WO2006018287A1 - Three-dimensional strcture of the human aspartyl protease beta-site amyloid precursor-protein-cleaving enzyme 2 (bace2), methods and use thereof - Google Patents

Three-dimensional strcture of the human aspartyl protease beta-site amyloid precursor-protein-cleaving enzyme 2 (bace2), methods and use thereof Download PDF

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WO2006018287A1
WO2006018287A1 PCT/EP2005/008900 EP2005008900W WO2006018287A1 WO 2006018287 A1 WO2006018287 A1 WO 2006018287A1 EP 2005008900 W EP2005008900 W EP 2005008900W WO 2006018287 A1 WO2006018287 A1 WO 2006018287A1
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atom
bace2
leu
phe
tyr
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PCT/EP2005/008900
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French (fr)
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Jörg EDER
Bernd Gerhartz
Ulf Eidhoff
Ulrich Hommel
Susanne Worpenberg
Nils Ostermann
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Novartis Ag
Novartis Pharma Gmbh
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Publication of WO2006018287A1 publication Critical patent/WO2006018287A1/en

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6478—Aspartic endopeptidases (3.4.23)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2299/00—Coordinates from 3D structures of peptides, e.g. proteins or enzymes

Definitions

  • the present invention relates to the aspartyl protease beta-site amyloid precursor protein- cleaving enzyme 2 (BACE2), in particular, the three-dimensional structure of BACE2.
  • BACE2 aspartyl protease beta-site amyloid precursor protein- cleaving enzyme 2
  • the invention also relates to the crystalline forms of liganded or unliganded human BACE2. Further, the invention provides methods of expression, refolding and purification of the recombinant human aspartyl protease BACE2 for the use in crystallization and methods of making crystals comprising BACE2 and its structure determination.
  • the invention also relates to the use of the three-dimensional structure of BACE2 for identifying and designing ligands or low molecular weight compounds which inhibit the biological function of BACE2 or any other aspartyl protease.
  • BACE2 was recently identified as a homolog of BACE1 through expressed sequence tags data base searching (Yan et al., 1999) and genomic cloning (Acquat et al., 2000).
  • BACE1 also known as beta-secretase or beta-site amyloid precursor protein-cleaving enzyme 1 , is an aspartyl protease involved in the process leading to the generation of amyloid plaques from the amyloid precursor protein in Alzheimer's disease (Vassar et al., 1999).
  • the two BACE proteins share 51% identity at the amino acid level.
  • BACE2 transcripts are expressed in the central nervous system and many peripheral tissues; however, its expression level in neurons is substantially lower than that of BACE1 (Bennett et al., 2000).
  • BACE2 cleaves ⁇ -secretase substrates similar to BACE1, processing both the wild-type and Swedish mutant amyloid precursor protein (Hussain et al., 2000).
  • BACE2 maps to chromosome 21q22.3 (Yan et al., 1999), the Down's syndrome critical region, and is up-regulated in Down's syndrome (Barbiero et al., 2003).
  • BACE2 is over expressed in human breast cancer (Kondoh et al., 2003) and participates, together with BACE1, in normal and abnormal processes of human muscle biology (Vattemi et al., 2003).
  • the present invention provides the three-dimensional structure of BACE2 thereby enabling the identification and design of ligands or low molecular weight molecules that either specifically inhibit BACE2, or avoid its inhibition.
  • the present invention relates to:
  • the three-dimensional structural information revealed from the crystal of BACE2 can be used for structure-based drug discovery, for screening, identifying and designing inhibitors of BACE2 and other members of the aspartyl protease family.
  • the present invention provides BACE2 in crystallized form.
  • it provides a crystal comprising BACE2 and a ligand bound to BACE2 as a complex.
  • the parameters characterising the unit cell may vary within a limited range, for example, a,b,c each vary by up to 5 Angstroms.
  • the space group of the present invention is R3 rhombohedral.
  • unit cell refers to the basic shape block.
  • the entire volume of a crystal is constructed by regular assembly of such blocks.
  • Each unit cell comprises a complete representation of the unit of pattern, the repetition of which builds up the crystal.
  • space group refers to the arrangement of symmetry elements of a crystal.
  • a crystal of. BACE2 comprising BACE2 in complex with a ligand is provided wherein said crystal has a three-dimensional structure characterized by the atomic structure coordinates of Table 1.
  • said BACE2 comprises the sequences of SEQ ID. No. 2 and SEQ ID. No. 3, a mutant, a fragment or homologue thereof.
  • said BACE2 comprises at least the substrate binding site.
  • a crystal comprising BACE2 (SEQ ID No. 3, a mutant, a fragment or homologue thereof) bound to at least one ligand or low molecular weight compound.
  • ligand refers to a molecule or group of molecules that bind to one or more specific sites of BACE2, most preferably to the active site of said BACE2.
  • Ligands according to the invention are preferably low molecular weight molecules. - A -
  • low molecular weight compound refers to preferably organic compounds generally having a molecular weight less than about 1000, more preferably less than about 600. Most preferably, said low molecular weight compounds or ligands inhibit biological activity of BACE2 or any other aspartyl protease.
  • peptide or “peptide derivative” are intended to embrace a “peptidomimetic” or “peptide analogue” which complement the three-dimensional structure of the binding site of BACE2 or can be designed with improved physical or chemical properties to bind with the three-dimensional binding site of the BACE2 as provided in the present invention.
  • mutant refers to differences within the wild-type sequence of BACE2 set forth in SEQ. ID No. 1 by deletion, insertion, extension, or replacement of one or more selected amino acids.
  • mutant also refers to a polypeptide, whose amino acid sequence differs from the sequence given in SEQ ID No.3 by deletion, insertion or preferably replacement of one or more selected amino acids.
  • a BACE2 mutant of the present invention is preferably at least 50% homologous to SEQ ID No. 3, more preferably at least 80% homologous to SEQ ID No. 3 most preferably at least 90% homologous to SEQ ID No. 3.
  • a "fragment" of BACE2 according to the invention comprises more than 50% of the full- length sequence of BACE2 according to SEQ ID No. 3, more preferably at least 80% of the full length sequence of BACE2 according to SEQ ID No. 3, most preferably at least 90% of the full-length sequence of BACE2 according to SEQ ID No. 3.
  • a BACE2 mutant may be crystallizable with or without at least one ligand or with or without the pro-sequence or parts of the pro-sequence of BACE2.
  • a BACE2 fragment may be crystallizable with or without at least one ligand or with or without the pro-sequence or parts of the pro-sequence of BACE2.
  • a method is provided wherein BACE2, a mutant, fragment or homologue thereof is bound to at least one ligand at any step prior to crystallization.
  • BACE2 crystals are stable if kept under suitable conditions.
  • the crystals are stable in there mother liquor at 2O 0 C for at least 3-4 weeks.
  • Preferable storage is frozen in liquid nitrogen.
  • BACE2 or a fragment or homologue thereof is advantageously obtained by expressing proBACE2 in a recombinant E. coli cell culture and subsequent refolding and auto-proteolytic cleavage of the pro-sequence.
  • a method for making a crystal of BACE2 comprising the following steps:
  • BACE2 SEQ ID No. 1
  • BACE2 homologue e.g. SEQ ID No. 2 or SEQ ID No. 1
  • said method for making a crystal involves BACE2 (SEQ ID No.3), a mutant, a fragment or homologue thereof.
  • BACE2 may be prepared by isolation from natural sources, e.g. cultured human cells or preferably by recombinant heterologous expression. Expression of recombinant BACE2 is achievable in eukaryotic or prokaryotic systems. For example, recombinant human BACE2 may be expressed in bacteria.
  • the protease may be expressed as a fusion protein, for example as a Strep-tag fusion protein, a glutathione-S-transferase (GST) fusion protein, a histidine-tagged fusion protein, or as an untagged protein. If desired, the fusion partner is removed before crystallization.
  • the heterologously produced BACE2 to be used for crystallization is potentially biologically active. Such ability may be determined by morphological, biochemical or viability analysis well-known in the art. Methods for the preparation of BACE2 mutants are commonly known in the art. For example, BACE2 mutants may be prepared by expression of BACE2 DNA previously modified in its coding region by oligo-nucleotide directed mutagenesis.
  • purified BACE2 is preferably at least 90 % homogeneous. Protein homogeneity is determinable according to analytical methods well-known in the art, e.g. sequence analysis, electrophoresis, spectroscopic or chromatographic techniques. The purified protein is potentially proteolytically active. Appropriate assays for determining BACE2 activity towards a suitable substrate, e.g. a natural substrate or a synthetic substrate, are known in the art.
  • BACE2 may be complexed with a low molecular weight compound or ligand which is capable of suitably binding to BACE2.
  • a compound inhibiting BACE2 activity Preferred is a compound inhibiting BACE2 activity.
  • Protease inhibition is determinable employing assays known in the art. Suitable inhibitors include protease inhibitors which act on the catalytic site to inhibit BACE2 activity.
  • cystallization can be used in the claimed invention including vapor diffusion, dialysis or batch crystallization.
  • vapor diffusion crystallization a small volume (i.e., a few microliters) of protein solution is mixed with a solution containing a precipitant. This mixed volume is suspended over a well containing a small amount, i.e. about 0.15-1 ml, of precipitant. Vapor diffusion between the drop and the well will result in crystal formation in the drop.
  • the dialysis method of crystallization utilizes a semipermeable size-exclusion membrane that retains the protein but allows small molecules (i.e. buffers and precipitants) to diffuse in and out.
  • small molecules i.e. buffers and precipitants
  • the precipitant is allowed to slowly diffuse through the membrane and reduce the solubility of the protein while keeping the protein concentration fixed.
  • the batch method generally involves the slow addition of a precipitant to an aqueous solution of protein until the solution just becomes turbid, at this point the container can be sealed and left undisturbed for a period of time until crystallization occurs.
  • the precipitant and the target molecule solution are simply mixed. Supersaturation is achieved directly rather than by diffusion.
  • the batch technique is performed under oil. The oil prevents evaporation and extremely small drops can be used. For this, the term "microbatch" is used.
  • a modification of this technique is not to use paraffin oil (which prevents evaporation completely) but rather use silicone oil or a mixture of silicone and paraffin oils so that a slow evaporation is possible.
  • the claimed invention can encompass any and all methods of crystallization.
  • One skilled in the art can choose any of such methods and vary the parameters such that the chosen method results in the desired crystals.
  • One preferred method of crystallization of BACE2 involves mixing a BACE2 solution with a "reservoir buffer", with a lower concentration of the precipitating agent necessary for crystal formation.
  • concentration of the precipitating agent has to be increased, e.g. by addition of precipitating agent, for example by titration, or by allowing the concentration of precipitating agent to balance by diffusion between the crystallization buffer and a reservoir buffer.
  • Diffusion may be achieved e.g. by vapour diffusion techniques allowing diffusion of water in the common gas phase.
  • vapour diffusion methods such as the "hanging drop” or the “sitting drop” method.
  • vapour diffusion method a drop of crystallization buffer containing the protein is hanging above or sitting beside a much larger pool of reservoir buffer.
  • the balancing of the precipitating agent can be achieved through a semipermeable membrane (dialysis method) that separates the crystallization buffer from the reservoir buffer and prevents dilution of the protein into the reservoir buffer.
  • Formation of BACE2 crystals can be achieved under various conditions which are essentially determined by the following parameters: pH, presence of salts and additives, precipitating agent, protein concentration and temperature.
  • the pH may range, for example, from about 3.0 to 11.0.
  • the present invention also relates to a computer readable medium having stored a model of the BACE2 crystal structure.
  • said model is built from all or part of the X-ray diffraction data. The atomic coordinates are shown in Table 1.
  • the present invention provides the structure coordinates of human BACE2.
  • structure coordinates or "atomic coordinates” refers to mathematical coordinates derived from the mathematical equations (fourier transformation) related to the diffraction pattern obtained on a monochromatic beam of X-rays by the atoms (scattering centers) of a crystal comprising a BACE2.
  • the diffraction data are used to calculate an electron density map of the repeating unit of the crystal.
  • the electron density maps are used to establish the positions of the individual atoms within the unit cell of the crystal.
  • Structural coordinates of a crystalline composition of this invention may be stored in a machine-readable form on a machine-readable storage medium, e.g. a computer hard drive, diskette, DAT tape, CD, DVD etc., for display as a three-dimensional shape or for other uses involving computer-assisted manipulation of, or computation based on, the structural coordinates or the three-dimensional structures they define.
  • a machine-readable storage medium e.g. a computer hard drive, diskette, DAT tape, CD, DVD etc.
  • data defining the three dimensional structure of a protein of BACE2, or portions or structurally similar homologues of such proteins may be stored in a machine-readable storage medium, and may be displayed as a graphical three-dimensional representation of the protein structure, typically using a computer capable of reading the data from said storage medium and programmed with instructions for creating the representation from such data.
  • a computer readable medium comprising data storage material encoded with computer readable data wherein said data comprises the atomic coordinates of Table 1 comprising BACE2.
  • a method for determining the three- dimensional structure of BACE2 comprising:
  • a method for determining the three- dimensional structure of a complex comprising BACE2 (SEQ ID No.3), a mutant fragment or homologue thereof bound to at least one ligand comprising the steps of: (i) obtaining x-ray diffraction data for a crystal of the complex
  • a three-dimensional BACE2 model is obtainable from a BACE2 crystal comprising BACE2, mutant, fragment or homologue thereof.
  • Such a model can be built or refined from all or part of the BACE2 structure data of the present invention using the x-ray diffraction coordinates, particularly the atomic structure coordinates of Table 1.
  • the knowledge obtained from the three-dimensional model of the catalytic binding site of - BACE2 can be used in various ways. For example, it can be used to identify chemical entities, for example, small organic and bioorganic molecules such as peptidomimetics and synthetic organic molecules that bind to BACE2 and preferably block or prevent a BACE2 mediated or associated process or event, or that bind to another aspartyl protease or prevent another aspartyl protease mediated or associated process or event.
  • the skilled artisan constructs a model of the BACE2. For example, every atom can be depicted as a sphere of the appropriate van der Waals radius, and a detailed surface map of BACE2 can be constructed.
  • Chemical entities that have a surface that mimics the accessible surface of the catalytic binding site of BACE2 can be constructed by those skilled in the art.
  • the skilled artisan can screen three-dimensional structural databases of compounds to identify those compounds that position appropriate functional groups in similar three dimensional structural arrangement, then build combinatorial chemistry libraries around such chemical entities to identify those with high affinity to the catalytic binding site of BACE2.
  • a method for identifying a ligand or low molecular weight compound that binds to BACE2 comprising:
  • a method for identifying a ligand or low molecular weight compound that binds to BACE2 wherein BACE2 comprises at least the substrate binding site of said protease.
  • Ligands or small molecular compounds can be identified from screening compound databases or libraries and using a computational means to form a fitting operation to a binding site on BACE2.
  • the three dimensional structure of BACE2 as provided in the present invention in whole or in part by the structural coordinates of Table 1 , can be used together with various docking programs.
  • the potential inhibitory or binding effect of a chemical entity on BACE2 may be analyzed prior to its actual synthesis and testing by the use of computer-modeling techniques. If the theoretical structure of the given chemical entity suggests insufficient interaction and association between it and BACE2, the need for synthesis and testing of the chemical entity is obviated. However, if computer modeling indicates a strong interaction, the molecule may then be synthesized and tested for its ability to bind to BACE2. Thus, expensive and time- consuming synthesis of inoperative compounds may be avoided.
  • An inhibitory or other binding compound of BACE2 may be computationally evaluated and designed by means of a series of steps in which chemical entities or fragments are screened and selected for their ability to associate with the individual binding sites of BACE2.
  • chemical entities or fragments are screened and selected for their ability to associate with the individual binding sites of BACE2.
  • one skilled in the art may use one of several methods to screen chemical entities or fragments for their ability to associate with BACE2. This process may begin by visual inspection of, for example, the binding site on a computer screen based on the structural coordinates of Table 1 in whole or in part. Selected fragments or chemical entities may then be positioned in a variety of orientations, or "docked,” within the catalytic binding site of BACE2.
  • Docking may be accomplished using software such as Quanta and SYBYL, followed by energy minimization and molecular dynamics with standard molecular mechanics force fields, such as CHARMM or AMBER.
  • Specialized computer programs may be of use for selecting interesting fragments or chemical entities. These programs include, for example, GRID, available from Oxford University, Oxford, UK; 5 MCSS or CATALYST, available from Molecular Simulations, Burlington, MA; AUTODOCK, available from Scripps Research Institute, La JoIIa, CA; DOCK, available from University of California, San Francisco, CA, and XSITE, available from University College of London, UK.
  • the structure of a crystalline BACE2 or portion thereof can for example, be bound to one or more ligands or low molecular weight compounds to form a complex.
  • molecular replacement refers to a method that involves generating a preliminary structural model of a crystal whose structural coordinates are unknown, by orienting and positioning a molecule whose structural coordinates are known, e.g., the BACE2 coordinates within the unit cell of the unknown crystal, so as to best account for the observed diffraction pattern of the unknown crystal. Phases can then be calculated from this model, and combined with the observed amplitudes to give an approximated Fourier synthesis of the structure whose coordinates are unknown. This in turn can be subject to any of the several forms of refinement to provide a final accurate structure.
  • molecular replacement may be used to determine the structural coordinates of a crystalline co complex, unknown ligand, mutant, or homolog, or of a different crystalline form of BACE2. Additionally, the claimed crystal and its coordinates may be used to determine the structural coordinates of a chemical entity that associates with BACE2.
  • Homology modeling involves constructing a model of an unknown structure using structural coordinates of one or more related proteins, protein domains and/or one subdomain. Homology modeling may be conducted by fitting common or homologous portions of the protein or peptide whose three dimensional structure is to be solved to the three dimensional structure of homologous structural elements. Homology modeling can include rebuilding part or all of a three dimensional structure by replacement of amino acids or other components by those of the related structure to be solved.
  • Molecular replacement uses a molecule having a known structure.
  • the three-dimensional structure of BACE2 provided in whole or in part in Table 1 in a machine-readable form on a data-carrier can be used as a starting point to model the structure of an unknown crystalline sample.
  • This technique is based on the principle that two molecules which have similar structures, orientations and positions in the unit cell diffract similarly.
  • Molecular replacement involves positioning the known structure in the unit cell in the same location and orientation as the unknown structure. Once positioned, the atoms of the known structure in the unit cell are used to calculate the structure factors that would result from a hypothetical diffraction experiment. This involves rotating the known structure in the six dimensions (three angular and three spatial dimensions) until alignment of the known structure with the experimental data is achieved.
  • This approximate structure can be fine-tuned to yield a more accurate and often higher resolution structure using various refinement techniques.
  • the resultant model for the structure defined by the experimental data may be subjected to rigid body refinement in which the model is subjected to limited additional rotation in the six dimensions yielding positioning shifts of under about 5%.
  • the refined model may then be further refined using other known refinement methods.
  • the present invention also enables homologues and mutants of BACE2 and the solving of their crystal structure. Based on the three-dimensional structure of BACE2 as provided in the present invention and using the atomic coordinates of Table 1 in whole or in part, the effects of site-specific mutations can be predicted.
  • the structural information provided herein permits the identification of desirable sites for amino acid modification, particularly amino acid mutation resulting in substitutional, insertional or deletional variants.
  • Such variants may be designed to have special properties, particularly properties distinct from wild-type BACE2, such as altered catalytic activity. Substitutions, deletions and insertions may be combined to arrive at a desired variant.
  • Such variants can be prepared by methods well-known in the art, e.g. starting from wild-type BACE2 or by de novo synthesis.
  • BACE2 may also crystallize in a form different from the one disclosed herein.
  • the structural information provided, for example, in SEQ ID No. 3 and Table 1 in whole or in part, is also useful for solving the structure of other crystal forms. Furthermore, it may serve to solve the structure of a BACE2 mutant, a BACE2 co-complex or a sufficiently homologous protein.
  • the BACE2 structural information provided herein is useful for the design of ligands or small molecule compounds which are capable of selectively interacting with BACE2 and thereby specifically modulating the biological activity of BACE2. Furthermore, this information can be used to design and prepare BACE2 mutants, e.g. mutants with altered catalytic activity, model the three-dimensional structure and solve the crystal structure of proteins, such as BACE2 homologues, BACE2 mutants or BACE2 co-complexes, involving e.g. molecular replacement.
  • the present invention provides a method for designing a ligand or low molecular weight compound capable of binding with BACE2, said method comprising: (i) using the atomic coordinates of Table 1 in whole or in part to determine the three- dimensional structure of BACE2
  • the present invention also relates to the chemical entity or ligand identified by such method.
  • the present invention may also be used to design ligands or low molecular weight compounds which bind to another aspartyl protease family member using the atomic coordinates of Table 1 in whole or in part to determine the three-dimensional structure of an aspartyl protease family member.
  • the present invention may also be used to design ligands or low molecular weight compounds which specifically inhibit other aspartyl protease family members and which specifically do not bind to BACE2.
  • One approach enabled by this invention is the use of the structural coordinates of BACE2 to design chemical entities that bind to or associate with BACE2 and alter the physical properties of the chemical entities in different ways.
  • properties such as, for example, solubility, affinity, specificity, potency, on/off rates, or other binding characteristics may all be altered and/or maximized.
  • One may design desired chemical entities by probing an BACE2 crystal comprising BACE2 with a library of different entities to determine optimal sites for interaction between candidate chemical entities and BACE2. For example, high-resolution x- ray diffraction data collected from crystals saturated with solutes allows the determination of where each type of solute molecule adheres. Small molecules that bind tightly to those sites can then be designed and synthesized and tested for the desired activity. Once the desired activity is obtained, the molecule can be further altered to maximize desired properties.
  • the invention also contemplates computational screening of small-molecule databases or designing of chemical entities that can bind in whole or in part to BACE2. They may also be used to solve the crystal structure of mutants, co-complexes, or the crystalline form of any other molecule homologous to, or capable of associating with, at least a portion of BACE2.
  • One method that may be employed for this purpose is molecular replacement.
  • An unknown crystal structure which may be any unknown structure, such as, for example, another crystal form of BACE2, an BACE2 mutant or peptide, or a co-complex with BACE2, or any other unknown crystal of a chemical entity that associates with BACE2 that is of interest, may be determined using the whole of part of the structural coordinates set forth in Table 1. This method provides an accurate structural form for the unknown crystal far more quickly and efficiently than attempting to determine such information without the invention herein.
  • candidate ligands are screened in silico.
  • the information obtained can thus be used to obtain maximally effective inhibitors of BACE2 or any other aspartyl protease.
  • a method is provided to design ligands which inhibit the activity of BACE2 or any other aspartyl protease.
  • the design of chemical entities that inhibit BACE2 generally involves consideration of at least two factors.
  • the chemical entity must be capable of physically or structurally associating with BACE2, preferably at the catalytic site of BACE2.
  • the association may be any physical, structural, or chemical association, such as, for example, covalent or non- covalent binding, or van der Waals, hydrophobic, or electrostatic interactions.
  • the chemical entity must be able to assume a conformation that allows it to associate with BACE2, preferentially at the catalytic site of BACE2. Although not all portions of the chemical entity will necessarily participate in the association with BACE2, those non-participating portions may still influence the overall conformation of the molecule. This in turn may have a significant impact on the desirability of the chemical entity.
  • conformational requirements include the overall three-dimensional structure and orientation of the chemical entity in relation to all or a portion of the binding site.
  • the efficiency with which that compound may bind to BACE2 may be tested and modified for the maximum desired characteristic(s) using computational or experimental evaluation.
  • Various parameters can be maximized depending on the desired result. These include, but are not limited to, specificity, affinity, on/off rates, hydrophobicity, solubility, and other characteristics readily identifiable by the skilled artisan.
  • the present invention also relates to identification of compounds which modulate or specifically spare BACE2 activity.
  • said compounds are useful in preventing or treating disorders mediated by BACE2 or other aspartyl proteases, for example, acute or chronic rejection or organ or tissue allografts or xenografts, atherosclerosis, vascular occlusion due to vascular injury such as angioplasty, restenosis, hypertension, heart failure, chronic obstructive pulmonary disease, CNS diseases such as Alzheimer disease or- amyotrophic lateral sclerosis, cancer, infectious diseases such as AIDS, septic shock or adult respiratory distress syndrome, ischemia/reperfusion injury e.g.
  • T-cell mediated acute or chronic inflammatory diseases or disorders or autoimmune diseases for example, rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, Hashimoto's thyroidis, multiple sclerosis, myasthenia gravis, diabetes type I or Il and disorders associated therewith, respiratory diseases such as asthma or inflammatory lung injury, inflammatory liver injury, inflammatory glomerular injury, cutaneous manifestations of immunologically-mediated disorders or illnesses, inflammatory and hyperproliferative skin diseases (such as psoriasis, atopic dermatitis, allergic contact dermatitis, irritant contact dermatitis, and further eczematous dermatitis, seberrhoeic dermatitis), inflammatory eye diseases, e.g. Sjoegren's syndrome, keratoconjunc
  • the required dosage will depend on the mode of administration, the particular condition to be treated and the desired effect. In general, satisfactory results are indicated to be obtained systematically at daily dosages from about 0.1 to about 100 mg/kg body weight.
  • a daily dosage in a larger mammal e.g. human
  • the compounds may be administered by any conventional route, in particular enterally e.g. orally, e.g. in the form or tablets or capsules, or parenterally, e.g. in the form of injectable solutions or suspensions, topically, e.g.
  • compositions comprising said compound in free form or in a pharmaceutically acceptable salt form in association with at least one pharmaceutically acceptable carrier or diluent may be manufactured in conventional manner by mixing with a pharmaceutically acceptable carrier or diluent.
  • Unit dosage forms for oral administration contain, for example, from about 0.1 mg to about 500 mg of active substance.
  • Topical administration is e.g. to the skin.
  • a further form of topical administration is to the eye.
  • Compounds may be administered in free form or in a pharmaceutically acceptable salt form. Such salts may be prepared in a conventional manner and exhibit the same order of activity as the free compounds.
  • the present invention enables the use of molecular design techniques, particularly the rational drug design approach, to prepare new" or improved chemical entities and compounds, including BACE2 inhibitors, capable of irreversibly or reversibly, modulating BACE2 activity.
  • Improved entities or compounds means that these entities or compounds are superior to the "original" or parent compound they are derived from with regard to a property relevant to therapeutic use including suitability for in vivo administration, e.g. cellular uptake, solubility, stability against (enzymatic) degradation, binding affinity or specificity, and the like.
  • BACE2 inhibitors which covalently, or preferably non-covalently, bind to BACE2.
  • Such inhibitors may act in a competitive or uncompetitive manner, bind at or close to the active site of BACE2 or act allosterically.
  • BACE2 modulators In the design of BACE2 modulators the following aspects should be considered: (i) if the candidate compound is capable of physically and structurally associating with BACE2 catalytic domain, and/or (ii) if the compound is capable of assuming a conformation allowing it to associate with BACE2.
  • computer modelling techniques are used in the process of assessing these abilities for the modulator as a whole, or a fragment thereof - in order to minimize efforts in the synthesis or testing of unsuccessful candidate compounds. Specialized computer software is well-known in the art.
  • Another design approach is to probe a BACE2 crystal with a variety of different chemical entities to determine optimal sites for interaction between candidate BACE2 inhibitors and the target enzyme.
  • Yet another possibility which arises from the present invention is to screen computationally small molecule data bases for chemical entities or compounds that are capable of binding, in whole or in part, to BACE2 catalytic domain.
  • the quality of fit to the binding site may be judged e.g. by shape complementarity or by estimated interaction energy.
  • Knowledge of the three-dimensional arrangement of the modifications can be then utilized for the design of new BACE2 ligands or low molecular weight compounds such as selective inhibitors.
  • Chemical entities that are capable of associating with the aspartyl protease family member may inhibit its interaction with naturally occurring ligands of the protein and may inhibit biological functions mediated by such interaction. Such chemical entities are potential drug candidates.
  • Compounds of the structures selected or designed by any of the foregoing means may be - tested for their ability to bind to an aspartyl protease family protease, inhibit the binding of an aspartyl protease family protease to a natural or non-natural ligand therefore, and/or inhibit a biological function mediated by an aspartyl protease family member.
  • the gene of human pro-BACE2 (amino acid A20-E465, SEQ ID. No. 1 ) is amplified into the expression vector pET17b using the primers given by SEQ ID No. 4 and SEQ ID No. 5 and is subsequently inserted into the expression vector BamH1/Xho1.
  • the resulting construct codes for an N-terminal T7 tag followed by pro-BACE2 (SEQ ID No. 2).
  • This construct is further modified using the primers given by SEQ ID No. 6 and SEQ ID No. 7 to code for a pro-BACE2 variant which carries a factor Xa cleavage site (IEGR) at position 76-79 and which terminates at amino acid residue 465 (SEQ ID No. 3).
  • IEGR factor Xa cleavage site
  • Example 2 Expression of BACE2 in E. coli, refolding and purification
  • E. coli cells (BL21(DE3)pl_ysS harboring the BACE2 expression plasmid are induced with IPTG. Cells are resuspended in 50 mM Tris/HCI buffer at pH 8.0 and ruptured by sonication. After centrifugation of the homogenate at 1650Og for 15 min, the inclusion body-containing pellet is washed twice with the same buffer and then dissolved in 50 mM Tris/HCI buffer at pH 8.0, containing 8 M guanidinium chloride and 30 mM DTE.
  • Pro-BACE2 is refolded by diluting the clear supernatant at a ratio of 1 :200 into a solution of 3 M guanidinium chloride, 0.7 M arginine (pH 10.4), 0.5 mM oxidized- glutathione and 1 mM reduced glutathione. After " incubation for 16 hours at 4 0 C, the solution is further diluted (17-fold) by addition of a solution of 0.7 M arginine (pH 9.4), 1 M NaCI, 0.5 mM oxidized glutathione and 1 mM reduced glutathione.
  • the pH of the protein solution is adjusted to pH 3.2 with citric acid (final concentration: 5-10 mM) and hydrochloric acid.
  • the precipitated protein is removed by centrifugation and the pH value of the clear supernatant adjusted to pH 6.8 by addition of Tris (final concentration: 20 mM) and NaOH.
  • Tris final concentration: 20 mM
  • NaOH sodium EDTA
  • the solution is loaded onto a butyl sepharose column.
  • BACE2 is eluted in a single step with 20 mM Tris/HCI buffer at pH 6.8, containing 350 mM NaCI.
  • the pH of the protein solution is again adjusted to pH 3.2 and the precipitated protein removed by centrifugation.
  • BACE2 is cleaved at the engineered factor Xa site by addition of 0.09 mg/ml trypsin and further purified by gel filtration chromatography using a 26/60 Superdex 75 column equilibrated and run with 10 mM Tris/HCI buffer at pH 6.8, containing 350 mM NaCI. Pure BACE2 is then concentrated to 6 mg/ml and subjected to crystallization trials. The activation and purification procedures result in a construct of BACE2 comprising amino acids Ala ⁇ O to Ala465 (numbering according to SEQ ID No. 3).
  • Example 3 Crystallization, data collection and structure determination of human BACE2
  • Human BACE2 (amino acids 75 ANFLAM-CVPA 460 , numbering according to SEQ ID No. 1) is crystallized at 20 0 C in hanging drops by mixing 1 ⁇ l protein solution, comprising 8.8 mg/ml BACE2, 10 mM Tris/HCI pH 6.8, 350 mM NaCI, 2 mM inhibitor and 2 % DMSO, with 1 ⁇ l reservoir solution, composed of 16 % PEG8000, 100 mM CaCI 2 and 5 % Glycerol, and equilibrating the drop against 600 ⁇ l of the reservoir solution. Diffracting quality crystals in form of thin needles, belonging to the rhombohedral space group R3, are obtained after approximately six weeks.
  • a crystal is cryoprotected by the addition of 0.25 ⁇ l Glycerol to the drop followed by flash-freezing the crystal in liquid nitrogen.
  • X-ray diffraction data are collected at the Swiss Light Source (SLS) beamline X06SA, Villingen, Switzerland with a MARCCD detector at 95 K. 70 images are collected with 1.0° oscillation each, using an exposure time of 3 sec. per frame and a crystal-to-detector distance of 210 mm.
  • the raw diffraction data are processed and scaled with the HKL program suite version 1.97.2 (Otwinowski et al. 1997).
  • the data collection statistics are summarized in Table 2.
  • BACE2 The structure of BACE2 is solved by molecular replacement with the program MOLREP (Vagin et al., 1997) using the coordinates of human BACE1 (Protein Data Bank accession code 1 FKN) as a search model. With a high resolution data cut off of 3.5 A, an unambiguous solution is found in space group R3 with four BACE2 molecules in the asymmetric unit (correlation coefficient of 0.47, R-factor of 0.44). An initial refinement cycle, using the rigid- body and simulated annealing protocols as implemented in CNX version 2000 (Accelrys, San Diego, USA, / Br ⁇ nger, 1996) results in a model which is used to calculate the initial electron density map.
  • BACE2 The overall structure of BACE2 follows the general fold of aspartic proteases of the A1 family (Baldwin et al. 1993, Metcalf et al. 1993) and comprises a N-terminal domain (amino acids Ser88-Asn223), a C-terminal domain (residues Lys269-Ala460) and a six-stranded anti-parallel ⁇ -sheet inter-domain (amino acid numbering according to SEQ ID No. 1).
  • the inter-domain consists of the ten N-terminal amino acids (Leu78-Asp87), building the outermost strand of the inter-domain ⁇ -sheet, amino acids He224-lle268, connecting the N- and C-terminal domains, and the amino acids Gly414-Cys433. Both, the N- and the C- terminal domain each contribute one catalytic aspartic acid residue, Asp101 and Asp303, respectively, to the active site.
  • The- center of the active site is completely shielded from solvent by a flexible stretch of amino acids, a ⁇ -hairpin loop also known as the flap (amino acids Val147 to Ser153), which folds back over the active site upon inhibitor binding.
  • the non-peptide based inhibitor 1 binds to the .center of the active site of BACE-2 and spans from the S3 to the S2' binding pockets.
  • the transition state hydroxy! group (atom 07) interacts with the outer oxygen atom (atom OD2) of the catalytic aspartate (Asp 110), while the transition state amino group (atom N 12) makes interactions with the outer oxygen atom of the second catalytic aspartate (Asp303, atom OD2) as well as the carbonyl group of Gly112 (atom O).
  • the methylbenzyl moiety points into the S2' binding pocket, while the methylene group is pointing towards SV.
  • the phenyl ring is occupying S1 and the tricycle is bridging S2 and S3.
  • the amide group interacts via atom N1 with the carbonyl of Gly305 and via atom 046 with the backbone nitrogen atom of Thr150.
  • One additional hydrogen bonding interaction is observed between the oxygen atom of the tricycle (atom O60) and the backbone nitrogen atom of Thr307.
  • additional hydrophobic and van-der-Waals interactions are formed.
  • phenyl group in S1 makes extensive hydrophobic interactions with the hydrophobic side chains of Tyr149, Phe186, He196, Leu108 and Trp193.
  • ATOM 140 N MET A 96 122 .958 37 .143 0 .029 1. 00 10 .47 A N
  • ATOM 326 CD PRO A 122 129.223 19.117 -0.125 1.00 22.06 A C ATOM 327 CA PRO A 122 127.576 19.968 -1.669 1.00 19.29 A C
  • ATOM 490 CA LYS A 141 126.230 26 .760 19 .166 1.00 19 .58 A C ATOM 491 CB LYS A 141 124.882 27.320 18.712 1.00 14.98 A C ATOM 492 CG LYS A 141 124.535 28.630 19.400 1.00 14.98 A C ATOM 493 CD LYS A 141 123.568 29.463 18.577 1.00 14.98 A C ATOM 494 CE LYS A 141 123.006 30.652 19.372 1.00 14.98 A C ATOM 495 NZ LYS A 141 121.953 30.245 20.365 1.00 14.98 A N ATOM 496 C LYS A 141 126.077 25.447 19.941 1.00 19.58 A C ATOM 497 O LYS A 141 125.445 25.400 21.003 1.00 19.58 A O ATOM 498 N GLY A 142 126.656 24.377 19.407 1.00 18.89 A N ATOM 499 CA GLY A 142 126.6
  • ATOM 882 CA ILE A 191 116.553 26.246 -8.106 1.00 22. 80 A C
  • ATOM 1142 CA PRO A 225 111.319 49.460 12.315 1.00 26.91 A C

Abstract

The present invention concerns the aspartyl protease beta-site amyloid precursor protein­cleaving enzyme 2 (BACE2), in particular, the three-dimensional structure of BACE2. Methods of expression, purification and crystallization of BACE2 are provided in preparation for crystallography. The atomic coordinates of a complex of BACE2 complexed with an inhibitor are also provided.

Description

Three-Dimensional Structure of the human Aspartyl Protease Beta-Site Amyloid Precursor Protein-Cleaving Enzyme 2 (BACE2), Methods and Use Thereof
Field of the Invention
The present invention relates to the aspartyl protease beta-site amyloid precursor protein- cleaving enzyme 2 (BACE2), in particular, the three-dimensional structure of BACE2. The invention also relates to the crystalline forms of liganded or unliganded human BACE2. Further, the invention provides methods of expression, refolding and purification of the recombinant human aspartyl protease BACE2 for the use in crystallization and methods of making crystals comprising BACE2 and its structure determination. The invention also relates to the use of the three-dimensional structure of BACE2 for identifying and designing ligands or low molecular weight compounds which inhibit the biological function of BACE2 or any other aspartyl protease.
Background of the Invention
BACE2 was recently identified as a homolog of BACE1 through expressed sequence tags data base searching (Yan et al., 1999) and genomic cloning (Acquat et al., 2000). BACE1 , also known as beta-secretase or beta-site amyloid precursor protein-cleaving enzyme 1 , is an aspartyl protease involved in the process leading to the generation of amyloid plaques from the amyloid precursor protein in Alzheimer's disease (Vassar et al., 1999). The two BACE proteins share 51% identity at the amino acid level. BACE2 transcripts are expressed in the central nervous system and many peripheral tissues; however, its expression level in neurons is substantially lower than that of BACE1 (Bennett et al., 2000). In vitro enzymatic assays with peptide substrates demonstrate that BACE2 cleaves β-secretase substrates similar to BACE1, processing both the wild-type and Swedish mutant amyloid precursor protein (Hussain et al., 2000). BACE2 maps to chromosome 21q22.3 (Yan et al., 1999), the Down's syndrome critical region, and is up-regulated in Down's syndrome (Barbiero et al., 2003). In addition, BACE2 is over expressed in human breast cancer (Kondoh et al., 2003) and participates, together with BACE1, in normal and abnormal processes of human muscle biology (Vattemi et al., 2003).
Other members of the human aspartyl protease family include: Renin, Cathepsin D, Cathepsin E, Pepsin A, Pepsin C and Napsin A. While structural information is available for BACE1 , Renin, Cathepsin D, Cathepsin E, Pepsin A and Pepsin C, there has been no description of the crystal structure of BACE2 in any species described prior to the present invention.
Summary of the Invention
The present invention provides the three-dimensional structure of BACE2 thereby enabling the identification and design of ligands or low molecular weight molecules that either specifically inhibit BACE2, or avoid its inhibition.
The present invention relates to:
(i) a crystal of BACE2 with or without the pro-sequence and with or without a ligand or low molecular weight compound
(ii) methods of expressing BACE2 with or without the pro-sequence
(iii) methods of refolding BACE2 with or without the pro-sequence
(iv) methods of purification of BACE2 with or without the pro-sequence
(v) methods of making a crystal comprising BACE2 with or without the pro-sequence
(vi) methods of using said BACE2 crystal with or without the pro-sequence and its structural coordinates to identify and design ligands or low molecular weight molecules that inhibit
BACE2 or any other aspartyl protease activity or that specifically do not inhibit BACE2 but any other aspartyl protease.
The three-dimensional structural information revealed from the crystal of BACE2 can be used for structure-based drug discovery, for screening, identifying and designing inhibitors of BACE2 and other members of the aspartyl protease family.
Detailed Description of the Invention
The full-length sequence of human BACE2 is given by SEQ ID No.1 (see: Genbank Accession number AF 05017 and related, Swissprot Accession number Q9Y5Z0).
The present invention provides BACE2 in crystallized form. In particular, it provides a crystal comprising BACE2 and a ligand bound to BACE2 as a complex. In one embodiment of the present invention, a crystal of BACE2 comprising a unit cell dimension of a = b = 228.407 + 5 Angstroms, c = 108.964 + 5 Angstroms, α = β = 90.0 degrees and γ = 120 degrees is provided. Depending on the particular conditions for crystallization, the parameters characterising the unit cell may vary within a limited range, for example, a,b,c each vary by up to 5 Angstroms. The space group of the present invention is R3 rhombohedral.
The term "unit cell" according to the invention refers to the basic shape block. The entire volume of a crystal is constructed by regular assembly of such blocks. Each unit cell comprises a complete representation of the unit of pattern, the repetition of which builds up the crystal.
The term "space group" according to the invention refers to the arrangement of symmetry elements of a crystal.
In another embodiment of the invention, a crystal of. BACE2 comprising BACE2 in complex with a ligand is provided wherein said crystal has a three-dimensional structure characterized by the atomic structure coordinates of Table 1.
In a further embodiment of the invention, said BACE2 comprises the sequences of SEQ ID. No. 2 and SEQ ID. No. 3, a mutant, a fragment or homologue thereof.
In yet another embodiment of the invention, said BACE2 comprises at least the substrate binding site.
Further provided by this invention is a crystal comprising BACE2 (SEQ ID No. 3, a mutant, a fragment or homologue thereof) bound to at least one ligand or low molecular weight compound.
The term "ligand" according to the invention, refers to a molecule or group of molecules that bind to one or more specific sites of BACE2, most preferably to the active site of said BACE2. Ligands according to the invention are preferably low molecular weight molecules. - A -
The term "low molecular weight compound" according to the invention refers to preferably organic compounds generally having a molecular weight less than about 1000, more preferably less than about 600. Most preferably, said low molecular weight compounds or ligands inhibit biological activity of BACE2 or any other aspartyl protease.
In context of a BACE2 inhibitor, the terms "peptide" or "peptide derivative" are intended to embrace a "peptidomimetic" or "peptide analogue" which complement the three-dimensional structure of the binding site of BACE2 or can be designed with improved physical or chemical properties to bind with the three-dimensional binding site of the BACE2 as provided in the present invention.
The term "mutant" refers to differences within the wild-type sequence of BACE2 set forth in SEQ. ID No. 1 by deletion, insertion, extension, or replacement of one or more selected amino acids.
According to the present invention, the term "mutant" also refers to a polypeptide, whose amino acid sequence differs from the sequence given in SEQ ID No.3 by deletion, insertion or preferably replacement of one or more selected amino acids. For example, a BACE2 mutant of the present invention is preferably at least 50% homologous to SEQ ID No. 3, more preferably at least 80% homologous to SEQ ID No. 3 most preferably at least 90% homologous to SEQ ID No. 3.
A "fragment" of BACE2 according to the invention comprises more than 50% of the full- length sequence of BACE2 according to SEQ ID No. 3, more preferably at least 80% of the full length sequence of BACE2 according to SEQ ID No. 3, most preferably at least 90% of the full-length sequence of BACE2 according to SEQ ID No. 3.
In one embodiment of the invention, a BACE2 mutant may be crystallizable with or without at least one ligand or with or without the pro-sequence or parts of the pro-sequence of BACE2.
In another embodiment of the invention, a BACE2 fragment may be crystallizable with or without at least one ligand or with or without the pro-sequence or parts of the pro-sequence of BACE2. In yet another embodiment of the invention, a method is provided wherein BACE2, a mutant, fragment or homologue thereof is bound to at least one ligand at any step prior to crystallization.
According to the present invention, BACE2 crystals are stable if kept under suitable conditions. For example, the crystals are stable in there mother liquor at 2O0C for at least 3-4 weeks. Preferable storage is frozen in liquid nitrogen.
In the present invention, BACE2 or a fragment or homologue thereof is advantageously obtained by expressing proBACE2 in a recombinant E. coli cell culture and subsequent refolding and auto-proteolytic cleavage of the pro-sequence.
In one embodiment of the invention, a method for making a crystal of BACE2 is provided comprising the following steps:
(i) purification of BACE2 (SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3)
(ii) expression of BACE2 (SEQ ID No. 1) or BACE2 homologue (e.g. SEQ ID No. 2 or SEQ
ID No. 3) in a suitable host cell
(iii) refolding and purification of the desired BACE2 protein.
In a preferred embodiment of the invention, said method for making a crystal involves BACE2 (SEQ ID No.3), a mutant, a fragment or homologue thereof.
According to the invention, BACE2 may be prepared by isolation from natural sources, e.g. cultured human cells or preferably by recombinant heterologous expression. Expression of recombinant BACE2 is achievable in eukaryotic or prokaryotic systems. For example, recombinant human BACE2 may be expressed in bacteria.
The protease may be expressed as a fusion protein, for example as a Strep-tag fusion protein, a glutathione-S-transferase (GST) fusion protein, a histidine-tagged fusion protein, or as an untagged protein. If desired, the fusion partner is removed before crystallization. The heterologously produced BACE2 to be used for crystallization is potentially biologically active. Such ability may be determined by morphological, biochemical or viability analysis well-known in the art. Methods for the preparation of BACE2 mutants are commonly known in the art. For example, BACE2 mutants may be prepared by expression of BACE2 DNA previously modified in its coding region by oligo-nucleotide directed mutagenesis.
In the present invention, purified BACE2 is preferably at least 90 % homogeneous. Protein homogeneity is determinable according to analytical methods well-known in the art, e.g. sequence analysis, electrophoresis, spectroscopic or chromatographic techniques. The purified protein is potentially proteolytically active. Appropriate assays for determining BACE2 activity towards a suitable substrate, e.g. a natural substrate or a synthetic substrate, are known in the art.
In one embodiment of the invention, at any step prior to crystallization BACE2 may be complexed with a low molecular weight compound or ligand which is capable of suitably binding to BACE2. Preferred is a compound inhibiting BACE2 activity. Protease inhibition is determinable employing assays known in the art. Suitable inhibitors include protease inhibitors which act on the catalytic site to inhibit BACE2 activity.
Various methods of cystallization can be used in the claimed invention including vapor diffusion, dialysis or batch crystallization. In vapor diffusion crystallization, a small volume (i.e., a few microliters) of protein solution is mixed with a solution containing a precipitant. This mixed volume is suspended over a well containing a small amount, i.e. about 0.15-1 ml, of precipitant. Vapor diffusion between the drop and the well will result in crystal formation in the drop.
The dialysis method of crystallization utilizes a semipermeable size-exclusion membrane that retains the protein but allows small molecules (i.e. buffers and precipitants) to diffuse in and out. In dialysis, rather than concentrating the protein and the precipitant by evaporation, the precipitant is allowed to slowly diffuse through the membrane and reduce the solubility of the protein while keeping the protein concentration fixed.
The batch method generally involves the slow addition of a precipitant to an aqueous solution of protein until the solution just becomes turbid, at this point the container can be sealed and left undisturbed for a period of time until crystallization occurs. In the batch technique the precipitant and the target molecule solution are simply mixed. Supersaturation is achieved directly rather than by diffusion. Often the batch technique is performed under oil. The oil prevents evaporation and extremely small drops can be used. For this, the term "microbatch" is used. A modification of this technique is not to use paraffin oil (which prevents evaporation completely) but rather use silicone oil or a mixture of silicone and paraffin oils so that a slow evaporation is possible.
The claimed invention can encompass any and all methods of crystallization. One skilled in the art can choose any of such methods and vary the parameters such that the chosen method results in the desired crystals.
One preferred method of crystallization of BACE2 involves mixing a BACE2 solution with a "reservoir buffer", with a lower concentration of the precipitating agent necessary for crystal formation. For crystal formation, the concentration of the precipitating agent has to be increased, e.g. by addition of precipitating agent, for example by titration, or by allowing the concentration of precipitating agent to balance by diffusion between the crystallization buffer and a reservoir buffer. Under suitable conditions such diffusion of water or volatile precipitating agent occurs along the gradient of precipitating agent, e.g. between the reservoir buffer having a higher concentration of precipitating agent and the crystallization buffer having a lower concentration of precipitating agent. Diffusion may be achieved e.g. by vapour diffusion techniques allowing diffusion of water in the common gas phase. Known techniques are e.g. vapour diffusion methods, such as the "hanging drop" or the "sitting drop" method. In the vapour diffusion method a drop of crystallization buffer containing the protein is hanging above or sitting beside a much larger pool of reservoir buffer. Alternatively, the balancing of the precipitating agent can be achieved through a semipermeable membrane (dialysis method) that separates the crystallization buffer from the reservoir buffer and prevents dilution of the protein into the reservoir buffer.
Formation of BACE2 crystals can be achieved under various conditions which are essentially determined by the following parameters: pH, presence of salts and additives, precipitating agent, protein concentration and temperature. The pH may range, for example, from about 3.0 to 11.0. The present invention also relates to a computer readable medium having stored a model of the BACE2 crystal structure. In a preferred embodiment, said model is built from all or part of the X-ray diffraction data. The atomic coordinates are shown in Table 1.
The present invention provides the structure coordinates of human BACE2. The term "structure coordinates" or "atomic coordinates" refers to mathematical coordinates derived from the mathematical equations (fourier transformation) related to the diffraction pattern obtained on a monochromatic beam of X-rays by the atoms (scattering centers) of a crystal comprising a BACE2. The diffraction data are used to calculate an electron density map of the repeating unit of the crystal. The electron density maps are used to establish the positions of the individual atoms within the unit cell of the crystal.
Structural coordinates of a crystalline composition of this invention may be stored in a machine-readable form on a machine-readable storage medium, e.g. a computer hard drive, diskette, DAT tape, CD, DVD etc., for display as a three-dimensional shape or for other uses involving computer-assisted manipulation of, or computation based on, the structural coordinates or the three-dimensional structures they define. For example, data defining the three dimensional structure of a protein of BACE2, or portions or structurally similar homologues of such proteins, may be stored in a machine-readable storage medium, and may be displayed as a graphical three-dimensional representation of the protein structure, typically using a computer capable of reading the data from said storage medium and programmed with instructions for creating the representation from such data.
In one embodiment of the invention, a computer readable medium is provided comprising data storage material encoded with computer readable data wherein said data comprises the atomic coordinates of Table 1 comprising BACE2.
In another embodiment of the invention, a method is provided for determining the three- dimensional structure of BACE2 comprising:
(i) crystallization of BACE2 with or without the pro-sequence (SEQ ID No.3), a mutant, a fragment or homologue thereof
(ii) collecting x-ray diffraction data in the form of indexed intensities for said crystal and generating atomic coordinates. (iii) utilizing the atomic coordinates of Table 1 in whole or in part to determine the three- dimensional structure of BACE2, fragment, or homologue thereof.
In yet another embodiment of the invention, a method is provided for determining the three- dimensional structure of a complex comprising BACE2 (SEQ ID No.3), a mutant fragment or homologue thereof bound to at least one ligand comprising the steps of: (i) obtaining x-ray diffraction data for a crystal of the complex
(ii) utilizing the atomic coordinates of Table 1 in whole or in part to determine the three- dimensional structure of the complex.
According to the present invention, a three-dimensional BACE2 model is obtainable from a BACE2 crystal comprising BACE2, mutant, fragment or homologue thereof. Such a model can be built or refined from all or part of the BACE2 structure data of the present invention using the x-ray diffraction coordinates, particularly the atomic structure coordinates of Table 1.
The knowledge obtained from the three-dimensional model of the catalytic binding site of - BACE2 can be used in various ways. For example, it can be used to identify chemical entities, for example, small organic and bioorganic molecules such as peptidomimetics and synthetic organic molecules that bind to BACE2 and preferably block or prevent a BACE2 mediated or associated process or event, or that bind to another aspartyl protease or prevent another aspartyl protease mediated or associated process or event. Using the three- dimensional structure of BACE2, the skilled artisan constructs a model of the BACE2. For example, every atom can be depicted as a sphere of the appropriate van der Waals radius, and a detailed surface map of BACE2 can be constructed.
Chemical entities that have a surface that mimics the accessible surface of the catalytic binding site of BACE2 can be constructed by those skilled in the art. By way of example, the skilled artisan can screen three-dimensional structural databases of compounds to identify those compounds that position appropriate functional groups in similar three dimensional structural arrangement, then build combinatorial chemistry libraries around such chemical entities to identify those with high affinity to the catalytic binding site of BACE2. In one embodiment of the invention, a method is provided for identifying a ligand or low molecular weight compound that binds to BACE2 comprising:
(i) using the three-dimensional structure of BACE2 derived in whole or in part from the set of atomic coordinates in Table 1 to select a potential ligand or low molecular weight compound that binds to BACE2
(ii) selecting those ligands or low molecular weight compounds that binds to BACE2
In another embodiment of the invention, a method is provided for identifying a ligand or low molecular weight compound that binds to BACE2 wherein BACE2 comprises at least the substrate binding site of said protease.
In yet another embodiment of the invention, a method is provided for identifying ligands which inhibit the activity of BACE2.
Ligands or small molecular compounds can be identified from screening compound databases or libraries and using a computational means to form a fitting operation to a binding site on BACE2. The three dimensional structure of BACE2 as provided in the present invention in whole or in part by the structural coordinates of Table 1 , can be used together with various docking programs.
The potential inhibitory or binding effect of a chemical entity on BACE2 may be analyzed prior to its actual synthesis and testing by the use of computer-modeling techniques. If the theoretical structure of the given chemical entity suggests insufficient interaction and association between it and BACE2, the need for synthesis and testing of the chemical entity is obviated. However, if computer modeling indicates a strong interaction, the molecule may then be synthesized and tested for its ability to bind to BACE2. Thus, expensive and time- consuming synthesis of inoperative compounds may be avoided.
An inhibitory or other binding compound of BACE2 may be computationally evaluated and designed by means of a series of steps in which chemical entities or fragments are screened and selected for their ability to associate with the individual binding sites of BACE2. Thus, one skilled in the art may use one of several methods to screen chemical entities or fragments for their ability to associate with BACE2. This process may begin by visual inspection of, for example, the binding site on a computer screen based on the structural coordinates of Table 1 in whole or in part. Selected fragments or chemical entities may then be positioned in a variety of orientations, or "docked," within the catalytic binding site of BACE2. Docking may be accomplished using software such as Quanta and SYBYL, followed by energy minimization and molecular dynamics with standard molecular mechanics force fields, such as CHARMM or AMBER. Specialized computer programs may be of use for selecting interesting fragments or chemical entities. These programs include, for example, GRID, available from Oxford University, Oxford, UK; 5 MCSS or CATALYST, available from Molecular Simulations, Burlington, MA; AUTODOCK, available from Scripps Research Institute, La JoIIa, CA; DOCK, available from University of California, San Francisco, CA, and XSITE, available from University College of London, UK.
Using molecular replacement to exploit a set of coordinates such as those of Table 1 of the invention, the structure of a crystalline BACE2 or portion thereof can for example, be bound to one or more ligands or low molecular weight compounds to form a complex.
The term "molecular replacement" refers to a method that involves generating a preliminary structural model of a crystal whose structural coordinates are unknown, by orienting and positioning a molecule whose structural coordinates are known, e.g., the BACE2 coordinates within the unit cell of the unknown crystal, so as to best account for the observed diffraction pattern of the unknown crystal. Phases can then be calculated from this model, and combined with the observed amplitudes to give an approximated Fourier synthesis of the structure whose coordinates are unknown. This in turn can be subject to any of the several forms of refinement to provide a final accurate structure. Using the structural coordinates provided by this invention, molecular replacement may be used to determine the structural coordinates of a crystalline co complex, unknown ligand, mutant, or homolog, or of a different crystalline form of BACE2. Additionally, the claimed crystal and its coordinates may be used to determine the structural coordinates of a chemical entity that associates with BACE2.
"Homology modeling" according to the invention involves constructing a model of an unknown structure using structural coordinates of one or more related proteins, protein domains and/or one subdomain. Homology modeling may be conducted by fitting common or homologous portions of the protein or peptide whose three dimensional structure is to be solved to the three dimensional structure of homologous structural elements. Homology modeling can include rebuilding part or all of a three dimensional structure by replacement of amino acids or other components by those of the related structure to be solved.
Molecular replacement according to the present invention, uses a molecule having a known structure. The three-dimensional structure of BACE2 provided in whole or in part in Table 1 in a machine-readable form on a data-carrier can be used as a starting point to model the structure of an unknown crystalline sample. This technique is based on the principle that two molecules which have similar structures, orientations and positions in the unit cell diffract similarly. Molecular replacement involves positioning the known structure in the unit cell in the same location and orientation as the unknown structure. Once positioned, the atoms of the known structure in the unit cell are used to calculate the structure factors that would result from a hypothetical diffraction experiment. This involves rotating the known structure in the six dimensions (three angular and three spatial dimensions) until alignment of the known structure with the experimental data is achieved. This approximate structure can be fine-tuned to yield a more accurate and often higher resolution structure using various refinement techniques. For instance, the resultant model for the structure defined by the experimental data may be subjected to rigid body refinement in which the model is subjected to limited additional rotation in the six dimensions yielding positioning shifts of under about 5%. The refined model may then be further refined using other known refinement methods. The present invention also enables homologues and mutants of BACE2 and the solving of their crystal structure. Based on the three-dimensional structure of BACE2 as provided in the present invention and using the atomic coordinates of Table 1 in whole or in part, the effects of site-specific mutations can be predicted. More specifically, the structural information provided herein permits the identification of desirable sites for amino acid modification, particularly amino acid mutation resulting in substitutional, insertional or deletional variants. Such variants may be designed to have special properties, particularly properties distinct from wild-type BACE2, such as altered catalytic activity. Substitutions, deletions and insertions may be combined to arrive at a desired variant. Such variants can be prepared by methods well-known in the art, e.g. starting from wild-type BACE2 or by de novo synthesis.
BACE2 may also crystallize in a form different from the one disclosed herein. The structural information provided, for example, in SEQ ID No. 3 and Table 1 in whole or in part, is also useful for solving the structure of other crystal forms. Furthermore, it may serve to solve the structure of a BACE2 mutant, a BACE2 co-complex or a sufficiently homologous protein. The BACE2 structural information provided herein is useful for the design of ligands or small molecule compounds which are capable of selectively interacting with BACE2 and thereby specifically modulating the biological activity of BACE2. Furthermore, this information can be used to design and prepare BACE2 mutants, e.g. mutants with altered catalytic activity, model the three-dimensional structure and solve the crystal structure of proteins, such as BACE2 homologues, BACE2 mutants or BACE2 co-complexes, involving e.g. molecular replacement.
The present invention provides a method for designing a ligand or low molecular weight compound capable of binding with BACE2, said method comprising: (i) using the atomic coordinates of Table 1 in whole or in part to determine the three- dimensional structure of BACE2
(ii) probing said three-dimensional structure of BACE2 with candidate ligands or low molecular weight compounds to determine which bind to BACE2 (iii) selecting those ligands or low molecular weight compounds which bind to BACE2 (iv) modifying those ligands or low molecular weight compounds which bind to maximize or minimize physical properties such as solubility, affinity, specificity or potency. ;
Preferred is a method for designing a BACE2 inhibitor which interacts at the catalytic binding site. The present invention also relates to the chemical entity or ligand identified by such method. The present invention may also be used to design ligands or low molecular weight compounds which bind to another aspartyl protease family member using the atomic coordinates of Table 1 in whole or in part to determine the three-dimensional structure of an aspartyl protease family member. The present invention may also be used to design ligands or low molecular weight compounds which specifically inhibit other aspartyl protease family members and which specifically do not bind to BACE2.
One approach enabled by this invention is the use of the structural coordinates of BACE2 to design chemical entities that bind to or associate with BACE2 and alter the physical properties of the chemical entities in different ways. Thus, properties such as, for example, solubility, affinity, specificity, potency, on/off rates, or other binding characteristics may all be altered and/or maximized. One may design desired chemical entities by probing an BACE2 crystal comprising BACE2 with a library of different entities to determine optimal sites for interaction between candidate chemical entities and BACE2. For example, high-resolution x- ray diffraction data collected from crystals saturated with solutes allows the determination of where each type of solute molecule adheres. Small molecules that bind tightly to those sites can then be designed and synthesized and tested for the desired activity. Once the desired activity is obtained, the molecule can be further altered to maximize desired properties.
The invention also contemplates computational screening of small-molecule databases or designing of chemical entities that can bind in whole or in part to BACE2. They may also be used to solve the crystal structure of mutants, co-complexes, or the crystalline form of any other molecule homologous to, or capable of associating with, at least a portion of BACE2. One method that may be employed for this purpose is molecular replacement. An unknown crystal structure, which may be any unknown structure, such as, for example, another crystal form of BACE2, an BACE2 mutant or peptide, or a co-complex with BACE2, or any other unknown crystal of a chemical entity that associates with BACE2 that is of interest, may be determined using the whole of part of the structural coordinates set forth in Table 1. This method provides an accurate structural form for the unknown crystal far more quickly and efficiently than attempting to determine such information without the invention herein.
In one preferred embodiment of the invention, candidate ligands are screened in silico. The information obtained can thus be used to obtain maximally effective inhibitors of BACE2 or any other aspartyl protease.
In another preferred embodiment of the invention, a method is provided to design ligands which inhibit the activity of BACE2 or any other aspartyl protease.
The design of chemical entities that inhibit BACE2 generally involves consideration of at least two factors. First, the chemical entity must be capable of physically or structurally associating with BACE2, preferably at the catalytic site of BACE2. The association may be any physical, structural, or chemical association, such as, for example, covalent or non- covalent binding, or van der Waals, hydrophobic, or electrostatic interactions. Second, the chemical entity must be able to assume a conformation that allows it to associate with BACE2, preferentially at the catalytic site of BACE2. Although not all portions of the chemical entity will necessarily participate in the association with BACE2, those non-participating portions may still influence the overall conformation of the molecule. This in turn may have a significant impact on the desirability of the chemical entity. Such conformational requirements include the overall three-dimensional structure and orientation of the chemical entity in relation to all or a portion of the binding site.
Once a compound has been designed or selected by the above methods, the efficiency with which that compound may bind to BACE2 may be tested and modified for the maximum desired characteristic(s) using computational or experimental evaluation. Various parameters can be maximized depending on the desired result. These include, but are not limited to, specificity, affinity, on/off rates, hydrophobicity, solubility, and other characteristics readily identifiable by the skilled artisan.
The present invention also relates to identification of compounds which modulate or specifically spare BACE2 activity. In particular, said compounds are useful in preventing or treating disorders mediated by BACE2 or other aspartyl proteases, for example, acute or chronic rejection or organ or tissue allografts or xenografts, atherosclerosis, vascular occlusion due to vascular injury such as angioplasty, restenosis, hypertension, heart failure, chronic obstructive pulmonary disease, CNS diseases such as Alzheimer disease or- amyotrophic lateral sclerosis, cancer, infectious diseases such as AIDS, septic shock or adult respiratory distress syndrome, ischemia/reperfusion injury e.g. myocardial infarction, stroke, gut ischemia, renal failure or hemorrhage shock or traumatic shock. Further, said compounds can be useful in preventing or treating T-cell mediated acute or chronic inflammatory diseases or disorders or autoimmune diseases, for example, rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, Hashimoto's thyroidis, multiple sclerosis, myasthenia gravis, diabetes type I or Il and disorders associated therewith, respiratory diseases such as asthma or inflammatory lung injury, inflammatory liver injury, inflammatory glomerular injury, cutaneous manifestations of immunologically-mediated disorders or illnesses, inflammatory and hyperproliferative skin diseases (such as psoriasis, atopic dermatitis, allergic contact dermatitis, irritant contact dermatitis, and further eczematous dermatitis, seberrhoeic dermatitis), inflammatory eye diseases, e.g. Sjoegren's syndrome, keratoconjunctivitis, or uveitis, inflammatory bowel disease, Crohn's disease or ulcerative colitis.
For the above uses, the required dosage will depend on the mode of administration, the particular condition to be treated and the desired effect. In general, satisfactory results are indicated to be obtained systematically at daily dosages from about 0.1 to about 100 mg/kg body weight. A daily dosage in a larger mammal (e.g. human) is in the range from about 0.5mg to about 2000mg, conveniently administered, for example, in divided doses up to four times a day or in retard form. The compounds may be administered by any conventional route, in particular enterally e.g. orally, e.g. in the form or tablets or capsules, or parenterally, e.g. in the form of injectable solutions or suspensions, topically, e.g. in the form of lotions, gels, ointments or creams, or in a nasal or a suppository form. Pharmaceutical compositions comprising said compound in free form or in a pharmaceutically acceptable salt form in association with at least one pharmaceutically acceptable carrier or diluent may be manufactured in conventional manner by mixing with a pharmaceutically acceptable carrier or diluent. Unit dosage forms for oral administration contain, for example, from about 0.1 mg to about 500 mg of active substance. Topical administration is e.g. to the skin. A further form of topical administration is to the eye. Compounds may be administered in free form or in a pharmaceutically acceptable salt form. Such salts may be prepared in a conventional manner and exhibit the same order of activity as the free compounds.
The present invention enables the use of molecular design techniques, particularly the rational drug design approach, to prepare new" or improved chemical entities and compounds, including BACE2 inhibitors, capable of irreversibly or reversibly, modulating BACE2 activity. Improved entities or compounds means that these entities or compounds are superior to the "original" or parent compound they are derived from with regard to a property relevant to therapeutic use including suitability for in vivo administration, e.g. cellular uptake, solubility, stability against (enzymatic) degradation, binding affinity or specificity, and the like. For example, on the basis on the information provided herein it is possible to specially design BACE2 inhibitors which covalently, or preferably non-covalently, bind to BACE2. Such inhibitors may act in a competitive or uncompetitive manner, bind at or close to the active site of BACE2 or act allosterically.
In the design of BACE2 modulators the following aspects should be considered: (i) if the candidate compound is capable of physically and structurally associating with BACE2 catalytic domain, and/or (ii) if the compound is capable of assuming a conformation allowing it to associate with BACE2. Advantageously, computer modelling techniques are used in the process of assessing these abilities for the modulator as a whole, or a fragment thereof - in order to minimize efforts in the synthesis or testing of unsuccessful candidate compounds. Specialized computer software is well-known in the art. Another design approach is to probe a BACE2 crystal with a variety of different chemical entities to determine optimal sites for interaction between candidate BACE2 inhibitors and the target enzyme. Yet another possibility which arises from the present invention is to screen computationally small molecule data bases for chemical entities or compounds that are capable of binding, in whole or in part, to BACE2 catalytic domain. The quality of fit to the binding site may be judged e.g. by shape complementarity or by estimated interaction energy. Knowledge of the three-dimensional arrangement of the modifications can be then utilized for the design of new BACE2 ligands or low molecular weight compounds such as selective inhibitors.
Chemical entities that are capable of associating with the aspartyl protease family member may inhibit its interaction with naturally occurring ligands of the protein and may inhibit biological functions mediated by such interaction. Such chemical entities are potential drug candidates.
Compounds of the structures selected or designed by any of the foregoing means may be - tested for their ability to bind to an aspartyl protease family protease, inhibit the binding of an aspartyl protease family protease to a natural or non-natural ligand therefore, and/or inhibit a biological function mediated by an aspartyl protease family member.
The following examples serve to illustrate embodiments of the present invention but should not be construed as a limitation thereof. Compounds identified by any of the methods described herein are also encompassed by this invention.
Examples
Standard protocols in molecular biology (Ausubel et al. 1997) are applied, if not otherwise stated. The manufacturer's recommendations are followed when using commercially available kits. PCR products are purified with the PCR purification kit (Qiagen). After restriction enzyme digestion, fragments are run and extracted from agarose gels using the QIAquick gel extraction kit (Qiagen). Ligations are performed overnight at 160C with T4 ligase (BRL) and aliquots of the ligation mixtures are transformed into E. coli strain DH5α (Gibco) according to standard protocols for CaCI2 competent cells. Example 1 : Generation of BACE2 variants for expression in E. coli
The gene of human pro-BACE2 (amino acid A20-E465, SEQ ID. No. 1 ) is amplified into the expression vector pET17b using the primers given by SEQ ID No. 4 and SEQ ID No. 5 and is subsequently inserted into the expression vector BamH1/Xho1. The resulting construct codes for an N-terminal T7 tag followed by pro-BACE2 (SEQ ID No. 2). This construct is further modified using the primers given by SEQ ID No. 6 and SEQ ID No. 7 to code for a pro-BACE2 variant which carries a factor Xa cleavage site (IEGR) at position 76-79 and which terminates at amino acid residue 465 (SEQ ID No. 3).
Example 2: Expression of BACE2 in E. coli, refolding and purification
E. coli cells (BL21(DE3)pl_ysS harboring the BACE2 expression plasmid are induced with IPTG. Cells are resuspended in 50 mM Tris/HCI buffer at pH 8.0 and ruptured by sonication. After centrifugation of the homogenate at 1650Og for 15 min, the inclusion body-containing pellet is washed twice with the same buffer and then dissolved in 50 mM Tris/HCI buffer at pH 8.0, containing 8 M guanidinium chloride and 30 mM DTE. Pro-BACE2 is refolded by diluting the clear supernatant at a ratio of 1 :200 into a solution of 3 M guanidinium chloride, 0.7 M arginine (pH 10.4), 0.5 mM oxidized- glutathione and 1 mM reduced glutathione. After " incubation for 16 hours at 4 0C, the solution is further diluted (17-fold) by addition of a solution of 0.7 M arginine (pH 9.4), 1 M NaCI, 0.5 mM oxidized glutathione and 1 mM reduced glutathione. Following incubation for 2-3 days at 4 0C, the pH of the protein solution is adjusted to pH 3.2 with citric acid (final concentration: 5-10 mM) and hydrochloric acid. The precipitated protein is removed by centrifugation and the pH value of the clear supernatant adjusted to pH 6.8 by addition of Tris (final concentration: 20 mM) and NaOH. After addition of ammonium sulfate to a final concentration of 1.5 M, the solution is loaded onto a butyl sepharose column. BACE2 is eluted in a single step with 20 mM Tris/HCI buffer at pH 6.8, containing 350 mM NaCI. The pH of the protein solution is again adjusted to pH 3.2 and the precipitated protein removed by centrifugation. BACE2 is cleaved at the engineered factor Xa site by addition of 0.09 mg/ml trypsin and further purified by gel filtration chromatography using a 26/60 Superdex 75 column equilibrated and run with 10 mM Tris/HCI buffer at pH 6.8, containing 350 mM NaCI. Pure BACE2 is then concentrated to 6 mg/ml and subjected to crystallization trials. The activation and purification procedures result in a construct of BACE2 comprising amino acids AlaδO to Ala465 (numbering according to SEQ ID No. 3). Example 3: Crystallization, data collection and structure determination of human BACE2
Crystallization
Human BACE2 (amino acids 75ANFLAM-CVPA460, numbering according to SEQ ID No. 1) is crystallized at 200C in hanging drops by mixing 1 μl protein solution, comprising 8.8 mg/ml BACE2, 10 mM Tris/HCI pH 6.8, 350 mM NaCI, 2 mM inhibitor and 2 % DMSO, with 1 μl reservoir solution, composed of 16 % PEG8000, 100 mM CaCI2 and 5 % Glycerol, and equilibrating the drop against 600 μl of the reservoir solution. Diffracting quality crystals in form of thin needles, belonging to the rhombohedral space group R3, are obtained after approximately six weeks.
Data collection
For data collection a crystal is cryoprotected by the addition of 0.25 μl Glycerol to the drop followed by flash-freezing the crystal in liquid nitrogen. X-ray diffraction data are collected at the Swiss Light Source (SLS) beamline X06SA, Villingen, Switzerland with a MARCCD detector at 95 K. 70 images are collected with 1.0° oscillation each, using an exposure time of 3 sec. per frame and a crystal-to-detector distance of 210 mm. The raw diffraction data are processed and scaled with the HKL program suite version 1.97.2 (Otwinowski et al. 1997). The data collection statistics are summarized in Table 2.
Structure determination and refinement
The structure of BACE2 is solved by molecular replacement with the program MOLREP (Vagin et al., 1997) using the coordinates of human BACE1 (Protein Data Bank accession code 1 FKN) as a search model. With a high resolution data cut off of 3.5 A, an unambiguous solution is found in space group R3 with four BACE2 molecules in the asymmetric unit (correlation coefficient of 0.47, R-factor of 0.44). An initial refinement cycle, using the rigid- body and simulated annealing protocols as implemented in CNX version 2000 (Accelrys, San Diego, USA, / Brϋnger, 1996) results in a model which is used to calculate the initial electron density map. This electron density map is of good quality and allows the unambiguous assignment and building of most amino acids residues using the program O version 7.0 (Jones et al. 1991). Alternating cycles of refinement, including overall anisotropic B-factor scaling, a bulk solvent correction, positional and unrestrained grouped B-factor refinement, and manual rebuilding results in the final model with R-factors of 0.225 and 0.245 (Rfree). Strict non crystallographic symmetry (NCS), using the NCS operaters given in Table 3, as well as cross-validation, using 10% of the reflections, is used throughout the refinement process. The stereochemical quality of the model is analyzed with the programs CNX version 2000 and PROCHECK (Laskowski et al. 1993). The refinement statistics are summarized in Table 4.
Example 4: Crystal Structure of BACE2 in complex with inhibitor 1
The overall structure of BACE2 follows the general fold of aspartic proteases of the A1 family (Baldwin et al. 1993, Metcalf et al. 1993) and comprises a N-terminal domain (amino acids Ser88-Asn223), a C-terminal domain (residues Lys269-Ala460) and a six-stranded anti-parallel β-sheet inter-domain (amino acid numbering according to SEQ ID No. 1). The inter-domain consists of the ten N-terminal amino acids (Leu78-Asp87), building the outermost strand of the inter-domain β-sheet, amino acids He224-lle268, connecting the N- and C-terminal domains, and the amino acids Gly414-Cys433. Both, the N- and the C- terminal domain each contribute one catalytic aspartic acid residue, Asp101 and Asp303, respectively, to the active site. The- center of the active site is completely shielded from solvent by a flexible stretch of amino acids, a β-hairpin loop also known as the flap (amino acids Val147 to Ser153), which folds back over the active site upon inhibitor binding.
Most amino acids are well defined by the electron density in the BACE2 structure with a few exceptions: The three N-terminal amino acids Ala75 to Phe77 and amino acids Gly236 to Thr244 are completely disordered and therefore not visible in the x-ray structure.
The non-peptide based inhibitor 1 binds to the .center of the active site of BACE-2 and spans from the S3 to the S2' binding pockets. The transition state hydroxy! group (atom 07) interacts with the outer oxygen atom (atom OD2) of the catalytic aspartate (Asp 110), while the transition state amino group (atom N 12) makes interactions with the outer oxygen atom of the second catalytic aspartate (Asp303, atom OD2) as well as the carbonyl group of Gly112 (atom O). The methylbenzyl moiety points into the S2' binding pocket, while the methylene group is pointing towards SV. The phenyl ring is occupying S1 and the tricycle is bridging S2 and S3. The amide group interacts via atom N1 with the carbonyl of Gly305 and via atom 046 with the backbone nitrogen atom of Thr150. One additional hydrogen bonding interaction is observed between the oxygen atom of the tricycle (atom O60) and the backbone nitrogen atom of Thr307. In addition to the above mentioned specific interaction, additional hydrophobic and van-der-Waals interactions are formed. Especially the phenyl group in S1 makes extensive hydrophobic interactions with the hydrophobic side chains of Tyr149, Phe186, He196, Leu108 and Trp193.
References:
References related to BACE2 and other aspartyl proteases
Vassar, R., Bennett, B.D., Babu-Khan, S., Kahn, S., Mendiaz, E.A., Denis, P., Teplow, D.B., Ross, S., Amarante, P., Loeloff, R., Luo, Y., Fisher, S., Fuller, J., Edenson, S., LiIe, J., Jarosinski, M.A., Biere, A.L., Curran, E., Burgess, T., Louis, J. C, Collins, F., Treanor, J., Rogers, G. & Citron, M., Science 286, 735-741(1999).
Yan, R., Bienkowski, M. E., Shuck, M. E., Miao, H., Tory, M. C, Pauley, A. M., Brashler, J. R., Stratman, N. C, Mathews, W. R., Buhl, A. E., Carter, D. B., Tomasselli, A. G., Parodi, L. A., Heinrikson, R. L. & Gurney, M. E., Nature 402, 533-537 (1999).
Acquat, F., Accarino, M., Nucci, C, Fumagalli, P., Jovine, L., Ottolenghi, S. & Taramelli, R., FEBS Lett. 468, 59-64 (2000). . .. . . .. .. . .
Bennett, B. D., Babu-Khan, S., Loeloff, R., Louis, J. C, Curran, E., Citron, M. & Vassar, R., J. Biol. Chem. 275, 20647-20651 (2000).
Hussain, I., Powell, D. J., Howlett, D. R., Chapman, G. A., Gilmour, L., Murdock, P. R., Tew, D. G., Meek, T. D., Chapman, C, Schneider, K., Ratcliffe, S. J., Tattersall, D., Testa, T. T., Southan, C, Ryan, D. M., Simmons, D. L., Walsh, F. S., Dingwall, C. & Christie, G., MoI. Cell. Neurosci. 16, 609-619 (2000).
Barbiero, L., Benussi, L., Ghidoni, R., Alberici, A., Russo, C, Schettini, G., Pagano, S.F., Parati, E.A., Mazzoli, F., Nicosia, F., Signorini, S., Feudatari, E. & Binetti, G., Exp. Neurol. 182, 335-345 (2003).
Vattemi, G., Engel, W. K., McFerrin, J., Pastorino, L., Buxbaum, J. D. & Askanas, V., Exp. Neurol. 179, 150-158 (2003).
Hong ,L., Koelsch, G., Lin, X., Wu, S., Terzyan, S., Ghosh, A.K., Zhang, X.C & Tang, J., Science 290, 150-153 (2000).
Baldwin E. T., Bhat, T. N., Gulnik, S., Hosur, M. V., Sowder, R. C, Cachau, R. E., Collins, J., Silva, A. M. & Erickson, J. W. (1993). Crystal structures of native and inhibited forms of human cathepsin D: implications for lysosomal targeting and drug design. Proc. Natl. Acad. ScL U.S.A. 90, 6796-6800.
Metcalf, P. & Fusek, M. (1993). Two crystal structures for cathepsin D: the lysosomal targeting signal and active site. EMBO J. 12, 1293-1302.
Kondoh K, Tsuji N, Kamagata C, Sasaki M, Kobayashi D, Yagihashi A, Watanabe N. (2003) A novel aspartic protease gene, ALP56, is up-regulated in human breast cancer independently from the cathepsin D gene. Breast Cancer Res 7ratf.78(l):37-44.
References related to computational programs and methods:
Ausubel F.M., Brent R., Kingston R.E., Moore D.D., Seidmann J. G., Struhl K. "Current protocols in molecular biology." Revised edition. New York: John Wiley & Sons, 1997.
Brϋnger AT. (1996). XPLOR version 3.843, Yale University, New Haven, CT.
Collaborative Computational Project, Number 4 (1994). "The CCP4 suite: Programs for Protein Crystallography." Acta Cryst, D50, 760-763.
Jones, T. A., Zou, J. Y., Cowan, S. W. & Kjeldgaard M (1991). "Improved methods for binding protein models in electron density maps and the location of errors in these models." Acta Cryst, A47, 110-119.
Laskowski, R.A., MacArthur M.W., Moss, D. S. & Thornton, J. M. (1993). "PROCHECK: a program to check the stereo chemical quality of protein structures." J. Appl. Crystallogr., 26, (2) 283-291.
Otwinowski Z. & Minor W. (1997) Methods in Enzymology, Volume 276: Macromolecular Crystallography, part A, p.307-326, CW. Carter, Jr. & R.M. Sweet, Eds., Academic Press. "Processing of X-ray Diffraction Data Collected in Oscillation Mode."
Vagin, A. & Teplyakov, A (1997). MOLREP: an automated program for molecular replacement. J. Appl. Cryst. 30, 1022-1025. Table 1 : Atomic Coordinates for BACE2 crystal structure
ATOM 1 CB LEU A 78 114.007 51.880 2.022 1 .00 21.82 A C
ATOM 2 CG LEU A 78 113.609 52.063 3.510 1 .00 21.82 A C
ATOM 3 CDl LEU A 78 112.118 52.365 3.564 1 .00 21.82 A C
ATOM 4 CD2 LBU A 78 113.914 50.833 4.375 1 .00 21.82 A C
ATOM 5 C LEU A 78 115.470 51.627 -0.002 1 .00 40.73 A C
ATOM 6 O LEU A 78 114.434 51.786 -0.648 1 .00 40.73 A O
ATOM 7 N LEU A 78 116.411 52.640 2.095 1 .00 40.73 A N
ATOM 8 CA LEU A 78 115.455 51.634 1.532 1 .00 40.73 A C
ATOM 9 N ALA A 79 116.662 51.485 -0.576 1 .00 44.77 A N
ATOM 10 CA ALA A 79 116.827 51.372 -2.025 1 .00 44.77 A C
ATOM 11 CB ALA A 79 117.870 52.323 -2.515 1 .00 36.11 A C
ATOM 12 C ALA A 79 117.300 49.916 -2.179 1 .00 44.77 A C
ATOM 13 O ALA A 79 118.439 49.624 -2.576 1 .00 44.77 A O
ATOM 14 N MET A 80 116.387 49.022 -1.791 1 .00 29.73 A N
ATOM 15 CA MET A 80 116.563 47.581 -1.809 1 .00 29.73 A C
ATOM 16 CB MET A 80 116.067 46.998 -0.487 1 .00 21.91 A C
ATOM 17 CG MET A 80 116.488 47.785 0.742 1 .00 21.91 A C
ATOM 18 SD MET A 80 115.748 47.141 2.271 1 .00 21.91 A S
ATOM 19 CE MET A 80 116.758 47.905 3.526 1 .00 21.91 A C
ATOM 20 C MET A 80 115.699 47.062 -2.951 1 .00 29.73 A C
ATOM 21 O MET A 80 115.404 45.874 -3.054 1 .00 29.73 A O
ATOM 22 N VAL A 81 115.274 47.980 -3.799 1 .00 20.39 A N
ATOM 23 CA VAL A 81 114.447 47.643 -4.939 1 .00 20.39 A C
ATOM 24 CB VAL A 81 114.068 48.925 -5.686 1 .00 15.77 A C
ATOM 25 CGl VAL A 81 113.335 48.594 -6.961 1 .00 15.77 A C
ATOM 26 CG2 VAL A 81 113.209 49.800 -4.784 1 .00 15.77 A C
ATOM 27 C VAL A 81 115.191 46.689 -5.875 1 .00 20.39 A C
ATOM 28 O VAL A 81 116.393 46.839 -6.083 1 .00 20.39 A O
ATOM 29 N ASP A 82 114.481 45.710 -6.432 1 .00 23.86 A N
ATOM 30 CA ASP A 82 115.092 44.743 -7.343 1 .00 23.86 A C
ATOM 31 CB ASP A 82 115.706 45.455 -8.551 1 .00 69.66 A C
ATOM 32 CG ASP A 82 114.666 46.087 -9.449 1 .00 69.66 A C
ATOM 33 ODl ASP A 82 115.046 46.926 -10.296 1 .00 69.66 A O
ATOM 34 OD2 ASP A 82 113.474 45.741 -9.314 1 .00 69.66 A O
ATOM 35 C ASP A 82 116.178 43.923 -6.651 1 .00 23.86 A C
ATOM 36 O ASP A 82 117.087 43.405 -7.307 1 .00 23.86 A O
ATOM 37 N ASN A 83 116.085 43.805 -5.328 1 .00 20.46 A N
ATOM 38 CA ASN A 83 117.068 43.047 -4.575 1 .00 20.46 A C
ATOM 39 CB ASN A 83 117.176 43.590 -3.144 1 .00 11.61 A C ATOM 40 CG ASN A 83 115.963 43.264 -2.285 1.00 11.61 A C
ATOM 41 ODl ASN A 83 114.910 42.886 -2.788 1.00 11.61 A O
ATOM 42 ND2 ASN A 83 116.109 43.425 -0.975 1.00 11.61 A N
ATOM 43 C ASN A 83 116.745 41.556 -4.559 1.00 20.46 A C
ATOM 44 O ASN A 83 117.428 40.777 -3.898 1.00 20.46 A O
ATOM 45 N LEU A 84 115.714 41.152 -5.296 1.00 10.68 A N
ATOM 46 CA LEU A 84 115.325 39.745 -5.356 1.00 10.68 A C
ATOM 47 CB LEU A 84 113.907 39.560 -4.830 1.00 12.02 A C
ATOM 48 CG LEU A 84 113.592 39.879 -3.381 1.00 12.02 A C
ATOM 49 CDl LEU A 84 112.207 39.352 -3.036 1.00 12.02 A C
ATOM 50 CD2 LEU A 84 114.645 39.233 -2.503 1.00 12.02 A C
ATOM 51 C LEU A 84 115.358 39.183 -6.769 1.00 10.68 A C
ATOM 52 O LEU A 84 114.978 39.868 -7.713 1.00 10.68 A Q
ATOM 53 N GLN A 85 115.805 37.939 -6.915 1.00 30.66 A N
ATOM 54 CA GLN A 85 115.814 37.281 -8.221 1.00 30.66 A C
ATOM 55 CB GLN A 85 117.213 36.816 -8.606 1.00 55.87 A C
ATOM 56 CG GLN A 85 118.175 37.917 -8.958 1.00 55.87 A C
ATOM 57 CD GLN A • 85 119.393 37.387 -9.696 1.00 55.87 A C
ATOM 58 OEl GLN A 85 120.015 36.410 -9.272 1.00 55.87 A o
ATOM ' 59 NE2 GLN A 85 119.743 38.033 -10.805 1.00 55.87 A N
ATOM 60 C GLN A 85 114.905 36.063 -8.097 1.00 30.66 A C
ATOM 61 O GLN A 85 114.696 35.567 -6.992 1.00 30.66 A O
ATOM 62 N GLY A 86 114.351 35.586 -9.210 1.00 26.36 A N
ATOM 63 CA GLY A 86 113.492 34.415 -9.137 1.00 26.36 A C
ATOM 64 C GLY A 86 112.113 34.554 -9.752 1.00 26.36 A C
ATOM 65 O GLY A 86 111.836 35.502 -10.477 1.00 26.36 A o
ATOM 66 N ASP A 87 111.240 33.600 -9.452 1.00 24.99 A N
ATOM 67 CA ASP A 87 109.886 33.608 -9.990 1.00 24.99 A C
ATOM 68 CB ASP A 87 109.908 33.208 -11.462 1.00 56.51 A C
ATOM 69 CG ASP A 87 110.328 31.761 -11.660 1.00 56.51 A C
ATOM 70 ODl ASP A 87 110.000 31.183 -12.718 1.00 56.51 A o
ATOM 71 OD2 ASP A 87 110.990 31.199 -10.758 1.00 56.51 A o
ATOM 72 C ASP A 87 108.968 32.633 -9.247 1.00 24.99 A C
ATOM 73 O ASP A 87 109.413 31.846 -8.411 1.00 24.99 A o
ATOM 74 N SER A 88 107.681 32.691 -9.582 1.00 23.55 A N
ATOM 75 CA SER A 88 106.664 31.830 -8.996 1.00 23.55 A C
ATOM 76 CB SER A 88 105.361 31.994 -9.778 1.00 60.38 A C
ATOM 77 OG SER A 88 104.424 30.996 -9.427 1.00 60.38 A O
ATOM 78 C SER A 88 107.088 30.363 -9.020 1.00 23.55 A C
ATOM 79 O SER A 88 106.758 29.600 -8.121 1.00 23.55 A o
ATOM 80 N GLY A 89 107.828 29.984 -10.056 1.00 27.01 A N ATOM 81 CA GLY A 89 108.281 28.609 -10.213 1.00 27.01 A C
ATOM 82 C GLY A 89 109.062 27.981 -9.074 1.00 27.01 A C
ATOM 83 O GLY A 89 108.618 26.998 -8.484 1.00 27.01 A O
ATOM 84 N ARG A 90 110.234 28.517 -8.762 1.00 23.02 A N
ATOM 85 CA ARG A 90 111.003 27.937 -7.678 1.00 23.02 A C
ATOM 86 CB ARG A 90 112.283 27.305 -8.220 1.00 13.34 A C
ATOM 87 CG ARG A 90 112.085 26.430 -9.451 1.00 13.34 A C
ATOM 88 CD ARG A 90 112.471 24.958 -9.230 1.00 13.34 A C
ATOM 89 NE ARG A 90 111.323 24.143 -8.841 1.00 13.34 A N
ATOM 90 CZ ARG A 90 111.168 22.857 -9.143 1.00 13.34 A C
ATOM 91 NHl ARG A 90 112.090 22.200 -9.841 1.00 13.34 A N
ATOM 92 NH2 ARG A 90 110.062 22.235 -8.767 1.00 13.34 A N
ATOM 93 C ARG A 90 111.335 28.925 -6.560 1.00 23.02 A C
ATOM 94 O ARG A 90 112.263 28.705 -5.794 1.00 23.02 A O
ATOM 95 N GLY A 91 110.581 30.016 -6.471 1.00 11.27 A N
ATOM 96 CA GLY A 91 110.799 30.977 -5.402 1.00 11.27 A C
ATOM 97 C GLY A 91 111.673 32.178 -5.697 1.00 11.27 A C
ATOM 98 O GLY A 91 112.410 32.205 -6.688 1.00 11.27 A O
ATOM 99 N TYR A 92 111.581 33.175 -4.821 1.00 10.00 A N
ATOM 100. "CA TYR A. 92 -: 112.359 34.394 -4.944 1.00 10.00 A C
ATOM 101 CB TYR A 92 111.466 35.606 -4.718 1.00 12.41 A C
ATOM 102. CG TYR A 92 110.442 35.804 -5.806 1.00 12.41 A C
ATOM 103 CDl TYR A 92 109.272 35.059 -5.832 1.00 12.41 A C
ATOM 104 CEl TYR A 92 108.348 35.214 -6.857 1.00 12.41 A C
ATOM 105 CD2 TYR A 92 110.665 36.714 -6.836 1.00 12.41 A C
ATOM 106 CE2 TYR A 92 109.754 36.875 -7.866 1.00 12.41 A C
ATOM 107 CZ TYR A 92 108.600 36.122 -7.871 1.00 12.41 A C
ATOM 108 OH TYR A 92 107.703 36.265 -8.903 1.00 12.41 A O
ATOM 109 C TYR A 92 113.500 34.390 -3.938 1.00 10.00 A C
ATOM 110 O TYR A 92 113.313 34.071 -2.767 1.00 10.00 A O
ATOM 111 N TYR A 93 114.688 34.758 -4.385 1.00 10.00 A N
ATOM 112 CA TYR A 93 115.820 34.742 -3.488 1.00 10.00 A C
ATOM 113 CB TYR A 93 116.717 33.565 -3.833 1.00 17.15 A C
ATOM 114 CG TYR A 93 117.151 33.552 -5.266 1.00 17.15 A C
ATOM 115 CDl TYR A 93 118.346 34.150 -5.655 1.00 17.15 A C
ATOM 116 CEl TYR A 93 118.741 34.154 -6.985 1.00 17.15 A C
ATOM 117 CD2 TYR A 93 116.357 32.958 -6.245 1.00 17.15 A C
ATOM 118 CE2 TYR A 93 116.740 32.960 -7.579 1.00 17.15 A C
ATOM 119 CZ TYR A 93 117.932 33.559 -7.941 1.00 17.15 A C
ATOM 120 OH TYR A 93 118.313 33.576 -9.262 1.00 17.15 A O
ATOM 121 C TYR A 93 116.647 36.010 -3.393 1.00 10.00 A C ATOM 122 O TYR A 93 116.833 36.755 -4.354 1.00 10.00 A O
ATOM 123 N LEU A 94 117 .145 36 .222 -2 .187 1. 00 14 .68 A N
ATOM 124 CA LEU A 94 117 .949 37 .372 -1 .829 1. 00 14 .68 A C
ATOM 125 CB LEU A 94 117 .490 37 .881 -0 .468 1. 00 10 .00 A C
ATOM 126 CG LEU A 94 118 .273 39 .019 0 .155 1. 00 10 .00 A C
ATOM 127 CDl LEU A 94 117 .922 40 .287 -0 .578 1. 00 10 .00 A C
ATOM 128 CD2 LEU A 94 117 .932 39 .145 1 .620 1. 00 10 .00 A C
ATOM 129 C LEU A 94 119 .393 36 .925 -1 .726 1. 00 14 .68 A C
ATOM 130 O LEU A 94 119 .664 35 .818 -1 .264 1. 00 14 .68 A O
ATOM 131 N GLU A 95 120 .322 37 .776 -2 .148 1. 00 23 .04 A N
ATOM 132 CA GLU A 95 121 .733 37 .429 -2 .061 1. 00 23 .04 A C
ATOM 133 CB GLU A 95 122 .510 38 .003 -3 .242 1. 00 63 .26 A C
ATOM 134 CG GLU A 95 124 .014 37 .865 -3 .062 1. 00 63 .26 A C
ATOM 135 CD GLU A 95 124 .822 38 .627 -4 .098 1. 00 63 .26 A C
ATOM 135 OEl GLU A 95 124 .636 38 .367 -5 .310 1. 00 63 .26 A O
ATOM 137 OE2 GLU A 95 125 .649 39 .480 -3 .695 1. 00 63 .26 A O
ATOM 138 C GLU A 95 122 .334 37 .988 -0 .784 1. 00 23 .04 A C
ATOM 139 O GLU A 95 122 .204 39 .174 -0 .521 1. 00 23 .04 A O
ATOM 140 N MET A 96 122 .958 37 .143 0 .029 1. 00 10 .47 A N
ATOM 141 CA MET A 96 123 .625 37 .641 1 .224 1. 00 10 .47 A C
ATOM 142 CB MET A 96 122 .827 37 .377 2 .508 1. 00 19 .34 A C
ATOM 143 CG MET A 96 121 .881 36 .223 2 .495 1. 00 19 .34 A C
ATOM 144 SD MET A 96 121 .077 36 .031 4 .128 1. 00 19 .34 A S
ATOM 145 CE MET A 96 119 .811 37 .283 4 .076 1. 00 19 .34 A C
ATOM 146 C MET A 96 125 .028 37 .054 1 .328 1. 00 10 .47 A C
ATOM 147 O MET A 96 125 .303 35 .987 0 .785 1. 00 10 .47 A O
ATOM 148 N LEU A 97 125 .922 37 .786 1 .989 1. 00 23 .00 A N
ATOM 149 CA LEU A 97 127 .307 37 .369 2 .174 1. 00 23 .00 A C
ATOM 150 CB LEU A 97 128 .235 38 .564 1 .977 1. 00 15 .84 A C
ATOM 151 CG LEU A 97 128 .115 39 .313 0 .650 1. 00 15 .84 A C
ATOM 152 CDl LEU A 97 129 .055 40 .498 0 .638 1. 00 15 .84 A C
ATOM 153 CD2 LEU A 97 128 .434 38 .380 -0 .491 1. 00 15 .84 A C
ATOM 154 C LEU A 97 127 .458 36 .831 3 .591 1. 00 23 .00 A C
ATOM 155 O LEU A 97 127 .047 37 .480 4 .555 1. 00 23 .00 A O
ATOM 156 N ILE A 98 128 .069 35 .662 3 .727 1. 00 12 .96 A N
ATOM 157 CA ILE A 98 128 .206 35 .068 5 .040 1. 00 12 .96 A C
ATOM 158 CB ILE A 98 127 .417 33 .763 5 .086 1. 00 13 .20 A C
ATOM .159 CG2 ILE A 98 127 .481 33 .142 6 .477 1. 00 13 .20 A C
ATOM 160 CGl ILE A 98 125 .977 34 .046 4 .677 1. 00 13 .20 A C
ATOM 161 CDl ILE A 98 125 .112 32 .821 4 .619 1. 00 13 .20 A C
ATOM 162 C ILE A 98 129 .626 34 .785 5 .505 1. 00 12 .96 A C ATOM 163 O ILE A 98 130.466 34.331 4.729 1.00 12.96 A O
ATOM 164 N GLY A 99 129.879 35.056 6.785 1.00 12 .78 A N
ATOM 165 CA GLY A 99 131.178 34.782 7.378 1.00 12 .78 A C
ATOM 166 C GLY A 99 132.330 35.707 7.050 1.00 12 .78 A C
ATOM 167 O GLY A 99 132.170 36.704 6.346 1.00 12 .78 A O
ATOM 168 N THR A 100 133.503 35.356 7.569 1.00 25 .39 A N
ATOM 169 CA THR A 100 134.720 36.131 7.363 1.00 25 .39 A C
ATOM 170 CB THR A 100 135.119 36.847 8.657 1.00 16 .63 A C
ATOM 171 OGl THR A 100 134.099 37.788 9.010 1.00 16 .63 A O
ATOM 172 CG2 THR A 100 136.436 37.572 8.478 1.00 16 .63 A C
ATOM 173 C THR A 100 135.890 35.249 6.914 1.00 25 .39 A C
ATOM 174 O THR A 100 136.335 34.376 7.655 1.00 25 .39 A o
ATOM 175 N PRO A 101 136.392 35.452 5.686 1.00 20 .95 A N
ATOM 176 CD PRO A 101 137.486 34.650 5.118 1.00 11 .50 A C
ATOM 177 CA PRO A 101 135.919 36.432 4.710 1.00 20 .95 A C
ATOM 178 CB PRO A 101 136.948 36.324 3.593 1.00 11 .50 A C
ATOM 179 CG PRO A 101 137.322 34.896 3.639 1.00 11 .50 A C
ATOM 180 C PRO A 101 134.528 36.039 4.255 1.00 20 .95 A C
ATOM 181 o PRO A 101 134.039 34..969 4.610 1.00 20 .95 A o
ATOM 182-. N PRO A 102 133.877 36.892 3.455 1.00 30 .26 A N
ATOM 183 CD PRO A 102 134.304 38.255 3.105 1.00 29 .56 A C
ATOM 184 CA PRO A 102 132.526 36.638 2.952 1.00 30 .26 A C
ATOM 185 CB PRO A 102 132.134 37.976 2.326 1.00 29 .56 A C
ATOM 186 CG PRO A 102 132.988 38.974 3.042 1.00 29 .56 A C
ATOM 187 C PRO A 102 132.382 35.496 1.949 1.00 30 .26 A C
ATOM 188 O PRO A 102 133.251 35.274 1.107 1.00 30 .26 A o
ATOM 189 N GLN A 103 131.268 34.779 2.064 1.00 15 .25 A N
ATOM 190 CA GLN A 103 130.924 33.691 1.166 1.00 15 .25 A C
ATOM 191 CB GLN A 103 130.842 32.370 1.918 1.00 14 .76 A C
ATOM 192 CG GLN A 103 132.190 31.793 2.300 1.00 14 .76 A C
ATOM 193 CD GLN A 103 132.081 30.466 3.046 1.00 14 .76 A C
ATOM 194 OEl GLN A 103 131.589 29.464 2.506 1.00 14 .76 A O
ATOM 195 NE2 GLN A 103 132.543 30.454 4.294 1.00 14 .76 A N
ATOM 196 C GLN A 103 129.551 34.071 0.609 1.00 15 .25 A C
ATOM 197 O GLN A 103 128.585 34.259 1.361 1.00 15 .25 A O
ATOM 198 N LYS A 104 129.478 34.201 -0.711 1.00 20 .45 A N
ATOM 199 CA LYS A 104 128.252 34.591 -1.397 1.00 20 .45 A C
ATOM 200 CB LYS A 104 128.618 35.022 -2.816 1.00 54 .46 A C
ATOM 201 CG LYS A 104 127.545 35.731 -3.599 1.00 54 .46 A C
ATOM 202 CD LYS A 104 128.152 36.225 -4.900 1.00 54 .46 A C
ATOM 203 CE LYS A 104 127.172 37.036 -5.731 1.00 54 .46 A C ATOM 204 NZ LYS A 104 127 813 37.599 -6.958 1.00 54.46 A N
ATOM 205 C LYS A 104 127.222 33.468 -1.438 1.00 20.45 A C
ATOM 206 O LYS A 104 127, 493 32.397 -1.965 1.00 20.45 A O
ATOM 207 N LEU A 105 126, 043 33.707 -0.876 1.00 20.39 A N
ATOM 208 CA LEU A 105 124, 979 32.705 -0.894 1.00 20.39 A C
ATOM 209 CB LEU A 105 124, 688 32.189 0.511 1.00 21.65 A C
ATOM 210 CG LEU A 105 125.813 31.415 1.170 1.00 21.65 A C
ATOM 211 CDl LEU A 105 125.230 30.597 2.302 1.00 21.65 A C
ATOM 212 CD2 LEU A 105 126.460 30.492 0.163 1.00 21.65 A C
ATOM 213 C LEU A 105 123.697 33.283 -1.474 1.00 20.39 A C
ATOM 214 O LEU A 105 123.502 34.499 -1.478 1.00 20.39 A O
ATOM 215 N GLN A 106 122.819 32.410 -1.953 1.00 18.44 A N
ATOM 216 CA GLN A 106 121.549 32.847 -2.522 1.00 18.44 A C
ATOM 217 CB GLN A 106 121.410 32.305 -3.938 1.00 30.25 A C
ATOM 218 CG GLN A 106 122.558 32.645 -4.851 1.00 30.25 A C
ATOM 219 CD GLN A 106 122.770 34.137 -4.980 1.00 30.25 A C
ATOM 220 OEl GLN A 106 121.824 34.926 -4.959 1.00 30.25 A O
ATOM 221 NE2 GLN A 106 124.018 34.534 -5.134 1.00 30.25 A N
ATOM 222 C GLN A 106 120.408 32.326 -1.653 1.00 18.44 A C
ATOM 223 ■ O GLN A 106 120.063 31.147 -1.725- 1.00 18.44 A O
ATOM 224 N ILE A 107 119.809 33.200 -0.853 1.00 10.00 A N
ATOM 225 CA ILE A 107 118.748 32.778 0.050 1.00 10.00 A C
ATOM 226 CB ILE A 107 118.861 33.511 1.379 1.00 10.00 A C
ATOM 227 CG2 ILE A 107 117.886 32.927 2.378 1.00 10.00 A C
ATOM 228 CGl ILE A 107 120.289 33.409 1.891 1.00 10.00 A C
ATOM 229 CDl ILE A 107 120.846 32.004 1.841 1.00 10.00 A C
ATOM 230 C ILE A 107 117.312 32.927 -0.428 1.00 10.00 A C
ATOM 231 O ILE A 107 116.907 33.975 -0.918 1.00 10.00 A O
ATOM 232 N LEU A 108 116.534 31.868 -0.251 1.00 20.17 A N
ATOM 233 CA LEU A 108 115.136 31.877 -0.634 1.00 20.17 A C
ATOM 234 CB LEU A 108 114.638 30.450 -0.759 1.00 10.36 A C
ATOM 235 CG LEU A 108 113.123 30.291 -0.804 1.00 10.36 A C
ATOM 236 CDl LEU A 108 112.557 31.094 -1.940 1.00 10.36 A C
ATOM 237 CD2 LEU A 108 112.778 28.837 -0.979 1.00 10.36 A C
ATOM 238 C LEU A 108 114.347 32.597 0.445 1.00 20.17 A C
ATOM 239 O LEU A 108 114.458 32.251 1.619 1.00 20.17 A O
ATOM 240 N VAL A 109 113.556 33.594 0.063 1.00 10.00 A N
ATOM 241 CA VAL A 109 112.772 34.331 1.047 1.00 10.00 A C
ATOM 242 CB VAL A 109 112.464 35.741 0.550 1.00 11.92 A C
ATOM 243 CGl VAL A 109 111.379 36.367 1.388 1.00 11.92 A C
ATOM 244 CG2 VAL A 109 113.712 36.584 0.631 1.00 11.92 A C ATOM 245 C VAL A 109 111.474 33.609 1.375 1.00 10.00 A C ATOM 246 O VAL A 109 110.596 33.474 0 .531 1. 00 10 .00 A O ATOM 247 N ASP A 110 111.346 33.168 2 .621 1. 00 10 .00 A N ATOM 248 CA ASP A 110 110.172 32.424 3 .057 1. 00 10 .00 A C ATOM 249 CB ASP A 110 110.590 31.006 3 .405 1. 00 10 .48 A C ATOM 250 CG ASP A 110 109.477 30.211 4 .033 1. 00 10 .48 A C ATOM 251 ODl ASP A 110 108.331 30.340 3 .571 1. 00 10 .48 A O ATOM 252 OD2 ASP A 110 109.749 29.442 4 .974 1. 00 10 .48 A O ATOM 253 C ASP A 110 109.463 33.022 4 .250 1. 00 10 .00 A C ATOM 254 O ASP A 110 109.961 32.934 5 .362 1. 00 10 .00 A O ATOM 255 N THR A 111 108.292 33.605 4 .036 1. 00 10 .00 A N ATOM 256 CA THR A 111 107.555 34.203 5 .143 1. 00 10 .00 A C ATOM 257 CB THR A 111 106.579 35.274 4 .669 1. 00 12 .20 A C ATOM 258 OGl THR A 111 105.554 34.660 3 .879 1. 00 12 .20 A O ATOM 259 CG2 THR A 111 107.297 36.323 3 .849 1. 00 12 .20 A C ATOM 260 C THR A 111 106.739 33.154 5 .867 1. 00 10 .00 A C ATOM 261 O THR A 111 106.040 33.450 6 .829 1. 00 10 .00 A O ATOM 262 N GLY A 112 106.825 31.921 5 .396 1. 00 10 .00 A N ATOM 263 CA GLY A 112 106.069 30.851 6 .016 1. 00 10 .00 A C ATOM 264 C GLY A 112 106.835 30.001 7 .009 1. 00 10 .00 A C ATOM 265 O GLY A 112 106.394 28.909 7 .339 1. 00 10 .00 A O ATOM 266 N SER A 113 107.983 30.475 7 .476 1. 00 10 .00 A N ATOM 267 CA SER A 113 108.751 29.715 8 .447 1. 00 10 .00 A C ATOM 268 CB SER A 113 109.505 28.571 7 .775 1. 00 17 .92 A C ATOM 269 OG SER A 113 110.806 28.972 7 .406 1. 00 17 .92 A O ATOM 270 C SER A 113 109.722 30.642 9 .158 1. 00 10 .00 A C ATOM 271 O SER A 113 109.843 31.811 8 .790 1. 00 10 .00 A O ATOM 272 N SER A 114 110.437 30.126 10 .158 1. 00 24 .75 A N ATOM 273 CA SER A 114 111.330 30.982 10 .918 1. 00 24 .75 A C ATOM 274 CB SER A 114 110.673 31.300 12 .248 1. 00 14 .20 A C ATOM 275 OG SER A 114 109.339 31.717 12 .031 1. 00 14 .20 A O ATOM 276 C SER A 114 112.756 30.538 11 .177 1. 00 24 .75 A C ATOM 111 O SER A 114 113.283 30.784 12 .258 1. 00 24 .75 A O ATOM 278 N ASN A 115 113.394 29.895 10 .211 1. 00 11 .02 A N ATOM 279 CA ASN A 115 114.780 29.492 10 .409 1. 00 11 .02 A C ATOM 280 CB ASN A 115 114.890 27.983 10 .590 1. 00 10 .00 A C ATOM 281 CG ASN A 115 114.576 27.548 11 .995 1. 00 10 .00 A C ATOM 282 ODl ASN A 115 113.418 27.525 12 .405 1. 00 10 .00 A O ATOM 283 ND2 ASN A 115 115.611 27.211 12 .753 1. 00 10 .00 A N ATOM 284 C ASN A 115 115.682 29.927 9 .269 1. 00 11 .02 A C ATOM 285 O ASN A 115 115.273 29.961 8 .115 1. 00 11 .02 A O ATOM 286 N PHE A 116 116.911 30.282 9.605 1.00 10.00 A N
ATOM 287 CA PHE A 116 117.875 30.690 8.606 1.00 10.00 A C
ATOM 288 CB PHE A 116 118.747 31.818 9.145 1.00 10.00 A C
ATOM 289 CG PHE A 116 119.664 32.415 8.125 1.00 10.00 A C
ATOM 290 CDl PHE A 116 120.805 33.099 8.518 1.00 10.00 A C
ATOM 291 CD2 PHE A 116 119.382 32.316 6.770 1.00 10.00 A C
ATOM 292 CEl PHE A 116 121.656 33.678 7.573 1.00 10.00 A C
ATOM 293 CE2 PHE A 116 120.226 32.893 5.813 1.00 10.00 A C
ATOM 294 CZ PHE A 116 121.362 33.572 6.217 1.00 10.00 A C
ATOM 295 C PHE A 116 118.714 29.450 8.397 1.00 10.00 A C
ATOM 296 O PHE A 116 119.266 28.904 9.346 1.00 10.00 A O
ATOM 297 N ALA A 117 118.801 28.979 7.168 1.00 10.00 A KT
ATOM 298 CA ALA A 117 119.592 27.792 6.918 1.00 10.00 A C
ATOM 299 CB ALA A 117 118.745 26.559 7.122 1.00 15.46 A C
ATOM 300 C ALA A 117 120.163 27.812 5.517 1.00 10.00 A C
ATOM 301 O ALA A 117 119.515 28.275 4.572 1.00 10.00 A O
ATOM 302 N VAL A 118 121.384 27.306 5.393 1.00 10.00 A N
ATOM 303 CA VAL A 118 122.066 27.264 4.112 1.00 10.00 A C
ATOM 304 CB VAL A 118 123.174 28.327 4.053 1.00 10.00 A C
ATOM 3 30055 CGl VAL A 118 122.646 29.643 4.534 1.00 10.00 A C
ATOM 306 CG2 VAL A 118 124.339 27.911 4.905 1.00 10.00 A C
ATOM 307 C VAL A 118 122.700 25.895 3.911 1.00 10.00 A C
ATOM 308 O VAL A 118 122.901 25.143 4.863 1.00 10.00 A O
ATOM 309 N ALA A 119 123.022 25.570 2.671 1.00 10.47 A N
ATOM 310 CA ALA A 119 123.639 24.289 2.394 1.00 10.47 A C
ATOM 311 CB ALA A 119 123.870 24.129 0.910 1.00 18.76 A C
ATOM 312 C ALA A 119 124.962 24.217 3.132 1.00 10.47 A C
ATOM 313 O ALA A 119 125.785 25.130 3.039 1.00 10.47 A O
ATOM 314 N GLY A 120 125.165 23.127 3.865 1.00 25.50 A N
ATOM 315 CA GLY A 120 126.402 22.958 4.601 1.00 25.50 A C
ATOM 316 C GLY A 120 127.337 21.972 3.936 1.00 25.50 A C
ATOM 317 O GLY A 120 128.457 21.769 4.392 1.00 25.50 A O
ATOM 318 N THR A 121 126.872 21.353 2.859 1.00 20.99 A N
ATOM 319 CA THR A 121 127.665 20.378 2.113 1.00 20.99 A C
ATOM 320 CB THR A 121 127.341 18.958 2.535 1.00 28.07 A C
ATOM 3 32211 OGl THR A 121 126.040 18.619 2.039 1.00 28.07 A O
ATOM 322 CG2 THR A 121 127.351 18.833 4.044 1.00 28.07 A C
ATOM 323 C THR A 121 127.233 20.495 0.668 1.00 20.99 A C
ATOM 324 O THR A 121 126.228 21.130 0.382 1.00 20.99 A O
ATOM 325 N PRO A 122 127.974 19.876 -0.262 1.00 19.29 A N
ATOM 326 CD PRO A 122 129.223 19.117 -0.125 1.00 22.06 A C ATOM 327 CA PRO A 122 127.576 19.968 -1.669 1.00 19.29 A C
ATOM 328 CB PRO A 122 128.721 19.282 -2.407 1.00 22.06 A C
ATOM 329 CG PRO A 122 129.869 19.369 -1.453 1.00 22.06 A C
ATOM 330 C PRO A 122 126.275 19.191 -1.809 1.00 19.29 A C
ATOM 331 O PRO A 122 125.972 18.344 -0.960 1.00 19.29 A O
ATOM 332 N HIS A 123 125.502 19.471 -2.855 1.00 25.47 A N
ATOM 333 CA HIS A 123 124.249 18.752 -3.041 1.00 25.47 A C
ATOM 334 CB HIS A 123 123.180 19.269 -2.093 1.00 32.28 A C
ATOM 335 CG HIS A 123 121.943 18.431 -2.084 1.00 32.28 A C
ATOM 336 CD2 HIS A 123 120.758 18.585 -2.721 1.00 32.28 A C
ATOM 337 NDl HIS A 123 121.854 17.249 -1.385 1.00 32.28 A N
ATOM 338 CEl HIS A 123 120.664 16.709 -1.587 1.00 32.28 A C
ATOM 339 NE2 HIS A 123 119.981 17.499 -2.394 1.00 32.28 A N
ATOM 340 C HIS A 123 123.690 18.777 -4.454 1.00 25.47 A C
ATOM 341 O HIS A 123 123.842 19.745 -5.202 1.00 25.47 A O
ATOM 342 N SER A 124 123.009 17.695 -4.789 1.00 61.35 A N
ATOM 343 CA SER A 124 122.436 17.504 -6.101 1.00 61.35 A C
ATOM 344 CB SER A 124 121.243 16.567 -5.990 1.00 61.73 A C
ATOM 345 OG SER A 124 121.673 15.286 -5.554 1.00 61.73 A o
ATOM 346 C SER A 124 - 122.066 18.712 -6.948 1.00 61.35 A C
ATOM 347 o SER A 124 122.385 18.730 -8.135 1.00 61.35 A o
ATOM 348 N TYR A 125 121.426 19.732 -6.386 1.00 11.50 A N
ATOM 349 CA TYR A 125 121.044 20.853 -7.254 1.00 11.50 A C
ATOM 350 CB TYR A 125 119.512 20.939 -7.344 1.00 44.84 A C
ATOM 351 CG TYR A 125 118.861 19.645 -7.784 1.00 44.84 A C
ATOM 352 CDl TYR A 125 118.268 18.789 -6.856 1.00 44.84 A C
ATOM 353 CEl TYR A 125 117.766 17.543 -7.239 1.00 44.84 A C
ATOM 354 CD2 TYR A 125 118.926 19.231 -9.117 1.00 44.84 A C
ATOM 355 CE2 TYR A 125 118.429 17.988 -9.515 1.00 44.84 A C
ATOM 356 CZ TYR A 125 117.856 17.144 -8.570 1.00 44.84 A C
ATOM 357 OH TYR A 125 117.421 15.889 -8.952 1.00 44.84 A o
ATOM 358 C TYR A 125 121.616 22.241 -6.964 1.00 11.50 A C
ATOM 359 O TYR A 125 121.140 23.241 -7.509 1.00 11.50 A o
ATOM 360 N ILE A 126 122.641 22.307 -6.125 1.00 28.45 A N
ATOM 361 CA ILE A 126 123.258 23.582 -5.781 1.00 28.45 A C
ATOM 362 CB ILE A 126 123.229 23.800 -4.263 1.00 10.00 A C
ATOM 363 CG2 ILE A 126 121.788 23.738 -3.757 1.00 10.00 A C
ATOM 364 CGl ILE A 126 124.086 22.730 -3.581 1.00 10.00 A C
ATOM 365 CDl ILE A 126 124.147 22.846 -2.104 1.00 10.00 A C
ATOM 366 C ILE A 126 124.703 23.561 -6.264 1.00 28.45 A C
ATOM 367 O ILE A 126 125.306 22.495 -6.386 1.00 28.45 A o ATOM 368 N ASP A 127 125.265 24.731 -6.536 1.00 33.23 A N ATOM 369 CA ASP A 127 126.635 24.797 -7.029 1.00 33.23 A C ATOM 370 CB ASP A 127 126.674 25.581 -8.347 1.00 90.00 A C ATOM 371 CG ASP A 127 126.367 27.061 -8.163 1.00 90.00 A C ATOM 372 ODl ASP A 127 125.417 27.401 -7.419 1.00 90.00 A O ATOM 373 OD2 ASP A 127 127.075 27.884 -8.780 1.00 90.00 A O ATOM 374 C ASP A 127 127.574 25.431 -6.010 1.00 33.23 A C ATOM 375 O ASP A 127 128.703 25.796 -6.336 1.00 33.23 A O ATOM 376 N THR A 128 127.105 25.555 -4.774 1.00 27.39 A N ATOM 377 CA THR A 128 127.905 26.148 -3.712 1.00 27.39 A C ATOM 378 CB THR A 128 128.093 27.656 -3.940 1.00 51.44 A C ATOM 379 OGl THR A 128 128.793 28.225 -2.829 1.00 51.44 A O ATOM 380 CG2 THR A 128 126.751 28.343 -4.095 1.00 51.44 A C ATOM 381 C THR A 128 127.219 25.931 -2.373 1.00 27.39 A C ATOM 382 O THR A 128 126.042 25.579 -2.321 1.00 27.39 A O ATOM 383 N TYR A 129 127.957 26.123 -1.287 1.00 10.00 A N ATOM 384 CA TYR A 129 127.392 25.948 0.044 1.00 10.00 A C ATOM 385 CB TYR A 129 127.378 24.468 0.411 1.00 27.96 A C ATOM 386 CG TYR A 129 128.757 23.848 0.489 1.00 27.96 A C ATOM 387 CDl TYR A 129 129.519 23.938 1.650 1.00 27.96 A C ATOM 388 CEl TYR A 129 130.803 23.401 1.715 1.00 27.96 A C ATOM 389 CD2 TYR A 129 129.314 23.199 -0.611 1.00 27.96 A C ATOM 390 CE2 TYR A 129 130.598 22.658 -0.559 1.00 27.96 A C ATOM 391 CZ TYR A 129 131.339 22.761 0.609 1.00 27.96 A C ATOM 392 OH TYR A 129 132.612 22.226 0.674 1.00 27.96 A O ATOM 393 C TYR A 129 128.259 26.723 1.014 1.00 10.00 A C ATOM 394 O TYR A 129 129.365 27.136 0.671 1.00 10.00 A O ATOM 395 N PHE A 130 127.764 26.934 2.223 1.00 14.26 A N ATOM 396 CA PHE A 130 128.539 27.661 3.210 1.00 14.26 A C ATOM 397 CB PHE A 130 127.624 28.338 4.207 1.00 15.19 A C ATOM 398 CG PHE A 130 128.354 29.028 5.311 1.00 15.19 A C ATOM 399 CDl PHE A 130 129.263 30.034 5.029 1.00 15.19 A C ATOM 400 CD2 PHE A 130 128.100 28.703 6.636 1.00 15.19 A C ATOM 401 CEl PHE A 130 129.904 30.711 6.046 1.00 15.19 A C ATOM 402 CE2 PHE A 130 128.737 29.376 7.669 1.00 15.19 A C ATOM 403 CZ PHE A 130 129.640 30.384 7.376 1.00 15.19 A C ATOM 404 C PHE A 130 129.461 26.718 3.958 1.00 14.26 A C ATOM 405 O PHE A 130 129.005 25.749 4.566 1.00 14.26 A O ATOM 406 N ASP A 131 130.757 26.999 3.927 1.00 23.74 A N ATOM 407 CA ASP A 131 131.725 26.144 4.605 1.00 23.74 A C ATOM 408 CB ASP A 131 132.976 26.015 3.736 1.00 40.38 A C ATOM 409 CG ASP A 131 134.004 25.078 4.328 1.00 40.38 A C
ATOM 410 ODl ASP A 131 134 .060 24.978 5.572 1.00 40.38 A O
ATOM 411 OD2 ASP A 131 134 .763 24.456 3.551 1.00 40.38 A O
ATOM 412 C ASP A 131 132 .092 26.760 5.947 1.00 23.74 A C
ATOM 413 O ASP A 131 132 .896 27.681 5.985 1.00 23.74 A O
ATOM 414 N THR A 132 131 .536 26.267 7.050 1.00 15.41 A N
ATOM 415 CA THR A 132 131 .873 26.877 8.334 1.00 15.41 A C
ATOM 416 CB THR A 132 131 .140 26.228 9.540 1.00 23.26 A C
ATOM 417 OGl THR A 132 131 .305 24.806 9.519 1.00 23.26 A O
ATOM 418 CG2 THR A 132 129 .674 26.582 9.518 1.00 23.26 A C
ATOM 419 C THR A 132 133 .358 26.896 8.653 1.00 15.41 A C
ATOM 420 O THR A 132 133 .825 27.803 9.334 1.00 15.41 A o
ATOM 421 N GLU A 133 134 .115 25.923 8.163 1.00 40.23 A N
ATOM 422 CA GLU A 133 135 .542 25.904 8.463 1.00 40.23 A C
ATOM 423 CB GLU A 133 136 .167 24.566 8.061 1.00 90.00 A C
ATOM 424 CG GLU A 133 136 .234 23.559 9.200 1.00 90.00 A C
ATOM 425 CD GLU A 133 137 .507 22.729 9.168 1.00 90.00 A C
ATOM 426 OEl GLU A 133 138 .606 23.327 9.225 1.00 90.00 A o
ATOM 427 OE2 GLU A 133 137 .410 21.483 9.088 1.00 90.00 A o
ATOM 428 C GLU A 133 136 .373 27.042 7.873 1.00 40.23 A C
ATOM 429 O GLU A 133 137 .515 27.236 8.278 1.00 40.23 A O
ATOM 430 N ARG A 134 135 .818 27.799 6.932 1.00 36.25 A N
ATOM 431 CA ARG A 134 136 .565 28.901 6.333 1.00 36.25 A C
ATOM 432 CB ARG A 134 136 .493 28.829 4.805 1.00 78.11 A C
ATOM 433 CG ARG A 134 137 .024 27.541 4.206 1.00 78.11 A C
ATOM 434 CD ARG A 134 137 .292 27.710 2.720 1.00 78.11 A C
ATOM 435 NE ARG A 134 136 .103 28.134 1.985 1.00 78.11 A N
ATOM 436 CZ ARG A 134 136 .114 28.604 0.738 1.00 78.11 A C
ATOM 437 NHl ARG A 134 137 .258 28.715 0.074 1.00 78.11 A N
ATOM 438 NH2 ARG A 134 134 .978 28.965 0.151 1.00 78.11 A N
ATOM 439 C ARG A 134 136 .083 30.277 6.797 1.00 36.25 A C
ATOM 440 O ARG A 134 136 .322 31.280 6.121 1.00 36.25 A O
ATOM 441 N SER A 135 135 .404 30.328 7.941 1.00 29.03 A N
ATOM 442 CA SER A 135 134 .907 31.597 8.473 1.00 29.03 A C
ATOM 443 CB SER A 135 133 .380 31.627 8.467 1.00 25.49 A C
ATOM 444 OG SER A 135 132 .897 32.822 9.062 1.00 25.49 A o
ATOM 445 C SER A 135 135 .400 31.815 9.894 1.00 29.03 A C
ATOM 446 O SER A 135 134 .915 31.175 10.830 1.00 29.03 A o
ATOM 447 N SER A 136 136 .350 32.729 10.061 1.00 22.22 A N
ATOM 448 CA SER A 136 136 .913 33.000 11.378 1.00 22.22 A C
ATOM 449 CB SER A 136 138 .121 33.929 11.256 1.00 34.39 A C ATOM 450 OG SER A 136 137.773 35.136 10.607 1.00 34.39 A O
ATOM 451 C SER A 136 135.912 33 .586 12 .366 1.00 22 .22 A C
ATOM 452 O SER A 136 136.172 33 .619 13 .568 1.00 22 .22 A O
ATOM 453 N THR A 137 134.763 34 .030 11 .868 1.00 19 .59 A N
ATOM 454 CA THR A 137 133.748 34 .626 12 .728 1.00 19 .59 A C
ATOM 455 CB THR A 137 133.154 35 .866 12 .056 1.00 22 .46 A C
ATOM 456 OGl THR A 137 132.789 35 .552 10 .705 1.00 22 .46 A o
ATOM 457 CG2 THR A 137 134.166 36 .983 12 .047 1.00 22 .46 A C
ATOM 458 C THR A 137 132.613 33 .678 13 .125 1.00 19 .59 A C
ATOM 459 O THR A 137 131.699 34 .060 13 .865 1.00 19 .59 A o
ATOM 460 N TYR A 138 132.672 32 .445 12 .639 1.00 21 .33 A N
ATOM 461 CA TYR A 138 131.648 31 .460 12 .958 1.00 21 .33 A C
ATOM 462 CB TYR A 138 131.630 30 .360 11 .902 1.00 22 .01 A C
ATOM 463 CG TYR A 138 130.689 29 .222 12 .228 1.00 22 .01 A C
ATOM 464 CDl TYR A 138 129.345 29 .281 11 .881 1.00 22 .01 A C
ATOM 465 CEl TYR A 138 128.478 28 .245 12 .198 1.00 22 .01 A C
ATOM 466 CD2 TYR A 138 131.140 28 .098 12 .904 1.00 22 .01 A C
ATOM 467 CE2 TYR A 138 130.285 27 .062 13 .228 1.00 22 .01 A C
ATOM 468 CZ TYR A 138 128.956 27 .138 12 .873 1.00 22 .01 A C
ATOM 469 OH TYR A 138 128.103 26 .102 13 .192 1.00 22 .01 A o
ATOM 470 C TYR A 138 131.905 30 .816 14 .310 1.00 21 .33 A C
ATOM 471 O TYR A 138 133.034 30 .437 14 .613 1.00 21 .33 A o
ATOM 472 N ARG A 139 130.861 30 .690 15 .119 1.00 23 .48 A N
ATOM 473 CA ARG A 139 130.981 30 .048 16 .421 1.00 23 .48 A C
ATOM 474 CB ARG A 139 130.705 31 .038 17 .555 1.00 90 .00 A C
ATOM 475 CG ARG A 139 131.389 32 .388 17 .402 1.00 90 .00 A C
ATOM 476 CD ARG A 139 132.914 32 .286 17 .300 1.00 90 .00 A C
ATOM 477 ME ARG A 139 133.524 33 .599 17 .064 1.00 90 .00 A N
ATOM 478 CZ ARG A 139 134.827 33 .808 16 .882 1.00 90 .00 A C
ATOM 479 NHl ARG A 139 135.676 32 .789 16 .907 1.00 90 .00 A N
ATOM 480 NH2 ARG A 139 135.281 35 .040 16 .670 1.00 90 .00 A N
ATOM 481 C ARG A 139 129.917 28 .961 16 .431 1.00 23 .48 A C
ATOM 482 O ARG A 139 128.787 29 .204 16 .015 1.00 23 .48 A o
ATOM 483 N SER A 140 130.263 27 .759 16 .878 1.00 26 .97 A N
ATOM 484 CA SER A 140 129.275 26 .687 16 .920 1.00 26 .97 A C
ATOM 485 CB SER A 140 129.949 25 .322 16 .961 1.00 18 .58 A C
ATOM 486 OG SER A 140 128.982 24 .295 17 .103 1.00 18 .58 A O
ATOM 487 C SER A 140 128.419 26 .847 18 .161 1.00 26 .97 A C
ATOM 488 O SER A 140 128.934 27 .163 19 .234 1.00 26 .97 A o
ATOM 489 N LYS A 141 127.116 26 .623 18 .025 1.00 19 .58 A N
ATOM 490 CA LYS A 141 126.230 26 .760 19 .166 1.00 19 .58 A C ATOM 491 CB LYS A 141 124.882 27.320 18.712 1.00 14.98 A C ATOM 492 CG LYS A 141 124.535 28.630 19.400 1.00 14.98 A C ATOM 493 CD LYS A 141 123.568 29.463 18.577 1.00 14.98 A C ATOM 494 CE LYS A 141 123.006 30.652 19.372 1.00 14.98 A C ATOM 495 NZ LYS A 141 121.953 30.245 20.365 1.00 14.98 A N ATOM 496 C LYS A 141 126.077 25.447 19.941 1.00 19.58 A C ATOM 497 O LYS A 141 125.445 25.400 21.003 1.00 19.58 A O ATOM 498 N GLY A 142 126.656 24.377 19.407 1.00 18.89 A N ATOM 499 CA GLY A 142 126.622 23.108 20.114 1.00 18.89 A C ATOM 500 C GLY A 142 125.552 22.061 19.875 1.00 18.89 A C ATOM 501 O GLY A 142 125.619 20.982 20.467 1.00 18.89 A O ATOM 502 N PHE A 143 124.580 22.340 19.019 1.00 29.88 A N ATOM 503 CA PHE A 143 123.527 21.367 18.775 1.00 29.88 A C ATOM 504 CB PHE A 143 122.394 21.576 19.773 1.00 27.89 A C ATOM 505 CG PHE A 143 121.787 22.945 19.722 1.00 27.89 A C ATOM 506 CDl PHE A 143 120.807 23.255 18.787 1.00 27.89 A C ATOM 507 CD2 PHE A 143 122.192 23.931 20.616 1.00 27.89 A C ATOM 508 CEl PHE A 143 120.235 24.536 18.746 1.00 27.89 A C ATOM 509 CE2 PHE A 143 121.629 25.209 20.582 1.00 27.89 A C ATOM 510 CZ PHE A 143 120.649 25.510 19.647 1.00 27.89 A C ATOM 511 C PHE A 143 122.974 21.398 17.365 1.00 29.88 A C ATOM 512 O PHE A 143 123.169 22.359 16.620 1.00 29.88 A O ATOM 513 N ASP A 144 122.286 20.320 17.012 1.00 15.35 A N ATOM 514 CA ASP A 144 121.676 20.185 15.705 1.00 15.35 A C ATOM 515 CB ASP A 144 121.819 18.741 15.208 1.00 29.75 A C ATOM 516 CG ASP A 144 123.265 18.347 14.978 1.00 29.75 A C ATOM 517 ODl ASP A 144 124.099 19.272 14.917 1.00 29.75 A O ATOM 518 OD2 ASP A 144 123.574 17.133 14.847 1.00 29.75 A O ATOM 519 C ASP A 144 120.196 20.572 15.794 1.00 15.35 A C ATOM 520 O ASP A 144 119.610 20.618 16.885 1.00 15.35 A O ATOM 521 N VAL A 145 119.597 20.863 14.645 1.00 10.00 A N ATOM 522 CA VAL A 145 118.194 21.236 14.592 1.00 10.00 A C ATOM 523 CB VAL A 145 118.013 22.763 14.565 1.00 10.00 A C ATOM 524 CGl VAL A 145 118.437 23.319 13.208 1.00 10.00 A C ATOM 525 CG2 VAL A 145 116.578 23.113 14.849 1.00 10.00 A C ATOM 526 C VAL A 145 117.627 20.666 13.309 1.00 10.00 A C ATOM 527 O VAL A 145 118.344 20.523 12.311 1.00 10.00 A O ATOM 528 N THR A 146 116.342 20.340 13.327 1.00 10.92 A N ATOM 529 CA THR A 146 115.717 19.795 12.139 1.00 10.92 A C ATOM 530 CB THR A 146 115.591 18.283 12.232 1.00 32.90 A C ATOM OGl THR A 146 114.996 17.788 11.033 1.00 32.90 A O ATOM 532 CG2 THR A 146 114.728 17.899 13.415 1.00 32.90 A C ATOM 533 C THR A 146 114.341 20.392 11.907 1.00 10.92 A C ATOM 534 O THR A 146 113.492 20.403 12.796 1.00 10.92 A O ATOM 535 N VAL A 147 114.122 20.886 10.699 1.00 12.21 A N ATOM 536 CA VAL A 147 112.855 21.497 10.353 1.00 12.21 A C ATOM 537 CB VAL A 147 113.073 22.931 9.868 1.00 10.19 A C ATOM 538 CGl VAL A 147 111.827 23.442 9.173 1.00 10.19 A C ATOM 539 CG2 VAL A 147 113.422 23.814 11.041 1.00 10.19 A C ATOM 540 C VAL A 147 112.104 20.742 9.268 1.00 12.21 A C
ATOM 541 O VAL A 147 112.692 20.334 8.269 1.00 12.21 A O ATOM 542 N LYS A 148 110.807 20.539 9.467 1.00 12.80 A N ATOM 543 CA LYS A 148 110.021 19.873 8.445 1.00 12.80 A C ATOM 544 CB LYS A 148 109.393 18.577 8.932 1.00 23.70 A C ATOM 545 CG LYS A 148 108.605 17.976 7.793 1.00 23.70 A C ATOM 546 CD LYS A 148 107.743 16.798 8.143 1.00 23.70 A C ATOM 547 CE LYS A 148 106.939 16.408 6.908 1.00 23.70 A C ATOM 548 NZ LYS A 148 107.836 16.363 5.707 1.00 23.70 A N ATOM 549 C LYS A 148 108.910 20.781 7.945 1.00 12.80 A C ATOM 550 O LYS A 148 108.011 21.167 8.693 1.00 12.80 A O ATOM 551 N TYR A 149 108.978 21.112 6.666 1.00 22.73 A N ATOM 552 CA TYR A 149 107.992 21.976 6.049 1.00 22.73 A C ATOM 553 CB TYR A 149 108.643 22.724 4.893 1.00 10.00 A C ATOM 554 CG TYR A 149 109.862 23.507 5.302 1.00 10.00 A C ATOM 555 CDl TYR A 149 109.737 24.734 5.932 1.00 10.00 A C ATOM 556 CEl TYR A 149 110.853 25.467 6.297 1.00 10.00 A C ATOM 557 CD2 TYR A 149 111.136 23.026 5.051 1.00 10.00 A C ATOM 558 CE2 TYR A 149 112.257 23.751 5.411 1.00 10.00 A C ATOM 559 CZ TYR A 149 112.112 24.971 6.035 1.00 10.00 A C ATOM 560 OH TYR A 149 113.222 25.700 6.398 1.00 10.00 A o ATOM 561 C TYR A 149 106.856 21.104 5.537 1.00 22.73 A C ATOM 562 O TYR A 149 106.805 19.915 5.839 1.00 22.73 A o ATOM 563 N THR A 150 105.947 21.694 4.766 1.00 30.78 A N ATOM 564 CA THR A 150 104.827 20.947 4.218 1.00 30.78 A C ATOM 565 CB THR A 150 104.031 21.781 3.237 1.00 33.38 A C ATOM 566 OGl THR A 150 103.295 22.772 3.957 1.00 33.38 A O ATOM 567 CG2 THR A 150 103.065 20.912 2.478 1.00 33.38 A C ATOM 568 C THR A 150 105.380 19.744 3.491 1.00 30.78 A C ATOM 569 O THR A 150 104.869 18.633 3.614 1.00 30.78 A o ATOM 570 N GLN A 151 106.419 19.969 2.709 1.00 53.39 A N ATOM 571 CA GLN A 151 107.044 18.875 2.003 1.00 53.39 A C ATOM 572 CB GLN A 151 106.406 18.671 0.632 1.00 90.00 A C ATOM 573 CG GLN A 151 105.072 17.961 0.751 1.00 90.00 A C
ATOM 574 CD GLN A 151 104.063 18.406 -0 .284 1.00 90 .00 A C
ATOM 575 OEl GLN A 151 104.161 19.505 -0 .833 1.00 90 .00 A O
ATOM 576 NE2 GLN A 151 103.066 17.566 -0 .537 1.00 90 .00 A N
ATOM 577 C GLN A 151 108.505 19.197 1 .893 1.00 53 .39 A C
ATOM 578 O GLN A 151 108.880 20.222 1 .316 1.00 53 .39 A O
ATOM 579 N GLY A 152 109.316 18.321 2 .488 1.00 21 .95 A N
ATOM 580 CA GLY A 152 110.754 18.494 2 .497 1.00 21 .95 A C
ATOM 581 C GLY A 152 111.209 18.801 3 .910 1.00 21 .95 A C
ATOM 582 O GLY A 152 110.412 19.192 4 .769 1.00 21 .95 A o
ATOM 583 N SER A 153 112.497 18.623 4 .160 1.00 14 .19 A N
ATOM 584 CA SER A 153 113.037 18.890 5 .476 1.00 14 .19 A C
ATOM 585 CB SER A 153 112.584 17.814 6 .437 1.00 24 .13 A C
ATOM 586 OG SER A 153 113.134 16.575 6 .035 1.00 24 .13 A O
ATOM 587 C SER A 153 114.540 18.860 5 .388 1.00 14 .19 A C
ATOM 588 O SER A 153 115.100 18.362 4 .415 1.00 14 .19 A O
ATOM 589 N TRP A 154 115.192 19.405 6 .404 1.00 13 .47 A N
ATOM 590 CA TRP A 154 116.645 19.397 6 .457 1.00 13 .47 A C
ATOM 591 CB TRP A 154 117.247 20.650 5 .792 1.00 10 .00 A C
ATOM 592 CG TRP A 154 116.650 21.943 6 .228 1.00 10 .00 ' A C
ATOM 593 CD2 TRP A 154 116.882 22.616 7 .464 1.00 10 .00 A C
ATOM 594 CE2 TRP A 154 116.074 23.772 7 .470 1.00 10 .00 A C
ATOM 595 CE3 TRP A 154 117.698 22.356 8 .574 1.00 10 .00 A C
ATOM 596 CDl TRP A 154 115.741 22.695 5 .547 1.00 10 .00 A C
ATOM 597 NEl TRP A 154 115.387 23.797 6 .284 1.00 10 .00 A N
ATOM 598 CZ2 TRP A 154 116.051 24.665 8 .541 1.00 10 .00 A C
ATOM 599 CZ3 TRP A 154 117.679 23.248 9 .646 1.00 10 .00 A C
ATOM 600 CH2 TRP A 154 116.859 24.388 9 .617 1.00 10 .00 A C
ATOM 601 C TRP A 154 117.083 19.295 7 .906 1.00 13 .47 A C
ATOM 602 O TRP A 154 116.279 19.446 8 .822 1.00 13 .47 A o
ATOM 603 N THR A 155 118.358 19.014 8 .108 1.00 10 .00 A N
ATOM 604 CA THR A 155 118.898 18.894 9 .440 1.00 10 .00 A C
ATOM 605 CB THR A 155 119.083 17.429 9 .829 1.00 14 .35 A C
ATOM 606 OGl THR A 155 117.919 16.683 9 .457 1.00 14 .35 A o
ATOM 607 CG2 THR A 155 119.281 17.310 11 .322 1.00 14 .35 A C
ATOM 608 C THR A 155 120.248 19.566 9 .378 1.00 10 .00 A C
ATOM 609 O THR A 155 120.991 19.393 8 .416 1.00 10 .00 A o
ATOM 610 N GLY A 156 120.571 20.356 10 .385 1.00 10 .00 A N
ATOM 611 CA GLY A 156 121.854 21.009 10 .345 1.00 10 .00 A C
ATOM 612 C GLY A 156 122.358 21.415 11 .700 1.00 10 .00 A C
ATOM 613 O GLY A 156 121.653 21.306 12 .707 1.00 10 .00 A O ATOM 614 N PHE A 157 123.598 21.882 11.723 1.00 10.00 A N ATOM 615 CA PHE A 157 124.198 22.331 12.955 1.00 10.00 A C ATOM 616 CB PHE A 157 125.720 22.302 12.863 1.00 27.66 A C ATOM 617 CG PHE A 157 126.282 21.026 12.309 1.00 27.66 A C ATOM 618 CDl PHE A 157 126.420 20.848 10.940 1.00 27.66 A C ATOM 619 CD2 PHE A 157 126.711 20.018 13.161 1.00 27.66 A C ATOM 620 CEl PHE A 157 126.984 19.685 10.431 1.00 27.66 A C ATOM 621 CE2 PHE A 157 127.271 18.859 12.661 1.00 27.66 A C ATOM 622 CZ PHE A 157 127.410 18.691 11.296 1.00 27.66 A C
ATOM 623 C PHE A 157 123.760 23.766 13.162 1.00 10.00 A C ATOM 624 O PHE A 157 123.644 24.528 12.206 1.00 10.00 A o ATOM 625 N VAL A 158 123.517 24.138 14.408 1.00 12.86 A N ATOM 626 CA VAL A 158 123.123 25.497 14.703 1.00 12.86 A C ATOM 627 CB VAL A 158 122.096 25.523 15.812 1.00 10.00 A C ATOM 628 CGl VAL A 158 121.772 26.938 16.172 1.00 10.00 A C ATOM 629 CG2 VAL A 158 120.855 24.819 15.357 1.00 10.00 A C ATOM 630 C VAL A 158 124.363 26.259 15.140 1.00 12.86 A C ATOM 631 O VAL A 158 125.184 25.740 15.901 1.00 12.86 A o ATOM 632 N GLY A 159 124.507 27.482 14.644 1.00 10.73 A N ATOM 633 CA GLY A 159 125.657 28.290 15.001 1.00" 10.73 A C ATOM 634 C GLY A 159 125.382 29.765 14.783 1.00 10.73 A C ATOM 635 O GLY A 159 124.243 30.158 14.532 1.00 10.73 A O ATOM 636 N GLU A 160 126.422 30.586 14.888 1.00 11.33 A N ATOM 637 CA GLU A 160 126.301 32.023 14.693 1.00 11.33 A C ATOM 638 CB GLU A 160 126.594 32.781 15.973 1.00 41.25 A C ATOM 639 CG GLU A 160 125.770 32.457 17.154 1.00 41.25 A C ATOM 640 CD GLU A 160 125.989 33.480 18.252 1.00 41.25 A C ATOM 641 OEl GLU A 160 127.148 33.623 18.711 1.00 41.25 A o ATOM 642 OE2 GLU A 160 125.000 34.150 18.646 1.00 41.25 A o ATOM 643 C GLU A 160 127.333 32.506 13.699 1.00 11.33 A C ATOM 644 O GLU A 160 128.370 31.874 13.498 1.00 11.33 A o ATOM 645 N ASP A 161 127.057 33.642 13.084 1.00 10.00 A N ATOM 646 CA ASP A 161 128.025 34.239 12.195 1.00 10.00 A C ATOM 647 CB ASP A 161 128.388 33.337 11.023 1.00 15.97 A C ATOM 648 CG ASP A 161 129.834 33.551 10.563 1.00 15.97 A C ATOM 649 ODl ASP A 161 130.293 34.718 10.530 1.00 15.97 A o ATOM 650 OD2 ASP A 161 130.517 32.558 10.233 1.00 15.97 A o ATOM 651 C ASP A 161 127.517 35.556 11.692 1.00 10.00 A C ATOM 652 O ASP A 161 126.334 35.860 11.798 1.00 10.00 A o ATOM 653 N LEU A 162 128.439 36.348 11.166 1.00 12.90 A N ATOM 654 CA LEU A 162 128.114 37.655 10.647 1.00 12.90 A C ATOM 655 CB LEU A 162 129.363 38.530 10.672 1.00 13.22 A C ATOM 656 CG LEU A 162 129.882 38.722 12.103 1.00 13.22 A C ATOM 657 CDl LEU A 162 131.198 39.468 12.102 1.00 13.22 A C ATOM 658 CD2 LEU A 162 128.839 39.475 12.923 1.00 13.22 A C ATOM 659 C LEU A 162 127.544 37.541 9.246 1.00 12.90 A C ATOM 660 O LEU A 162 127.982 36.714 8.435 1.00 12.90 A O ATOM 661 N VAL A 163 126.540 38.367 8.982 1.00 12.08 A N ATOM 662 CA VAL A 163 125.875 38.380 7.696 1.00 12.08 A C ATOM 663 CB VAL A 163 124.427 37.927 7.820 1.00 17.15 A C ATOM 664 CGl VAL A 163 123.776 37.861 6.452 1.00 17.15 A C ATOM 665 CG2 VAL A 163 124.385 36.595 8.501 1.00 17.15 A C ATOM 666 C VAL A 163 125.872 39.796 7.201 1.00 12.08 A C ATOM 667 O VAL A 163 125.834 40.740 7.991 1.00 12.08 A O ATOM 668 N THR A 164 125.925 39.938 5.888 1.00 18.20 A N ATOM 669 CA THR A 164 125.903 41.242 5.263 1.00 18.20 A C ATOM 670 CB THR A 164 127.287 41.634 4.740 1.00 24.40 A C ATOM 671 OGl THR A 164 128.138 41.946 5.845 1.00 24.40 A O ATOM 672 CG2 THR A 164 127.190 42.839 3.838 1.00 24.40 A C ATOM 673 C THR A 164 124.958 41.118 4.094 1.00 18.20 A C ATOM 674 O THR A 164 125.109 40.215 3.278 1.00 18.20 A O ATOM 675 N ILE A 165 123.962 41.990 4.021 1.00 28.66 A N ATOM 676 CA ILE A 165 123.035 41.951 2.904 1.00 28.66 A C ATOM 677 CB ILE A 165 121.586 42.191 3.357 1.00 10.34 A C ATOM 678 CG2 ILE A 165 120.652 42.233 2.153 1.00 10.34 A C ATOM 679 CGl ILE A 165 121.155 41.068 4.296 1.00 10.34 A C ATOM 680 CDl ILE A 165 119.667 41.075 4.583 1.00 10.34 A C ATOM 681 C ILE A 165 123.478 43.079 1.994 1.00 28.66 A C ATOM 682 O ILE A 165 123.123 44.237 2.209 1.00 28.66 A O ATOM 683 N PRO A 166 124.270 42.756 0.968 1.00 35.08 A N ATOM 684 CD PRO A 166 124.406 41.373 0.485 1.00 51.23 A C ATOM 685 CA PRO A 166 124.813 43.690 -0.018 1.00 35.08 A C ATOM 686 CB PRO A 166 124.890 42.837 -1.271 1.00 51.23 A C ATOM 687 CG PRO A 166 125.319 41.536 -0.721 1.00 51.23 A C ATOM 688 C PRO A 166 123.980 44.945 -0.233 1.00 35.08 A C ATOM 689 O PRO A 166 124.295 46.028 0.268 1.00 35.08 A O ATOM 690 N LYS A 167 122.905 44.778 -0.989 1.00 44.28 A N ATOM 691 CA LYS A 167 121.996 45.866 -1.303 1.00 44.28 A C ATOM 692 CB LYS A 167 121.200 45.515 -2.562 1.00 72.00 A C ATOM 693 CG LYS A 167 122.045 44.954 -3.697 1.00 72.00 A C ATOM 694 CD LYS A 167 121.200 44.488 -4.873 1.00 72.00 A C ATOM 695 CE LYS A 167 122.072 43.835 -5.933 1.00 72.00 A C ATOM 696 NZ LYS A 167 121.281 43.282 -7.066 1.00 72.00 A N
ATOM 697 C LYS A 167 121.045 46.059 -0.143 1.00 44.28 A C
ATOM 698 O LYS A 167 120.087 45.292 0.007 1.00 44.28 A O
ATOM 699 N GLY A 168 121.308 47.071 0.679 1.00 38.87 A N
ATOM 700 CA GLY A 168 120.435 47.326 1.810 1.00 38.87 A C
ATOM 701 C GLY A 168 121.174 47.722 3.070 1.00 38.87 A C
ATOM 702 O GLY A 168 121.110 48.870 3.506 1.00 38.87 A O
ATOM 703 N PHE A 169 121.861 46.762 3.675 1.00 81.64 A N
ATOM 704 CA PHE A 169 122.633 47.030 4.879 1.00 81.64 A C
ATOM 705 CB PHE A 169 122.082 46.274 6.083 1.00 33.15 A C
ATOM 706 CG PHE A 169 120.598 46.284 6.188 1.00 33.15 A C
ATOM 707 CDl PHE A 169 119.823 45.521 5.326 1.00 33.15 A C
ATOM 708 CD2 PHE A 169 119.974 47.016 7.187 1.00 33.15 A C
ATOM 709 CEl PHE A 169 118.441 45.488 5.456 1.00 33.15 A C
ATOM 710 CE2 PHE A 169 118.597 46.994 7.330 1.00 33.15 A C
ATOM 711 CZ PHE A 169 117.823 46.226 6.466 1.00 33.15 A C
ATOM 712 C PHE A 169 124.041 46.525 4.623 1.00 81.64 A C
ATOM 713 O PHE A 169 124.242 45.326 4.413 1.00 81.64 A O
ATOM 714 N ASN A 170 125.017 47.424 4.650 1.00 88.96 A N
ATOM 715_ CA ASN A 170 126.395 47.014 4.415 1.00 88.96 A C
ATOM 716 CB ASN A 170 127.060 47.960 3.412 1.00 90.00 A C
ATOM 717 CG ASN A 170 126.421 47.885 2.034 1.00 90.00 A C
ATOM 718 ODl ASN A 170 125.757 48.824 1.590 1.00 90.00 A O
ATOM 719 ND2 ASN A 170 126.613 46.754 1.354 1.00 90.00 A N
ATOM 720 C ASN A 170 127.203 46.930 5.707 1.00 88.96 A C
ATOM 721 O ASN A 170 128.432 46.832 5.686 1.00 88.96 A O
ATOM 722 N THR A 171 126.491 46.966 6.828 1.00 38.43 A N
ATOM 723 CA THR A 171 127.092 46.871 8.151 1.00 38.43 A C
ATOM 724 CB THR A 171 126.663 48.048 9.017 1.00 49.94 A C
ATOM 725 OGl THR A 171 127.245 49.246 8.488 1.00 49.94 A O
ATOM 726 CG2 THR A 171 127.097 47.840 10.463 1.00 49.94 A C
ATOM 727 C THR A 171 126.605 45.566 8.774 1.00 38.43 A C
ATOM 728 O THR A 171 125.524 45.513 9.355 1.00 38.43 A O
ATOM 729 N SER A 172 127.424 44.525 8.644 1.00 22.40 A N
ATOM 730 CA SER A 172 127.123 43.176 9.121 1.00 22.40 A C
ATOM 731 CB SER A 172 128.368 42.304 8.994 1.00 23.27 A C
ATOM 732 OG SER A 172 129.423 42.820 9.786 1.00 23.27 A O
ATOM 733 C SER A 172 126.560 43.008 10.520 1.00 22.40 A C
ATOM 734 O SER A 172 126.866 43.775 11.434 1.00 22.40 A O
ATOM 735 N PHE A 173 125.736 41.975 10.676 1.00 14.82 A N
ATOM 736 CA PHE A 173 125.132 41.675 11.964 1.00 14.82 A C ATOM 737 CB PHE A 173 123.697 42.176 12.013 1.00 37.09 A C
ATOM 738 CG PHE A 173 123.065 42.273 10.682 1.00 37.09 A C
ATOM 739 CDl PHE A 173 122.598 41.140 10.042 1.00 37.09 A C
ATOM 740 CD2 PHE A 173 122.969 43.502 10.044 1.00 37.09 A C
ATOM 741 CEl PHE A 173 122.042 41.223 8.111 1.00 37.09 A C
ATOM 742 CE2 PHE A 173 122.419 43.605 8.779 1.00 37.09 A C
ATOM 743 CZ PHE A 173 121.951 42.458 8.139 1.00 37.09 A C
ATOM 744 C PHE A 173 125.185 40.192 12.275 1.00 14.82 A C
ATOM 745 O PHE A 173 125.258 39.348 11.380 1.00 14.82 A o
ATOM 746 N LEU A 174 125.149 39.899 13.568 1.00 11.61 A N
ATOM 747 CA LEU A 174 125.239 38.547 14.062 1.00 11.61 A C
ATOM 748 CB LEU A 174 125.794 38.576 15.470 1.00 11.90 A C
ATOM 749 CG LEU A 174 126.326 37.215 15.875 1.00 11.90 A C
ATOM 750 CDl LEU A 174 127.486 36.852 14.957 1.00 11.90 A C
ATOM 751 CD2 LEU A 174 126.759 37.247 17.323 1.00 11.90 A C
ATOM 752 C LEU A 174 123.911 37.836 14.070 1.00 11.61 A C
ATOM 753 O LEU A 174 122.975 38.285 14.721 1.00 11.61 A o
ATOM 754 N VAL A 175 123.836 36.707 13.376 1.00 11.57 A N
ATOM 755 CA VAL A 175 122.595 35.948 13.311 1.00 11.57 A C
ATOM 756 CB VAL A 175 121.944 36.122 11.944 1.00 10.00 A C
ATOM 757 CGl VAL A 175 121.820 37.582 11.618 1.00 10.00 A C
ATOM 758 CG2 VAL A 175 122.771 35.427 10.891 1.00 10.00 A C
ATOM 759 C VAL A 175 122.808 34.453 13.539 1.00 11.57 A C
ATOM 760 O VAL A 175 123.907 33.946 13.319 1.00 11.57 A o
ATOM 761 N ASN A 176 121.769 33.750 13.994 1.00 10.00 A N
ATOM 762 CA ASN A 176 121.872 32.309 14.190 1.00 10.00 A C
ATOM 763 CB ASN A 176 120.661 31.752 14.913 1.00 13.76 A C
ATOM 764 CG ASN A 176 120.572 32.224 16.324 1.00 13.76 A C
ATOM 765 ODl ASN A 176 121.530 32.093 17.086 1.00 13.76 A o
ATOM 766 ND2 ASN A 176 119.416 32.774 16.700 1.00 13.76 A N
ATOM 767 C ASN A 176 121.879 31.753 12.792 1.00 10.00 A C
ATOM 768 O ASN A 176 121.375 32.392 11.874 1.00 10.00 A o
ATOM 769 N ILE A 111 122.423 30.560 12.614 1.00 11.51 A N
ATOM 770 CA ILE A 111 122.473 29.989 11.284 1.00 11.51 A C
ATOM 771 CB ILE A 111 123.685 30.547 10.523 1.00 10.00 A C
ATOM 772 CG2 ILE A 111 124.949 30.154 11.224 1.00 10.00 A C
ATOM 773 CGl ILE A 111 123.686 30.055 9.085 1.00 10.00 A C
ATOM 774 CDl ILE A 111 124.764 30.696 8.258 1.00 10.00 A C
ATOM 775 C ILE A 111 122.525 28.471 11.326 1.00 11.51 A C
ATOM 776 O ILE A 111 123.299 27.884 12.080 1.00 11.51 A o
ATOM 111 N ALA A 178 121.669 27.845 10.524 1.00 11.24 A N ATOM 778 CA ALA A 178 121.592 26.396 10.436 1.00 11.24 A C
ATOM 779 CB ALA A 178 120.155 25 .967 10.328 1. 00 10.00 A C
ATOM 780 C ALA A 178 122.351 25 .959 9.203 1. 00 11.24 A C
ATOM 781 O ALA A 178 122.099 26 .449 8.104 1. 00 11.24 A o
ATOM 782 N THR A 179 123.281 25 .035 9.389 1. 00 10.00 A N
ATOM 783 CA THR A 179 124.094 24 .521 8.301 1. 00 10.00 A C
ATOM 784 CB THR A 179 125.544 24 .463 8.739 1. 00 14.43 A C
ATOM 785 OGl THR A 179 125.942 25 .760 9.175 1. 00 14.43 A o
ATOM 786 CG2 THR A 179 126.421 24 .074 7.610 1. 00 14.43 A C
ATOM 787 C THR A 179 123.575 23 .131 7.965 1. 00 10.00 A C
ATOM 788 O THR A 179 123.784 22 .180 8.712 1. 00 10.00 A o
ATOM 789 N ILE A 180 122.891 23 .021 6.833 1. 00 27.64 A N
ATOM 790 CA ILE A 180 122.285 21 .761 6.416 1. 00 27.64 A C
ATOM 791 CB ILE A 180 121.354 21 .965 5.203 1. 00 10.00 A C
ATOM 792 CG2 ILE A 180 120.724 20 .649 4.809 1. 00 10.00 A C
ATOM 793 CGl ILE A 180 120.253 22 .962 5.542 1. 00 10.00 A C
ATOM 794 CDl ILE A 180 119.376 23 .291 4.366 1. 00 10.00 A C
ATOM 795 C ILE A 180 123.262 20 .668 6.049 1. 00 27.64 A C
ATOM 796 O ILE A 180 124.034 20 .817 5.105 1. 00 27.64 A o
ATOM 797 N PHE A 181 123.223 19 .561 6.779 1. 00 22.58 A N
ATOM 798 CA PHE A 181 124.103 18 .452 6.457 1. 00 22.58 A C
ATOM 799 CB PHE A 181 125.007 18 .111 7.649 1. 00 10.27 A C
ATOM 800 CG PHE A 181 124.281 17 .585 8.844 1. 00 10.27 A C
ATOM 801 CDl PHE A 181 123.890 16 .257 8.906 1. 00 10.27 A C
ATOM 802 CD2 PHE A 181 123.996 18 .418 9.919 1. 00 10.27 A C
ATOM 803 CEl PHE A 181 123.226 15 .765 10.020 1. 00 10.27 A C
ATOM 804 CE2 PHE A 181 123.328 17 .933 11.044 1. 00 10.27 A C
ATOM 805 CZ PHE A 181 122.944 16 .606 11.093 1. 00 10.27 A C
ATOM 806 C PHE A 181 123.299 17 .232 5.999 1. 00 22.58 A C
ATOM 807 o PHE A 181 123.863 16 .198 5.647 1. 00 22.58 A o
ATOM 808 N GLU A 182 121.977 17 .369 6.004 1. 00 23.55 A N
ATOM 809 CA GLU A 182 121.059 16 .319 5.572 1. 00 23.55 A C
ATOM 810 CB GLU A 182 120.827 15 .302 6.693 1. 00 67.99 A C
ATOM 811 CG GLU A 182 119.930 14 .136 6.291 1. 00 67.99 A C
ATOM 812 CD GLU A 182 118.465 14 .313 6.692 1. 00 67.99 A C
ATOM 813 OEl GLU A 182 117.885 15 .398 6.457 1. 00 67.99 A o
ATOM 814 OE2 GLU A 182 117.884 13 .348 7.236 1. 00 67.99 A o
ATOM 815 C GLU A 182 119.728 16 .971 5.177 1. 00 23.55 A C
ATOM 816 O GLU A 182 119.160 17 .768 5.923 1. 00 23.55 A o
ATOM 817 N SER A 183 119.233 16 .653 3.994 1. 00 16.05 A N
ATOM 818 CA SER A 183 117.971 17 .215 3.559 1. 00 16.05 A C ATOM B19 CB SER A 183 118.208 18.417 2.653 1.00 35.68 A C
ATOM 820 OG SER A 183 118.759 18.019 1.407 1.00 35.68 A O
ATOM 821 C SER A 183 117.275 16.133 2.774 1.00 16.05 A C
ATOM 822 O SER A 183 117.912 15.171 2.346 1.00 16.05 A O
ATOM 823 N GLU A 184 115.969 16.284 2.599 1.00 29.27 A N
ATOM 824 CA GLU A 184 115.172 15.340 1.826 1.00 29.27 A C
ATOM 825 CB GLU A 184 114.558 14.283 2.746 1.00 85.80 A C
ATOM 826 CG GLU A 184 114.535 12.864 2.161 1.00 85.80 A C
ATOM 827 CD GLU A 184 115.930 12.285 1.901 1.00 85.80 A C
ATOM 828 OEl GLU A 184 116.810 12.405 2.787 1.00 85.80 A O
ATOM 829 OE2 GLU A 184 116.143 11.694 0.817 1.00 85.80 A o
ATOM 830 C GLU A 184 114.089 16.197 1.158 1.00 29.27 A C
ATOM 831 O GLU A 184 113.383 16.952 1.832 1.00 29.27 A o
ATOM 832 N ASN A 185 113.987 16.108 -0.167 1.00 24.26 A N
ATOM 833 CA ASN A 185. 113.014 16.896 -0.921 1.00 24.26 A C
ATOM 834 CB ASN A 185 111.599 16.367 -0.701 1.00 49.00 A C
ATOM 835 CG ASN A 185 111.280 15.185 -1.583 1.00 49.00 A C
ATOM 836 ODl ASN A 185 111.382 15.272 -2.805 1.00 49.00 A O
ATOM 837 ND2 ASN A 185 110.885 14.072 -0.973 1.00 49.00 A N
ATOM 838. ASN A 185 113.054 18.380 -0.576 1.00 24.26 A C
ATOM 839 o ASN A 185 112.020 19.049 -0.567 1.00 24.26 A O
ATOM 840 N PHE A 186 114.244 18.897 -0.287 1.00 27.48 A N
ATOM 841 CA PHE A 186 114.373 20.310 0.035 1.00 27.48 A C
ATOM 842 CB PHE A 186 115.327 20.512 1.210 1.00 10.00 A C
ATOM 843 CG PHE A 186 115.406 21.934 1.680 1.00 10.00 A C
ATOM 844 CDl PHE A 186 114.311 22.537 2.287 1.00 10.00 A C
ATOM 845 CD2 PHE A 186 116.558 22.680 1.490 1.00 10.00 A C
ATOM 846 CEl PHE A 186 114.360 23.863 2.697 1.00 10.00 A C
ATOM 847 CE2 PHE A 186 116.614 24.001 1.894 1.00 10.00 A C
ATOM 848 CZ PHE A 186 115.511 24.596 2.499 1.00 10.00 A C
ATOM 849 C PHE A 186 114.887 21.050 -1.195 1.00 27.48 A C
ATOM 850 O PHE A 186 114.227 21.950 -1.709 1.00 27.48 A O
ATOM 851 N PHE A 187 116.064 20.677 -1.678 1.00 16.69 A N
ATOM 852 CA PHE A 187 116.582 21.331 -2.864 1.00 16.69 A C
ATOM 853 CB PHE A 187 118.102 21.283 -2.890 1.00 16.13 A C
ATOM 854 CG PHE A 187 118.755 21.870 -1.678 1.00 16.13 A C
ATOM 855 CDl PHE A 187 119.303 21.045 -0.701 1.00 16.13 A C
ATOM .856 CD2 PHE A 187 118.873 23.251 -1.532 1.00 16.13 A C
ATOM 857 CEl PHE A 187 119.968 21.585 0.403 1.00 16.13 A C
ATOM 858 CE2 PHE A 187 119.537 23.803 -0.428 1.00 16.13 A C
ATOM 859 CZ PHE A 187 120.086 22.967 0.538 1.00 16.13 A C ATOM 860 C PHE A 187 116.038 20.582 -4.073 1.00 16..69 A C
ATOM 861 O PHE A 187 116.281 19.387 -4.228 1.00 16. 69 A O
ATOM 862 N LEU A 188 115.293 21.273 -4.925 1.00 24. ,04 A N
ATOM 863 CA LEU A 188 114.725 20.647 -6.114 1.00 24. 04 A C
ATOM 864 CB LEU A 188 113.299 21.132 -6.327 1.00 39. 58 A C
ATOM 865 CG LEU A 188 112.336 20.814 -5.195 1.00 39. 58 A C
ATOM 866 CDl LEU A 188 111.042 21.621 -5.369 1.00 39. 58 A C
ATOM 867 CD2 LEU A 188 112.082 19.321 -5.187 1.00 39. 58 A C
ATOM 868 C LEU A 188 115.562 21.025 -7.317 1.00 24. 04 A C
ATOM 869 O LEU A 188 116.436 21.873 -7.210 1.00 24. 04 A O
ATOM 870 N PRO A 189 115.292 20.417 -8.484 1.00 12. 24 A N
ATOM 871 CD PRO A 189 114.323 19.333 -8.701 1.00 17. 55 A C
ATOM 872 CA PRO A 189 116.029 20.693 -9.720 1.00 12. 24 A C
ATOM 873 CB PRO A 189 115.470 19.674 -10.695 1.00 17. 55 A C
ATOM 874 CG PRO A 189 114.961 18.590 -9.822 1.00 17. 55 A C
ATOM 875 C PRO A 189 115.779 22.095 -10.222 1.00 12. 24 A C
ATOM 876 O PRO A 189 114.653 22.567 -10.181 1.00 12. 24 A O
ATOM 877 N GLY A 190 116.829 22.758 -10.691 1.00 35. 49 A N
ATOM 878 CA GLY A 190 116.677 24.091 -11.241 1.00 35. 49 A C
ATOM 879 C GLY A 190 116.610 25.293 -10.317 1.00 35. 49 A C
ATOM 880 O GLY A 190 116.547 26.421 -10.804 1.00 35. 49 A O
ATOM 881 N ILE A 191 116.609 25.094 -9.003 1.00 22. 80 A N
ATOM 882 CA ILE A 191 116.553 26.246 -8.106 1.00 22. 80 A C
ATOM 883 CB ILE A 191 116.354 25.845 -6.627 1.00 21. 12 A C
ATOM 884 CG2 ILE A 191 114.942 25.347 -6.394 1.00 21. 12 A C
ATOM 885 CGl ILE A 191 117.375 24.779 -6.239 1.00 21. 12 A C
ATOM 886 CDl ILE A 191 117.398 24.486 -4.757 1.00 21. 12 A C
ATOM 887 C ILE A 191 117.888 26.941 -8.216 1.00 22. 80 A C
ATOM 888 O ILE A 191 118.889 26.307 -8.546 1.00 22. 80 A O
ATOM 889 N LYS A 192 117.916 28.239 -7.953 1.00 23. 12 A N
ATOM 890 CA LYS A 192 119.177 28.956 -8.021 1.00 23. 12 A C
ATOM 891 CB LYS A 192 119.059 30.188 -8.916 1.00 67. 53 A C
ATOM 892 CG LYS A 192 118.694 29.863 -10.353 1.00 67. 53 A C
ATOM 893 CD LYS A 192 118.861 31.080 -11.253 1.00 67. 53 A C
ATOM 894 CE LYS A 192 117.738 31.194 -12.298 1.00 67. 53 A C
ATOM 895 NZ LYS A 192 116.410 31.606 -11.716 1.00 67. 53 A N
ATOM 896 C LYS A 192 119.633 29.353 -6.625 1.00 23. 12 A C
ATOM 897 O LYS A 192 120.698 29.937 -6.459 1.00 23. 12 A O
ATOM 898 N TRP A 193 118.827 29.020 -5.622 1.00 10. 00 A N
ATOM 899 CA TRP A 193 119.163 29.332 -4.241 1.00 10. 00 A C
ATOM 900 CB TRP A 193 117.929 29.791 -3.487 1.00 10. 00 A C ATOM 901 CG TRP A 193 116.730 28.942 -3.720 1.00 10.00 A C
ATOM 902 CD2 TRP A 193 116 .317 27.813 -2.950 1.00 10.00 A C
ATOM 903 CE2 TRP A 193 115 .100 27.356 -3.498 1.00 10.00 A C
ATOM 904 CE3 TRP A 193 116 .855 27.141 -1.851 1.00 10.00 A C
ATOM 905 CDl TRP A 193 115 .780 29.117 -4.682 1.00 10.00 A C
ATOM 906 NEl TRP A 193 114 .795 28.171 -4.553 1.00 10.00 A N
ATOM 907 CZ2 TRP A 193 114 .411 26.264 -2.983 1.00 10.00 A C
ATOM 908 CZ3 TRP A 193 116 .165 26.049 -1.338 1.00 10.00 A C
ATOM 909 CH2 TRP A 193 114 .957 25.623 -1.906 1.00 10.00 A C
ATOM 910 C TRP A 193 119 .755 28.123 -3.539 1.00 10.00 A C
ATOM 911 O TRP A 193 119 .717 27.019 -4.070 1.00 10.00 A O
ATOM 912 N ASN A 194 120 .299 28.337 -2.346 1.00 10.00 A N
ATOM 913 CA ASN A 194 120 .897 27.258 -1.577 1.00 10.00 A C
ATOM 914 CB ASN A 194 122 .372 27.153 -1.902 1.00 19.35 A C
ATOM 915 CG ASN A 194 1 12233 ., 0 01100 28.502 -2.090 1.00 19.35 A C
ATOM 916 ODl ASN A 194 112222 .,885544 29.400 -1.265 1.00 19.35 A O
ATOM 917 ND2 ASN A 194 112233 .,774411 28.658 -3.185 1.00 19.35 A N
ATOM 918 C ASN A 194 112200 ..772255 27.475 -0.085 1.00 10.00 A C
ATOM 919 O ASN A 194 112211 ..445588 26.917 0.731 1.00 10.00 A O
ATOM 920' N GLY A 195 111199 ..774499 28.293 0.269 1.00 10.00 A N
ATOM 921 CA GLY A 195 111199 ..550066 28.568 1.664 1.00 10.00 A C
ATOM 922 C GLY A 195 111188 ..112255 29.151 1.743 1.00 10.00 A C
ATOM 923 O GLY A 195 111177 ..559922 29.600 0.729 1.00 10.00 A O
ATOM 924 N ILE A 196 111177 ..554422 29.152 2.935 1.00 15.56 A N
ATOM 925 CA ILE A 196 111166 ..119999 29.681 3.111 1.00 15.56 A C
ATOM 926 CB ILE A 196 111155 ..222200 28.536 3.341 1.00 10.00 A C
ATOM 927 CG2 ILE A 196 1 11155 ..668855 27.710 4.510 1.00 10.00 A C
ATOM 928 CGl ILE A 196 1 11133 ..881199 29.077 3.591 1.00 10.00 A C
ATOM 929 CDl ILE A 196 111122 ..776611 27.990 3.643 1.00 10.00 A C
ATOM 930 C ILE A 196 1 11166 ..114477 30.635 4.293 1.00 15.56 A C
ATOM 931 O ILE A 196 111166 ..770033 30.344 5.347 1.00 15.56 A O
ATOM 932 N LEU A 197 111155 ..448866 31.773 4.107 1.00 12.96 A N
ATOM 933 ■ CA LEU A 197 111155 ..335522 32.787 5.154 1.00 12.96 A C
ATOM 934 CB LEU A 197 1 11155 .,7 71199 34.162 4.589 1.00 10.00 A C
ATOM .935 CG LEU A 197 111155 ..335588 35.408 5.404 1.00 10.00 A C
ATOM 936 CDl LEU A 197 111166 ., 000044 35.376 6.763 1.00 10.00 A C
ATOM 937 CD2 LEU A 197 111155 ..881133 36.631 4.657 1.00 10.00 A C
ATOM 938 C LEU A 197 111133 .,992233 32.824 5.694 1.00 12.96 A C
ATOM 939 O LEU A 197 111133 ..000066 33.250 5.001 1.00 12.96 A O
ATOM 940 N GLY A 198 111133 .,772233 32.380 6.926 1.00 21.03 A N
ATOM 941 CA GLY A 198 112 .381 32.393 7.479 1.00 21.03 A C ATOM 942 C GLY A 198 112.072 33.730 8.111 1.00 21.03 A C
ATOM 943 O GLY A 198 112.771 34.145 9.034 1.00 21.03 A O
ATOM 944 N LEU A 199 111.037 34.414 7.627 1.00 16.18 A N
ATOM 945 CA LEU A 199 110.668 35.722 8.175 1.00 16.18 A C
ATOM 946 CB LEU A 199 110.487 36.736 7.047 1.00 10.00 A C
ATOM 947 CG LEU A 199 111.720 36.937 6.176 1.00 10.00 A C
ATOM 948 CDl LEU A 199 111.483 38.069 5.206 1.00 10.00 A C
ATOM 949 CD2 LEU A 199 112.905 37.245 7.059 1.00 10.00 A C
ATOM 950 C LEU A 199 109.402 35.689 9.022 1.00 16.18 A C
ATOM 951 O LEU A 199 108.772 36.726 9.237 1.00 16.18 A O
ATOM 952 N ALA A 200 109.036 34.503 9.501 1.00 10.78 A N
ATOM 953 CA ALA A 200 107.841 34.346 10.321 1.00 10.78 A C
ATOM 954 CB ALA A 200 107.310 32.932 10.206 1.00 24.63 A C
ATOM 955 C ALA A 200 108.167 34.665 11.768 1.00 10.78 A C
ATOM 956 O ALA A 200 109.230 35.202 12.062 1.00 10.78 A O
ATOM 957 N TYR A 201 107.258 34.322 12.671 1.00 10.27 A N
ATOM 958 CA TYR A 201 107.452 34.607 14.084 1.00 10.27 A C
ATOM 959 CB TYR A 201 106.101 34.741 14.783 1.00 16.05 A C
ATOM 960 CG TYR A 201 105.360 35.987 14.383 1.00 16.05 A C
ATOM 961 ■ CDl TYR A 201 104.349 35.944~ 13.430 1.00 16.05 -A C
ATOM 962 CEl TYR A 201 103.697 37.108 13.026 1.00 16.05 A C
ATOM 963 CD2 TYR A 201 105.702 37.222 14.924 1.00 16.05 A C
ATOM 964 CE2 TYR A 201 105.061 38.381 14.531 1.00 16.05 A C
ATOM 965 CZ TYR A 201 104.059 38.321 13.583 1.00 16.05 A C
ATOM 966 OH TYR A 201 103.406 39.471 13.203 1.00 16.05 A O
ATOM 967 C TYR A 201 108.301 33.602 14.831 1.00 10.27 A C
ATOM 968 O TYR A 201 108.464 32.463 14.397 1.00 10.27 A O
ATOM 969 N ALA A 202 108.829 34.035 15.973 1.00 14.81 A N
ATOM 970 CA ALA A 202 109.675 33.193 16.808 1.00 14.81 A C
ATOM 971 CB ALA A 202 110.072 33.943 18.052 1.00 14.78 A C
ATOM 972 C ALA A 202 109.000 31.884 17.192 1.00 14.81 A C
ATOM 973 O ALA A 202 109.631 30.827 17.172 1.00 14.81 A O
ATOM 974 N THR A 203 107.720 31.952 17.538 1.00 10.65 A N
ATOM 975 CA THR A 203 106.994 30.760 17.938 1.00 10.65 A C
ATOM 976 CB THR A 203 105.498 30.999 17.938 1.00 37.67 A C
ATOM 977 OGl THR A 203 105.234 32.363 18.275 1.00 37.67 A O
ATOM 978 CG2 THR A 203 104.838 30.101 18.966 1.00 37.67 A C
ATOM 979 C THR A 203 107.283 29.593 17.006 1.00 10.65 A C
ATOM 980 O THR A 203 107.512 28.473 17.457 1.00 10.65 A O
ATOM 981 N LBU A 204 107.290 29.859 15.705 1.00 19.10 A N
ATOM 982 CA LEU A 204 107.535 28.816 14.714 1.00 19.10 A C ATOM 983 CB LEU A 204 107.110 29.298 13.338 1.00 27.48 A C
ATOM 984 CG LEU A 204 105.651 28.983 13 .066 1.00 27.48 A C
ATOM 985 CDl LEU A 204 105.168 29.828 11 .909 1.00 27.48 A C
ATOM 986 CD2 LEU A 204 105.498 27.498 12 .773 1.00 27.48 A C
ATOM 987 C LEU A 204 108.955 28.297 14 .625 1.00 19.10 A C
ATOM 988 O LEU A 204 109.193 27.235 14 .047 1.00 19.10 A O
ATOM 989 N ALA A 205 109.898 29.039 15 .190 1.00 11.65 A N
ATOM 990 CA ALA A 205 111.292 28.633 15 .135 1.00 11.65 A C
ATOM 991 CB ALA A 205 112.169 29.712 15 .711 1.00 10.71 A C
ATOM 992 C ALA A 205 111.568 27.326 15 .849 1.00 11.65 A C
ATOM 993 O ALA A 205 111.006 27.046 16 .916 1.00 11.65 A O
ATOM 994 N LYS A 206 112.435 26.529 15 .228 1.00 11.16 A N
ATOM 995 CA LYS A 206 112.872 25.248 15 .757 1.00 11.16 A C
ATOM 996 CB LYS A 206 112.668 24.136 14 .725 1.00 63.74 A C
ATOM 997 CG LYS A 206 111.427 23.282 14 .962 1.00 63.74 A C
ATOM 998 CD LYS A 206 110.169 24.140 15 .082 1.00 63.74 A C
ATOM 999 CE LYS A 206 108.987 23.354 15 .658 1.00 63.74 A C
ATOM 1000 NZ LYS A 206 107.897 24.261 16 .153 1.00 63.74 A N
ATOM 1001 C LYS A 206 114.352 25.444 16 .032 1.00 11.16 A C
ATOM 1002 O LYS A 206 115.031 26.159 15 .299 1.00 11.16 A O
ATOM 1003 N PRO A 207 114.878 24.812 17 .087 1.00 18.15 A N
ATOM 1004 CD PRO A 207 116.291 24.948 17 .475 1.00 10.00 A C
ATOM 1005 CA PRO A 207 114.180 23.926 18 .016 1.00 18.15 A C
ATOM 1006 CB PRO A 207 115.310 23.365 18 .860 1.00 10.00 A C
ATOM 1007 CG PRO A 207 116.260 24.485 18 .902 1.00 10.00 A C
ATOM 1008 C PRO A 207 113.118 24.592 18 .866 1.0-0 18.15 A C
ATOM 1009 O PRO A 207 112.206 23.923 19 .346 1.00 18.15 A O
ATOM 1010 N SER A 208 113.222 25.898 19 .065 1.00 16.24 A N
ATOM 1011 CA SER A 208 112.230 26.578 19 .890 1.00 16.24 A C
ATOM 1012 CB SER A 208 112.443 26.226 21 .359 1.00 52.75 A C
ATOM 1013 OG SER A 208 113.761 26.545 21 .761 1.00 52.75 A O
ATOM 1014 C SER A 208 112.217 28.087 19 .740 1.00 16.24 A C
ATOM 1015 O SER A 208 113.122 28.681 19 .151 1.00 16.24 A O
ATOM 1016 N SER A 209 111.184 28.705 20 .295 1.00 29.98 A N
ATOM 1017 CA SER A 209 111.030 30.146 20 .216 1.00 29.98 A C
ATOM 1018 CB SER A 209 109.774 30.585 20 .960 1.00 45.73 A C
ATOM 1019 OG SER A 209 109.974 30.499 22 .361 1.00 45.73 A O
ATOM 1020 C SER A 209 112.218 30.880 20 .807 1.00 29.98 A C
ATOM 1021 O SER A 209 112.206 32.106 20 .859 1.00 29.98 A O
ATOM 1022 N SER A 210 113.241 30.156 21 .254 1.00 16.12 A N
ATOM 1023 CA SER A 210 114.386 30.827 21 .854 1.00 16.12 A C ATOM 1024 CB SER A 210 114.814 30.122 23.146 1.00 38.69 A C
ATOM 1025 OG SER A 210 115 .390 28.861 22 .877 1.00 38.69 A O
ATOM 1026 C SER A 210 115 .579 31.000 20 .931 1.00 16.12 A C
ATOM 1027 O SER A 210 116 .578 31.607 21 .325 1.00 16.12 A O
ATOM 1028 N LEU A 211 115 .487 30.470 19 .713 1.00 13.42 A N
ATOM 1029 CA LEU A 211 116 .564 30.630 18 .733 1.00 13.42 A C
ATOM 1030 CB LEU A 211 116 .672 29.405 17 .826 1.00 10.00 A C
ATOM 1031 CG LEU A 211 117 .789 29.435 16 .776 1.00 10.00 A C
ATOM 1032 CDl LEU A 211 119 .088 29.137 17 .454 1.00 10.00 A C
ATOM 1033 CD2 LEU A 211 117 .547 28.408 15 .687 1.00 10.00 A C
ATOM 1034 C LEU A 211 116 .162 31.849 17 .905 1.00 13.42 A C
ATOM 1035 O LEU A 211 115 .557 31.717 16 .843 1.00 13.42 A o
ATOM 1036 N GLU A 212 116 .501 33.032 18 .402 1.00 10.00 A N
ATOM 1037 CA GLU A 212 116 .143 34.291 17 .760 1.00 10.00 A C
ATOM 1038 CB GLU A 212 117 .086 35.401 18 .228 1.00 44.52 A C
ATOM 1039 CG GLU A 212 116 .481 36.799 18 .168 1.00 44.52 A C
ATOM 1040 CD GLU A 212 117 .494 37.888 18 .453 1.00 44.52 A C
ATOM 1041 OEl GLU A 212 118 .399 37.655 19 .282 1.00 44.52 A o
ATOM 1042 OE2 GLU A 212 117 .381 38.982 17 .859 1.00 44.52 A o
ATOM 1043 C GLU A 212 116 .102 34.301 16 .239 1.00 10.00 A C
ATOM 1044 o GLU A 212 117 .035 33.868 15 .575 1.00 10.00 A o
ATOM 1045 N THR A 213 115 .010 34.842 15 .711 1.00 10.00 A M
ATOM 1046 CA THR A 213 114 .764 34.978 14 .282 1.00 10.00 A C
ATOM 1047 CB THR A 213 113 .396 35.604 14 .075 1.00 27.22 A C
ATOM 1048 OGl THR A 213 112 .405 34.591 14 .252 1.00 27.22 A o
ATOM 1049 CG2 THR A 213 113 .270 36.256 12 .695 1.00 27.22 A C
ATOM 1050 C THR A 213 115 .779 35.845 13 .558 1.00 10.00 A C
ATOM 1051 O THR A 213 116 .297 36.802 14 .127 1.00 10.00 A o
ATOM 1052 N PHE A 214 116 .054 35.524 12 .296 1.00 16.17 A N
ATOM 1053 CA PHE A 214 116 .989 36.329 11 .506 1.00 16.17 A C
ATOM 1054 CB PHE A 214 116 .951 35.940 10 .027 1.00 10.00 A C
ATOM 1055 CG PHE A 214 117 .897 36.725 9 .164 1.00 10.00 A C
ATOM 1056 CDl PHE A 214 119 .176 36.253 8 .903 1.00 10.00 A C
ATOM 1057 CD2 PHE A 214 117 .514 37.929 8 .615 1.00 10.00 A C
ATOM 1058 CEl PHE A 214 120 .061 36.972 8 .102 1.00 10.00 A C
ATOM 1059 CE2 PHE A 214 118 .386 38.658 7 .816 1.00 10.00 A C
ATOM 1060 CZ PHE A 214 119 .659 38.181 7 .558 1.00 10.00 A C
ATOM 1061 C PHE A 214 116 .526 37.769 11 .619 1.00 16.17 A C
ATOM 1062 O PHE A 214 117 .273 38.640 12 .050 1.00 16.17 A o
ATOM 1063 N PHE A 215 115 .275 38.009 11 .244 1.00 13.84 A N
ATOM 1064 CA PHE A 215 114 .739 39.352 11 .294 1.00 13.84 A C ATOM 1065 CB PHE A 215 113.300 39.382 10.805 1.00 10.00 A C
ATOM 1066 CG PHE A 215 112.815 40.759 10.481 1.00 10.00 A C
ATOM 1067 CDl PHE A 215 113.413 41.494 9.472 1.00 10.00 A C
ATOM 1068 CD2 PHE A 215 111.778 41.329 11.193 1.00 10.00 A C
ATOM 1069 CEl PHE A 215 112.985 42.781 9.177 1.00 10.00 A C
ATOM 1070 CE2 PHE A 215 111.344 42.615 10.903 1.00 10.00 A C
ATOM 1071 CZ PHE A 215 111.951 43.340 9.892 1.00 10.00 A C
ATOM 1072 C PHE A 215 114.814 39.972 12.680 1.00 13.84 A C
ATOM 1073 O PHE A 215 115.161 41.147 12.801 1.00 13.84 A O
ATOM 1074 N ASP A 216 114.488 39.201 13.718 1.00 10.13 A N
ATOM 1075 CA ASP A 216 114.547 39.717 15.089 1.00 10.13 A C
ATOM 1076 CB ASP A 216 114.304 38.611 16.111 1.00 62.27 A C
ATOM 1077 CG ASP A 216 112.842 38.318 16.312 1.00 62.27 A C
ATOM 1078 ODl ASP A 216 112.054 39.284 16.374 1.00 62.27 A O
ATOM 1079 OD2 ASP A 216 112.485 37.125 16.426 1.00 62.27 A O
ATOM 1080 C ASP A 216 115.916 40.322 15.351 1.00 10.13 A C
ATOM 1081 O ASP A 216 116.034 41.366 15.995 1.00 10.13 A O
ATOM 1082 N SER A 217 116.954 39.658 14.858 1.00 13.42 A N
ATOM 1083 CA SER A 217 118.298 40.163 15.043 1.00 13.42 A C
ATOM 1084. CB SER A 217 . 119.330 39.145 14.575 1.00 12.05 A C
ATOM 1085 OG SER A 217 119.272 37.969 15.352 1.00 12.05 A O
ATOM 1086 C SER A 217 118.457 41.432 14.239 1.00 13.42 A C
ATOM 1087 O SER A 217 118.827 42.470 14.772 1.00 13.42 A O
ATOM 1088 N LEU A 218 118.160 41.345 12.949 1.00 10.00 A N
ATOM 1089 CA LEU A 218 118.293 42.486 12.062 1.00 10.00 A C
ATOM 1090 CB LEU A 218 117.662 42.181 10.711 1.00 11.77 A C
ATOM 1091 CG LEU A 218 117.851 43.280 9.670 1.00 11.77 A C
ATOM 1092 CDl LEU A 218 119.305 43.653 9.585 1.00 11.77 A C
ATOM 1093 CD2 LEU A 218 117.347 42.805 8.322 1.00 11.77 A C
ATOM 1094 C LEU A 218 117.655 43.712 12.663 1.00 10.00 A C
ATOM 1095 O LEU A 218 118.232 44.789 12.639 1.00 10.00 A O
ATOM 1096 N VAL A 219 116.464 43.553 13.215 1.00 17.45 A N
ATOM 1097 CA VAL A 219 115.795 44.690 13.815 1.00 17.45 A C
ATOM 1098 CB VAL A 219 114.433 44.313 14.402 1.00 18.52 A C
ATOM 1099 CGl VAL A 219 113.971 45.378 15.372 1.00 18.52 A C
ATOM 1100 CG2 VAL A 219 113.423 44.182 13.290 1.00 18.52 A C
ATOM 1101 C VAL A 219 116.641 45.302 14.910 1.00 17.45 A C
ATOM 1102 O VAL A 219 116.986 46.469 14.829 1.00 17.45 A O
ATOM 1103 N THR A 220 116.983 44.525 15.930 1.00 19.16 A N
ATOM 1104 CA THR A 220 117.784 45.053 17.031 1.00 19.16 A C
ATOM 1105 CB THR A 220 118.184 43.977 18.034 1.00 15.28 A C ATOM 1106 OGl THR A 220 117.018 43.412 18.635 1.00 15.28 A O
ATOM 1107 CG2 THR A 220 119.053 44.581 19.111 1.00 15.28 A C
ATOM 1108 C THR A 220 119.082 45.694 16.598 1.00 19.16 A C
ATOM 1109 O THR A 220 119.366 46.836 16.940 1.00 19.16 A o
ATOM 1110 N GLN A 221 119.878 44.945 15.856 1.00 14.81 A N
ATOM 1111 CA GLN A 221 121.171 45.426 15.419 1.00 14.81 A C
ATOM 1112 CB GLN A 221 122.004 44.247 14.912 1.00 20.33 A C
ATOM 1113 CG GLN A 221 122.365 43.265 16.020 1.00 20.33 A C
ATOM 1114 CD GLN A 221 123.030 42.009 15.509 1.00 20.33 A C
ATOM 1115 OEl GLN A 221 124.092 42.056 14.890 1.00 20.33 A O
ATOM 1116 NE2 GLN A 221 122.404 40.870 15.769 1.00 20.33 A N
ATOM 1117 C GLN A 221 121.161 46.553 14.395 1.00 14.81 A C
ATOM 1118 O GLN A 221 122.015 47.438 14.454 1.00 14.81 A O
ATOM 1119 N ALA A 222 120.220 46.536 13.459 1.00 18.62 A N
ATOM 1120 CA ALA A 222 120.165 47.600 12.460 1.00 18.62 A C
ATOM 1121 CB ALA A 222 119.585 47.075 11.158 1.00 10.00 A C
ATOM 1122 C ALA A 222 119.302 48.736 12.988 1.00 18.62 A C
ATOM 1123 O ALA A 222 119.201 49.801 12.376 1.00 18.62 A o
ATOM 1124 N ASN A 223 118.691 48.504 14.143 1.00 25.09 A N
ATOM 1125 CA ASN A "223 ' 117.810 49.479 14.765 1.00 25.09 A C
ATOM 1126 CB ASN A 223 118.617 50.596 15.423 1.00 59.24 A C
ATOM 1127 CG ASN A 223 117.797 51.382 16.430 1.00 59.24 A C
ATOM 1128 ODl ASN A 223 117.355 50.841 17.448 1.00 59.24 A o
ATOM 1129 ND2 ASN A 223 117.584 52.663 16.149 1.00 59.24 A N
ATOM 1130 C ASN A 223 116.837 50.059 13.737 1.00 25.09 A C
ATOM 1131 O ASN A 223 116.744 51.273 13.571 1.00 25.09 A O
ATOM 1132 N ILE A 224 116.127 49.175 13.040 1.00 19.20 A N
ATOM 1133 CA ILE A 224 115.142 49.583 12.041 1.00 19.20 A C
ATOM 1134 CB ILE A 224 115.322 48.831 10.710 1.00 16.45 A C
ATOM 1135 CG2 ILE A 224 116.702 49.085 10.155 1.00 16.45 A C
ATOM 1136 CGl ILE A 224 115.089 47.337 10.926 1.00 16.45 A C
ATOM 1137 CDl ILE A 224 115.020 46.523 9.642 1.00 16.45 A C
ATOM 1138 C ILE A 224 113.752 49.252 12.578 1.00 19.20 A C
ATOM 1139 O ILE A 224 113.620 48.591 13.614 1.00 19.20 A o
ATOM 1140 N PRO A 225 112.698 49.720 11.890 1.00 26.91 A N
ATOM 1141 CD PRO A 225 112.725 50.713 10.807 1.00 14.34 A C
ATOM 1142 CA PRO A 225 111.319 49.460 12.315 1.00 26.91 A C
ATOM 1143 CB PRO A 225 110.495 50.332 11.371 1.00 14.34 A C
ATOM 1144 CG PRO A 225 111.428 51.442 11.028 1.00 14.34 A C
ATOM 1145 C PRO A 225 110.990 47.979 12.160 1.00 26.91 A C
ATOM 1146 O PRO A 225 111.446 47.336 11.214 1.00 26.91 A o ATOM 1147 N ASN A 226 110.202 47.443 13.085 1.00 10.00 A N
ATOM 1148 CA ASN A 226 109.839 46 .035 13.044 1. 00 10.00 A C
ATOM 1149 CB ASN A 226 109.293 45 .610 14.401 1. 00 15.97 A C
ATOM 1150 CG ASN A 226 108.883 44 .170 14.426 1. 00 15.97 A C
ATOM 1151 ODl ASN A 226 109.562 43 .312 13.861 1. 00 15.97 A O
ATOM 1152 ND2 ASN A 226 107.768 43 .883 15.090 1. 00 15.97 A N
ATOM 1153 C ASN A 226 108.811 45 .814 11.946 1. 00 10.00 A C
ATOM 1154 O ASN A 226 107.658 45 .450 12.197 1. 00 10.00 A O
ATOM 1155 N VAL A 227 109.261 46 .031 10.715 1. 00 15.12 A N
ATOM 1156 CA VAL A 227 108.418 45 .908 9.536 1. 00 15.12 A C
ATOM 1157 CB VAL A 227 107.808 47 .274 9.172 1. 00 14.90 A C
ATOM 1158 CGl VAL A 227 106.953 47 .144 7.945 1. 00 14.90 A C
ATOM 1159 CG2 VAL A 227 107.004 47 .816 10.321 1. 00 14.90 A C
ATOM 1160 C VAL A 227 109.227 45 .470 8.325 1. 00 15.12 A C
ATOM 1161 O VAL A 227 110.434 45 .665 8.282 1. 00 15.12 A O
ATOM 1162 N PHE A 228 108.563 44 .871 7.347 1. 00 10.92 A N
ATOM 1163 CA PHE A 228 109.229 44 .497 6.107 1. 00 10.92 A C
ATOM 1164 CB PHE A 228 110.162 43 .283 6.277 1. 00 10.00 A C
ATOM 1165 CG PHE A 228 109.462 41 .966 6.442 1. 00 10.00 A C
ATOM 1166'. CDl PHE A 228 : 109-141 41 .486 7.707 1. 00 10.00 A - C
ATOM 1167 CD2 PHE A 228 109.178 41 .172 5.334 1. 00 10.00 A C
ATOM 1168 CEl PHE A 228 108.554 40 .229 7.869 1. 00 10.00 A C
ATOM 1169 CE2 PHE A 228 108.591 39 .917 5.485 1. 00 10.00 A C
ATOM 1170 CZ PHE A 228 108.282 39 .446 6.755 1. 00 10.00 A C
ATOM 1171 C PHE A 228 108.148 44 .230 5.079 1. 00 10.92 A C
ATOM 1172 o PHE A 228 107.072 43 .755 5.429 1. 00 10.92 A O
ATOM 1173 N SER A 229 108.407 44 .573 3.824 1. 00 10.00 A N
ATOM 1174 CA SER A 229 107.414 44 .369 2.777 1. 00 10.00 A C
ATOM 1175 CB SER A 229 106.871 45 .707 2.311 1. 00 17.85 A C
ATOM 1176 OG SER A 229 107.938 46 .541 1.897 1. 00 17.85 A O
ATOM 1177 C SER A 229 108.023 43 .634 1.605 1. 00 10.00 A C
ATOM 1178 O SER A 229 109.236 43 .689 1.390 1. 00 10.00 A o
ATOM 1179 N MET A 230 107.192 42 .950 0.834 1. 00 12.33 A N
ATOM 1180 CA MET A 230 107.716 42 .191 -0.289 1. 00 12.33 A C
ATOM 1181 CB MET A 230 107.747 40 .706 0.070 1. 00 13.34 A C
ATOM 1182 CG MET A 230 108.597 39 .854 -0.851 1. 00 13.34 A C
ATOM 1183 SD MET A 230 108.432 38 .056 -0.571 1. 00 13.34 A S
ATOM 1184 CE MET A 230 108.241 38 .038 1.179 1. 00 13.34 A C
ATOM 1185 C MET A 230 106.897 42 .392 -1.553 1. 00 12.33 A C
ATOM 1186 O MET A 230 105.669 42 .528 -1.506 1. 00 12.33 A o
ATOM 1187 N GLN A 231 107.586 42 .408 -2.688 1. 00 25.59 A N ATOM 1188 CA GLN A 231 106.933 42.566 -3.977 1.00 25.59 A C
ATOM 1189 CB GLN A 231 107.112 43.974 -4.513 1.00 33.44 A C
ATOM 1190 CG GLN A 231 106.432 44.151 -5.847 1.00 33.44 A C
ATOM 1191 CD GLN A 231 106.861 45.414 -6.542 1.00 33.44 A C
ATOM 1192 OEl GLN A 231 108.019 45.550 -6.942 1.00 33.44 A O
ATOM 1193 NE2 GLN A 231 105.935 46.349 -6.696 1.00 33.44 A N
ATOM 1194 C GLN A 231 107.523 41.595 -4.982 1.00 25.59 A C
ATOM 1195 O GLN A 231 108.700 41.690 -5.309 1.00 25.59 A O
ATOM 1196 N MET A 232 106.718 40.664 -5.477 1.00 24.36 A N
ATOM 1197 CA MET A 232 107.218 39.694 -6.444 1.00 24.36 A C
ATOM 1198 CB MET A 232 106.712 38.299 -6.094 1.00 36.06 A C
ATOM 1199 CG MET A 232 106.839 37.955 -4.635 1.00 36.06 A C
ATOM 1200 SD MET A 232 106.519 36.211 -4.353 1.00 36.06 A S
ATOM 1201 CE MET A 232 104.799 36.175 -4.268 1.00 36.06 A C
ATOM 1202 C MET A 232 106.758 40.057 -7.847 1.00 24.36 A C
ATOM 1203 O MET A 232 105.578 40.332 -8.068 1.00 24.36 A o
ATOM 1204 N CYS A 233 107.685 40.071 -8.798 1.00 29.42 A N
ATOM 1205 CA CYS A 233 107.337 40.391 -10.178 1.00 29.42 A C
ATOM 1206 C CYS A 233 107.685 39.165 -11.012 1.00 29.42 A C
ATOM 1207 O CYS A 233 - 108.741 38.578 -10.835 1.00 29.42 A- o
ATOM 1208 CB CYS A 233 108.129 41.607 -10.639 1.00 55.38 A C
ATOM 1209 SG CYS A 233 107.962 43.041 -9.513 1.00 55.38 A S
ATOM 1210 N GLY A 234 106.789 38.764 -11.900 1.00 53.45 A N
ATOM 1211 CA GLY A 234 107.028 37.589 -12.717 1.00 53.45 A C
ATOM 1212 C GLY A 234 105.708 37.132 -13.298 1.00 53.45 A C
ATOM 1213 O GLY A 234 104.731 36.965 -12.568 1.00 53.45 A O
ATOM 1214 N ALA A 235 105.656 36.949 -14.613 1.00 89.89 A N
ATOM 1215 CA ALA A 235 104.414 36.529 -15.256 1.00 89.89 A C
ATOM 1216 CB ALA A 235 103.392 37.686 -15.202 1.00 15.71 A C
ATOM 1217 C ALA A 235 104.641 36.084 -16.701 1.00 89.89 A C
ATOM 1218 o ALA A 235 105.278 35.050 -16.956 1.00 89.89 A o
ATOM 1219 N ASN A 245 112.839 39.227 -14.695 1.00 79.68 A N
ATOM 1220 CA ASN A 245 112.603 40.165 -13.602 1.00 79.68 A C
ATOM 1221 CB ASN A 245 111.334 40.983 -13.865 1.00 90.00 A C
ATOM 1222 CG ASN A 245 111.345 41.662 -15.228 1.00 90.00 A C
ATOM 1223 ODl ASN A 245 112.341 42.276 -15.628 1.00 90.00 A o
ATOM 1224 ND2 ASN A 245 110.229 41.561 -15.946 1.00 90.00 A N
ATOM 1225 C ASN A 245 112.467 39.412 -12.280 1.00 79.68 A C
ATOM 1226 O ASN A 245 112.204 38.209 -12.270 1.00 79.68 A O
ATOM 1227 N GLY A 246 112.636 40.125 -11.168 1.00 24.58 A N
ATOM 1228 CA GLY A 246 112.548 39.489 -9.866 1.00 24.58 A C ATOM 1229 C GLY A 246 111.598 40.149 -8.891 1.00 24.58 A C
ATOM 1230 O GLY A 246 110.389 40.163 -9.108 1.00 24.58 A O
ATOM 1231 N GLY A 247 112.139 40.698 -7.810 1.00 11.90 A N
ATOM 1232 CA GLY A 247 111.289 41.335 -6.821 1.00 11.90 A C
ATOM 1233 C GLY A 247 112.050 42.171 -5.816 1.00 11.90 A C
ATOM 1234 O GLY A 247 113.233 42.448 -6.008 1.00 11.90 A O
ATOM 1235 N SER A 248 111.387 42.564 -4.731 1.00 10.58 A N
ATOM 1236 CA SER A 248 112.040 43.396 -3.734 1.00 10.58 A C
ATOM 1237 CB SER A 248 111.634 44.851 -3.933 1.00 12.54 A C
ATOM 1238 OG SER A 248 111.479 45.146 -5.308 1.00 12.54 A O
ATOM 1239 C SER A 248 111.697 43.002 -2.321 1.00 10.58 A C
ATOM 1240 O SER A 248 110.535 42.830 -1.992 1.00 10.58 A o
ATOM 1241 N LEU A 249 112.708 42.851 -1.480 1.00 11.94 A N
ATOM 1242 CA LEU A 249 112.464 42.534 -0.088 1.00 11.94 A C
ATOM 1243 CB LEU A 249 113.296 41.340 0.365 1.00 10.00 A C
ATOM 1244 CG LEU A 249 113.175 41.077 1.870 1.00 10.00 A C
ATOM 1245 CDl LEU A 249 111.737 40.797 2.212 1.00 10.00 A C
ATOM 1246 CD2 LEU A 249 114.031 39.911 2.275 1.00 10.00 A C
ATOM 1247 C LEU A 249 112.896 43.763 0.684 1.00 11.94 A C
ATOM 1248 O LEU A 249 114.062 43.882 1.053 1.00 11.94 A o
ATOM 1249 N VAL A 250 111.972 44.690 0.905 1.00 11.17 A N
ATOM 1250 CA VAL A 250 112.291 45.911 1.640 1.00 11.17 A C
ATOM 1251 CB VAL A 250 111.294 47.025 1.319 1.00 11.50 A C
ATOM 1252 CGl VAL A 250 111.679 48.277 2.056 1.00 11.50 A C
ATOM 1253 CG2 VAL A 250 111.259 47.279 -0.166 1.00 11.50 A C
ATOM 1254 C VAL A 250 112.237 45.624 3.138 1.00 11.17 A C
ATOM 1255 o VAL A 250 111.153 45.555 3.731 1.00 11.17 A o
ATOM 1256 N LEU A 251 113.408 45.466 3.747 1.00 17.23 A N
ATOM 1257 CA LEU A 251 113.492 45.143 5.165 1.00 17.23 A C
ATOM 1258 CB LEU A 251 114.764 44.341 5.435 1.00 11.87 A C
ATOM 1259 CG LEU A 251 114.933 43.017 4.690 1.00 11.87 A C
ATOM 1260 CDl LEU A 251 116.353 42.540 4.876 1.00 11.87 A C
ATOM 1261 CD2 LEU A 251 113.969 41.975 5.205 1.00 11.87 A C
ATOM 1262 C LEU A 251 113.456 46.343 6.094 1.00 17.23 A C
ATOM 1263 O LEU A 251 114.416 47.099 6.171 1.00 17.23 A o
ATOM 1264 N GLY A 252 112.351 46.516 6.809 1.00 20.78 A N
ATOM 1265 CA GLY A 252 112.257 47.628 7.737 1.00 20.78 A C
ATOM 1266 C GLY A 252 111.409 48.812 7.303 1.00 20.78 A C
ATOM 1267 O GLY A 252 111.456 49.871 7.930 1.00 20.78 A O
ATOM 1268 N GLY A 253 110.626 48.658 6.243 1.00 28.33 A N
ATOM 1269 CA GLY A 253 109.808 49.774 5.811 1.00 28.33 A C ATOM 1270 C GLY A 253 108.972 49.495 4.585 1.00 28.33 A C
ATOM 1271 O GLY A 253 108.854 48.355 4.140 1.00 28.33 A O
ATOM 1272 N ILE A 254 108.394 50.552 4.035 1.00 10.81 A N
ATOM 1273 CA ILE A 254 107.558 50.436 2.854 1.00 10.81 A C
ATOM 1274 CB ILE A 254 106.136 50.874 3.172 1.00 10.92 A C
ATOM 1275 CG2 ILE A 254 105.297 50.841 1.918 1.00 10.92 A C
ATOM 1276 CGl ILE A 254 105.572 49.981 4.277 1.00 10.92 A C
ATOM 1277 CDl ILE A 254 104.262 50.457 4.851 1.00 10.92 A C
ATOM 1278 C ILE A 254 108.104 51.339 1.766 1.00 10.81 A C
ATOM 1279 O ILE A 254 108.262 52.534 1.986 1.00 10.81 A o
ATOM 1280 N GLU A 255 108.409 50.781 0.600 1.00 18.04 A N
ATOM 1281 CA GLU A 255 108.929 51.600 -0.486 1.00 18.04 A C
ATOM 1282 CB GLU A 255 109.949 50.837 -1.323 1.00 51.79 A C
ATOM 1283 CG GLU A 255 110.300 51.588 -2.585 1.00 51.79 A C
ATOM 1284 CD GLU A 255 110.531 53.066 -2.320 1.00. 51.79 A C
ATOM 1285 OEl GLU A 255 110.158 53.899 -3.178 1.00 51.79 A o
ATOM 1286 OE2 GLU A 255 111.089 53.393 -1.252 1.00 51.79 A o
ATOM 1287 C GLU A 255 107.787 52.057 -1.373 1.00 18.04 A C
ATOM 1288 O GLU A 255 107.283 51.298 -2.192 1.00 18.04 A o
ATOM 1289. • N PRO A 256. _ 107.375 53.322 -1.235 1.00 32.21. A N
ATOM 1290 CD PRO A 256 108.024 54.363 -0.420 1.00 26.00 A C
ATOM 1291 CA PRO A 256 106.280 53.892 -2.018 1.00 32.21 A C
ATOM 1292 CB PRO A 256 106.224 55.334 -1.524- 1.00 26.00 A C
ATOM 1293 CG PRO A 256 107.642 55.613 -1.151 1.00 26.00 A C
ATOM 1294 C PRO A 256 106.383 53.797 -3.537 1.00 32.21 A C
ATOM 1295 O PRO A 256 105.363 53.796 -4.220 1.00 32.21 A o
ATOM 1296 N SER A 257 107.591 53.710 -4.077 1.00 15.08 A N
ATOM 1297 CA SER A 257 107.709 53.632 -5.528 1.00 15.08 A C
ATOM 1298 CB SER A 257 109.146 53.926 -5.970 1.00 19.19 A C
ATOM 1299 OG SER A 257 109.951 52.762 -5.951 1.00 19.19 A O
ATOM 1300 C SER A 257 107^272 52.272 -6.074 1.00 15.08 A C
ATOM 1301 O SER A 257 107.195 52.077 -7.286 1.00 15.08 A O
ATOM 1302 N LEU A 258 106.974 51.340 -5.176 1.00 27.11 A N
ATOM 1303 CA LEU A 258 106.570 50.000 -5.575 1.00 27.11 A C
ATOM 1304 CB LEU A 258 107.151 48.972 -4.617 1.00 10.81 A C
ATOM 1305 CG LEU A 258 108.664 48.932 -4.553 1.00 10.81 A C
ATOM 1306 CDl LEU A 258 109.092 48.011 -3.438 1.00 10.81 A C
ATOM 1307 CD2 LEU A 258 109.206 48.462 -5.876 1.00 10.81 A C
ATOM 1308 C LEU A 258 105.073 49.781 -5.634 1.00 27.11 A C
ATOM 1309 O LEU A 258 104.627 48.671 -5.902 1.00 27.11 A o
ATOM 1310 M TYR A 259 104.283 50.810 -5.376 1.00 29.42 A N ATOM 1311 CA TYR A 259 102.846 50.604 -5.421 1.00 29.42 A C
ATOM 1312 CB TYR A 259 102.366 49.967 -4.121 1.00 15.71 A C
ATOM 1313 CG TYR A 259 102.286 50.943 -2.974 1.00 15.71 A C
ATOM 1314 CDl TYR A 259 103.422 51.308 -2.263 1.00 15.71 A C
ATOM 1315 CEl TYR A 259 103.349 52.222 -1.215 1.00 15.71 A C
ATOM 1316 CD2 TYR A 259 101.072 51.517 -2.613 1.00 15.71 A C
ATOM 1317 CE2 TYR A 259 100.988 52.430 -1.567 1.00 15.71 A C
ATOM 1318 CZ TYR A 259 102.127 52.777 -0.869 1.00 15.71 A C
ATOM 1319 OH TYR A 259 102.039 53.649 0.198 1.00 15.71 A O
ATOM 1320 C TYR A 259 102.043 51.863 -5.656 1.00 29.42 A C
ATOM 1321 O TYR A 259 102.339 52.920 -5.103 1.00 29.42 A O
ATOM 1322 N LYS A 260 101.010 51.743 -6.473 1.00 38.75 A N
ATOM 1323 CA LYS A 260 100.149 52.872 -6.746 1.00 38.75 A C
ATOM 1324 CB LYS A 260 99.988 53.074 -8.257 1.00 87.08 A C
ATOM 1325 CG LYS A 260 100.485 54.436 -8.749 1.00 87.08 A C
ATOM 1326 CD LYS A 260 100.721 54.463 -10.260 1.00 87.08 A C
ATOM 1327 CE LYS A 260 101.929 53.611 -10.664 1.00 87.08 A C
ATOM 1328 NZ LYS A 260 102.169 53.594 -12.140 1.00 87.08 A N
ATOM 1329 C LYS A 260 98.826 52.528 -6.094 1.00 38.75 A C
ATOM 1330 O LYS A 260 98.497 51.351 -5.929 1.00 38.75 A O
ATOM 1331 N GLY A 261 98.081 53.549 -5.694 1.00 32.46 A N
ATOM 1332 CA GLY A 261 96.798 53.303 -5.070 1.00 32.46 A C
ATOM 1333 C GLY A 261 96.912 53.215 -3.568 1.00 32.46 A C
ATOM 1334 o GLY A 261 97.983 53.431 -3.007 1.00 32.46 A o
ATOM 1335 N ASP A 262 95.795 52.912 -2.918 1.00 35.99 A N
ATOM 1336 CA ASP A 262 95.750 52.787 -1.468 1.00 35.99 A C
ATOM 1337 CB ASP A 262 94.313 52.939 -0.956 1.00 87.73 A C
ATOM 1338 CG ASP A 262 93.866 54.382 -0.867 1.00 87.73 A C
ATOM 1339 ODl ASP A 262 94.484 55.146 -0.095 1.00 87.73 A o
ATOM 1340 OD2 ASP A 262 92.894 54.748 -1.563 1.00 87.73 A o
ATOM 1341 C ASP A 262 96.259 51.416 -1.074 1.00 35.99 A C
ATOM 1342 O ASP A 262 96.248 50.483 -1.876 1.00 35.99 A o
ATOM 1343 N ILE A 263 96.703 51.302 0.168 1.00 15.15 A N
ATOM 1344 CA ILE A 263 97.191 50.037 0.691 1.00 15.15 A C
ATOM 1345 CB ILE A 263 98.658 50.163 1.180 1.00 27.37 A C
ATOM 1346 CG2 ILE A 263 99.071 51.621 1.244 1.00 27.37 A C
ATOM 1347 CGl ILE A 263 98.829 49.486 2.530 1.00 27.37 A C
ATOM 1348 CDl ILE A 263 100.155 49.770 3.125 1.00 27.37 A C
ATOM 1349 C ILE A 263 96.268 49.625 1.833 1.00 15.15 A C
ATOM 1350 O ILE A 263 96.159 50.325 2.837 1.00 15.15 A o
ATOM 1351 N TRP A 264 95.588 48.498 1.660 1.00 13.65 A N ATOM 1352 CA TRP A 264 94.658 48.012 2.669 1.00 13.65 A C
ATOM 1353 CB TRP A 264 93.492 47.264 2.009 1.00 17.73 A C
ATOM 1354 CG TRP A 264 92.657 48.147 1.124 1.00 17.73 A C
ATOM 1355 CD2 TRP A 264 91.459 48.829 1.491 1.00 17.73 A C
ATOM 1356 CE2 TRP A 264 91.061 49.604 0.381 1.00 17.73 A C
ATOM 1357 CE3 TRP A 264 90.685 48.866 2.653 1.00 17.73 A C
ATOM 1358 CDl TRP A 264 92.928 48.518 -0.163 1.00 17.73 A C
ATOM 1359 NEl TRP A 264 91.974 49.395 -0.617 1.00 17.73 A N
ATOM 1360 CZ2 TRP A 264 89.925 50.402 0.397 1.00 17.73 A C
ATOM 1361 CZ3 TRP A 264 89.556 49.660 2.673 1.00 17.73 A C
ATOM 1362 CH2 TRP A 264 89.185 50.420 1.550 1.00 17.73 A C
ATOM 1363 C TRP A 264 95.333 47.109 3.677 1.00 13.65 A C
ATOM 1364 o TRP A 264 96.257 46.379 3.340 1.00 13.65 A o
ATOM 1365 N TYR A 265 94.867 47.164 4.918 1.00 14.30 A N
ATOM 1366 CA TYR A 265 95.441 46.341 5.964 1.00 14.30 A C
ATOM 1367 CB TYR A 265 96.024 47.202 7.083 1.00 10.00 A C
ATOM 1368 CG TYR A 265 97.320 47.886 6.746 1.00 10.00 A C
ATOM 1369 CDl TYR A 265 97.344 49.224 6.392 1.00 10.00 A C
ATOM 1370 CEl TYR A 265 98.532 49.873 6.111 1.00 10.00 A C
ATOM 1371 CD2 TYR A 265 98.530 47.202 6.804 1.00 10.00 • A C
ATOM 1372 CE2 TYR A 265 99.728 47.845 6.519 1.00 10.00 A C
ATOM 1373 CZ TYR A 265 99.719 49.186 6.175 1.00 10.00 A C
ATOM 1374 OH TYR A 265 100.893 49.860 5.902 1.00 10.00 A o
ATOM 1375 C TYR A 265 94.451 45.383 6.592 1.00 14.30 A C
ATOM 1376 O TYR A 265 93.280 45.698 6.777 1.00 14.30 A o
ATOM 1377 N THR A 266 94.935 44.198 6.922 1.00 13.85 A N
ATOM 1378 CA THR A 266 94.113 43.212 7.589 1.00 13.85 A C
ATOM 1379 CB THR A 266 93.881 41.976 6.736 1.00 30.28 A C
ATOM 1380 OGl THR A 266 92.917 41.146 7.388 1.00 30.28 A o
ATOM 1381 CG2 THR A 266 95.179 41.197 6.555 1.00 30.28 A C
ATOM 1382 C THR A 266 94.894 42.832 8.838 1.00 13.85 A C
ATOM 1383 O THR A 266 96.116 42.695 8.814 1.00 13.85 A O
ATOM 1384 N PRO A 267 94.197 42.667 9.954 1.00 10.00 A N
ATOM 1385 CD PRO A 267 92.736 42.664 10.097 1.00 14.02 A C
ATOM ' 1386 CA PRO A 267 94.840 42.314 11.212 1.00 10.00 A C
ATOM 1387 CB PRO A 267 93.712 42.474 12.203 1.00 14.02 A C
ATOM 1388 CG PRO A 267 92.556 41.959 11.410 1.00 14.02 A C
ATOM 1389 C PRO A 267 95.414 40.914 11.232 1.00 10.00 A C
ATOM 1390 O PRO A 267 94.839 39.995 10.657 1.00 10.00 A O
ATOM 1391 N ILE A 268 96.554 40.758 11.892 1.00 12.60 A N
ATOM 1392 CA ILE A 268 97.177 39.453 12.011 1.00 12.60 A C ATOM 1393 CB ILE A 268 98.671 39.582 12.279 1.00 10.00 A C
ATOM 1394 CG2 ILE A 268 99.311 38.208 12.333 1.00 10.00 A C
ATOM 1395 CGl ILE A 268 99.307 40.427 11.180 1.00 10.00 A C
ATOM 1396 CDl ILE A 268 100.803 40.562 11.302 1.00 10.00 A C
ATOM 1397 C ILE A 268 96.506 38.766 13.197 1.00 12.60 A C
ATOM 1398 O ILE A 268 96.590 39.241 14.325 1.00 12.60 A O
ATOM 1399 N LYS A 269 95.831 37.655 12.942 1.00 24.52 A N
ATOM 1400 CA LYS A 269 95.127 36.950 14.001 1.00 24.52 A C
ATOM 1401 CB LYS A 269 94.151 35.942 13.392 1.00 43.79 A C
ATOM 1402 CG LYS A 269 92.854 36.572 12.885 1.00 43.79 A C
ATOM 1403 CD LYS A 269 92.038 37.161 14.034 1.00 43.79 A C
ATOM 1404 CE LYS A 269 90.666 37.638 13.578 1.00 43.79 A C
ATOM 1405 NZ LYS A 269 89.811 38.101 14.712 1.00 43.79 A N
ATOM 1406 C LYS A 269 96.006 36.271 15.042 1.00 24.52 A C
ATOM 1407 O LYS A 269 95.855 36.531 16.234 1.00 24.52 A O
ATOM 1408 N GLU A 270 96.908 35.397 14.606 1.00 23.88 A N
ATOM 1409 CA GLU A 270 97.803 34.696 15.529 1.00 23.88 A C
ATOM 1410 CB GLU A 270 97.480 33.199 15.550 1.00 89.34 A C
ATOM 1411 CG GLU A 270 97.582 32.552 16.931 1.00 89.34 A C
ATOM 1412 CD GLU A 270 96.581 33.129 17.940 1.00 89.34 A C
ATOM 1413 OEl GLU A 270 95.358 33.085 17.674 1.00 89.34 A O
ATOM 1414 OE2 GLU A 270 97.017 33.622 19.006 1.00 89.34 A O
ATOM 1415 C GLU A 270 99.235 34.929 15.055 1.00 23.88 A C
ATOM 1416 O GLU A 270 99.521 34.811 13.864 1.00 23.88 A O
ATOM 1417 N GLU A 271 100.136 35.271 15.974 1.00 22.35 A N
ATOM 1418 CA GLU A 271 101.515 35.536 15.585 1.00 22.35 A C
ATOM 1419 CB GLU A 271 102.102 36.663 16.445 1.00 50.89 A C
ATOM 1420 CG GLU A 271 101.213 37.904 16.488 1.00 50.89 A C
ATOM 1421 CD GLU A 271 101.873 39.131 17.125 1.00 50.89 A C
ATOM 1422 OEl GLU A 271 102.721 39.776 16.464 1.00 50.89 A O
ATOM 1423 OE2 GLU A 271 101.538 39.457 18.289 1.00 50.89 A O
ATOM 1424 C GLU A 271 102.427 34.306 15.609 1.00 22.35 A C
ATOM 1425 O GLU A 271 103.137 34.047 16.580 1.00 22.35 A O
ATOM 1426 N TRP A 272 102.367 33.540 14.525 1.00 13.14 A N
ATOM 1427 CA TRP A 272 103.188 32.350 14.307 1.00 13.14 A C
ATOM 1428 CB TRP A 272 102.445 31.070 14.727 1.00 49.42 A C
ATOM 1429 CG TRP A 272 101.041 30.905 14.214 1.00 49.42 A C
ATOM 1430 CD2 TRP A 272 100.250 29.712 14.269 1.00 49.42 A C
ATOM 1431 CE2 TRP A 272 98.991 30.017 13.705 1.00 49.42 A C
ATOM 1432 CE3 TRP A 272 100.483 28.413 14.743 1.00 49.42 A C
ATOM 1433 CDl TRP A 272 100.251 31.858 13.636 1.00 49.42 A C ATOM 1434 NEl TRP A 272 99.019 31.333 13.326 1.00 49.42 A N
ATOM 1435 CZ2 TRP A 272 97.967 29.072 13.598 1.00 49.42 A C
ATOM 1436 CZ3 TRP A 272 99.467 27.473 14.637 1.00 49.42 A C
ATOM 1437 CH2 TRP A 272 98.222 27.809 14.068 1.00 49.42 A C
ATOM 1438 C TRP A 272 103.443 32.418 12.801 1.00 13.14 A C
ATOM 1439 O TRP A 272 104.531 32.784 12.361 1.00 13.14 A O
ATOM 1440 N TYR A 273 102.437 32.067 12.016 1.00 10.00 A N
ATOM 1441 CA TYR A 273 102.513 32.209 10.575 1.00 10.00 A C
ATOM 1442 CB TYR A 273 101.607 31.206 9.867 1.00 17.33 A C
ATOM 1443 CG TYR A 273 102.011 29.768 10.013 1.00 17.33 A C
ATOM 1444 CDl TYR A 273 103.139 29.273 9.366 1.00 17.33 A C
ATOM 1445 CEl TYR A 273 103.517 27.944 9.496 1.00 17.33 A C
ATOM 1446 CD2 TYR A 273 101.264 28.896 10.796 1.00 17.33 A C
ATOM 1447 CE2 TYR A 273 101.628 27.564 10.937 1.00 17.33 A C
ATOM 1448 CZ TYR A 273 102.756 27.091 10.286 1.00 17.33 A C
ATOM 1449 OH TYR A 273 103.126 25.767 10.429 1.00 17.33 A o
ATOM 1450 C TYR A 273 101.858 33.580 10.483 1.00 10.00 A C
ATOM 1451 o TYR A 273 101.368 34.096 11.484 1.00 10.00 A o
ATOM 1452 N TYR A 274 101.843 34.190 9.313 1.00 10.20 A N
ATOM 1453" CA TYR A 274 101.164 35.466 9.225 1.00 10.20 A C
ATOM 1454 CB TYR A 274 101.762 36.330 8.120 1.00 13.19 A C
ATOM 1455 CG TYR A 274 103.106 36.882 8.513 1.00 13.19 A C
ATOM 1456 CDl TYR A 274 104.281 36.315 8.034 1.00 13.19 A C
ATOM 1457 CEl TYR A 274 105.516 36.775 8.457 1.00 13.19 A C
ATOM 1458 CD2 TYR A 274 103.202 37.931 9.427 1.00 13.19 A C
ATOM 1459 CE2 TYR A 274 104.429 38.396 9.856 1.00 13.19 A C
ATOM 1460 CZ TYR A 274 105.582 37.815 9.368 1.00 13.19 A C
ATOM 1461 OH TYR A 274 106.806 38.270 9.793 1.00 13.19 A o
ATOM 1462 C TYR A 274 99.731 35.101 8.925 1.00 10.20 A C
ATOM 1463 O TYR A 274 99.337 34.998 7.763 1.00 10.20 A o
ATOM 1464 N GLN A 275 98.961 34.865 9.983 1.00 11.87 A N
ATOM 1465 CA GLN A 275 97.565 34.471 9.826 1.00 11.87 A C
ATOM 1466 CB GLN A 275 97.158 33.515 10.944 1.00 19.69 A C
ATOM 1467 CG GLN A 275 95.661 33.368 11.096 1.00 19.69 A C
ATOM 1468 CD GLN A 275 95.277 32.208 11.985 1.00 19.69 A C
ATOM 1469 OEl GLN A 275 96.048 31.801 12.852 1.00 19.69 A o
ATOM 1470 NE2 GLN A 275 94.070 31.676 11.784 1.00 19.69 A N
ATOM 1471 C GLN A 275 96.582 35.626 9.772 1.00 11.87 A C
ATOM 1472 O GLN A 275 96.637 36.548 10.581 1.00 11.87 A O
ATOM 1473 N ILE A 276 95.672 35.564 8.812 1.00 10.00 A N
ATOM 1474 CA ILE A 276 94.662 36.592 8.656 1.00 10.00 A C ATOM 1475 CB ILE A 276 94.977 37.445 7.438 1.00 10.39 A C
ATOM 1476 CG2 ILE A 276 96.324 38.111 7.617 1.00 10.39 A C
ATOM 1477 CGl ILE A 276 95.052 36.576 6.190 1.00 10.39 A C
ATOM 1478 CDl ILE A 276 95.397 37.371 4.940 1.00 10.39 A C
ATOM 1479 C ILE A 276 93.317 35.896 8.489 1.00 10.00 A C
ATOM 1480 O ILE A 276 93.280 34.679 8.270 1.00 10.00 A O
ATOM 1481 N GLU A 277 92.210 36.628 8.614 1.00 18.17 A N
ATOM 1482 CA GLU A 277 90.919 35.960 8.457 1.00 18.17 A C
ATOM 1483 CB GLU A 277 89.955 36.256 9.623 1.00 35.65 A C
ATOM 1484 CG GLU A 277 89.224 37.587 9.584 1.00 35.65 A C
ATOM 1485 CD GLU A 277 87.961 37.590 10.454 1.00 35.65 A C
ATOM 1486 OEl GLU A 277 87.041 36.783 10.175 1.00 35.65 A O
ATOM 1487 OE2 GLU A 277 87.884 38.395 11.415 1.00 35.65 A O
ATOM 1488 C GLU A 277 90.262 36.292 7.135 1.00 18.17 A C
ATOM 1489 O GLU A 277 90.060 37.462 6.785 1.00 18.17 A O
ATOM 1490 N ILE A 278 89.956 35.239 6.389 1.00 17.53 A N
ATOM 1491 CA ILE A 278 89.313 35.366 5.094 1.00 17.53 A C
ATOM 1492 CB ILE A 278 89.760 34.213 4.176 1.00 13.20 A C
ATOM 1493 CG2 ILE A 278 89.031 34.276 2.849 1.00 13.20 A C
ATOM 1494" ' CGl ILE A' 278 91.271 34.295 3.983 1.00 13.20 A C
ATOM 1495 CDl ILE A 278 91.793 33.502 2.821 1.00 13.20 A C
ATOM 1496 C ILE A 278 87.797 35.330 5.297 1.00 17.53 A C
ATOM 1497 O ILE A 278 87.292 34.567 6.121 1.00 17.53 A O
ATOM 1498 N LEU A 279 87.061 36.152 4.565 1.00 27.13 A N
ATOM 1499 CA LEU A 279 85.623 36.148 4.747 1.00 27.13 A C
ATOM 1500 CB LEU A 279 85.112 37.572 4.855 1.00 10.00 A C
ATOM 1501 CG LEU A 279 85.864 38.328 5.947 1.00 10.00 A C
ATOM 1502 CDl LEU A 279 85.176 39.657 6.242 1.00 10.00 A C
ATOM 1503 CD2 LEU A 279 85.923 37.458 7.192 1.00 10.00 A C
ATOM 1504 C LEU A 279 84.905 35.409 3.641 1.00 27.13 A C
ATOM 1505 O LEU A 279 84.275 34.385 3.891 1.00 27.13 A O
ATOM 1506 N LYS A 280 84.993 35.930 2.422 1.00 19.60 A N
ATOM 1507 CA LYS A 280 84.354 35.297 1.272 1.00 19.60 A C
ATOM 1508 CB LYS A 280 83.386 36.251 0.565 1.00 67.50 A C
ATOM 1509 CG LYS A 280 82.128 36.617 1.322 1.00 67.50 A C
ATOM 1510 CD LYS A 280 81.245 37.530 0.469 1.00 67.50 A C
ATOM 1511 CE LYS A 280 80.039 38.055 1.245 1.00 67.50 A C
ATOM 1512 NZ LYS A 280 79.220 39.006 0.435 1.00 67.50 A N
ATOM 1513 C LYS A 280 85.432 34.928 0.285 1.00 19.60 A C
ATOM 1514 O LYS A 280 86.576 35.339 0.414 1.00 19.60 A O
ATOM 1515 N LEU A 281 85.042 34.156 -0.713 1.00 19.62 A N ATOM 1516 CA LEU A 281 85.936 33.742 -1.773 1.00 19.62 A C
ATOM 1517 CB LEU A 281 86.392 32.317 -1.545 1 .00 25.43 A C
ATOM 1518 CG LEU A 281 87.767 32.127 -2.148 1 .00 25.43 A C
ATOM 1519 CDl LEU A 281 88.795 32.664 -1.170 1 .00 25.43 A C
ATOM 1520 CD2 LEU A 281 88.014 30.662 -2.430 1 .00 25.43 A C
ATOM 1521 C LEU A 281 85.041 33.824 -2.998 1 .00 19.62 A C
ATOM 1522 O LEU A 281 84.165 32.989 -3.193 1 .00 19.62 A O
ATOM 1523 N GLU A 282 85.235 34.853 -3.804 1 .00 13.51 A N
ATOM 1524 CA GLU A 282 84.408 35.053 -4.983 1 .00 13.51 A C
ATOM 1525 CB GLU A 282 84.174 36.544 -5.189 1 .00 43.20 A C
ATOM 1526 CG GLU A 282 82.732 36.991 -5.111 1 .00 43.20 A C
ATOM 1527 CD GLU A 282 82.612 38.500 -4.959 1 .00 43.20 A C
ATOM 1528 OEl GLU A 282 83.238 39.236 -5.763 1 .00 43.20 A O
ATOM 1529 OE2 GLU A 282 81.889 38.943 -4.036 1 .00 43.20 A O
ATOM 1530 C GLU A 282 85.044 34.478 -6.233 1 .00 13.51 A C
ATOM 1531 O GLU A 282 86.270 34.465 -6.369 1 .00 13.51 A o
ATOM 1532 N ILE A 283 84.206 34.021 -7.155 1 .00 13.94 A N
ATOM 1533 CA ILE A 283 84.694 33.462 -8.404 1 .00 13.94 A C
ATOM 1534 CB ILE A 283 84.780 31.946 -8.315 1 .00 10.00 A C
ATOM 1535 CG2 ILE A 283 85.186 31.358 -9.660 1 .00 10.00 A C
ATOM 1536 CGl ILE A 283 85.775 31.594 -7.212 1 .00 10.00 A C
ATOM 1537 CDl ILE A 283 86.159 30.140 -7.145 1 .00 10.00 A C
ATOM 1538' C ILE A 283 83.820 33.871 -9.579 1 .00 13.94 A C
ATOM 1539 O ILE A 283 82.673 33.434 -9.713 1 .00 13.94 A o
ATOM 1540 N GLY A 284 84.374 34.713 -10.438 1 .00 30.98 A N
ATOM 1541 CA GLY A 284 83.606 35.183 -11.566 1 .00 30.98 A C
ATOM 1542 C GLY A 284 82.440 35.965 -11.002 1 .00 30.98 A C
ATOM 1543 O GLY A 284 81.338 35.943 -11.549 1 .00 30.98 A O
ATOM 1544 N GLY A 285 82.688 36.649 -9.888 1 .00 40.17 A N
ATOM 1545 CA GLY A 285 81.654 37.441 -9.248 1 .00 40.17 A C
ATOM 1546 C GLY A 285 80.728 36.623 -8.368 1 .00 40.17 A C
ATOM 1547 O GLY A 285 80.023 37.171 -7.517 1 .00 40.17 A o
ATOM 1548 N GLN A 286 80.725 35.308 -8.565 1 .00 18.63 A N
ATOM 1549 CA GLN A 286 79.863 34.435 -7.781 1 .00 18.63 A C
ATOM 1550 CB GLN A 286 79.467 33.207 -8.594 1 .00 63.81 A C
ATOM 1551 CG GLN A 286 78.476 32.329 -7.872 1 .00 63.81 A C
ATOM 1552 CD GLN A 286 77.202 33.074 -7.552 1 .00 63.81 A C
ATOM 1553 OEl GLN A 286 76.434 33.415 -8.451 1 .00 63.81 A O
ATOM 1554 NE2 GLN A 286 76.974 33.346 -6.269 1 .00 63.81 A N
ATOM 1555 C GLN A 286 80.572 33.988 -6.519 1 .00 18.63 A C
ATOM 1556 O GLN A 286 81.621 33.355 -6.595 1 .00 18.63 A O ATOM 1557 N SER A 287 80.012 34.320 -5.360 1.00 24.89 A N
ATOM 1558 CA SER A 287 80.628 33.924 -4.099 1.00 24.89 A C
ATOM 1559 CB SER A 287 79.954 34.625 -2.928 1.00 43.09 A C
ATOM 1560 OG SER A 287 78.592 34.263 -2.866 1.00 43.09 O
ATOM 1561 C SER A 287 80.461 32.423 -3.975 1.00 24.89 A C
ATOM 1562 O SER A 287 79.586 31.843 -4.609 1.00 24.89 A O
ATOM 1563 N LEU A 288 81.298 31.786 -3.168 1.00 30.18 A N
ATOM 1564 CA LEU A 288 81.211 30.345 -3.023 1.00 30.18 A C
ATOM 1565 CB LEU A 288 82.525 29.780 -2.496 1.00 13.86 A C
ATOM 1566 CG LEU A 288 83.649 29.627 -3.508 1.00 13.86 A C
ATOM 1567 CDl LEU A 288 84.774 28.838 -2.876 1.00 13.86 A C
ATOM 1568 CD2 LEU A 288 83.141 28.898 -4.727 1.00 13.86 A C
ATOM 1569 C LEU A 288 80.086 29.899 -2.118 1.00 30.18 A C
ATOM 1570 O LEU A 288 79.642 28.750 -2.188 1.00 30.18 A O
ATOM 1571 N ASN A 289 79.630 30.802 -1.262 1.00 44.92 A N
ATOM 1572 CA ASN A 289 78.557 30.475 -0.333 1.00 44..92 A C
ATOM 1573 CB ASN A 289 77.245 30.226 -1.087 1.00 90..00 A C
ATOM 1574 CG ASN A 289 76.727 31.472 -1.789 1.00 90..00 A C
ATOM 1575 ODl ASN A 289 76.466 32.497 -1.153 1.00 90..00 A O
ATOM 1576 ND2 ASN A 289 76.573 31.388 -3.109 1.00 90..00 A N
ATOM 1577 C ASN A 289 78.930 29.238 0.478 1.00 44..92 A C
ATOM 1578 O ASN A 289 78.392 28.148 0.264 1.00 44..92 A O
ATOM 1579 N LEU A 290 79.876 29.424 1.391 1.00 46..73 A N
ATOM 1580 CA LEU A 290 80.338 28.361 2.271 1.00 46..73 A C
ATOM 1581 CB LEU A 290 81.683 27.810 1.813 1.00 41..93 A C
ATOM 1582 CG LEU A 290 81.733 27.058 0.493 1.00 41..93 A C
ATOM 1583 CDl LEU A 290 83.125 26.471 0.322 1.00 41..93 A C
ATOM 1584 CD2 LEU A 290 80.682 25.960 0.487 1.00 41..93 A C
ATOM 1585 C LEU A 290 80.519 28.967 3.640 1.00 46..73 A C
ATOM 1586 O LEU A 290 80.839 30.152 3.753 1.00 46..73 A O
ATOM 1587 N ASP A 291 80.312 28.163 4.678 1.00 53..93 A N
ATOM 1588 CA ASP A 291 80.489 28.651 6.038 1.00 53..93 A C
ATOM 1589 CB ASP A 291 80.363 27.491 7.028 1.00 68..54 A C
ATOM 1590 CG ASP A 291 80.536 27.929 8.465 1.00 68..54 A C
ATOM 1591 ODl ASP A 291 79.962 28.973 8.848 1.00 68..54 A O
ATOM 1592 OD2 ASP A 291 81.239 27.218 9.214 1.00 68..54 A O
ATOM 1593 C ASP A 291 81.889 29.265 6.077 1.00 53.93 A C
ATOM 1594 O ASP A 291 82.889 28.556 5.980 1.00 53.93 A O
ATOM 1595 N CYS A 292 81.954 30.587 6.200 1.00 33.07 A N
ATOM 1596 CA CYS A 292 83.230 31.282 6.196 1.00 33.07 A C
ATOM 1597 C CYS A 292 84.285 30.650 7.093 1.00 33.07 A C ATOM 1598 O CYS A 292 85.480 30.878 6.903 1.00 33.07 A O
ATOM 1599 CB CYS A 292 83.026 32. 755 6.552 1.00 55 .55 A C
ATOM 1600 SG CYS A 292 82.737 33. 120 8.306 1.00 55 .55 A S
ATOM 1601 N ARG A 293 83.863 29. 850 8.066 1.00 26 .90 A N
ATOM 1602 CA ARG A 293 84.835 29. 198 8.937 1.00 26 .90 A C
ATOM 1603 CB ARG A 293 84.137 28. 505 10.115 1.00 90 .00 A C
ATOM 1604 CG ARG A 293 83.604 29. 471 11.176 1.00 90 .00 A C
ATOM 1605 CD ARG A 293 83.184 28. 748 12.461 1.00 90 .00 A C
ATOM 1606 NE ARG A 293 81.877 28. 090 12.373 1.00 90 .00 A N
ATOM 1607 CZ ARG A 293 80.704 28. 716 12.471 1.00 90 .00 A C
ATOM 1608 NHl ARG A 293 80.659 30. 032 12.662 1.00 90 .00 A N
ATOM 1609 NH2 ARG A 293 79.571 28. 024 12.385 1.00 90 .00 A N
ATOM 1610 C ARG A 293 85.632 28. 187 8.111 1.00 26 .90 A C
ATOM 1611 O ARG A 293 86.749 27. 830 8.466 1.00 26 .90 A O
ATOM 1612 N GLU A 294 85.042 27. 746 7.001 1.00 29 .91 A N
ATOM 1613 CA GLU A 294 85.670 26. 795 6.083 1.00 29 .91 A C
ATOM 1614 CB GLU A 294 84.777 26. 569 4.863 1.00 62 .40 A C
ATOM 1615 CG GLU A 294 83.505 25. 834 5.153 1.00 62 .40 A C
ATOM 1615 CD GLU A 294 83.748 24. 365 5.376 1.00 62 .40 A C
ATOM 1617" OEl GLU A 294 84.827 24. 022 5.915 1.00 62 .40 A O
ATOM 1618 OE2 GLU A 294 82.860 23. 557 5.021 1.00 62 .40 A O
ATOM 1619 C GLU A 294 87.011 27. 325 5.595 1.00 29 .91 A C
ATOM 1620 O GLU A 294 88.019 26. 623 5.613 1.00 29 .91 A O
ATOM 1621 N TYR A 295 87.005 28. 574 5.146 1.00 24 .04 A N
ATOM 1622 CA TYR A 295 88.199 29. 205 4.622 1.00 24 .04 A C
ATOM 1623 CB TYR A 295 87.860 30. 557 4.011 1.00 38 .13 A C
ATOM 1624 CG TYR A 295 86.661 30. 562 3.098 1.00 38 .13 A C
ATOM 1625 CDl TYR A 295 85.615 31. 451 3.319 1.00 38 .13 A C
ATOM 1626 CEl TYR A 295 84.532 31. 522 2.459 1.00 38 .13 A C
ATOM 1627 CD2 TYR A 295 86.593 29. 729 1.984 1.00 38 .13 A C
ATOM 1628 CE2 TYR A 295 85.507 29. 791 1.108 1.00 38 .13 A C
ATOM 1629 CZ TYR A 295 84.477 30. 696 1.353 1.00 38 .13 A C
ATOM 1630 OH TYR A 295 83.395 30. 801 0.497 1.00 38 .13 A O
ATOM 1631 C TYR A 295 89.243 29. 420 5.697 1.00 24 .04 A C
ATOM 1632 O TYR A 295 90.420 29. 555 5.398 1.00 24 .04 A O
ATOM 1633 N ASN A 296 88.824 29. 464 6.952 1.00 35 .07 A N
ATOM 1634 CA ASN A 296 89.781 29. 696 8.020 1.00 35 .07 A C
ATOM 1635 CB ASN A 296 89.301 30. 845 8.891 1.00 31 .44 A C
ATOM 1636 CG ASN A 296 89.495 32. 179 8.227 1.00 31 .44 A C
ATOM 1637 ODl ASN A 296 90.606 32. 705 8.187 1.00 31 .44 A O
ATOM 1638 ND2 ASN A 296 88.421 32. 730 7.679 1.00 31 .44 A N ATOM 1639 C ASN A 296 90.067 28.485 8.879 1.00 35.07 A C
ATOM 1640 O ASN A 296 90.581 28.609 9.986 1.00 35.07 A O
ATOM 1641 N ALA A 297 89.733 27.308 8.377 1.00 79.01 A N
ATOM 1642 CA ALA A 297 89.989 26.105 9.140 1.00 79.01 A C
ATOM 1643 CB ALA A 297 88.728 25.260 9.227 1.00 36.41 A C
ATOM 1644 C ALA A 297 91.134 25.321 8.499 1.00 79.01 A C
ATOM 1645 O ALA A 297 91.056 24.895 7.344 1.00 79.01 A O
ATOM 1646 N ASP A 298 92.211 25.157 9.259 1.00 72.08 A N
ATOM 1647 CA ASP A 298 92.262 25.705 10.606 1.00 72.08 A C
ATOM 1648 CB ASP A 298 92.857 24.674 11.571 1.00 90.00 A C
ATOM 1649 CG ASP A 298 94.243 24.213 11.155 1.00 90.00 A C
ATOM 1650 ODl ASP A 298 94.780 23.282 11.797 1.00 90.00 A O
ATOM 1651 OD2 ASP A 298 94.797 24.783 10.189 1.00 90.00 A O
ATOM 1652 C ASP A 298 93.077 26.994 10.625 1.00 72.08 A C
ATOM 1653 O ASP A 298 93.362 27.536 11.699 1.00 72.08 A O
ATOM 1654 N LYS A 299 93.436 27.487 9.436 1.00 54.52 A N
ATOM 1655 CA LYS A 299 94.223 28.718 9.314 1.00 54.52 A C
ATOM 1656 CB LYS A 299 95.596 28.520 9.966 1.00 50.20 A C
ATOM 1657 CG LYS A 299 96.450 27.516 9.217 1.00 50.20 A C
ATOM 1658 CD LYS A 299 97.612 26.976 10.034 1.00 50.20 A C
ATOM 1659 CE LYS A 299 98.285 25.822 9.270 1.00 50.20 A C
ATOM 1660 NZ. LYS A 299 99.369 25.103 10.019 1.00 50.20 A N
ATOM 1661 C LYS A 299 94.434 29.164 7.865 1.00 54.52 A C
ATOM 1662 O LYS A 299 94.513 28.343 6.951 1.00 54.52 A O
ATOM 1663 N ALA A 300 94.513 30.476 7.668 1.00 17.89 A W
ATOM 1664 CA ALA A 300 94.779 31.063 6.357 1.00 17.89 A C
ATOM 1665 CB ALA A 300 93.601 31.885 5.893 1.00 10.00 A C
ATOM 1666 C ALA A 300 96.007 31.958 6.569 1.00 17.89 A C
ATOM 1667 O ALA A 300 95.947 32.947 7.302 1.00 17.89 A O
ATOM 1668 N ILE A 301 97.126 31.610 5.946 1.00 10.37 A N
ATOM 1669 CA ILE A 301 98.344 32.387 6.121 1.00 10.37 A C
ATOM 1670 CB ILE A 301 99.450 31.513 6.717 1.00 10.00 A C
ATOM 1671 CG2 ILE A 301 99.012 30.958 8.045 1.00 10.00 A C
ATOM 1672 CGl ILE A 301 99.741 30.344 5.783 1.00 10.00 A C
ATOM 1673 CDl ILE A 301 100.838 29.453 6.268 1.00 10.00 A C
ATOM 1674 C ILE A 301 98.885 32.972 4.830 1.00 10.37 A C
ATOM 1675 O ILE A 301 98.615 32.456 3.749 1.00 10.37 A O
ATOM 1676 N VAL A 302 99.642 34.055 4.941 1.00 10.73 A N
ATOM 1677 CA VAL A 302 100.269 34.656 3.775 1.00 10.73 A C
ATOM 1678 CB VAL A 302 100.441 36.128 3.971 1.00 10.00 A C
ATOM 1679 CGl VAL A 302 101.216 36.698 2.816 1.00 10.00 A C ATOM 1680 CG2 VAL A 302 99.085 36.771 4.106 1.00 10.00 A C
ATOM 1681 C VAL A 302 101.635 33.986 3.766 1.00 10.73 A C
ATOM 1682 O VAL A 302 102.354 34.068 4.752 1.00 10.73 A O
ATOM 1683 N ASP A 303 102.016 33.339 2.671 1.00 11.00 A N
ATOM 1684 CA ASP A 303 103.281 32.603 2.672 1.00 11.00 A C
ATOM 1685 CB ASP A 303 102.948 31.174 3.139 1.00 14.90 A C
ATOM 1686 CG ASP A 303 104.067 30.180 2.918 1.00 14.90 A C
ATOM 1687 ODl ASP A 303 105.221 30.590 2.704 1.00 14.90 A O
ATOM 1688 OD2 ASP A 303 103.783 28.965 2.979 1.00 14.90 A o
ATOM 1689 C ASP A 303 104.096 32.598 1.368 1.00 11.00 A C
ATOM 1690 O ASP A 303 103.901 31.746 0.502 1.00 11.00 A O
ATOM 1691 N SER A 304 105.026 33.542 1.247 1.00 10.00 A N
ATOM 1692 CA SER A 304 105.877 33.656 0.062 1.00 10.00 A C
ATOM 1693 CB SER A 304 106.875 34.797 0.247 1.00 11.24 A C
ATOM 1694 OG SER A 304 107.848 34.471 1.237 1.00 11.24 A O
ATOM 1695 C SER A 304 106.651 32.362 -0.195 1.00 10.00 A C
ATOM 1696 O SER A 304 107.086 32.083 -1.315 1.00 10.00 A O
ATOM 1697 W GLY A 305 106.827 31.585 0.863 1.00 11.66 A N
ATOM 1698 CA GLY A 305 107.552 30.338 0.762 1.00 11.66 A C
ATOM 1699_ C GLY A 305_ 106.745 29.212 0-161 1.00 11.66 A C
ATOM 1700 o GLY A 305 107.222 28.079 0.119 1.00 11.66 A o
ATOM 1701 N THR A 306 105.525 29.507 -0.284 1.00 10.00 A N
ATOM 1702 CA THR A 306 104.676 28.496 -0.914 1.00 10.00 A C
ATOM 1703 CB THR A 306 103.408 28.201 -0.107 1.00 13.37 A C
ATOM 1704 OGl THR A 306 103.750 27.431 1.049 1.00 13.37 A o
ATOM 1705 CG2 THR A 306 102.425 27.406 -0.938 1.00 13.37 A C
ATOM 1706 C THR A 306 104.271 28.968 -2.293 1.00 10.00 A C
ATOM 1707 O THR A 306 103.592 29.979 -2.450 1.00 10.00 A o
ATOM 1708 N THR A 307 104.694 28.211 -3.291 1.00 10.00 A N
ATOM 1709 CA THR A 307 104.442 28.513 -4.683 1.00 10.00 A C
ATOM 1710 CB THR A 307 105.061 27.403 -5.539 1.00 26.92 A C
ATOM 1711 OGl THR A 307 106.396 27.781 -5.869 1.00 26.92 A o
ATOM 1712 CG2 THR A 307 104.274 27.154 -6.808 1.00 26.92 A C
ATOM 1713 C THR A 307 102.998 28.750 -5.113 1.00 10.00 A C
ATOM 1714 O THR A 307 102.711 29.714 -5.823 1.00 10.00 A O
ATOM 1715 N LEU A 308 102.091 27.885 -4.680 1.00 11.64 A N
ATOM 1716 CA LEU A 308 100.702 27.985 -5.088 1.00 11.64 A C
ATOM 1.717 CB LEU A 308 100.220 26.615 -5.512 1.00 10.00 A C
ATOM 1718 CG LEU A 308 101.060 25.982 -6.606 1.00 10.00 A C
ATOM 1719 CDl LEU A 308 100.601 24.549 -6.850 1.00 10.00 A C
ATOM 1720 CD2 LEU A 308 100.931 26.820 -7.859 1.00 10.00 A C ATOM 1721 C LEU A 308 99.716 28.533 -4.084 1.00 11.64 A C
ATOM 1722 O LEU A 308 100.046 28.749 -2.929 1.00 11.64 A O
ATOM 1723 N LEU A 309 98.493 28.770 -4.553 1.00 16.77 A N
ATOM 1724 CA LEU A 309 97.414 29.241 -3.700 1.00 16.77 A C
ATOM 1725 CB LEU A 309 96.397 30.078 -4.487 1.00 10.00 A C
ATOM 1726 CG LEU A 309 95.029 30.221 -3.799 1.00 10.00 A C
ATOM 1727 CDl LEU A 309 95.229 30.752 -2.404 1.00 10.00 A C
ATOM 1728 CD2 LEU A 309 94.117 31.138 -4.574 1.00 10.00 A C
ATOM 1729 C LEU A 309 96.774 27.934 -3.271 1.00 16.77 A C
ATOM 1730 O LEU A 309 96.059 27.297 -4.052 1.00 16.77 A O
ATOM 1731 N ARG A 310 97.052 27.516 -2.043 1.00 11.41 A N
ATOM 1732 CA ARG A 310 96.510 26.266 -1.536 1.00 11.41 A C
ATOM 1733 CB ARG A 310 97.538 25.592 -0.639 1.00 17.26 A C
ATOM 1734 CG ARG A 310 98.844 25.297 -1.356 1.00 17.26 A C
ATOM 1735 CD ARG A 310 99.809 24.561 -0.454 1.00 17.26 A C
ATOM 1736 NE ARG A 310 99.263 23.278 -0.036 1.00 17.26 A N
ATOM 1737 CZ ARG A 310 99.506 22.724 1.142 1.00 17.26 A C
ATOM 1738 NHl ARG A 310 98.970 21.551 1.455 1.00 17.26 A N
ATOM 1739 NH2 ARG A 310 100.280 23.360 2.010 1.00 17.26 A N
ATOM 1740 C ARG A 310— 95.220 26.493. -0.779 1.00 11.41 A C
ATOM 1741 O ARG A 310 95.142 27.366 0.072 1.00 11.41 A O
ATOM 1742 N LEU A 311 94.203 25.711 -1.104 1.00 16.42 A N
ATOM 1743 CA LEU A 311 92.922 25.843 -0.442 1.00 16.42 A C
ATOM 1744 CB LEU A 311 91.842 26.266 -1.431 1.00 10.67 A C
ATOM 1745 CG LEU A 311 92.138 27.307 -2.502 1.00 10.67 A C
ATOM 1746 CDl LEU A 311 90.880 27.556 -3.315 1.00 10.67 A C
ATOM 1747 CD2 LEU A 311 92.598 28.588 -1.877 1.00 10.67 A C
ATOM 1748 C LEU A 311 92.518 24.500 0.142 1.00 16.42 A C
ATOM 1749 0 LEU A 311 92.718 23.455 -0.490 1.00 16.42 A O
ATOM 1750 N PRO A 312 91.961 24.504 1.367 1.00 13.89 A N
ATOM 1751 CD PRO A 312 91.791 25.631 2.296 1.00 10.70 A C
ATOM 1752 CA PRO A 312 91.531 23.249 1.990 1.00 13.89 A C
ATOM 1753 CB PRO A 312 90.929 23.705 3.320 1.00 10.70 A C
ATOM 1754 CG PRO A 312 90.622 25.164 3.104 1.00 10.70 A C
ATOM 1755 C PRO A 312 90.520 22.570 1.072 1.00 13.89 A C
ATOM 1756 O PRO A 312 89.604 23.214 0.546 1.00 13.89 A O
ATOM 1757 N GLN A 313 90.711 21.266 0.888 1.00 24.25 A N
ATOM 1758 CA GLN A 313 89.899 20.429 0.002 1.00 24.25 A C
ATOM 1759 CB GLN A 313 89.813 19.012 0.545 1.00 16.82 A C
ATOM 1760 CG GLN A 313 89.394 18.020 -0.507 1.00 16.82 A C
ATOM 1761 CD GLN A 313 90.481 17.782 -1.539 1.00 16.82 A C ATOM 1762 OEl GLN A 313 91.608 17.420 -1.188 1.00 16.82 A O
ATOM 1763 NE2 GLN A 313 90.151 17.973 -2.817 1.00 16.82 A N
ATOM 1764 C GLN A 313 88.497 20.879 -0.367 1.00 24.25 A C
ATOM 1765 O GLN A 313 88.251 21.260 -1.512 1.00 24.25 A O
ATOM 1766 F LYS A 314 87.575 20.823 0.588 1.00 17.40 A N
ATOM 1767 CA LYS A 314 86.199 21.208 0.303 1.00 17.40 A C
ATOM 1768 CB LYS A 314 85.397 21.347 1.598 1.00 64.16 A C
ATOM 1769 CG LYS A 314 83.902 21.448 1.357 1.00 64.16 A C
ATOM 1770 CD LYS A 314 83.119 21.574 2.649 1.00 64.16 A C
ATOM 1771 CE LYS A 314 81.628 21.716 2.362 1.00 64.16 A C
ATOM 1772 NZ LYS A 314 80.831 21.986 3.595 1.00 64.16 A N
ATOM 1773 C LYS A 314 86.126 22.502 -0.509 1.00 17.40 A C
ATOM 1774 O LYS A 314 85.321 22.613 -1.438 1.00 17.40 A O
ATOM 1775 N VAL A 315 86.977 23.470 -0.172 1.00 12.53 A N
ATOM 1776 CA VAL A 315 86.994 24.747 -0.884 1.00 12.53 A C
ATOM 1777 CB VAL A 315 87.807 25.821 -0.137 1.00 10.00 A C
ATOM 1778 CGl VAL A 315 87.706 27.130 -0.885 1.00 10.00 A C
ATOM 1779 CG2 VAL A 315 87.290 25.990 1.279 1.00 10.00 A C
ATOM 1780 C VAL A 315 87.610 24.568 -2.263 1.00 12.53 A C
ATOM 1781. O VAL A 315 87.095 25.076 -3.264 1.00 12.53 A o
ATOM 1782 N PHE A 316 88.722 23.848 -2.310 1.00 20.85 A N
ATOM 1783 CA PHE A 316 89.379 23.601 -3.579 1.00 20.85 A C
ATOM 1784 CB PHE A 316 90.480 22.569 -3.421 1.00 11.82 A C
ATOM 1785 CG PHE A 316 91.211 22.273 -4.693 1.00 11.82 A C
ATOM 1786 CDl PHE A 316 92.050 23.218 -5.261 1.00 11.82 A C
ATOM 1787 CD2 PHE A 316 91.095 21.032 -5.303 1.00 11.82 A C
ATOM 1788 CEl PHE A 316 92.768 22.931 -6.413 1.00 11.82 A C
ATOM 1789 CE2 PHE A 316 91.809 20.730 -6.457 1.00 11.82 A C
ATOM 1790 CK PHE A 316 92.647 21.680 -7.011 1.00 11.82 A C
ATOM 1791 C PHE A 316 88.355 23.077 -4.577 1.00 20.85 A C
ATOM 1792 o PHE A 316 88.233 23.593 -5.692 1.00 20.85 A o
ATOM 1793 N ASP A 317 87.615 22.050 -4.170 1.00 14.79 A N
ATOM 1794 CA ASP A 317 86.612 21.468 -5.045 1.00 14.79 A C
ATOM 1795 CB ASP A 317 85.886 20.324 -4.337 1.00 40.22 A C
ATOM 1796 CG ASP A 317 86.768 19.095 -4.160 1.00 40.22 A C
ATOM 1797 ODl ASP A 317 87.416 18.683 -5.148 1.00 40.22 A o
ATOM 1798 OD2 ASP A 317 86.808 18.533 -3.045 1.00 40.22 A o
ATOM 1799 C ASP A 317 85.624 22.529 -5.504 1.00 14.79 A C
ATOM 1800 O ASP A 317 85.405 22.712 -6.700 1.00 14.79 A o
ATOM 1801 N ALA A 318 85.038 23.243 -4.555 1.00 18.97 A N
ATOM 1802 CA ALA A 318 84.085 24.279 -4.908 1.00 18.97 A C ATOM 1803 CB ALA A 318 83.735 25.099 -3.686 1.00 31.46 A C
ATOM 1804 C ALA A 318 84.678 25.177 -5.987 1.00 18.97 A C
ATOM 1805 O ALA A 318 84.047 25.426 -7.016 1.00 18.97 A O
ATOM 1806 N VAL A 319 85.899 25.651 -5.752 1.00 11.35 A N
ATOM 1807 CA VAL A 319 86.550 26.530 -6.710 1.00 11.35 A C
ATOM 1808 CB VAL A 319 87.928 26.973 -6.225 1.00 10.00 A C
ATOM 1809 CGl VAL A 319 88.633 27.753 -7.325 1.00 10.00 A C
ATOM 1810 CG2 VAL A 319 87.783 27.834 -4.983 1.00 10.00 A C
ATOM 1811 C VAL A 319 86.707 25.878 -8.068 1.00 11.35 A C
ATOM 1812 O VAL A 319 86.266 26.427 -9.073 1.00 11.35 A O
ATOM 1813 N VAL A 320 87.341 24.713 -8.105 1.00 10.26 A N
ATOM 1814 CA VAL A 320 87.528 24.013 -9.369 1.00 10.26 A C
ATOM 1815 CB VAL A 320 88.066 22.607 -9.156 1.00 10.00 A C
ATOM 1816 CGl VAL A 320 87.992 21.835 -10.449 1.00 10.00 A C
ATOM 1817 CG2 VAL A 320 89.496 22.675 -8.657 1.00 10.00 A C
ATOM 1818 C VAL A 320 86.203 23.912 -10.102 1.00 10.26 A C
ATOM 1819 O VAL A 320 86.082 24.356 -11.238 1.00 10.26 A O
ATOM 1820 N GLU A 321 85.207 23.332 -9.449 1.00 18.83 A N
ATOM 1821 CA GLU A 321 83.892 23.202 -10.065 1.00 18.83 A C
ATOM 1822 ■ CB GLU A 321 82.851 22.815 -9.015- 1.00 88.72 A C
ATOM 1823 CG GLU A 321 81.436 22.707 -9.555 1.00 88.72 A C
ATOM 1824 CD GLU A 321 80.396 22.600 -8.450 1.00 88.72 A C
ATOM 1825 OEl GLU A 321 80.285 23.554 -7.643 1.00 88.72 A O
ATOM 1826 OE2 GLU A 321 79.690 21.565 -8.387 1.00 88.72 A O
ATOM 1827 C GLU A 321 83.523 24.551 -10.682 1.00 18.83 A C
ATOM 1828 O GLU A 321 83.150 24.644 -11.851 1.00 18.83 A O
ATOM 1829 N ALA A 322 83.660 25.597 -9.881 1.00 16.72 A N
ATOM 1830 CA ALA A 322 83.339 26.939 -10.317 1.00 16.72 A C
ATOM 1831 CB ALA A 322 83.599 27.914 -9.191 1.00 13.02 A C
ATOM 1832 C ALA A 322 84.125 27.349 -11.551 1.00 16.72 A C
ATOM 1833 O ALA A 322 83.540 27.698 -12.570 1.00 16.72 A O
ATOM 1834 N VAL A 323 85.449 27.320 -11.455 1.00 22.69 A N
ATOM 1835 CA VAL A 323 86.302 27.712 -12.570 1.00 22.69 A C
ATOM 1836 CB VAL A 323 87.775 27.455 -12.260 1.00 10.00 A C
ATOM 1837 CGl VAL A 323 88.643 27.940 -13.406 1.00 10.00 A C
ATOM 1838 CG2 VAL A 323 88.144 28.143 -10.971 1.00 10.00 A C
ATOM 1839 C VAL A 323 85.945 26.937 -13.819 1.00 22.69 A C
ATOM 1840 O VAL A 323 85.999 27.469 -14.922 1.00 22.69 A O
ATOM 1841 N ALA A 324 85.580 25.675 -13.643 1.00 33.37 A N
ATOM 1842 CA ALA A 324 85.214 24.844 -14.774 1.00 33.37 A C
ATOM 1843 CB ALA A 324 85.043 23.414 -14.327 1.00 30.70 A C ATOM 1844 C ALA A 324 83.924 25.360 -15.403 1.00 33.37 A C ATOM 1845 O ALA A 324 83.918 25.758 -16.563 1.00 33.37 A O ATOM 1846 N ARG A 325 82.836 25.360 -14.637 1.00 70.79 A N ATOM 1847 CA ARG A 325 81.542 25.833 -15.136 1.00 70.79 A C ATOM 1848 CB ARG A 325 80.581 26.097 -13.971 1.00 90.00 A C ATOM 1849 CG ARG A 325 79.955 24.859 -13.347 1.00 90.00 A C ATOM 1850 CD ARG A 325 79.094 25.241 -12.148 1.00 90.00 A C
ATOM 1851 NE ARG A 325 78.227 24.147 -11.711 1.00 90.00 A N ATOM 1852 CZ ARG A 325 77.402 24.216 -10.668 1.00 90.00 A C ATOM 1853 NHl ARG A 325 77.333 25.329 -9.946 1.00 90.00 A N ATOM 1854 NH2 ARG A 325 76.636 23.176 -10.350 1.00 90.00 A N ATOM 1855 C ARG A 325 81.656 27.108 -15.970 1.00 70.79 A C ATOM 1856 O ARG A 325 81.059 27.214 -17.044 1.00 70.79 A O ATOM 1857 N ALA A 326 82.429 28.067 -15.466 1.00 64.59 A N ATOM 1858 CA ALA A 326 82.622 29.357 -16.126 1.00 64.59 A C ATOM 1859 CB ALA A 326 83.278 30.339 -15.152 1.00 48.66 A C ATOM 1860 C ALA A 326 83.423 29.300 -17.426 1.00 64.59 A C ATOM 1861 O ALA A 326 84.037 30.289 -17.826 1.00 -64.59 A O ATOM 1862 N SER A 327 83.403 28.145 -18.082 1.00 82.24 A N ATOM 1863 CA SΞR A 327 84.108 27.943 -19.345 1.00 82.24 A C ATOM 1864 CB SER A 327 85.523 28.509 -19.281 1.00 37.77 A C ATOM 1865 OQ SER A 327 86.314 27.788 -18.352 1.00 37.77 A O ATOM 1866 C SER A 327 84.181 26.447 -19.616 1.00 82.24 A C ATOM 1867 o SER A 327 85.235 25.910 -19.970 1.00 82.24 A O ATOM 1868 N LEU A 328 83.047 IS.Ill -19.440 1.00 90.00 A N ATOM 1869 CA LEU A 328 82.958 24.336 -19.645 1.00 90.00 A C ATOM 1870 CB LEU A 328 81.506 23.880 -19.399 1.00 90.00 A C ATOM 1871 CG LEU A 328 81.168 22.398 -19.158 1.00 90.00 A C ATOM 1872 CDl LEU A 328 81.962 21.856 -17.963 1.00 90.00 A C ATOM 1873 CD2 LEU A 328 79.659 22.258 -18.908 1.00 90.00 A C ATOM 1874 C LEU A 328 83.416 23.968 -21.064 1.00 90.00 A C ATOM 1875 O LEU A 328 83.630 22.789 -21.377 1.00 90.00 A o ATOM 1876 N ILE A 329 83.591 24.989 -21.905 1.00 90.00 A N ATOM 1877 CA ILE A 329 83.995 24.798 -23.299 1.00 90.00 A C ATOM 1878 CB ILE A 329 84.025 26.157 -24.090 1.00 74.25 A C ATOM 1879 CG2 ILE A 329 83.584 25.929 -25.545 1.00 74.25 A C ATOM 1880 CGl ILE A 329 83.110 27.195 -23.425 1.00 74.25 A C ATOM 1881 CDl ILE A 329 83.827 28.127 -22.460 1.00 74.25 A C ATOM 1882 C ILE A 329 85.350 24.102 -23.476 1.00 90.00 A C ATOM 1883 O ILE A 329 85.416 22.986 -24.000 1.00 90.00 A O ATOM 1884 N PRO A 330 86.447 24.745 -23.036 1.00 90.00 A N ATOM 1885 CD PRO A 330 86.512 26.017 -22.294 1.00 46.52 A C
ATOM 1886 CA PRO A 330 87.786 24.153 -23.173 1.00 90.00 A C
ATOM 1887 CB PRO A 330 88.701 25.238 -22.594 1.00 46.52 A C
ATOM 1888 CG PRO A 330 87.828 25.898 -21.572 1.00 46.52 A C
ATOM 1889 C PRO A 330 87.963 22.792 -22.488 1.00 90.00 A C
ATOM 1890 O PRO A 330 87.226 22.453 -21.554 1.00 90.00 A O
ATOM 1891 N GLU A 331 88.932 22.010 -22.968 1.00 89.40 A M
ATOM 1892 CA GLU A 331 89.192 20.697 -22.388 1.00 89.40 A C
ATOM 1893 CB GLU A 331 89.155 19.595 -23.457 1.00 90.00 A C
ATOM 1894 CG GLU A 331 89.103 18.179 -22.856 1.00 90.00 A C
ATOM 1895 CD GLU A 331 88.901 17.065 -23.890 1.00 90.00 A C
ATOM 1896 OEl GLU A 331 89.809 16.834 -24.724 1.00 90.00 A O
ATOM 1897 OE2 GLU A 331 87.826 16.417 -23.868 1.00 90.00 A O
ATOM 1898 C GLU A 331 90.511 20.621 -21.618 1.00 89.40 A C
ATOM 1899 O GLU A 331 91.596 20.418 -22.186 1.00 89.40 A O
ATOM 1900 N PHE A 332 90.384 20.809 -20.308 1.00 89.49 A N
ATOM 1901 CA PHE A 332 91.486 20.741 -19.358 1.00 89.49 A C
ATOM 1902 CB PHE A 332 91.614 22.083 -18.605 1.00 54.68 A C
ATOM 1903 CG PHE A 332 92.386 23.157 -19.369 1.00 54.68 A C
ATOM 1904 CDl PHE A 332 92.170 23.377- -20.729 1.00 54.68 A C
ATOM 1905 CD2 PHE A 332 93.317 23.964 -18.716 1.00 54.68 A C
ATOM 1906 CEl PHE A 332 92.873 24.390 -21.427 1.00 54.68 A C
ATOM 1907 CE2 PHE A 332 94.022 24.976 -19.401 1.00 54.68 A C
ATOM 1908 CZ PHE A 332 93.798 25.186 -20.755 1.00 54.68' A C
ATOM 1909 C PHE A 332 91.052 19.596 -18.421 1.00 89.49 A C
ATOM 1910 O PHE A 332 90.141 19.756 -17.602 1.00 89.49 A O
ATOM 1911 N SER A 333 91.692 18.436 -18.582 1.00 54.84 A N
ATOM 1912 CA SER A 333 91.390 17.226 -17.810 1.00 54.84 A C
ATOM 1913 CB SER A 333 92.262 16.064 -18.280 1.00 65.14 A C
ATOM 1914 OG SER A 333 93.541 16.132 -17.670 1.00 65.14 A O
ATOM 1915 C SER A 333 91.590 17.375 -16.316 1.00 54.84 A C
ATOM 1916 O SER A 333 92.452 18.124 -15.868 1.00 54.84 A O
ATOM 1917 N ASP A 334 90.811 16.629 -15.541 1.00 66.94 A N
ATOM 1918 CA ASP A 334 90.918 16.701 -14.090 1.00 66.94 A C
ATOM 1919 CB ASP A 334 89.934 15.723 -13.417 1.00 90.00 A C
ATOM 1920 CG ASP A 334 89.977 14.322 -14.013 1.00 90.00 A C
ATOM 1921 ODl ASP A 334 89.760 14.180 -15.237 1.00 90.00 A O
ATOM 1922 OD2 ASP A 334 90.212 13.361 -13.247 1.00 90.00 A O
ATOM 1923 C ASP A 334 92.341 16.476 -13.588 1.00 66.94 A C
ATOM 1924 O ASP A 334 92.635 16.727 -12.422 1.00 66.94 A O
ATOM 1925 N GLY A 335 93.222 16.011 -14.468 1.00 20.14 A N ATOM 1926 CA GLY A 335 94.606 15.806 -14.071 1.00 20.14 A C
ATOM 1927 C GLY A 335 95.284 17.164 -13.985 1.00 20.14 A C
ATOM 1928 O GLY A 335 96.199 17.385 -13.195 1.00 20.14 A O
ATOM 1929 N PHE A 336 94.815 18.081 -14.822 1.00 14.66 A N
ATOM 1930 CA PHE A 336 95.323 19.443 -14.876 1.00 14.66 A C
ATOM 1931 CB PHE A 336 94.591 20.204 -15.969 1.00 10.50 A C
ATOM 1932 CG PHE A 336 94.862 21.665 -15.970 1.00 10.50 A C
ATOM 1933 CDl PHE A 336 96.080 22.158 -16.415 1.00 10.50 A C
ATOM 1934 CD2 PHE A 336 93.906 22.556 -15.517 1.00 10.50 A C
ATOM 1935 CEl PHE A 336 96.344 23.522 -16.411 1.00 10.50 A C
ATOM 1936 CΞ2 PHE A 336 94.160 23.929 -15.507 1.00 10.50 A C
ATOM 1937 CZ PHE A 336 95.383 24.408 -15.955 1.00 10.50 A C
ATOM 1938 C PHE A 336 95.089 20.137 -13.544 1.00 14.66 A C
ATOM 1939 o PHE A 336 95.960 20.837 -13.044 1.00 14.66 A O
ATOM 1940 N TRP A 337 93.898 19.938 -12.983 1.00 10.00 A N
ATOM 1941 CA TRP A 337 93.524 20.539 -11.703 1.00 10.00 A C
ATOM 1942 CB TRP A 337 92.043 20.272 -11.399 1.00 30.90 A C
ATOM 1943 CG TRP A 337 91.092 20.675 -12.489 1.00 30.90 A C
ATOM 1944 CD2 TRP A 337 90.954 21.975 -13.085 1.00 30.90 A C
ATOM 1945.. CE2 TRP A 337 89.956 21.873 -14.077 1.00 30.90 A C
ATOM 1946 CE3 TRP A 337 91.578 23.213 -12.878 1.00 30.90 A C
ATOM 1947 CDl TRP A 337 90.198 19.871 -13.120 1.00 30.90 A C
ATOM 1948 NEl TRP A 337 89.512 20.580 -14.077 1.00 30.90 A N
ATOM 1949 CZ2 TRP A 337 89.567 22.957 -14.863 1.00 30.90 A C
ATOM 1950 CZ3 TRP A 337 9 911..119900 24.297 -13.664 1 1..0000 3300..9900 A C
ATOM 1951 CH2 TRP A 337 9900..119944 24.158 -14.644 11..0000 3300..9900 A C
ATOM 1952 C TRP A 337 9 944..336677 19.978 -10.562 11..0000 1100..0000 A C
ATOM 1953 O TRP A 337 9 944..771133 20.689 -9.615 11..0000 1100..0000 A o
ATOM 1954 N THR A 338 9 944..667777 18.691 -10.657 11..0000 1177..3322 A N
ATOM 1955 CA THR A 338 9 955..447744 18.007 -9.650 11..0000 1177..3322 A C
ATOM 1956 CB THR A 338 9 955..447777 1 166..449922 -9.888 11..0000 6600..5522 A C
ATOM 1957 OGl THR A 338 94.150 15.986 - 9 . 721 1 . 00 60 . 52 A O
ATOM 1958 CG2 THR A 338 96.403 15.795 -8 . 911 1 . 00 60 . 52 A C
ATOM 1959 C THR A 338 96.908 18 . 500 -9 . 696 1 . 00 17 . 32 A C
ATOM 1960 O THR A 338 97.629 18 . 440 -8.699 1. 00 17 . 32 A O
ATOM 1961 N GLY A 339 97.317 18.992 -10.859 1.00 14.22 A N
ATOM 1962 CA GLY A 339 98.673 19.475 -11.014 1.00 14.22 A C
ATOM 1963 C GLY A 339 99.576 18.372 -11.529 1.00 14.22 A C
ATOM 1964 O GLY A 339 100.782 18.545 -11.650 1.00 14.22 A o
ATOM 1965 N SER A 340 98.985 17.225 -11.827 1.00 22.17 A N
ATOM 1966 CA SER A 340 99.739 16.095 -12.331 1.00 22.17 A C ATOM 1967 CB SER A 340 98.844 14.859 -12.380 1.00 49.75 A C
ATOM 1968 OG SER A 340 98.140 14.696 -11.159 1.00 49.75 A O
ATOM 1969 C SER A 340 100.236 16.415 -13.732 1.00 22.17 A C
ATOM 1970 O SER A 340 101.342 16.026 -14.119 1.00 22.17 A O
ATOM 1971 N GLN A 341 99.423 17.143 -14.490 1.00 21.08 A N
ATOM 1972 CA GLN A 341 99.784 17.482 -15.852 1.00 21.08 A C
ATOM 1973 CB GLN A 341 98.877 16.730 -16.816 1.00 77.32 A C
ATOM 1974 CG GLN A 341 98.817 15.250 -16.546 1.00 77.32 A C
ATOM 1975 CD GLN A 341 97.761 14.561 -17.377 1.00 77.32 A C
ATOM 1976 OEl GLN A 341 96.582 14.925 -17.327 1.00 77.32 A O
ATOM 1977 NE2 GLN A 341 98.173 13.556 -18.147 1.00 77.32 A N
ATOM 1978 C GLN A 341 99.693 18.968 -16.147 1.00 21.08 A C
ATOM 1979 O GLN A 341 99.186 19.741 -15.341 1.00 21.08 A O
ATOM 1980 N LEU A 342 100.195 19.350 -17.319 1.00 19.48 A N
ATOM 1981 CA LEU A 342 100.160 20.731 -17.790 1.00 19.48 A C
ATOM 1982 CB LEU A 342 101.565 21.248 -18.072 1.00 24.80 A C
ATOM 1983 CG LEU A 342 102.622 21.012 -17.005 1.00 24.80 A C
ATOM 1984 CDl LEU A 342 103.972 21.460 -17.523 1.00 24.80 A C
ATOM 1985 CD2 LEU A 342 102.246 21.765 -15.758 1.00 24.80 A C
ATOM 1986 C LEU A 342 - 99.421 20-661 -19.106 1.00 19.48 A C
ATOM 1987 O LEU A 342 99.498 19.656 -19.796 1.00 19.48 A o
ATOM 1988 N ALA A 343 98.709 21.717 -19.459 1.00 12.61 A N
ATOM 1989 CA ALA A 343 97.990 21.736 -20.719 1.00 12.61 A C
ATOM 1990 CB ALA A 343 96.632 22.345 -20.511 1.00 10.00 A C
ATOM 1991 C ALA A 343 98.801 22.576 -21.703 1.00 12.61 A C
ATOM 1992 O ALA A 343 99.251 23.670 -21.348 1.00 12.61 A O
ATOM 1993 N CYS A 344 99.013 22.085 -22.923 1.00 10.81 A N
ATOM 1994 CA CYS A 344 99.779 22.870 -23.895 1.00 10.81 A C
ATOM 1995 C CYS A 344 98.902 23.455 -25.000 1.00 10.81 A C
ATOM 1996 O CYS A 344 98.006 22.792 -25.522 1.00 10.81 A O
ATOM 1997 CB CYS A 344 100.881 22.031 -24.517 1.00 38.94 A C
ATOM 1998 SG CYS A 344 102.066 21.336 -23.331 1.00 38.94 A S
ATOM 1999 N TRP A 345 99.176 24.700 -25.366 1.00 20.07 A N
ATOM 2000 CA TRP A 345- 98.399 25.387 -26.385 1.00 20.07 A C
ATOM 2001 CB TRP A 345 98.048 26.786 -25.885 1.00 61.04 A C
ATOM 2002 CG TRP A 345 96.733 27.270 -26.346 1.00 61.04 A C
ATOM 2003 CD2 TRP A 345 95.453 26.914 -25.806 1.00 61.04 A C
ATOM 2004 CE2 TRP A 345 94.478 27.619 -26.545 1.00 61.04 A - C
ATOM 2005 CE3 TRP A 345 95.034 26.069 -24.767 1.00 61.04 A C
ATOM 2006 CDl TRP A 345 96.493 28.144 -27.362 1.00 61.04 A C
ATOM 2007 NEl TRP A 345 95.141 28.361 -27.489 1.00 61.04 A N ATOM 2008 CZ2 TRP A 345 93.105 27.504 -26.281 1.00 61.04 A C
ATOM 2009 CZ3 TRP A 345 93.667 25.953 -24 .504 1.00 61.04 A C
ATOM 2010 CH2 TRP A 345 92.721 26.670 -25 .261 1.00 61.04 A C
ATOM 2011 C TRP A 345 99.189 25.472 -27 .683 1.00 20.07 A C
ATOM 2012 O TRP A 345 100.379 25.789 -27 .671 1.00 20.07 A O
ATOM 2013 N THR A 346 98.514 25.199 -28 .797 1.00 31.99 A N
ATOM 2014 CA THR A 345 99.135 25.214 -30 .119 1.00 31.99 A C
ATOM 2015 CB THR A 346 98.610 24.048 -30 .966 1.00 63.74 A C
ATOM 2016 OGl THR A 346 98.761 22.830 -30 .233 1.00 63.74 A O
ATOM 2017 CG2 THR A 346 99.380 23.937 -32 .270 1.00 63.74 A C
ATOM 2018 C THR A 346 98.891 26.505 -30 .894 1.00 31.99 A C
ATOM 2019 O THR A 346 99.394 26.673 -32 .003 1.00 31.99 A O
ATOM 2020 N ASN A 347 98.129 27.'421 -30 .309 1.00 47.34 A N
ATOM 2021 CA ASW A 347 97.811 28.673 -30 .983 1.00 47.34 A C
ATOM 2022 CB ASN A 347 96.292 28.847 -31 .031 1.00 77.27 A C
ATOM 2023 CG ASN A 347 95.867 30.077 -31 .798 1.00 77.27 A C
ATOM 2024 ODl ASN A 347 95.899 31.189 -31 .279 1.00 77.27 A O
ATOM 2025 ND2 ASN A 347 95.471 29.883 -33 .049 1.00 77.27 A N
ATOM 2026 C ASN A 347 98.462 29.889 -30 .338 1.00 47.34 A C
ATOM 2027 O ASN A 347 98.833 29.857 -29 .167 1.00 47.34 A O
ATOM 2028 N SER A 348 98.599 30.959 -31 .113 1.00 36.72 A N
ATOM 2029 CA SER A 348 99.208 32.196 -30 .626 1.00 36.72 A C
ATOM 2030 CB SER A 348 99.477 33.140 -31 .800 1.00 49.88 A C
ATOM 2031 OG SER A 348 98.267 33.517 -32 .437 1.00 49.88 A O
ATOM 2032 C SER A 348 98.334 32.921 -29 .599 1.00 36.72 A C
ATOM 2033 O SER A 348 98.820 33.753 -28 .829 1.00 36.72 A O
ATOM 2034 N GLU A 349 97.043 32.605 -29 .598 1.00 28.54 A N
ATOM 2035 CA GLU A 349 96.095 33.230 -28 .688 1.00 28.54 A C
ATOM 2036 CB GLU A 349 94.679 33.138 -29 .269 1.00 90.00 A C
ATOM 2037 CG GLU A 349 93.661 34.075 -28 .626 1.00 90.00 A C
ATOM 2038 CD GLU A 349 93.715 35.483 -29 .200 1.00 90.00 A C
ATOM 2039 OEl GLU A 349 94.810 36.090 -29 .194 1.00 90.00 A O
ATOM 2040 OE2 GLU A 349 92.660 35.979 -29 .657 1.00 90.00 A O
ATOM 2041 C GLU A 349 96.133 32.536 -27 .334 1.00 28.54 A C
ATOM 2042 O GLU A 349 96.063 31.309 -27 .259 1.00 28.54 A O
ATOM 2043 N THR A 350 96.246 33.320 -26 .265 1.00 17.77 A N
ATOM 2044 CA THR A 350 96.268 32.760 -24 .917 1.00 17.77 A C
ATOM 2045 CB THR A 350 96.813 33.773 -23 .887 1.00 47.56 A C
ATOM 2046 OGl THR A 350 95.909 34.878 -23 .769 1.00 47.56 A O
ATOM 2047 CG2 THR A 350 98.176 34.291 -24 .325 1.00 47.56 A C
ATOM 2048 C THR A 350 94.849 32.373 -24 .517 1.00 17.77 A C ATOM 2049 O THR A 350 93.878 32.984 -24.952 1.00 17.77 A O
ATOM 2050 N PRO A 351 94.713 31.357 -23.669 1.00 26.71 A N
ATOM 2051 CD PRO A 351 95.797 30.536 -23.101 1.00 44.86 A C
ATOM 2052 CA PRO A 351 93.413 30.876 -23.203 1.00 26.71 A C
ATOM 2053 CB PRO A 351 93.709 29.435 -22.867 1.00 44.86 A C
ATOM 2054 CG PRO A 351 95.037 29.585 -22.167 1.00 44.86 A C
ATOM 2055 C PRO A 351 92.923 31.617 -21.969 1.00 26.71 A C
ATOM 2056 O PRO A 351 92.074 31.107 -21.241 1.00 26.71 A O
ATOM 2057 N TRP A 352 93.445 32.810 -21.721 1.00 14.06 A N
ATOM 2058 CA TRP A 352 93.040 33.526 -20.521 1.00 14.06 A C
ATOM 2059 CB TRP A 352 94.045 34.625 -20.196 1.00 16.13 A C
ATOM 2060 CG TRP A 352 95.367 34.096 -19.746 1.00 16.13 A C
ATOM 2061 CD2 TRP A 352 96.654 34.622 -20.070 1.00 16.13 A C
ATOM 2062 CE2 TRP A 352 97.609 33.848 -19.372 1.00 16.13 A C
ATOM 2063 CE3 TRP A 352 97.095 35.674 -20.878 1.00 16.13 A C
ATOM 2064 CDl TRP A 352 95.582 33.055 -18.894 1.00 16.13 A C
ATOM 2065 NEl TRP A 352 96.927 32.899 -18.661 1.00 16.13 A N
ATOM 2066 CZ2 TRP A 352 98.985 34.092 -19.457 1.00 16.13 A C
ATOM 2067 CZ3 TRP A 352 98.474 35.922 -20.964 1.00 16.13 A C
ATOM 2068 • CH2 TRP A 352 99.399 35.129 -20.256 1.00 16.13 A C
ATOM 2069 C TRP A 352 91.639 34.102 -20.542 1.00 14.06 A C
ATOM 2070 O TRP A 352 90.918 34.031 -19.550 1.00 14.06 A o
ATOM 2071 N SER A 353 91.244 34.668 -21.669 1.00 38.81 A N
ATOM 2072 CA SER A 353 89.919 35.261 -21.771 1.00 38.81 A C
ATOM 2073 CB SER A 353 89.734 35.840 -23.176 1.00 52.74 A C
ATOM 2074 OG SER A 353 90.297 34.978 -24.152 1.00 52.74 A O
ATOM 2075 C SER A 353 88.768 34.302 -21.437 1.00 38.81 A C
ATOM 2076 O SER A 353 87.624 34.739 -21.274 1.00 38.81 A o
ATOM 2077 N TYR A 354 89.065 33.010 -21.303 1.00 29.32 A N
ATOM 2078 CA TYR A 354 88.016 32.033 -21.026 1.00 29.32 A C
ATOM 2079 CB TYR A 354 88.242 30.784 -21.881 1.00 53.56 A C
ATOM 2080 CG TYR A 354 88.377 31.118 -23.349 1.00 53.56 A C
ATOM 2081 CDl TYR A 354 89.543 31.707 -23.840 1.00 53.56 A C
ATOM 2082 CEl TYR A 354 89.648 32.102 -25.171 1.00 53.56 A C
ATOM 2083 CD2 TYR A 354 87.315 30.923 -24.233 1.00 53.56 A C
ATOM 2084 CE2 TYR A 354 87.408 31.314 -25.570 1.00 53.56 A C
ATOM 2085 CZ TYR A 354 88.577 31.906 -26.030 1.00 53.56 A C
ATOM 2086 OH TYR A 354 88.682 32.321 -27.339 1.00 53.56 A o
ATOM 2087 C TYR A 354 87.829 31.652 -19.563 1.00 29.32 A C
ATOM 2088 o TYR A 354 86.892 30.937 -19.223 1.00 29.32 A o
ATOM 2089 N PHE A 355 88.707 32.147 -18.698 1.00 17.58 A N ATOM 2090 CA PHE A 355 88.633 31.870 -17.267 1.00 17.58 A C
ATOM 2091 CB PHE A 355 90.011 31.509 -16.744 1. 00 24.58 A C
ATOM 2092 CG PHE A 355 90.537 30.228 -17.291 1. 00 24.58 A C
ATOM 2093 CDl PHE A 355 90.293 29.030 -16.634 1. 00 24.58 A C
ATOM 2094 CD2 PHE A 355 91.230 30.210 -18.494 1. 00 24.58 A C
ATOM 2095 CEl PHE A 355 90.726 27.833 -17.166 1. 00 24.58 A C
ATOM 2096 CΞ2 PHE A 355 91.668 29.020 -19.037 1. 00 24.58 A C
ATOM 2097 CZ PHE A 355 91.415 27.824 -18.372 1. 00 24.58 A C
ATOM 2098 C PHE A 355 88.113 33.070 -16.494 1. 00 17.58 A C
ATOM 2099 O PHE A 355 88.254 34.212 -16.925 1. 00 17.58 A O
ATOM 2100 N PRO A 356 87.518 32.823 -15.325 1. 00 10.90 A N
ATOM 2101 CD PRO A 356 87.223 31.479 -14.805 1. 00 10.00 A C
ATOM 2102 CA PRO A 356 86.956 33.843 -14.439 1. 00 10.90 A C
ATOM 2103 CB PRO A 356 85.931 33.055 -13.654 1. 00 10.00 A C
ATOM 2104 CG PRO A 356 86.657 31.782 -13.433 1. 00 10.00 A C
ATOM 2105 C PRO A 356 88.004 34.445 -13.514 1. 00 10.90 A C
ATOM 2106 O PRO A 356 89.079 33.886 -13.362 1. 00 10.90 A O
ATOM 2107 N LYS A 357 87.690 35.585 -12.906 1. 00 12.25 A N
ATOM 2108 CA LYS A 357 88.600 36.214 -11.955 1. 00 12.25 A C
ATOM 2109 CB LYS A 357 88.249 37.677 -11.719 1. 00 19.75 A C
ATOM 2110 CG LYS A 357 88.298 38.557 -12.939 1. 00 19.75 A C
ATOM 2111 CD LYS A 357 88.013 39.999 -12.551 1. 00 19.75 A C
ATOM 2112 CE LYS A 357 88.195 40.938 -13.728 1. 00 19.75 A C
ATOM 2113 NZ LYS A 357 87.940 42.358 -13.355 1. 00 19.75 A N
ATOM 2114 C LYS A 357 88.374 35.477 -10.648 1. 00 12.25 A C
ATOM 2115 O LYS A 357 87.359 34.798 -10.489 1. 00 12.25 A O
ATOM 2116 N ILE A 358 89.307 35.601 -9.714 1. 00 11.54 A N
ATOM 2117 CA ILE A 358 89.155 34.951 -8.419 1. 00 11.54 A C
ATOM 2118 CB ILE A 358 90.154 33.800 -8.235 1. 00 10.00 A C
ATOM 2119 CG2 ILE A 358 90.081 33.283 -6.810 1. 00 10.00 A C
ATOM 2120 CGl ILE A 358 89.856 32.678 -9.232 1. 00 10.00 A C
ATOM 2121 CDl ILE A 358 90.833 31.527 -9.154 1. 00 10.00 A C
ATOM 2122 C ILE A 358 89.415 36.006 -7.365 1. 00 11.54 A C
ATOM 2123 O ILE A 358 90.450 36.678 -7.396 1. 00 11.54 A O
ATOM 2124 N SER A 359 88.478 36.164 -6.436 1. 00 12.14 A N
ATOM 2125 CA SER A 359 88.637 37.172 -5.403 1. 00 12.14 A C
ATOM 2126 CB SER A 359 87.591 38.254 -5.579 1. 00 36.81 A C
ATOM 2i27 OG SER A 359 87.766 38.888 -6.826 1. 00 36.81 A O
ATOM 2i28 C SER A 359 88.557 36.638 -3.994 1. 00 12.14 A C
ATOM 2129 O SER A 359 87.787 35.717 -3.707 1. 00 12.14 A O
ATOM 2130 N ILE A 360 89.357 37.235 -3.116 1. 00 10.00 A M ATOM 2131 CA ILE A 360 89.395 36.855 -1.711 1.00 10.00 A C
ATOM 2132 CB ILE A 360 90.787 36.380 -1.313 1.00 10.00 A C
ATOM 2133 CG2 ILE A 360 90.847 36.158 0.180 1.00 10.00 A C
ATOM 2134 CGl ILE A 360 91.127 35.099 -2.058 1.00 10.00 A C
ATOM 2135 CDl ILE A 360 92.533 34.662 -1.846 1.00 10.00 A C
ATOM 2136 C ILE A 360 89.059 38.059 -0.846 1.00 10.00 A C
ATOM 2137 O ILE A 360 89.710 39.091 -0.952 1.00 10.00 A o
ATOM 2138 N TYR A 361 88.047 37.939 0.004 1.00 11.82 A N
ATOM 2139 CA TYR A 361 87.688 39.048 0.877 1.00 11.82 A C
ATOM 2140 CB TYR A 361 86.176 39.122 1.086 1.00 15.89 A C
ATOM 2141 CG TYR A 361 85.398 39.644 -0.097 1.00 15.89 A C
ATOM 2142 CDl TYR A 361 85.130 38.833 -1.190 1.00 15.89 A C
ATOM 2143 CEl TYR A 361 84.418 39.308 -2.282 1.00 15.89 A C
ATOM 2144 CD2 TYR A 361 84.932 40.953 -0.125 1.00 15.89 A C
ATOM 2145 CE2 TYR A 361 84.219 41.440 -1.214 1.00 15.89 A C
ATOM 2146 CZ TYR A 361 83.968 40.606 -2.287 1.00 15.89 A C
ATOM 2147 OH TYR A 361 83.263 41.062 -3.370 1.00 15.89 A O
ATOM 2148 C TYR A 361 88.358 38.903 2.237 1.00 11.82 A C
ATOM 2149 O TYR A 361 88.249 37.857 2.883 1.00 11.82 A O
ATOM 2150 N LEU A 362 89.049 39.955 2.665 1.00 20.28 A N
ATOM 2151 CA LEU A 362 89.722 39.967 3.962 1.00 20.28 A C
ATOM 2152 CB LEU A 362 91.216 40.234 3.781 1.00 10.00 A C
ATOM 2153 CG LEU A 362 91.963 39.269 2.859 1.00 10.00 A C
ATOM 2154 CDl LEU A 362 93.423 39.656 2.814 1.00 10.00 A C
ATOM 2155 CD2 LEU A 362 91.806 37.840 3.355 1.00 10.00 A C
ATOM 2156 C LEU A 362 89.095 41.060 4.830 1.00 20.28 A C
ATOM 2157 O LEU A 362 88.750 42.140 4.340 1.00 20.28 A o
ATOM 2158 N ARG A 363 88.939 40.788 6.118 1.00 10.00 A N
ATOM 2159 CA ARG A 363 88.333 41.775 7.000 1.00 10.00 A C
ATOM 2160 CB ARG A 363 88.038 41.153 8.355 1.00 23.08 A C
ATOM 2161 CG ARG A 363 87.290 42.076 9.279 1.00 23.08 A C
ATOM 2162 CD ARG A 363 86.988 41.409 10.612 1.00 23.08 A C
ATOM 2163 NE ARG A 363 86.127 40.230 10.490 1.00 23.08 A N
ATOM 2164 CZ ARG A 363 84.832 40.266 10.189 1.00 23.08 A C
ATOM 2165 NHl ARG A 363 84.219 41.425 9.966 1.00 23.08 A N
ATOM 2166 NH2 ARG A 363 84.142 39.135 10.132 1.00 23.08 A N
ATOM 2167 C ARG A 363 89.255 42.960 7.182 1.00 10.00 A C
ATOM 2168 O ARG A 363 90.444 42.787 7.429 1.00 10.00 A o
ATOM 2169 N ASP A 364 88.727 44.169 7.048 1.00 20.10 A N
ATOM 2170 CA ASP A 364 89.563 45.352 7.226 1.00 20.10 A C
ATOM 2171 CB ASP A 364 88.879 46.575 6.638 1.00 34.81 A C ATOM 2172 CG ASP A 364 89.695 47.823 6.816 1.00 34.81 A C
ATOM 2173 ODl ASP A 364 89.801 48 .309 7.958 1.00 34.81 A O
ATOM 2174 OD2 ASP A 364 90.248 48 .316 5.817 1.00 34.81 A O
ATOM 2175 C ASP A 364 89.796 45 .557 8.715 1.00 20.10 A C
ATOM 2176 O ASP A 364 89.116 44 .937 9.528 1.00 20.10 A O
ATOM 2177 N GLU A 365 90.752 46 .405 9.089 1.00 42.33 A N
ATOM 2178 CA GLU A 365 91.006 46 .643 10.511 1.00 42.33 A C
ATOM 2179 CB GLU A 365 92.124 47 .674 10.703 1.00 29.36 A C
ATOM 2180 CG GLU A 365 93.530 47 .074 10.632 1.00 29.36 A C
ATOM 2181 CD GLU A 365 94.634 48 .079 10.951 1.00 29.36 A C
ATOM 2182 OEl GLU A 365 94.762 49 .089 10.220 1.00 29.36 A O
ATOM 2183 OE2 GLU A 365 95.377 47 .853 11.933 1.00 29.36 A o
ATOM 2184 C GLU A 365 89.737 47 .105 11.228 1.00 42.33 A C
ATOM 2185 O GLU A 365 89.584 46 .917 12.442 1.00 42.33 A o
ATOM 2186 N ASN A 366 88.825 47 .697 10.461 1.00 24.53 A N
ATOM 2187 CA ASN A 366 87.550 48 .181 10.982 1.00 24.53 A C
ATOM 2188 CB ASN A 366 87.203 49 .519 10.323 1.00 72.79 A C
ATOM 2189 CG ASN A 366 85.788 49 .963 10.613 1.00 72.79 A C
ATOM 2190 ODl ASN A 366 85.238 49 .674 11.678 1.00 72.79 A O
ATOM 2191 ND2 ASN A 366 85.190 50 .684 9.668 1.00 72.79 A N
ATOM 2192 C ASN A 366 86.442 47 .148 10.743 1.00 24.53 A C
ATOM 2193 O ASN A 366 85.688 47 .225 9.781 1.00 24.53 A o
ATOM 2194 N SER A 367 86.372 46 .177 11.643 1.00 27.97 A N
ATOM 2195 CA SER A 367 85.398 45 .085 11.606 1.00 27.97 A C
ATOM 2196 CB SER A 367 84.804 44 .903 13.007 1.00 68.19 A C
ATOM 2197 OG SER A 367 85.812 44 .994 14.004 1.00 68.19 A o
ATOM 2198 C SER A 367 84.252 45 .202 10.591 1.00 27.97 A C
ATOM 2199 O SER A 367 84.094 44 .363 9.701 1.00 27.97 A o
ATOM 2200 N SER A 368 83.447 46 .243 10.744 1.00 49.26 A N
ATOM 2201 CA SER A 368 82.302 46 .462 9.875 1.00 49.26 A C
ATOM 2202 CB SER A 368 81.613 47 .774 10.273 1.00 80.35 A C
ATOM 2203 OG SER A 368 82.559 48 .802 10.519 1.00 80.35 A O
ATOM 2204 C SER A 368 82.575 46 .449 8.364 1.00 49.26 A C
ATOM 2205 O SER A 368 81.649 46 .301 7.563 1.00 49.26 A O
ATOM 2206 N ARG A 369 83.834 46 .600 7.970 1.00 24.17 A N
ATOM 2207 CA ARG A 369 84.179 46 .608 6.555 1.00 24.17 A C
ATOM 2208 CB ARG A 369 84.759 47 .959 6.154 1.00 90.00 A C
ATOM 2209 CG ARG A 369 83.820 49 .129 6.305 1.00 90.00 A C
ATOM 2210 CD ARG A 369 84.623 50 .396 6.149 1.00 90.00 A C
ATOM 2211 NE ARG A 369 83.851 51 .605 6.403 1.00 90.00 A N
ATOM 2212 CZ ARG A 369 84.406 52 .790 6.638 1.00 90.00 A C ATOM 2213 NHl ARG A 369 85.729 52.910 6.653 1.00 90.00 A N
ATOM 2214 NH2 ARG A 369 83 .643 53 .853 6 .859 1.00 90.00 A N
ATOM 2215 C ARG A 369 85 .186 45 .524 6 .203 1.00 24.17 A C
ATOM 2216 O ARG A 369 85 .731 44 .856 7 .082 1.00 24.17 A O
ATOM 2217 N SER A 370 8 855. .441199 4 455. .335566 4 .906 1.00 10.55 A N
ATOM 2218 CA SER A 370 8 866. .335588 4 444. .336688 4 .392 1.00 10.55 A C
ATOM 2219 CB SER A 370 8 855. .666644 4 433 ..004400 4 .147 1.00 17.12 A C
ATOM 2220 OG SER A 370 8 844. .669944 4433 ..119922 3 .126 1.00 17.12 A O
ATOM 2221 C SER A 370 8 866. .778866 4444 ..990033 3 .060 1.00 10.55 A C
ATOM 2222 O SER A 370 8 B66. .110066 4455 ..7744--99 2 .503 1.00 10.55 A O
ATOM 2223 N PHE A 371 8 877. .990088 4444 ..442200 2 .550 1.00 10.00 A N
ATOM 2224 CA PHE A 371 8 388 ..337755 4444 ..885533 1 .248 1.00 10.00 A C
ATOM 2225 CB PHE A 371 8 B99 ..666688 4455 ..665522 1 .381 1.00 16.37 A C
ATOM 2226 CG PHE A 371 9 900 ..881133 4444 ..889900 1 .991 1.00 16.37 A C
ATOM 2227 CDl PHE A 371 9 911 ..669988 4444 ..117788 1 .191 1.00 16.37 A C
ATOM 2228 CD2 PHE A 371 9 911 ..003377 4444 ..992277 3 .365 1.00 16.37 A C
ATOM 2229 CEl PHE A 371 9 922 ..779933 4 433 ..551199 1 .754 1.00 16.37 A C
ATOM 2230 CE2 PHE A 371 9 922 ..113322 4444 ..226699 ' 3 .939 1.00 16.37 A C
ATOM 2231 CZ PHE A 371 9 933 ..001100 4433 ..556677 3 .134 1.00 16.37 A C
ATOM 2232 - C PHE A 371 8 388 ..559955 4433 ..556677 0 .497 1.00 10.00 A C
ATOM 2233 O PHE A 371 8 388 ..553333 4422 ..550055 1 .100 1.00 10.00 A O
ATOM 2234 N ARG A 372 8 388 ..881188 4433 ..662211 -0 .806 1.00 13.50 A N
ATOM 2235 CA ARG A 372 8 399 ..003322 4422 ..336688 -1 .508 1.00 13.50 A C
ATOM 2236 CB ARG A 372 8 377 ..776611 4411 ..993333 -2 .239 1.00 25.41 A C
ATOM 2237 CG ARG A 372 8 377 ..668888 4422 ..442222 -3 .666 1.00 25.41 A C
ATOM 2238 CD ARG A 372 8 366 ..440000 4422 ..001199 -4 .354 1.00 25.41 A C
ATOM 2239 NE ARG A 372 8 366 ..223355 4422 ..779933 -5 .581 1..00 25.41 A N
ATOM 2240 CZ ARG A 372 8 355 ..111111 4422. .885577 -6 .281 1.00 25.41 A C
ATOM 2241 NHl ARG A 372 8 344 ..004455 4422. .118844 -5 .876 1.00 25.41 A N
ATOM 2242 NH2 ARG A 372 8 355 ..004488 4 433 ..660055 -7 .375 1.00 25.41 A N
ATOM 2243 C ARG A 372 9 300. .117722 4422. .444499 -2 .499 1.00 13.50 A C
ATOM 2244 O ARG A 372 9 500 ..331122 4433. .444499 -3 .203 1.00 13.50 A O
ATOM 2245 N ILE A 373 9 300. .998877 4411. .339933 -2 .540 1.00 10.66 A N
ATOM 2246 CA ILE A 373 9 322. .110044 4411. .330022 -3 .475 1.00 10.66 A C
ATOM 2247 CB ILE A 373 9 333,. .336666 4400,. .776688 -2 .805 1.00 10.00 A C
ATOM 2248 CG2 ILE A 373 9 333. .888844 4 411. .778822 -1 .819 1.00 10.00 A C
ATOM 2249 CGl ILE A 373 9 333,. .007700 3399,. .444499 -2 .106 1.00 10.00 A C
ATOM 2250 CDl ILE A 373 9 344,. .226699 3388,. .990088 -1 .379 1.00 10.00 A C
ATOM 2251 C ILE A 373 9 311.. .668844 4400.. .335522 -4 .583 1.00 10.66 A C
ATOM 2252 O ILE A 373 9 300,. .995599 3399.. .338844 -4 .343 1.00 10.66 A O
ATOM 2253 N THR A 374 9 322.. .114422 4400.. .662222 -5 .797 1.00 10.24 A N ATOM 2254 CA THR A 374 91.748 39.801 -6.928 1.00 10.24 A C
ATOM 2255 CB THR A 374 90.623 40.483 -7.692 1.00 16.01 A C
ATOM 2256 OGl THR A 374 89.574 40.815 -6.778 1.00 16.01 A O
ATOM 2257 CG2 THR A 374 90.088 39.577 -8.773 1.00 16.01 A C
ATOM 2258 C THR A 374 92.858 39.506 -7.914 1.00 10.24 A C
ATOM 2259 O THR A 374 93.707 40.348 -8.194 1.00 10.24 A O
ATOM 2260 N ILE A 375 92.837 38.302 -8.455 1.00 10.00 A N
ATOM 2261 CA ILE A 375 93.831 37.912 -9.427 1.00 10.00 A C
ATOM 2262 CB ILE A 375 94.645 36.731 -8.919 1.00 10.00 A C
ATOM 2263 CG2 ILE A 375 95.584 37.180 -7.830 1.00 10.00 A C
ATOM 2264 CGl ILE A 375 93.688 35.651 -8.416 1.00 10.00 A C
ATOM 2265 CDl ILE A 375 94.334 34.331 -8.148 1.00 10.00 A C
ATOM 2266 C ILE A 375 93.118 37.480 -10.697 1.00 10.00 A C
ATOM 2267 O ILE A 375 92.130 36.752 -10.637 1.00 10.00 A O
ATOM 2268 N LEU A 376 93.596 37.930 -11.848 1.00 13.35 A N
ATOM 2269 CA LEU A 376 92.983 37.505 -13.099 1.00 13.35 A C
ATOM 2270 CB LEU A 376 93.244 38.541 -14.187 1.00 16.28 A C
ATOM 2271 CG LEU A 376 92.842 39.963 -13.798 1.00 16.28 A C
ATOM 2272 CDl LEU A 376 93.106 40.908 -14.961 1.00 16.28 A C
ATOM 2273 CD2- LEU A 376 91.385 39.985 -13.408 1.00 16.28 A C
ATOM 2274 C LEU A 376 93.622 36.162 -13.475 1.00 13.35 A C
ATOM 2275 O LEU A 376 94.613 35.752 -12.874 1.00 13.35 A o
ATOM 2276 N PRO A 377 93.070 35.457 -14.470 1.00 10.35 A N
ATOM 2277 CD PRO A 377 91.900 35.771 -15.299 1.00 24.79 A C
ATOM 2278 CA PRO A 377 93.650 34.165 -14.856 1.00 10.35 A C
ATOM 2279 CB PRO A 377 92.737 33.702 -15.993 1.00 24.79 A C
ATOM 2280 CG PRO A 377 92.196 34.972 -16.539 1.00 24.79 A C
ATOM 2281 C PRO A 377 95.135 34.152 -15.241 1.00 10.35 A C
ATOM 2282 O PRO A 377 95.795 33.113 -15.164 1.00 10.35 A o
ATOM 2283 N GLN A 378 95.682 35.284 -15.655 1.00 20.06 A N
ATOM 2284 CA GLN A 378 97.091 35.274 -16.005 1.00 20.06 A C
ATOM 2285 CB GLN A 378 97.555 36.641 -16.497 1.00 32.98 A C
ATOM 2286 CG GLN A 378 97.038 36.996 -17.863 1.00 32.98 A C
ATOM 2287 CD GLN A 378 95.643 37.581 -17.829 1.00 32.98 A C
ATOM 2288 OEl GLN A 378 94.747 37.070 -17.142 1.00 32.98 A o
ATOM 2289 NE2 GLN A 378 95.445 38.662 -18.582 1.00 32.98 A N
ATOM 2290 C GLN A 378 97.910 34.871 -14.789 1.00 20.06 A C
ATOM 2291 O GLN A 378 99.026 34.380 -14.917 1.00 20.06 A O
ATOM 2292 KT LEU A 379 97.359 35.058 -13.600 1.00 12.95 A N
ATOM 2293 CA LEU A 379 98.103 34.706 -12.412 1.00 12.95 A C
ATOM 2294 CB LEU A 379 97.805 35.686 -11.283 1.00 15.99 A C ATOM 2295 CG LEU A 379 98.218 37.135 -11.513 1.00 15.99 A C ATOM 2296 CDl LEU A 379 98.127 37.879 -10.199 1.00 15.99 A C ATOM 2297 CD2 LEU A 379 99.631 37.198 -12.043 1.00 15.99 A C ATOM 2298 C LEU A 379 97.880 33.296 -11.908 1.00 12.95 A C ATOM 2299 O LEU A 379 98.670 32.820 -11.096 1.00 12.95 A O ATOM 2300 N TYR A 380 96.826 32.620 -12.361 1.00 12.16 A N ATOM 2301 CA TYR A 380 96.590 31.262 -11.880 1.00 12.16 A C ATOM 2302 CB TYR A 380 95..373 31.224 -10.946 1.00 14.36 A C
ATOM 2303 CG TYR A 380 94..023 31.310 -11.601 1.00 14.36 A C ATOM 2304 CDl TYR A 380 93..421 30.181 -12.140 1.00 14.36 A C ATOM 2305 CEl TYR A 380 92..141 30.237 -12.674 1.00 14.36 A C ATOM 2306 CD2 TYR A 380 93..314 32.512 -11.623 1.00 14.36 A C ATOM 2307 CE2 TYR A 380 92..034 32.585 -12.158 1.00 14.36 A C ATOM 2308 CZ TYR A 380 91..451 31.440 -12.678 1.00 14.36 A C ATOM 2309 OH TYR A 380 90..168 31.486 -13.178 1.00 14.36 A o ATOM 2310 C TYR A 380 96..497 30.189 -12.958 1.00 12..16 A C ATOM 2311 O TYR A 380 96..251 29.024 -12.669 1.00 12..16 A o ATOM 2312 N ILE A 381 96..676 30.596 -14.205 1.00 14..31 A N ATOM 2313 CA ILE A 381 96..727 29.669 -15.332 1.00 14..31 A C ATOM 2314 CB ILE A 381 - 95..656 29.958 -16.384 1.00 10..00 A C ATOM 2315 CG2 ILE A 381 95..822 29.010 -17.551 1.00 10..00 A C ATOM 2316 CGl ILE A 381 94..266 29.766 -15.786 1.00 10..00 A C ATOM 2317 CDl ILE A 381 93..940 28.344 -15.491 1.00 10..00 A C ATOM 2318 C ILE A 381 98..096 30.104 -15.842 1.00 14..31 A C ATOM 2319 O ILE A 381 98..219 30.829 -16.829 1.00 14..31 A o ATOM 2320 N GLN A 382 99..113 29.681 -15.093 1.00 25..48 A N ATOM 2321 CA GLN A 382 100..514 30.024 -15.318 1.00 25..48 A C ATOM 2322 CB GLN A 382 101..274 29.792 -14.011 1.00 31..95 A C ATOM 2323 CG GLN A 382 100..499 30.311 -12.790 1.00 31..95 A C ATOM 2324 CD GLN A 382 100..960 29.707 -11.475 1.00 31..95 A C ATOM 2325 OEl GLN A 382 101..292 28.526 -11.410 1.00 31..95 A o ATOM 2326 NE2 GLN A 382 100..961 30.513 -10.415 1.00 31..95 A N ATOM 2327 C GLN A 382 101.179 29.276 -16.458 1.00 25..48 A C ATOM 2328 O GLN A 382 101.120 28.051 -16.528 1.00 25..48 A O ATOM 2329 N PRO A 383 101.829 30.014 -17.372 1.00 20..39 A N ATOM 2330 CD PRO A 383 101.742 31.479 -17.451 1.00 10..00 A C ATOM 2331 CA PRO A 383 102.531 29.483 -18.544 1.00 20..39 A C ATOM 2332 CB PRO A 383 102.540 30.672 -19.486 1.00 10..00 A C ATOM 2333 CG PRO A 383 102.712 31.792 -18.557 1.00 10.00 A C ATOM 2334 C PRO A 383 103.939 28.950 -18.285 1.00 20.39 A C ATOM 2335 O PRO A 383 104.625 29.393 -17.366 1.00 20.39 A O ATOM 2336 N MET A 384 104.347 27.996 --19.119 1.00 18.85 A N
ATOM 2337 CA MET A 384 105.654 27.351 -19.053 1 .00 18.85 A C
ATOM 2338 CB MET A 384 105.511 25.907 -18.579 1 .00 49.90 A C
ATOM 2339 CG MET A 384 104.788 25.731 -17.267 1 .00 49.90 A C
ATOM 2340 SD MET A 384 105.905 25.606 -15.864 1 .00 49.90 A S
ATOM 2341 CE MET A 384 106.158 23.823 -15.784 1 .00 49.90 A C
ATOM 2342 C MET A 384 106.233 27.332 -20.471 1 .00 18.85 A C
ATOM 2343 O MET A 384 105.482 27.342 -21.458 1 .00 18.85 A O
ATOM 2344 N MET A 385 107.563 27.280 -20.559 1 .00 31.18 A N
ATOM 2345 CA MET A 385 108.282 27.257 -21.833 1 .00 31.18 A C
ATOM 2346 CB MET A 385 109.708 26.724 -21.633 1 .00 76.66 A C
ATOM 2347 CG MET A 385 110.548 26.609 -22.917 1 .00 76.66 A C
ATOM 2348 SD MET A 385 111.079 28.182 -23.663 1 .00 76.66 A S
ATOM 2349 CE MET A 385 109.780 28.468 -24.894 1 .00 76.66 A C
ATOM 2350 C MET A 385 107.559 26.399 -22.855 1 .00 31.18 A C
ATOM 2351 O MET A 385 107.127 25.289 -22.551 1 .00 31.18 A O
ATOM 2352 N GLY A 386 107.448 26.931 -24.070 1 .00 55.08 A N
ATOM 2353 CA GLY A 386 106.770 26.243 -25.151 1 .00 55.08 A C
ATOM 2354 C GLY A 386 107.225 24.837 -25.478 1 .00 55.08 A C
ATOM 2355 O GLY A 386 106.563 23.869 -25.115 1 .00 55.08 A O
ATOM 2356 N ALA A 387 108.350 24.721 -26.172 1 .00 22.65 A N
ATOM 2357 CA ALA A 387 108.883 23.421 -26.581 1 .00 22.65 A C
ATOM 2358 CB ALA A 387 109.070 22.520 -25.381 1 .00 37.06 A C
ATOM 2359 C ALA A 387 107.994 22.729 -27.618 1 .00 22.65 A C
ATOM 2360 O ALA A 387 106.767 22.692 -27.497 1 .00 22.65 A O
ATOM 2361 N GLY A 388 108.636 22.183 -28.644 1 .00 27.08 A N
ATOM 2362 CA GLY A 388 107.917 21.501 -29.701 1 .00 27.08 A C
ATOM 2363 C GLY A 388 107.198 22.465 -30.619 1 .00 27.08 A C
ATOM 2364 O GLY A 388 107.710 23.519 -30.988 1 .00 27.08 A o
ATOM 2365 N LEU A 389 105.982 22.089 -30.973 1 .00 21.57 A N
ATOM 2366 CA LEU A 389 105.141 22.868 -31.861 1 .00 21.57 A C
ATOM 2367 CB LEU A 389 104.456 21.896 -32.814 1 .00 47.39 A C
ATOM 2368 CG LEU A 389 103.444 22.338 -33.856 1 .00 47.39 A C
ATOM 2369 CDl LEU A 389 104.102 23.173 -34.957 1 .00 47.39 A C
ATOM 2370 CD2 LEU A 389 102.822 21.076 -34.421 1 .00 47.39 A C
ATOM 2371 C LEU A 389 104.106 23.653 -31.047 1 .00 21.57 A C
ATOM 2372 o LEU A 389 103.153 24.210 -31.599 1 .00 21.57 A o
ATOM 2373 N ASN A 390 104.306 23.684 -29.728 1 .00 31.10 A N
ATOM 2374 CA ASN A 390 103.406 24.380 -28.809 1 .00 31.10 A C
ATOM 2375 CB ASN A 390 103.257 23.595 -27.506 1 .00 33.25 A C
ATOM 2376 CG ASN A 390 102.689 22.202 -27.711 1 .00 33.25 A C ATOM 2377 ODl ASW A 390 101.530 22.030 -28.108 1.00 33.25 A O
ATOM 2378 ND2 ASN A 390 103.506 21.192 -27.427 1.00 33 .25 A N
ATOM 2379 C ASN A 390 103.950 25.752 -28.458 1.00 31 .10 A C
ATOM 2380 O ASN A 390 105.151 25.910 -28.280 1.00 31 .10 A O
ATOM 2381 N TYR A 391 103.083 26.749 -28.350 1.00 31 .41 A N
ATOM 2382 CA TYR A 391 103.572 28.062 -27.980 1.00 31 .41 A C
ATOM 2383 CB TYR A 391 102.503 29.119 -28.170 1.00 19 .64 A C
ATOM 2384 CG TYR A 391 102.438 29.580 -29.594 1.00 19 .64 A C
ATOM 2385 CDl TYR A 391 102.039 28.706 -30.610 1.00 19 .64 A C
ATOM 2386 CEl TYR A 391 102.013 29.117 -31.946 1.00 19 .64 A C
ATOM 2387 CD2 TYR A 391 102.810 30.878 -29.941 1.00 19 .64 A C
ATOM 2388 CE2 TYR A 391 102.788 31.303 -31.263 1.00 19 .64 A C
ATOM 2389 CZ TYR A 391 102.390 30.420 -32.267 1.00 19 .64 A C
ATOM 2390 OH TYR A 391 102.372 30.840 -33.585 1.00 19 .64 A o
ATOM 2391 C TYR A 391 104.002 27.991 -26.537 1.00 31 .41 A C
ATOM 2392 O TYR A 391 105.066 28.502 -26.175 1.00 31 .41 A o
ATOM 2393 N GLU A 392 103.172 27.355 -25.717 1.00 20 .20 A N
ATOM 2394 CA GLU A 392 103.491 27.160 -24.308 1.00 20 .20 A C
ATOM 2395 CB GLU A 392 103.496 28.477 -23.528 1.00 51 .39 A C
ATOM 239~6 : CG GLU A 392 102.225 29.272 -23.606 1.00 51 .39 A C
ATOM 2397 CD GLU A 392 102.279 30.310 -24.696 1.00 51 .39 A C
ATOM 2398 OEl GLU A 392 103.249 31.101 -24.703 1.00 51 .39 A O
ATOM 2399 OE2 GLU A 392 101.355 30.340 -25.538 1.00 51 .39 A o
ATOM 2400 C GLU A 392 102.537 26.189 -23.649 1.00 20 .20 A C
ATOM 2401 o GLU A 392 101.545 25.765 -24.240 1.00 20 .20 A O
ATOM 2402 N CYS A 393 102.865 25.820 -22.421 1.00 16 .36 A N
ATOM 2403 CA CYS A 393 102.039 24.907 -21.670 1.00 16 .36 A C
ATOM 2404 C CYS A 393 101.681 25.622 -20.373 1.00 16 .36 A C
ATOM 2405 O CYS A 393 102.427 26.477 -19.899 1.00 16 .36 A o
ATOM 2406 CB CYS A 393 102.816 23.622 -21.416 1.00 37 .03 A C
ATOM 2407 SG CYS A 393 103.425 22.812 -22.939 1.00 37 .03 A S
ATOM 2408 N TYR A 394 100.534 25.291 -19.799 1.00 11 .14 A N
ATOM 2409 CA TYR A 394 100.105 25.963 -18.586 1.00 11 .14 A C
ATOM 2410 CB TYR A 394 98.815 26.731 -18.843 1.00 15 .24 A C
ATOM 2411 CG TYR A 394 98.855 27.678 -20.008 1.00 15 .24 A C
ATOM 2412 CDl TYR A 394 98.567 27.243 -21.294 1.00 15 .24 A C
ATOM 2413 CEl TYR A 394 98.581 28.131 -22.371 1.00 15 .24 A C
ATOM 2414 CD2 TYR A 394 99.162 29.020 -19.821 1.00 15 .24 A C
ATOM 2415 CE2 TYR A 394 99.181 29.916 -20.887 1.00 15 .24 A C
ATOM 2416 CZ TYR A 394 98.890 29.467 -22.157 1.00 15 .24 A C
ATOM 2417 OH TYR A 394 98.921 30.351 -23.207 1.00 15 .24 A O ATOM 2418 C TYR A 394 99.842 25.026 -17.442 1.00 11.14 A C
ATOM 2419 O TYR A 394 99 .357 23.922 -17.651 1. 00 11. 14 A O
ATOM 2420 N ARG A 395 100 .146 25.481 -16.231 1. 00 10. 00 A N
ATOM 2421 CA ARG A 395 99 .878 24.705 -15.030 1. 00 10. 00 A C
ATOM 2422 CB ARG A 395 101 .138 24.545 -14.185 1. 00 39. 77 A C
ATOM 2423 CG ARG A 395 101 .727 25.834 -13.702 1. 00 39. 77 A C
ATOM 2424 CD ARG A 395 102 .838 25.584 -12.698 1. 00 39. 77 A C
ATOM 2425 NE ARG A 395 103 .303 26.831 -12.091 1. 00 39. 77 A N
ATOM 2426 CZ ARG A 395 104 .144 27.684 -12.674 1. 00 39. 77 A C
ATOM 2427 NHl ARG A 395 104 .625 27.418 -13.885 1. 00 39. 77 A N
ATOM 2428 NH2 ARG A 395 104 .494 28.811 -12.054 1. 00 39. 77 A N
ATOM 2429 C ARG A 395 98 .800 25.435 -14.228 1. 00 10. 00 A C
ATOM 2430 O ARG A 395 98 .609 26.636 -14.379 1. 00 10. 00 A O
ATOM 2431 N PHE A 396 98 .071 24.703 -13.400 1. 00 10. 00 A W
ATOM 2432 CA PHE A 396 97 .029 25.294 -12.574 1. 00 10. 00 A C
ATOM 2433 CB PHE A 396 96 .020 24.223 -12.182 1. 00 10. 92 A C
ATOM 2434 CG PHE A 396 94 .794 24.753 -11.496 1. 00 10. 92 A C
ATOM 2435 CDl PHE A 396 94 .108 25.849 -12.018 1. 00 10. 92 A C
ATOM 2436 CD2 PHE A 396 94 .280 24.110 -10.369 1. 00 10. 92 A C
ATOM 2437 CEl PHE A 396 92 .932 26.290 -11.432 1. 00 10. 92 A C
ATOM 2438 CE2 PHE A 396 93 .102 24.545 -9.776 1. 00 10. 92 A C
ATOM 2439 CZ PHE A 396 92 .426 25.635 -10.309 00 10. 92 A C
ATOM 2440 C PHE A 396 97 .704 25.848 -11.327 1. 00 10. 00 A C
ATOM 2441 O PHE A 396 98 .377 25.118 -10.606 1. 00 10. 00 A O
ATOM 2442 N GLY A 397 97 .531 27.137 -11.074 1. 00 14. 24 A N
ATOM 2443 CA GLY A 397 98 .159 27.747 -9.916 1. 00 14. 24 A C
ATOM 2444 C GLY A 397 97 .426 27.561 -8.600 1. 00 14. 24 A C
ATOM 2445 O GLY A 397 97 .672 28.296 -7.643 1. 00 14. 24 A O
ATOM 2446 N ILE A 398 96 .520 26.595 -8.538 1. 00 10. 00 A N
ATOM 2447 CA ILE A 398 95 .795 26.365 -7.309 1. 00 10. 00 A C
ATOM 2448 CB ILE A 398 94 .332 26.731 -7.447 1. 00 11. 81 A C
ATOM 2449 CG2 ILE A 398 93 .688 26.735 -6.087 1. 00 11. 81 A C
ATOM 2450 CGl ILE A 398 94 .203 28.124 -8.054 1. 00 11. 81 A C
ATOM 2451 CDl ILE A 398 92 .764 28.595 -8.211 1. 00 11. 81 A C
ATOM 2452 C ILE A 398 95 .911 24.905 -6.930 1. 00 10. 00 A C
ATOM 2453 O ILE A 398 95 .714 24.014 -7.755 1. 00 10. 00 A O
ATOM 2454 N SER A 399 96 .237 24.667 -5.669 1. 00 21. 53 A N
ATOM 2455 CA SER A 399 96 .422 23.321 -5.154 1. 00 21. 53 A C
ATOM 2456 CB SER A 399 97 .892 23.144 -4.764 1. 00 22. 13 A C
ATOM 2457 OG SER A 399 98 .076 22.063 -3.871 1. 00 22. 13 A O
ATOM 2458 C SER A 399 95 .529 23.095 -3.943 1. 00 21. 53 A C ATOM 2459 O SER A 399 95.233 24.027 -3.202 1.00 21.53 A O
ATOM 2460 N PRO A 400 95.084 21.854 -3.725 1.00 15.83 A N
ATOM 2461 CD PRO A 400 95.275 20.684 -4.592 1.00 10.00 A C
ATOM 2462 CA PRO A 400 94.222 21.509 -2.592 1.00 15.83 A C
ATOM 2463 CB PRO A 400 93.538 20.260 -3.077 1.00 10.00 A C
ATOM 2464 CG PRO A 400 94.698 19.566 -3.743 1.00 10.00 A C
ATOM 2465 C PRO A 400 95.091 21.195 -1.386 1.00 15.83 A C
ATOM 2466 O PRO A 400 96.117 20.530 -1.529 1.00 15.83 A o
ATOM 2467 N SER A 401 94.687 21.646 -0.203 1.00 31.51 A N
ATOM 2468 CA SER A 401 95.463 21.368 1.003 1.00 31.51 A C
ATOM 2469 CB SER A 401 95.891 22.664 1.684 1.00 37.01 A C
ATOM 2470 OG SER A 401 95.284 22.788 2.962 1.00 37.01 A O
ATOM 2471 C SER A 401 94.630 20.565 1.968 1.00 31.51 A C
ATOM 2472 O SER A 401 93.419 20.463 1.802 1.00 31.51 A o
ATOM 2473 N THR A 402 95.282 20.011 2.984 1.00 39.39 A N
ATOM 2474 CA THR A 402 94.601 19.214 4.000 1.00 39.39 A C
ATOM 2475 CB THR A 402 95.512 18.102 4.540 1.00 60.45 A C
ATOM 2476 OGl THR A 402 95.743 17.134 3.511 1.00 60.45 A o
ATOM 2477 CG2 THR A 402 94.871 17.426 5.736 1.00 60.45 A C
ATOM 2478 C THR A 402 94.118 20.042 5.187 1.00 39.39 A C
ATOM 2479 O THR A 402 92.963 19.929 5.588 1.00 39.39 A o
ATOM 2480 N ASN A 403 94.997 20.874 5.741 1.00 48.58 A N
ATOM 2481 CA ASN A 403 94.641 21.688 6.892 1.00 48.58 A C
ATOM 2482 CB ASN A 403 95.207 21.054 8.167 1.00 90.00 A C
ATOM 2483 CG ASN A 403 94.439 19.823 8.600 1.00 90.00 A C
ATOM 2484 ODl ASN A 403 93.275 19.907 9.000 1.00 90.00 A o
ATOM 2485 ND2 ASN A 403 95.091 18.666 8.525 1.00 90.00 A N
ATOM 2486 C ASN A 403 95.095 23.138 6.839 1.00 48.58 A C
ATOM 2487 O ASN A 403 95.743 23.602 7.777 1.00 48.58 A O
ATOM 2488 N ALA A 404 94.759 23.870 5.780 1.00 29.35 A N
ATOM 2489 CA ALA A 404 95.176 25.275 5.706 1.00 29.35 A C
ATOM 2490 CB ALA A 404 96.657 25.397 6.030 1.00 15.73 A C
ATOM 2491 C ALA A 404 94.911 25.987 4.393 1.00 29.35 A C
ATOM 2492 O ALA A 404 94.870 25.383 3.325 1.00 29.35 A O
ATOM 2493 N LEU A 405 94.730 27.293 4.490 1.00 15.82 A N
ATOM 2494 CA LEU A 405 94.508 28.112 3.316 1.00 15.82 A C
ATOM 2495 CB LEU A 405 93.327 29.054 3.530 1.00 20.54 A C
ATOM 2496 CG LEU A 405 92.838 29.753 2.262 1.00 20.54 A C
ATOM 2497 CDl LEU A 405 92.693 28.739 1.177 1.00 20.54 A C
ATOM 2498 CD2 LEU A 405 91.494 30.392 2.498 1.00 20.54 A C
ATOM 2499 C LEU A 405 95.797 28.899 3.190 1.00 15.82 A C ATOM 2500 O LEU A 405 96.062 29.794 3.992 1.00 15.82 A O ATOM 2501 N VAL A 406 96.612 28.556 2.201 1.00 10.00 A N ATOM 2502 CA VAL A 406 97.885 29.230 2.034 1.00 10.00 A C ATOM 2503 CB VAL A 406 99.006 28.214 1.902 1.00 10.34 A C ATOM 2504 CGl VAL A 406 100.354 28.904 1.989 1.00 10.34 A C ATOM 2505 CG2 VAL A 406 98.866 27.178 2.984 1.00 10.34 A C ATOM 2506 C VAL A 406 97.922 30.161 0.845 1.00 10.00 A C ATOM 2507 O VAL A 406 97.924 29.729 -0.305 1.00 10.00 A O
ATOM 2508 N ILE A 407 97.940 31.452 1.138 1.00 10.00 A N ATOM 2509 CA ILE A 407 97.993 32.457 0.103 1.00 10.00 A C ATOM 2510 CB ILE A 407 97.515 33.808 0.625 1.00 10.00 A C ATOM 2511 CG2 ILE A 407 97.567 34.835 -0.470 1.00 10.00 A C ATOM 2512 CGl ILE A 407 96.092 33.671 1.143 1.00 10.00 A C ATOM 2513 CDl ILE A 407 95.504 34.945 1.637 1.00 10.00 A C ATOM 2514 C ILE A 407 99.455 32.535 -0.262 1.00 10.00 A C ATOM 2515 O ILE A 407 100.211 33.292 0.340 1.00 10..00 A O ATOM 2516 N GLY A 408 99.849 31.724 -1.239 1.00 16..67 A N ATOM 2517 CA GLY A 408 101.233 31.685 -1.671 1.00 16..67 A C ATOM 2518 C GLY A 408 101.579 32.623 -2.806 1.00 16..67 A C ATOM 2519- O GLY A 408 100.894 33.625 -3.038 1.00 16..67 A O ATOM 2520 N ALA A 409 102.646 32.281 -3.522 1.00 10..00 A N ATOM 2521 CA ALA A 409 103.140 33.077 -4.638 1.00 10..00 A C ATOM 2522 CB ALA A 409 104.316 32.394 -5.262 1.00 10..00 A C ATOM 2523 C ALA A 409 102.123 33.402 -5.716 1.00 10..00 A C ATOM 2524 O ALA A 409 102.033 34.541 -6.150 1.00 10..00 A o ATOM 2525 N THR A 410 101.343 32.428 -6.159 1.00 15..94 A N ATOM 2526 CA THR A 410 100.408 32.744 -7.220 1.00 15..94 A C ATOM 2527 CB THR A 410 99.537 31.529 -7.638 1.00 15..01 A C ATOM 2528 OGl THR A 410 98.153 31.814 -7.418 1.00 15..01 A o ATOM 2529 CG2 THR A 410 99.938 30.303 -6.875 1.00 15..01 A C ATOM 2530 C THR A 410 99.530 33.925 -6.867 1.00 15..94 A C ATOM 2531 O THR A 410 99.075 34.628 -7.761 1.00 15..94 A o ATOM 2532 N VAL A 411 99.298 34.177 -5.585 1.00 10..22 A N ATOM 2533 CA VAL A 411 98.469 35.323 -5.242 1.00 10..22 A C ATOM 2534 CB VAL A 411 97.515 35.039 -4.057 1.00 10..00 A C ATOM 2535 CGl VAL A 411 97.003 36.346 -3.456 1.00 10..00 A C ATOM 2536 CG2 VAL A 411 96.329 34.246 -4.545 1.00 10..00 A C ATOM 2537 C VAL A 411 99.321 36.530 -4.914 1.00 10..22 A C ATOM 2538 O VAL A 411 99.013 37.645 -5.329 1.00 10.22 A o ATOM 2539 N MET A 412 100.399 36.324 -4.178 1.00 35.77 A N ATOM 2540 CA MET A 412 101.246 37.448 -3.832 1.00 35.77 A C ATOM 2541 CB MET A 412 102.322 37.003 -2.861 1.00 15.25 A C
ATOM 2542 CG MET A 412 101.848 36.792 -1.464 1.00 15.25 A C
ATOM 2543 SD MET A 412 103.180 36.127 -0.464 1.00 15.25 A S
ATOM 2544 CE MET A 412 104.482 37.355 -0.740 1.00 15.25 A C
ATOM 2545 C MET A 412 101.899 38.096 -5.048 1.00 35.77 A C
ATOM 2546 O MET A 412 102.264 39.270 -5.013 1.00 35.77 A O
ATOM 2547 N GLU A 413 102.036 37.338 -6.130 1.00 11.29 A N
ATOM 2548 CA GLU A 413 102.678 37.856 -7.330 1.00 11.29 A C
ATOM 2549 CB GLU A 413 102.797 36.757 -8.375 1.00 70.05 A C
ATOM 2550 CG GLU A 413 104.173 36.660 -8.982 1.00 70.05 A C
ATOM 2551 CD GLU A 413 104.429 35.296 -9.588 1.00 70.05 A C
ATOM 2552 OEl GLU A 413 105.588 35.021 -9.976 1.00 70.05 A o
ATOM 2553 OE2 GLU A 413 103.466 34.497 -9.675 1.00 70.05 A o
ATOM 2554 C GLU A 413 101..915 39.023 -7.908 1.00 11.29 A C
ATOM 2555 o GLU A 413 102..388 39.682 -8.827 1.00 11.29 A o
ATOM 2556 N GLY A 414 100..732 39.277 -7.366 1.00 15.32 A N
ATOM 2557' CA GLY A 414 99..930 40.363 -7.872 1.00 15.32 A C
ATOM 2558 C GLY A 414 99..868 41.568 -6.959 1.00 15.32 A C
ATOM 2559 O GLY A 414 99..285 42.583 -7.329 1.00 15.32 A o
ATOM 2560 N ■ PHE A 415 100..463 41,489 -5.774 1.00 13.83 A N
ATOM 2561 CA PHE A 415 100..400 42.626 -4.872 1.00 13.83 A C
ATOM 2562 CB PHE A 415 99..317 42.410 -3.834 1.00 10.00 A C
ATOM 2563 CG PHE A 415 98..043 41.921 -4.399 1.00 10.00 A C
ATOM 2564 CDl PHE A 415 97..906 40.602 -4.772 1.00 10.00 A C
ATOM 2565 CD2 PHE A 415 96..986 42.785 -4.593 1.00 10.00 A C
ATOM 2566 CEl PHE A 415 96..731 40.151 -5.333 1.00 10.00 A C
ATOM 2567 CE2 PHE A 415 95..806 42.345 -5.154 1.00 10.00 A C
ATOM 2568 CZ PHE A 415 95..676 41.027 -5.526 1.00 10.00 A C
ATOM 2569 C PHE A 415 101..667 42.920 -4.131 1.00 13.83 A C
ATOM 2570 O PHE A 415 102..581 42.112 -4.081 1.00 13.83 A o
ATOM 2571 N TYR A 416 101..700 44.101 -3.538 1.00 14.40 A N
ATOM 2572 CA TYR A 416 102..825 44.522 -2.729 1.00 14.40 A C
ATOM 2573 CB TYR A 416 103..020 46.027 -2.848 1.00 10.00 A C
ATOM 2574 CG TYR A 416 104..186 46.579 -2.072 1.00 10.00 A C
ATOM 2575 CDl TYR A 416 105..333 45.822 -1.854 1.00 10.00 A C
ATOM 2576 CEl TYR A 416 106..442 46.368 -1.210 1.00 10.00 A C
ATOM 2577 CD2 TYR A 416 104..172 47.893 -1.620 1.00 10.00 A C
ATOM 2578 CE2 TYR A 416 105..269 48.448 -0.977 1.00 10.00 A C
ATOM 2579 CZ TYR A 416 106..398 47.684 -0.776 1.00 10.00 A C
ATOM 2580 OH TYR A 416 107..476 48.245 -0.137 1.00 10.00 A o
ATOM 2581 C TYR A 416 102.339 44.166 -1.344 1.00 14.40 A C ATOM 2582 O TYR A 416 101.366 44.739 -0.869 1.00 14.40 A O
ATOM 2583 N VAL A 417 102.983 43.201 -0.707 1.00 10.44 A N
ATOM 2584 CA VAL A 417 102.559 42.787 0.621 1.00 10.44 A C
ATOM 2585 CB VAL A 417 102.573 41.274 0.718 1.00 10.00 A C
ATOM 2586 CGl VAL A 417 102.170 40.839 2.106 1.00 10.00 A C
ATOM 2587 CG2 VAL A 417 101.640 40.704 -0.322 1.00 10.00 A C
ATOM 2588 C VAL A 417 103.400 43.382 1.748 1.00 10.44 A C
ATOM 2589 O VAL A 417 104.633 43.283 1.754 1.00 10.44 A O
ATOM 2590 N ILE A 418 102.720 43.993 2.708 1.00 10.00 A N
ATOM 2591 CA ILE A 418 103.384 44.621 3.834 1.00 10.00 A C
ATOM 2592 CB ILE A 418 102.844 46.010 4.048 1.00 10.00 A C
ATOM 2593 CG2 ILE A 418 103.440 46.611 5.299 1.00 10.00 A C
ATOM 2594 CGl ILE A 418 103.126 46.844 2.809 1.00 10.00 A C
ATOM 2595 CDl ILE A 418 102.921 48.293 3.021 1.00 10.00 A C
ATOM 2596 C ILE A 418 103.191 43.856 5.117 1.00 10.00 A C
ATOM 2597 O ILE A 418 102.073 43.755 5.612 1.00 10.00 A o
ATOM 2598 N PHE A 419 104.277 43.325 5.663 1.00 10.00 A N
ATOM 2599 CA PHE A 419 104.216 42.572 6.913 1.00 10.00 A C
ATOM 2600 CB PHE A 419 105.203 41.416 6.864 1.00 10.00 A C
ATOM 2601 CG PHE A 419 104.911 40.437 5.773 1.00 10.00 A C
ATOM 2602 CDl PHE A 419 104.134 39.317 6.019 1.00 10.00 A C
ATOM 2603 CD2 PHE A 419 105.365 40.663 4.483 1.00, 10.00 A C
ATOM 2604 CEl PHE A 419 103.811 38.434 4.990 1.00 10.00 A C
ATOM 2605 CE2 PHE A 419 105.049 39.793 3.454 1.00 10.00 A C
ATOM 22660066 CZ PHE A 419 104.269 38.675 3.706 1.00 10.00 A C
ATOM 2607 C PHE A 419 104.545 43.520 8.048 1.00 10.00 A C
ATOM 2608 O PHE A 419 105.701 43.666 8.444 1.00 10.00 A o
ATOM 2609 N ASP A 420 103.503 44.177 8.546 1.00 10.88 A N
ATOM 2610 CA ASP A 420 103.610 45.159 9.617 1.00 10.88 A C
ATOM 2611 CB ASP A 420 102.465 46.163 9.503 1.00 33.25 A C
ATOM 2612 CG ASP A 420 102.787 47.489 10.143 1.00 33.25 A C
ATOM 2613 ODl ASP A 420 103.438 47.484 11.208 1.00 33.25 A o
ATOM 2614 OD2 ASP A 420 102.379 48.535 9.581 1.00 33.25 A o
ATOM 2615 C ASP A 420 103.543 44.471 10.967 1.00 10.88 A C
ATOM 2616 O ASP A 420 102.546 44.576 11.683 1.00 10.88 A o
ATOM 2617 N ARG A 421 104.613 43.768 11.310 1.00 14.85 A N
ATOM 2618 CA ARG A 421 104.675 43.052 12.569 1.00 14.85 A C
ATOM 2619 CB ARG A 421 106.016 42.346 12.686 1.00 20.78 A C
ATOM 2620 CG ARG A 421 106.229 41.309 11.615 1.00 20.78 A C
ATOM 2621 CD ARG A 421 107.685 41.259 11.246 1.00 20.78 A C
ATOM 2622 NE ARG A 421 108.497 40.940 12.407 1.00 20.78 A N ATOM 2623 CZ ARG A 421 108.615 39.717 12.911 1.00 20.78 A C
ATOM 2624 NHl ARG A 421 107.980 38.694 12.346 1.00 20.78 A N
ATOM 2625 NH2 ARG A 421 109.355 39.516 13.995 1.00 20.78 A N
ATOM 2626 C ARG A 421 104.453 43.960 13.770 1.00 14.85 A C
ATOM 2627 O ARG A 421 103.867 43.539 14.766 1.00 14.85 A O
ATOM 2628 N ALA A 422 104.911 45.202 13.672 1.00 20.85 A N
ATOM 2629 CA ALA A 422 104.759 46.166 14.761 1.00 20.85 A C
ATOM 2630 CB ALA A 422 105.466 47.458 14.413 1.00 18.13 A C
ATOM 2631 C ALA A 422 103.307 46.466 15.111 1.00 20.85 A C
ATOM 2632 O ALA A 422 102.933 46.431 16.282 1.00 20.85 A O
ATOM 2633 N GLN A 423 102.497 46.773 14.098 1.00 17.38 A N
ATOM 2634 CA GLN A 423 101.082 47.090 14.305 1.00 17.38 A C
ATOM 2635 CB GLN A 423 100.658 48.261 13.410 1.00 33.32 A C
ATOM 2636 CG GLN A 423 101.480 49.523 13.605 1.00 33.32 A C
ATOM 2637 CD GLN A 423 100.980 50.680 12.768 1.00 33.32 A C
ATOM 2638 OEl GLN A 423 99.905 51.229 13.021 1.00 33.32 A O
ATOM 2639 NE2 GLN A 423 101.753 51.054 11.758 1.00 33.32 A N
ATOM 2640 C GLN A 423 100.168 45.890 14.047 1.00 17.38 A C
ATOM 2641 O GLN A 423 99.004 46.042 13.680 1.00 17.38 A O
ATOM 2642 N LYS A 424 100.721 44.699 14.233 1.00 12.11 A N
ATOM 2643 CA LYS A 424 99.988 43.452 14.070 1.00 12.11 A C
ATOM 2644 CB LYS A 424 99.225 43.145 15.366 1.00 26.08 A C
ATOM 2645 CG LYS A 424 98.873 41.682 15.579 1.00 26.08 A C
ATOM 2646 CD LYS A 424 98.311 41.464 16.980 1.00 26.08 A C
ATOM 2647 CE LYS A 424 97.864 40.021 17.205 1.00 26.08 A C
ATOM 2648 NZ LYS A 424 97.180 39.825 18.523 1.00 26.08 A N
ATOM 2649 C LYS A 424 99.028 43.463 12.890 1.00 12.11 A C
ATOM 2650 O LYS A 424 97.836 43.245 13.053 1.00 12.11 A o
ATOM 2651 N ARG A 425 99.544 43.693 11.694 1.00 10.06 A N
ATOM 2652 CA ARG A 425 98.670 43.717 10.540 1.00 10.06 A C
ATOM 2653 CB ARG A 425 98.007 45.065 10.451 1.00 13.89 A C
ATOM 2654 CG ARG A 425 99.014 46.165 10.323 1.00 13.89 A C
ATOM 2655 CD ARG A 425 98.349 47.507 10.282 1.00 13.89 A C
ATOM 2656 NE ARG A 425 99.289 48.519 9.830 1.00 13.89 A N
ATOM 2657 CZ ARG A 425 98.977 49.796 9.685 1.00 13.89 A C
ATOM 2658 NHl ARG A 425 97.746 50.203 9.965 1.00 13.89 A N
ATOM 2659 NH2 ARG A 425 99.886 50.660 9.251 1.00 13.89 A N
ATOM 2660 C ARG A 425 99.429 43.467 9.260 1.00 10.06 A C
ATOM 2661 o ARG A 425 100.633 43.690 9.189 1.00 10.06 A O
ATOM 2662 N VAL A 426 98.711 43.012 8.244 1.00 10.00 A N
ATOM 2663 CA VAL A 426 99.301 42.738 6.949 1.00 10.00 A C ATOM 2664 CB VAL A 426 99.101 41.288 6.555 1.00 10.00 A C
ATOM 2665 CGl VAL A 426 99.683 41.052 5.199 1.00 10.00 A C
ATOM 2666 CG2 VAL A 426 99.731 40.386 7.579 1.00 10.00 A C
ATOM 2667 C VAL A 426 98.579 43.603 5.938 1.00 10.00 A C
ATOM 2668 O VAL A 426 97.355 43.631 5.908 1.00 10.00 A O
ATOM 2669 N GLY A 427 99.323 44.312 5.105 1.00 13.86 A N
ATOM 2670 CA GLY A 427 98.671 45.157 4.127 1.00 13.86 A C
ATOM 2671 C GLY A 427 98.942 44.736 2.700 1.00 13.86 A C
ATOM 2672 O GLY A 427 99.981 44.146 2.413 1.00 13.86 A O
ATOM 2673 N PHE A 428 98.004 45.026 1.804 1.00 10.00 A N
ATOM 2674 CA PHE A 428 98.175 44.696 0.403 1.00 10.00 A C
ATOM 2675 CB PHE A 428 97.154 43.682 -0.056 1.00 10.00 A C
ATOM 2676 CG PHE A 428 97.216 42.391 0.657 1.00 10.00 A C
ATOM 2677 CDl PHE A 428 96.868 42.307 1.989 1.00 10.00 A C
ATOM 2678 CD2 PHE A 428 97.547 41.234 -0.027 1.00 10.00 A C
ATOM 2679 CEl PHE A 428 96.840 41.085 2.632 1.00 10.00 A C
ATOM 2680 CE2 PHE A 428 97.522 40.008 0.607 1.00 10.00 A C
ATOM 2681 CZ PHE A 428 97.166 39.930 1.940 1.00 10.00 A C
ATOM 2682 C PHE A 428 ■ 97.971 45.934 -0.438 1.00 10.00 A C
ATOM 2683 O PHE A 428 97.215 46.832 -0.071 1.00 10.00 A O
ATOM 2684 N ALA A 429 98.638 45.964 -1.582 1.00 10.00 A N
ATOM 2685 CA ALA A 429 98.508 47.076 -2.500 1.00 10.00 A C
ATOM 2686 CB ALA A 429 99.504 48.145 -2.172 1.00 10.00 A C
ATOM 2687 C ALA A 429 98.718 46.577 -3.917 1.00 10.00 A C
ATOM 2688 O ALA A 429 99.520 45.673 -4.166 1.00 10.00 A O
ATOM 2689 N ALA A 430 97.971 47.166 -4.841 1.00 22.55 A N
ATOM 2690 CA ALA A 430 98.057 46.799 -6.241 1.00 22.55 A C
ATOM 2691 CB ALA A 430 97.196 47.731 -7.061 1.00 54.13 A C
ATOM 2692 C ALA A 430 99.506 46.921 -6.663 1.00 22.55 A C
ATOM 2693 O ALA A 430 100.106 47.984 -6.529 1.00 22.55 A O
ATOM 2694 N SER A 431 100.067 45.834 -7.174 1.00 13.46 A N
ATOM 2695 CA SER A 431 101.461 45.825 -7.606 1.00 13.46 A C
ATOM 2696 CB SER A 431 102.059 44.444 -7.336 1.00 44.68 A C
ATOM 2697 OG SER A 431 103.472 44.486 -7.398 1.00 44.68 A O
ATOM 2698 C SER A 431 101.626 46.197 -9.090 1.00 13.46 A C
ATOM 2699 O SER A 431 101.220 45.459 -9.979 1.00 13.46 A O
ATOM 2700 N PRO A 432 102.240 47.350 -9.368 1.00 19.93 A N
ATOM 2701 CD PRO A 432 102.878 48.219 -8.371 1.00 15.14 A C
ATOM 2702 CA PRO A 432 102.481 47.862 -10.719 1.00 19.93 A C
ATOM 2703 CB PRO A 432 103.383 49.062 -10.478 1.00 15.14 A C
ATOM 2704 CG PRO A 432 102.995 49.513 -9.123 1.00 15.14 A C ATOM 2705 C PRO A 432 103.158 46.857 -11.640 1.00 19.93 A C ATOM 2706 O PRO A 432 102.691 46.604 -12.750 1.00 19.93 A O ATOM 2707 N CYS A 433 104.268 46.292 -11.177 1.00 53.46 A N ATOM 2708 CA CYS A 433 105.019 45.340 -11.979 1.00 53.46 A C ATOM 2709 C CYS A 433 104.187 44.120 -12.362 1.00 53.46 A C ATOM 2710 O CYS A 433 104.618 43.306 -13.172 1.00 53.46 A O ATOM 2711 CB CYS A 433 106.298 44.914 -11.240 1.00 71.62 A C ATOM 2712 SG CYS A 433 106.082 43.765 -9.844 1.00 71.62 A S
ATOM 2713 N ALA A 434 102.991 44.000 -11.789 1.00 16.86 A N ATOM 2714 CA ALA A 434 102..110 42.871 -12.084 1.00 16.86 A C ATOM 2715 CB ALA A 434 101..161 42.618 -10.921 1.00 15.50 A C ATOM 2716 C ALA A 434 101..315 43.165 -13.345 1.00 16.86 A C ATOM 2717 O ALA A 434 100..095 43.025 -13.375 1.00 16.86 A o ATOM 2718 N GLU A 435 102..020 43.574 -14.388 1.00 35.46 A N ATOM 2719 CA GLU A 435 101..399 43.901 -15.659 1.00 35.46 A C ATOM 2720 CB GLU A 435 101..945 45.254 -16.151 1.00 90.00 A C ATOM 2721 CG GLU A 435 102..216 45.375 -17.655 1.00 90.00 A C ATOM 2722 CD GLU A 435 103..664 45.057 -18.044 1.00 90.00 A C ATOM 2723 OEl GLU A 435 104..106 43.900 -17.852 1.00 90.00 A o ATOM 2724 OE2 GLU A 435 104..365 45.973 -18.537 1.00 90.00 A o ATOM 2725 C GLU A 435 101..659 42.794 -16.666 1.00 35.46 A C ATOM 2726 O GLU A 435 102..633 42.051 -16.548 1.00 35.46 A o ATOM 2727 N ILE A 436 100..772 42.680 -17.645 1.00 31.33 A N ATOM 2728 CA ILE A 436 100..895 41.671 -18.698 1.00 31.33 A C ATOM 2729 CB ILE A 436 99..998 40.435 -18.412 1.00 70.34 A C ATOM 2730 CG2 ILE A 436 99..612 39.745 -19.714 1.00 70.34 A C ATOM 2731 CGl ILE A 436 100..718 39.478 -17.449 1.00 70.34 A C ATOM 2732 CDl ILE A 436 101..983 38.851 -18.010 1.00 70.34 A C ATOM 2733 C ILE A 436 100..479 42.326 -20.015 1.00 31.33 A C ATOM 2734 O ILE A 436 99..284 42.476 -20.316 1.00 31.33 A o ATOM 2735 N ALA A 437 101..481 42.740 -20.784 1.00 56.95 A N ATOM 2736 CA ALA A 437 101..232 43.392 -22.062 1.00 56.95 A C ATOM 2737 CB ALA A 437 100..465 42.448 -22.995 1.00 57.54 A C ATOM 2738 C ALA A 437 100..436 44.678 -21.845 1.00 56.95 A C ATOM 2739 O ALA A 437 99..404 44.899 -22.483 1.00 56.95 A o ATOM 2740 N GLY A 438 100..912 45.516 -20.931 1.00 65.43 A N ATOM 2.741 CA GLY A 438 100.236 46.773 -20.669 1.00 65.43 A C ATOM 2742 C GLY A 438 99.006 46.713 -19.781 1.00 65.43 A C ATOM 2743 O GLY A 438 98.517 47.758 -19.349 1.00 65.43 A O ATOM 2744 N ALA A 439 98.511 45.512 -19.487 1.00 45.63 A N ATOM 2745 CA ALA A 439 97.310 45.363 -18.665 1.00 45.63 A C ATOM 2746 CB ALA A 439 96.309 44.470 -19.382 1.00 40.32 A C
ATOM 2747 C ALA A 439 97.544 44.834 -17.253 1.00 45.63 A C
ATOM 2748 O ALA A 439 98.417 43.998 -17.024 1.00 45.63 A O
ATOM 2749 N ALA A 440 96.736 45.335 -16.318 1.00 39.87 A N
ATOM 2750 CA ALA A 440 96.793 44.942 -14.912 1.00 39.87 A C
ATOM 2751 CB ALA A 440 95.872 45.809 -14.072 1.00 50.44 A C
ATOM 2752 C ALA A 440 96.364 43.498 -14.813 1.00 39.87 A C
ATOM 2753 O ALA A 440 95.532 43.031 -15.585 1.00 39.87 A O
ATOM 2754 N VAL A 441 96.907 42.791 -13.840 1.00 13.76 A N
ATOM 2755 CA VAL A 441 96.590 41.391 -13.721 1.00 13.76 A C
ATOM 2756 CB VAL A 441 97.848 40.592 -13.991 1.00 18.98 A C
ATOM 2757 CGl VAL A 441 98.699 40.539 -12.736 1.00 18.98 A C
ATOM 2758 CG2 VAL A 441 97.491 39.229 -14.504 1.00 18.98 A C
ATOM 2759 C VAL A 441 96.039 41.089 -12.335 1.00 13.76 A C
ATOM 2760 O VAL A 441 95.734 39.944 -11.997 1.00 13.76 A O
ATOM 2761 N SER A 442 95.908 42.137 -11.535 1.00 18.60 A N
ATOM 2762 CA SER A 442 95.390 42.004 -10.185 1.00 18.60 A C
ATOM 2763 CB SER A 442 96.531 41.794 -9.204 1.00 12.54 A C
ATOM 2764 OG SER A 442 97.472 42.840 -9.345 1.00 12.54 A O
ATOM 2765 C SER A 442 94.659 43.277 -9.820 1.00 18.60 A C
ATOM 2766 O SER A 442 95.000 44.364 -10.290 1.00 18.60 A O
ATOM 2767 N GLU A 443 93.658 43.143 -8.968 1.00 19.83 A N
ATOM 2768 CA GLU A 443 92.883 44.285 -8.540 1.00 19.83 A C
ATOM 2769 CB GLU A 443 91.525 44.271 -9.232 1.00 64.46 A C
ATOM 2770 CG GLU A 443 91.578 44.571 -10.716 1.00 64.46 A C
ATOM 2771 CD GLU A 443 90.309 44.142 -11.438 1.00 64.46 A C
ATOM 2772 OEl GLU A 443 89.237 44.105 -10.788 1.00 64.46 A O
ATOM 2773 OE2 GLU A 443 90.381 43.851 -12.655 1.00 64.46 A O
ATOM 2774 C GLU A 443 92.692 44.248 -7.029 1.00 19.83 A C
ATOM 2775 O GLU A 443 92.851 43.208 -6.388 1.00 19.83 A O
ATOM 2776 N ILE A 444 92.373 45.398 -6.461 1.00 14.84 A N
ATOM 2777 CA ILE A 444 92.118 45.488 -5.042 1.00 14.84 A C
ATOM 2778 CB ILE A 444 93.399 45.763 -4.236 1.00 13.04 A C
ATOM 2779 CG2 ILE A 444 93.991 47.109 -4.629 1.00 13.04 A C
ATOM 2780 CGl ILE A 444 93.075 45.747 -2.740 1.00 13.04 A C
ATOM 2781 CDl ILE A 444 94.286 45.794 -1.868 1.00 13.04 A C
ATOM 2782 C ILE A 444 91.164 46.650 -4.886 1.00 14.84 A C
ATOM 2783 O ILE A 444 91.366 47.702 -5.488 1.00 14.84 A O
ATOM 2784 N SER A 445 90.113 46.459 -4.098 1.00 21.82 A N
ATOM 2785 CA SER A 445 89.142 47.520 -3.888 1.00 21.82 A C
ATOM 2786 CB SER A 445 88.142 47.542 -5.032 1.00 38.82 A C ATOM 2787 OG SER A 445 87.438 46.315 -5.077 1.00 38.82 A O
ATOM 2788 C SER A 445 88.394 47.340 -2.582 1.00 21.82 A C
ATOM 2789 O SER A 445 88.354 46.244 -2.006 1.00 21.82 A O
ATOM 2790 N GLY A 446 87.791 48.430 -2.125 1.00 21.94 A N
ATOM 2791 CA GLY A 446 87.042 48.383 -0.890 1.00 21.94 A C
ATOM 2792 C GLY A 446 86.619 49.765 -0.453 1.00 21.94 A C
ATOM 2793 O GLY A 446 86.895 50.756 -1.133 1.00 21.94 A O
ATOM 2794 N PRO A 447 85.953 49.858 0.697 1.00 10.00 A N
ATOM 2795 CD PRO A 447 85.700 51.116 1.407 1.00 10.00 A C
ATOM 2796 CA PRO A 447 85.614 48.720 1.548 1.00 10.00 A C
ATOM 2797 CB PRO A 447 85.705 49.315 2.929 1.00 10.00 A C
ATOM 2798 CG PRO A 447 85.076 50.639 2.698 1.00 10.00 A C
ATOM 2799 C PRO A 447 84.208 48.235 1.251 1.00 10.00 A C
ATOM 2800 O PRO A 447 83.388 49.009 0.771 1.00 10.00 A O
ATOM 2801 N PHE A 448 83.936 46.964 1.539 1.00 12.27 A N
ATOM 2802 CA PHE A 448 82.618 46.372 1.327 1.00 12.27 A C
ATOM 2803 CB PHE A 448 82.734 45.037 0.594 1.00 10.66 A C
ATOM 2804 CG PHE A 448 83.319 45.144 -0.778 1.00 10.66 A C
ATOM 2805 CDl PHE A 448 84.692 45.147 -0.965 1.00 10.66 A C
ATOM 2806 CD2 PHE A 448 82.495 45.249 -1.888 1.00 10.66 A • C
ATOM 2807 CEl PHE A 448 85.239 45.253 -2.245 1.00 10.66 A C
ATOM 2808 CE2 PHE A 448 83.025 45.355 -3.163 1.00 10.66 A C
ATOM 2809 CZ PHE A 448 84.399 45.357 -3.346 1.00 10.66 A C
ATOM 2810 C PHE A 448 82.004 46.122 2.698 1.00 12.27 A C
ATOM 2811 O PHE A 448 82.731 45.960 3.671 1.00 12.27 A o
ATOM 2812 N SER A 449 80.679 46.082 2.794 1.00 31.38 A N
ATOM 2813 CA SER A 449 80.057 45.837 4.090 1.00 31.38 A C
ATOM 2814 CB SER A 449 78.563 46.134 4.034 1.00 57.01 A C
ATOM 2815 OG SER A 449 77.935 45.732 5.241 1.00 57.01 A O
ATOM 2816 C SER A 449 80.266 44.387 4.518 1.00 31.38 A C
ATOM 2817 O SER A 449 80.105 43.471 3.711 1.00 31.38 A o
ATOM 2818 N THR A 450 80.628 44.182 5.782 1.00 62.24 A N
ATOM 2819 CA THR A 450 80.853 42.838 6.312 1.00 62.24 A C
ATOM 2820 CB THR A 450 82.135 42.743 7.137 1.00 56.54 A C
ATOM 2821 OGl THR A 450 81.954 43.417 8.390 1.00 56.54 A o
ATOM 2822 CG2 THR A 450 83.272 43.372 6.395 1.00 56.54 A C
ATOM 2823 C THR A 450 79.729 42.493 7.250 •1.00 62.24 A C
ATOM 2824 O THR A 450 79.454 41.326 7.507 1.00 62.24 A o
ATOM 2825 N GLU A 451 79.098 43.529 7.781 1.00 76.26 A N
ATOM 2826 CA GLU A 451 78.001 43.347 8.714 1.00 76.26 A C
ATOM 2827 CB GLU A 451 77.810 44.626 9.534 1.00 90.00 A C ATOM 2828 CG GLU A 451 79.144 45.175 10.048 1.00 90.00 A C
ATOM 2829 CD GLU A 451 79.190 45.347 11.561 1.00 74.75 A C
ATOM 2830 OEl GLU A 451 78.431 46.221 12.089 1.00 74.75 A O
ATOM 2831 OE2 GLU A 451 79.992 44.612 12.218 1.00 74.75 A O
ATOM 2832 C GLU A 451 76.746 42.966 7.934 1.00 76.26 A C
ATOM 2833 O GLU A 451 75.975 43.813 7.461 1.00 76.26 A O
ATOM 2834 N ASP A 452 76.584 41.654 7.803 1.00 78.40 A N
ATOM 2835 CA ASP A 452 75.477 41.038 7.092 1.00 78.40 A C
ATOM 2836 CB ASP A 452 75.342 41.635 5.687 1.00 90.00 A C
ATOM 2837 CG ASP A 452 76.556 41.349 4.808 1.00 90.00 A C
ATOM 2838 ODl ASP A 452 77.668 41.807 5.149 1.00 90.00 A O
ATOM 2839 OD2 ASP A 452 76.393 40.666 3.775 1.00 90.00 A O
ATOM 2840 C ASP A 452 75.825 39.559 6.989 1.00 78.40 A C
ATOM 2841 O ASP A 452 74.938 38.703 6.902 1.00 78.40 A O
ATOM 2842 N VAL A 453 77.128 39.272 7.006 1.00 83.06 A N
ATOM 2843 CA VAL A 453 77.613 37.900 6.913 1.00 83.06 A C
ATOM 2844 CB VAL A 453 77.906 37.513 5.437 1.00 68.59 A C
ATOM 2845 CGl VAL A 453 77.977 35.994 5.316 1.00 68.59 A C
ATOM 2846 CG2 VAL A 453 76.833 38.080 4.497 1.00 68.59 A C
ATOM 2847 C VAL A 453 78.880 37.604 7.750 1.00 83.06 A C
ATOM 2848 O VAL A 453 79.991 38.006 7.384 1.00 83.06 A O
ATOM 2849 N ALA A 454 78.685 36.896 8.867 1.00 74.47 A N
ATOM 2850 CA ALA A 454 79.754 36.472 9.786 1.00 74.47 A C
ATOM 2851 CB ALA A 454 80.867 35.790 8.999 1.00 47.99 A C
ATOM 2852 C ALA A 454 80.354 37.540 10.705 1.00 74.47 A C
ATOM 2853 O ALA A 454 80.476 38.710 10.330 1.00 74.47 A O
ATOM 2854 N SER A 455 80.736 37.114 11.911 1.00 52.62 A N
ATOM 2855 CA SER A 455 81.327 38.005 12.915 1.00 52.62 A C
ATOM 2856 CB SER A 455 80.575 37.891 14.246 1.00 89.80 A C
ATOM 2857 OG SER A 455 79.215 38.273 14.113 1.00 89.80 A O
ATOM 2858 C SER A 455 82.795 37.671 13.147 1.00 52.62 A C
ATOM 2859 O SER A 455 83.635 38.558 13.304 1.00 52.62 A O
ATOM 2860 N ASN A 456 83.086 36.376 13.188 1.00 72.17 A N
ATOM 2861 CA ASN A 456 84.445 35.888 13.377 1.00 72.17 A C
ATOM 2862 CB ASN A 456 84.750 35.700 14.860 1.00 58.46 A C
ATOM 2863 CG ASN A 456 86.199 35.347 15.107 1.00 58.46 A C
ATOM 2864 ODl ASN A 456 87.105 36.103 14.745 1.00 58.46 A O
ATOM 2865 ND2 ASN A 456 86.431 34.192 15.722 1.00 58.46 A N
ATOM 2866 C ASN A 456 84.556 34.556 12.647 1.00 72.17 A C
ATOM 2867 O ASN A 456 83.959 33.557 13.057 1.00 72.17 A O
ATOM 2868 N CYS A 457 85.321 34.543 11.562 1.00 51.38 A N ATOM 2869 CA CYS A 457 85.463 33.338 10.766 1.00 51.38 A C
ATOM 2870 C CYS A 457 86.605 32.399 11.141 1 .00 51 .38 A C
ATOM 2871 O CYS A 457 86.846 31.416 10.438 1 .00 51 .38 A o
ATOM 2872 CB CYS A 457 85.559 33.717 9.290 1 .00 58 .98 A C
ATOM 2873 SG CYS A 457 84.081 34.600 8.700 1 .00 58 .98 A S
ATOM 2874 N VAL A 458 87.302 32.688 12.240 1 .00 63 .49 A N
ATOM 2875 CA VAL A 458 88.400 31.825 12.685 1 .00 63 .49 A C
ATOM 2876 CB VAL A 458 89.634 32.646 13.153 1 .00 47 .39 A C
ATOM 2877 CGl VAL A 458 90.251 33.368 11.972 1 .00 47 .39 A C
ATOM 2878 CG2 VAL A 458 89.233 33.646 14.234 1 .00 47 .39 A C
ATOM 2879 C VAL A 458 87.934 30.918 13.826 1 .00 63 .49 A C
ATOM 2880 O VAL A 458 87.890 31.328 14.989 1 .00 63 .49 A o
ATOM 2881 N PRO A 459 87.589 29.660 13.504 1 .00 79 .55 A N
ATOM 2882 CD PRO A 459 87.830 28.960 12.228 1 .00 66 .69 A C
ATOM 2883 CA PRO A 459 87.126 28.721 14.528 1 .00 79 .55 A C
ATOM 2884 CB PRO A 459 86.893 27.432 13.736 1 .00 66 .69 A C
ATOM 2885 CG PRO A 459 87.930 27.509 12.665 1 .00 66 .69 A C
ATOM 2886 C PRO A 459 88.126 28.543 15.662 1 .00 79 .55 A C
ATOM 2887 O PRO A 459 89.336 28.486 15.438 1 .00 79 .55 A o
ATOM 2888 N ALA A 460 87.606 28.472 16.883 1 .00 90 .00 A N
ATOM 2889 CA ALA A 460 88.438 28.288 18.066 1 .00 90 .00 A C
ATOM 2890 CB ALA A 460 87.965 29.218 19.196 1 .00 69 .03 A C
ATOM 2891 C ALA A 460 88.361 26.821 18.507 1 .00 90 .00 A C
ATOM 2892 O ALA A 460 89.422 26.151 18.526 1 .00 90 .00 A o
ATOM 2893 OXT ALA A 460 87.238 26.357 18.815 1 .00 69 .03 A o
ATOM 2894 Nl INH I 1 107.187 25.733 1.630 1 .00 10 .00 I N
ATOM 2895 C3 INH I 1 107.889 26.169 2.883 1 .00 10 .00 I C
ATOM 2896 C5 INH I 1 107.048 27.135 3.723 1 .00 10 .00 I C
ATOM 2897 07 INH I 1 107.734 27.512 4.854 1 .00 10 .00 I o
ATOM 2898 C9 INH I 1 105.762 26.516 4.189 1 .00 10 .00 I C
ATOM 2899 N12 INH I 1 104.977 27.431 4.997 1 .00 10 .00 I N
ATOM 2900 C14 INH I 1 104.120 26.849 6.055 1 .00 10 .00 I C
ATOM 2901 C17 INH I 1 104.743 25.732 6.940 1 .00 10 .00 I C
ATOM 2902 C18 INH I 1 105.951 25.957 7.857 1 .00 10 .00 I C
ATOM 2903 C20 INH I 1 106.526 24.841 8.705 1 .00 10 .00 I C
ATOM 2904 C21 INH I 1 105.878 23.456 8.639 1 .00 10 .00 I C
ATOM 2905 C23 INH I 1 104.668 23.217 7.725 1 .00 10 .00 I C
ATOM 2906 C25 INH I 1 104.112 24.354 6.886 1 .00 10 .00 I C
ATOM 2907 C27 INH I 1 107.750 25.123 9.615 1 .00 10 .00 I C
ATOM 2908 C31 INH I 1 109.214 26.749 2.398 1 .00 10 .00 I C
ATOM 2909 C34 INH I 1 110.092 25.789 1.566 1 .00 10 .00 I C ATOM 2910 C35 INH I 1 110.775 26.310 0.343 1.00 10.00 I C
ATOM 2911 C37 INH I 1 111. 653 25 .405 -0.508 1 .00 10 .00 I C
ATOM 2912 C39 INH I 1 111. 826 23 .965 -0.099 1 .00 10 .00 I C
ATOM 2913 C41 INH I 1 111. 143 23 .442 1.126 1 .00 10 .00 I C
ATOM 2914 C43 INH I 1 110. 298 24 .320 1.942 1 .00 10 .00 I C
ATOM 2915 C45 INH I 1 106. 551 24 .505 1.425 1 .00 10 .00 I C
ATOM 2916 046 INH I 1 106. 489 23 .593 2.287 1 .00 10 .00 I o
ATOM 2917 C47 INH I 1 105. 912 24 .209 0.161 1 .00 10 .00 I C
ATOM 2918 C48 INH I 1 104. 567 23 .844 0.209 1 .00 10 .00 I C
ATOM 2919 C50 INH I 1 103. 693 23 .482 -0.960 1 .00 10 .00 I C
ATOM 2920 C51 INH I 1 103. 842 24 .187 -2.324 1 .00 10 .00 I C
ATOM 2921 C52 INH I 1 102. 980 23 .823 -3.450 1 .00 10 .00 I C
ATOM 2922 C54 INH I 1 101. 975 22 .773 -3.267 1 .00 10 .00 I C
ATOM 2923 C56 INH I 1 101. 826 22 .080 -1.933 1 .00 10 .00 I C
ATOM 2924 C58 INH I 1 102. 698 22 .444 -0.779 1 .00 10 .00 I C
ATOM 2925 O60 INH I 1 104. 810 25 .204 -2.500 1 .00 10 .00 I o
ATOM 2926 C61 INH I 1 106. 127 24 .812 -2.503 1 .00 10 .00 I C
ATOM 2927 C62 INH I 1 106. 774 24 .298 -1.210 1 .00 10 .00 I C
ATOM 2928 C63 INH I 1 108. 222 23 .895 -1.314 1 .00 10 .00 I C
ATOM 2929 C65 INH I 1 108. 984 23 .997 -2.638 1 .00 10 .00 I C
ATOM 2930 C67 INH I 1 108. 304 24 .509 -3.887 1 .00 10 .00 I C
ATOM 2931 C69 INH I 1 106. 864 24 .915 -3.808 1 .00 10 .00 I C
ATOM 2932 OH2 WAT S 1 112. 943 28 .010 7.768 1 .00 27 .44 S o
ATOM 2933 OH2 WAT S 2 111. 919 48 .198 16.807 1 .00 33 .52 S o
ATOM 2934 OH2 WAT S 3 87. 871 44 .432 -7.370 1 .00 35 .33 S o
ATOM 2935 OH2 WAT S 4 107. 661 16 .265 2.068 1 .00 36 .53 S o
ATOM 2936 OH2 WAT S 5 109. 763 33 .281 -2.537 1 .00 27 .32 S o
ATOM 2937 OH2 WAT S 6 125. 767 26 .255 12.194 1 .00 31 .58 S o
ATOM 2938 OH2 WAT S 7 98. 672 21 .415 -1.487 1 .00 36 .29 S o
ATOM 2939 OH2 WAT S 8 92. 997 36 .779 17.300 1 .00 38 .27 S o
ATOM 2940 OH2 WAT S 9 103. 156 28 .771 -9.220 1 .00 35 .23 S o
ATOM 2941 OH2 WAT S 10 113. 897 42 .802 18.893 1 .00 39 .93 S o
ATOM 2942 OH2 WAT S 11 103. 128 33 .093 7.478 1 .00 32 .04 S o
ATOM 2943 OH2 WAT S 12 90. 900 23 .828 -24.610 1 .00 41 .37 S o
ATOM 2944 OH2 WAT S 13 98. 792 22 .390 -13.543 1 .00 36 .01 S o
ATOM 2945 OH2 WAT S 14 139. 515 32 .592 7.733 1 .00 36 .83 S o
ATOM 2946 OH2 WAT S 15 107. 806 30 .358 -3.206 1 .00 35 .31 S o
ATOM 2947 OH2 WAT S 16 121. 284 18 .203 2.043 1 .00 33 .86 S o
ATOM 2948 OH2 WAT S 17 115. 976 15 .677 -3.204 1 .00 36 .75 S o
ATOM 2949 OH2 WAT S 18 89. 317 17 .691 -7.427 1 .00 35 .91 S o
ATOM 2950 OH2 WAT S 19 93. 504 21 .301 -24.645 1 .00 35 .14 S o ATOM 2951 OH2 WAT S 20 128.257 21.915 7.395 1.00 35.55 S O
ATOM 2952 OH2 WAT S 21 117.896 28.785 12.137 1.00 33.03 S O
ATOM 2953 OH2 WAT S 22 128.719 43.083 13.600 1.00 36.53 S o
ATOM 2954 OH2 WAT S 23 121.860 37.272 17.704 1.00 29.74 S O
ATOM 2955 OH2 WAT S 24 85.059 40.360 -8.727 1.00 33.79 S o
ATOM 2956 OH2 WAT S 25 111.673 56.480 -0.016 1.00 39.07 S o
ATOM 2957 OH2 WAT S 26 111.736 28.446 -12.364 1.00 37.21 S O
ATOM 2958 OH2 WAT S 27 126.594 43.645 15.318 1.00 37.39 S O
ATOM 2959 OH2 WAT S 28 101.663 25.778 -33.638 1.00 38.26 S O
ATOM 2960 OH2 WAT S 29 118.806 34.606 13.709 1.00 36.05 S o
ATOM 2961 OH2 WAT S 30 135.630 32.225 2.911 1.00 38.09 S O
ATOM 2962 OH2 WAT S 31 103.440 41.371 -6.394 1.00 32.95 S O
ATOM 2963 OH2 WAT S 32 106.435 40.370 -14.368 1.00 39.38 S o
ATOM 2964 OH2 WAT S 33 108.329 55.949 2.705 1.00 37.55 S o
ATOM 2965 OH2 WAT S 34 99.666 21.016 4.823 1.00 37.00 S O
END
Table 2: Crystal Data and X-ray data collection statistics
Number of crystals 1 Space group R3 (rhombohedral)
Unit cell dimensions a = b = 228.407 c= 108.964 A α=β= 90 γ= 120°
Number of monomers / a.u. 1
Packing coefficient 3.25 A3/Da
Solvent content 61.9%
Resolution range 61.65 -3.05 A
Number of observations 88192
Number of unique reflections 39813
Mosaicity 0.64
Overall
Data redundancy 2.2
Data completeness 99.0%
< I/ σ (l)> 6.5
■Emerge 0.111
Highest resolution shell
Resolution range 3.16 -3.05A
Completeness for shell 98.9%
< I/ σ (l)> 1.8
Rmerqe for Shell 0.365 Table 3: Non crystallographic symmetry operators
NCS operator 1 real-space rotation matrix
{===>} ncs_matrix_1=( 0.30485 0.95240 -0.00220 ) ( 0.95240 -0.30484 0.00064 ) ( -0.00006 -0.00229 -1.00000 ); real-space translation vector
{===>} ncs_vector_1=( 52.63405 -72.33963 -37.90527 );
NCS operator 2 real-space rotation matrix
{===>} ncs_matrix_2=( 0.51120 0.85946 -0.00251 ) ( -0.85946 0.51119 -0.00234 ) ( -0.00072 0.00335 0.99999 ); real-space translation vector
{===>} ncs_vector_2=( 37.14735 64.74499 18.10184 );
NCS operator 3 real-space rotation matrix
{===>} ncs_matrix_3=( 0.97976 0.19980 -0.01239 ) ( 0.19995 -0.97972 0.01268 ) ( -0.00961 -0.01490 -0.99984 ); real-space translation vector
{===>} ncs_vector_3=( 1.85155 -14.51931 -18.56605 );
Table 4: Refinement Statistics
Figure imgf000097_0001
Figure imgf000098_0001

Claims

Claims
1. A crystal of BACE2 comprising BACE2 with a unit cell dimension of a = 228.407 + 5 Angstroms, b = 228.407 + 5 Angstroms, c = 108.964 + 5 Angstroms ; α = 90.0 degrees, β = 90.0 degrees, γ = 120.0 degrees.
2. A crystal of BACE2 comprising BACE2 wherein said BACE2 has a three-dimensional structure comprising the atomic structure coordinates of Table 1.
3. A crystal according to claims 1 or 2 wherein BACE2 comprises the sequence of SEQ ID. No. 3, a fragment or a homologue thereof.
4. A crystal according to claim 3 wherein BACE2 comprises at least the substrate binding site.
5. A crystal according to any of claims 1-4 bound to at least one ligand or low molecular weight compound.
6. A computer readable medium comprising data storage material encoded with computer readable data wherein said data comprises the atomic coordinates of Table 1 comprising BACE2.
7. A method for making a crystal of a BACE2 comprising the steps of: (i) purification of the full-length BACE2 of SEQ ID No.1
(ii) expression of the full-length BACE2 (SEQ ID No.1) or expression of BACE2 (SEQ ID No.
2 or SEQ ID No. 3) in a suitable host cell
(iii) refolding and purification of the desired BACE2.
8. A method of making a crystal according to claim 7 wherein BACE2 (SEQ ID No. 3), a mutant, fragment or homologue thereof is used.
9. A method according to claim 7 wherein BACE2 (SEQ ID No. 3), a mutant, fragment or homologue thereof is bound to at least one ligand or low molecule weight chemical compound at any step prior to crystallisation.
10. A method of determining the three-dimensional structure of BACE2 comprising:
(i) crystallisation of BACE2 comprising BACE2 (SEQ ID No.3), a mutant, fragment or homologue thereof
(ii) utilizing the atomic coordinates of Table 1 in whole or in part to determine the three- dimensional structure of BACE2, a mutant, fragment or homologue thereof.
11. A method for determining the three-dimensional structure of a complex comprising BACE2 (SEQ ID No.3), a mutant, fragment or homologue thereof bound to at least one ligand comprising the steps of:
(i) obtaining x-ray diffraction data for crystals of the complex
(ii) utilizing the atomic coordinates of Table 1 in whole or in part to define the three- dimensional structure of the complex.
12. A method of identifying a ligand or low molecular weight compound that binds to BACE2 comprising the steps of:
(i) using the three dimensional structure of BACE2 derived in whole or in part from the set of atomic coordinates in Table 1 to select a potential ligand or low molecular weight compound that binds to BACE2 or any other aspartyl protease
(ii) selecting those ligands or low molecular weight compound that bind to BACE2 or any other aspartyl protease.
13. A method of identifying a iigand or low molecular weight compound that binds to BACE2 according to claim 12 wherein BACE2 comprises at least the substrate binding site of said protease.
14. A method according to claim 12 or 13 for use in selecting ligands which inhibit the activity of BACE2 or any other aspartyl protease.
15. A method of designing a ligand or low molecular weight compound capable of binding to BACE2 or any other aspartyl protease comprising:
(i) using the atomic coordinates of Table 1 in whole or in part to determine the three dimensional structure of BACE2
(ii) probing said BACE2 with candidate ligands or low molecular weight compounds to determine which bind to BACE2 or any other aspartyl protease (iii) selecting those iigands or low molecular weight compounds which bind to BACE2 or any other aspartyl protease
(iv) modifying those Iigands or low molecular weight compounds which bind to maximize physical properties such as solubility, affinity, specificity or potency.
16. A method according to claim 15 wherein the candidate Iigands or low molecular weight compounds are screened in silico.
17. A method of designing a ligand or low molecular weight compound capable of binding to an aspartyl protease family member using the atomic coordinates of Table 1 in whole or in part to determine the three dimensional structure of an aspartyl protease member's catalytic domain.
18. A method of designing a ligand or low molecular weight compound capable of binding to an aspartyl protease family member and specifically not binding to BACE2 using the atomic coordinates of Table 1 in whole or in part.
19. A method according to any of claims 15-17 for use in designing Iigands which inhibit the activity of BACE2 or any other aspartyl protease.
20. A pharmaceutical composition comprising a ligand identified or designed by a method according to any of claims 12-18 for use in preventing or treating of diseases and conditions involving an aspartyl protease family member.
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