATOM 398 C GLU 24 9.850 1 .233 4.970 1.00 0.00
ATOM 399 O GLU 24 8.838 1 1.766 5.425 1.00 0.00
ATOM 400 N THR 25 9.935 -0.070 4.718 1.00 0.00
ATOM 401 HN THR 25 10.772 -0.433 4.360 1.00 0.00 ATOM 402 CA THR 25 8.820 ■ -0.974 4.967 1.00 0.00
ATOM 403 HA THR 25 7.977 ■ -0.630 4.386 1.00 0.00
ATOM 404 CB THR 25 9.180 - ■2.394 4.527 1.00 0.00
ATOM 405 HB THR 25 9.908 - -2.799 5.215 1.00 0.00
ATOM 406 OG l THR 25 9.748 -2.387 3.230 1.00 0.00 ATOM 407 HG1 THR 25 10.680 -2.613 3.287 1.00 0.00
ATOM 408 CG2 THR 25 7.993 -3.332 4.503 1.00 0.00
ATOM 409 HG21 THR 25 7.424 -3.170 3.599 1.00 0.00
ATOM 410 HG22 THR 25 7.366 -3.142 5.361 1.00 0.00
ATOM 41 1 HG23 THR 25 8.341 -4.354 4.530 1.00 0.00
ATOM 412 C THR 25 8.435 -0.968 6.442 1.00 0.00
ATOM 413 O THR 25 7.295 -0.666 6.795 1.00 0.00
ATOM 414 N VAL 26 9.395 -1.302 7.303 1.00 0.00
ATOM 415 HN VAL 26 10.285 -1.532 6.963 1.00 0.00
ATOM 416 CA VAL 26 9.153 -1.331 8.742 1.00 0.00
ATOM 417 HA VAL 26 8.446 -2.123 8.942 1.00 0.00
ATOM 418 CB VAL 26 10.443 -1.628 9.533 1.00 0.00
ATOM 419 HB VAL 26 10.203 -1.626 10.586 1.00 0.00
ATOM 420 CG I VAL 26 10.985 -3.002 9.173 1.00 0.00
ATOM 421 HG 1 1 VAL 26 10.380 -3.762 9.646 1.00 0.00
ATOM 422 HG12 VAL 26 12.005 -3.089 9.517 1.00 0.00
ATOM 423 HG 13 VAL 26 10.954 -3.133 8.102 1.00 0.00
ATOM 424 CG2 VAL 26 1 1.491 -0.554 9.282 1.00 0.00
ATOM 425 HG21 VAL 26 1 1.737 -0.530 8.232 1.00 0.00
ATOM 426 HG22 VAL 26 12.379 -0.778 9.854 1.00 0.00
ATOM 427 HG23 VAL 26 1 1.102 0.407 9.583 1.00 0.00
ATOM 428 C VAL 26 8.562 -0.010 9.224 1.00 0.00
ATOM 429 O VAL 26 7.657 0.010 10.057 1.00 0.00
ATOM 430 N ASN 27 9.078 1.092 8.689 1.00 0.00
ATOM 431 HN ASN 27 9.796 1.011 8.027 1.00 0.00
ATOM 432 CA ASN 27 8.600 2.420 9.059 1.00 0.00
ATOM 433 HA ASN 27 8.795 2.560 10.112 1.00 0.00
ATOM 434 CB ASN 27 9.351 3.494 8.267 1.00 0.00
ATOM 435 HB1 ASN 27 8.662 3.990 7.599 1.00 0.00
ATOM 436 HB2 ASN 27 10.131 3.024 7.687 1.00 0.00
ATOM 437 CG ASN 27 9.985 4.538 9.165 1.00 0.00
ATOM 438 OD1 ASN 27 10.991 4.277 9.825 1.00 0.00
ATOM 439 ND2 ASN 27 9.397 5.728 9.195 1.00 0.00
ATOM 440 HD21 ASN 27 8.599 5.864 8.643 1.00 0.00
ATOM 441 HD22 ASN 27 9.786 6.422 9.767 1.00 0.00
ATOM 442 C ASN 27 7.098 2.546 8.818 1.00 0.00
ATOM 443 O ASN 27 6.365 3.065 9.660 1.00 0.00
ATOM 444 N VAL 28 6.647 2.066 7.662 1.00 0.00
ATOM 445 HN VAL 28 7.280 1.664 7.032 1.00 0.00
ATOM 446 CA VAL 28 5.233 2.125 7.31 1 1.00 0.00
ATOM 447 HA VAL 28 4.917 3.156 7.369 1.00 0.00
ATOM 448 CB VAL 28 4.988 1.624 5.873 1.00 0.00
ATOM 449 HB VAL 28 5.241 0.575 5.830 1.00 0.00
ATOM 450 CGI VAL 28 3.522 1.775 5.492 1.00 0.00
ATOM 451 HG1 1 VAL 28 3.428 1.781 4.417 1.00 0.00
ATOM 452 HG 12 VAL 28 3.140 2.702 5.892 1.00 0.00
ATOM 453 HG 13 VAL 28 2.958 0.948 5.899 1.00 0.00
ATOM 454 CG2 VAL 28 5.878 2.369 4.888 1.00 0.00
ATOM 455 HG21 VAL 28 6.790 2.670 5.383 1.00 0.00
ATOM 456 HG22 VAL 28 5.360 3.245 4.526 1.00 0.00
ATOM 457 HG23 VAL 28 6.1 16 1.722 4.057 1.00 0.00
ATOM 458 C VAL 28 4.393 1.295 8.278 1.00 0.00
ATOM 459 O VAL 28 3.450 1.801 8.887 1.00 0.00
ATOM 460 N ILE 29 4.742 0.020 8.416 1.00 0.00
ATOM 461 HN ILE 29 5.503 -0.326 7.904 1.00 0.00
ATOM 462 CA ILE 29 4.019 -0.877 9.310 1.00 0.00
ATOM 463 HA ILE 29 2.978 -0.868 9.021 1.00 0.00
ATOM 464 CB ILE 29 4.539 -2.322 9.201 1.00 0.00
ATOM 465 HB ILE 29 4.007 -2.929 9.918 1.00 0.00 ATOM 466 CG I ILE 29 6.034 -2.372 9.517 1.00 0.00
ATOM 467 HG 1 1 ILE 29 6.197 -2.004 10.519 1.00 0.00
ATOM 468 HG 12 ILE 29 6.563 -1.744 8.817 1.00 0.00
ATOM 469 CG2 ILE 29 4.266 -2.881 7.813 1.00 0.00
ATOM 470 HG21 ILE 29 3.484 -2.305 7.340 1.00 0.00
ATOM 471 HG22 ILE 29 3.955 -3.912 7.895 1.00 0.00
ATOM 472 HG23 ILE 29 5.165 -2.822 7.218 1.00 0.00
ATOM 473 CDl ILE 29 6.625 -3.763 9.430 1.00 0.00
ATOM 474 HDl 1 ILE 29 7.635 -3.750 9.812 1.00 0.00
ATOM 475 HDl 2 ILE 29 6.634 -4.086 8.399 1.00 0.00
ATOM 476 HDl 3 ILE 29 6.027 -4.445 10.016 1.00 0.00
ATOM 477 C ILE 29 4.133 -0.416 10.759 1.00 0.00
ATOM 478 O ILE 29 3.178 -0.514 1 1.529 1.00 0.00
ATOM 479 N THR 30 5.306 0.091 1 1.124 1.00 0.00
ATOM 480 HN THR 30 6.030 0.147 10.466 1.00 0.00
ATOM 481 CA THR 30 5.540 0.571 12.481 1.00 0.00
ATOM 482 HA THR 30 5.246 -0.212 13.165 1.00 0.00
ATOM 483 CB THR 30 7.023 0.885 12.689 1.00 0.00
ATOM 484 HB THR 30 7.331 1.619 1 1.958 1.00 0.00
ATOM 485 OGl THR 30 7.81 1 -0.279 12.509 1.00 0.00
ATOM 486 HG 1 THR 30 8.712 -0.026 12.294 1.00 0.00
ATOM 487 CG2 THR 30 7.335 1.439 14.063 1.00 0.00
ATOM 488 HG21 THR 30 6.786 0.883 14.809 1.00 0.00
ATOM 489 HG22 THR 30 7.046 2.479 14.105 1.00 0.00
ATOM 490 HG23 THR 30 8.394 1.351 14.255 1.00 0.00
ATOM 491 C THR 30 4.697 1.81 1 12.761 1.00 0.00
ATOM 492 O THR 30 4.231 2.018 13.881 1.00 0.00
ATOM 493 N LEU 31 4.501 2.628 1 1.732 1.00 0.00
ATOM 494 HN LEU 31 4.895 2.405 10.863 1.00 0.00
ATOM 495 CA LEU 31 3.708 3.843 1 1.862 1.00 0.00
ATOM 496 HA LEU 31 3.916 4.274 12.830 1.00 0.00
ATOM 497 CB LEU 31 4.092 4.849 10.775 1.00 0.00
ATOM 498 HB1 LEU 31 3.775 4.455 9.821 1.00 0.00
ATOM 499 HB2 LEU 31 5.168 4.944 10.767 1.00 0.00
ATOM 500 CG LEU 31 3.487 6.244 10.940 1.00 0.00
ATOM 501 HG LEU 31 2.471 6.149 1 1.295 1.00 0.00
ATOM 502 CDl LEU 31 4.270 7.048 11.966 1.00 0.00
ATOM 503 HDl 1 LEU 31 5.301 7.124 1 1.653 1.00 0.00
ATOM 504 HDl 2 LEU 31 4.220 6.553 12.925 1.00 0.00
ATOM 505 HDl 3 LEU 31 3.845 8.037 12.049 1.00 0.00
ATOM 506 CD2 LEU 31 3.454 6.971 9.604 1.00 0.00
ATOM 507 HD21 LEU 31 4.427 6.916 9.140 1.00 0.00
ATOM 508 HD22 LEU 31 3.189 8.005 9.763 1.00 0.00
ATOM 509 HD23 LEU 31 2.721 6.507 8.960 1.00 0.00
ATOM 510 C LEU : 31 2.220 3.522 1 1.775 1.00 0.00
ATOM 51 1 O LEU : 31 1.399 4.146 12.447 1.00 0.00
ATOM 512 N TYR 32 1.882 2.541 10.944 1.00 0.00
ATOM 513 HN TYR 32 2.583 2.079 10.438 1.00 0.00
ATOM 514 CA TYR 32 0.494 2.130 10.771 1.00 0.00
ATOM 515 HA TYR 32 -0.1 13 3.019 10.742 1.00 0.00
ATOM 516 CB TYR 32 0.330 1.358 9.456 1.00 0.00
ATOM 517 HB1 TYR 32 -0.270 0.478 9.638 1.00 0.00
ATOM 518 HB2 TYR 32 1.304 1.052 9.107 1.00 0.00
ATOM 519 CG TYR 32 -0.330 2.144 8.339 1.00 0.00
ATOM 520 CDl TYR 32 -1.263 3.141 8.606 1.00 0.00
ATOM 521 HDl TYR 32 -1.518 3.362 9.631 1.00 0.00
ATOM 522 CD2 TYR 32 -0.021 1.878 7.010 1.00 0.00
ATOM 523 HD2 TYR 32 0.702 1.108 6.783 1.00 0.00
ATOM 524 CE1 TYR 32 -1.866 3.846 7.583 1.00 0.00 ATOM 525 HEI TYR 32 -2.588 4.616 7.812 1.00 0.00
ATOM 526 CE2 TYR 32 -0.620 2.581 5.983 1.00 0.00
ATOM 527 HE2 TYR 32 -0.365 2.359 4.957 1.00 0.00
ATOM 528 CZ TYR 32 -1.542 3.563 6.275 1.00 0.00
ATOM 529 OH TYR 32 -2.144 4.261 5.254 1.00 0.00
ATOM 530 HH TYR 32 -3.079 4.367 5.446 1.00 0.00
ATOM 531 C TYR 32 0.042 1.259 1 1.939 1.00 0.00
ATOM 532 O TYR 32 -0.943 1.564 12.61 1 1.00 0.00
ATOM 533 N LYS 33 0.774 ( 3.169 12.168 1.00 0.00
ATOM 534 HN LYS 33 1.544 -0.01 1 1 1.592 1.00 0.00
ATOM 535 CA LYS 33 0.471 -0.771 13.249 1.00 0.00
ATOM 536 HA LYS 33 1.367 -1.347 13.431 1.00 0.00
ATOM 537 CB LYS 33 0.1 10 -0.013 14.538 1.00 0.00
ATOM 538 HB 1 LYS 33 0.372 1.027 14.407 1.00 0.00
ATOM 539 HB2 LYS 33 0.692 -0.418 15.352 1.00 0.00
ATOM 540 CG LYS 33 -1.361 -0.087 14.928 1.00 0.00
ATOM 541 HG1 LYS 33 -1.620 -1.1 18 15.120 1.00 0.00
ATOM 542 HG2 LYS 33 -1.960 0.290 14.1 13 1.00 0.00
ATOM 543 CD LYS 33 -1.650 0.736 16.173 1.00 0.00
ATOM 544 HDl LYS 33 -2.655 1.126 16.109 1.00 0.00
ATOM 545 HD2 LYS 33 -0.947 1.554 16.224 1.00 0.00
ATOM 546 CE LYS 33 -1.524 • -0.102 17.436 1.00 0.00
ATOM 547 HEI LYS 33 -1.521 0.558 18.291 1.00 0.00
ATOM 548 HE2 LYS 33 -0.593 -0.647 17.399 1.00 0.00
ATOM 549 NZ LYS 33 -2.646 -1.070 17.575 1.00 0.00
ATOM 550 HZ1 LYS 33 -3.558 -0.577 17.484 1.00 0.00
ATOM 551 HZ2 LYS 33 -2.607 -1.533 18.505 1.00 0.00
ATOM 552 HZ3 LYS 33 -2.584 -1.799 16.835 1.00 0.00
ATOM 553 C LYS 33 -0.647 - 1.743 12.854 1.00 0.00
ATOM 554 O LYS 33 -0.927 - 2.699 13.576 1.00 0.00
ATOM 555 N ASP 34 -1.280 - 1.498 1 1.708 1.00 0.00
ATOM 556 HN ASP 34 -1.017 -0.726 1 1.169 1.00 0.00
ATOM 557 CA ASP 34 -2.357 -2.361 1 1.233 1.00 0.00
ATOM 558 HA ASP 34 -2.513 -3.132 1 1.972 1.00 0.00
ATOM 559 CB ASP 34 -3.647 ■ -1.556 1 1.076 1.00 0.00
ATOM 560 HB1 ASP 34 -4.466 -2.234 10.885 1.00 0.00
ATOM 561 HB2 ASP 34 -3.543 -0.879 10.241 1.00 0.00
ATOM 562 CG ASP 34 -3.975 -0.743 12.313 1.00 0.00
ATOM 563 OD1 ASP 34 -4.160 -1.348 13.390 1.00 0.00
ATOM 564 OD2 ASP 34 -4.047 0.500 12.205 1.00 0.00
ATOM 565 C ASP : 34 -1.990 -3.021 9.904 1.00 0.00
ATOM 566 O ASP : 34 -2.518 -' 4.078 9.560 1.00 0.00
ATOM 567 N LEU 35 -1.082 - 2.392 9.162 1.00 0.00
ATOM 568 HN LEU 35 -0.697 -1.553 9.487 1.00 0.00
ATOM 569 CA LEU 35 -0.646 -2.918 7.874 1.00 0.00
ATOM 570 HA LEU 35 -1.480 -3.438 7.426 1.00 0.00
ATOM 571 CB LEU 35 -0.221 -1.769 6.956 1.00 0.00
ATOM 572 HB 1 LEU 35 0.829 -1.577 7.1 19 1.00 0.00
ATOM 573 HB2 LEU 35 -0.778 -0.888 7.238 1.00 0.00
ATOM 574 CG LEU 35 -0.435 -2.014 5.461 1.00 0.00
ATOM 575 HG LEU 35 -0.410 -3.077 5.269 1.00 0.00
ATOM 576 CD l LEU 35 -1.793 -1.487 5.021 1.00 0.00
ATOM 577 HD1 1 LEU 35 -2.484 -1.535 5.849 1.00 0.00
ATOM 578 HD12 LEU 35 -2.167 -2.090 4.206 1.00 0.00
ATOM 579 HD13 LEU 35 -1.694 -0.463 4.693 1.00 0.00
ATOM 580 CD2 LEU 35 0.678 -1.361 4.654 1.00 0.00
ATOM 581 HD21 LEU 35 1.635 -1.656 5.057 1.00 0.00
ATOM 582 HD22 LEU 35 0.580 -0.287 4.710 1.00 0.00
ATOM 583 HD23 LEU 35 0.608 -1.676 3.624 1.00 0.00 ATOM 584 C LEU 35 0.510 -3.898 8.055 1.00 0.00
ATOM 585 O LEU 35 1.644 -3.494 8.31 1 1.00 0.00
ATOM 586 N LYS 36 0.214 -5.188 7.927 1.00 0.00
ATOM 587 HN LYS 36 -0.709 -5.449 7.726 1.00 0.00
ATOM 588 CA LYS 36 1.229 -6.224 8.085 1.00 0.00
ATOM 589 HA LYS 36 1.983 -5.845 8.759 1.00 0.00
ATOM 590 CB LYS 36 0.608 -7.483 8.694 1.00 0.00
ATOM 591 HB1 LYS 36 0.497 -8.228 7.919 1.00 0.00
ATOM 592 HB2 LYS 36 -0.367 -7.236 9.085 1.00 0.00
ATOM 593 CG LYS 36 1.434 -8.086 9.818 1.00 0.00
ATOM 594 HG 1 LYS 36 2.053 -7.314 10.251 1.00 0.00
ATOM 595 HG2 LYS 36 2.060 -8.867 9.414 1.00 0.00
ATOM 596 CD LYS 36 0.549 -8.677 10.904 1.00 0.00
ATOM 597 HDl LYS 36 -0.418 -8.908 10.480 1.00 0.00
ATOM 598 HD2 LYS 36 0.433 -7.952 1 1.695 1.00 0.00
ATOM 599 CE LYS 36 1.150 -9.947 1 1.484 1.00 0.00
ATOM 600 HE I LYS 36 2.225 -9.895 1 1.392 1.00 0.00
ATOM 601 HE2 LYS 36 0.782 -10.793 10.923 1.00 0.00
ATOM 602 NZ LYS 36 0.793 -10.126 12.918 1.00 0.00
ATOM 603 HZ1 LYS 36 0.889 -1 1.125 13.188 1.00 0.00
ATOM 604 HZ2 LYS 36 -0.189 -9.826 13.083 1.00 0.00
ATOM 605 HZ3 LYS 36 1.423 -9.554 13.517 1.00 0.00
ATOM 606 C LYS 36 1.888 -6.562 6.748 1.00 0.00
ATOM 607 O LYS 36 1.227 -6.588 5.710 1.00 0.00
ATOM 608 N PRO 37 3.207 -6.833 6.757 1.00 0.00
ATOM 609 CA PRO 37 3.952 -7.177 5.545 1.00 0.00
ATOM 610 HA PRO 37 3.695 -6.527 4.721 1.00 0.00
ATOM 61 1 CB PRO 37 5.402 -6.941 5.958 1.00 0.00
ATOM 612 HB1 PRO 37 5.676 -5.916 5.757 1.00 0.00
ATOM 613 HB2 PRO 37 6.051 -7.609 5.409 1.00 0.00
ATOM 614 CG PRO 37 5.425 -7.233 7.419 1.00 0.00
ATOM 615 HG 1 PRO 37 6.203 -6.656 7.896 1.00 0.00
ATOM 616 HG2 PRO 37 5.590 -8.289 7.578 1.00 0.00
ATOM 617 CD PRO 37 4.074 -6.830 7.953 1.00 0.00
ATOM 618 HD l PRO 37 4.123 -5.843 8.390 1.00 0.00
ATOM 619 HD2 PRO 37 3.728 -7.548 8.681 1.00 0.00
ATOM 620 C PRO 37 3.740 -8.631 5.136 1.00 0.00
ATOM 621 O PRO 37 3.678 -9.520 5.986 1.00 0.00
ATOM 622 N VAL 38 3.626 -8.869 3.834 1.00 0.00
ATOM 623 HN VAL 38 3.680 -8.121 3.203 1.00 0.00
ATOM 624 CA VAL 38 3.416 -10.221 3.323 1.00 0.00
ATOM 625 HA VAL 38 3.736 -10.913 4.090 1.00 0.00
ATOM 626 CB VAL 38 1.915 -10.497 3.023 1.00 0.00
ATOM 627 HB VAL 38 1.657 -1 1.451 3.458 1.00 0.00
ATOM 628 CG I VAL 38 1.028 -9.439 3.662 1.00 0.00
ATOM 629 HG1 1 VAL , 38 1.366 -9.247 4.670 1.00 0.00
ATOM 630 HG 12 VAL , 38 0.008 -9.791 3.685 1.00 0.00
ATOM 63 1 HG 13 VAL , 38 1.082 -8.528 3.085 1.00 0.00
ATOM 632 CG2 VAL 38 1.649 -10.575 1.523 1.00 0.00
ATOM 633 HG21 VAL . 38 2.1 14 -9.734 1.031 1.00 0.00
ATOM 634 HG22 VAL , 38 0.585 -10.554 1.343 1.00 0.00
ATOM 635 HG23 VAL . 38 2.062 -1 1.493 1.132 1.00 0.00
ATOM 636 C VAL 38 4.247 -10.472 2.066 1.00 0.00
ATOM 637 O VAL 38 4.342 -9.61 1 1.193 1.00 0.00
ATOM 638 N LEU 39 4.833 -1 1.661 1.976 1.00 0.00
ATOM 639 HN LEU 39 4.712 -12.309 2.701 1.00 0.00
ATOM 640 CA LEU 39 5.640 -12.028 0.818 1.00 0.00
ATOM 641 HA LEU 39 6.026 -1 1.121 0.382 1.00 0.00
ATOM 642 CB LEU 39 6.812 - 12.929 1.234 1.00 0.00 ATOM 643 HB1 LEU 39 7.003-13.623 0.428 1.000.00
ATOM 644 HB2LEU 39 6.506-13.494 2.101 1.000.00
ATOM 645 CG LEU 39 8.135-12.219 1.572 1.000.00
ATOM 646 HG LEU 39 8.201-12.096 2.643 1.000.00 ATOM 647 CDl LEU 39 9.315-13.067 1.128 1.000.00
ATOM 648 HDl 1 LEU 39 9.036-13.641 0.256 1.000.00
ATOM 649HD12LEU 39 9.598-13.736 1.925 1.000.00
ATOM 650HD13LEU 39 10.147-12.423 0.883 1.000.00
ATOM 651 CD2LEU 39 8.215-10.841 0.932 1.000.00 ATOM 652HD21LEU 39 7.463-10.199 1.366 1.000.00
ATOM 653HD22LEU 39 8.046-10.927 -0.131 1.000.00
ATOM 654HD23LEU 39 9.194-10.419 1.108 1.000.00
ATOM 655 C LEU 39 4.788-12.744 -0.225 1.000.00
ATOM 656 O LEU 39 3.776-13.362 0.105 1.000.00 ATOM 657 N ASP 40 5.210-12.663 -1.482 1.000.00
ATOM 658 HN ASP 40 6.029-12.163 -1.680 1.000.00
ATOM 659 CA ASP 40 4.496-13.308 -2.574 1.000.00
ATOM 660 HA ASP 40 4.144-14.266 -2.221 1.000.00
ATOM 661 CB ASP 40 3.299-12.467 -3.0101.000.00 ATOM 662 HB1 ASP 40 2.804-12.957 -3.835 1.000.00
ATOM 663 HB2ASP 40 3.651-11.503 -3.329 1.000.00
ATOM 664 CG ASP 40 2.292-12.267 -1.895 1.000.00
ATOM 665 OD1 ASP 40 1.261-12.971 -1.893 1.000.00
ATOM 6660D2ASP 40 2.536-11.407 -1.024 1.000.00 ATOM 667 C ASP 40 5.429-13.532 -3.754 1.000.00
ATOM 6680 ASP 40 5.950-12.584 -4.342 1.000.00
ATOM 669 N SER 41 5.641 -14.793 -4.083 1.000.00
ATOM 670 HN SER 41 5.197-15.494 -3.567 1.000.00
ATOM 671 CA SER 41 6.520-15.166 -5.183 1.000.00 ATOM 672 HA SER 41 7.397-14.540 -5.130 1.000.00
ATOM 673 CB SER 41 6.947-16.626 -5.037 1.000.00
ATOM 674 HB1 SER 41 6.104-17.212 -4.701 1.000.00
ATOM 675 HB2SER 41 7.742-16.693 -4.309 1.000.00
ATOM 676 OG SER 41 7.410-17.153 -6.268 1.000.00 ATOM 677 HG SER 41 7.721 -18.051 -6.136 1.000.00
ATOM 678 C SER 41 5.844-14.947 -6.533 1.000.00
ATOM 679 O SER 41 5.109-15.808 -7.018 1.000.00
ATOM 680 N TYR 42 6.104-13.793 -7.137 1.000.00
ATOM 681 HN TYR 42 6.702-13.150 -6.702 1.000.00 ATOM 682 CA TYR 42 5.529-13.462 -8.436 1.000.00
ATOM 683 HA TYR 42 4.716-14.148 -8.623 1.000.00
ATOM 684 CB TYR 42 4.984-12.032 -8.428 1.000.00
ATOM 685 HB1TYR 42 5.803-11.341 -8.557 1.000.00
ATOM 686 HB2TYR 42 4.507-11.842 -7.478 1.000.00 ATOM 687 CG TYR 42 3.970-11.764 -9.518 1.000.00
ATOM 688 CDl TYR 42 4.368-11.282-10.759 1.000.00
ATOM 689 HD1TYR 42 5.417-11.098-10.939 1.000.00
ATOM 690 CD2TYR 42 2.617-11.993 -9.306 1.000.00
ATOM 691 HD2TYR 42 2.292-12.368 -8.347 1.000.00 ATOM 692 CE1TYR 42 3.445-11.035-11.757 1.000.00
ATOM 693 HEI TYR 42 3.773-10.660-12.715 1.000.00
ATOM 694 CE2TYR 42 1.688-11.750-10.300 1.000.00
ATOM 695 HE2TYR 42 0.639-11.934-10.116 1.000.00
ATOM 696 CZ TYR 42 2.107-11.271-11.523 1.000.00 ATOM 697 OH TYR 42 1.185-11.027-12.515 1.000.00
ATOM 698 HH TYR 42 0.564-11.758-12.562 1.000.00
ATOM 699 C TYR 42 6.570-13.618 -9.539 1.000.00
ATOM 700 O TYR 42 7.749-13.329 -9.337 1.000.00
ATOM 701 N VAL 43 6.131-14.079-10.705 1.000.00 ATOM 702 HN VAL 43 5.181 -14.294-10.808 1.000.00
ATOM 703 CA VAL 43 7.033-14.273-11.835 1.000.00
ATOM 704 HA VAL 43 7.998-14.562-11.443 1.000.00
ATOM 705 CB VAL 43 6.535-15.395-12.765 1.000.00
ATOM 706 HB VAL 43 7.214-15.467-13.602 1.000.00
ATOM 707 CGI VAL 43 6.533-16.731 -12.039 1.000.00
ATOM 708 HG 11 VAL 43 5.956-16.646-11.130 1.000.00
ATOM 709 HG 12 VAL 43 7.548-17.010-11.797 1.000.00
ATOM 710HG13VAL 43 6.094-17.485-12.675 1.000.00
ATOM 711 CG2VAL 43 5.149-15.069-13.302 1.000.00
ATOM 712HG21VAL 43 4.433-15.104-12.495 1.000.00
ATOM 713HG22VAL 43 4.877-15.793-14.057 1.000.00
ATOM 714HG23VAL 43 5.154-14.081 -13.737 1.000.00
ATOM 715 C VAL 43 7.191 -12.989-12.642 1.000.00
ATOM 716 O VAL 43 6.267-12.180-12.727 1.000.00
ATOM 717 N PHE 44 8.370-12.806-13.232 1.000.00
ATOM 718 HN PHE 44 9.069-13.481 -13.127 1.000.00
ATOM 719 CA PHE 44 8.647-11.619-14.028 1.000.00
ATOM 720 HA PHE 44 7.716-11.279-14.457 1.000.00
ATOM 721 CB PHE 44 9.217-10.517-13.138 1.000.00
ATOM 722 HB1 PHE 44 9.585 -9.720-13.762 1.000.00
ATOM 723 HB2PHE 44 10.035-10.920-12.560 1.000.00
ATOM 724 CG PHE 44 8.219 -9.936-12.179 1.000.00
ATOM 725 CDl PHE 44 7.283 -9.009-12.609 1.000.00
ATOM 726 HDl PHE 44 7.275 -8.706-13.646 1.000.00
ATOM 727 CD2 PHE 44 8.218-10.316-10.847 1.000.00
ATOM 728 HD2PHE 44 8.943-11.038-10.502 1.000.00
ATOM 729 CE1 PHE 44 6.365 -8.472-11.728 1.000.00
ATOM 730 HEI PHE 44 5.641 -7.750-12.075 1.000.00
ATOM 731 CE2PHE 44 7.302 -9.783 -9.961 1.000.00
ATOM 732 HE2 PHE 44 7.312-10.088 -8.925 1.000.00
ATOM 733 CZ PHE 44 6.374 -8.859-10.401 1.000.00
ATOM 734 HZ PHE 44 5.657 -8.441 -9.711 1.000.00
ATOM 735 C PHE 44 9.629-11.929-15.154 1.000.00
ATOM 736 O PHE 44 9.272-11.889-16.331 1.000.00
ATOM 737 N ASN 45 10.869-12.235-14.781 1.000.00
ATOM 738 HN ASN 45 11.091 -12.248-13.827 1.000.00
ATOM 739 CA ASN 45 11.910-12.551 -15.755 1.000.00
ATOM 740 HA ASN 45 12.035-11.689-16.394 1.000.00
ATOM 741 CB ASN 45 13.234-12.834-15.042 1.000.00
ATOM 742 HB1 ASN 45 13.721 -13.673-15.518 1.000.00
ATOM 743 HB2ASN 45 13.035-13.077-14.009 1.000.00
ATOM 744 CG ASN 45 14.177-11.647-15.081 1.000.00
ATOM 745 OD1 ASN 45 15.230-11.696-15.718 1.000.00
ATOM 746 ND2 ASN 45 13.802-10.572-14.399 1.000.00
ATOM 747HD21ASN 45 12.951-10.604-13.915 1.000.00
ATOM 748HD22ASN 45 14.393 -9.789-14.407 1.000.00
ATOM 749 C ASN 45 11.516-13.746-16.619 1.000.00
ATOM 750 O ASN 45 11.904-14.880-16.338 1.000.00
ATOM 751 N ASP 46 10.747-13.486-17.672 1.000.00
ATOM 752 HN ASP 46 10.472-12.561 -17.845 1.000.00
ATOM 753 CA ASP 46 10.304-14.542-18.577 1.000.00
ATOM 754 HA ASP 46 9.612-14.105-19.281 1.000.00
ATOM 755 CB ASP 46 11.497-15.114-19.344 1.000.00
ATOM 756 HB1 ASP 46 11.167-15.958-19.932 1.000.00
ATOM 757 HB2 ASP 46 12.245-15.442-18.639 1.000.00
ATOM 758 CG ASP 46 12.128-14.098-20.275 1.000.00
ATOM 759 OD1 ASP 46 13.070-13.401 -19.842 1.000.00
ATOM 760 OD2 ASP 46 11.681 -13.998-21.437 1.000.00 ATOM 761 C ASP 46 9.593-15.659-17.818 1.000.00
ATOM 7620 ASP 46 9.529-16.796-18.286 1.000.00
ATOM 763 N GLY 47 9.061-15.330-16.645 1.000.00
ATOM 764 HN GLY 47 9.142-14.410-16.321 1.000.00 ATOM 765 CA GLY 47 8.364-16.319-15.844 1.000.00
ATOM 766 HA 1 GLY 47 8.144-17.176-16.464 1.000.00
ATOM 767 HA2GLY 47 7.435-15.893-15.497 1.000.00
ATOM 768 C GLY 47 9.172-16.778-14.643 1.000.00
ATOM 7690 GLY 47 8.834-17.777-14.007 1.000.00 ATOM 770 N SER 48 10.241-16.050-14.329 1.000.00
ATOM 771 HN SER 48 10.463-15.265-14.871 1.000.00
ATOM 772 CA SER 48 11.094-16.394-13.196 1.000.00
ATOM 773 HA SER 48 11.166-17.471-13.151 1.000.00
ATOM 774 CB SER 48 12.494-15.809-13.388 1.000.00 ATOM 775 HB1 SER 48 12.870-15.459-12.438 1.000.00
ATOM 776 HB2SER 48 12.445-14.984-14.082 1.000.00
ATOM 777 OG SER 48 13.388-16.782-13.901 1.000.00
ATOM 778 HG SER 48 14.068-16.968-13.250 1.000.00
ATOM 779 C SER 48 10.491-15.887-11.889 1.000.00 ATOM 780 O SER 48 10.198-14.700-11.749 1.000.00
ATOM 781 N SER 49 10.308-16.796-10.937 1.000.00
ATOM 782 HN SER 49 10.560-17.727-11.110 1.000.00
ATOM 783 CA SER 49 9.738-16.443 -9.641 1.000.00
ATOM 784 HA SER 49 8.876-15.818 -9.818 1.000.00 ATOM 785 CB SER 49 9.292-17.704 -8.900 1.000.00
ATOM 786 HB1 SER 49 8.859-18.400 -9.6041.000.00
ATOM 787 HB2SER 49 8.555-17.441 -8.156 1.000.00
ATOM 788 OG SER 49 10.387-18.331 -8.2541.000.00
ATOM 789 HG SER 49 10.953-18.744 -8.911 1.000.00 ATOM 790 C SER 49 10.741 -15.669 -8.792 1.000.00
ATOM 791 0 SER 49 11.943-15.930 -8.840 1.000.00
ATOM 792 N ARG 50 10.237-14.716 -8.013 1.000.00
ATOM 793 HN ARG 50 9.270-14.557 -8.018 1.000.00
ATOM 794 CA ARG 50 11.086-13.903 -7.149 1.000.00 ATOM 795 HA ARG 50 11.928-14.508 -6.846 1.000.00
ATOM 796 CB ARG 50 11.601-12.679 -7.910 1.000.00
ATOM 797 HB1 ARG 50 12.364-12.997 -8.604 1.000.00
ATOM 798 HB2ARG 50 12.035-11.987 -7.203 1.000.00
ATOM 799 CG ARG 50 10.518-11.952 -8.692 1.000.00 ATOM 800 HG1ARG 50 9.570-12.434 -8.503 1.000.00
ATOM 801 HG2ARG 50 10.748-12.011 -9.745 1.000.00
ATOM 802 CD ARG 50 10.414-10.487 -8.293 1.000.00
ATOM 803 HDl ARG 50 11.152-10.279 -7.532 1.000.00
ATOM 804 HD2ARG 50 9.427-10.308 -7.895 1.000.00 ATOM 805 NE ARG 50 10.638 -9.595 -9.429 1.000.00
ATOM 806 HE ARG 50 11.222 -9.916-10.147 1.000.00
ATOM 807 CZ ARG 50 10.095 -8.384 -9.542 1.000.00
ATOM 808 NH1 ARG 50 9.303 -7.908 -8.589 1.000.00
ATOM 809HH11ARG 50 9.110 -8.457 -7.777 1.000.00 ATOM 810HH12ARG 50 8.897 -7.000 -8.684 1.000.00
ATOM 811 NH2ARG 50 10.347 -7.643-10.613 1.000.00
ATOM 812HH21ARG 50 10.945 -7.993-11.334 1.000.00
ATOM 813HH22ARG 50 9.940 -6.734-10.699 1.000.00
ATOM 814 C ARG 50 10.325-13.459 -5.903 1.000.00 ATOM 815 O ARG 50 9.121 -13.210 -5.9571.000.00
ATOM 816 N GLU 51 11.035-13.361 -4.784 1.000.00
ATOM 817 HN GLU 51 11.992-13.572 -4.803 1.000.00
ATOM 818 CA GLU 51 10.423-12.945 -3.526 1.000.00
ATOM 819 HA GLU 51 9.535-13.541 -3.377 1.000.00 ATOM 820 CB GLU 551 11.386-13.186 -2.362 1.000.00
ATOM 821 HB1 GLU .51 10.935-12.813 -1.454 1.000.00
ATOM 822 HB2 GLU .51 12.301 -12.643 -2.548 1.000.00
ATOM 823 CG GLU 551 11.735-14.651 -2.154 1.000.00
ATOM 824 HG 1 GLU .5 ' 1 11.030-15.257 -2.704 1.000.00
ATOM 825 HG2 GLU .51 11.660-14.880 -1.101 1.000.00
ATOM 826 CD GLU 551 13.136-14.989 -2.623 1.000.00
ATOM 827 OEl GLU - 51 13.316-15.220 -3.837 1.000.00
ATOM 828 OE2 GLU - 51 14.054-15.022 -1.777 1.000.00
ATOM 829 C GLU 5 511 10.026-11.473 -3.576 1.000.00
ATOM 830 O GLU 5 511 10.868-10.587 -3.428 1.000.00
ATOM 831 N LEU 5 522 8.738-11.219 -3.788 1.000.00
ATOM 832 HN LEU 552 8.115-11.967 -3.900 1.000.00
ATOM 833 CA LEU 55i2 8.230 -9.853 -3.860 1.000.00
ATOM 834 HA LEU 552 9.063 -9.202 -4.078 1.000.00
ATOM 835 CB LEU 5 5:2 7.198 -9.731 -4.984 1.000.00
ATOM 836 HB1 LEU 552 6.349-10.348 -4.731 1.000.00
ATOM 837 HB2 LEU 552 7.641 -10.114 -5.892 1.000.00
ATOM 838 CG LEU 55!2 6.692 -8.312 -5.259 1.000.00
ATOM 839 HG LEU 55:2 6.210 -8.292 -6.225 1.000.00
ATOM 840 CDl LEU 552 5.664 -7.900 -4.216 1.000.00
ATOM 841 HDl 1 LEU ;52 5.033 -8.744 -3.980 1.000.00
ATOM 842 HDl 2 LEU .52 5.058 -7.095 -4.607 1.000.00
ATOM 843 HDl 3 LEU .52 6.171 -7.567 -3.323 1.000.00
ATOM 844 CD2 LEU 552 7.848 -7.322 -5.290 1.000.00
ATOM 845 HD21 LEU .52 8.371 -7.351 -4.346 1.000.00
ATOM 846 HD22 LEU ;52 7.464 -6.327 -5.458 1.000.00
ATOM 847 HD23 LEU :52 8.527 -7.586 -6.086 1.000.00
ATOM 848 C LEU 52 7.609 -9.428 -2.533 1.000.00
ATOM 849 O LEU 52 6.602 -9.987 -2.099 1.000.00
ATOM 850 N MET 53 8.220 -8.436 -1.893 1.000.00
ATOM 851 HN MET 5 53 9.020 -8.034 -2.289 1.000.00
ATOM 852 CA MET 553 7.732 -7.933 -0.613 1.000.00
ATOM 853 HA MET 553 7.388 -8.776 -0.037 1.000.00
ATOM 854 CB MET 5 5:3 8.862 -7.238 0.151 1.000.00
ATOM 855 HB 1 MET -53 8.738 -6.169 0.060 1.000.00
ATOM 856 HB2 MET -53 9.806 -7.519 -0.290 1.000.00
ATOM 857 CG MET 553 8.903 -7.589 1.629 1.000.00
ATOM 858 HG 1 MET -53 9.934 -7.717 1.926 1.000.00
ATOM 859 HG2 MET -53 8.369 -8.514 1.781 1.000.00
ATOM 860 SD MET 5 5:3 8.157 -6.317 2.666 1.000.00
ATOM 861 CE MET 5 5:3 9.158 -4.899 2.228 1.00 0.00
ATOM 862 HEI MET 553 8.515 -4.076 1.950 1.00 0.00
ATOM 863 HE2 MET 553 9.797 -5.153 1.395 1.00 0.00
ATOM 864 HE3 MET 553 9.765 -4.612 3.073 1.00 0.00
ATOM 865 C MET 5 533 6.567 -6.966 -0.805 1.00 0.00
ATOM 866 O MET 5 533 6.618 -6.071 ■1.648 1.00 0.00
ATOM 867 N ASN 5544 5.522 -7.153 0.005 1.00 0.00
ATOM 868 HN ASN 5 5'4 5.550 -7.881 0.650 1.00 0.00
ATOM 869 CA ASN 5 5'4 4.341 -6.300 -0.065 1.00 0.00
ATOM 870 HA ASN 5 54* 4.663 -5.315 -0.371 1.00 0.00
ATOM 871 CB ASN 5 5'4 3.328 -6.831 -1.086 1.00 0.00
ATOM 872 HB 1 ASN 554 3.606 -6.483 -2.069 1.00 0.00
ATOM 873 HB2 ASN 554 2.348 -6.451 -0.839 1.00 0.00
ATOM 874 CG ASN 5 54' 3.252 -8.346 -1.121 1.00 0.00
ATOM 875 OD1 ASN 554 4.273 -9.031 -1.189 1.00 0.00
ATOM 876 ND2 ASN 554 2.035 -8.875 -1.085 1.00 0.00
ATOM 877 HD21 ASN :54 1.268 -8.267 -1.039 1.00 0.00
ATOM 878 HD22 ASN :54 1.954 -9.851 -1.106 1.00 0.00 ATOM 879 C ASN 54 3.696 -6.195 1.312 1.00 0.00
ATOM 880 O ASN 54 4.100 -6.888 2.245 1.00 0.00
ATOM 881 N LEU 55 2.702 -5.322 1.443 1.00 0.00
ATOM 882 HN LEU 55 2.423 -4.788 0.669 1.00 0.00
ATOM 883 CA LEU 55 2.025 -5.138 2.722 1.00 0.00
ATOM 884 HA LEU 55 2.276 -5.977 3.353 1.00 0.00
ATOM 885 CB LEU 55 2.507 -3.851 3.395 1.00 0.00
ATOM 886 HB1 LEU 55 2.153 -3.850 4.415 1.00 0.00
ATOM 887 HB2 LEU 55 2.065 -3.013 2.877 1.00 0.00
ATOM 888 CG LEU 55 4.028 -3.662 3.414 1.00 0.00
ATOM 889 HG LEU 55 4.486 -4.418 2.795 1.00 0.00
ATOM 890 CDl LEU 55 4.406 -2.303 2.847 1.00 0.00
ATOM 891 HDl 1 LEU 55 5.471 -2.155 2.949 1.00 0.00
ATOM 892 HD12 LEU 55 3.881 -1.529 3.386 1.00 0.00
ATOM 893 HD13 LEU 55 4.136 -2.261 1.802 1.00 0.00
ATOM 894 CD2 LEU 55 4.570 -3.820 4.827 1.00 0.00
ATOM 895 HD21 LEU 55 3.964 -4.531 5.368 1.00 0.00
ATOM 896 HD22 LEU 55 4.542 -2.865 5.332 1.00 0.00
ATOM 897 HD23 LEU 55 5.590 -4.174 4.783 1.00 0.00
ATOM 898 C LEU 55 0.51 1 -5.096 2.544 1.00 0.00
ATOM 899 O LEU 55 0.005 -4.588 1.543 1.00 0.00
ATOM 900 N THR 56 -0.205 -5.637 3.525 1.00 0.00
ATOM 901 HN THR 56 0.258 -6.026 4.296 1.00 0.00
ATOM 902 CA THR 56 -1.662 -5.667 3.484 1.00 0.00
ATOM 903 HA THR 56 -1.994 -4.849 2.861 1.00 0.00
ATOM 904 CB THR 56 -2.146 -6.986 2.875 1.00 0.00
ATOM 905 HB THR 56 -1.623 -7.154 1.944 1.00 0.00
ATOM 906 OGl THR 56 -3.535 -6.932 2.600 1.00 0.00
ATOM 907 HG1 THR 56 -3.696 -6.315 1.883 1.00 0.00
ATOM 908 CG2 THR 56 -1.901 -8.187 3.765 1.00 0.00
ATOM 909 HG21 THR 56 -2.704 -8.274 4.481 1.00 0.00
ATOM 910 HG22 THR 56 -0.964 -8.062 4.288 1.00 0.00
ATOM 91 1 HG23 THR 56 -1.859 -9.080 3.160 1.00 0.00
ATOM 912 C THR 56 -2.246 -5.489 4.883 1.00 0.00
ATOM 913 O THR 56 -1.598 -5.810 5.880 1.00 0.00
ATOM 914 N GLY 57 -3.471 -4.979 4.951 1.00 0.00
ATOM 915 HN GLY 57 -3.942 -4.743 4.125 1.00 0.00
ATOM 916 CA GLY 57 -4.1 14 .4.774 6.236 1.00 0.00
ATOM 917 HA1 GLY 57 -3.352 -4.615 6.984 1.00 0.00
ATOM 918 HA2 GLY 57 -4.673 -5.661 6.491 1.00 0.00
ATOM 919 C GLY 57 -5.055 -3.585 6.236 1.00 0.00
ATOM 920 O GLY 57 -5.169 -2.873 5.239 1.00 0.00
ATOM 921 N THR 58 -5.730 -3.373 7.361 1.00 0.00
ATOM 922 HN THR 58 -5.592 -3.977 8.121 1.00 0.00
ATOM 923 CA THR 58 -6.667 -2.264 7.498 1.00 0.00
ATOM 924 HA THR 58 -7.057 -2.034 6.518 1.00 0.00
ATOM 925 CB THR 58 -7.826 -2.662 8.416 1.00 0.00
ATOM 926 HB THR 58 -8.513 -1.832 8.487 1.00 0.00
ATOM 927 OGl THR 58 -7.354 -2.959 9.717 1.00 0.00
ATOM 928 HG1 THR 58 -6.838 -3.768 9.694 1.00 0.00
ATOM 929 CG2 THR 58 -8.602 -3.865 7.923 1.00 0.00
ATOM 930 HG21 THR 58 -9.354 -4.131 8.653 1.00 0.00
ATOM 931 HG22 THR 58 -7.928 -4.696 7.782 1.00 0.00
ATOM 932 HG23 THR 58 -9.081 -3.626 6.985 1.00 0.00
ATOM 933 C THR 58 -5.967 -1.029 8.056 1.00 0.00
ATOM 934 O THR 58 -5.532 -1.020 9.206 1.00 0.00
ATOM 935 N ILE 59 - 5.859 0.013 7.237 1.00 0.00
ATOM 936 HN ILE 59 -6.223 -0.050 6.329 1.00 0.00
ATOM 937 CA ILE 59 -5.206 1.247 7.661 1.00 0.00 ATOM 938 HA ILE 59 -4.505 0.995 8.441 1.00 0.00
ATOM 939 CB ILE 59 -4.423 1.902 6.505 1.00 0.00
ATOM 940 HB ILE 59 -3.923 2.775 6.893 1.00 0.00
ATOM 941 CG I ILE 59 -5.370 2.329 5.381 1.00 0.00
ATOM 942 HG 1 1 ILE 59 -6.047 3.081 5.759 1.00 0.00
ATOM 943 HG 12 ILE 59 -5.939 1.472 5.053 1.00 0.00
ATOM 944 CG2 ILE 59 -3.362 0.946 5.979 1.00 0.00
ATOM 945 HG21 ILE 59 -3.820 0.000 5.732 1.00 0.00
ATOM 946 HG22 ILE 59 -2.608 0.794 6.737 1.00 0.00
ATOM 947 HG23 ILE 59 -2.905 1.367 5.096 1.00 0.00
ATOM 948 CDl ILE 59 -4.659 2.905 4.175 1.00 0.00
ATOM 949 HDl 1 ILE 59 -4.972 2.378 3.286 1.00 0.00
ATOM 950 HDl 2 ILE 59 -3.592 2.797 4.301 1.00 0.00
ATOM 951 HD13 ILE 59 -4.906 3.952 4.078 1.00 0.00
ATOM 952 C ILE 59 - -6.216 2.247 8.220 1.00 0.00
ATOM 953 O ILE 59 -7.355 2.318 7.758 1.00 0.00
ATOM 954 N PRO 60 -5.808 3.032 9.234 1.00 0.00
ATOM 955 CA PRO 60 -6.680 4.027 9.865 1.00 0.00
ATOM 956 HA PRO 60 -7.624 3.594 10.159 1.00 0.00
ATOM 957 CB PRO 60 -5.897 4.444 1 1.1 1 1 1.00 0.00
ATOM 958 HB 1 PRO 60 -6.200 3.837 1 1.951 1.00 0.00
ATOM 959 HB2 PRO 60 -6.083 5.486 1 1.325 1.00 0.00
ATOM 960 CG PRO 60 -4.471 4.205 10.755 1.00 0.00
ATOM 961 HG 1 PRO 60 -3.899 4.003 1 1.648 1.00 0.00
ATOM 962 HG2 PRO 60 -4.072 5.067 10.240 1.00 0.00
ATOM 963 CD PRO 60 -4.466 3.005 9.849 1.00 0.00
ATOM 964 HDl PRO 60 -4.324 2.101 10.422 1.00 0.00
ATOM 965 HD2 PRO 60 -3.697 3.103 9.098 1.00 0.00
ATOM 966 C PRO 60 -6.936 5.234 8.971 1.00 0.00
ATOM 967 O PRO 60 -6.014 5.969 8.619 1.00 0.00
ATOM 968 N VAL 61 -8.199 5.431 8.613 1.00 0.00
ATOM 969 HN VAL 61 -8.886 4.809 8.930 1.00 0.00
ATOM 970 CA VAL 61 -8.591 6.550 7.765 1.00 0.00
ATOM 971 HA VAL 61 -7.730 7.191 7.644 1.00 0.00
ATOM 972 CB VAL 61 -9.028 6.058 6.364 1.00 0.00
ATOM 973 HB VAL 61 -9.525 5.107 6.480 1.00 0.00
ATOM 974 CGI VAL 61 -10.004 7.028 5.710 1.00 0.00
ATOM 975 HG 1 1 VAL , 61 -9.804 8.029 6.058 1.00 0.00
ATOM 976 HG 12 VAL 61 -11.015 6.752 5.970 1.00 0.00
ATOM 977 HG 13 VAL 61 -9.886 6.989 4.637 1.00 0.00
ATOM 978 CG2 VAL 61 -7.81 1 5.850 5.476 1.00 0.00
ATOM 979 HG21 VAL . 61 -8.124 5.441 4.527 1.00 0.00
ATOM 980 HG22 VAL . 61 -7.128 5.166 5.956 1.00 0.00
ATOM 981 HG23 VAL . 61 -7.319 6.798 5.314 1.00 0.00
ATOM 982 C VAL 61 -9.725 7.353 8.413 1.00 0.00
ATOM 983 O VAL 61 -10.843 6.857 8.553 1.00 0.00
ATOM 984 N PRO 62 -9.451 8.610 8.813 1.00 0.00
ATOM 985 CA PRO 62 - 10.457 9.476 9.440 1.00 0.00
ATOM 986 HA PRO 62 -10.919 9.000 10.290 1.00 0.00
ATOM 987 CB PRO 62 -9.649 10.686 9.910 1.00 0.00
ATOM 988 HB 1 PRO 62 -9.368 10.552 10.942 1.00 0.00
ATOM 989 HB2 PRO 62 - 10.245 1 1.581 9.806 1.00 0.00
ATOM 990 CG PRO 62 -8.456 10.719 9.019 1.00 0.00
ATOM 991 HG 1 PRO 62 -7.623 1 1.168 9.539 1.00 0.00
ATOM 992 HG2 PRO 62 -8.683 1 1.275 8.122 1.00 0.00
ATOM 993 CD PRO 62 -8.147 9.286 8.680 1.00 0.00
ATOM 994 HDl PRO 62 -7.431 8.879 9.377 1.00 0.00
ATOM 995 HD2 PRO 62 -7.776 9.210 7.669 1.00 0.00
ATOM 996 C PRO ι 62 -1 1.535 9.908 8.460 1.00 0.00 ATOM 997 O PRO 62 - ■1 1.236 10.435 7.388 1.00 0.00
ATOM 998 N TYR ( 53 - -12.792 9.688 8.830 1.00 0.00
ATOM 999 HN TYR 63 -12.978 9.267 9.703 1.00 0.00
ATOM 1000 CA TYR 63 -13.906 10.063 7.979 1.00 0.00
ATOM 1001 HA TYR 63 -13.513 10.370 7.021 1.00 0.00
ATOM 1002 CB TYR 63 - 14.834 8.864 7.785 1.00 0.00
ATOM 1003 HB 1 TYR 63 -15.560 8.852 8.584 1.00 0.00
ATOM 1004 HB2 TYR 63 -14.249 7.957 7.827 1.00 0.00
ATOM 1005 CG TYR 63 -15.580 8.872 6.470 1.00 0.00
ATOM 1006 CDl TYR 63 -16.968 8.827 6.437 1.00 0.00
ATOM 1007 HD l TYR 63 -17.515 8.784 7.368 1.00 0.00
ATOM 1008 CD2 TYR 63 -14.897 8.926 5.262 1.00 0.00
ATOM 1009 HD2 TYR 63 -13.817 8.961 5.271 1.00 0.00
ATOM 1010 CE1 TYR 63 -17.654 8.835 5.237 1.00 0.00
ATOM 101 1 HEI TYR 63 -18.733 8.799 5.233 1.00 0.00
ATOM 1012 CE2 TYR 63 -15.575 8.935 4.058 1.00 0.00
ATOM 1013 HE2 TYR 63 -15.026 8.978 3.129 1.00 0.00
ATOM 1014 CZ TYR 63 -16.953 8.889 4.051 1.00 0.00
ATOM 1015 OH TYR 63 -17.633 8.899 2.855 1.00 0.00
ATOM 1016 HH TYR 63 -17.697 9.800 2.530 1.00 0.00
ATOM 1017 C TYR 63 -14.662 1 1.225 8.605 1.00 0.00
ATOM 1018 O TYR 63 -14.195 1 1.825 9.573 1.00 0.00
ATOM 1019 N ARG 64 -15.835 1 1.535 8.069 1.00 0.00
ATOM 1020 HN ARG 64 -16.169 1 1.020 7.307 1.00 0.00
ATOM 1021 CA ARG 64 -16.644 12.617 8.609 1.00 0.00
ATOM 1022 HA ARG 64 -16.086 13.534 8.501 1.00 0.00
ATOM 1023 CB ARG 64 -17.958 12.738 7.835 1.00 0.00
ATOM 1024 HB 1 ARG 64 - 17.741 13.045 6.823 1.00 0.00
ATOM 1025 HB2 ARG 64 -18.572 13.491 8.307 1.00 0.00
ATOM 1026 CG ARG 64 -18.752 1 1.443 7.780 1.00 0.00
ATOM 1027 HG1 ARG 64 -18.555 10.872 8.676 1.00 0.00
ATOM 1028 HG2 ARG 64 -18.440 10.877 6.915 1.00 0.00
ATOM 1029 CD ARG 64 -20.246 1 1.708 7.682 1.00 0.00
ATOM 1030 HDl ARG 64 -20.676 1 1.014 6.975 1.00 0.00
ATOM 1031 HD2 ARG 64 -20.397 12.718 7.331 1.00 0.00
ATOM 1032 NE ARG 64 -20.916 1 1.549 8.970 1.00 0.00
ATOM 1033 HE ARG 64 -20.397 1 1.160 9.705 1.00 0.00
ATOM 1034 CZ ARG 64 -22.180 1 1.899 9.197 1.00 0.00
ATOM 1035 NH1 ARG 64 -22.913 12.429 8.226 1.00 0.00
ATOM 1036 HH 1 1 ARG 64 -22.518 12.567 7.318 1.00 0.00
ATOM 1037 HH12 ARG 64 -23.862 12.690 8.402 1.00 0.00
ATOM 1038 NH2 ARG 64 -22.712 1 1.720 10.398 1.00 0.00
ATOM 1039 HH21 ARG 64 -22.164 1 1.321 1 1.133 1.00 0.00
ATOM 1040 HH22 ARG 64 -23.662 1 1.983 10.569 1.00 0.00
ATOM 1041 C ARG 64 -16.930 12.385 10.091 1.00 0.00
ATOM 1042 O ARG 64 -17.331 13.302 10.807 1.00 0.00
ATOM 1043 N GLY 65 -16.726 1 1.147 10.545 1.00 0.00
ATOM 1044 HN GLY 65 -16.415 10.452 9.932 1.00 0.00
ATOM 1045 CA GLY 65 - 16.973 10.818 1 1.933 1.00 0.00
ATOM 1046 HA 1 GLY 65 - 17.698 10.018 1 1.973 1.00 0.00
ATOM 1047 HA2 GLY 65 - 17.389 1 1.684 12.425 1.00 0.00
ATOM 1048 C GLY . 65 -15.727 10.384 12.688 1.00 0.00
ATOM 1049 O GLY 65 -15.384 10.981 13.709 1.00 0.00
ATOM 1050 N ASN 66 -15.050 9.337 12.209 1.00 0.00
ATOM 1051 HN ASN 66 -15.357 8.888 1 1.392 1.00 0.00
ATOM 1052 CA ASN 66 -13.854 8.845 12.887 1.00 0.00
ATOM 1053 HA ASN 66 -13.331 9.699 13.289 1.00 0.00
ATOM 1054 CB ASN 66 -14.247 7.922 14.041 1.00 0.00
ATOM 1055 HB 1 ASN 66 -14.869 8.469 14.735 1.00 0.00 ATOM 1056 HB2 ASN 66 -13.354 7.590 14.550 1.00 0.00
ATOM 1057 CG ASN 66 -15.012 6.700 13.571 1.00 0.00
ATOM 1058 OD1 ASN 66 -16.237 6.643 13.675 1.00 0.00
ATOM 1059 ND2 ASN 66 -14.290 5.715 13.049 1.00 0.00
ATOM 1060 HD21 ASN 66 -13.318 5.830 12.998 1.00 0.00
ATOM 1061 HD22 ASN 66 -14.759 4.913 12.737 1.00 0.00
ATOM 1062 C ASN 66 -12.920 8.109 1 1.932 1.00 0.00
ATOM 1063 O ASN 66 -13.179 8.016 10.733 1.00 0.00
ATOM 1064 N THR 67 -11.837 7.575 12.488 1.00 0.00
ATOM 1065 HN THR 67 -1 1.699 7.678 13.452 1.00 0.00
ATOM 1066 CA THR 67 -10.853 6.829 11.714 1.00 0.00
ATOM 1067 HA THR 67 -10.776 7.285 10.742 1.00 0.00
ATOM 1068 CB THR 67 -9.488 6.890 12.401 1.00 0.00
ATOM 1069 HB THR 67 -9.355 5.997 12.995 1.00 0.00
ATOM 1070 OG l THR 67 -9.409 8.013 13.261 1.00 0.00
ATOM 1071 HG 1 THR 67 -9.478 8.818 12.743 1 .00 0.00
ATOM 1072 CG2 THR 67 -8.334 6.975 1 1.429 1.00 0.00
ATOM 1073 HG21 THR 67 -8.487 7.808 10.760 1.00 0.00
ATOM 1074 HG22 THR 67 -8.279 6.061 10.858 1.00 0.00
ATOM 1075 HG23 THR 67 -7.413 7.1 15 1 1.974 1.00 0.00
ATOM 1076 C THR 67 -1 1.281 5.377 1 1.536 1.00 0.00
ATOM 1077 O THR 67 -1 1.396 4.630 12.508 1.00 0.00
ATOM 1078 N TYR 68 -1 1.507 4.980 10.289 1.00 0.00
ATOM 1079 HN TYR 68 -1 1.392 5.619 9.556 1.00 0.00
ATOM 1080 CA TYR 68 -1 1.912 3.613 9.988 1.00 0.00
ATOM 1081 HA TYR 68 -12.352 3.194 10.880 1.00 0.00
ATOM 1082 CB TYR 68 -12.949 3.587 8.862 1.00 0.00
ATOM 1083 HB1 TYR 68 -12.934 2.614 8.393 1.00 0.00
ATOM 1084 HB2 TYR 68 -12.696 4.336 8.128 1.00 0.00
ATOM 1085 CG TYR 68 -14.360 3.851 9.336 1.00 0.00
ATOM 1086 CDl TYR 68 -14.747 5.119 9.749 1.00 0.00
ATOM 1087 HDl TYR 68 -14.026 5.922 9.724 1.00 0.00
ATOM 1088 CD2 TYR 68 -15.302 2.831 9.374 1.00 0.00
ATOM 1089 HD2 TYR 68 -15.017 1.839 9.055 1.00 0.00
ATOM 1090 CE1 TYR 68 -16.035 5.363 10.189 1.00 0.00
ATOM 1091 HEI TYR 68 -16.317 6.356 10.506 1.00 0.00
ATOM 1092 CE2 TYR 68 - 16.592 3.068 9.81 1 1.00 0.00
ATOM 1093 HE2 TYR 68 -17.31 1 2.262 9.834 1.00 0.00
ATOM 1094 CZ TYR 68 -16.953 4.335 10.218 1.00 0.00
ATOM 1095 OH TYR 68 -18.235 4.575 10.654 1.00 0.00
ATOM 1096 HH TYR 68 -18.212 5.174 1 1.404 1.00 0.00
ATOM 1097 C TYR 68 -10.706 2.770 9.595 1.00 0.00
ATOM 1098 O TYR 68 -9.648 3.300 9.258 1.00 0.00
ATOM 1099 N ASN 69 - 10.876 1.457 9.639 1.00 0.00
ATOM 1 100 HN ASN 69 -1 1.746 1.097 9.913 1.00 0.00
ATOM 1 101 CA ASN 69 -9.803 0.535 9.286 1.00 0.00
ATOM 1 102 HA ASN 69 -8.869 1.072 9.360 1.00 0.00
ATOM 1 103 CB ASN 69 -9.772 -0.658 10.249 1.00 0.00
ATOM 1 104 HB1 ASN 69 -8.745 -0.881 10.499 1.00 0.00
ATOM 1 105 HB2 ASN 69 -10.21 1 -1.514 9.763 1.00 0.00
ATOM 1 106 CG ASN 69 -10.533 -0.398 1 1.538 1.00 0.00
ATOM 1 107 OD1 ASN 69 -10.029 0.259 12.448 1.00 0.00
ATOM 1 108 ND2 ASN 69 -1 1.755 -0.915 1 1.620 1.00 0.00
ATOM 1 109 HD21 ASN 69 -12.094 -1.429 10.857 1.00 0.00
ATOM 1 1 10 HD22 ASN 69 -12.267 -0.763 12.439 1.00 0.00
ATOM 1 1 1 1 C ASN ι 69 -9.976 0.047 7.852 1.00 0.00
ATOM 1 1 12 O ASN 69 -10.421 - 1.075 7.615 1.00 0.00
ATOM 1 1 13 N ILE 70 - 9.635 0.903 6.898 1.00 0.00
ATOM 1 1 14 HN ILE 70 -9.299 1.789 7.140 1.00 0.00 ATOM 1115 CA ILE 70 -9.761 0.581 5.497 1.000.00
ATOM 1116 HA ILE 70 -10.729 0.132 5.342 1.000.00
ATOM 1117 CB ILE 70 -9.693 1.876 4.676 1.000.00
ATOM 1118 HB ILE 70 -10.276 2.625 5.191 1.000.00
ATOM 1119 CGI ILE 70 -10.282 1.663 3.297 1.000.00
ATOM 1120HG11 ILE 70 -10.302 0.606 3.074 1.000.00
ATOM 1121 HG12ILE 70 -9.663 2.169 2.584 1.000.00
ATOM 1122 CG2 ILE 70 -8.263 2.390 4.582 1.000.00
ATOM 1123HG21 ILE 70 -7.674 1.711 3.982 1.000.00
ATOM 1124HG22ILE 70 -7.840 2.455 5.573 1.000.00
ATOM 1125HG23ILE 70 -8.261 3.369 4.125 1.000.00
ATOM 1126 CDl ILE 70 -11.689 2.198 3.164 1.000.00
ATOM 1127 HDl 1 ILE 70 -11.689 3.262 3.349 1.000.00
ATOM 1128HD12ILE 70 -12.326 1.708 3.883 1.000.00
ATOM 1129HD13ILE 70 -12.056 2.006 2.170 1.000.00
ATOM 1130 C ILE 70 -8.670 -0.394 5.040 1.000.00
ATOM 1131 O ILE 70 -7.481 -0.135 5.224 1.000.00
ATOM 1132 N PRO 71 -9.060 -1.535 4.439 1.000.00
ATOM 1133 CA PRO 71 -8.106 -2.540 3.962 1.000.00
ATOM 1134 HA PRO 71 -7.335 -2.736 4.693 1.000.00
ATOM 1135 CB PRO 71 -8.976 -3.782 3.787 1.000.00
ATOM 1136 HB1 PRO 71 -8.997 -4.345 4.708 1.000.00
ATOM 1137 HB2 PRO 71 -8.579 -4.395 2.991 1.000.00
ATOM 1138 CG PRO 71 -10.324 -3.247 3.446 1.000.00
ATOM 1139 HG1 PRO 71 -11.087 -3.938 3.775 1.000.00
ATOM 1140 HG2 PRO 71 -10.397 -3.089 2.380 1.000.00
ATOM 1141 CD PRO 71 -10.457 -1.937 4.179 1.000.00
ATOM 1142 HDl PRO 71 -10.995 -2.076 5.105 1.000.00
ATOM 1143 HD2 PRO 71 -10.957 -1.208 3.558 1.000.00
ATOM 1144 C PRO 71 -7.463 -2.147 2.636 1.000.00
ATOM 1145 O PRO 71 -8.134 -1.643 1.736 1.000.00
ATOM 1146 N ILE 72 -6.158 -2.379 2.520 1.000.00
ATOM 1147 HN ILE 72 -5.674 -2.781 3.271 1.000.00
ATOM 1148 CA ILE 72 -5.431 -2.044 1.301 1.000.00
ATOM 1149 HA ILE 72 -6.128 -2.108 0.477 1.000.00
ATOM 1150 CB ILE 72 -4.886 -0.594 1.359 1.000.00
ATOM 1151 HB ILE 72 -5.375 -0.088 2.177 1.000.00
ATOM 1152 CGI ILE 72 -5.210 0.146 0.062 1.000.00
ATOM 1153HG11 ILE 72 -6.106 -0.274 -0.371 1.000.00
ATOM 1154HG12ILE 72 -4.390 0.026 -0.629 1.000.00
ATOM 1155 CG2 ILE 72 -3.384 -0.562 1.625 1.000.00
ATOM 1156HG21 ILE 72 -2.851 -0.779 0.711 1.000.00
ATOM 1157HG22ILE 72 -3.133 -1.301 2.372 1.000.00
ATOM 1158HG23ILE 72 -3.103 0.418 1.981 1.000.00
ATOM 1159 CDl ILE 72 -5.438 1.627 0.261 1.000.00
ATOM 1160 HDl 1 ILE 72 -5.028 2.170 -0.577 1.000.00
ATOM 1161 HD12ILE 72 -4.949 1.946 1.170 1.000.00
ATOM 1162HD13ILE 72 -6.497 1.822 0.334 1.000.00
ATOM 1163 C ILE 72 -4.291 -3.028 1.045 1.000.00
ATOM 1164 0 ILE 72 -4.055 -3.944 1.832 1.000.00
ATOM 1165 N CYS 73 -3.591 -2.825 -0.065 1.000.00
ATOM 1166 HN CYS 73 -3.832 -2.076 -0.649 1.000.00
ATOM 1167 CA CYS 73 -2.475 -3.682 -0.439 1.000.00
ATOM 1168 HA CYS 73 -1.940 -3.945 0.462 1.000.00
ATOM 1169 CB CYS 73 -3.000 -4.961 -1.101 1.000.00
ATOM 1170 HB1 CYS 73 -3.732 -4.692 -1.849 1.000.00
ATOM 1171 HB2 CYS 73 -3.475 -5.573 -0.349 1.000.00
ATOM 1172 SG CYS 73 -1.731 -5.972 -1.903 1.000.00
ATOM 1173 HG CYS 73 -1.823 -6.872 -1.582 1.000.00 ATOM 1 174 C CYS 73 -1.526 -2.939 -1.379 1.00 0.00
ATOM 1 175 O CYS 73 -1.967 -2.231 -2.284 1.00 0.00
ATOM 1 176 N LEU 74 -0.224 -3.097 -1.155 1.00 0.00
ATOM 1177 HN LEU 74 0.070 -3.669 -0.415 1.00 0.00
ATOM 1 178 CA LEU 74 0.775 -2.429 -1.983 1.00 0.00
ATOM 1 179 HA LEU 74 0.293 -2.103 -2.892 1.00 0.00
ATOM 1 180 CB LEU 74 1.330 ■1.208 -1.245 1.00 0.00
ATOM 1 181 HB1 LEU 74 2.401 -1.188 - 1.376 1.00 0.00
ATOM 1 182 HB2 LEU 74 1.1 15 -1.322 -0.202 1.00 0.00
ATOM 1 183 CG LEU 74 0.774 0.136 -1.690 1.00 0.00
ATOM 1 184 HG LEU 74 1.326 0.927 -1.202 1.00 0.00
ATOM 1 185 CDl LEU 74 0.943 0.301 -3.183 1.00 0.00
ATOM 1 186 HDl 1 LEU 74 0.016 0.055 -3.676 1.00 0.00
ATOM 1 187 HD12 LEU 74 1.724 -0.362 -3.529 1.00 0.00
ATOM 1 188 HD13 LEU 74 1.212 1.321 -3.403 1.00 0.00
ATOM 1 189 CD2 LEU 74 -0.688 0.263 -1.293 1.00 0.00
ATOM 1 190 HD21 LEU 74 -1.312 -0.072 -2.107 1.00 0.00
ATOM 1 191 HD22 LEU 74 -0.91 1 1.295 - 1.068 1.00 0.00
ATOM 1192 HD23 LEU 74 -0.877 -0.345 -0.420 1.00 0.00
ATOM 1193 C LEU 74 1.920 -3.373 -2.339 1.00 0.00
ATOM 1194 O LEU 74 2.558 -3.951 -1.458 1.00 0.00
ATOM 1 195 N TRP 75 2.186 -3.512 -3.634 1.00 0.00
ATOM 1 196 HN TRP 75 1.650 -3.015 -4.289 1.00 0.00
ATOM 1197 CA TRP 75 3.267 -4.370 -4.103 1.00 0.00
ATOM 1198 HA TRP 75 3.358 -5.189 -3.407 1.00 0.00
ATOM 1 199 CB TRP 75 2.942 -4.934 -5.486 1.00 0.00
ATOM 1200 HB1 TRP 75 3.860 -5.138 -6.015 1.00 0.00
ATOM 1201 HB2 TRP 75 2.367 -4.207 -6.037 1.00 0.00
ATOM 1202 CG TRP 75 2.145 -6.200 -5.421 1.00 0.00
ATOM 1203 CDl TRP 75 0.891 -6.343 -4.906 1.00 0.00
ATOM 1204 HDl TRP 75 0.315 -5.536 -4.482 1.00 0.00
ATOM 1205 CD2 TRP 75 2.546 -7.501 -5.868 1.00 0.00
ATOM 1206 NE1 TRP 75 0.478 -7.647 -5.018 1.00 0.00
ATOM 1207 HEI TRP 75 -0.391 -7.995 -4.725 1.00 0.00
ATOM 1208 CE2 TRP 75 1.478 -8.380 -5.602 1.00 0.00
ATOM 1209 CE3 TRP 75 3.700 -8.007 -6.471 1.00 0.00
ATOM 1210 HE3 TRP 75 4.541 -7.367 -6.692 1.00 0.00
ATOM 121 1 CZ2 TRP 75 1.531 -9.734 -5.918 1.00 0.00
ATOM 1212 HZ2 TRP 75 0.708 -10.403 -5.71 1 1.00 0.00
ATOM 1213 CZ3 TRP 75 3.752 -9.354 -6.782 1.00 0.00
ATOM 1214 HZ3 TRP 75 4.638 -9.764 -7.244 1.00 0.00
ATOM 1215 CH2 TRP 75 2.674 -10.203 -6.505 1.00 0.00
ATOM 1216 HH2 TRP 75 2.759 -1 1.248 -6.765 1.00 0.00
ATOM 1217 C TRP ' 75 4.588 -3.610 -4.131 1.00 0.00
ATOM 1218 O TRP 75 4.778 -2.709 -4.948 1.00 0.00
ATOM 1219 N LEU 76 5.495 -3.971 -3.230 1.00 0.00
ATOM 1220 HN LEU 76 5.286 -4.692 -2.600 1.00 0.00
ATOM 1221 CA LEU 76 6.793 -3.313 -3.152 1.00 0.00
ATOM 1222 HA LEU 76 6.687 -2.328 -3.579 1.00 0.00
ATOM 1223 CB LEU 76 7.228 -3.175 -1.691 1.00 0.00
ATOM 1224 HB1 LEU 76 8.158 -3.706 -1.559 1.00 0.00
ATOM 1225 HB2 LEU 76 6.476 -3.641 -1.069 1.00 0.00
ATOM 1226 CG LEU 76 7.426 - 1.737 -1.209 1.00 0.00
ATOM 1227 HG LEU 76 8.171 -1.257 -1.826 1.00 0.00
ATOM 1228 CDl LEU 76 6.131 -0.948 -1.339 1.00 0.00
ATOM 1229 HDl 1 LEU 76 5.559 -1.329 -2.172 1.00 0.00
ATOM 1230 HD12 LEU 76 6.360 0.095 - 1.506 1.00 0.00
ATOM 1231 HD13 LEU 76 5.555 -1.049 -0.431 1.00 0.00
ATOM 1232 CD2 LEU 76 7.921 - 1.720 0.229 1.00 0.00 ATOM 1233 HD21 LEU 76 7.519 -0.856 0.738 1.00 0.00
ATOM 1234 HD22 LEU 76 9.000 - 1.673 0.238 1.00 0.00
ATOM 1235 HD23 LEU 76 7.595 -2.618 0.733 1.00 0.00
ATOM 1236 C LEU 76 7.847 -4.079 -3.946 1.00 0.00 ATOM 1237 0 LEU 76 8.313 -5.135 -3.520 1.00 0.00
ATOM 1238 N LEU 77 8.221 -3.537 -5.101 1.00 0.00
ATOM 1239 HN LEU 77 7.814 -2.692 -5.386 1.00 0.00
ATOM 1240 CA LEU 77 9.223 -4.165 -5.953 1.00 0.00
ATOM 1241 HA LEU 77 8.972 -5.21 1 -6.047 1.00 0.00 ATOM 1242 CB LEU 77 9.216 -3.526 -7.342 1.00 0.00
ATOM 1243 HB1 LEU 77 9.890 -2.683 -7.330 1.00 0.00
ATOM 1244 HB2 LEU 77 8.219 -3.165 -7.541 1.00 0.00
ATOM 1245 CG LEU 77 9.631 -4.457 -8.486 1.00 0.00
ATOM 1246 HG LEU 77 9.903 -5.419 -8.076 1.00 0.00 ATOM 1247 CDl LEU 77 8.476 -4.669 -9.452 1.00 0.00
ATOM 1248 HDl 1 LEU 77 7.997 -3.722 -9.654 1.00 0.00
ATOM 1249 HDl 2 LEU 77 7.759 -5.348 -9.014 1.00 0.00
ATOM 1250 HD13 LEU 77 8.850 -5.087 - 10.375 1.00 0.00
ATOM 1251 CD2 LEU 77 10.842 -3.897 -9.217 1.00 0.00 ATOM 1252 HD21 LEU 77 10.513 -3.255 -10.020 1.00 0.00
ATOM 1253 HD22 LEU 77 1 1.426 -4.71 1 -9.622 1.00 0.00
ATOM 1254 HD23 LEU 77 1 1.448 -3.328 -8.527 1.00 0.00
ATOM 1255 C LEU 77 10.612 -4.047 -5.337 1.00 0.00
ATOM 1256 O LEU 77 10.794 -3.393 -4.310 1.00 0.00 ATOM 1257 N ASP 78 1 1.590 -4.682 -5.973 1.00 0.00
ATOM 1258 HN ASP 78 1 1.382 -5.183 -6.789 1.00 0.00
ATOM 1259 CA ASP 78 12.966 -4.646 -5.490 1.00 0.00
ATOM 1260 HA ASP 78 12.968 -4.999 -4.471 1.00 0.00
ATOM 1261 CB ASP 78 13.858 -5.561 -6.334 1.00 0.00 ATOM 1262 HB1 ASP 78 14.775 -5.752 -5.797 1.00 0.00
ATOM 1263 HB2 ASP 78 14.089 -5.069 -7.266 1.00 0.00
ATOM 1264 CG ASP 78 13.198 -6.891 -6.645 1.00 0.00
ATOM 1265 OD1 ASP 78 13.679 -7.925 -6.137 1.00 0.00
ATOM 1266 OD2 ASP 78 12.201 -6.898 -7.397 1.00 0.00 ATOM 1267 C ASP 78 13.51 1 -3.222 -5.516 1.00 0.00
ATOM 1268 O ASP 78 13.960 -2.699 -4.496 1.00 0.00
ATOM 1269 N THR 79 13.470 -2.600 -6.691 1.00 0.00
ATOM 1270 HN THR 79 13.102 -3.071 -7.467 1.00 0.00
ATOM 1271 CA THR 79 13.960 -1.237 -6.854 1.000.00 ATOM 1272 HA THR 79 13.399 -0.600 -6.187 1.000.00
ATOM 1273 CB THR 79 15.443 ■ -1.161 -6.485 1.000.00
ATOM 1274 HB THR 79 15.546 • -1.303 -5.419 1.000.00
ATOM 1275 OGl THR 79 15.980 0.106 -6.820 1.000.00
ATOM 1276 HG 1 THR 79 16.011 0.199 -7.775 1.000.00 ATOM 1277 CG2 THR 79 16.282 -2.214 -7.176 1.000.00
ATOM 1278 HG21 THR 79 17.240 -1.792 -7.443 1.000.00
ATOM 1279 HG22 THR 79 15.775 -2.549 -8.069 1.00 0.00
ATOM 1280 HG23 THR 79 16.430 -3.050 -6.510 1.00 0.00
ATOM 1281 C THR 79 13.755 -0.752 -8.287 1.00 0.00 ATOM 1282 O THR 79 14.669 -0.207 -8.906 1.00 0.00
ATOM 1283 N TYR 80 12.551 -0.957 -8.810 1.00 0.00
ATOM 1284 HN TYR 80 1 1.863 -1.397 -8.269 1.00 0.00
ATOM 1285 CA TYR 80 12.228 -0.542 -10.170 1.00 0.00
ATOM 1286 HA TYR 80 12.788 0.356 -10.382 1.00 0.00 ATOM 1287 CB TYR 80 12.639 -1.631 -1 1.165 1.00 0.00
ATOM 1288 HB1 TYR 80 1 1.751 -2.108 - 1 1.555 1.00 0.00
ATOM 1289 HB2 TYR 80 13.240 -2.367 -10.653 1.00 0.00
ATOM 1290 CG TYR 80 13.441 -1.1 12 -12.338 1.00 0.00
ATOM 1291 CDl TYR 80 13.031 -1.350 -13.644 1.00 0.00 ATOM 1292 HDl TYR 80 12.127 -1.915 -13.815 1.00 0.00
ATOM 1293 CD2 TYR 80 14.607 -0.383 - 12.138 1.00 0.00
ATOM 1294 HD2 TYR 80 14.939 -0.190 -1 1.129 1.00 0.00
ATOM 1295 CE1 TYR 80 13.761 -0.877 -14.718 1.00 0.00
ATOM 1296 HEI TYR 80 13.426 - 1.072 - 15.726 1.00 0.00
ATOM 1297 CE2 TYR 80 15.342 0.094 -13.207 1.00 0.00
ATOM 1298 HE2 TYR 80 16.246 0.658 - 13.032 1.00 0.00
ATOM 1299 CZ TYR 80 14.915 -0.156 - 14.494 1.00 0.00
ATOM 1300 OH TYR 80 15.644 0.318 - 15.561 1.00 0.00
ATOM 1301 HH TYR 80 15.1 1 1 0.939 -16.062 1.00 0.00
ATOM 1302 C TYR 80 10.735 -0.242 -10.310 1.00 0.00
ATOM 1303 O TYR 80 9.906 -0.886 -9.667 1.00 0.00
ATOM 1304 N PRO 81 10.367 0.744 -1 1.151 1.00 0.00
ATOM 1305 CA PRO 81 11.314 1.541 -1 1.938 1.00 0.00
ATOM 1306 HA PRO 81 12.045 0.915 -12.428 1.00 0.00
ATOM 1307 CB PRO 81 10.431 2.227 -12.996 1.00 0.00
ATOM 1308 HB1 PRO 81 10.817 2.009 -13.981 1.00 0.00
ATOM 1309 HB2 PRO 81 10.439 3.295 -12.834 1.00 0.00
ATOM 1310 CG PRO 81 9.056 1.663 -12.817 1.00 0.00
ATOM 1311 HG 1 PRO 81 8.901 0.851 -13.511 1.00 0.00
ATOM 1312 HG2 PRO 81 8.320 2.437 -12.974 1.00 0.00
ATOM 1313 CD PRO 81 8.987 1.161 -1 1.405 1.00 0.00
ATOM 1314 HDl PRO 81 8.310 0.323 -1 1.331 1.00 0.00
ATOM 1315 HD2 PRO 81 8.690 1.954 - 10.733 1.00 0.00
ATOM 1316 C PRO 81 12.031 2.587 -1 1.090 1.00 0.00
ATOM 1317 O PRO 81 13.163 2.971 -1 1.384 1.00 0.00
ATOM 1318 N TYR 82 1 1.361 3.046 -10.039 1.00 0.00
ATOM 1319 HN TYR 82 10.467 2.709 -9.860 1.00 0.00
ATOM 1320 CA TYR 82 1 1.921 4.046 -9.150 1.00 0.00
ATOM 1321 HA TYR 82 12.968 3.821 -9.015 1.00 0.00
ATOM 1322 CB TYR 82 1 1.788 5.430 -9.774 1.00 0.00
ATOM 1323 HB1 TYR 82 10.771 5.776 -9.657 1.00 0.00
ATOM 1324 HB2 TYR 82 12.028 5.371 -10.825 1.00 0.00
ATOM 1325 CG TYR 82 12.700 6.442 -9.143 1.00 0.00
ATOM 1326 CDl TYR 82 12.482 6.878 -7.846 1.00 0.00
ATOM 1327 HDl TYR 82 11.638 6.488 -7.296 1.00 0.00
ATOM 1328 CD2 TYR 82 13.786 6.950 -9.837 1.00 0.00
ATOM 1329 HD2 TYR 82 13.965 6.618 -10.849 1.00 0.00
ATOM 1330 CE1 TYR 82 13.320 7.796 -7.255 1.00 0.00
ATOM 1331 HEI TYR 82 13.131 8.1 19 -6.244 1.00 0.00
ATOM 1332 CE2 TYR 82 14.631 7.870 -9.257 1.00 0.00
ATOM 1333 HE2 TYR 82 15.469 8.252 -9.815 1.00 0.00
ATOM 1334 CZ TYR 82 14.396 8.292 -7.964 1.00 0.00
ATOM 1335 OH TYR 82 15.239 9.210 -7.379 1.00 0.00
ATOM 1336 HH TYR 82 15.458 8.922 -6.489 1.00 0.00
ATOM 1337 C TYR 82 1 1.230 4.020 -7.788 1.00 0.00
ATOM 1338 O TYR 82 1 1.869 4.210 -6.754 1.00 0.00
ATOM 1339 N ASN 83 9.921 3.780 -7.797 1.00 0.00
ATOM 1340 HN ASN 83 9.467 3.637 -8.652 1.00 0.00
ATOM 1341 CA ASN 83 9.143 3.726 -6.565 1.00 0.00
ATOM 1342 HA ASN 83 9.803 3.420 -5.768 1.00 0.00
ATOM 1343 CB ASN 83 8.568 5.106 -6.237 1.00 0.00
ATOM 1344 HB 1 ASN 83 7.599 5.202 -6.704 1.00 0.00
ATOM 1345 HB2 ASN 83 9.227 5.867 -6.626 1.00 0.00
ATOM 1346 CG ASN 83 8.404 5.330 -4.746 1.00 0.00
ATOM 1347 OD1 ASN 83 7.446 4.854 -4.138 1.00 0.00
ATOM 1348 ND2 ASN 83 9.340 6.058 -4.149 1.00 0.00
ATOM 1349 HD21 ASN 83 10.075 6.406 -4.696 1.00 0.00
ATOM 1350 HD22 ASN 83 9.258 6.217 -3.185 1.00 0.00 ATOM 1351 C ASN 83 8.01 1 2.708 - 6.694 1.00 0.00
ATOM 1352 O ASN 83 7.379 2.605 - -7.745 1.00 0.00
ATOM 1353 N PRO 84 7.742 1.937 - 5.626 1.00 0.00
ATOM 1354 C A PRO 84 6.685 0.921 -5.627 1.00 0.00
ATOM 1355 HA PRO 84 6.941 0.091 -6.269 1.00 0.00
ATOM 1356 CB PRO 84 6.633 0.440 -4.168 1.00 0.00
ATOM 1357 HB 1 PRO 84 7.073 -0.543 -4.099 1.00 0.00
ATOM 1358 HB2 PRO 84 5.606 0.402 -3.836 1.00 0.00
ATOM 1359 CG PRO 84 7.420 1.440 -3.388 1.00 0.00
ATOM 1360 HG 1 PRO 84 7.904 0.956 -2.553 1.00 0.00
ATOM 1361 HG2 PRO 84 6.769 2.229 -3.041 1.00 0.00
ATOM 1362 CD PRO 84 8.443 1.988 -4.337 1.00 0.00
ATOM 1363 HDl PRO 84 9.322 1.365 -4.351 1.00 0.00
ATOM 1364 HD2 PRO 84 8.699 3.003 -4.072 1.00 0.00
ATOM 1365 C PRO 84 5.331 1.486 - 6.050 1.00 0.00
ATOM 1366 O PRO 84 4.687 2.208 - 5.289 1.00 0.00
ATOM 1367 N PRO 85 4.877 1.165 - 7.276 1.00 0.00
ATOM 1368 CA PRO 85 3.599 1.643 -7.792 1.00 0.00
ATOM 1369 HA PRO 85 3.406 2.658 -7.481 1.00 0.00
ATOM 1370 CB PRO 85 3.822 1.606 -9.304 1.00 0.00
ATOM 1371 HB 1 PRO 85 4.255 2.540 -9.628 1.00 0.00
ATOM 1372 HB2 PRO 85 2.880 1.447 -9.808 1.00 0.00
ATOM 1373 CG PRO 85 4.763 0.466 -9.524 1.00 0.00
ATOM 1374 HG 1 PRO 85 5.414 0.689 -10.357 1.00 0.00
ATOM 1375 HG2 PRO 85 4.205 -0.437 -9.721 1.00 0.00
ATOM 1376 CD PRO 85 5.574 0.31 1 -8.258 1.00 0.00
ATOM 1377 HDl PRO 85 6.585 0.653 -8.416 1.00 0.00
ATOM 1378 HD2 PRO 85 5.573 -0.720 -7.936 1.00 0.00
ATOM 1379 C PRO 85 2.427 l 3.753 - 7.357 1.00 0.00
ATOM 1380 O PRO 85 1.959 0.873 - 6.227 1.00 0.00
ATOM 1381 N ILE 86 1.970 -0.135 -8.253 1.00 0.00
ATOM 1382 HN ILE 86 2.400 - •0.179 - -9.127 1.00 0.00
ATOM 1383 CA ILE 86 0.858 - 1.063 - ■7.986 1.00 0.00
ATOM 1384 HA ILE 86 0.180 - 1.005 - ■8.824 1.00 0.00
ATOM 1385 CB ILE 86 1.360 - 2.516 - 7.886 1.00 0.00
ATOM 1386 HB ILE 86 1.756 - 2.666 - ■6.895 1.00 0.00
ATOM 1387 CGI ILE 86 2.465 -2.777 -8.913 1.00 0.00
ATOM 1388 HG 1 1 ILE 86 3.281 -2.091 -8.736 1.00 0.00
ATOM 1389 HG 12 ILE 86 2.072 -2.614 -9.905 1.00 0.00
ATOM 1390 CG2 ILE 86 . 0.207 -3.485 -8.088 1.00 0.00
ATOM 1391 HG21 ILE 86 -0.677 -3.097 -7.606 1.00 0.00
ATOM 1392 HG22 ILE 86 0.462 -4.442 -7.658 1.00 0.00
ATOM 1393 HG23 ILE 86 0.018 -3.604 -9.145 1.00 0.00
ATOM 1394 CDl ILE 86 3.020 -4.184 -8.859 1.00 0.00
ATOM 1395 HDl 1 ILE 86 2.244 -4.864 -8.542 1.00 0.00
ATOM 1396 HDl 2 ILE 86 3.840 -4.221 -8.158 1.00 0.00
ATOM 1397 HDl 3 ILE 86 3.371 -4.470 -9.840 1.00 0.00
ATOM 1398 C ILE 86 0.081 -0.722 -6.713 1.00 0.00
ATOM 1399 O ILE 86 0.584 -0.895 -5.603 1.00 0.00
ATOM 1400 N CYS 87 -1.148 - 0.241 - 6.883 1.00 0.00
ATOM 1401 HN CYS 87 - 1.499 -0.125 -7.787 1.00 0.00
ATOM 1402 CA CYS 87 -1.986 0.129 -5.751 1.00 0.00
ATOM 1403 HA CYS 87 -1.576 -0.326 -4.863 1.00 0.00
ATOM 1404 CB CYS 87 -1.992 1.648 -5.581 1.00 0.00
ATOM 1405 HB1 CYS 87 -2.196 1.884 -4.552 1.00 0.00
ATOM 1406 HB2 CYS 87 -2.774 2.062 -6.196 1.00 0.00
ATOM 1407 SG CYS 87 -0.444 2.464 -6.039 1.00 0.00
ATOM 1408 HG CYS 87 0.001 1.912 -6.688 1.00 0.00
ATOM 1409 C CYS 87 -3.418 - 0.355 - 5.946 1.00 0.00 ATOM 1410 O CYS 87 -4.082 0.022 -6.912 1.00 0.00
ATOM 141 1 N PHE 88 -3.895 -1.178 -5.019 1.00 0.00
ATOM 1412 HN PHE 88 -3.325 -1.436 -4.265 1.00 0.00
ATOM 1413 CA PHE 88 -5.256 -1.690 -5.094 1.00 0.00 ATOM 1414 HA PHE 88 -5.856 -0.944 -5.592 1.00 0.00
ATOM 1415 CB PHE 88 -5.326 -2.991 -5.899 1.00 0.00
ATOM 1416 HB1 PHE 88 -5.707 -2.771 -6.883 1.00 0.00
ATOM 1417 HB2 PHE 88 -6.003 -3.665 -5.405 1.00 0.00
ATOM 1418 CG PHE 88 -4.018 -3.708 -6.059 1.00 0.00 ATOM 1419 CDl PHE 88 -3.622 -4.175 -7.303 1.00 0.00
ATOM 1420 HDl PHE 88 -4.260 -4.009 -8.158 1.00 0.00
ATOM 1421 CD2 PHE 88 -3.191 -3.927 -4.971 1.00 0.00
ATOM 1422 HD2 PHE 88 -3.489 -3.569 -3.997 1.00 0.00
ATOM 1423 CE1 PHE 88 -2.427 -4.845 -7.458 1.00 0.00 ATOM 1424 HEI PHE 88 -2.131 -5.204 -8.432 1.00 0.00
ATOM 1425 CE2 PHE 88 -1.993 -4.596 -5.120 1.00 0.00
ATOM 1426 HE2 PHE 88 -1.357 -4.759 -4.263 1.00 0.00
ATOM 1427 CZ PHE 88 -1.61 1 -5.056 -6.366 1.00 0.00
ATOM 1428 HZ PHE 88 -0.677 -5.580 -6.487 1.00 0.00 ATOM 1429 C PHE 88 -5.835 -1.925 -3.706 1.00 0.00
ATOM 1430 O PHE 88 -5.106 -2.198 -2.753 1.00 0.00
ATOM 1431 N VAL 89 -7.155 -1.828 -3.607 1.00 0.00
ATOM 1432 HN VAL 89 -7.681 -1.617 -4.408 1.00 0.00
ATOM 1433 CA VAL 89 -7.842 -2.042 -2.344 1.00 0.00 ATOM 1434 HA VAL 89 -7.128 -1.893 -1.547 1.00 0.00
ATOM 1435 CB VAL 89 -8.996 -1.036 -2.156 1.00 0.00
ATOM 1436 HB VAL 89 -8.612 -0.046 -2.355 1.00 0.00
ATOM 1437 CGI VAL 89 -10.127 -1.308 -3.139 1.00 0.00
ATOM 1438 HG1 1 VAL 89 -9.776 -1.969 -3.917 1.00 0.00 ATOM 1439 HG 12 VAL 89 -10.454 -0.378 -3.578 1.00 0.00
ATOM 1440 HG13 VAL 89 -10.952 -1.771 -2.619 1.00 0.00
ATOM 1441 CG2 VAL 89 -9.504 -1.071 -0.723 1.00 0.00
ATOM 1442 HG21 VAL 89 -8.819 -0.532 -0.085 1.00 0.00
ATOM 1443 HG22 VAL 89 -9.574 -2.097 -0.391 1.00 0.00 ATOM 1444 HG23 VAL 89 -10.479 -0.610 -0.676 1.00 0.00
ATOM 1445 C VAL 89 -8.384 -3.465 -2.263 1.00 0.00
ATOM 1446 O VAL 89 -9.042 -3.939 -3.188 1.00 0.00
ATOM 1447 N LYS 90 -8.099 -4.143 -1.157 1.00 0.00
ATOM 1448 HN LYS 90 -7.566 -3.713 -0.457 1.00 0.00 ATOM 1449 CA LYS 90 -8.558 -5.515 -0.965 1.00 0.00
ATOM 1450 HA LYS 90 -8.712 -5.951 -1.940 1.00 0.00
ATOM 1451 CB LYS 90 -7.497 -6.332 -0.221 1.00 0.00
ATOM 1452 HB1 LYS 90 -6.646 -6.470 -0.872 1.00 0.00
ATOM 1453 HB2 LYS 90 -7.911 -7.299 0.023 1.00 0.00 ATOM 1454 CG LYS 90 -7.012 -5.680 1.065 1.00 0.00
ATOM 1455 HG1 LYS 90 -7.482 -4.714 1.168 1.00 0.00
ATOM 1456 HG2 LYS 90 -5.941 -5.556 1.012 1.00 0.00
ATOM 1457 CD LYS 90 -7.348 -6.526 2.284 1.00 0.00
ATOM 1458 HDl LYS 90 -8.410 -6.720 2.293 1.00 0.00 ATOM 1459 HD2 LYS 90 -7.071 -5.982 3.175 1.00 0.00
ATOM 1460 CE LYS 90 -6.603 -7.851 2.265 1.00 0.00
ATOM 1461 HEI LYS 90 -5.576 -7.668 1.987 1.00 0.00
ATOM 1462 HE2 LYS 90 -7.063 -8.498 1.533 1.00 0.00
ATOM 1463 NZ LYS 90 -6.634 -8.525 3.592 1.00 0.00 ATOM 1464 HZ1 LYS 90 -7.614 -8.756 3.853 1.00 0.00
ATOM 1465 HZ2 LYS 90 -6.233 -7.900 4.320 1.00 0.00
ATOM 1466 HZ3 LYS 90 -6.078 -9.403 3.561 1.00 0.00
ATOM 1467 C LYS 90 -9.876 -5.546 -0.192 1.00 0.00
ATOM 1468 O LYS 90 -9.898 -5.304 1.015 1.00 0.00 ATOM 1469 N PRO 91 -1 1.000 -5.843 -0.875 1.00 0.00
ATOM 1470 CA PRO 91 -12.315 -5.900 -0.243 1.00 0.00
ATOM 1471 HA PRO 91 -12.459 -5.073 0.436 1.00 0.00
ATOM 1472 CB PRO 91 -13.300 -5.778 -1.419 1.00 0.00
ATOM 1473 HB1 PRO 91 -13.914 -4.900 -1.280 1.00 0.00
ATOM 1474 HB2 PRO 91 - 13.930 -6.654 - 1.452 1.00 0.00
ATOM 1475 CG PRO 91 - 12.467 -5.663 -2.660 1.00 0.00
ATOM 1476 HG1 PRO 91 - 12.431 -4.632 -2.981 1.00 0.00
ATOM 1477 HG2 PRO 91 - 12.887 -6.281 -3.439 1.00 0.00
ATOM 1478 CD PRO 91 -1 1.089 -6.145 -2.306 1.00 0.00
ATOM 1479 HDl PRO 91 -10.344 -5.601 -2.864 1.00 0.00
ATOM 1480 HD2 PRO 91 -1 1.000 -7.207 -2.485 1.00 0.00
ATOM 1481 C PRO 91 - 12.536 -7.210 0.506 1.00 0.00
ATOM 1482 O PRO 91 -12.025 -8.259 0.1 13 1.00 0.00
ATOM 1483 N THR 92 -13.300 -7.137 1.589 1.00 0.00
ATOM 1484 HN THR 92 -13.675 -6.269 1.848 1.00 0.00
ATOM 1485 CA THR 92 -13.596 -8.308 2.406 1.00 0.00
ATOM 1486 HA THR 92 -12.687 -8.879 2.517 1.00 0.00
ATOM 1487 CB THR 92 -14.080 -7.864 3.786 1.00 0.00
ATOM 1488 HB THR 92 -14.415 -8.731 4.336 1.00 0.00
ATOM 1489 OGl THR 92 -15.170 -6.967 3.667 1.00 0.00
ATOM 1490 HG1 THR 92 -15.622 -6.898 4.512 1.00 0.00
ATOM 1491 CG2 THR 92 -13.010 -7.175 4.604 1.00 0.00
ATOM 1492 HG21 THR 92 -13.279 -6.139 4.747 1.00 0.00
ATOM 1493 HG22 THR 92 -12.066 -7.232 4.084 1.00 0.00
ATOM 1494 HG23 THR 92 -12.923 -7.659 5.565 1.00 0.00
ATOM 1495 C THR 92 -14.658 -9.183 1.750 1.00 0.00
ATOM 1496 O THR 92 -14.368 -10.263 1.236 1.00 0.00
ATOM 1497 N SER 93 -15.892 -8.699 1.785 1.00 0.00
ATOM 1498 HN SER 93 - 16.045 -7.833 2.218 1.00 0.00
ATOM 1499 CA SER 93 - 17.030 -9.407 1.21 1 1.00 0.00
ATOM 1500 HA SER 93 - 16.880 -9.477 0.144 1.00 0.00
ATOM 1501 CB SER 93 -17.142 -10.816 1.800 1.00 0.00
ATOM 1502 HB 1 SER 93 -17.898 -10.822 2.572 1.00 0.00
ATOM 1503 HB2 SER 93 - 16.192 - 1 1.103 2.226 1.00 0.00
ATOM 1504 OG SER 93 - 17.499 -1 1.759 0.805 1.00 0.00
ATOM 1505 HG SER 93 - 18.212 -1 1.404 0.268 1.00 0.00
ATOM 1506 C SER 93 -18.304 -8.621 1.484 1.00 0.00
ATOM 1507 O SER 93 -19.178 -8.506 0.626 1.00 0.00
ATOM 1508 N SER 94 -18.380 -8.057 2.685 1.00 0.00
ATOM 1509 HN SER 94 - 17.635 -8.173 3.313 1.00 0.00
ATOM 1510 CA SER 94 -19.522 -7.246 3.085 1.00 0.00
ATOM 151 1 HA SER 94 -20.381 -7.576 2.520 1.00 0.00
ATOM 1512 CB SER 94 -19.804 -7.419 4.578 1.00 0.00
ATOM 1513 HB1 SER 94 -20.190 -6.494 4.979 1.00 0.00
ATOM 1514 HB2 SER 94 -18.888 -7.678 5.088 1.00 0.00
ATOM 1515 OG SER 94 -20.755 -8.446 4.802 1.00 0.00
ATOM 1516 HG SER 94 -21.549 -8.068 5.190 1.00 0.00
ATOM 1517 C SER 94 ■ -19.256 -5.774 2.769 1.00 0.00
ATOM 1518 O SER 94 -20.032 -4.895 3.144 1.00 0.00
ATOM 1519 N MET 95 -18.142 -5.518 2.083 1.00 0.00
ATOM 1520 HN MET 95 - 17.563 -6.263 1.822 1.00 0.00
ATOM 1521 CA MET 95 -17.747 -4.165 1.717 1.00 0.00
ATOM 1522 HA MET 95 - 18.091 -3.490 2.489 1.00 0.00
ATOM 1523 CB MET 95 -16.221 -4.087 1.624 1.00 0.00
ATOM 1524 HB1 MET 95 -15.930 -4.181 0.588 1.00 0.00
ATOM 1525 HB2 MET 95 -15.797 -4.909 2.183 1.00 0.00
ATOM 1526 CG MET 95 - 15.637 -2.796 2.166 1.00 0.00
ATOM 1527 HG1 MET 95 -16.266 -2.438 2.964 1.00 0.00 ATOM 1528 HG2 MET ' 95 -15.617 -2.071 1.376 1.00 0.00
ATOM 1529 SD MET 95 -13.962 -3.002 2.794 1.00 0.00
ATOM 1530 CE MET 95 -14.302 -3.380 4.508 1.00 0.00
ATOM 1531 HEI MET 95 -15.353 -3.234 4.706 1.00 0.00
ATOM 1532 HE2 MET 95 -13.721 -2.726 5.142 1.00 0.00
ATOM 1533 HE3 MET 95 -14.037 -4.405 4.709 1.00 0.00
ATOM 1534 C MET 95 - 18.365 -3.760 0.382 1.00 0.00
ATOM 1535 O MET 95 -18.920 -4.593 -0.334 1.00 0.00
ATOM 1536 N THR 96 -18.267 -2.475 0.054 1.00 0.00
ATOM 1537 HN THR 96 -17.812 -1.859 0.667 1.00 0.00
ATOM 1538 CA THR 96 -18.820 -1.963 -1.198 1.00 0.00
ATOM 1539 HA THR 96 -18.950 -2.798 -1.870 1.00 0.00
ATOM 1540 CB THR 96 -20.181 -1.310 -0.949 1.00 0.00
ATOM 1541 HB THR 96 -20.044 -0.243 -0.850 1.00 0.00
ATOM 1542 OG l THR 96 -20.759 -1.796 0.249 1.00 0.00
ATOM 1543 HG 1 THR 96 -21.575 -1.322 0.427 1.00 0.00
ATOM 1544 CG2 THR 96 -21.172 -1.548 -2.067 1.00 0.00
ATOM 1545 HG21 THR : 96 -22.160 - 1.258 -1.740 1.00 0.00
ATOM 1546 HG22 THR . 96 -21.173 -2.596 -2.330 1.00 0.00
ATOM 1547 HG23 THR . 96 -20.891 -0.961 -2.929 1.00 0.00
ATOM 1548 C THR 96 -17.874 -0.961 -1.850 1.00 0.00
ATOM 1549 O THR 96 -17.523 0.058 - 1.255 1.00 0.00
ATOM 1550 N ILE 97 - 17.471 -1.258 -3.080 1.00 0.00
ATOM 1551 HN ILE 97 -17.791 -2.083 -3.500 1.00 0.00
ATOM 1552 CA ILE 97 -16.570 -0.388 -3.823 1.00 0.00
ATOM 1553 HA ILE 97 -15.731 -0.156 -3.183 1.00 0.00
ATOM 1554 CB ILE 97 -16.031 -1.102 -5.088 1.00 0.00
ATOM 1555 HB ILE 97 - 16.745 - 1.863 -5.365 1.00 0.00
ATOM 1556 CG I ILE 97 - 14.687 -1.771 -4.779 1.00 0.00
ATOM 1557 HG 1 1 ILE 97 - 14.853 -2.599 -4.104 1.00 0.00
ATOM 1558 HG 12 ILE 97 -14.036 -1.053 -4.304 1.00 0.00
ATOM 1559 CG2 ILE 97 -15.893 -0.133 -6.260 1.00 0.00
ATOM 1560 HG21 ILE 97 -16.871 0.217 -6.555 1.00 0.00
ATOM 1561 HG22 ILE 97 -15.426 -0.637 -7.092 1.00 0.00
ATOM 1562 HG23 ILE 97 -15.285 0.709 -5.961 1.00 0.00
ATOM 1563 CD l ILE 97 -13.970 -2.306 -6.003 1.00 0.00
ATOM 1564 HDl 1 ILE 97 -13.541 -1.483 -6.555 1.00 0.00
ATOM 1565 HD 12 ILE 97 - 14.673 -2.833 -6.631 1.00 0.00
ATOM 1566 HD 13 ILE 97 - 13.186 -2.981 -5.695 1.00 0.00
ATOM 1567 C ILE 97 - 17.266 0.915 -4.210 1.00 0.00
ATOM 1568 O ILE 97 - 18.353 0.904 -4.788 1.00 0.00
ATOM 1569 N LYS 98 -16.628 2.033 -3.885 1.00 0.00
ATOM 1570 HN LYS 98 -15.764 1.972 -3.427 1.00 0.00
ATOM 1571 CA LYS 98 -17.176 3.348 -4.196 1.00 0.00
ATOM 1572 HA LYS 98 -18.224 3.225 -4.426 1.00 0.00
ATOM 1573 CB LYS 98 -17.037 4.277 -2.990 1.00 0.00
ATOM 1574 HB 1 LYS 98 -15.998 4.545 -2.878 1.00 0.00
ATOM 1575 HB2 LYS 98 -17.361 3.750 -2.105 1.00 0.00
ATOM 1576 CG LYS 98 -17.850 5.556 -3.108 1.00 0.00
ATOM 1577 HG 1 LYS 98 -18.174 5.857 -2.122 1.00 0.00
ATOM 1578 HG2 LYS 98 -18.712 5.368 -3.730 1.00 0.00
ATOM 1579 CD LYS 98 -17.034 6.682 -3.724 1.00 0.00
ATOM 1580 HDl LYS 98 -16.398 6.272 -4.495 1.00 0.00
ATOM 1581 HD2 LYS 98 - 16.426 7.135 -2.956 1.00 0.00
ATOM 1582 CE LYS 98 -17.929 7.747 -4.336 1.00 0.00
ATOM 1583 HEI LYS 98 -18.730 7.967 -3.645 1.00 0.00
ATOM 1584 HE2 LYS 98 - 18.344 7.366 -5.257 1.00 0.00
ATOM 1585 NZ LYS 98 - 17.182 9.002 -4.625 1.00 0.00
ATOM 1586 HZ1 LYS 98 - 16.347 9.072 -4.009 1.00 0.00 ATOM 1587 HZ2 LYS 98 -17.791 9.828 -4.459 1.00 0.00
ATOM 1588 HZ3 LYS 98 -16.869 9.011 -5.617 1.00 0.00
ATOM 1589 C LYS 98 -16.474 3.957 -5.405 1.00 0.00
ATOM 1590 O LYS 98 -15.307 4.343 -5.328 1.00 0.00 ATOM 1591 N THR 99 -17.190 4.041 -6.520 1.00 0.00
ATOM 1592 HN THR 99 -18.1 15 3.717 -6.520 1.00 0.00
ATOM 1593 CA THR 99 -16.632 4.604 -7.744 1.00 0.00
ATOM 1594 HA THR 99 -15.665 4.152 -7.904 1.00 0.00
ATOM 1595 CB THR 99 -17.534 4.278 -8.935 1.00 0.00 ATOM 1596 HB THR 99 -17.141 4.769 -9.814 1.00 0.00
ATOM 1597 OGl THR 99 -18.851 4.750 -8.713 1.00 0.00
ATOM 1598 HG 1 THR 99 -19.277 4.21 1 -8.043 1.00 0.00
ATOM 1599 CG2 THR 99 -17.617 2.796 -9.231 1.00 0.00
ATOM 1600 HG21 THR 99 -17.813 2.650 -10.283 1.00 0.00 ATOM 1601 HG22 THR 99 -18.415 2.357 -8.652 1.00 0.00
ATOM 1602 HG23 THR 99 -16.680 2.325 -8.971 1.00 0.00
ATOM 1603 C THR 99 -16.453 6.1 14 -7.620 1.00 0.00
ATOM 1604 O THR 99 -17.366 6.826 -7.201 1.00 0.00
ATOM 1605 N GLY 100 -15.271 6.595 -7.990 1.00 0.00 ATOM 1606 HN GLY 100 -14.583 5.979 -8.317 1.00 0.00
ATOM 1607 CA GLY 100 -14.990 8.017 -7.915 1.00 0.00
ATOM 1608 HA 1 GLY 100 -14.755 8.273 -6.893 1.00 0.00
ATOM 1609 HA2 GLY 100 -15.870 8.564 -8.219 1.00 0.00
ATOM 1610 C GLY 100 -13.829 8.427 -8.802 1.00 0.00 ATOM 161 1 O GLY 100 -13.244 7.596 -9.495 1.00 0.00
ATOM 1612 N LYS 101 -13.494 9.71 1 -8.781 1.00 0.00
ATOM 1613 HN LYS 101 -13.996 10.328 -8.209 1.00 0.00
ATOM 1614 CA LYS 101 -12.395 10.228 -9.590 1.00 0.00
ATOM 1615 HA LYS 101 -12.657 10.091 -10.629 1.00 0.00 ATOM 1616 CB LYS 101 -12.197 1 1.721 -9.322 1.00 0.00
ATOM 1617 HB1 LYS 101 -13.088 12.250 -9.624 1.00 0.00
ATOM 1618 HB2 LYS 101 -1 1.363 12.073 -9.91 1 1.00 0.00
ATOM 1619 CG LYS 101 -11.921 12.045 -7.863 1.00 0.00
ATOM 1620 HG1 LYS 101 -10.883 1 1.838 -7.649 1.00 0.00 ATOM 1621 HG2 LYS 101 -12.550 11.425 -7.242 1.00 0.00
ATOM 1622 CD LYS 101 -12.208 13.505 -7.553 1.00 0.00
ATOM 1623 HDl LYS 101 -12.1 19 14.080 -8.463 1.00 0.00
ATOM 1624 HD2 LYS 101 -1 1.488 13.858 -6.830 1.00 0.00
ATOM 1625 CE LYS 101 -13.607 13.690 -6.986 1.00 0.00 ATOM 1626 HEI LYS 101 -13.563 14.410 -6.182 1.00 0.00
ATOM 1627 HE2 LYS 101 -13.954 12.743 -6.601 1.00 0.00
ATOM 1628 NZ LYS 101 -14.565 14.173 -8.018 1.00 0.00
ATOM 1629 HZ1 LYS 101 -14.123 14.915 -8.597 1.00 0.00
ATOM 1630 HZ2 LYS 101 -15.414 14.564 -7.562 1.00 0.00 ATOM 1631 HZ3 LYS 101 -14.849 13.387 -8.638 1.00 0.00
ATOM 1632 C LYS 101 -1 1.096 9.473 -9.309 1.00 0.00
ATOM 1633 0 LYS 101 -10.190 9.449 -10.143 1.00 0.00
ATOM 1634 N HIS 102 -1 1.007 8.867 -8.128 1.00 0.00
ATOM 1635 HN HIS 102 -1 1.756 8.927 -7.501 1.00 0.00 ATOM 1636 CA HIS 102 -9.814 8.124 -7.738 1.00 0.00
ATOM 1637 HA HIS 102 -8.981 8.523 -8.297 1.00 0.00
ATOM 1638 CB HIS 102 -9.542 8.318 -6.247 1.00 0.00
ATOM 1639 HB1 HIS 102 -8.764 7.636 -5.938 1.00 0.00
ATOM 1640 HB2 HIS 102 -10.443 8.102 -5.693 1.00 0.00 ATOM 1641 CG HIS 102 -9.107 9.706 -5.894 1.00 0.00
ATOM 1642 ND1 HIS 102 -9.991 10.713 -5.570 1.00 0.00
ATOM 1643 HDl HIS 102 -10.967 10.629 -5.536 1.00 0.00
ATOM 1644 CD2 HIS 102 -7.871 10.254 -5.817 1.00 0.00
ATOM 1645 HD2 HIS 102 -6.933 9.751 -6.007 1.00 0.00 ATOM 1646 CE1 HIS 102 -9.319 11.821 -5.310 1.000.00 ATOM 1647 HEI HIS 102 -9.749 12.770 -5.028 1.000.00 ATOM 1648 NE2 HIS 102 -8.031 11.568 -5.453 1.000.00 ATOM 1649 HE2 HIS 102 -7.306 12.194 -5.244 1.000.00 ATOM 1650 C HIS 102 ■9.943 6.633 -8.051 1.000.00 ATOM 1651 0 HIS 102 -8.966 5.890 -7.958 1.000.00 ATOM 1652 N VAL 103 -11.145 6.195 -8.419 1.000.00 ATOM 1653 HN VAL 103 -11.891 6.828 -8.476 1.000.00 ATOM 1654 CA VAL 103 -11.378 4.789 -8.738 1.000.00 ATOM 1655 HA VAL 103 -10.497 4.411 -9.239 1.000.00 ATOM 1656 CB VAL 103 -11.604 3.952 -7.462 1.000.00 ATOM 1657 HB VAL 103 -12.500 4.308 -6.976 1.000.00 ATOM 1658 CGI VAL 103 -11.801 2.483 -7.808 1.000.00 ATOM 1659 HG11 VAL 103 -11.618 1.879 -6.932 1.00 0.00 ATOM 1660 HG12 VAL 103 -11.111 2.202 -8.590 1.00 0.00 ATOM 1661 HG13 VAL 103 -12.814 2.326 -8.148 1.000.00 ATOM 1662 CG2 VAL 103 -10.440 4.124 6.499 1.000.00 ATOM 1663 HG21 VAL 103 -10.547 3.429 -5.679 1.000.00 ATOM 1664 HG22 VAL 103 -10.435 5.134 -6.118 1.000.00 ATOM 1665 HG23 VAL 103 -9.513 3.929 -7.018 1.000.00 ATOM 1666 C VAL 103 -12.583 4.625 -9.658 1.000.00 ATOM 1667 O VAL 103 -13.629 5.235 -9.446 1.000.00 ATOM 1668 N ASP 1 104 -12.427 3.798-10.684 1.000.00 ATOM 1669 HN ASP 104 -11.573 3.343-10.809 1.000.00 ATOM 1670 CA ASP 104 -13.485 3.553-11.642 1.000.00 ATOM 1671 HA ASP 104 -14.040 4.466-11.777 1.000.00 ATOM 1672 CB ASP 104 -12.865 3.140-12.968 1.000.00 ATOM 1673 HB1 ASP 104 -13.643 3.014-13.689 1.000.00 ATOM 1674 HB2 ASP 104 -12.347 2.201 -12.836 1.000.00 ATOM 1675 CG ASP 104 -11.878 4.164-13.493 1.000.00 ATOM 1676 OD1 ASP 104 -10.670 4.024-13.211 1.000.00 ATOM 1677 OD2 ASP 104 -12.314 5.107-14.187 1.000.00 ATOM 1678 C ASP 104 -14.426 2.461-11.154 1.000.00 ATOM 1679 O ASP 1 104 -15.612 2.699-10.939 1.000.00 ATOM 1680 N ALA 105 -13.885 1.262-10.990 1.000.00 ATOM 1681 HN ALA 105 -12.934 1.143-11.185 1.000.00 ATOM 1682 CA ALA 105 -14.660 0.115-10.531 1.000.00 ATOM 1683 HA ALA 105 -14.922 0.284 -9.498 1.000.00 ATOM 1684 CB ALA 105 -15.946 -0.022-11.336 1.000.00 ATOM 1685 HB1 ALA 105 -16.352 -1.013-11.198 1.000.00 ATOM 1686 HB2 ALA 105 -15.735 0.138-12.383 1.000.00 ATOM 1687 HB3 ALA 105 -16.663 0.711 -10.996 1.000.00 ATOM 1688 C ALA 105 -13.832 -1.159-10.632 1.000.00 ATOM 1689 0 ALA 105 -14.327 -2.207-11.047 1.000.00 ATOM 1690 N ASN 106 -12.562 -1.054-10.258 1.000.00 ATOM 1691 HN ASN 106 -12.226 -0.188 -9.946 1.000.00 ATOM 1692 CA ASN 106 -11.648 -2.188-10.314 1.000.00 ATOM 1693 HA ASN 106 -12.199 -3.047-10.661 1.000.00 ATOM 1694 CB ASN 106 -10.521 -1.889-11.297 1.000.00 ATOM 1695 HB1 ASN 106 -9.579 -2.159-10.844 1.000.00 ATOM 1696 HB2 ASN 106 -10.519 -0.831 -11.515 1.000.00 ATOM 1697 CG ASN 106 -10.668 -2.650-12.601 1.000.00 ATOM 1698 OD1 ASN 106 -10.722 -2.055-13.677 1.000.00 ATOM 1699 ND2 ASN 106 -10.733 -3.973-12.509 1.000.00 ATOM 1700 HD21 ASN 106 -10.683 -4.378-11.618 1.000.00 ATOM 1701 HD22ASN 106 -10.827 -4.490-13.336 1.000.00 ATOM 1702 C ASN i 106 -11.052 -2.498 -8.946 1.000.00 ATOM 1703 0 ASN 106 -10.129 -3.306 -8.836 1.000.00 ATOM 1704 N GLY 107 -11.562 -1.847 -7.910 1.000.00 ATOM 1705 HN GLY 107 - 12.286 -1.204 -8.048 1.00 0.00
ATOM 1706 CA GLY 107 -1 1.036 -2.073 -6.581 1.00 0.00
ATOM 1707 HA 1 GLY 107 -1 1.1 14 -3.122 -6.342 1.00 0.00
ATOM 1708 HA2 GLY 107 -1 1.618 -1.504 -5.870 1.00 0.00
ATOM 1709 C GLY 107 -9.586 -1.654 -6.479 1.00 0.00
ATOM 1710 O GLY 107 -8.778 -2.329 -5.841 1.00 0.00
ATOM 171 1 N LYS 108 -9.254 -0.538 -7.120 1.00 0.00
ATOM 1712 HN LYS 108 -9.943 -0.051 -7.623 1.00 0.00
ATOM 1713 CA LYS 108 -7.888 -0.031 -7.106 1.00 0.00
ATOM 1714 HA LYS 108 -7.514 -0.115 -6.098 1.00 0.00
ATOM 1715 CB LYS 108 -7.003 -0.864 -8.035 1.00 0.00
ATOM 1716 HB1 LYS 108 -7.053 -1.897 -7.731 1.00 0.00
ATOM 1717 HB2 LYS 108 -5.984 -0.521 -7.946 1.00 0.00
ATOM 1718 CG LYS 108 -7.409 -0.780 -9.498 1.00 0.00
ATOM 1719 HG 1 LYS 108 -8.026 0.095 -9.640 1.00 0.00
ATOM 1720 HG2 LYS 108 -7.970 -1.665 -9.758 1.00 0.00
ATOM 1721 CD LYS 108 -6.195 -0.682 -10.409 1.00 0.00
ATOM 1722 HD l LYS 108 -5.345 -1.122 -9.909 1.00 0.00
ATOM 1723 HD2 LYS 108 -5.994 0.359 -10.614 1.00 0.00
ATOM 1724 CE LYS 108 -6.426 -1.407 -1 1.725 1.00 0.00
ATOM 1725 HEI LYS 108 -7.068 -2.256 -1 1.545 1.00 0.00
ATOM 1726 HE2 LYS 108 -5.475 -1.750 -12.103 1.00 0.00
ATOM 1727 NZ LYS 108 -7.061 -0.524 -12.741 1.00 0.00
ATOM 1728 HZ1 LYS 108 -8.068 -0.391 -12.519 1.00 0.00
ATOM 1729 HZ2 LYS 108 -6.980 -0.951 -13.686 1.00 0.00
ATOM 1730 HZ3 LYS 108 -6.593 0.404 -12.751 1.00 0.00
ATOM 1731 C LYS 108 -7.837 1.432 -7.529 1.00 0.00
ATOM 1732 O LYS 108 -8.816 1.983 -8.031 1.00 0.00
ATOM 1733 N ILE 109 -6.684 2.053 -7.310 1.00 0.00
ATOM 1734 HN ILE 109 -5.946 1.555 -6.901 1.00 0.00
ATOM 1735 CA ILE 109 -6.486 3.454 -7.654 1.00 0.00
ATOM 1736 HA ILE 109 -7.394 3.990 -7.417 1.00 0.00
ATOM 1737 CB ILE 109 -5.332 4.061 -6.830 1.00 0.00
ATOM 1738 HB ILE 109 -4.415 3.572 -7.123 1.00 0.00
ATOM 1739 CGI ILE 109 -5.565 3.824 -5.335 1.00 0.00
ATOM 1740 HG 1 1 ILE 109 -6.441 3.204 -5.207 1.00 0.00
ATOM 1741 HG 12 ILE 109 -5.728 4.773 -4.846 1.00 0.00
ATOM 1742 CG2 ILE 109 -5.185 5.547 -7.1 18 1.00 0.00
ATOM 1743 HG21 ILE 109 -6.133 5.944 -7.448 1.00 0.00
ATOM 1744 HG22 ILE 109 -4.444 5.691 -7.891 1.00 0.00
ATOM 1745 HG23 ILE 109 -4.872 6.057 -6.219 1.00 0.00
ATOM 1746 CDl ILE 109 -4.407 3.140 -4.643 1.00 0.00
ATOM 1747 HDl 1 ILE 109 -3.483 3.623 -4.924 1.00 0.00
ATOM 1748 HDl 2 ILE 109 -4.374 2.101 -4.937 1.00 0.00
ATOM 1749 HD13 ILE 109 -4.537 3.207 -3.573 1.00 0.00
ATOM 1750 C ILE 109 -6.189 3.617 -9.141 1.00 0.00
ATOM 1751 O ILE 109 -5.492 2.798 -9.740 1.00 0.00
ATOM 1752 N TYR 1 10 -6.730 4.677 -9.732 1.00 0.00
ATOM 1753 HN TYR 1 10 -7.281 5.290 -9.201 1.00 0.00
ATOM 1754 CA TYR 1 10 -6.533 4.947 -1 1.151 1.00 0.00
ATOM 1755 HA TYR 1 10 -6.285 4.015 -1 1.634 1.00 0.00
ATOM 1756 CB TYR 1 10 -7.821 5.497 -1 1.765 1.00 0.00
ATOM 1757 HB 1 TYR 1 10 -7.918 6.541 -1 1.507 1.00 0.00
ATOM 1758 HB2 TYR 1 10 -8.663 4.953 -1 1.364 1.00 0.00
ATOM 1759 CG TYR 1 10 -7.871 5.383 -13.271 1.00 0.00
ATOM 1760 CDl TYR 1 10 -8.074 6.505 -14.065 1.00 0.00
ATOM 1761 HDl TYR 1 10 -8.196 7.468 -13.591 1.00 0.00
ATOM 1762 CD2 TYR 1 10 -7.716 4.154 -13.899 1.00 0.00
ATOM 1763 HD2 TYR 1 10 -7.558 3.273 -13.295 1.00 0.00 ATOM 1764 CE1 TYR 110 -8.121 6.405-15.443 1.000.00
ATOM 1765 HEI TYR 110 -8.279 7.289-16.043 1.000.00
ATOM 1766 CE2TYR 110 -7.761 4.046-15.276 1.000.00
ATOM 1767 HE2TYR 110 -7.638 3.081 -15.746 1.000.00
ATOM 1768 CZ TYR 110 -7.964 5.174-16.043 1.000.00
ATOM 1769 OH TYR 110 -8.009 5.070-17.414 1.000.00
ATOM 1770 HH TYR 110 -7.126 4.905-17.753 1.000.00
ATOM 1771 C TYR 110 -5.391 5.935-11.371 1.000.00
ATOM 1772 O TYR 110 -4.732 5.913-12.411 1.000.00
ATOM 1773 N LEU 111 -5.164 6.802-10.390 1.000.00
ATOM 1774 HN LEU 111 -5.723 6.774 -9.586 1.000.00
ATOM 1775 CA LEU 111 -4.102 7.799-10.484 1.000.00
ATOM 1776 HA LEU 111 -4.325 8.438-11.324 1.000.00
ATOM 1777 CB LEU 111 -4.059 8.647 -9.212 1.000.00
ATOM 1778 HB1LEU 111 -3.208 9.308 -9.274 1.000.00
ATOM 1779 HB2LEU 111 -3.920 7.986 -8.368 1.000.00
ATOM 1780 CG LEU 111 -5.305 9.496 -8.957 1.000.00
ATOM 1781 HG LEU 111 -6.161 8.845 -8.851 1.000.00
ATOM 1782 CDl LEU 111 -5.156 10.290 -7.669 1.000.00
ATOM 1783 HDl 1 LEU 111 -5.112 9.611 -6.831 1.000.00
ATOM 1784 HD12 LEU 111 -6.003 10.951 -7.553 1.000.00
ATOM 1785 HD13 LEU 111 -4.247 10.872 -7.709 1.000.00
ATOM 1786 CD2LEU 111 -5.564 10.427-10.132 1.000.00
ATOM 1787 HD21 LEU 111 -4.625 10.688-10.598 1.000.00
ATOM 1788 HD22 LEU 111 -6.052 11.324 -9.781 1.000.00
ATOM 1789 HD23 LEU 111 -6.197 9.931 -10.853 1.000.00
ATOM 1790 C LEU 111 -2.745 7.134-10.712 1.000.00
ATOM 1791 0 LEU 111 -2.406 6.156-10.045 1.000.00
ATOM 1792 N PRO 112 -1.945 7.658-11.659 1.000.00
ATOM 1793 CA PRO 112 -0.619 7.107-11.966 1.000.00
ATOM 1794 HA PRO 112 -0.683 6.075-12.278 1.000.00
ATOM 1795 CB PRO 112 -0.128 7.967-13.136 1.000.00
ATOM 1796 HB1 PRO 112 -0.303 7.447-14.066 1.000.00
ATOM 1797 HB2PRO 112 0.928 8.165-13.021 1.000.00
ATOM 1798 CG PRO 112 -0.928 9.221 -13.057 1.000.00
ATOM 1799 HG1 PRO 112 -1.044 9.646-14.043 1.000.00
ATOM 1800 HG2PRO 112 -0.443 9.926-12.399 1.000.00
ATOM 1801 CD PRO 112 -2.265 8.824-12.501 1.000.00
ATOM 1802 HDl PRO 112 -2.940 8.550-13.298 1.000.00
ATOM 1803 HD2PRO 112 -2.682 9.625-11.909 1.000.00
ATOM 1804 C PRO 112 0.339 7.216-10.786 1.000.00
ATOM 1805 O PRO 112 1.131 6.308-10.535 1.000.00
ATOM 1806 N TYR 113 0.260 8.333-10.066 1.000.00
ATOM 1807 HN TYR 113 -0.393 9.018-10.319 1.000.00
ATOM 1808 CA TYR 113 1.122 8.567 -8.910 1.000.00
ATOM 1809 HA TYR 113 0.814 9.495 -8.452 1.000.00
ATOM 1810 CB TYR 113 0.971 7.434 -7.890 1.000.00
ATOM 1811 HB1 TYR 113 1.927 7.250 -7.423 1.000.00
ATOM 1812 HB2TYR 113 0.646 6.540 -8.399 1.000.00
ATOM 1813 CG TYR 113 -0.030 7.732 -6.796 1.000.00
ATOM 1814 CDl TYR 113 0.226 8.707 -5.840 1.000.00
ATOM 1815 HDl TYR 113 1.155 9.255 -5.885 1.000.00
ATOM 1816 CD2TYR 113 -1.232 7.038 -6.720 1.000.00
ATOM 1817 HD2TYR 113 -1.446 6.277 -7.456 1.000.00
ATOM 1818 CE1 TYR 113 -0.686 8.981 -4.839 1.000.00
ATOM 1819 HEI TYR 113 -0.468 9.743 -4.104 1.000.00
ATOM 1820 CE2TYR 113 -2.149 7.308 -5.722 1.000.00
ATOM 1821 HE2TYR 113 -3.077 6.757 -5.680 1.000.00
ATOM 1822 CZ TYR 113 -1.871 8.279 -4.784 1.000.00 ATOM 1823 OH TYR 113 -2.782 8.550 -3.789 1.000.00
ATOM 1824 HH TYR 113 -2.435 8.247 -2.946 1.000.00
ATOM 1825 C TYR 113 2.581 8.693 -9.338 1.000.00
ATOM 1826 O TYR 113 3.162 9.777 -9.285 1.000.00
ATOM 1827 N LEU 114 3.164 7.580 -9.767 1.000.00
ATOM 1828 HN LEU 114 2.647 6.748 -9.789 1.000.00
ATOM 1829 CA LEU 114 4.552 7.564-10.210 1.000.00
ATOM 1830 HA LEU 114 5.145 8.079 -9.470 1.000.00
ATOM 1831 CB LEU 114 5.051 6.124-10.337 1.000.00
ATOM 1832 HB1 LEU 114 4.617 5.694-11.227 1.000.00
ATOM 1833 HB2LEU 114 4.698 5.568 -9.481 1.000.00
ATOM 1834 CG LEU 114 6.572 5.970-10.422 1.000.00
ATOM 1835 HG LEU 114 7.017 6.943-10.568 1.000.00
ATOM 1836 CDl LEU 114 7.125 5.391 -9.129 1.000.00
ATOM 1837 HDl 1 LEU 114 7.421 6.196 -8.472 1.000.00
ATOM 1838 HD12 LEU 114 7.983 4.772 -9.349 1.000.00
ATOM 1839 HD13 LEU 114 6.365 4.794 -8.647 1.000.00
ATOM 1840 CD2LEU 114 6.955 5.093-11.606 1.000.00
ATOM 1841 HD21 LEU 114 7.150 5.716-12.466 1.000.00
ATOM 1842 HD22 LEU 114 6.145 4.414-11.828 1.000.00
ATOM 1843 HD23 LEU 114 7.843 4.527-11.362 1.000.00
ATOM 1844 C LEU 114 4.699 8.279-11.548 1.000.00
ATOM 18450 LEU 114 5.570 9.131-11.717 1.000.00
ATOM 1846 N HIS 115 3.840 7.923-12.496 1.000.00
ATOM 1847 HN HIS 115 3.167 7.236-12.299 1.000.00
ATOM 1848 CA HIS 115 3.872 8.529-13.823 1.000.00
ATOM 1849 HA HIS 115 4.863 8.384-14.226 1.000.00
ATOM 1850 CB HIS 115 2.860 7.840-14.742 1.000.00
ATOM 1851 HB1 HIS 115 2.233 8.589-15.204 1.000.00
ATOM 1852 HB2HIS 115 2.244 7.177-14.153 1.000.00
ATOM 1853 CG HIS 115 3.494 7.033-15.831 1.000.00
ATOM 1854 ND1 HIS 115 4.056 5.791 -15.618 1.000.00
ATOM 1855 HDl HIS 115 4.099 5.322-14.759 1.000.00
ATOM 1856 CD2HIS 115 3.653 7.294-17.150 1.000.00
ATOM 1857 HD2HIS 115 3.330 8.185-17.671 1.000.00
ATOM 1858 CE1 HIS 115 4.534 5.325-16.758 1.000.00
ATOM 1859 HEI HIS 115 5.029 4.375-16.895 1.000.00
ATOM 1860 NE2HIS 115 4.302 6.217-17.703 1.000.00
ATOM 1861 HE2HIS 115 4.473 6.085-18.659 1.000.00
ATOM 1862 C HIS 115 3.584 10.029-13.759 1.000.00
ATOM 1863 O HIS 115 3.828 10.755-14.723 1.000.00
ATOM 1864 N GLU 116 3.056 10.490-12.627 1.000.00
ATOM 1865 HN GLU 116 2.874 9.868-11.893 1.000.00
ATOM 1866 CA GLU 116 2.731 11.901 -12.457 1.000.00
ATOM 1867 HA GLU 116 2.63012.336-13.440 1.000.00
ATOM 1868 CB GLU 116 1.402 12.050-11.714 1.000.00
ATOM 1869 HB1 GLU 116 1.595 12.442-10.726 1.000.00
ATOM 1870 HB2GLU 116 0.944 11.077-11.621 1.000.00
ATOM 1871 CG GLU 116 0.41712.975-12.410 1.000.00
ATOM 1872 HG1 GLU 116 -0.282 12.376-12.975 1.000.00
ATOM 1873 HG2GLU 116 0.961 13.621 -13.082 1.000.00
ATOM 1874 CD GLU 116 -0.361 13.837-11.435 1.000.00
ATOM 1875 OEl GLU 116 0.004 15.020-11.2661.000.00
ATOM 1876 OE2GLU 116 -1.335 13.330-10.840 1.000.00
ATOM 1877 C GLU 116 3.833 12.645-11.705 1.000.00
ATOM 18780 GLU 116 4.505 13.510-12.267 1.000.00
ATOM 1879 N TRP 117 4.000 12.317-10.427 1.000.00
ATOM 1880 HN TRP 117 3.425 11.630-10.031 1.000.00
ATOM 1881 CA TRP 117 5.006 12.970 -9.596 1.000.00 ATOM 1882 HA TRP 117 4.952 14.029 -9.801 1.000.00
ATOM 1883 CB TRP 117 4.688 12.746 -8.113 1.000.00
ATOM 1884 HB1 TRP 117 4.825 11.703 -7.873 1.000.00
ATOM 1885 HB2TRP 117 3.659 13.017 -7.931 1.000.00
ATOM 1886 CG TRP 117 5.544 13.554 -7.185 1.000.00
ATOM 1887 CDl TRP 117 6.225 13.096 -6.095 1.000.00
ATOM 1888 HDl TRP 117 6.227 12.067 -5.767 1.000.00
ATOM 1889 CD2 TRP 117 5.805 14.961 -7.261 1.000.00
ATOM 1890 NE1 TRP 117 6.895 14.131 -5.488 1.000.00
ATOM 1891 HEI TRP 117 7.455 14.054 -4.688 1.000.00
ATOM 1892 CE2TRP 117 6.655 15.285 -6.186 1.000.00
ATOM 1893 CE3TRP 117 5.407 15.978 -8.133 1.000.00
ATOM 1894 HE3 TRP 117 4.755 15.774 -8.970 1.000.00
ATOM 1895 CZ2TRP 117 7.111 16.581 -5.960 1.000.00
ATOM 1896 HZ2TRP 117 7.764 16.822 -5.134 1.000.00
ATOM 1897 CZ3TRP 117 5.860 17.265 -7.908 1.000.00
ATOM 1898 HZ3TRP 117 5.562 18.063 -8.571 1.000.00
ATOM 1899 CH2TRP 117 6.705 17.556 -6.830 1.000.00
ATOM 1900 HH2TRP 117 7.034 18.576 -6.692 1.000.00
ATOM 1901 C TRP 117 6.421 12.489 - 9.936 1.000.00
ATOM 1902 O TRP 117 7.086 13.078- 10.787 1.000.00
ATOM 1903 N LYS 118 6.883 11.428 - ■9.266 1.000.00
ATOM 1904 HN LYS 118 6.313 11.002 -8.595 1.000.00
ATOM 1905 CA LYS 118 8.223 10.884 -9.502 1.000.00
ATOM 1906 HA LYS 118 8.463 10.245 -8.664 1.00 0.00
ATOM 1907 CB LYS 118 8.255 10.041 ■ -10.782 1.000.00
ATOM 1908 HB1 LYS 118 7.513 9.260 -10.700 1.000.00
ATOM 1909 HB2 LYS 118 9.230 9.586 -10.872 1.000.00
ATOM 1910 CG LYS 118 7.980 10.828 -12.054 1.000.00
ATOM 1911 HG1 LYS 118 8.360 11.831 -11.936 1.000.00
ATOM 1912 HG2 LYS 118 6.915 10.861 -12.223 1.000.00
ATOM 1913 CD LYS 118 8.651 10.188 -13.262 1.000.00
ATOM 1914 HDl LYS 118 9.723 10.235 -13.131 1.000.00
ATOM 1915 HD2 LYS 118 8.372 10.738 -14.148 1.000.00
ATOM 1916 CE LYS 118 8.237 8.734- 13.435 1.000.00
ATOM 1917 HEI LYS 118 7.452 8.509- -12.729 1.000.00
ATOM 1918 HE2 LYS 118 9.091 8.104- ■13.234 1.000.00
ATOM 1919 NZ LYS 118 7.745 8.457- 14.812 1.000.00
ATOM 1920 HZ1 LYS 118 8.249 9.055- ■15.499 1.000.00
ATOM 1921 HZ2 LYS 118 6.727 8.659- •14.876 1.000.00
ATOM 1922 HZ3 LYS 118 7.905 7.459- •15.055 1.000.00
ATOM 1923 C LYS 118 9.271 11.995 - 9.572 1.000.00
ATOM 1924 O LYS 118 10.007 12.113- 10.551 1.000.00
ATOM 1925 N HIS 119 9.327 12.807 -8.522 1.000.00
ATOM 1926 HN HIS 119 8.712 12.661 ■ -7.773 1.000.00
ATOM 1927 CA HIS 119 10.275 13.912 -8.455 1.000.00
ATOM 1928 HA HIS 119 10.248 14.408 -9.407 1.000.00
ATOM 1929 CB HIS 119 9.849 14.908 - 7.376 1.000.00
ATOM 1930 HB1 HIS 119 10.621 14.966 -6.622 1.000.00
ATOM 1931 HB2 HIS 119 8.933 14.564 -6.920 1.000.00
ATOM 1932 CG HIS 119 9.609 16.291 - •7.899 1.000.00
ATOM 1933 ND1 HIS 119 9.139 16.543 -9.171 1.000.00
ATOM 1934 HDl HIS 119 8.920 15.867 -9.845 1.000.00
ATOM 1935 CD2 HIS 119 9.776 17.501 -7.314 1.000.00
ATOM 1936 HD2 HIS 119 10.133 17.684 -6.311 1.000.00
ATOM 1937 CE1 HIS 119 9.027 17.848 -9.345 1.000.00
ATOM 1938 HEI HIS 119 8.683 18.339- 10.244 1.000.00
ATOM 1939 NE2HIS 119 9.407 18.451 -8.234 1.000.00
ATOM 1940 HE2 HIS 119 9.492 19.420 -8.117 1.000.00 ATOM 1941 C HIS 1 19 11.716 13.444 -8.200 1.00 0.00
ATOM 1942 O HIS 1 19 12.654 14.018 -8.754 1.00 0.00
ATOM 1943 N PRO 120 1 1.932 12.412 -7.356 1.00 0.00
ATOM 1944 CA PRO 120 10.865 1 1.683 -6.662 1.00 0.00
ATOM 1945 HA PRO 120 10.107 1 1.355 -7.353 1.00 0.00
ATOM 1946 CB PRO 120 1 1.581 10.462 -6.081 1.00 0.00
ATOM 1947 HB 1 PRO 120 1 1.485 9.629 -6.761 1.00 0.00
ATOM 1948 HB2 PRO 120 1 1.143 10.206 -5.127 1.00 0.00
ATOM 1949 CG PRO 120 13.001 10.881 -5.933 1.00 0.00
ATOM 1950 HG 1 PRO 120 13.648 10.023 -6.041 1.00 0.00
ATOM 1951 HG2 PRO 120 13.151 1 1.341 -4.968 1.00 0.00
ATOM 1952 CD PRO 120 13.267 1 1.873 -7.033 1.00 0.00
ATOM 1953 HD l PRO 120 13.699 1 1.377 -7.889 1.00 0.00
ATOM 1954 HD2 PRO 120 13.922 12.657 -6.681 1.00 0.00
ATOM 1955 C PRO 120 10.210 12.495 -5.548 1.00 0.00
ATOM 1956 O PRO 120 8.994 12.676 -5.539 1.00 0.00
ATOM 1957 N GLN 121 1 1.019 12.972 -4.604 1.00 0.00
ATOM 1958 HN GLN 121 1 1.979 12.788 -4.662 1.00 0.00
ATOM 1959 CA GLN 121 10.515 13.755 -3.475 1.00 0.00
ATOM 1960 HA GLN 121 1 1.368 14.145 -2.940 1.00 0.00
ATOM 1961 CB GLN 121 9.659 14.929 -3.963 1.00 0.00
ATOM 1962 HB 1 GLN 121 8.741 14.953 -3.394 1.00 0.00
ATOM 1963 HB2 GLN 121 9.421 14.779 -5.003 1.00 0.00
ATOM 1964 CG GLN 121 10.339 16.280 -3.821 1.00 0.00
ATOM 1965 HG 1 GLN 121 9.848 16.986 -4.474 1.00 0.00
ATOM 1966 HG2 GLN 121 1 1.374 16.181 -4.1 13 1.00 0.00
ATOM 1967 CD GLN 121 10.286 16.814 -2.403 1.00 0.00
ATOM 1968 OE l GLN 121 9.404 17.599 -2.055 1.00 0.00
ATOM 1969 NE2 GLN 121 1 1.234 16.390 - 1.574 1.00 0.00
ATOM 1970 HE21 GLN 121 1 1.905 15.766 -1.920 1.00 0.00
ATOM 1971 HE22 GLN 121 1 1.223 16.719 -0.651 1.00 0.00
ATOM 1972 C GLN 121 9.702 12.880 -2.522 1.00 0.00
ATOM 1973 O GLN 121 10.042 12.746 -1.346 1.00 0.00
ATOM 1974 N SER 122 8.626 12.290 -3.035 1.00 0.00
ATOM 1975 HN SER 122 8.403 12.437 -3.977 1.00 0.00
ATOM 1976 CA SER 122 7.765 1 1.433 -2.230 1.00 0.00
ATOM 1977 HA SER 122 7.722 1 1.848 -1.234 1.00 0.00
ATOM 1978 CB SER 122 6.352 1 1.403 -2.818 1.00 0.00
ATOM 1979 HB 1 SER 122 6.192 10.459 -3.319 1.00 0.00
ATOM 1980 HB2 SER 122 6.243 12.209 -3.529 1.00 0.00
ATOM 1981 OG SER 122 5.374 1 1.553 -1.804 1.00 0.00
ATOM 1982 HG SER 122 4.980 10.700 -1.609 1.00 0.00
ATOM 1983 C SER 122 8.324 10.016 -2.148 1.00 0.00
ATOM 1984 O SER 122 8.714 9.431 -3.159 1.00 0.00
ATOM 1985 N ASP 123 8.359 9.471 -0.937 1.00 0.00
ATOM 1986 HN ASP 123 8.033 9.989 -0.172 1.00 0.00
ATOM 1987 CA ASP 123 8.867 8.122 -0.715 1.00 0.00
ATOM 1988 HA ASP 123 9.228 7.743 -1.660 1.00 0.00
ATOM 1989 CB ASP 123 10.025 8.149 0.286 1.00 0.00
ATOM 1990 HB 1 ASP 123 9.682 7.763 1.236 1.00 0.00
ATOM 1991 HB2 ASP 123 10.357 9.168 0.416 1.00 0.00
ATOM 1992 CG ASP 123 1 1.205 7.315 -0.173 1.00 0.00
ATOM 1993 OD1 ASP 123 1 1.932 6.787 0.695 1.00 0.00
ATOM 1994 OD2 ASP 123 1 1.403 7.191 -1.400 1.00 0.00
ATOM 1995 C ASP 123 7.758 7.205 -0.208 1.00 0.00
ATOM 1996 O ASP 123 6.616 7.633 -0.043 1.00 0.00
ATOM 1997 N LEU 124 8.100 5.943 0.039 1.00 0.00
ATOM 1998 HN LEU 124 9.026 5.661 -0.1 12 1.00 0.00
ATOM 1999 CA LEU 124 7.129 4.966 0.528 1.00 0.00 ATOM 2000 HA LEU 124 6.464 4.724 -0.287 1.00 0.00
ATOM 2001 CB LEU 124 7.844 3.689 0.980 1.00 0.00
ATOM 2002 HB1 LEU 124 7.743 3.601 2.051 1.00 0.00
ATOM 2003 HB2 LEU 124 8.893 3.787 0.741 1.00 0.00
ATOM 2004 CG LEU 124 7.323 2.398 0.343 1.00 0.00
ATOM 2005 HG LEU 124 6.762 2.645 -0.547 1.00 0.00
ATOM 2006 CD l LEU 124 8.478 1.498 -0.066 1.00 0.00
ATOM 2007 HD l 1 LEU 124 9.014 1.177 0.815 1.00 0.00
ATOM 2008 HDl 2 LEU 124 9.147 2.045 -0.715 1.00 0.00
ATOM 2009 HDl 3 LEU 124 8.095 0.635 -0.590 1.00 0.00
ATOM 2010 CD2 LEU 124 6.391 1.669 1.301 1.00 0.00
ATOM 201 1 HD21 LEU 124 6.098 0.724 0.868 1.00 0.00
ATOM 2012 HD22 LEU 124 5.513 2.272 1.478 1.00 0.00
ATOM 2013 HD23 LEU 124 6.902 1.494 2.236 1.00 0.00
ATOM 2014 C LEU 124 6.304 5.540 1.678 1.00 0.00
ATOM 2015 O LEU 124 5.098 5.312 1.764 1.00 0.00
ATOM 2016 N LEU 125 6.962 6.291 2.554 1.00 0.00
ATOM 2017 HN LEU 125 7.923 6.441 2.430 1.00 0.00
ATOM 2018 CA LEU 125 6.289 6.903 3.693 1.00 0.00
ATOM 2019 HA LEU 125 5.714 6.136 4.190 1.00 0.00
ATOM 2020 CB LEU 125 7.317 7.472 4.675 1.00 0.00
ATOM 2021 HB 1 LEU 125 6.967 8.435 5.016 1.00 0.00
ATOM 2022 HB2 LEU 125 8.248 7.613 4.145 1.00 0.00
ATOM 2023 CG LEU 125 7.590 6.602 5.903 1.00 0.00
ATOM 2024 HG LEU 125 8.268 7.125 6.562 1.00 0.00
ATOM 2025 CDl LEU 125 6.302 6.342 6.669 1.00 0.00
ATOM 2026 HDl 1 LEU 125 5.760 7.268 6.787 1.00 0.00
ATOM 2027 HDl 2 LEU 125 6.536 5.935 7.642 1.00 0.00
ATOM 2028 HD13 LEU 125 5.693 5.637 6.122 1.00 0.00
ATOM 2029 CD2 LEU 125 8.247 5.290 5.494 1.00 0.00
ATOM 2030 HD21 LEU 125 8.473 5.313 4.438 1.00 0.00
ATOM 2031 HD22 LEU 125 7.575 4.470 5.700 1.00 0.00
ATOM 2032 HD23 LEU 125 9.160 5.155 6.054 1.00 0.00
ATOM 2033 C LEU 125 5.341 8.006 3.232 1.00 0.00
ATOM 2034 O LEU 125 4.167 8.024 3.602 1.00 0.00
ATOM 2035 N GLY 126 5.859 8.923 2.421 1.00 0.00
ATOM 2036 HN GLY 126 6.801 8.856 2.159 1.00 0.00
ATOM 2037 CA GLY 126 5.046 10.015 1.921 1.00 0.00
ATOM 2038 HA 1 GLY 126 5.678 10.703 1.380 1.00 0.00
ATOM 2039 HA2 GLY 126 4.603 10.533 2.760 1.00 0.00
ATOM 2040 C GLY 126 3.940 9.538 1.001 1.00 0.00
ATOM 2041 O GLY 126 2.879 10.157 0.922 1.00 0.00
ATOM 2042 N LEU 127 4.189 8.434 0.304 1.00 0.00
ATOM 2043 HN LEU 127 5.054 7.985 0.410 1.00 0.00
ATOM 2044 CA LEU 127 3.206 7.872 -0.615 1.00 0.00
ATOM 2045 HA LEU 127 3.012 8.606 -1.383 1.00 0.00
ATOM 2046 CB LEU 127 3.754 6.601 -1.267 1.00 0.00
ATOM 2047 HB 1 LEU 127 3.507 5.762 -0.635 1.00 0.00
ATOM 2048 HB2 LEU 127 4.830 6.686 -1.322 1.00 0.00
ATOM 2049 CG LEU 127 3.222 6.314 -2.672 1.00 0.00
ATOM 2050 HG LEU 127 2.979 7.248 -3.156 1.00 0.00
ATOM 2051 CDl LEU 127 4.280 5.612 -3.510 1.00 0.00
ATOM 2052 HDl 1 LEU 127 4.952 6.347 -3.929 1.00 0.00
ATOM 2053 HD12 LEU 127 3.802 5.065 -4.309 1.00 0.00
ATOM 2054 HDl 3 LEU 127 4.837 4.928 -2.887 1.00 0.00
ATOM 2055 CD2 LEU 127 1.955 5.476 -2.600 1.00 0.00
ATOM 2056 HD21 LEU 127 1.801 4.973 -3.543 1.00 0.00
ATOM 2057 HD22 LEU 127 1.1 1 1 6.1 17 -2.391 1.00 0.00
ATOM 2058 HD23 LEU 127 2.053 4.742 -1.813 1.00 0.00 ATOM 2059 C LEU 127 1.901 7.563 0.1 1 1 1.00 ( 3.00
ATOM 2060 O LEU 127 0.841 8.075 ■ •0.250 1.00 0.00
ATOM 2061 N ILE 128 1.986 6.726 1 .141 1.00 0.00
ATOM 2062 HN ILE 128 2.860 6.354 1.384 1.00 0.00 ATOM 2063 CA ILE 128 0.814 6.353 1.922 1.00 i 0.00
ATOM 2064 HA ILE 128 0.1 17 5.860 1.259 1.00 0.00
ATOM 2065 CB ILE 128 1.189 5.366 3.052 1.00 ( 3.00
ATOM 2066 HB ILE 128 2.097 5.717 3.518 1.00 0.00
ATOM 2067 CGI ILE 128 1.433 3.971 2.473 1.00 0.00 ATOM 2068 HG 1 1 ILE 128 0.745 3.801 1.658 1.00 0.00
ATOM 2069 HG 12 ILE 128 1.260 3.234 3.243 1.00 0.00
ATOM 2070 CG2 ILE 128 0.102 5.313 4.117 1.00 0.00
ATOM 2071 HG21 ILE 128 0.340 4.542 4.835 1.00 0.00
ATOM 2072 HG22 ILE 128 -0.847 5.091 3.651 1.00 0.00 ATOM 2073 HG23 ILE 128 0.043 6.267 4.619 1.00 0.00
ATOM 2074 CDl ILE 128 2.837 3.767 1.946 1.00 0.00
ATOM 2075 HDl 1 ILE 128 2.967 2.734 1.659 1.00 0.00
ATOM 2076 HDl 2 ILE 128 3.550 4.019 2.717 1.00 0.00
ATOM 2077 HD13 ILE 128 2.995 4.402 1.087 1.00 0.00 ATOM 2078 C ILE 128 0.139 7.590 2.514 1.00 0.00
ATOM 2079 O ILE 128 -1.082 7.632 2.660 1.00 0.00
ATOM 2080 N GLN 129 0.942 8.596 2.850 1.00 0.00
ATOM 2081 HN GLN 129 1.908 8.505 2.709 1.00 0.00
ATOM 2082 CA GLN 129 0 0..442211 9.832 3.424 1.00 0.00 ATOM 2083 HA GLN 129 --00..005511 9.587 4.366 1.00 0.00
ATOM 2084 CB GLN 129 1.563 10.819 3.681 1.00 0.00
ATOM 2085 HB 1 GLN 129 1.473 1 1.646 2.993 1.00 0.00
ATOM 2086 HB2 GLN 129 2.503 10.317 3.506 1.00 0.00
ATOM 2087 CG GLN 129 1.577 1 1.375 5.095 1.00 0.00 ATOM 2088 HG 1 GLN 129 2.194 10.739 5.712 1.00 0.00
ATOM 2089 HG2 GLN 129 0.567 1 1.376 5.477 1.00 0.00
ATOM 2090 CD GLN 129 2.119 12.789 5.160 1.00 0.00
ATOM 2091 OEl GLN 129 3.033 13.081 5.932 1.00 0.00
ATOM 2092 NE2 GLN 129 1.558 13.677 4.347 1.00 0.00 ATOM 2093 HE21 GLN 129 0.835 13.374 3.759 1.00 0.00
ATOM 2094 HE22 GLN 129 1.891 14.598 4.368 1.00 0.00
ATOM 2095 C GLN 129 -0.621 10.462 2.505 1.00 0.00
ATOM 2096 O GLN 129 -1.683 10.888 2.957 1.00 0.00
ATOM 2097 N VAL 130 -0.314 10.510 1.212 1.00 0.00 ATOM 2098 HN VAL 130 0.545 10.150 0.908 1.00 0.00
ATOM 2099 CA VAL 130 -1 1..223333 11 111..008800 0 i 0..223366 1.00 0.00
ATOM 2100 HA VAL 130 -1 1..448844 1 i 122..008811 0 0..555588 1.00 0.00
ATOM 2101 CB VAL 130 -0 0..559922 111 1..116666 --1 1..116633 1.00 0.00
ATOM 2102 HB VAL 130 -0 0..333388 11 100..116666 --1 1..448833 1.00 0.00 ATOM 2103 CG I VAL 130 - -11..556699 1 111..775566 - ■ -22..117711 1.00 0.00
ATOM 2104 HG 1 1 VAL 130 -1.027 12.092 -3.043 1.00 0.00
ATOM 2105 HG12 VAL 130 -2.086 12.592 -1.724 1.00 0.00
ATOM 2106 HG 13 VAL 130 -2.286 1 1.002 -2.461 1.00 0.00
ATOM 2107 CG2 VAL 130 0.685 1 1.988 - •1.109 1.00 0.00 ATOM 2108 HG21 VAL 130 1.278 11.790 -1.989 1.000.00
ATOM 2109 HG22 VAL 130 1.248 11.720 -0.227 1.000.00
ATOM 21 10 HG23 VAL 130 0.435 13.038 -1.071 1.000.00
ATOM 21 1 1 C VAL 130 -2.509 10.251 0.159 1.000.00
ATOM 21 12 O VAL 130 3.615 i 10.790 0.206 1.000.00 ATOM 21 13 N MET 131 -2.348 8.935 0.058 1.000.00
ATOM 21 14 HN MET 131 -1.442 8.563 0.037 1.000.00
ATOM 21 15 CA MET 131 -3.490 8.033 -0.006 1.000.00
ATOM 21 16 HA MET 131 -4.074 8.293 -0.876 1.000.00
ATOM 21 17 CB MET 131 -3.020 6.582 -0.130 1.000.00 ATOM 21 18 HB1 MET 131 -3.1 1 1 6.101 0.833 1.00 0.00
ATOM 21 19 HB2 MET 131 -1.981 6.577 -0.427 1.00 0.00
ATOM 2120 CG MET 131 -3.810 5.771 -1.144 1.00 0.00
ATOM 2121 HG1 MET 131 -4.735 6.288 -1.355 1.00 0.00
ATOM 2122 HG2 MET 131 -4.030 4.803 -0.718 1.00 0.00
ATOM 2123 SD MET 131 -2.916 5.529 -2.691 1.00 0.00
ATOM 2124 CE MET 131 -2.029 4.014 -2.337 1.00 0.00
ATOM 2125 HEI MET 131 -2.505 3.191 -2.848 1.00 0.00
ATOM 2126 HE2 MET 131 -2.040 3.832 -1.272 1.00 0.00
ATOM 2127 HE3 MET 131 - 1.008 4.108 -2.675 1.00 0.00
ATOM 2128 C MET 131 -4.354 8.201 1.238 1.00 0.00
ATOM 2129 O MET 131 -5.581 8.234 1.158 1.00 0.00
ATOM 2130 N ILE 132 -3.695 8.322 2.386 1.00 0.00
ATOM 2131 HN ILE 132 -2.716 8.298 2.378 1.00 0.00
ATOM 2132 CA ILE 132 -4.387 8.504 3.655 1.00 0.00
ATOM 2133 HA ILE 132 -5.065 7.675 3.793 1.00 0.00
ATOM 2134 CB ILE 132 -3.385 8.522 4.834 1.00 0.00
ATOM 2135 HB ILE 132 -2.569 9.177 4.571 1.00 0.00
ATOM 2136 CG I ILE 132 -2.833 7.1 19 5.087 1.00 0.00
ATOM 2137 HG1 1 ILE 132 -2.419 6.730 4.169 1.00 0.00
ATOM 2138 HG 12 ILE 132 -3.636 6.476 5.416 1.00 0.00
ATOM 2139 CG2 ILE 132 -4.035 9.069 6.099 1.00 0.00
ATOM 2140 HG21 ILE 132 -3.361 8.937 6.934 1.00 0.00
ATOM 2141 HG22 ILE 132 -4.954 8.536 6.291 1.00 0.00
ATOM 2142 HG23 ILE 132 -4.246 10.120 5.969 1.00 0.00
ATOM 2143 CDl ILE 132 - 1.748 7.083 6.142 1.00 0.00
ATOM 2144 HDl 1 ILE 132 -1.490 6.057 6.359 1.00 0.00
ATOM 2145 HD12 ILE 132 -2.106 7.561 7.042 1.00 0.00
ATOM 2146 HD13 ILE 132 -0.876 7.605 5.779 1.00 0.00
ATOM 2147 C ILE 132 - 5.184 9.806 3.645 1.00 0.00
ATOM 2148 O ILE 132 - 6.333 9.848 4.085 1.00 0.00
ATOM 2149 N VAL 133 -4.564 10.864 3.133 1.00 0.00
ATOM 2150 HN VAL 133 -3.652 10.762 2.789 1.00 0.00
ATOM 2151 CA VAL 133 -5.209 12.167 3.055 1.00 0.00
ATOM 2152 HA VAL 133 -5.577 12.419 4.039 1.00 0.00
ATOM 2153 CB VAL 133 -4.213 13.259 2.61 1 1.00 0.00
ATOM 2154 HB VAL 133 -3.869 13.022 1.614 1.00 0.00
ATOM 2155 CG I VAL 133 -4.888 14.622 2.572 1.00 0.00
ATOM 2156 HG 1 1 VAL 133 -4.146 15.395 2.700 1.00 0.00
ATOM 2157 HG 12 VAL 133 -5.617 14.686 3.366 1.00 0.00
ATOM 2158 HG 13 VAL 133 -5.382 14.751 1.620 1.00 0.00
ATOM 2159 CG2 VAL 133 -3.005 13.283 3.536 1.00 0.00
ATOM 2160 HG21 VAL 133 -2.951 12.354 4.084 1.00 0.00
ATOM 2161 HG22 VAL 133 -3.099 14.105 4.231 1.00 0.00
ATOM 2162 HG23 VAL 133 -2.106 13.408 2.951 1.00 0.00
ATOM 2163 C VAL 133 -6.380 12.127 2.083 1.00 0.00
ATOM 2164 O VAL 133 -7.498 12.518 2.416 1.00 0.00
ATOM 2165 N VAL 134 -6.106 1 1.646 0.878 1.00 0.00
ATOM 2166 HN VAL 134 -5.193 1 1.350 0.681 1.00 0.00
ATOM 2167 CA VAL 134 -7.120 1 1.541 -0.159 1.00 0.00
ATOM 2168 HA VAL 134 -7.502 12.531 -0.359 1.00 0.00
ATOM 2169 CB VAL 134 -6.503 10.986 -1.458 1.00 0.00
ATOM 2170 HB VAL 134 -5.949 10.091 -1.208 1.00 0.00
ATOM 2171 CG I VAL 134 -7.580 10.618 -2.470 1.00 0.00
ATOM 2172 HG 1 1 VAL 134 -8.400 1 1.316 -2.393 1.00 0.00
ATOM 2173 HG 12 VAL 134 -7.938 9.619 -2.268 1.00 0.00
ATOM 2174 HG 13 VAL 134 -7.166 10.658 -3.467 1.00 0.00
ATOM 2175 CG2 VAL 134 -5.529 1 1.991 -2.053 1.00 0.00
ATOM 2176 HG21 VAL 134 -6.028 12.565 -2.820 1.00 0.00 ATOM 2177 HG22 VAL 134 -4.689 1 1.467 -2.484 1.00 0.00
ATOM 2178 HG23 VAL 134 -5.179 12.656 -1.277 1.00 0.00
ATOM 2179 C VAL 134 -8.272 10.641 0.286 1.00 0.00
ATOM 2180 O VAL 134 -9.439 1 1.026 0.21 1 1.00 0.00
ATOM 2181 N PHE 135 -7.935 9.442 0.751 1.00 0.00
ATOM 2182 HN PHE 135 -6.988 9.193 0.787 1.00 0.00
ATOM 2183 CA PHE 135 -8.939 8.487 1.209 1.00 0.00
ATOM 2184 HA PHE 135 -9.677 8.385 0.428 1.00 0.00
ATOM 2185 CB PHE 135 -8.298 7.120 1.466 1.00 0.00
ATOM 2186 HB1 PHE 135 -8.955 6.538 2.095 1.00 0.00
ATOM 2187 HB2 PHE 135 -7.358 7.262 1.975 1.00 0.00
ATOM 2188 CG PHE 135 -8.029 6.324 0.215 1.00 0.00
ATOM 2189 CDl PHE 135 -7.817 6.954 -1.003 1.00 0.00
ATOM 2190 HDl PHE 135 -7.846 8.032 -1.055 1.00 0.00
ATOM 2191 CD2 PHE 135 -7.987 4.939 0.262 1.00 0.00
ATOM 2192 HD2 PHE 135 -8.150 4.436 1.203 1.00 0.00
ATOM 2193 CE1 PHE 135 -7.570 6.219 -2.147 1.00 0.00
ATOM 2194 HE I PHE 135 -7.407 6.722 -3.088 1.00 0.00
ATOM 2195 CE2 PHE 135 -7.741 4.199 -0.879 1.00 0.00
ATOM 2196 HE2 PHE 135 -7.71 1 3.121 -0.828 1.00 0.00
ATOM 2197 CZ PHE 135 -7.532 4.840 -2.085 1.00 0.00
ATOM 2198 HZ PHE 135 -7.339 4.263 -2.977 1.00 0.00
ATOM 2199 C PHE 135 -9.632 8.982 2.477 1.00 0.00
ATOM 2200 O PHE 135 - 10.719 8.516 2.822 1.00 0.00
ATOM 2201 N GLY 136 -8.996 9.922 3.169 1.00 0.00
ATOM 2202 HN GLY 136 -8.133 10.254 2.850 1.00 0.00
ATOM 2203 CA GLY 136 -9.566 10.457 4.392 1.00 0.00
ATOM 2204 HA 1 GLY 136 -8.910 1 1.225 4.775 1.00 0.00
ATOM 2205 HA2 GLY 136 -9.634 9.664 5.120 1.00 0.00
ATOM 2206 C GLY 136 -10.945 1 1.049 4.184 1.00 0.00
ATOM 2207 O GLY 136 -1 1.830 10.888 5.025 1.00 0.00
ATOM 2208 N ASP 137 -1 1.130 1 1.733 3.062 1.00 0.00
ATOM 2209 HN ASP 137 -10.387 1 1.826 2.429 1.00 0.00
ATOM 2210 CA ASP 137 -12.414 12.349 2.748 1.00 0.00
ATOM 2211 HA ASP 137 - 13.016 12.335 3.643 1.00 0.00
ATOM 2212 CB ASP 137 -12.213 13.800 2.306 1.00 0.00
ATOM 2213 HB 1 ASP 137 -12.978 14.061 1.590 1.00 0.00
ATOM 2214 HB2 ASP 137 -1 1.243 13.897 1.841 1.00 0.00
ATOM 2215 CG ASP 137 -12.287 14.773 3.466 1.00 0.00
ATOM 2216 OD1 ASP 137 - 1 1.546 14.580 4.452 1.00 0.00
ATOM 2217 OD2 ASP 137 -13.087 15.729 3.388 1.00 0.00
ATOM 2218 C ASP 137 ■ - 13.136 1 1.569 1.656 1.00 0.00
ATOM 2219 O ASP 137 -14.359 1 1.428 1.685 1.00 0.00
ATOM 2220 N GLU 138 - 12.372 1 1.066 0.692 1.00 0.00
ATOM 2221 HN GLU 138 -1 1.403 1 1.214 0.725 1.00 0.00
ATOM 2222 CA GLU 138 -12.938 10.302 -0.413 1.00 0.00
ATOM 2223 HA GLU 138 - 13.922 10.694 -0.616 1.00 0.00
ATOM 2224 CB GLU 138 -12.073 10.466 -1.665 1.00 0.00
ATOM 2225 HB 1 GLU 138 - 1 1.459 9.586 -1.784 1.00 0.00
ATOM 2226 HB2 GLU 138 - 1 1.433 1 1.327 - 1.536 1.00 0.00
ATOM 2227 CG GLU 138 - 12.879 10.661 -2.940 1.00 0.00
ATOM 2228 HG1 GLU 138 -13.766 10.046 -2.887 1.00 0.00
ATOM 2229 HG2 GLU 138 -12.278 10.351 -3.781 1.00 0.00
ATOM 2230 CD GLU 138 -13.299 12.102 -3.149 1.00 0.00
ATOM 2231 OEl GLU 138 -14.037 12.636 -2.294 1.00 0.00
ATOM 2232 OE2 GLU 138 -12.890 12.698 -4.168 1.00 0.00
ATOM 2233 C GLU 138 -13.058 8.819 -0.056 1.00 0.00
ATOM 2234 O GLU 138 - 12.054 8.109 0.005 1.00 0.00
ATOM 2235 N PRO 139 -14.289 8.325 0.176 1.00 0.00 ATOM 2236 CA PRO 139 -14.520 6.917 0.516 1.00 0.00
ATOM 2237 HA PRO 139 - 13.919 6.608 1.359 1.00 0.00
ATOM 2238 CB PRO 139 - 16.002 6.879 0.896 1.00 0.00
ATOM 2239 HB 1 PRO 139 - 16.107 6.998 1.964 1.00 0.00
ATOM 2240 HB2 PRO 139 -16.432 5.936 0.587 1.00 0.00
ATOM 2241 CG PRO 139 - 16.607 8.024 0.160 1.00 0.00
ATOM 2242 HG 1 PRO 139 - 17.479 8.381 0.687 1.00 0.00
ATOM 2243 HG2 PRO 139 -16.872 7.717 -0.842 1.00 0.00
ATOM 2244 CD PRO 139 -15.549 9.091 0.1 17 1.00 0.00
ATOM 2245 HD l PRO 139 -15.641 9.748 0.969 1.00 0.00
ATOM 2246 HD2 PRO 139 -15.616 9.653 -0.803 1.00 0.00
ATOM 2247 C PRO 139 -14.253 5.995 -0.671 1.00 0.00
ATOM 2248 O PRO 139 - 14.988 6.020 -1.657 1.00 0.00
ATOM 2249 N PRO 140 - 13.192 5.172 -0.599 1.00 0.00
ATOM 2250 CA PRO 140 -12.837 4.251 - 1.682 1.00 0.00
ATOM 2251 HA PRO 140 -12.845 4.742 -2.637 1.00 0.00
ATOM 2252 CB PRO 140 -1 1.409 3.839 -1.332 1.00 0.00
ATOM 2253 HB 1 PRO 140 -10.710 4.512 - 1.804 1.00 0.00
ATOM 2254 HB2 PRO 140 -11.230 2.828 -1.670 1.00 0.00
ATOM 2255 CG PRO 140 -1 1.345 3.939 0.151 1.00 0.00
ATOM 2256 HG1 PRO 140 -10.332 4.145 0.462 1.00 0.00
ATOM 2257 HG2 PRO 140 -1 1.693 3.020 0.595 1.00 0.00
ATOM 2258 CD PRO 140 - 12.250 5.080 0.534 1.00 0.00
ATOM 2259 HD l PRO 140 - 1 1.682 5.993 0.637 1.00 0.00
ATOM 2260 HD2 PRO 140 -12.773 4.854 1.452 1.00 0.00
ATOM 2261 C PRO 140 -13.745 3.031 -1.740 1.00 0.00
ATOM 2262 O PRO 140 - 14.072 2.540 -2.820 1.00 0.00
ATOM 2263 N VAL 141 -14.136 2.535 -0.575 1.00 0.00
ATOM 2264 HN VAL 141 - 13.834 2.961 0.254 1.00 0.00
ATOM 2265 CA VAL 141 -14.991 1.360 -0.502 1.00 0.00
ATOM 2266 HA VAL 141 - 15.688 1.394 -1.325 1.00 0.00
ATOM 2267 CB VAL 141 -14.142 0.083 -0.631 1.00 0.00
ATOM 2268 HB VAL 141 - 13.568 0.150 - 1.544 1.00 0.00
ATOM 2269 CG I VAL 141 -13.167 -0.01 1 0.533 1.00 0.00
ATOM 2270 HG 1 1 VAL 141 -12.248 -0.466 0.201 1.00 0.00
ATOM 2271 HG 12 VAL 141 - 13.603 -0.606 1.322 1.00 0.00
ATOM 2272 HG 13 VAL 141 -12.963 0.983 0.906 1.00 0.00
ATOM 2273 CG2 VAL 141 -15.023 -1.154 -0.710 1.00 0.00
ATOM 2274 HG21 VAL 141 -15.943 -0.975 -0.175 1.00 0.00
ATOM 2275 HG22 VAL 141 -14.506 -1.992 -0.267 1.00 0.00
ATOM 2276 HG23 VAL 141 -15.243 -1.374 -1.744 1.00 0.00
ATOM 2277 C VAL 141 -15.764 1.321 0.815 1.00 0.00
ATOM 2278 O VAL 141 - 15.273 0.802 1.807 1.00 0.00
ATOM 2279 N PHE 142 ■ - 16.972 1.868 0.825 1.00 0.00
ATOM 2280 HN PHE 142 -17.321 2.272 0.010 1.00 0.00
ATOM 2281 CA PHE 142 -17.781 1.881 2.040 1.00 0.00
ATOM 2282 HA PHE 142 -17.1 1 1 1.938 2.883 1.00 0.00
ATOM 2283 CB PHE 142 - 18.709 3.091 2.063 1.00 0.00
ATOM 2284 HB 1 PHE 142 -18.1 13 3.986 2.061 1.00 0.00
ATOM 2285 HB2 PHE 142 - 19.301 3.062 2.966 1.00 0.00
ATOM 2286 CG PHE 142 - 19.652 3.149 0.896 1.00 0.00
ATOM 2287 CD l PHE 142 -20.913 2.580 0.981 1.00 0.00
ATOM 2288 HD l PHE 142 -21.215 2.094 1.898 1.00 0.00
ATOM 2289 CD2 PHE 142 - 19.279 3.769 -0.285 1.00 0.00
ATOM 2290 HD2 PHE 142 -18.298 4.214 -0.362 1.00 0.00
ATOM 2291 CE1 PHE 142 -21.784 2.630 -0.091 1.00 0.00
ATOM 2292 HE I PHE 142 -22.764 2.182 -0.012 1.00 0.00
ATOM 2293 CE2 PHE 142 -20.146 3.821 -1.360 1.00 0.00
ATOM 2294 HE2 PHE 142 -19.843 4.308 -2.275 1.00 0.00 ATOM 2295 CZ PHE 142 -21.400 3.251 -1.263 1.00 0.00
ATOM 2296 HZ PHE 142 -22.079 3.291 -2.102 1.00 0.00
ATOM 2297 C PHE 142 -18.610 0.615 2.159 1.00 0.00
ATOM 2298 O PHE 142 -19.265 0.193 1.206 1.00 0.00 ATOM 2299 N SER 143 -18.578 0.017 3.340 1.00 0.00
ATOM 2300 HN SER 143 -18.037 0.410 4.065 1.00 0.00
ATOM 2301 CA SER 143 -19.332 -1.203 3.589 1.00 0.00
ATOM 2302 HA SER 143 -19.398 -1.745 2.657 1.00 0.00
ATOM 2303 CB SER 143 -18.609 -2.072 4.614 1.00 0.00 ATOM 2304 HB1 SER 143 -18.398 -1.483 5.492 1.00 0.00
ATOM 2305 HB2 SER 143 -17.681 -2.424 4.189 1.00 0.00
ATOM 2306 OG SER 143 -19.397 -3.189 4.988 1.00 0.00
ATOM 2307 HG SER 143 -19.713 -3.071 5.887 1.00 0.00
ATOM 2308 C SER 143 -20.743 -0.883 4.068 1.00 0.00 ATOM 2309 O SER 143 -21.044 0.254 4.433 1.00 0.00
ATOM 2310 N ARG 144 -21.604 -1.893 4.064 1.00 0.00
ATOM 231 1 HN ARG 144 -21.301 -2.774 3.762 1.00 0.00
ATOM 2312 CA ARG 144 -22.987 -1.726 4.499 1.00 0.00
ATOM 2313 HA ARG 144 -23.470 -2.690 4.440 1.00 0.00 ATOM 2314 CB ARG 144 -23.034 -1.234 5.947 1.00 0.00
ATOM 2315 HB1 ARG 144 -24.067 -1.1 15 6.241 1.00 0.00
ATOM 2316 HB2 ARG 144 -22.539 -0.276 6.007 1.00 0.00
ATOM 2317 CG ARG 144 -22.365 -2.178 6.933 1.00 0.00
ATOM 2318 HG1 ARG 144 -21.303 -1.980 6.941 1.00 0.00 ATOM 2319 HG2 ARG 144 -22.541 -3.196 6.618 1.00 0.00
ATOM 2320 CD ARG 144 -22.914 -1.997 8.339 1.00 0.00
ATOM 2321 HDl ARG 144 -22.725 -0.982 8.656 1.00 0.00
ATOM 2322 HD2 ARG 144 -22.405 -2.681 9.001 1.00 0.00
ATOM 2323 NE ARG 144 -24.350 -2.255 8.404 1.00 0.00 ATOM 2324 HE ARG 144 -24.820 -2.413 7.559 1.00 0.00
ATOM 2325 CZ ARG 144 -25.047 -2.286 9.537 1.00 0.00
ATOM 2326 NH1 ARG 144 -24.444 -2.076 10.701 1.00 0.00
ATOM 2327 HH 1 1 ARG 144 -23.462 -1.894 10.731 1.00 0.00
ATOM 2328 HH 12 ARG 144 -24.973 -2.101 1 1.549 1.00 0.00 ATOM 2329 NH2 ARG 144 -26.351 -2.526 9.507 1.00 0.00
ATOM 2330 HH21 ARG 144 -26.810 -2.685 8.633 1.00 0.00
ATOM 2331 HH22 ARG 144 -26.875 -2.550 10.359 1.00 0.00
ATOM 2332 C ARG 144 -23.729 -0.748 3.591 1.00 0.00
ATOM 2333 O ARG 144 -23.1 17 0.1 16 2.964 1.00 0.00 ATOM 2334 N PRO 145 -25.065 -0.873 3.510 1.00 0.00
ATOM 2335 CA PRO 145 -25.891 0.004 2.674 1.00 0.00
ATOM 2336 HA PRO 145 -25.535 0.027 1.654 1.00 0.00
ATOM 2337 CB PRO 145 -27.271 -0.653 2.722 1.00 0.00
ATOM 2338 HB 1 PRO 145 -27.390 -1.312 1.875 1.00 0.00 ATOM 2339 HB2 PRO 145 -28.037 0.109 2.703 1.00 0.00
ATOM 2340 CG PRO 145 -27.286 -1.410 4.005 1.00 0.00
ATOM 2341 HG 1 PRO 145 -27.953 -2.255 3.925 1.00 0.00
ATOM 2342 HG2 PRO 145 -27.596 -0.760 4.811 1.00 0.00
ATOM 2343 CD PRO 145 -25.874 -1.878 4.226 1.00 0.00 ATOM 2344 HDl PRO 145 -25.732 -2.861 3.801 1.00 0.00
ATOM 2345 HD2 PRO 145 -25.639 -1.883 5.280 1.00 0.00
ATOM 2346 C PRO 145 -25.958 1.427 3.219 1.00 0.00
ATOM 2347 O PRO 145 -25.721 2.371 2.436 1.00 0.00
ATOM 2348 OXT PRO 145 -26.249 1.585 4.423 1.00 0.00 ATOM 2349 N PRO 205 -8.160 -4.648 14.175 1.00 0.00
ATOM 2350 HT1 PRO 205 -7.985 -5.169 13.299 1.00 0.00
ATOM 2351 HT2 PRO 205 -8.088 -5.372 14.927 1.00 0.00
ATOM 2352 CA PRO 205 -9.630 -4.421 14.128 1.00 0.00
ATOM 2353 HA PRO 205 -10.101 -5.019 14.893 1.00 0.00 ATOM 2354 CB PRO 205 -9.868 -2.950 14.418 1.00 0.00
ATOM 2355 HB1 PRO 205 -10.108 -2.814 15.461 1.00 0.00
ATOM 2356 HB2 PRO 205 -10.670 -2.582 13.802 1.00 0.00
ATOM 2357 CG PRO 205 -8.576 -2.310 14.068 1.00 0.00 ATOM 2358 HG1 PRO 205 -8.425 -1.432 14.679 1.00 0.00
ATOM 2359 HG2 PRO 205 -8.571 -2.043 13.022 1.00 0.00
ATOM 2360 CD PRO 205 -7.504 -3.333 14.352 1.00 0.00
ATOM 2361 HDl PRO 205 -7.146 -3.222 15.363 1.00 0.00
ATOM 2362 HD2 PRO 205 -6.692 -3.220 13.651 1.00 0.00 ATOM 2363 C PRO 205 -10.210 -4.790 12.765 1.00 0.00
ATOM 2364 O PRO 205 -9.470 -4.995 1 1.803 1.00 0.00
ATOM 2365 N GLU 206 -11.534 -4.868 12.686 1.00 0.00
ATOM 2366 HN GLU 206 -12.075 -4.691 13.483 1.00 0.00
ATOM 2367 CA GLU 206 -12.195 -5.208 11.432 1.00 0.00 ATOM 2368 HA GLU 206 -11.846 -6.180 11.116 1.00 0.00
ATOM 2369 CB GLU 206 -13.717 -5.251 1 1.591 1.00 0.00
ATOM 2370 HB1 GLU 206 -13.994 -6.191 12.026 1.00 0.00
ATOM 2371 HB2 GLU 206 -14.166 -5.182 10.615 1.00 0.00
ATOM 2372 CG GLU 206 -14.286 -4.120 12.436 1.00 0.00 ATOM 2373 HG1 GLU 206 -15.232 -3.81 1 12.008 1.00 0.00
ATOM 2374 HG2 GLU 206 -13.597 -3.286 12.409 1.00 0.00
ATOM 2375 CD GLU 206 -14.512 -4.521 13.880 1.00 0.00
ATOM 2376 OEl GLU 206 -15.339 -5.425 14.123 1.00 0.00
ATOM 2377 OE2 GLU 206 -13.862 -3.932 14.769 1.00 0.00 ATOM 2378 C GLU 206 -1 1.869 -4.197 10.357 1.00 0.00
ATOM 2379 O GLU 206 -1 1.268 -3.159 10.619 1.00 0.00
ATOM 2380 N PRO 207 -12.305 -4.484 9.133 1.00 0.00
ATOM 2381 CA PRO 207 -12.122 -3.615 7.999 1.00 0.00
ATOM 2382 HA PRO 207 -1 1.216 -3.034 8.079 1.00 0.00 ATOM 2383 CB PRO 207 -12.028 -4.603 6.829 1.00 0.00
ATOM 2384 HB1 PRO 207 -10.992 -4.739 6.558 1.00 0.00
ATOM 2385 HB2 PRO 207 -12.572 -4.212 5.985 1.00 0.00
ATOM 2386 CG PRO 207 -12.635 -5.893 7.322 1.00 0.00
ATOM 2387 HG1 PRO 207 -11.903 -6.685 7.263 1.00 0.00 ATOM 2388 HG2 PRO 207 -13.496 -6.138 6.722 1.00 0.00
ATOM 2389 CD PRO 207 -13.055 -5.678 8.755 1.00 0.00
ATOM 2390 HDl PRO 207 -12.778 -6.520 9.378 1.00 0.00
ATOM 2391 HD2 PRO 207 -14.118 -5.501 8.819 1.00 0.00
ATOM 2392 C PRO 207 -13.328 -2.691 7.871 1.00 0.00 ATOM 2393 O PRO 207 -13.283 -1.537 8.295 1.00 0.00
ATOM 2394 N THR 208 -14.421 -3.227 7.331 1.00 0.00
ATOM 2395 HN THR 208 -14.398 -4.159 7.043 1.00 0.00
ATOM 2396 CA THR 208 -15.665 -2.483 7.189 1.00 0.00
ATOM 2397 HA THR 208 -16.394 -3.164 6.773 1.00 0.00 ATOM 2398 CB THR 208 -16.164 -2.033 8.572 1.00 0.00
ATOM 2399 HB THR 208 -15.497 -2.432 9.324 1.00 0.00
ATOM 2400 OGl THR 208 -17.461 -2.545 8.822 1.00 0.00
ATOM 2401 HG 1 THR 208 -17.714 -2.349 9.727 1.00 0.00
ATOM 2402 CG2 THR 208 -16.227 -0.534 8.764 1.00 0.00 ATOM 2403 HG21 THR 208 -16.703 -0.314 9.707 1.00 0.00
ATOM 2404 HG22 THR 208 -16.798 -0.093 7.960 1.00 0.00
ATOM 2405 HG23 THR 208 -15.227 -0.130 8.761 1.00 0.00
ATOM 2406 C THR 208 -15.522 -1.305 6.228 1.00 0.00
ATOM 2407 O THR 208 -16.255 -1.217 5.250 1.00 0.00 ATOM 2408 N ALA 209 -14.584 -0.402 6.500 1.00 0.00
ATOM 2409 HN ALA 209 -14.023 -0.514 7.293 1.00 0.00
ATOM 2410 CA ALA 209 -14.374 0.756 5.638 1.00 0.00
ATOM 241 1 HA ALA 209 -13.347 1.073 5.748 1.00 0.00
ATOM 2412 CB ALA 209 -14.601 0.373 4.181 1.00 0.00 ATOM 2413 HB1 ALA 209 -14.292 -0.652 4.025 1.00 0.00
ATOM 2414 HB2 ALA 209 -14.028 1.022 3.540 1.00 0.00
ATOM 2415 HB3 ALA 209 -15.652 0.468 3.943 1.00 0.00
ATOM 2416 C ALA 209 -15.296 1.906 6.039 1.00 0.00
ATOM 2417 O ALA 209 -16.324 1.690 6.681 1.00 0.00
ATOM 2418 N PRO 210 -14.942 3.148 5.665 1.00 0.00
ATOM 2419 CA PRO 210 -15.747 4.329 5.991 1.00 0.00
ATOM 2420 HA PRO 210 -15.885 4.432 7.051 1.00 0.00
ATOM 2421 CB PRO 210 -14.915 5.505 5.474 1.00 0.00
ATOM 2422 HB1 PRO 210 -14.888 6.283 6.222 1.00 0.00
ATOM 2423 HB2 PRO 210 -15.363 5.884 4.576 1.00 0.00
ATOM 2424 CG PRO 210 -13.552 4.954 5.216 1.00 0.00
ATOM 2425 HG 1 PRO 210 -12.938 5.068 6.098 1.00 0.00
ATOM 2426 HG2 PRO 210 -13.102 5.465 4.378 1.00 0.00
ATOM 2427 CD PRO 210 -13.740 3.500 4.898 1.00 0.00
ATOM 2428 HDl PRO 210 -12.888 2.926 5.231 1.00 0.00
ATOM 2429 HD2 PRO 210 -13.901 3.362 3.839 1.00 0.00
ATOM 2430 C PRO 210 -17.1 10 4.301 5.307 1.00 0.00
ATOM 2431 O PRO 210 - 17.262 3.71 1 4.239 1.00 0.00
ATOM 2432 N PRO 21 1 -18.126 4.938 5.916 1.00 0.00
ATOM 2433 CA PRO 211 -19.480 4.978 5.360 1.00 0.00
ATOM 2434 HA PRO 21 1 -19.799 4.003 5.021 1.00 0.00
ATOM 2435 CB PRO 211 -20.328 5.411 6.554 1.00 0.00
ATOM 2436 HB1 PRO 21 1 -20.661 4.540 7.099 1.00 0.00
ATOM 2437 HB2 PRO 21 1 -21.181 5.976 6.208 1.00 0.00
ATOM 2438 CG PRO 21 1 -19.412 6.250 7.376 1.00 0.00
ATOM 2439 HG 1 PRO 21 1 -19.706 6.205 8.414 1.00 0.00
ATOM 2440 HG2 PRO 21 1 -19.434 7.270 7.023 1.00 0.00
ATOM 2441 CD PRO 21 1 -18.034 5.665 7.198 1.00 0.00
ATOM 2442 HDl PRO 21 1 - 17.805 4.989 8.007 1.00 0.00
ATOM 2443 HD2 PRO 21 1 -17.296 6.451 7.142 1.00 0.00
ATOM 2444 C PRO 21 1 -19.614 5.981 4.221 1.00 0.00
ATOM 2445 O PRO 21 1 -18.661 6.681 3.880 1.00 0.00
ATOM 2446 N GLU 212 -20.805 6.045 3.635 1.00 0.00
ATOM 2447 HN GLU 212 -21.525 5.461 3.951 1.00 0.00
ATOM 2448 CA GLU 212 -21.069 6.962 2.535 1.00 0.00
ATOM 2449 HA GLU 212 -20.505 7.865 2.717 1.00 0.00
ATOM 2450 CB GLU 212 -20.604 6.341 1.214 1.00 0.00
ATOM 2451 HB1 GLU 212 -21.432 5.820 0.760 1.00 0.00
ATOM 2452 HB2 GLU 212 -19.823 5.634 1.421 1.00 0.00
ATOM 2453 CG GLU 212 -20.071 7.359 0.216 1.00 0.00
ATOM 2454 HG 1 GLU 212 -19.014 7.184 0.074 1.00 0.00
ATOM 2455 HG2 GLU 212 -20.219 8.350 0.619 1.00 0.00
ATOM 2456 CD GLU 212 -20.761 7.278 -1.132 1.00 0.00
ATOM 2457 OEl GLU 212 -21.749 8.014 -1.338 1.00 0.00
ATOM 2458 OE2 GLU 212 -20.313 6.481 -1.982 1.00 0.00
ATOM 2459 C GLU 212 -22.557 7.317 2.480 1.00 0.00
ATOM 2460 O GLU 212 -23.178 7.565 3.513 1.00 0.00
ATOM 2461 N GLU 213 -23.128 7.339 1.277 1.00 0.00
ATOM 2462 HN GLU 213 -22.594 7.133 0.488 1.00 0.00
ATOM 2463 CA GLU 213 -24.532 7.659 1.099 1.00 0.00
ATOM 2464 HA GLU 213 -24.681 8.687 1.391 1.00 0.00
ATOM 2465 CB GLU 213 -24.907 7.499 -0.371 1.00 0.00
ATOM 2466 HB1 GLU 213 -24.539 8.352 -0.921 1.00 0.00
ATOM 2467 HB2 GLU 213 -25.975 7.467 -0.449 1.00 0.00
ATOM 2468 CG GLU 213 -24.346 6.240 -1.01 1 1.00 0.00
ATOM 2469 HG 1 GLU 213 -24.337 5.451 -0.273 1.00 0.00
ATOM 2470 HG2 GLU 213 -23.336 6.437 -1.338 1.00 0.00
ATOM 2471 CD GLU 213 -25.160 5.779 -2.204 1.00 0.00 TOM 2472 OEl GLU 213 -25.913 4.792 -2.064 1.00 0.00
TOM 2473 OE2 GLU 213 -25.045 6.404 -3.279 1.00 0.00
TOM 2474 C GLU : 213 -25.415 6.764 1.965 1.00 0.00
TOM 2475 0 GLU : 213 -26.577 7.147 2.218 1.00 0.00
TOM 2476 OXT GLU 213 -24.938 5.687 2.381 1.00 0.00
EN.REFLIST
B. References
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368. Yuan, B., Li, X , and Goff, S. P. (1999). Mutations altering the moloney murine leukemia virus pl2 Gag protein affect virion production and early events of the virus life cycle, Embo J 18, 4700-10. 369 Zhong, Q., Chen, Y„ Jones, D , and Lee, W. H. (1998) Perturbation of TSGIOI protein affects cell cycle progression, Cancer Res 58, 2699-702 EN.REFLIST 370. C. Sequences
1. SEQ ID NO:l is the 145 amino acid TSGIOIUEV sequence in Figure 1, designated as TSGIOI.
2. SEQ ID NO:2 TSGIOI protein sequence one example Genbank accession number Q99816.
1 mavsesqlkk mvskykyrdl tvretvnvit lykdlkpvld syvfndgssr elmnltgtip 61 vpyrgntyni piclwlldty pynppicfvk ptssmtiktg khvdangkiy lpylhewkhp 121 qsdllgliqv mivvfgdepp vfsrpisasy ppyqatgppn tsympgmpgg ispypsgypp 181 npsgypgcpy ppggpypatt ssqypsqppv ttvgpsrdgt isedtirasl isavsdklrw 241 rmkeemdraq aelnalkrte edlkkghqkl eemvtrldqe vaevdkniel lkkkdeelss
301 alekmenqse nndideviip taplykqiln lyaeenaied tifylgealr rgvidldvfl 361 khvrllsrkq fqlralmqka rktaglsdly
3. SEQ ID NO:3 DNA for TSGIOI NM_006292. human TSGIOI gene 1 gtagtggtgc cgacttcctg ttgtttgagg ccgggttggg ggtgtgcgat tgtgtgggac 61 ggtctggggc agcccagcag cggctgaccc tctgcctgcg gggaagggag tcgccaggcg
121 gccgtcatgg cggtgtcgga gagccagctc aagaaaatgg tgtccaagta caaatacaga
181 gacctaactg tacgtgaaac tgtcaatgtt attactctat acaaagatct caaacctgtt
241 ttggattcat atgtttttaa cgatggcagt tccagggaac taatgaacct cactggaaca
301 atccctgtgc cttatagagg taatacatac aatattccaa tatgcctatg gctactggac 361 acatacccat ataatccccc tatctgtttt gttaagccta ctagttcaat gactattaaa
421 acaggaaagc atgttgatgc aaatgggaag atatatcttc cttatctaca tgaatggaaa
481 cacccacagt cagacttgtt ggggcttatt caggtcatga ttgtggtatt tggagatgaa
541 cctccagtct tctctcgtcc tatttcggca tcctatccgc cataccaggc aacggggcca
601 ccaaatactt cctacatgcc aggcatgcca ggtggaatct ctccataccc atccggatac 661 cctcccaatc ccagtggtta cccaggctgt ccttacccac ctggtggtcc atatcctgcc
721 acaacaagtt ctcagtaccc ttctcagcct cctgtgacca ctgttggtcc cagtagggat
781 ggcacaatca gcgaggacac catccgagcc tctctcatct ctgcggtcag tgacaaactg
841 agatggcgga tgaaggagga aatggatcgt gcccaggcag agctcaatgc cttgaaacga
901 acagaagaag acctgaaaaa gggtcaccag aaactggaag agatggttac ccgtttagat 961 caagaagtag ccgaggttga taaaaacata gaacttttga aaaagaagga tgaagaactc
1021 agttctgctc tggaaaaaat ggaaaatcag tctgaaaaca atgatatcga tgaagttatc
1081 attcccacag ctcccttata caaacagatc ctgaatctgt atgcagaaga aaacgctatt
1 141 gaagacacta tcttttactt gggagaagcc ttgagaaggg gcgtgataga cctggatgtc
1201 ttcctgaagc atgtacgtct tctgtcccgt aaacagttcc agctgagggc actaatgcaa 1261 aaagcaagaa agactgccgg tctcagtgac ctctactgac ttctctgata ccagctggag
1321 gttgagctct tcttaaagta ttcttctctt ccttttatca gtaggtgccc agaataagtt
1381 attgcagttt atcattcaag tgtaaaatat tttgaatcaa taatatattt tctgttttct
1441 tttggtaaag actggctttt attaatgcac tttctatcct ctgtaaactt tttgtgctga
1501 atgttgggac tgctaaataa aatttgttgc ataaaaaaaa aaaaaaaaaa //
4. SEQ ID NO:4 TSGIOI protein encoded by SEQ ID NO:3
MAVSESQLKKMVSKYKYRDLTVRETVNVITLYKDLKPVLDSYVF
NDGSSRELMNLTGTIPVPYRGNTYNIPICLWLLDTYPYNPPICFVKPTSSMTIKTGKH VDANGKIYLPYLHEWKHPQSDLLGL1QVMIVVFGDEPPVFSRPISASYPPYQATGPPN
TSYMPGMPGGISPYPSGYPPNPSGYPGCPYPPGGPYPATTSSQYPSQPPVTTVGPSRD GTISEDTIRASLISAVSDKLRWRMKEEMDRAQAELNALKRTEEDLKKGHQKLEEMVTR LDQEVAEVDKNIELLKKKDEELSSALEKMENQSENNDIDEVIIPTAPLYKQILNLYAE ENAIEDTIFYLGEALRRGVIDLDVFLKHVRLLSRKQFQLRALMQKARKTAGLSDLY

Claims

VII. CLAIMS
What is claimed is
1 A method for reducing interactions between TSGIOI and GAG, comprising incubating an inhibitor with TSG IOI , GAG, or TSG IOI and GAG, wherein the inhibitor is an inhibitor of the interaction between TSGIOI and GAG, wherein the inhibitor can interact with an amino acid selected from the group consisting of amino acid 58, 61, 63, 68, 69, 70, 71, 92, 95, 139, 141, 142, 143, and 144 of SEQ ID NO 1
2 A method for inhibiting HIV budding comprising administering an inhibitor of the interaction between TSGIOI and HIV GAG, wherein the inhibitor can interact with an amino acid selected from the group consisting of amino acid 58, 61 , 63, 68, 69, 70, 71, 92, 95, 139, 141, 142, 143, and 144 of SEQ ID NO 1
3 A method of treating a subject comprising administering to the subject an inhibitor of HIV budding, wherein the inhibitor reduces the interaction between TSGIOI and HIV GAG, wherein the subject is in need of such treatment, wherein the inhibitor can interacts with an amino acid selected from the group consisting of amino acid 58, 61 , 63, 68, 69, 70, 71 , 92, 95, 139, 141 , 142, 143, and 144 of SEQ ID NO 1 4 A method of identifying an inhibitor of an interaction between TSG 101 and retroviral GAG comprising incubating a set of molecules with TSGIOI, conserved variant, fragment thereof, or combination thereof, forming a mixture, and isolating the molecules that can disrupt the interaction between TSGIOI and retroviral GAG, wherein the interaction disrupted comprises an interaction between the retroviral GAG and an amino acid of TSGIOI, wherein the amino acid is selected from the group consisting of amino acid 58, 61, 63, 68, 69, 70, 71 , 92, 95, 139, 141, 142, 143, and 144 of SEQ ID NO 1
5 A method of identifying an inhibitor of an interaction between TSGIOI and retroviral GAG comprising incubating a set of molecules with retroviral GAG, conserved vaπant, fragment thereof, or combination thereof, forming a mixture, and isolating the molecules that can disrupt the interaction between retroviral GAG and TSGIOI, wherein the interaction disrupted comprises an interaction between the retroviral GAG and an amino acid of TSGIOI , wherein the amino acid is selected from the group consisting of amino acid 58, 61, 63, 68, 69, 70, 71 , 92, 95, 139, 141 , 142, 143, and 144 of SEQ ID NO 1
6 A method of identifying an inhibitor of an interaction between TSGIOI and retroviral GAG comprising displaying the structure of the TSG IOI, TSG101-UEV, TSGIOI PTAP binding domain, or TSGIOI Ub binding domain in a computer medium, and identifying a molecule that interacts with the displayed structure
7 A method of manufacturing a composition for inhibiting the interaction between TSGIOI and GAG comprising admixing the inhibitor with a pharmaceutical carrier
8 A method of identifying an inhibitor of TSG 101-GAG interaction comprising,
(a) administering a composition to a system, wherein the system supports TSG101-GAG interaction,
(b) assaying the effect of the composition on the amount of TSG 101 -GAG in the system, and (c) selecting a composition which causes a decrease in the amount of TSG 101 -GAG present in the system relative to the system without the addition of the composition.
9. A method of identifying an inhibitor of HIV budding comprising,
(a) administering a composition to a system, wherein the system supports HIV budding via a TSG 101 -GAG interaction,
(b) assaying the effect of the composition on the amount of HIV budding in the system, and
(c) selecting a composition which causes a decrease in the amount of HIV budding present in the system because of an inhibition of the TSG IOI-GAG interaction relative to the system without the addition of the composition. 10. A method of inhibiting HIV budding comprising administering a composition, wherein the composition reduces HIV budding, wherein the composition is defined as a composition capable of being identified by administering the composition to a system, wherein the system supports HIV budding via a TSG101-GAG interaction, assaying the effect of the composition on the amount of HIV budding in the system, and selecting a composition which causes a decrease in the amount of HIV budding present in the system because of an inhibition of the TSG101-GAG interaction relative to the system without the addition of the composition.
1 1. A method of inhibiting HIV budding comprising administering a composition that reduces an interaction between TSGIOI and GAG.
12. A method of making a composition capable of inhibiting HIV budding comprising admixing a compound with a pharmaceutically acceptable carrier, wherein the compound is identified by administering the compound to a system, wherein the system supports HIV budding via a TSG 101 -GAG interaction, assaying the effect of the compound on the amount of HIV budding in the system, and selecting a compound which causes a decrease in the amount of HIV budding in the system because of an inhibition of the TSGIOI- GAG interaction, relative to the system without the addition of the compound. 13. A method of manufacturing an inhibitor to HIV budding comprising,
(a) administering a composition to a system, wherein the system supports HIV budding via a TSG 101 -GAG interaction,
(b) assaying the effect of the composition on the amount of HIV budding in the system,
(c) selecting a composition which causes a decrease in the amount of HIV budding present in the system because of an inhibition of the TSG101-GAG interaction, relative to the system without the addition of the composition, and
(d) synthesizing the composition.
14. A method of identifying an inhibitor of an interaction between TSGIOI and GAG comprising (a) administering a composition to a system, wherein the system comprises TSGIOI , (b) assaying the effect of the composition on a TSGIOI-GAG interaction, and
(c) selecting a composition which inhibits the TSG 101 -GAG interaction.
15. A cell comprising,
(a) an exogenous nucleic acid comprising sequence encoding a TSGIOI gene, conserved variant, or fragment thereof, and
(b) a nucleic acid comprising sequence encoding a GAG gene, conserved variant, or fragment thereof.
16. A method for reducing interactions between TSGIOI and GAG, comprising incubating an inhibitor with TSG 101, GAG, or TSG 101 and GAG, wherein the inhibitor is an inhibitor of the interaction between TSGIOI and GAG, wherein the inhibitor can interact with at least one atom selected from the group consisting of the atoms ofamino acids 58, 61, 63, 68, 69, 70, 71, 92, 95, 139, 141, 142, 143, and 144 set forth in Table 5 or in Table 6.
17. A method for inhibiting HIV budding comprising administering an inhibitor of the interaction between TSGIOI and HIV GAG, wherein the inhibitor can interact with at least one atom selected from the group consisting of the atoms of amino acids 58, 61, 63, 68, 69, 70, 71, 92, 95, 139, 141 , 142, 143, and 144 set forth in Table 5 or in Table 6.
18. A method of treating a subject comprising administering to the subject an inhibitor of HIV budding, wherein the inhibitor reduces the interaction between TSGIOI and HIV GAG, wherein the subject is in need of such treatment, wherein the inhibitor can interact with at least one atom selected from the group consisting ofthe atoms of amino acids 58, 61, 63, 68, 69, 70, 71, 92, 95, 139, 141, 142, 143, and 144 set forth in Table 5 or in Table 6.
19. A method of characterizing protein structures comprising the steps: (a) determining a TSGIOI PTAP binding domain three-dimensional structure; (b) determining an experimental protein three-dimensional structure ; (c) comparing the experimental protein three-dimensional structure to the TSGIOI PTAP binding domain three-dimensional structure; and (d) recording variances between the TSGIOI PTAP binding domain three-dimensional structure and the experimental protein three-dimensional structure.
20. A method of evaluating two or more experimental proteins in respect to the TSGIOI PTAP binding domain, comprising: (i) evaluating the variances of (d) of claim 5 for a first experimental protein; (ii) evaluating the variances of (d) of claim 5 for a second experimental protein; and (iii) ranking the experimental protein with the least variance from the structure of TSGIOI PTAP binding domain as being most similar.
21. A method of displaying a representation of a TSG-101 PTAP binding domain on a computer having a processing means, a memory means, an input means and an output means comprising: receiving the three-dimensional coordinates of atoms of a TSG-101 PTAP binding domain; producing a representation ofthe TSG-101 PTAP binding domain based upon the received coordinates; and displaying the representation ofthe TSG 101 PTAP binding domain on the visual display means.
22. A method of displaying a representation of an analog of a TSGIOI PTAP binding domain comprising: (a) determining the three-dimensional coordinates of atoms of a TSGIOI PTAP binding domain;
(b) providing a computer having a memory means, a data input means, a visual display means, the memory means containing three-dimensional molecular simulation software operable to retrieve coordinate data from the memory means and to display a three-dimensional representation of a molecule on the visual display means and being operable to produce a representation of an analog ofthe molecule responsive to operator-selected changes to the chemical structure ofthe molecule and to display the representation ofthe analog;
(c) inputting three-dimensional coordinate data of the atoms ofthe TSGIOI PTAP binding domain into the computer and storing the data in the memory means; (d) displaying the representation of the TSG 101 PTAP binding domain on the visual display means;
(e) inputting into the data input means ofthe computer at least one operator-selected change in chemical structure of the TSG I OI PTAP binding domain forming a TSGIOI PTAP binding domain analog structure; (f) executing the molecular simulation software to produce a modified three-dimensional molecular representation ofthe analog structure; and
(g) displaying the representation ofthe analog structure on the visual display means, whereby changes in three-dimensional structure ofthe TSGIOI PTAP binding domain consequent on changes in chemical structure can be visually determined. 24. A method for identifying a potential ligand of a protein comprising a TSGIOI PTAP binding domain comprising:
(a) using a three-dimensional structure ofthe TSGIOI PTAP binding domain function or portions thereof formed from the atomic coordinates of the TSGIOI PTAP binding domain;
(b) employing the three-dimensional structure to design or select the potential ligand. 25. An apparatus for determining whether a compound will interact with a protein containing a
TSGIOI PTAP binding domain, comprising:
(a) a memory that stores a set of coordinates and identities of the atoms of the TSGIOI PTAP binding domain that together form a solvent-accessible surface; and executable instructions; and
(b) a processor, wherein the executes instructions to receive structural information for a candidate compound; determine if the structure ofthe candidate compound is complementary to the structure of the solvent-accessible surface ofthe TSGIOI PTAP binding domain; and output the results ofthe determination.
26. Computer-readable storage media comprising one or more computer readable media storing digitally-encoded structural data, wherein the data comprise the identity and three-dimensional coordinates, or coordinates providing a structural homolog, of at least 2 amino acids set forth in SEQ ID NO:l .
27. An apparatus comprising:
(a) a system data store capable of storing coordinate sets; and
(b) a system processor in communication with the system data store that:
(i) receives and stores a subject set of coordinates for a subject structure; (ii) compares the subject set of coordinates to a reference set of coordinates related to the TSG 101 PTAP binding domain by:
(1) calculating the root mean squared deviation of the subject set of coordinates from the reference set of coordinates; and
(2) comparing the root mean squared deviation to limit values; and (iii) assigns the subject structure a function based on the subject structure's similarity to the reference structures if the root mean squared deviation is less than or equal to the limit values.
28. A method of determining relationships between two or more polypeptide structures, comprising:
(a) obtaining a reference structure, wherein the reference structure is a structure of a polypeptide comprising the TSGIOI PTAP binding domain or a portion thereof; (b) obtaining at least one subject structure;
(c) determining a reference structure topology diagram and a subject structure topology diagram;
(d) comparing the reference structure topology diagram and the subject structure topology diagram; and (e) assigning a relationship between the reference structure and any subject structure based on deviations between the reference structure and subject structure.
29. A method for reducing interactions between TSGIOI and Ubiquitin, comprising incubating an inhibitor with TSGIOI, Ubiquitin, or TSGIOI and Ubiquitin, wherein the inhibitor is an inhibitor ofthe interaction between TSGIOI and Ubiquitin, wherein the inhibitor can interact with an amino acid selected from the group consisting of amino acid 43, 45,and 46 of SEQ ID NO: 1.
30. A method for inhibiting HIV budding comprising administering an inhibitor of the interaction between TSGIOI and Ubiquitin, wherein the inhibitor can interact with an amino acid selected from the group consisting of amino acid 43, 45,and 46 of SEQ ID NO: l .
31. A method of treating a subject comprising administering to the subject an inhibitor of HIV budding, wherein the inhibitor reduces the interaction between TSGI OI and Ubiquitin, wherein the subject is in need of such treatment, wherein the inhibitor can interacts with an amino acid selected from the group consisting ofamino acid 43, 45,and 46 of SEQ ID NO: l . 32. A method of identifying an inhibitor of an interaction between TSG IO I and Ubiquitin comprising incubating a set of molecules with TSGIOI, conserved variant, fragment thereof, or combination thereof, forming a mixture, and isolating the molecules that can disrupt the interaction between TSGIOI and Ubiquitin, wherein the interaction disrupted comprises an interaction between the Ubiquitin and an amino acid of TSG IOI, wherein the amino acid is selected from the group consisting of amino acid 43, 45,and 46 of SEQ ID NO: l .
33. A method of identifying an inhibitor of an interaction between TSGIOI and Ubiquitin comprising incubating a library of molecules with Ubiquitin, conserved variant, fragment thereof, or combination thereof, forming a mixture, and isolating the molecules that can disrupt the interaction between Ubiquitin and TSGIOI , wherein the interaction disrupted comprises an interaction between the Ubiquitin and an amino acid of TSG IOI , wherein the amino acid is selected from the group consisting of amino acid 43, 45,and 46 of SEQ ID NO: l .
34. A method of manufacturing a composition for inhibiting the interaction between TSG 101 and Ubiquitin comprising admixing the inhibitor with a pharmaceutical carrier.
35. A method of identifying an inhibitor of TSG 101 -Ubiquitin interaction comprising, (a) administering a composition to a system, wherein the system supports TSG 101 -Ubiquitin interaction,
(b) assaying the effect ofthe composition on the amount of TSGIOI-Ubiquitin in the system, and
(c) selecting a composition which causes a decrease in the amount of TSG 101 -Ubiquitin present in the system relative to the system without the addition ofthe composition.
36. A method of identifying an inhibitor of HIV budding comprising,
(a) administering a composition to a system, wherein the system supports HIV budding via a TSG IO I-Ubiquitin interaction,
(b) assaying the effect ofthe composition on the amount of HIV budding in the system, and (c) selecting a composition which causes a decrease in the amount of HIV budding present in the system because of an inhibition of the TSG IOI -Ubiquitin interaction relative to the system without the addition ofthe composition.
37. A method of inhibiting HIV budding comprising administering a composition, wherein the composition reduces HIV budding, wherein the composition is defined as a composition capable of being identified by administering the composition to a system, wherein the system supports HIV budding via a TSG 101 -Ubiquitin interaction, assaying the effect ofthe composition on the amount of HIV budding in the system, and selecting a composition which causes a decrease in the amount of HIV budding present in the system because of an inhibition of the TSG 101 -Ubiquitin interaction relative to the system without the addition of the composition 38 A method of inhibiting HIV budding comprising administering a composition that reduces an interaction between TSGIOI and Ubiquitin
39 A method of making a composition capable of inhibiting HIV budding comprising admixing a compound with a pharmaceutically acceptable carrier, wherein the compound is identified by administering the compound to a system, wherein the system supports HIV budding via a TSGIOI-Ubiquitin interaction, assaying the effect ofthe compound on the amount of HIV budding in the system, and selecting a compound which causes a decrease in the amount of HIV budding in the system because of an inhibition ofthe TSG 101- Ubiquitin interaction, relative to the system without the addition ofthe compound
40 A method of manufacturing an inhibitor to HIV budding comprising,
(a) administering a composition to a system, wherein the system supports HIV budding via a TSG 101 -Ubiquitin interaction,
(b) assaying the effect of the composition on the amount of HIV budding in the system,
(c) selecting a composition which causes a decrease in the amount of HIV budding present in the system because of an inhibition of the TSG 101 -Ubiquitin interaction, relative to the system without the addition of the composition, and (d) synthesizing the composition
41 A method of identifying an inhibitor of an interaction between TSGIOI and Ubiquitin comprising
(a) administering a composition to a system, wherein the system comprises TSGIOI,
(b) assaying the effect ofthe composition on a TSG 101 -Ubiquitin interaction, and
(c) selecting a composition which inhibits the TSG 101 -Ubiquitin interaction. 42 A cell comprising,
(a) an exogenous nucleic acid comprising sequence encoding a TSGIOI gene, conserved variant, or fragment thereof, and
(b) ubiquitin
43 A method for reducing interactions between TSGIOI and Ubiquitin, comprising incubating an inhibitor with TSG 101, Ubiquitin, or TSG 101 and Ubiquitin, wherein the inhibitor is an inhibitor of the interaction between TSGIOI and Ubiquitin, wherein the inhibitor can interact with at least one atom selected from the group consisting of the atoms of amino acids 43, 45, and 46 set forth in Table 5 or in Table 6
44 A method for inhibiting HIV budding comprising administering an inhibitor ofthe interaction between TSGIOI and Ubiquitin, wherein the inhibitor can interact with at least one atom selected from the group consisting of the atoms of amino acids 43, 45, and 46 set forth in Table 5 or in Table 6.
45. A method of treating a subject comprising administering to the subject an inhibitor of HIV budding, wherein the inhibitor reduces the interaction between TSGIOI and Ubiquitin, wherein the subject is in need of such treatment, wherein the inhibitor can interact with at least one atom selected from the group consisting ofthe atoms of amino acids 43, 45, and 46 set forth in Table 5 or in Table 6.
46. A method of characterizing protein structures comprising the steps: (a) determining a TSG 101 Ubiquitin binding domain three-dimensional structure; (b) determining an experimental protein three- dimensional structure ; (c) comparing the experimental protein three-dimensional structure to the TSG IOI Ubiquitin binding domain three-dimensional structure; and (d) recording variances between the TSG IOI Ubiquitin binding domain three-dimensional structure and the experimental protein three-dimensional structure.
47. A method of evaluating two or more experimental proteins in respect to the TSG IOI Ubiquitin binding domain, comprising: (i) evaluating the variances of (d) of claim 5 for a first experimental protein; (ii) evaluating the variances of (d) of claim 5 for a second experimental protein; and (iii) ranking the experimental protein with the least variance from the structure of TSG IOI Ubiquitin binding domain as being most similar.
48. A method of displaying a representation of a TSG-101 Ubiquitin binding domain on a computer having a processing means, a memory means, an input means and an output means comprising: receiving the three-dimensional coordinates of atoms of a TSG-101 Ubiquitin binding domain; producing a representation ofthe TSG-101 Ubiquitin binding domain based upon the received coordinates; and displaying the representation ofthe TSG IOI Ubiquitin binding domain on the visual display means.
49. A method of displaying a representation of an analog of a TSG IOI Ubiquitin binding domain comprising:
(a) determining the three-dimensional coordinates of atoms of a TSG IOI Ubiquitin binding domain;
(b) providing a computer having a memory means, a data input means, a visual display means, the memory means containing three-dimensional molecular simulation software operable to retrieve coordinate data from the memory means and to display a three-dimensional representation of a molecule on the visual display means and being operable to produce a representation of an analog ofthe molecule responsive to operator-selected changes to the chemical structure ofthe molecule and to display the representation of the analog;
(c) inputting three-dimensional coordinate data of the atoms ofthe TSG 101 Ubiquitin binding domain into the computer and storing the data in the memory means; (d) displaying the representation ofthe TSG I OI Ubiquitin binding domain on the visual display means;
(e) inputting into the data input means of the computer at least one operator-selected change in chemical structure ofthe TSG IOI Ubiquitin binding domain forming a TSG IOI Ubiquitin binding domain analog structure;
(f) executing the molecular simulation software to produce a modified three-dimensional molecular representation ofthe analog structure; and
(g) displaying the representation ofthe analog structure on the visual display means, whereby changes in three-dimensional structure ofthe TSGIOI Ubiquitin binding domain consequent on changes in chemical structure can be visually determined.
50. A method for identifying the TSG IOI Ubiquitin binding domain analogs that mimic the three- dimensional structure ofthe TSGIOI Ubiquitin binding domain, comprising: producing a multiplicity of analog structures of the TSG IO I Ubiquitin binding domain by the method of claim 1 1 , and selecting an analog structure with a structure of the Ubiquitin binding domain which is substantially like the TSG 101 Ubiquitin binding domain.
51. A method for identifying a potential ligand of a protein comprising a TSG IOI Ubiquitin binding domain comprising:
(a) using a three-dimensional structure ofthe TSGIOI Ubiquitin binding domain function or portions thereof formed from the atomic coordinates ofthe TSG I OI Ubiquitin binding domain; (b) employing the three-dimensional structure to design or select the potential ligand.
52. An apparatus for determining whether a compound will interact with a protein containing a TSG IOI Ubiquitin binding domain, comprising:
(a) a memory that stores a set of coordinates and identities ofthe atoms ofthe TSGIOI Ubiquitin binding domain that together form a solvent-accessible surface; and executable instructions; and (b) a processor, wherein the executes instructions to receive structural information for a candidate compound; determine if the structure ofthe candidate compound is complementary to the structure of the solvent-accessible surface ofthe TSG I O I Ubiquitin binding domain; and output the results of the determination.
53. An apparatus comprising: (a) a system data store capable of storing coordinate sets; and
(b) a system processor in communication with the system data store that:
(i) receives and stores a subject set of coordinates for a subject structure;
(ii) compares the subject set of coordinates to a reference set of coordinates related to the TSG 101 Ubiquitin binding domain by: (1) calculating the root mean squared deviation ofthe subject set of coordinates from the reference set of coordinates; and
(2) comparing the root mean squared deviation to limit values; and
(iii) assigns the subject structure a function based on the subject structure's similarity ,5 to the reference structures if the root mean squared deviation is less than or equal to the limit values..
54. A method of determining relationships between two or more polypeptide structures, comprising:
(a) obtaining a reference structure, wherein the reference structure is a structure of a polypeptide comprising the TSGIOI Ubiquitin binding domain or a portion thereof;
(b) obtaining at least one subject structure; 0 (c) determining a reference structure topology diagram and a subject structure topology diagram;
(d) comparing the reference structure topology diagram and the subject structure topology diagram; and
(e) assigning a relationship between the reference structure and any subject structure based 5 on deviations between the reference structure and subject structure.
PCT/US2003/015616 2002-05-15 2003-05-15 3d structure of the tsg101 uev domain WO2003096985A2 (en)

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