CRYSTAL STRUCTURES OF ANTI-FACTOR IX Fab FRAGMENTS AND METHODS OF USE FOR PEPTIDOMIMETIC DESIGN

Abstract: Novel anti-Factor IX Fab fragment crystalline structures are identified. Methods of identifying peptidomimetics of these fragments are disclosed.

Description: CRYSTAL STRUCTURES OF ANTI-FACTOR IX Fah FRAGMENTS AND METHODS OF USE FOR PEPTIDOMIMETIC DESIGN This application claims the benefit of U.S. Provisional Application No. 60/051,645, filed 3 July 1997. FIELD OF THE INVENTION This invention relates to anti-Factor IX Fab fragment crystals and the use of complementarity determining region (CDR) structural parameters for design and selection of peptidomimetics. BACKGROUND OF THE INVENTION Under normal circumstances, an injury, be it minor or major, to vascular endothelial cells lining a blood vessel triggers a hemostatic response through a sequence of events commonly r rred to as the coagulation "cascade." The cascade culminates in the conversion of soluble fibrinogen to insoluble fibrin which, together with platelets, forms a localized clot or thrombus which prevents extravasation of blood components. Wound healing can then occur followed by clot dissolution and restoration of blood vessel integrity and flow. The events which occur between injury and clot formation are a carefully regulated and linked series of reactions. In brief, a number of plasma coagulation proteins in inactive proenzyme forms and cofactors circulate in the blood. Active enzyme complexes are assembled at an injury site and are sequentially activated to serine proteases, with each successive serine protease catalyzing the subsequent proenzyme to protease activation. This enzymatic cascade results in each step magnifying the effect of the succeeding step. For an overview of the coagulation cascade see the first chapter of "Thombosis and Hemorrhage", J. Loscalzo and A. Schafer, eds., Blackwell Scientific Publications, Oxford, England (1994). While efficient clotting limits the loss of blood at an injury site, inappropriate formation of thrombi in veins or arteries is a common cause of disability and death. Abnormal clotting activity can result in and/or from pathologies or treatments such as myocardial infarction, unstable angina, atrial fibrillation, stroke, renal damage, percutaneous translumenal coronary angioplasty, disseminated intravascular coagulation, sepsis, pulmonary embolism and deep vein thrombosis. The formation of clots on foreign surfaces of artificial organs, shunts and prostheses such as artificial heart valves is also problematic Approved anticoagulant agents currently used in treatment of these pathologies and other thrombotic and embolic disorders include the sulfated heteropolysacchaπdes heparin and low molecular weight (LMW) heparin These agents are administered parenterally and can cause rapid and complete inhibition of clotting by activation of the thrombin inhibitor, antithrombin III and mactivation of all of the clotting factors However, due to their potency, heparin and LMW heparin suffer drawbacks Uncontrolled bleeding as a result of the simple stresses of motion and accompanying contacts with physical objects or at surgical sites is the major complication and is observed in 1 to 7% of patients receiving continuous infusion and in 8 to 14% of patients given intermittent bolus doses To minimize this risk, samples are continuously drawn to enable ex vivo clotting times to be continuously monitored, which contπbutes substantially to the cost of therapy and the patient's inconvenience Further, the therapeutic target range to achieve the desired level of efficacy without placing the patient at risk for bleeding is narrow The therapeutic range is approximately 1 to less than 3 ug hepaπn/ml plasma which results in activated partial thromboolastin time (aPTT) assay times of about 35 to about 100 seconds Increasing the heparin concentration to 3 ug/ml exceeds the target range and at concentrations greater than 4 ug/ml, clotting activity is not detectable Thus, great care must be taken to keep the patient's plasma concentrations within the therapeutic range Another approved anticoagulant with slower and longer lasting effect is warfarin, a coumaπn derivative Warfarin acts by competing with Vitamin K dependent post- translational modification of prothrombin and other Vitamin K-dependent clotting factors The general pattern of anticoagulant actιon,ιn which blood is rendered non- clottable at concentrations only slightly higher than the therapeutic range is seen for warfarin as well as for heparin and LMW hepaπn Clearly, a need exists for an anticoagulant agent which is efficacious in controlling thrombotic and embolic disorders yet does not cause uncontrolled bleeding or its possibility Accordingly, there is also a need for anticoagulant agent structural information to enable identification and structure- based design of new anticoagulant agents SUMMARY OF THE INVENTION Accordingly, an aspect of the present invention is a BC2 Fab fragment crystal. Another aspect of the invention is a Fab fragment crystal containing BC2 CDRs. Another aspect of the invention is a SB249417 Fab fragment crystal. Another aspect of the invention is a method for identifying a peptidomimetics having Factor IX binding activity comprising the steps of searching a small molecule structural database with CDR structural parameters derived from anti-Factor IX Fab fragment crystals; selecting a molecular structure from the database which mimics the CDR structural parameters; synthesizing the selected molecular structure; and screening the synthesized molecule for Factor IX binding activity. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a three-dimensional structure of the residues of BC2 HC-CDR1. Figure 2 is a three-dimensional structure of the residues of BC2 HC-CDR2. Figure 3 is a three-dimensional structure of the residues of BC2 HC-CDR3. Figure 4 is a three-dimensional structure of the residues of BC2 LC-CDR1. Figure 5 is a three-dimensional structure of the residues of BC2 LC-CDR2. Figure 6 is a three-dimensional structure of the residues of BC2 LC-CDR3. Figure 7 is a three-dimensional structure of the residues of SB249417 HC-CDR 1. Figure 8 is a three-dimensional structure of the residues of SB249417 HC-CDR2. Figure 9 is a three-dimensional structure of the residues of SB249417 HC-CDR3. Figure 10 is a three-dimensional structure of the residues of SB249417 LC-CDR1. Figure 1 1 is a three-dimensional structure of the residues of SB249417 LC-CDR2. Figure 12 is a three-dimensional structure of the residues of SB249417 LC-CDR3. DETAILED DESCRIPTION OF THE INVENTION All publications, including but not limited to patents and patent applications, cited in this specification are herein incorporated by reference as though fully set forth. Factor IX (fIX) is a vitamin K-dependent serine protease zymogen which plays an important role in the amplification of the blood coagulation cascade by catalyzing the activation of factor X on the membrane surface in the presence of activated factor VIII and calcium. Murine anti-human factor IX monoclonal antibody (mAb) BC2, as described in U.S. Patent Application No. 08/783,853 is an IgGl kappa monoclonal antibody having useful properties for anticoagulant therapy in arterial and venous thrombosis. BC2 down- regulates the blood clotting cascade in a self-limiting manner. BC2 inhibits the activation of fIX to fIXa by fXI as well as its activation by the complex of tissue factor and fVIIa. BC2 also inhibits fIXa coagulant activity. BC2 binds to human fIX and fIXa in a calcium- dependent manner with a dissociation constant Kd=4 nM. BC2 also cross-reacts with and inhibits rat fIX. Humanized constructs of BC2 have been made and tested for anticoagulant activity in vitro and in animal models. These constructs are described in U.S. Patent Application No. 08/783,853 and, like BC2, are novel anticoagulants exhibiting self-limiting, neutralizing activity, namely they down-regulate the blood clotting cascade in a self- limiting manner, minimizing the bleeding risks associated with heparin and other anticoagulant therapies. One such humanized construct of BC2 is SB249417. As used herein, the term "self-limiting, neutralizing activity" refers to the activity of a peptidomimetic that binds to human coagulation factor IX or IXa and inhibits thrombosis in a manner such that limited modulation of coagulation is produced. "Limited modulation of coagulation" is defined as an increase in clotting time, as measured by prolongation of the activated partial thromboplastin time (aPTT), where plasma remains clottable with aPTT reaching a maximal value despite increasing concentrations of monoclonal antibody. This limited modulation of coagulation is in contrast to plasma being rendered unclottable and exhibiting an infinite aPTT in the presence of increasing concentrations of heparin. Preferably, the maximal aPTT values are within the heparin therapeutic range. Most preferably, maximal aPTT is within the range of about 35 seconds to about 100 seconds which corresponds to about 1.5 times to about 3.5 times the normal control aPTT value. In the humanization process, the mouse antibody framework is changed to that from a human antibody, leaving the antigen-binding site unchanged. This site is formed by certain regions in the mAb amino acid sequence which are termed the complementarity determining regions (CDRs), or hypervariable segments. The antigen-binding site, which determines its specificity to its antigen, is located in the Fab fragment of the antibody, which consists of the entire light chain (LC) and part of the heavy chain (HC). As part of an effort to develop functional small-molecule mimics of these therapeutic macromolecules, the structural and mechanistic features of the anticoagulant activity of the anti-flX mAbs BC2 and SB249417 have been determined. This information is useful for design and testing of small peptides that functionally mimic the mAb's anticoagulant properties and to develop these peptides for therapeutic use. The three-dimensional structures of the Fab fragments of BC2 and SB249417 were determined using X-ray crystallography as described in the Examples. The structural information can be stored on a computer-readable medium. The CDRs from the mouse and humanized Fab fragments have generally similar conformations. R.m.s. differences between corresponding CDR C α positions between the two Fabs are below 0.5 A, except in HC-CDR2 and HC-CDR3 where r.m.s. values are 1.97 and 3.7 A, respectively. The slight change in the conformations of HC-CDR2 and HC- CDR3 amount to an angular shift in the planes of these loops, keeping the angle between them unchanged. In both Fabs, the three HC CDRs and LC-CDR3 form a groove (27 A long, 8 A wide and 9 A deep) which runs through the CDR surface. CDR residues HC- Asn35, HC-Trp50, and LC-Arg95, which line a deep hole in the center of the groove, are considered important for antigen binding. Structural information obtained for the CDRs of the BC2 and SB249417 Fab structures is useful for discovery of small molecule peptidomimetics. Preferred peptidomimetics include peptides and synthetic organic molecules which bind to Factor DC and have self-limiting, neutralizing activity in an in vitro clotting assay. An exemplary approach to such a structure-based peptide mimic design follows (Zhao, et al, 1995; Monfardini C. et ai, 1996). A search of several small-molecule structural data bases such as Available Chemicals Directory, Cambridge Crystallographic Database, Fine Chemical Database and CONCORD database (for a review, see Rusinko A., 1993) is carried out using parameters derived from the CDR structures. The search can be 2-dimensional, 3-dimensional or both and can be done using a combination of software such as UNITY version 2.3.1 (Tripos, Inc.), MACCS 3D, CAVEAT and DOCK. Conformational flexibility of the small molecules is allowed. The strategy for conducting the search takes into account conformations of individual CDRs as well as combinations of CDRs and/or key residues in the mAb combining site. An initial approach is to focus on structural parameters from HC-CDR3, LC-CDR3 and HC-CDR2 since these CDRs have been found in other Fabs to participate intimately in antigen recognition. A search for small-molecule mimics of HC-CDR3, LC-CDR3 and HC-CDR2 is separately conducted. The structural parameters from each two of these three CDRs are combined and the search repeated. The next step will be using parameters from all three CDRs. The conformational parameters of the remaining three CDRs will be included at a later stage, resulting in a search combining all six CDRs. Preferably, the selected molecular structure mimics the parameters of CDR residues HC-Asn35, HC- Trp50, and LC-Arg95 Small-molecule hits resulting from the searches are synthesized and screened for factor-IX binding in an ELISA assay and preferably, for anti-thrombotic activity in a standard in vitro clotting assay Most preferably, the hits will also exhibit self- limiting, neutralizing activity Peptidomimetics produced by the method of the invention are expected to be useful in therapy of thrombotic and embolic disorders such as those associated with myocardial infarction, unstable angina, atπal fibrillation, stroke, renal damage, pulmonary embolism, deep vein thrombosis, percutaneous translumenal coronary angioplasty, disseminated intravascular coagulation, sepsis, artificial organs, shunts or prostheses The present invention will now be descπbed with reference to the following specific, non-limiting examples Example 1 Preparation and Purification of Fab Fragments Both BC2 and SB249417 Fab fragments were prepared and puπfied as follows 50 mL of freshly puπfied monoclonal anti-human fIX antibody sample (1 2mg/mL in PBS buffer) was concentrated in an Amicon cell using a 30-kDa molecular weight cutoff membrane (YM30, at 65 psi, 4°C) to a final volume of 5 0 mL and final concentration of 120 mg/mL A papain digest of the mAb was started by adding to the concentrated mAb sample 20μg/mL papain (Boehπnger Manheim, cat # 108014), 2 5 mM EDTA (pH 7 5) and 5 0 mM cysteine-HCL monohydrate (PIERCE, cat # 44889) and incubating the mixture at 37°C for 4 hours and shaking gently The reaction was stopped by cooling the mixture on The Fc fragment was removed by incubating the digest with 5 mL of protein A- Sepharose resin (Pharmacia) and mixing at 4°C for 1 hour The mixture was transferred into a 15 mL gravity-fed column, and the unbound fraction (containing the Fab fragment) was collected. The column was washed twice with a 8 mL volume of 20mM Na2HPθ4, 150mM NaCl, pH 7 5 The eluate and 2 washes were pooled and concentrated to 5 3 mL using an Amicon cell with a YM10 membrane at 4°C The sample was loaded on a Pharmacia Superdex 75 column (volume 320mL), pre- equihbrated with 20mM Na2HPO 150mM NaCl, pH 7 5 The column was then eluted with the same buffer at a rate of 2 5 mL/mm, and 1 mL fractions collected after 30 min of void-volume collection The Fab fragment eluted as a single molecular species as indicated by a large A28O peak appearing in fractions 26-36, which were pooled and assayed for protein concentration by A28O absorption. A total of 25 mg of Fab were generated using this standard protocol (purification yield = 50-60%). SDS-PAGE analysis of the Superdex 75 eluate revealed a single species with an apparent molecular weight of 47,000Da. IEF analysis of the BC2 Fab sample revealed the presence of multiple isoelectric variants; the two major isoforms have apparent pi values of 8.9 and 7.35. These two species were separated using an ion exchange chromatography step which proved necessary and sufficient for obtaining usable crystals. The 25 mg SEC eluate was buffer exchanged by thorough and repeated dialysis against 20mM Tris, pH 9.2, concentrated to 5 mL in an Amicon cell, and loaded on a 1 mL Pharmacia Mono Q column, pre-equilibrated with buffer A (20mM Tris, pH 9.2). The column was washed with 10 mL buffer A, and no protein eluted in the flow through. Three protein species were eluted with a 0-15% gradient of buffer B (20mM Tris, pH 9.2, 1.0M NaCl) followed by a 15-100% gradient of buffer B, at a rate of l.OmL/min. 1 mL fractions were collected. Fractions corresponding to the first (sharp) peak in the chromatogram were pooled, assayed for A28O absorption, buffer exchanged in an Amicon cell against 20mM HEPES, pH 7.4, concentrated to 8mg/mL and used for crystallization. Fractions from the other two peaks did not crystallize. The final yield of the protocol was approximately 36% (crystallizable fraction only). Example 2 Crystallization of Fab Fragments BC2 Fab: Protein isoform from peak 1 of the ion exchange step was crystallized using the vapor diffusion method in a sitting-drop setup. The well solution contained 14% PEG6K, 20mM ammonium sulfate (or lOOmM LiCl), lOmM CaAc 2 and 200mM imidazole/HEPES, pH 7.0. The drops were prepared by mixing 3 μL of the well solution with 3 μL of protein solution (8mg/mL in 20mM HEPES, pH 7.0). Large orthorhombic crystals grew in 5 days at 21 °C to a size of 0.8x0.3x0.25 mm 3 . The crystals diffracted to 3.0 A, in space group P21212, unit cell dimensions a=89.3, b=120.6, c=43.4 A, and one molecule in the asymmetric unit. SB249417 Fab: A similar sitting drop method was used. The well solution contained 30-40% saturated ammonium sulfate and 50mM MES, pH 6.0. The drops were prepared by mixing equal volumes of well solution and protein solution (10 mg/mL in 10 mM HEPES, pH 7.0). Large crystals grew in one week at 15 °C to a size of 0.6x0.4x0.3 mm 3 . The crystals diffracted to 2.2 A, in space group PI, unit cell dimensions a=56.6, b=56.6, c=73.7 A, α=86.0, β= 86.0, γ= 64.9°, and two molecules in the asymmetric unit. Example 3 X-Rav Data Collection X-ray diffraction data were collected on a MAR area detector mounted on a Rigaku high-brilliance source operated at 50 kV/100 mA with monochromatic CuK o radiation in 1° oscillations frames. Data from three and two different crystals were collected, merged and used for structure determination of the BC2 Fab and SB249417 Fab, respectively. All data were processed using the HKL program, edition 4 (Otwinowski, 1993). Table 1 summarizes the data collection parameters. For BC2, the merged data were used for structure determination, whereas structure refinement was done against a single-crystal data set with the best R-sym values. For SB249417, merged data were used for structure determination and refinement. Table 1: Summary of X-ray Diffraction Data. Parameter BC2 249417 cell a,b,c (A) 89.60, 120.69, 43.58 56.6, 56.6, 73.7 alpha, beta, gamma 90.0, 90.0, 90.0 deg. 86.0, 86.0, 64.9 deg. Resolution (A) 3.0 2.2 Number of observed reflections 132,951 145,877 Number of unique reflections 12,211 21,122 mosaicity 0.16 0.22 < I/ σ > 1 1.5 7.0 Completeness 99.7 99.9 % of data >2 σ 76.0 71.4 R-sym 0.12 0.07 Example 4 Structure Determination The structures of the Fabs were determined using generalized molecular replacement methods following the standard protocol of Brϋnger (1991). The procedure includes a real-space cross-rotation Patterson search (Huber, 1985) followed by Patterson coefficient (PC) refinement (Brϋnger, 1990), a translation search, and finally rigid-body refinement. The X-PLOR program suite was used (Brϋnger, 1992) for all four steps. A search model was constructed for BC2 from the PDB-deposited 1.9A structures of two Fabs: the light chain model from murine IgG2a Fab that neutralizes human rhinovirus 14 (PDB entry IFOR), and the heavy chain model from murine idiotype Fab 730.1.4 (PDB entry 1IAI). The two were combined by least-square fitting of the two-chain models. Sequence identity of the resulting probe with BC2 Fab is as follows: V L 84% C L 100% V H 84% C H 1 95%, A similar search model was constructed for SB249417 from the PDB-deposited 3.0 A humanized anti-CD 18 antibody Fab fragment (PDB entry 2FGW). Sequence identity of the search model with SB249417 Fab is as follows: V L 81% C L 100% V H 59% C H 1 99% In eachmodel, residues different from those in the amino acid sequence of the Fab were mutated to alanine. In the case of BC2, a cross-rotation search was done with this model which represents the entire asymmetric unit. Eulerian space was searched in the rotation- function's asymmetric unit (0 < θ, < 2rr, 0 < θ 2 < rr/2, 0 < θ 3 < π, where θ, , θ 2 , θ 3 are the Eulerian angles as defined by Rossmann & Blow (1962)) with a constant increment of 2.5° in each dimension. Data in the resolution range 15.0-4.0 A was used in this search. The top 6000 peaks of the rotation function (RF) were used for cluster analysis. The solutions of the rotation function were then subjected to PC refinement followed by rigid-body minimization of the solution with the highest PC value. The latter was done in three steps: 1) treating the entire molecular model as a rigid body, 2) treating the heavy chain and light chain each as a rigid body and 3) treating the variable (VJJ and VjJ and constant (Cpj 1 and CL) domains of each chain as a rigid body. In the case of SB249417, an initial self-rotation search converged to a single solution representing a non-crystallographic two-fold axis defined by spherical angles psi, phi = 147, 0. A cross-rotation search (0 < θ, < 2π, 0 < θ 2 < rr, 0 < θ 3 <2π) was followed by PC refinement, resulting in two solutions, which were related by non-crystallographic symmetry. Using the structure corresponding to the highest RF peak after PC refinement (one peak in the case of BC2 and two peaks related by NCS in the case of SB249417) and 15.0- 4.θA data, a translation search was carried out. For BC2, the search was restricted to half of the unit cell in all three dimensions. For SB249417, NCS was directly applied to the translation function solution to generate the other molecule in the PI cell. For each Fab, the structure corresponding to the top solution of the translation function was then rigid-body refined as described above. The rigid-body refined structure was then used to phase the reflections from a single-crystal data set, in the case of BC2, or merged data from multiple crystals in the case of SB249417. F 0 -F c and 2F 0 -F C electron density maps were calculated and inspected. The model was re-built to fit the map in the CDR regions and elsewhere using the true amino acid sequence of the Fab. The structures were refined using the simulated annealing protocols of X-PLOR (Brunger, 1992). Refinement parameters are summarized in Table 2. Table 2:Structure Refinement Statistics Parameter BC2 SB249417 5 Space group P2ι 2ι 2 PI Observations (N) 47,643 145,877 Unique reflections (N) 11,353 40,746 R-sym (on I, %) 0.09 0.07 0 Average I/s 8.8 7.1 Reflections use in refinement (N) 8469 36,628 Completeness of refinement data 92.2 94.3 Refinement resolution range (A) 20.0-3.0 15.0-2.2 Atoms used in refinement (N) 3157 6481 .5 Rcryst (%) 22.0 23.0 Rfree (%) 29.0 27.9 R.m.s. deviations from standard values: Bond length (A) 0.019 0.014 !0 Bond angles (deg.) 3.3 1.27 Mean B -factor (A^) 29.0 27.3 Like all Fab fragments, BC2 and SB249417 Fab structures are made up of a tetrahedral array of four globular domains - VL, VJ-Ϊ, CL and Cj-jl - which follow the 5 immunoglobulin fold. Each domain is constituted of two broad sheets of antiparallel β- strands held together by hydrophobic interactions. The CDR loops are ordered with varying temperature-factor values. The three-dimensional coordinates of the residues belonging to all six CDRs of BC2 and SB249417 are listed in Tables 3-8 and Tables 9-14, respectively. Figures 1-6 and 7-12 show the corresponding three dimensional structures. Table 3: Three dimensional coordinates of HC - CDR1 (HC: ASN31 - ASN35 from BC2 y z Q B ATOM 22 87 N ASN 31 38.145 52.427 -13.427 1.00 48.47 ATOM 2289 CA ASN 31 37.357 53.503 -12.856 1.00 48.47 ATOM 2290 CB ASN 31 35.961 53.611 -13.477 1.00 49.47 ATOM 2291 CG ASN 31 35.742 52.671 -14.676 1.00 49.47 ATOM 2292 OD1 ASN 31 36.684 52.260 -15.365 1.00 49.47 ATOM 2293 ND2 ASN 31 34.477 52.330 -14.916 1.00 49.47 ATOM 2296 C ASN 31 37.231 53.540 -11.325 1.00 48.47 ATOM 2297 0 ASN 31 36.898 54.595 -10.776 1.00 49.47 ATOM 2298 N TYR 32 37.491 52.428 -10.636 1.00 55.29 ATOM 2300 CA TYR 32 37.341 52.392 -9.167 1.00 55.29 ATOM 2301 CB TYR 32 36.051 51.709 -8.737 1.00 25.46 ATOM 2302 CG TYR 32 34.839 51.959 -9.549 1.00 25.46 ATOM 2303 CD1 TYR 32 34.842 51.790 -10.936 1.00 25.46 ATOM 2304 CE1 TYR 32 33.672 51.848 -11.656 1.00 25.46 ATOM 2305 CD2 TYR 32 33.642 52.198 -8.911 1.00 25.46 ATOM 2306 CE2 TYR 32 32.466 52.244 -9.600 1.00 25.46 ATOM 2307 CZ TYR 32 32.475 52.071 -10.966 1.00 25.46 ATOM 2308 OH TYR 32 31.269 52.059 -11.601 1.00 25.46 ATOM 2310 C TYR 32 38.442 51.679 -8.402 1.00 55.29 ATOM 2311 0 TYR 32 38.845 50.570 -8.772 1.00 25.46 ATOM 2312 N GLY 33 38.774 52.229 -7.237 1.00 17.19 ATOM 2314 CA GLY 33 39.817 51.656 -6.405 1.00 17.19 ATOM 2315 C GLY 33 39.406 50.378 -5.697 1.00 17.19 ATOM 2316 O GLY 33 38.237 50.200 -5.296 1.00 65.52 ATOM 2317 N MET 34 40.382 49.487 -5.526 1.00 36.25 ATOM 2319 CA MET 34 40.143 48.215 -4.854 1.00 36.25 ATOM 2320 CB MET 34 40.888 47.087 -5.555 1.00 15.05 ATOM 2321 CG MET 34 40.667 45.723 -4.926 1.00 15.05 ATOM 2322 SD MET 34 38.944 45.396 -4.815 1.00 15.05 ATOM 2323 CE MET 34 38.703 44.674 -6.413 1.00 15.05 ATOM 2324 C MET 34 40.635 48.287 -3.430 1.00 36.25 ATOM 2325 O MET 34 41.514 49.072 -3.107 1.00 15.05 ATOM 2326 N ASN 35 40.072 47.454 -2.570 1.00 16.44 ATOM 2328 CA ASN 35 40.513 47.391 -1.182 1.00 16.44 ATOM 2329 CB ASN 35 39.359 47.668 -0.196 1.00 23.13 ATOM 2330 CG ASN 35 38.947 49.118 -0.149 1.00 23.13 ATOM 2331 OD1 ASN 35 38.491 49.623 0.888 1.00 23.13 ATOM 2332 ND2 ASN 35 39.065 49.793 -1.275 1.00 23.13 ATOM 2335 C ASN 35 41.038 45.954 -0.980 1.00 16.44 ATOM 2336 O ASN 35 41.058 45.182 -1.920 1.00 23.13 Table 4: Three dimensional coordinates of HC - CDR2 (HC: TRP50 - GLY66 from BC2 X y z Q B ATOM 2474 N TRP 50 45.028 49.852 -0.044 1.00 2.00 ATOM 2476 CA TRP 50 44.159 50.501 -1.002 1.00 2.00 ATOM 2477 CB TRP 50 44.044 51.944 -0.556 1.00 57.49 ATOM 2478 CG TRP 50 42.874 52.695 -1.042 1.00 57.49 ATOM 2479 CD2 TRP 50 42.803 53.588 -2.163 1.00 57.49 ATOM 2480 CE2 TRP 50 41.556 54.226 -2.120 1.00 57.49 ATOM 2481 CE3 TRP 50 43.669 53.919 -3.196 1.00 57.49 ATOM 2482 CD1 TRP 50 41.703 52.803 -0.412 1.00 57.49 ATOM 2483 NE1 TRP 50 40.904 53.723 -1.037 1.00 57.49 ATOM 2485 CZ2 TRP 50 41.155 55.182 -3.058 1.00 57.49 ATOM 2486 CZ3 TRP 50 43.267 54.872 -4.132 1.00 57.49 ATOM 2487 CH2 TRP 50 42.033 55.486 -4.056 1.00 57.49 ATOM 2488 C TRP 50 44.923 50.556 -2.296 1.00 2.00 ATOM 2489 O TRP 50 46.141 50.436 -2.292 1.00 57.49 ATOM 2490 N ILE 51 44.239 50.756 -3.407 1.00 2.58 ATOM 2492 CA ILE 51 44.957 50.921 -4.652 1.00 2.58 ATOM 2493 CB ILE 51 45.528 49.623 -5.217 1.00 4.23 ATOM 2494 CG2 ILE 51 44.516 48.983 -6.161 1.00 4.23 ATOM 2495 CGI ILE 51 46.800 49.968 -5.991 1.00 4.23 ATOM 2496 CD1 ILE 51 47.581 48.788 -6.481 1.00 4.23 ATOM 2497 C ILE 51 44.113 51.616 -5.693 1.00 2.58 ATOM 2498 O ILE 51 42.925 51.332 -5.854 1.00 4.23 ATOM 2499 N ASN 52 44.738 52.546 -6.398 1.00 33.49 ATOM 2501 CA ASN 52 44.042 53.268 -7.441 1.00 33.49 ATOM 2502 CB ASN 52 44.451 54.725 -7.525 1.00 15.27 ATOM 2503 CG ASN 52 43.618 55.455 -8.514 1.00 15.27 ATOM 2504 OD1 ASN 52 43.668 55.173 -9.715 1.00 15.27 ATOM 2505 ND2 ASN 52 42.740 56.301 -8.015 1.00 15.27 ATOM 2508 C ASN 52 44.369 52.571 -8.732 1.00 33.49 ATOM 2509 O ASN 52 45.373 52.841 -9.404 1.00 15.27 ATOM 2510 N THR 53 43.386 51.808 -9.129 1.00 16.45 ATOM 2512 CA THR 53 43.414 50.928 -10.257 1.00 16.45 ATOM 2513 CB THR 53 42.142 50.216 -10.205 1.00 42.20 ATOM 2514 OG1 THR 53 41.089 51.138 -10.536 1.00 42.20 ATOM 2516 CG2 THR 53 41.936 49.718 -8.773 1.00 42.20 ATOM 2517 C THR 53 43.536 51.480 -11.656 1.00 16.45 ATOM 2518 O THR 53 42.981 50.923 -12.616 1.00 42.20 ATOM 2 519 N ARG 54 44.229 52.583 -11.795 1.00 50.54 ATOM 2521 CA ARG 54 44.366 53.184 -13.107 1.00 50.54 ATOM 2522 CB ARG 54 43.377 54.373 -13.131 1.00 42.70 ATOM 2523 CG ARG 54 43.078 54.966 -14.495 1.00 42.70 ATOM 2524 CD ARG 54 43.317 56.486 -14.569 1.00 42.70 ATOM 2525 NE ARG 54 42.980 56.929 -15.921 1.00 42.70 ATOM 2527 CZ ARG 54 43.854 57.134 -16.902 1.00 42.70 ATOM 2528 NH1 ARG 54 45.163 56.985 -16.697 1.00 42.70 ATOM 2531 NH2 ARG 54 43.407 57.341 -18.139 1.00 42.70 ATOM 2534 C ARG 54 45.798 53.722 -13.122 1.00 50.54 ATOM 2535 0 ARG 54 46.453 53.897 -14.161 1.00 42.70 ATOM 2536 N ASN 55 46.349 53.636 -11.933 1.00 22.51 ATOM 2538 CA ASN 55 47.588 54.260 -11.622 1.00 22.51 ATOM 2539 CB ASN 55 47.182 55.219 -10.536 1.00 62.29 ATOM 2540 CG ASN 55 48.043 56.422 -10.448 1.00 62.29 ATOM 2541 OD1 ASN 55 48.996 56.618 -11.205 1.00 62.29 ATOM 2542 ND2 ASN 55 47.679 57.279 -9.517 1.00 62.29 ATOM 2545 C ASN 55 48.594 53.325 -11.040 1.00 22.51 ATOM 2546 O ASN 55 49.771 53.374 -11.369 1.00 62.29 ATOM 2547 N GLY 56 48.129 52.529 -10.088 1.00 49.54 ATOM 2549 CA GLY 56 49.031 51.639 -9.397 1.00 49.54 ATOM 2550 C GLY 56 49.476 52.347 -8.124 1.00 49.54 ATOM 2551 O GLY 56 50.042 51.719 -7.214 1.00 47.80 ATOM 2552 N LYS 57 49.244 53.661 -8.044 1.00 54.37 ATOM 2554 CA LYS 57 49.608 54.400 -6.833 1.00 54.37 ATOM 2555 CB LYS 57 49.354 55.911 -6.963 1.00 38.06 ATOM 2556 CG LYS 57 50.526 56.635 -7.654 1.00 38.06 ATOM 2557 CD LYS 57 50.180 58.024 -8.266 1.00 38.06 ATOM 2558 CE LYS 57 50.217 59.176 -7.281 1.00 38.06 ATOM 2559 NZ LYS 57 51.151 60.258 -7.772 1.00 38.06 ATOM 2563 C LYS 57 48.819 53.662 -5.761 1.00 54.37 ATOM 2564 O LYS 57 47.726 53.131 -6.030 1.00 38.06 ATOM 2565 N SER 58 49.419 53.582 -4.581 1.00 54.98 ATOM 2567 CA SER 58 48.887 52.742 -3.525 1.00 54.98 ATOM 2568 CB SER 58 49.664 51.452 -3.702 1.00 58.93 ATOM 2569 OG SER 58 51.012 51.786 -4.083 1.00 58.93 ATOM 2571 C SER 58 49.025 53.181 -2.050 1.00 54.98 ATOM 2572 O SER 58 50.106 53.608 -1.630 1.00 58.93 ATOM 2573 N THR 59 47.982 52.953 -1.247 1.00 34.76 ATOM 2575 CA THR 59 47.991 53.360 0.163 1.00 34.76 ATOM 2576 CB THR 59 46.808 54.265 0.424 1.00 50.04 ContJTable 4 X y z Q B ATOM 2577 OG1 THR 59 46.669 55.185 -0.672 1.00 50.04 ATOM 2579 CG2 THR 59 47.012 55.055 1.720 1.00 50.04 ATOM 2580 C THR 59 47.812 52.183 1.085 1.00 34.76 ATOM 2581 O THR 59 46.880 51.425 0.888 1.00 50.04 ATOM 2582 N TYR 60 48.648 52.037 2.111 1.00 21.76 ATOM 2584 CA TYR 60 48.543 50.877 3.040 1.00 21.76 ATOM 2585 CB TYR 60 49.768 49.964 2.990 1.00 21.25 ATOM 2586 CG TYR 60 50.373 49.642 1.661 1.00 21.25 ATOM 2587 CD1 TYR 60 49.743 49.934 0.468 1.00 21.25 ATOM 2588 CE1 TYR 60 50.336 49.623 -0.751 1.00 21.25 ATOM 2589 CD2 TYR 60 51.614 49.022 1.600 1.00 21.25 ATOM 2590 CE2 TYR 60 52.191 48.699 0.407 1.00 21.25 ATOM 2591 CZ TYR 60 51.557 49.000 -0.763 1.00 21.25 ATOM 2592 OH TYR 60 52.147 48.629 -1.923 1.00 21.25 ATOM 2594 C TYR 60 48.452 51.284 4.495 1.00 21.76 ATOM 2595 O TYR 60 49.056 52.274 4.882 1.00 21.25 ATOM 2596 N VAL 61 47.793 50.459 5.307 1.00 2.00 ATOM 2598 CA VAL 61 47.636 50.717 6.748 1.00 2.00 ATOM 2599 CB VAL 61 46.724 49.642 7.436 1.00 36.32 ATOM 2600 CGI VAL 61 47.388 49.056 8.727 1.00 36.32 ATOM 2601 CG2 VAL 61 45.318 50.258 7.783 1.00 36.32 ATOM 2602 C VAL 61 48.997 50.684 7.395 1.00 2.00 ATOM 2603 O VAL 61 49.909 50.132 6.812 1.00 36.32 ATOM 2604 N ASP 62 49.126 51.225 8.610 1.00 69.13 ATOM 2606 CA ASP 62 50.439 51.226 9.291 1.00 69.13 ATOM 2607 CB ASP 62 50.443 52.071 10.580 1.00 34.42 ATOM 2608 CG ASP 62 50.989 53.499 10.376 1.00 34.42 ATOM 2609 OD1 ASP 62 51.241 54.198 11.375 1.00 34.42 ATOM 2610 OD2 ASP 62 51.149 53.950 9.218 1.00 34.42 ATOM 2611 C ASP 62 51.020 49.843 9.620 1.00 69.13 ATOM 2612 O ASP 62 52.212 49.614 9.403 1.00 34.42 ATOM 2613 N ASP 63 50.219 48.932 10.176 1.00 37.05 ATOM 2615 CA ASP 63 50.841 47.653 10.476 1.00 37.05 ATOM 2616 CB ASP 63 50.404 47.047 11.818 1.00 31.00 ATOM 2617 CG ASP 63 49.130 47.638 12.344 1.00 31.00 ATOM 2618 OD1 ASP 63 49.206 48.353 13.380 1.00 31.00 ATOM 2619 OD2 ASP 63 48.083 47.396 11.705 1.00 31.00 ATOM 2620 C ASP 63 50.729 46.662 9.365 1.00 37.05 ATOM 2621 O ASP 63 50.195 45.574 9.558 1.00 31.00 ATOM 2622 N PHE 64 51.151 47.070 8.179 1.00 9.67 ATOM 2624 CA PHE 64 51.163 46.178 7.041 1.00 9.67 ATOM 2625 CB PHE 64 49.824 46.205 6.333 1.00 25.09 ATOM 2626 CG PHE 64 48.767 45.403 7.020 1.00 25.09 ATOM 2627 CD1 PHE 64 47.897 45.998 7.930 1.00 25.09 ATOM 2628 CD2 PHE 64 48.641 44.050 6.761 1.00 25.09 ATOM 2629 CE1 PHE 64 46.931 45.264 8.573 1.00 25.09 ATOM 2630 CE2 PHE 64 47.666 43.294 7.403 1.00 25.09 ATOM 2631 CZ PHE 64 46.805 43.902 8.312 1.00 25.09 ATOM 2632 c PHE 64 52.293 46.600 6.112 1.00 9.67 ATOM 2633 0 PHE 64 52.075 46.831 4.923 1.00 25.09 ATOM 2634 N LYS 65 53.521 46.632 6.649 1.00 35.36 ATOM 2636 CA LYS 65 54.705 47.077 5.895 1.00 35.36 ATOM 2637 CB LYS 65 55.323 48.312 6.556 1.00 32.71 ATOM 2638 CG LYS 65 54.338 49.329 7.073 1.00 32.71 ATOM 2639 CD LYS 65 53.444 49.804 5.960 1.00 32.71 ATOM 2640 CE LYS 65 54.174 50.709 5.006 1.00 32.71 ATOM 2641 NZ LYS 65 53.726 52.139 5.153 1.00 32.71 ATOM 2645 C LYS 65 55.847 46.104 5.692 1.00 35.36 ATOM 2646 O LYS 65 56.414 45.574 6.651 1.00 32.71 ATOM 2647 N GLY 66 56.262 45.981 4.431 1.00 89.30 ATOM 2649 CA GLY 66 57.401 45.142 4.072 1.00 89.30 ATOM 2650 C GLY 66 57.055 44.153 2.973 1.00 89.30 ATOM 2651 O GLY 66 57.389 44.293 1.781 1.00 46.24 Table 5: Three dimensional coordinates of HC - CDR3 (HC: GLU99 - TYR110 from B ( C2 X y z Q B ATOM 2965 N GLϋ 99 35.523 49.858 -3.257 1.00 25.76 ATOM 2967 CA GLU 99 34.886 51.032 -2.668 1.00 25.76 ATOM 2968 CB GLU 99 35.928 51.777 -1.791 1.00 63.63 ATOM 2969 CG GLU 99 35.878 53.373 -1.706 1.00 63.63 ATOM 2970 CD GLU 99 37.307 54.052 -1.532 1.00 63.63 ATOM 2971 OE1 GLU 99 38.278 53.384 -1.090 1.00 63.63 ATOM 2972 OE2 GLU 99 37.460 55.269 -1.828 1.00 63.63 ATOM 2973 C GLU 99 34.507 51.829 -3.943 1.00 25.76 ATOM 2974 0 GLU 99 35.321 51.930 -4.866 1.00 63.63 ATOM 2975 N GLY 100 33.234 52.203 -4.085 1.00 36.41 ATOM 2977 CA GLY 100 32.814 52.965 -5.257 1.00 36.41 ATOM 2978 C GLY 100 31.914 54.127 -4.831 1.00 36.41 ATOM 2979 O GLY 100 31.060 53.923 -3.995 1.00 41.46 ATOM 2980 N ASN 101 31.966 55.277 -5.502 1.00 33.66 ATOM 2982 CA ASN 101 31.196 56.434 -5.060 1.00 33.66 ATOM 2983 CB ASN 101 31.810 57.744 -5.534 1.00 24.12 ATOM 2984 CG ASN 101 32.059 58.676 -4.388 1.00 24.12 ATOM 2985 OD1 ASN 101 31.122 59.065 -3.700 1.00 24.12 ATOM 2986 ND2 ASN 101 33.320 58.941 -4.099 1.00 24.12 ATOM 2989 C ASN 101 29.689 56.506 -5.183 1.00 33.66 ATOM 2990 O ASN 101 29.117 56.182 -6.233 1.00 24.12 ATOM 2991 N MET 102 29.083 57.024 -4.102 1.00 83.69 ATOM 2993 CA MET 102 27.625 57.284 -3.908 1.00 83.69 ATOM 2994 CB MET 102 26.730 56.030 -4.143 1.00 59.11 ATOM 2995 CG MET 102 25.270 56.204 -3.635 1.00 59.11 ATOM 2996 SD MET 102 23.981 55.029 -4.261 1.00 59.11 ATOM 2997 CE MET 102 22.477 56.146 -4.344 1.00 59.11 ATOM 2998 C MET 102 27.430 57.829 -2.459 1.00 83.69 ATOM 2999 O MET 102 27.367 57.011 -1.513 1.00 59.11 ATOM 3000 N ASP 103 27.313 59.177 -2.335 1.00 81.57 ATOM 3002 CA ASP 103 27.125 59.990 -1.086 1.00 81.57 ATOM 3003 CB ASP 103 26.625 59.139 0.117 1.00 22.70 ATOM 3004 CG ASP 103 26.176 59.987 1.343 1.00 22.70 ATOM 3005 OD1 ASP 103 26.907 60.892 1.813 1.00 22.70 ATOM 3006 OD2 ASP 103 25.106 59.666 1.902 1.00 22.70 ATOM 3007 C ASP 103 28.446 60.681 -0.759 1.00 81.57 ATOM 3008 O ASP 103 28.961 60.589 0.366 1.00 22.70 ATOM 3009 N GLY 104 28.984 61.379 -1.761 1.00 86.53 ATOM 3011 CA GLY 104 30.272 62.065 -1.608 1.00 86.53 ATOM 3012 C GLY 104 31.473 61.122 -1.460 1.00 86.53 ATOM 3013 O GLY 104 32.234 60.889 -2.412 1.00 46.20 ATOM 3014 N TYR 105 31.716 60.669 -0.228 1.00 98.58 ATOM 3016 CA TYR 105 32.808 59.688 0.036 1.00 98.58 ATOM 3017 CB TYR 105 33.017 59.412 1.557 1.00 64.10 ATOM 3018 CG TYR 105 33.326 60.523 2.585 1.00 64.10 ATOM 3019 CD1 TYR 105 34.643 60.884 2.881 1.00 64.10 ATOM 3020 CE1 TYR 105 34.952 61.681 3.977 1.00 64.10 ATOM 3021 CD2 TYR 105 32.318 61.015 3.435 1.00 64.10 ATOM 3022 CE2 TYR 105 32.620 61.810 4.531 1.00 64.10 ATOM 3023 CZ TYR 105 33.936 62.128 4.802 1.00 64.10 ATOM 3024 OH TYR 105 34.269 62.843 5.920 1.00 64.10 ATOM 3026 C TYR 105 32.256 58.342 -0.529 1.00 98.58 ATOM 3027 O TYR 105 31.153 58.311 -1.096 1.00 64.10 ATOM 3028 N PHE 106 32.944 57.243 -0.170 1.00 48.28 ATOM 3030 CA PHE 106 32.570 55.829 -0.484 1.00 48.28 ATOM 3031 CB PHE 106 32.058 55.183 0.800 1.00 53.07 ATOM 3032 CG PHE 106 30.689 55.652 1.196 1.00 53.07 ATOM 3033 CD1 PHE 106 30.486 56.963 1.576 1.00 53.07 ATOM 3034 CD2 PHE 106 29.597 54.794 1.117 1.00 53.07 ATOM 3035 CE1 PHE 106 29.255 57.405 1.875 1.00 53.07 ATOM 3036 CE2 PHE 106 28.347 55.232 1.414 1.00 53.07 ATOM 3037 CZ PHE 106 28.161 56.548 1.791 1.00 53.07 ATOM 3038 C PHE 106 31.498 55.596 -1.605 1.00 48.28 ATOM 3039 O PHE 106 31.316 56.481 -2.420 1.00 53.07 ATOM 3040 N PRO 107 30.807 54.401 -1.651 1.00 76.34 ATOM 3041 CD PRO 107 29.472 54.859 -2.148 1.00 42.84 ATOM 3042 CA PRO 107 30.633 53.080 -0.965 1.00 76.34 ATOM 3043 CB PRO 107 29.321 52.561 -1.567 1.00 42.84 ATOM 3044 CG PRO 107 28.479 53.811 -1.600 1.00 42.84 ATOM 3045 C PRO 107 31.730 51.933 -0.822 1.00 76.34 Cont./ Table 5 X y z Q B ATOM 3046 O PRO 107 32.951 52. 163 -0.993 1.00 42.84 ATOM 3047 N PHE 108 31.227 50. 700 -0.638 1.00 52.21 ATOM 3049 CA PHE 108 31.951 49 437 -0.323 1.00 52.21 ATOM 3050 CB PHE 108 31.919 49 332 1.174 1.00 28.72 ATOM 3051 CG PHE 108 30.743 50 065 1.736 1.00 28.72 ATOM 3052 CD1 PHE 108 30.900 51 325 2.267 1.00 28.72 ATOM 3053 CD2 PHE 108 29.464 49 611 1.445 1.00 28.72 ATOM 3054 CE1 PHE 108 29.788 52 112 2.467 1.00 28.72 ATOM 3055 CE2 PHE 108 28.351 50 384 1.636 1.00 28.72 ATOM 3056 CZ PHE 108 28.508 51 635 2.135 1.00 28.72 ATOM 3057 C PHE 108 30.973 48 375 -0.826 1.00 52.21 ATOM 3058 O PHE 108 30.487 47 516 -0.077 1.00 28.72 ATOM 3059 N THR 109 30.699 48 439 -2.115 1.00 26.26 ATOM 3061 CA THR 109 29.735 47 613 -2.797 1.00 26.26 ATOM 3062 CB THR 109 29.620 48 129 -4.186 1.00 36.21 ATOM 3063 OG1 THR 109 30.948 48 431 -4.661 1.00 36.21 ATOM 3065 CG2 THR 109 28.723 49 376 -4.229 1.00 36.21 ATOM 3066 C THR 109 29.831 46 122 -2.998 1.00 26.26 ATOM 3067 O THR 109 28.942 45 377 -2.617 1.00 36.21 ATOM 3068 N TYR 110 30.817 45 735 -3.796 1.00 20.44 ATOM 3070 CA TYR 110 31.000 44 328 -4.171 1.00 20.44 ATOM 3071 CB TYR 110 30.912 44 207 -5.686 1.00 60.15 ATOM 3072 CG TYR 110 29.897 45 158 -6.284 1.00 60.15 ATOM 3073 CD1 TYR 110 28.578 45 .154 -5.841 1.00 60.15 ATOM 3074 CE1 TYR 110 27.628 45 .978 -6.424 1.00 60.15 ATOM 3075 CD2 TYR 110 30.246 46 .025 -7.321 1.00 60.15 ATOM 3076 CE2 TYR 110 29.315 46 .848 -7.903 1.00 60.15 ATOM 3077 CZ TYR 110 27.998 46 .822 -7.470 1.00 60.15 ATOM 3078 OH TYR 110 27.074 47 .577 -8.158 1.00 60.15 ATOM 3080 C TYR 110 32.284 43 .665 -3.691 1.00 20.44 ATOM 3081 O TYR 110 33.283 43 .680 -4.404 1.00 60.15 Table 6: Three dimensional coordinates of LC - CDRl (LC: ARG24 - HIS33) from BC2 Q B ATOM 199 N ARG 24 31. 034 53. 669 19. 975 1.00 35. 70 ATOM 201 CA ARG 24 31. 810 54. 840 20. 383 1.00 35. 70 ATOM 202 CB ARG 24 32. 226 54. 801 21. 876 1.00 43. 83 ATOM 203 CG ARG 24 31. 253 54. 267 22. 939 1.00 43. 83 ATOM 204 CD ARG 24 31. 676 54. 727 24. 383 1.00 43. 83 ATOM 205 NE ARG 24 33. 056 54. 377 24. 755 1.00 43. 83 ATOM 207 CZ ARG 24 33. 426 53. 850 25. 931 1.00 43. 83 ATOM 208 NH1 ARG 24 32. 531 53. 605 26. 891 1.00 43. 83 ATOM 211 NH2 ARG 24 34. 697 53. .526 26. 132 1.00 43. 83 ATOM 214 C ARG 24 33. 123 54. .991 19. 621 1.00 35. 70 ATOM 215 O ARG 24 33. 959 54. .092 19. 630 43. .83 ATOM 216 N ALA 25 33. 326 56. .123 18. 974 82. ,87 ATOM 218 CA ALA 25 34. ,622 56, .346 18. ,320 82. .87 ATOM 219 CB ALA 25 34. .436 57, .225 17. .056 87, .02 ATOM 220 C ALA 25 35. .461 57, .105 19. ,369 82. .87 ATOM 221 O ALA 25 34. .882 57. .853 20. .152 1.00 87. .02 ATOM 222 N SER 26 36. .786 56 .920 19. .422 44 .67 ATOM 224 CA SER 26 37, .565 57 .688 20. .410 44 .67 ATOM 225 CB SER 26 39. .000 57 .177 20. .557 4. .82 ATOM 226 OG SER 26 39. .698 57 .261 19, .336 4, .82 ATOM 228 C SER 26 37 .582 59 .186 20 .040 44 .67 ATOM 229 O SER 26 37 .708 60 .047 20 .912 1.00 4 .82 ATOM 230 N SER 27 37 .430 59 .501 18 .755 1.00 27 .16 ATOM 232 CA SER 27 37 .462 60 .916 18 .351 1.00 27 .16 ATOM 233 CB SER 27 38 .837 61 .282 17 .765 00 37 .32 ATOM 234 OG SER 27 39 .886 61 .091 18 .724 00 37 .32 ATOM 236 C SER 27 36 .374 61 .225 17 .362 00 27 .16 ATOM 237 O SER 27 35 .718 60 .310 16 .860 00 37 .32 ATOM 238 N SER 28 36 .185 62 .501 17 .060 00 32 .79 ATOM 240 CA SER 28 35 .117 62 .876 16 .134 1.00 32 .79 ATOM 241 CB SER 28 34 .817 64 .378 16 .238 1.00 44 .89 ATOM 242 OG SER 28 34 .248 64 .686 17 .509 1.00 44 .89 ATOM 244 C SER 28 35 .316 62 .487 14 .671 1.00 32 .79 ATOM 245 O SER 28 36 .334 62 .847 14 .060 1.00 44 .89 Cont./ Table 6 X y z Q B ATOM 246 N VAL 29 34.333 61.749 14.132 1.00 25.47 ATOM 248 CA VAL 29 34.322 61.309 12.731 1.00 25.47 ATOM 249 CB VAL 29 34.592 59.832 12.597 1.00 6.08 ATOM 250 CGI VAL 29 33.479 59.053 13.249 1.00 6.08 ATOM 251 CG2 VAL 29 34.735 59.486 11.152 1.00 6.08 ATOM 252 C VAL 29 32.990 61.664 12.049 1.00 25.47 ATOM 253 O VAL 29 31.974 61.820 12.715 1.00 6.08 ATOM 254 N ASN 30 32.994 61.694 10.711 1.00 14.73 ATOM 256 CA ASN 30 31.843 62.139 9.908 1.00 14.73 ATOM 257 CB ASN 30 32.372 62.765 8.606 1.00 54.87 ATOM 258 CG ASN 30 33.253 64.006 8.853 1.00 54.87 ATOM 259 OD1 ASN 30 33.627 64.730 7.915 1.00 54.87 ATOM 260 ND2 ASN 30 33.581 64.265 10.123 1.00 54.87 ATOM 263 C ASN 30 30.530 61.380 9.587 1.00 14.73 ATOM 264 O ASN 30 29.515 62.046 9.304 1.00 54.87 ATOM 265 N TYR 31 30.508 60.040 9.619 1.00 32.69 ATOM 267 CA TYR 31 29.296 59.231 9.272 1.00 32.69 ATOM 268 CB TYR 31 28.842 59.474 7.827 1.00 35.47 ATOM 269 CG TYR 31 29.807 58.968 6.782 1.00 35.47 ATOM 270 CD1 TYR 31 29.369 58.639 5.509 1.00 35.47 ATOM 271 CE1 TYR 31 30.253 58.276 4.526 1.00 35.47 ATOM 272 CD2 TYR 31 31.180 58.883 7.021 1.00 35.47 ATOM 273 CE2 TYR 31 32.065 58.497 6.034 1.00 35.47 ATOM 274 CZ TYR 31 31.597 58.200 4.776 1.00 35.47 ATOM 275 OH TYR 31 32.441 57.819 3.774 1.00 35.47 ATOM 277 C TYR 31 29.598 57.764 9.380 1.00 32.69 ATOM 278 O TYR 31 30.758 57.393 9.362 1.00 35.47 ATOM 279 N MET 32 28.582 56.902 9.311 1.00 32.43 ATOM 281 CA MET 32 28.871 55.457 9.421 1.00 32.43 ATOM 282 CB MET 32 28.762 54.944 10.841 1.00 25.19 ATOM 283 CG MET 32 30.091 54.566 11.416 1.00 25.19 ATOM 284 ΞD MET 32 29.802 53.661 12.911 1.00 25.19 ATOM 285 CE MET 32 30.987 54. ~23 14.048 1.00 25.19 ATOM 286 C MET 32 28.286 54.415 8.494 1.00 32.43 ATOM 287 O MET 32 27.156 54.486 8.031 1.00 25.19 ATOM 288 N HIS 33 29.094 53.397 8.266 1.00 41.58 ATOM 290 CA HIS 33 28.729 52.285 7.411 1.00 41.58 ATOM 291 CB HIS 33 29.763 52.135 6.303 1.00 27.09 ATOM 292 CG HIS 33 29.889 53.329 5.438 1.00 27.09 ATOM 293 CD2 HIS 33 28.963 54.054 4.784 1.00 27.09 ATOM 294 ND1 HIS 33 31.084 53.947 5.213 1.00 27.09 ATOM 296 CE1 HIS 33 30.912 55.005 4.445 1.00 27.09 ATOM 297 NE2 HIS 33 29.619 55.085 4.178 1.00 27.09 ATOM 299 C HIS 33 28.741 51.040 8.265 1.00 41.58 ATOM 300 O HIS 33 29.751 50.763 8.934 1.00 27.09 Table 7: Three dimensional coordinates ol 1 C- CDR2 (ALA49 - SER55 from BC2 X y Z Q B ATOM 462 N ALA 49 26.073 55.473 5.034 1.00 33.29 ATOM 464 CA ALA 49 25.852 56.839 5.537 1.00 33.29 ATOM 465 CB ALA 49 25.280 57.702 4.416 1.00 20.38 ATOM 466 C ALA 49 24.957 56.935 6.776 1.00 33.29 ATOM 467 O ALA 49 23.917 57.578 6.722 1.00 20.38 ATOM 468 N THR 50 25.356 56.269 7.854 1.00 27.27 ATOM 470 CA THR 50 24.647 56.254 9.128 1.00 27.27 ATOM 471 CB THR 50 24.727 57.596 9.824 1.00 38.91 ATOM 472 OG1 THR 50 26.101 57.970 9.914 1.00 38.91 ATOM 474 CG2 THR 50 24.118 57.496 11.237 1.00 38.91 ATOM 475 C THR 50 23.205 55.813 9.182 1.00 27.27 ATOM 476 O THR 50 22.882 54.921 9.943 1.00 38.91 ATOM 477 N SER 51 22.320 56.513 8.481 1.00 17.32 ATOM 479 CA SER 51 20.912 56.148 8.500 1.00 17.32 ATOM 480 CB SER 51 20.080 57.295 9.084 1.00 61.11 ATOM 481 OG SER 51 20.699 57.780 10.281 1.00 61.11 ATOM 483 C SER 51 20.422 55.717 7.121 1.00 17.32 ATOM 484 O SER 51 19.258 55.405 6.945 1.00 61.11 ATOM 485 N ASN 52 21.304 55.713 6.139 1.00 28.10 ATOM 487 CA ASN 52 20.921 55.255 4.809 1.00 28.10 ATOM 488 CB ASN 52 21.851 55.873 3.788 1.00 33.84 ATOM 489 CG ASN 52 21.631 57.348 3.607 1.00 33.84 ATOM 490 OD1 ASN 52 20.881 58.004 4.349 1.00 33.84 ATOM 491 ND2 ASN 52 22.323 57.893 2.620 1.00 33.84 ATOM 494 C ASN 52 20.954 53.713 4.650 1.00 28.10 ATOM 495 O ASN 52 22.032 53.113 4.686 1.00 33.84 ATOM 496 N LEU 53 19.797 53.084 4.392 1.00 46.86 ATOM 498 CA LEU 53 19.714 51.607 4.228 1.00 46.86 ATOM 499 CB LEU 53 18.296 51.079 4.477 1.00 14.22 ATOM 500 CG LEU 53 17.803 51.184 5.911 1.00 14.22 ATOM 501 CD1 LEU 53 16.468 50.481 6.075 1.00 14.22 ATOM 502 CD2 LEU ;3 18.826 50.577 6.823 1.00 14.22 ATOM 503 C LEU .3 20.224 51.072 2.880 1.00 46.86 ATOM 504 O LEU 53 20.184 51.769 1.857 1.00 14.22 ATOM 505 N ALA 54 20.731 49.838 2.911 1.00 41.00 ATOM 507 CA ALA 54 21.272 49.153 1.737 1.00 41.00 ATOM 508 CB ALA 54 22.309 48.157 2.174 1.00 26.54 ATOM 509 C ALA 54 20.166 48.465 0.946 1.00 41.00 ATOM 510 O ALA 54 19.073 48.220 1.460 1.00 26.54 ATOM 511 N SER 55 20.480 48.052 -0.272 1.00 19.96 ATOM 513 CA SER 55 19.452 47.470 -1.097 1.00 19.96 ATOM 514 CB SER 55 19.787 47.612 -2.576 1.00 64.54 ATOM 515 OG SER 55 18.587 47.553 -3.340 1.00 64.54 ATOM 517 C SER 55 19.037 46.060 -0.792 1.00 19.96 ATOM 518 O SER 55 19.652 45.088 -1.257 1.00 64.54 Table 8: Three dimensional coordinates of LC - CDR3 (GLN88-THR96)mτm BC2 X Z Q B ATOM 803 N y GLN 88 31.968 50.434 10.331 1.00 11.01 ATOM 805 CA GLN 88 33.222 50.903 9.776 1.00 11.01 ATOM 806 CB GLN 88 33.420 50.334 8.398 1.00 23.74 ATOM 807 CG GLN 88 34.485 50.965 7.564 1.00 23.74 ATOM 808 CD GLN 88 33.951 51.156 6.176 1.00 23.74 ATOM 809 OEl GLN 88 32.768 51.520 6.006 1.00 23.74 ATOM 810 NE2 GLN 88 34.780 50.887 5.164 1.00 23.74 ATOM 813 C GLN 88 33.131 52.420 9.743 1.00 11.01 ATOM 814 O GLN 88 32.034 52.987 9.802 1.00 23.74 ATOM 815 N GLN 89 34.289 53.063 9.641 1.00 22.56 ATOM 817 CA GLN 89 34.453 54.515 9.651 1.00 22.56 ATOM 818 CB GLN 89 35.447 54.806 10.813 1.00 21.80 ATOM 819 CG GLN 89 36.354 56.035 10.763 1.00 21.80 ATOM 820 CD GLN 89 37.702 55.805 10.084 1.00 21.80 ATOM 821 OEl GLN 89 37.886 56.146 8.907 1.00 21.80 ATOM 822 NE2 GLN 89 38.650 55.247 10.817 1.00 21.80 ATOM 825 C GLN 89 34.989 54.900 8.266 1.00 22.56 ATOM 826 O GLN 89 35.529 54.045 7.606 1.00 21.80 ATOM 827 N TRP 90 34.781 56.120 7.772 1.00 27.74 ATOM 829 CA TRP 90 35.345 56.493 6.449 1.00 27.74 ATOM 830 CB TRP 90 34.369 56.131 5.308 1.00 90.21 ATOM 831 CG TRP 90 34.940 55.660 3.942 1.00 90.21 ATOM 832 CD2 TRP 90 35.677 56.438 3.003 1.00 90.21 ATOM 833 CE2 TRP 90 35.840 55.671 1.829 1.00 90.21 ATOM 834 CE3 TRP 90 36.214 57.722 3.022 1.00 90.21 ATOM 835 CDl TRP 90 34.714 54.453 3.320 1.00 90.21 ATOM 836 NE1 TRP 90 35.249 54.456 2.041 1.00 90.21 ATOM 838 CZ2 TRP 90 36.510 56.156 0.702 1.00 90.21 ATOM 839 CZ3 TRP 90 36.884 58.194 1.890 1.00 90.21 ATOM 840 CH2 TRP 90 37.019 57.413 0.752 1.00 90.21 ATOM 841 C TRP 90 35.614 57.999 6.437 1.00 27.74 ATOM 842 O TRP 90 34.962 58.721 5.694 1.00 90.21 ATOM 843 N SER 91 36.590 58.456 7.236 1.00 33.90 ATOM 845 CA SER 91 36.919 59.882 7.305 1.00 33.90 ATOM 846 CB SER 91 35.972 60.566 8.290 1.00 33.23 ATOM 847 OG SER 91 34.617 60.159 8.093 1.00 33.23 ATOM 849 C SER 91 38.345 60.167 7.787 1.00 33.90 ATOM 850 O SER 91 38.725 61.333 7.955 1.00 33.23 ATOM 851 N ILE 92 39.144 59.128 7.999 1.00 2.00 ATOM 853 CA ILE 92 40.460 59.355 8.562 1.00 2.00 ATOM 854 CB ILE 92 40.486 58.910 10.044 1.00 6.47 ATOM 855 CG2 ILE 92 41.380 59.809 10.888 1.00 6.47 ATOM 856 CGI ILE 92 39.063 58.849 10.607 1.00 6.47 ATOM 857 CDl ILE 92 38.423 60.168 10.911 1.00 6.47 ATOM 858 C ILE 92 41.495 58.514 7.947 1.00 2.00 ATOM 859 O ILE 92 41.199 57.590 7.204 1.00 6.47 ATOM 860 N ASN 93 42.732 58.864 8.266 1.00 50.27 ATOM 862 CA ASN 93 43.854 58.038 7.897 1.00 50.27 ATOM 863 CB ASN 93 45.208 58.800 7.682 1.00 86.79 ATOM 864 CG ASN 93 46.486 57.828 7.455 1.00 86.79 ATOM 865 OD1 ASN 93 47.427 57.772 8.308 1.00 86.79 ATOM 866 ND2 ASN 93 46.515 57.093 6.321 1.00 86.79 ATOM 869 C ASN 93 43.951 57.245 9.226 1.00 50.27 ATOM 870 O ASN 93 43.982 57.844 10.306 1.00 86.79 ATOM 871 N PRO 94 43.557 55.965 9.198 1.00 31.00 ATOM 872 CD PRO 94 44.264 54.985 10.018 1.00 20.78 ATOM 873 CA PRO 94 43.071 55.322 7.987 1.00 31.00 ATOM 874 CB PRO 94 43.911 54.060 7.900 1.00 20.78 ATOM 875 CG PRO 94 45.051 54.288 8.974 1.00 20.78 ATOM 876 C PRO 94 41.636 55.034 8.421 1.00 31.00 ATOM 877 O PRO 94 41.243 55.377 9.550 1.00 20.78 ATOM 878 N ARG 95 40.833 54.492 7.530 1.00 12.98 ATOM 880 CA ARG 95 39.478 54.164 7.925 1.00 12.98 ATOM 881 CB ARG 95 38.592 54.022 6.711 1.00 25.66 ATOM 882 CG ARG 95 39.316 53.550 5.504 1.00 25.66 ATOM 883 CD ARG 95 38.629 54.020 4.254 1.00 25.66 ATOM 884 NE ARG 95 39.628 54.435 3.283 1.00 25.66 ATOM 886 CZ ARG 95 39.431 54.489 1.973 1.00 25.66 ATOM 887 NH1 ARG 95 38.274 54.150 1.454 1.00 25.66 ATOM 890 NH2 ARG 95 40.412 54.885 1.183 1.00 25.66 ATOM 893 C ARG 95 39.599 52.868 8.709 1.00 12.98 ATOM 894 O ARG 95 40.633 52.213 8.651 1.00 25.66 ATOM 895 N THR 96 38.605 52.532 9.520 1.00 14.80 Cont/Table 8 ATOM 898 CB THR 96 39.459 51 542 11 670 1 00 36 32 ATOM 899 OG1 THR 96 38.718 52 498 12 439 1 00 36 32 ATOM 901 CG2 THR 96 40.908 52 045 11 476 1 00 36 32 ATOM 902 C THR 96 37.365 50 730 10 607 1 00 14 80 ATOM 903 0 THR 96 36.340 51 326 10 292 1 00 36 32 Table 9: Ηiree dimensional coordinates of HC- CDRl (ASN31 - ASN35)fromSB249417 ATOM 2300 N ASN 31 53.647 23.490 34.881 1.00 20. 53 ATOM 2302 CA ASN 31 54.400 24.257 33.887 1.00 20. 53 ATOM 2303 CB ASN 31 53.820 25.666 33.715 1.00 39. 50 ATOM 2304 CG ASN 31 53.118 25.859 32.376 1.00 39 50 ATOM 2305 OD1 ASN 31 53.469 25.236 31.370 1.00 39 50 ATOM 2306 ND2 ASN 31 52.128 26.741 32.358 1.00 39 50 ATOM 2309 C ASN 31 55.860 24.369 34.306 1.00 20 53 ATOM 2310 O ASN 31 56.746 24.530 33.466 1.00 39 50 ATOM 2311 N TYR 32 56.103 24.314 35.612 1.00 18 56 ATOM 2313 CA TYR 32 57.458 24.408 36.148 1.00 18 56 ATOM 2314 CB TYR 32 57.571 25.582 37.122 41 90 ATOM 2315 CG TYR 32 57.374 26.943 36.499 41 90 ATOM 2316 CDl TYR 32 56.107 27.516 36.415 41 90 ATOM 2317 CE1 TYR 32 55.923 28.782 35.869 41 90 ATOM 2318 CD2 TYR 32 58.459 27.672 36.018 41 90 ATOM 2319 CE2 TYR 32 58.288 28.940 35.472 41 90 ATOM 2320 CZ TYR 32 57.017 29.489 35.402 41 90 ATOM 2321 OH TYR 32 56.836 30.745 34.875 41 90 ATOM 2323 C TYR 32 57.824 23.124 36.875 18 56 ATOM 2324 O TYR 32 57.024 22.590 37.642 41 90 ATOM 2325 N GLY 33 59.032 22.631 36.626 1.00 32 09 ATOM 2327 CA GLY 33 59.480 21.415 37.276 1.00 32 09 ATOM 2328 C GLY 33 59.805 21.659 38.736 1.00 32 09 ATOM 2329 O GLY 33 60.028 22.802 39.140 1.00 20 56 ATOM 2330 N MET 34 59.813 20.593 39.530 8 75 ATOM 2332 CA MET 34 60.119 20.700 40.949 8 75 ATOM 2333 CB MET 34 58.988 20.101 41.787 26 05 ATOM 2334 CG MET 34 59.129 20.334 43.283 26 05 ATOM 2335 SD MET 34 59.069 22.082 43.705 26 .05 ATOM 2336 CE MET 34 57.315 22.344 43.849 26 .05 ATOM 2337 C MET 34 61.417 19.972 41.256 8 .75 ATOM 2338 O MET 34 61.514 18.759 41.073 1.00 26 .05 ATOM 2339 N ASN 35 62.425 20.722 41.687 1.00 25 .14 ATOM 2341 CA ASN 35 63.720 20.147 42.034 00 25 .14 ATOM 2342 CB ASN 35 64.859 21.091 41.642 00 22 .15 ATOM 2343 CG ASN 35 65.135 21.097 40.156 00 22 .15 ATOM 2344 OD1 ASN 35 65.207 22.152 39.533 00 22 .15 ATOM 2345 ND2 ASN 35 65.347 19.921 39.588 00 22 .15 ATOM 2348 C ASN 35 63.785 19.906 43.533 1.00 25 .14 ATOM 2349 O ASN 35 63.256 20.693 44.316 1.00 22.15 Table 10: Three dimensional coordinates of HC-CDR2(TRP50-GLY66)fromSB 249417 ATOM 2490 N TRP 50 64.690 15.841 39.634 1.00 10.37 ATOM 2492 CA TRP 50 63.706 16.753 39.073 1.00 10.37 ATOM 2493 CB TRP 50 64.255 17.405 37.796 1.00 82.57 ATOM 2494 CG TRP 50 64.648 16.439 36.697 1.00 82.57 ATOM 2495 CD2 TRP 50 64.574 16.669 35.282 1.00 82.57 ATOM 2496 CE2 TRP 50 65.053 15.504 34.643 1.00 82.57 ATOM 2497 CE3 TRP 50 64.150 17.748 34.494 1.00 82.57 ATOM 2498 CDl TRP 50 65.155 15.177 36.849 1.00 82.57 ATOM 2499 NE1 TRP 50 65.400 14.610 35.622 1.00 82.57 ATOM 2501 CZ2 TRP 50 65.121 15.386 33.249 1.00 82.57 ATOM 2502 CZ3 TRP 50 64.219 17.629 33.106 1.00 82.57 ATOM 2503 CH2 TRP 50 64.701 16.456 32.501 1.00 82.57 ATOM 2504 C TRP 50 62.412 16.021 38.760 1.00 10.37 ATOM 2505 O TRP 50 62.403 14.800 38.616 1.00 82.57 ATOM 2506 N ILE 51 61.315 16.766 38.728 1.00 26.53 ATOM 2508 CA ILE 51 60.001 16.222 38.405 1.00 26.53 ATOM 2509 CB ILE 51 59.025 16.284 39.603 1.00 25.59 ATOM 2510 CG2 ILE 51 57.689 15.659 39.225 1.00 25.59 ATOM 2511 CGI ILE 51 59.599 15.545 40.810 1.00 25.59 ATOM 2512 CDl ILE 51 58.687 15.577 42.024 1.00 25.59 ATOM 2513 C ILE 51 59.476 17.151 37.319 1.00 26.53 ATOM 2514 O ILE 51 59.386 18.359 37.531 1.00 25.59 ATOM 2515 N ASN 52 59.153 16.601 36.155 1.00 46.03 ATOM 2517 CA ASN 52 58.651 17.415 35.047 1.00 46.03 ATOM 2518 CB ASN 52 58.528 16.569 33.783 1.00 45.75 ATOM 2519 CG ASN 52 58.447 17.406 32.528 1.00 45.75 ATOM 2520 OD1 ASN 52 57.625 18.311 32.421 1.00 45.75 ATOM 2521 ND2 ASN 52 59.298 17.097 31.561 1.00 45.75 ATOM 2524 C ASN 52 57.300 18.040 35.377 1.00 46.03 ATOM 2525 O ASN 52 56.899 19.032 34.768 1.00 45.75 ATOM 2526 N THR 53 56.605 17.449 36.343 1.00 38.29 ATOM 2528 CA THR 53 55.293 17.917 36.778 1.00 38.29 ATOM 2529 CB THR 53 55.272 19.452 37.009 1.00 46.19 ATOM 2530 OG1 THR 53 56.181 19.781 38.067 1.00 46.19 ATOM 2532 CG2 THR 53 53.880 19.924 37.393 1.00 46.19 ATOM 2533 C THR 53 54.194 17.476 35.812 1.00 38.29 ATOM 2534 O THR 53 53.298 16.727 36.203 1.00 46.19 ATOM 2535 N ARG 54 54.265 17.906 34.555 1.00 53.63 ATOM 2537 CA ARG 54 53.261 17.500 33.573 1.00 53.63 ATOM 2538 CB ARG 54 53.359 18.345 32.298 1.00 31.29 ATOM 2539 CG ARG 54 54.717 18.334 31.631 1.00 31.29 ATOM 2540 CD ARG 54 54.742 19.227 30.409 1.00 31.29 ATOM 2541 NE ARG 54 56.062 19.229 29.782 1.00 31.29 ATOM 2543 CZ ARG 54 56.666 20.315 29.312 1.00 31.29 ATOM 2544 NH1 ARG 54 56.071 21.499 29.396 1.00 31.29 ATOM 2547 NH2 ARG 54 57.871 20.218 28.766 1.00 31.29 ATOM 2550 C ARG 54 53.457 16.013 33.267 1.00 53.63 ATOM 2551 O ARG 54 54.507 15.603 32.771 1.00 31.29 ATOM 2552 N ASN 55 52.477 15.208 33.670 1.00 58.18 ATOM 2554 CA ASN 55 52.500 13.754 33.486 1.00 58.18 ATOM 2555 CB ASN 55 52.879 13.373 32.044 1.00 44.20 ATOM 2556 CG ASN 55 52.809 11.870 31.785 1.00 44.20 ATOM 2557 OD1 ASN 55 53.602 11.326 31.017 1.00 44.20 ATOM 2558 ND2 ASN 55 51.847 11.197 32.411 1.00 44.20 ATOM 2561 C ASN 55 53.462 13.105 34.481 1.00 58.18 ATOM 2562 O ASN 55 53.658 11.888 34.468 1.00 44.20 ATOM 2563 N GLY 56 54.013 13.916 35.381 1.00 35.82 ATOM 2565 CA GLY 56 54.947 13.406 36.370 1.00 35.82 ATOM 2566 C GLY 56 56.103 12.672 35.723 1.00 35.82 ATOM 2567 O GLY 56 56.637 11.715 36.281 1.00 33.62 ATOM 2568 N LYS 57 56.477 13.118 34.529 1.00 56.46 ATOM 2570 CA LYS 57 57.571 12.505 33.790 1.00 56.46 ATOM 2571 CB LYS 57 57.305 12.584 32.281 1.00 42.16 ATOM 2572 CG LYS 57 57.015 13.984 31.749 1.00 42.16 ATOM 2573 CD LYS 57 56.585 13.927 30.289 1.00 42.16 ATOM 2574 CE LYS 57 56.184 15.294 29.747 1.00 42.16 ATOM 2575 NZ LYS 57 57.344 16.189 29.495 1.00 42.16 ATOM 2579 C LYS 57 58.900 13.160 34.138 1.00 56.46 ATOM 2580 O LYS 57 58.987 13.933 35.098 1.00 42.16 ATOM 2581 N SER 58 59.930 12.832 33.361 1.00 69.70 ATOM 2583 CA SER 58 61.273 13.374 33.548 1.00 69.70 ATOM 2584 CB SER 58 61.377 14.767 32.920 1.00 51.34 ATOM 2585 OG SER 58 61.034 14.740 31.541 1.00 51.34 ATOM 2587 C SER 58 61.679 13.421 35.016 1.00 69.70 ATOM 2588 O SER 58 61.711 14.489 35.631 1.00 51.34 ATOM 2589 N THR 59 61.928 12.245 35.578 1.00 66.55 ATOM 2591 CA THR 59 62.336 12.118 36.969 1.00 66.55 ATOM 2592 CB THR 59 61.465 11.076 37.702 1.00 41.34 ATOM 2593 OG1 THR 59 60.280 10.821 36.937 1.00 41.34 Cont. /Table 10 ATOM 2595 CG2 THR 59 61.058 11.594 39.066 1.00 41.34 ATOM 2596 C THR 59 63.774 11.622 36.924 1.00 66.55 ATOM 2597 O THR 59 64.129 10.848 36.029 1.00 41.34 ATOM 2598 N TYR 60 64.621 12.091 37.835 1.00 40.30 ATOM 2600 CA TYR 60 66.002 11.629 37.823 1.00 40.30 ATOM 2601 CB TYR 60 66.869 12.381 38.835 1.00 68.57 ATOM 2602 CG TYR 60 68.285 11.842 38.911 1.00 68.57 ATOM 2603 CDl TYR 60 68.980 11.483 37.755 1.00 68.57 ATOM 2604 CE1 TYR 60 70.255 10.929 37.821 1.00 68.57 ATOM 2605 CD2 TYR 60 68.910 11.639 40.137 1.00 68.57 ATOM 2606 CE2 TYR 60 70.186 11.087 40.214 1.00 68.57 ATOM 2607 CZ TYR 60 70.852 10.734 39.055 1.00 68.57 ATOM 2608 OH TYR 60 72.108 10.181 39.136 1.00 68.57 ATOM 2610 C TYR 60 66.035 10.136 38.119 1.00 40.30 ATOM 2611 O TYR 60 65.463 9.683 39.106 1.00 68.57 ATOM 2612 N VAL 61 66.720 9.387 37.258 1.00 78.68 ATOM 2614 CA VAL 61 66.857 7.935 37.386 1.00 78.68 ATOM 2615 CB VAL 61 67.864 7.381 36.341 1.00 61.99 ATOM 2616 CGI VAL 61 67.881 5.852 36.363 1.00 61.99 ATOM 2617 CG2 VAL 61 67.518 7.891 34.945 1.00 61.99 ATOM 2618 C VAL 61 67.323 7.531 38.788 1.00 78.68 ATOM 2619 O VAL 61 67.113 6.396 39.218 1.00 61.99 ATOM 2620 N ASP 62 67.955 8.468 39.491 1.00 56.17 ATOM 2622 CA ASP 62 68.455 8.234 40.840 1.00 56.17 ATOM 2623 CB ASP 62 67.298 7.887 41.784 1.00 45.87 ATOM 2624 CG ASP 62 66.192 8.938 41.764 1.00 45.87 ATOM 2625 OD1 ASP 62 66.499 10.131 41.559 1.00 45.87 ATOM 2626 OD2 ASP 62 65.009 8.573 41.936 1.00 45.87 ATOM 2627 C ASP 62 69.511 7.134 40.810 1.00 56.17 ATOM 2628 O ASP 62 69.207 5.953 40.977 1.00 45.87 ATOM 2629 N ASP 63 70.755 7.543 40.574 1.00 73.06 ATOM 2631 CA ASP 63 71.885 6.623 40.492 1.00 73.06 ATOM 2632 CB ASP 63 73.194 7.404 40.344 1.00 43.18 ATOM 2633 CG ASP 63 73.946 7.051 39.072 1.00 43.18 ATOM 2634 OD1 ASP 63 73.828 5.897 38.604 1.00 43.18 ATOM 2635 OD2 ASP 63 74.667 7.924 38.546 1.00 43.18 ATOM 2636 C ASP 63 71.972 5.697 41.696 1.00 73.06 ATOM 2637 O ASP 63 72.399 6.110 42.776 1.00 43.18 ATOM 2638 N PHE 64 71.509 4.461 41.515 1.00 77.35 ATOM 2640 CA PHE 64 71.521 3.437 42.562 1.00 77.35 ATOM 2641 CB PHE 64 72.948 3.202 43.071 1.00 68.41 ATOM 2642 CG PHE 64 73.486 1.836 42.762 1.00 68.41 ATOM 2643 CDl PHE 64 73.432 1.328 41.467 1.00 68.41 ATOM 2644 CD2 PHE 64 74.047 1.053 43.766 1.00 68.41 ATOM 2645 CE1 PHE 64 73.930 0.058 41.177 1.00 68.41 ATOM 2646 CE2 PHE 64 74.548 -0.219 43.485 1.00 68.41 ATOM 2647 CZ PHE 64 74.489 -0.717 42.188 1.00 68.41 ATOM 2648 C PHE 64 70.592 3.723 43.740 1.00 77.35 ATOM 2649 O PHE 64 70.141 2.795 44.419 1.00 68.41 ATOM 2550 N LYS 65 70.284 4.996 43.967 1.00 77.80 ATOM 2652 CA LYS 65 69.414 5.395 45.066 1.00 77.80 ATOM 2653 CB LYS 65 69.749 6.824 45.525 1.00 59.28 ATOM 2654 CG LYS 65 71.243 7.133 45.654 1.00 59.28 ATOM 2655 CD LYS 65 72.017 6.042 46.394 1.00 59.28 ATOM 2656 CE LYS 65 71.576 5.890 47.841 1.00 59.28 ATOM 2657 NZ LYS 65 72.374 4.831 48.536 1.00 59.28 ATOM 2661 C LYS 65 67.940 5.296 44.675 1.00 77.80 ATOM 2662 O LYS 65 67.188 6.271 44.781 1.00 59.28 ATOM 2663 N GLY 66 67.523 4.105 44.255 1.00 33.49 ATOM 2665 CA GLY 66 66.141 3.893 43.863 1.00 33.49 ATOM 2666 C GLY 66 65.248 3.671 45.067 1.00 33.49 ATOM 2667 O GLY 66 64.479 2.710 45.117 1.00 26.03 Tablell:TJhureedimens )nalcoordirιatesof HC-CDR3(GLU99-TYR110 fiOmSB249417 ATOM 2507 N GLU 99 61.719 25.581 38.831 1.00 50.46 ATOM 2508 CA GLU 99 62.445 25.725 37.560 1.00 50.46 ATOM 2509 CB GLU 99 63.093 27.110 37.435 1.00 52.10 ATOM 2510 CG GLU 99 62.109 28.216 37.059 1.00 52.10 ATOM 2511 CD GLU 99 62.112 29.390 38.028 1.00 52.10 ATOM 2512 OEl GLU 99 61.436 30.397 37.735 1.00 52.10 ATOM 2513 OE2 GLU 99 62.772 29.310 39.086 1.00 52.10 ATOM 2514 C GLU 99 63.461 24.618 37.297 1.00 50.46 ATOM 2515 O GLU 99 63.484 23.616 38.010 1.00 52.10 ATOM 2516 N GLY 100 64.259 24.775 36.242 1.00 42.17 ATOM 2517 CA GLY 100 65.249 23.764 35.914 1.00 42.17 ATOM 2518 C GLY 100 66.331 24.192 34.937 1.00 42.17 ATOM 2519 O GLY 100 66.089 24.997 34.033 1.00 27.11 ATOM 2520 N ASN 101 67.526 23.635 35.132 1.00 59.61 ATOM 2521 CA ASN 101 68.704 23.902 34.306 1.00 59.61 ATOM 2522 CB ASN 101 68.654 23.089 33.006 1.00 55.09 ATOM 2523 CG ASN 101 68.926 21.612 33.229 1.00 55.09 ATOM 2524 OD1 ASN 101 68.323 20.985 34.102 1.00 55.09 ATOM 2525 ND2 ASN 101 69.834 21.046 32.439 1.00 55.09 ATOM 2528 C ASN 101 68.940 25.379 34.011 1.00 59.61 ATOM 2529 O ASN 101 69.643 26.062 34.763 1.00 55.09 ATOM 2530 N MET 102 68.369 25.867 32.914 1.00 51.25 ATOM 2531 CA MET 102 68.514 27.265 32.530 1.00 51.25 ATOM 2532 CB MET 102 69.931 27.556 32.037 1.00 39.15 ATOM 2533 CG MET 102 70.367 29.002 32.229 1.00 39.15 ATOM 2534 ΞD MET 102 69.099 30.248 31.922 1.00 39.15 ATOM 2535 CE MET 102 69.132 31.094 33.482 1.00 39.15 ATOM 2536 C MET 102 67.519 27.571 31.424 1.00 51.25 ATOM 2537 O MET 102 67.866 27.577 30.241 1.00 39.15 ATOM 2538 N ASP 103 66.270 27.787 31.814 1.00 52.39 ATOM 2539 CA ASP 103 65.210 28.095 30.867 1.00 52.39 ATOM 2540 CB ASP 103 64.309 26.865 30.664 1.00 81.62 ATOM 2541 CG ASP 103 65.099 25.592 30.350 1.00 81.62 ATOM 2542 OD1 ASP 103 64.784 24.533 30.939 1.00 81.62 ATOM 2543 OD2 ASP 103 66.028 25.642 29.514 1.00 81.62 ATOM 2544 C ASP 103 64.391 29.250 31.440 1.00 52.39 ATOM 2545 O ASP 103 64.181 29.324 32.653 1.00 81.62 ATOM 2546 N GLY 104 63.980 30.176 30.577 1.00 38.36 ATOM 2547 CA GLY 104 63.181 31.309 31.019 1.00 38.36 ATOM 2548 C GLY 104 63.874 32.286 31.954 1.00 38.36 ATOM 2549 O GLY 104 63.209 33.068 32.630 1.00 35.81 ATOM 2550 N TYR 105 65.204 32.221 32.005 1.00 78.70 ATOM 2551 CA TYR 105 66.028 33.098 32.843 1.00 78.70 ATOM 2552 CB TYR 105 66.298 34.426 32.125 1.00 41.71 ATOM 2553 CG TYR 105 67.726 34.593 31.653 1.00 41.71 ATOM 2554 CDl TYR 105 68.492 33.493 31.266 1.00 41.71 ATOM 2555 CE1 TYR 105 69.812 33.644 30.838 1.00 41.71 ATOM 2556 CD2 TYR 105 68.315 35.854 31.599 1.00 41.71 ATOM 2557 CE2 TYR 105 69.632 36.017 31.172 1.00 41.71 ATOM 2558 CZ TYR 105 70.372 34.910 30.794 1.00 41.71 ATOM 2559 OH TYR 105 71.671 35.077 30.382 1.00 41.71 ATOM 2560 C TYR 105 65.515 33.355 34.263 1.00 78.70 ATOM 2561 O TYR 105 65.349 34.503 34.679 1.00 41.71 ATOM 2562 N PHE 106 65.297 32.275 35.006 1.00 53.79 ATOM 2563 CA PHE 106 64.815 32.362 36.381 1.00 53.79 ATOM 2564 CB PHE 106 63.302 32.606 36.355 1.00 64.88 ATOM 2565 CG PHE 106 62.867 33.837 37.093 1.00 64.88 ATOM 2566 CDl PHE 106 63.142 35.104 36.586 1.00 64.88 ATOM 2567 CD2 PHE 106 62.162 33.732 38.286 1.00 64.88 ATOM 2568 CE1 PHE 106 62.722 36.246 37.255 1.00 64.88 ATOM 2569 CE2 PHE 106 61.736 34.868 38.964 1.00 64.88 ATOM 2570 CZ PHE 106 62.016 36.129 38.447 1.00 64.88 ATOM 2571 C PHE 106 65.099 31.140 37.282 1.00 53.79 ATOM 2572 O PHE 106 64.552 31.055 38.381 1.00 64.88 ATOM 2573 N PRO 107 66.005 30.221 3-6.878 1.00 52.80 ATOM 2574 CD PRO 107 66.836 30.142 35.667 1.00 42.34 ATOM 2575 CA PRO 107 66.268 29.051 37.725 1.00 52.80 ATOM 2576 CB PRO 107 67.393 28.338 36.977 1.00 42.34 ATOM 2577 CG PRO 107 67.103 28.666 35.568 1.00 42.34 ATOM 2578 C PRO 107 66.623 29.241 39.198 1.00 52.80 ATOM 2579 O PRO 107 67.275 30.212 39.596 1.00 42.34 ATOM 2580 N PHE 108 66.199 28.252 39.980 1.00 39.89 ATOM 2581 CA PHE 108 66.421 28.160 41.417 1.00 39.89 ATOM 2582 CB PHE 108 67.823 27.639 41.713 1.00 29.53 Con . /Tablβ 11 ATOM 2583 CG PHE 108 67.986 26.177 41 417 1 00 29 53 ATOM 2584 CDl PHE 108 67.950 25.711 40 107 1 00 29 53 ATOM 2585 CD2 PHE 108 68.127 25.258 42 450 1 00 29 53 ATOM 2586 CΞ1 PHE 108 68.049 24.350 39 833 1 00 29 53 ATOM 2587 CΞ2 PHE 108 68.228 23.894 42 186 1 00 29 53 ATOM 2588 CZ PHE 108 68.188 23.440 40 878 1 00 29 53 ATOM 2589 C PHE 108 66.057 29.348 42 287 1 00 39 89 ATOM 2590 O PHE 108 66.654 29.578 43 342 1 00 29 53 ATOM 2591 N THR 109 65.082 30.115 41 821 1 00 37 60 ATOM 2592 CA THR 109 64.572 31.243 42 571 1 00 37 60 ATOM 2593 CB THR 109 64.110 32.374 41 638 1 00 39 99 ATOM 2594 OG1 THR 109 63.235 31.842 40 638 1 00 39 99 ATOM 2595 CG2 THR 109 65.303 33.016 40 950 1 00 39 99 ATOM 2596 C THR 109 63.369 30.609 43 267 1 00 37 60 ATOM 2597 O THR 109 62.694 29.761 42 676 1 00 39 99 ATOM 2598 N TYR 110 63.113 30.999 44 511 1 00 23 43 ATOM 2599 CA TYR 110 62.006 30.449 45 292 1 00 23 43 ATOM 2600 CB TYR 110 60.701 30.367 44 481 1 00 42 41 ATOM 2601 CG TYR 110 60.156 31.673 43 951 1 00 42 41 ATOM 2602 CDl TYR 110 60.138 31.931 42 583 1 00 42 41 ATOM 2603 CE1 TYR 110 59.587 33.104 42 077 1 00 42 41 ATOM 2604 CD2 TYR 110 59.611 32.628 44 807 1 00 42 41 ATOM 2605 CE2 TYR 110 59.055 33.807 44 309 1 00 42 41 ATOM 2606 CZ TYR 110 59.047 34.035 42 942 1 00 42 41 ATOM 2607 OH TYR 110 58.484 35.185 42 439 1 00 42 41 ATOM 2608 C TYR 110 62.358 29.042 45 .763 1 .00 23 .43 ATOM 2609 O TYR 110 62.436 28.111 44 .960 1 .00 42 .41 Table12:Threedimensionalcoordinatesof L C-CDRl(ARG24-HES33)fromSB24941' 7 ATOM 161 N ARG 24 85.923 25.430 39.568 1.00 40.61 ATOM 162 CA ARG 24 86.364 24.572 38.468 1.00 40.61 ATOM 163 CB ARG 24 87.477 23.636 38.953 1.00 54.47 ATOM 164 CG ARG 24 88.672 23.525 38.021 1.00 54.47 ATOM 165 CD ARG 24 89.786 24.476 38.433 1.00 54.47 ATOM 166 NE ARG 24 89.329 25.861 38.511 1.00 54.47 ATOM 167 CZ ARG 24 90.019 26.850 39.069 1.00 54.47 ATOM 168 NH1 ARG 24 91.212 26.619 39.605 1.00 54.47 ATOM 171 NH2 ARG 24 89.510 28.073 39.101 1.00 54.47 ATOM 174 C ARG 24 85.191 23.729 37.974 1.00 40.61 ATOM 175 O ARG 24 84.258 23.455 38.735 1.00 54.47 ATOM 176 N ALA 25 85.251 23.296 36.718 1.00 33.05 ATOM 177 CA ALA 25 84.185 22.475 36.146 1.00 33.05 ATOM 178 CB ALA 25 83.270 23.332 35.275 1.00 58.44 ATOM 179 C ALA 25 84.702 21.278 35.348 1.00 33.05 ATOM 180 O ALA 25 83.923 20.409 34.958 1.00 58.44 ATOM 181 N SER 26 86.006 21.249 35.087 1.00 57.44 ATOM 182 CA SER 26 86.641 20.165 34.330 1.00 57.44 ATOM 183 CB SER 26 86.518 18.828 35.080 1.00 65.59 ATOM 184 OG SER 26 87.351 17.828 34.505 1.00 65.59 ATOM 185 C SER 26 86.093 20.030 32.903 1.00 57.44 ATOM 186 O SER 26 86.698 20.533 31.952 1.00 65.59 ATOM 187 N SER 27 84.946 19.366 32.762 1.00 55.02 ATOM 188 CA SER 27 84.317 19.158 31.459 1.00 55.02 ATOM 189 CB SER 27 82.987 18.420 31.627 1.00 53.39 ATOM 190 OG SER 27 83.183 17.167 32.259 1.00 53.39 ATOM 191 C SER 27 84.091 20.476 30.725 1.00 55.02 ATOM 192 O SER 27 84.718 20.717 29.690 1.00 53.39 ATOM 193 N SER 28 83.232 21.316 31.307 1.00 33.90 ATOM 194 CA SER 28 82.834 22.647 30.825 1.00 33.90 ATOM 195 CB SER 28 83.830 23.274 29.833 1.00 57.68 ATOM 196 OG SER 28 83.804 22.660 28.552 1.00 57.68 ATOM 197 C SER 28 81.430 22.670 30.238 1.00 33.90 ATOM 198 O SER 28 81.089 21.866 29.368 1.00 57.68 ATOM 199 N VAL 29 80.619 23.592 30.742 1.00 39.14 ATOM 200 CA VAL 29 79.244 23.773 30.294 1.00 39.14 ATOM 201 CB VAL 29 78.226 23.123 31.278 1.00 50.11 ATOM 202 CGI VAL 29 78.394 21.612 31.295 1.00 50.11 ATOM 203 CG2 VAL 29 78.401 23.688 32.681 1.00 50.11 ATOM 204 C VAL 29 79.031 25.282 30.251 1.00 39.14 ATOM 205 O VAL 29 79.981 26.036 30.028 1.00 50.11 ATOM 206 N ASN 30 77.798 25.731 30.449 1.00 34.36 ATOM 207 CA ASN 30 77.518 27.157 30.446 1.00 34.36 ATOM 208 CB ASN 30 77.105 27.633 29.051 1.00 69.95 ATOM 209 CG ASN 30 77.315 29.129 28.859 1.00 69.95 ATOM 210 OD1 ASN 30 76.945 29.938 29.712 1.00 69.95 ATOM 211 ND2 ASN 30 77.935 29.501 27.744 1.00 69.95 ATOM 214 C ASN 30 76.405 27.416 31.437 1.00 34.36 ATOM 215 O ASN 30 75.668 26.496 31.799 1.00 69.95 ATOM 216 N TYR 31 76.313 28.662 31.895 1.00 51.94 ATOM 217 CA TYR 31 75.299 29.094 32.853 1.00 51.94 ATOM 218 CB TYR 31 73.896 28.690 32.379 1.00 66.29 ATOM 219 CG TYR 31 73.464 29.386 31.105 1.00 66.29 ATOM 220 CDl TYR 31 72.980 28.661 30.016 1.00 66.29 ATOM 221 CE1 TYR 31 72.567 29.305 28.844 1.00 66.29 ATOM 222 CD2 TYR 31 73.528 30.773 30.993 1.00 66.29 ATOM 223 CE2 TYR 31 73.120 31.424 29.832 1.00 66.29 ATOM 224 CZ TYR 31 72.641 30.687 28.763 1.00 66.29 ATOM 225 OH TYR 31 72.237 31.345 27.626 1.00 66.29 ATOM 226 C TYR 31 75.562 28.609 34.276 1.00 51.94 ATOM 227 O TYR 31 74.995 27.610 34.729 1.00 66.29 ATOM 228 N MET 32 76.435 29.331 34.972 1.00 31.75 ATOM 229 CA MET 32 76.788 29.013 36.351 1.00 31.75 ATOM 230 CB MET 32 78.246 29.392 36.631 1.00 29.56 ATOM 231 CG MET 32 78.807 28.822 37.925 1.00 29.56 ATOM 232 ΞD MET 32 78.874 27.021 37.900 1.00 29.56 ATOM 233 CE MET 32 80.515 26.716 38.506 1.00 29.56 ATOM 234 C MET 32 75.857 29.820 37.246 1.00 31.75 ATOM 235 O MET 32 75.576 30.984 36.960 1.00 29.56 ATOM 236 N HIS 33 75.355 29.192 38.303 1.00 18.73 ATOM 237 CA HIS 33 74.441 29.848 39.231 1.00 18.73 ATOM 238 CB HIS 33 73.154 29.022 39.412 1.00 59.11 ATOM 239 CG HIS 33 72.630 28.395 38.153 1.00 59.11 ATOM 240 CD2 HIS 33 73.216 27.574 37.249 1.00 59.11 ATOM 241 ND1 HIS 33 71.325 28.548 37.736 1.00 59.11 ATOM 242 CE1 HIS 33 71.130 27.850 36.631 1.00 59.11 ATOM 243 NE2 HIS 33 72.262 27.250 36.315 1.00 59.11 ATOM 244 C HIS 33 75.136 29.943 40.584 1.00 18.73 ATOM 245 O HIS 33 75.667 28.945 41.071 1.00 59.11 Table 13: Three dimensional coordinates of IX-CDR2(ALA49-SER55 fromSB249417 ATOM 385 N ALA 49 73. 341 32.762 35.709 1.00 21. 70 ATOM 386 CA ALA 49 73. 888 32.759 34.358 1.00 21. 70 ATOM 387 CB ALA 49 72. 879 33.352 33.379 1.00 50. 17 ATOM 388 C ALA 49 75. 206 33.523 34.298 1.00 21. 70 ATOM 389 O ALA 49 75. 335 34.507 33.564 1.00 50. 17 ATOM 390 N THR 50 76. 154 33.083 35.119 1.00 36. 52 ATOM 391 CA THR 50 77. 494 33.655 35.211 1.00 36. 52 ATOM 392 CB THR 50 78. 362 33.294 33.978 1.00 58. 15 ATOM 393 OG1 THR 50 77 656 33.610 32.773 58 15 ATOM 394 CG2 THR 50 78 692 31.819 33.979 58 15 ATOM 395 THR 50 77 605 35.152 35.482 36 52 ATOM 396 THR 50 77 942 35.558 36.594 58 15 ATOM 397 SER 51 77 327 35.965 34.471 31 35 ATOM 398 CA SER 51 77 441 37.413 34.592 31 35 ATOM 399 CB SER 51 77 862 38.009 33.245 1.00 35 38 ATOM 400 OG SER 51 79 126 37.511 32.836 1.00 35 38 ATOM 401 C SER 51 76 228 38.169 35.120 1.00 31 35 ATOM 402 O SER 51 76 352 39.325 35.528 1.00 35 38 ATOM 403 N ASN 52 75 060 37.540 35.129 1.00 34 69 ATOM 404 CA ASN 52 73 863 38.238 35.592 34 69 ATOM 405 CB ASN 52 72 614 37.715 34.879 34 18 ATOM 406 CG ASN 52 72 561 38.131 33.420 1.00 34 18 ATOM 407 OD1 ASN 52 72 529 39.322 33.102 1.00 34 18 ATOM 408 ND2 ASN 52 72 576 37.151 32.525 1.00 34 18 ATOM 411 C ASN 52 73 653 38.278 37.098 1.00 34 69 ATOM 412 ASN 52 73 720 37.260 37.786 1.00 34 18 ATOM 413 LEU 53 73 386 39.480 37.593 1.00 28 58 ATOM 414 CA LEU 53 73 156 39.733 39.008 1.00 28 58 ATOM 415 CB LEU 53 73 805 41.074 39.380 1.00 36 89 ATOM 416 CG LEU 53 73 657 41.716 40.761 1.00 36 89 ATOM 417 CDl LEU 53 74 .996 42.266 41.209 1.00 36 89 ATOM 418 CD2 LEU 53 72 624 42.829 40.711 1.00 36 89 ATOM 419 C LEU 53 71 .649 39.753 39.266 1.00 28 58 ATOM 420 O LEU 53 70 .876 40.229 38.432 36 89 ATOM 421 N ALA 54 71 .233 39.208 40.406 17 .93 ATOM 422 CA ALA 54 69 .817 39.157 40.763 17 .93 ATOM 423 CB ALA 54 69 .579 38.092 41.823 27 .99 ATOM 424 C ALA 54 69 .307 40.507 41.248 1.00 17 .93 ATOM 425 O ALA 54 70 .083 41.433 41.459 00 27 .99 ATOM 426 N SER 55 67 .996 40.617 41.417 00 46 .64 ATOM 427 CA SER 55 67 .390 41.857 41.881 1.00 46 .64 ATOM 428 CB SER 55 65 .914 41.917 41.473 1.00 60 .10 ATOM 429 OG SER 55 65 .769 41.953 40.062 1.00 60 .10 ATOM 430 C SER 55 67 .513 41.947 43.396 1.00 46 .64 ATOM 431 O SER 55 67 .249 40.973 44.104 1.00 60 .10 Table 14: TTireedirnensional coordinates of I -CTR3(GI^88-THR96 fromSB249417 ATOM 677 N GLN 76 228 26 138 40 949 1.00 23.98 ATOM 678 CA GLN 75 808 24 954 40 213 1.00 23.98 ATOM 679 CB GLN 74 400 24 510 40 616 1.00 33.56 ATOM 680 CG GLN 73 285 25 370 40 066 1.00 33.56 ATOM 681 CD GLN 71 932 24 738 40 259 1.00 33.56 ATOM 682 OEl GLN 71 415 24 691 41 369 1.00 33.56 ATOM 683 NE2 GLN 71 346 24 251 39 179 I. 00 33 56 ATOM 686 C GLN 75 850 25 282 38 730 1. 00 23 98 ATOM 687 GLN 75 909 26 452 38 349 1. 00 33 56 ATOM 688 GLN 89 75 775 24 254 37 897 1. 00 53 56 ATOM 689 CA GLN 89 75 833 24 439 36 456 1. 00 53 56 ATOM 690 CB GLN 89 77 082 23 752 35 888 1. 00 50 20 ATOM 691 CG GLN 89 77 610 22 557 36 694 1. 00 50 20 ATOM 692 CD GLN 89 76 615 21 414 36 823 1 00 50 20 ATOM 693 OEl GLN 89 75 598 21 532 37 510 1 00 50 20 ATOM 694 NE2 GLN 89 76 923 20 .289 36 194 1 00 50 20 ATOM 697 C GLN 89 74 596 23 944 35 728 1 00 53 56 ATOM 698 GLN 89 73 772 23 .224 36 298 1 00 50 20 ATOM 699 TRP 90 74 447 24 383 34 481 1 00 42 71 ATOM 700 CA TRP 90 73 331 23 .967 33 641 1 00 42 71 ATOM 701 CB TRP 90 73 .336 24 .762 32 .327 1 00107 30 ATOM 702 CG TRP 90 72 .630 24 .093 31 .185 1 00107 .30 ATOM 703 CD2 TRP 90 73 .219 23 .652 29 .955 1 00107 .30 ATOM 704 CE2 TRP 90 72 .197 23 .037 29 .200 1 00107 30 ATOM 705 CE3 TRP 90 74.513 23.715 29.418 1.00107.30 ATOM 706 CDl TRP 90 71.313 23. 748 31. 124 1.00107.30 ATOM 707 NE1 TRP 90 71.044 23. 111 29. 935 1.00107.30 ATOM 708 CZ2 TRP 90 72.427 22. 485 27. 935 1.00107.30 ATOM 709 CZ3 TRP 90 74.742 23. 165 28. 157 1.00107.30 ATOM 710 CH2 TRP 90 73.702 22. 559 27 432 1.00107.30 ATOM 711 C TRP 90 73.497 22. 473 33 371 .00 42.71 ATOM 712 O TRP 90 72.522 21. 720 33 366 .00107.30 ATOM 713 N SER 91 74.746 22. 068 33 154 00 53.84 ATOM 714 CA SER 91 75.130 20. 683 32 897 00 53.84 ATOM 715 CB SER 91 74.815 19. 789 34 106 00 38.65 ATOM 716 OG SER 91 73.457 19 379 34 150 00 38.65 ATOM 717 C SER 91 74.545 20 057 31 639 1 00 53 84 ATOM 718 O SER 91 73.464 20 425 31 184 1 00 38 65 ATOM 719 N ILE 92 75.313 19 148 31 051 1 00 51 50 ATOM 720 CA ILE 92 74.874 18 421 29 867 1 00 51 50 ATOM 721 CB ILE 92 76.070 17 967 28 991 1 00 66 93 ATOM 722 CG2 ILE 92 75.598 17 678 27 570 1 00 66 93 ATOM 723 CGI ILE 92 77.154 19 047 28 948 1 00 66 93 ATOM 724 CDl ILE 92 78.444 18 594 28 271 1 00 66 93 ATOM 725 C ILE 92 74.211 17 171 30 446 1 00 51 50 ATOM 726 O ILE 92 73.268 16 621 29 881 1 00 66 93 ATOM 727 N ASN 93 74.714 16 755 31 605 1 00 60 16 ATOM 728 CA ASN 93 74.232 15 580 32 319 1 00 60 16 ATOM 729 CB ASN 93 75.290 14 473 32 228 1 00 59 88 ATOM 730 CG ASN 93 74.696 13 083 32 312 .00 59 . 88 ATOM 731 OD1 ASN 93 74.187 12 673 33 354 . 00 59 . 88 ATOM 732 ND2 ASN 93 74.769 12 345 31 213 . 00 59 . 88 ATOM 735 C ASN 93 74.046 16 023 33 775 . 00 60 . 16 ATOM 736 O ASN 93 74.952 16 620 34 363 . 00 59 . 88 ATOM 737 N PRO 94 72.883 15 709 34 377 . 00 45 .30 ATOM 738 CD PRO 94 72.057 14 607 33 849 00 61 . 85 ATOM 739 CA PRO 94 72.443 16 011 35 740 00 45 .30 ATOM 740 CB PRO 94 72.227 14 621 36 .314 1 . 00 61 . 85 ATOM 741 CG PRO 94 71.516 13 930 35 .137 1 . 00 61. 85 ATOM 742 C PRO 94 73.280 16 922 36 .644 1 .00 45 . 30 ATOM 743 O PRO 94 74.461 16 670 36 .913 1 . 00 61. 85 ATOM 744 N ARG 95 72.607 17 959 37 141 1 . 00 55 .22 ATOM 745 CA ARG 95 73.181 18 975 38 .024 1 .00 55 .22 ATOM 746 CB ARG 95 72.097 19 992 38 .393 1 .00 42 .76 ATOM 747 CG ARG 95 71.364 20 .575 37 .194 1 . 00 42 .76 ATOM 748 CD ARG 95 70.022 21 .178 37 .591 1 .00 42 .76 ATOM 749 NE ARG 95 68.909 20 .524 36 .902 1 .00 42 .76 ATOM 750 CZ ARG 95 67.634 20 .899 36 .995 00 42.76 ATOM 751 NH1 ARG 95 67.286 21 .931 37 .752 00 42.76 ATOM 754 NH2 ARG 95 66.701 20 .246 36 .315 00 42.76 ATOM 757 C ARG 95 73.753 18 .352 39 .294 .00 55.22 ATOM 758 O ARG 95 73.351 17 .255 39 .684 .00 42.76 ATOM 759 N THR 96 74.657 19 .066 39 .963 .00 47.74 ATOM 760 CA THR 96 75.270 18 .543 41 .183 .00 47.74 ATOM 761 CB THR 96 76.630 17 .877 40 .875 .00 32.33 ATOM 762 OG1 THR 96 77.370 18 .701 39 .967 .00 32.33 ATOM 763 CG2 THR 96 76.433 16 .494 40 .264 1 . 00 32 . 33 ATOM 764 C THR 96 75.456 19 .495 42 .370 1 . 00 47 . 74 ATOM 765 O THR 96 75.379 19 .052 43 .515 1 . 00 32 . 33 References Brunger A.T., (1990) Ada Cryst. A46:46-57. Brunger A.T., (1991) Acta Cryst. A47:195-204. Brunger A.T., X-PLOR 3.0 Manual (Yale University, 1992). Huber R., (1985). In Molecular Replacement. Proc. of the Daresbury Study Weekend, Daresbury, February 1985, pp. 58-61. SERC Daresbury Laboratory, Daresbury, Warrington, England. Monfardini C, Kieber-Emmons T., Voet D., Godillot A.P., Weiner D.B., Williams W.V., (1996) J. Biol. Chem. 271:2966-2971. Otwinowski Z., "Oscillation Data Reduction," in Proceedings of the CCP4 Study Weekend: "Data Collection and Processing, " 29-30 January 1993, comiled by L. Sawyer, N. Isaacs and S. Bailey (SERC Daresbury Laboratory, England), pp. 56-62. Rossmann M.G. and Blow D.M., (1962). Acta Cryst. 15:24-31. Rusinko, A., (1993) Chem. Des. Auto. News 8:44-47. Zhao B., Helms L.R., DesJarlais R.L., Abdel-Meguid S.S. & Wetzel R., (1995) Nature Struct. Biol. 2: 1131 - 1137. The present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof, and, accordingly, reference should be made to the appended claims, rather than to the foregoing specification, as indicating the scope of the invention. CLAIMS 1. A BC2 Fab fragment crystal. 2. A Fab fragment crystal containing BC2 complementarity determining regions (CDRs). 3. The crystal of claim 2 wherein the CDRs are characterized by the coordinates of Tables 3-8. 4. A SB249417 Fab fragment crystal. 5. The crystal of claim 4 wherein the CDRs are characterized by the coordinates of Tables 9-14. 6. A method for identifying a peptidomimetic having Factor IX binding activity comprising: a. searching a small molecule structural database with CDR structural parameters derived from the crystal of claim 1, 2 or 4; b. selecting a molecular structure from the database which mimics the CDR structural parameters; c. synthesizing the selected molecular structure; and d. screening the synthesized molecule for Factor IX binding activity. 7. The method of claim 6 wherein the synthesized molecule is further screened for antithrombotic activity. 8. The method of claim 7 wherein the synthesized molecule is further screened for self-limiting, neutralizing activity. 9. The method of claim 6 wherein the selected molecular structure mimics the parameters of CDR residues HC-Asn35, HC-Trp50, and LC-Arg95. 10. A computer- readable medium having BC2 CDR structural information stored thereon. 11. A computer-readable medium having SB249417 CDR structural information stored thereon.

Claims: CLAIMS 1. A BC2 Fab fragment crystal. 2. A Fab fragment crystal containing BC2 complementarity determining regions (CDRs). 3. The crystal of claim 2 wherein the CDRs are characterized by the coordinates of Tables 3-8. 4. A SB249417 Fab fragment crystal. 5. The crystal of claim 4 wherein the CDRs are characterized by the coordinates of Tables 9-14. 6. A method for identifying a peptidomimetic having Factor IX binding activity comprising: a. searching a small molecule structural database with CDR structural parameters derived from the crystal of claim 1, 2 or 4; b. selecting a molecular structure from the database which mimics the CDR structural parameters; c. synthesizing the selected molecular structure; and d. screening the synthesized molecule for Factor IX binding activity. 7. The method of claim 6 wherein the synthesized molecule is further screened for antithrombotic activity. 8. The method of claim 7 wherein the synthesized molecule is further screened for self-limiting, neutralizing activity. 9. The method of claim 6 wherein the selected molecular structure mimics the parameters of CDR residues HC-Asn35, HC-Trp50, and LC-Arg95. 10. A computer-readable medium having BC2 CDR structural information stored thereon. 11. A computer-readable medium having SB249417 CDR structural information stored thereon.

Inventors: SWAIRJO MANAL A, SWAIRJO, MANAL, A.
Applicants: SMITHKLINE BEECHAM CORP, SWAIRJO MANAL A, SMITHKLINE BEECHAM CORPORATION, SWAIRJO, MANAL, A.
Application year: 1998
Main classification: C07K16
IPC codes: C07K16, C12N15, G01N33