AU752547B2

AU752547B2 - Small molecule mimetics of erythropoietin

Info

Publication number: AU752547B2
Application number: AU19427/00A
Authority: AU
Inventors: Dana L. Johnson; Linda K. Jolliffe; Oded Livnah; Enrico A. Stura; Ian A Wilson
Original assignee: Scripps Research Institute
Current assignee: Scripps Research Institute
Priority date: 1996-04-26
Filing date: 2000-02-23
Publication date: 2002-09-19
Anticipated expiration: 2017-04-28
Also published as: AU1942700A

Description

AUSTRALIA

Patents Act 1990 COMPLETE SPECIFICATION STANDARD PATENT S.

S

SS

Applicant: THE SCRIPPS RESEARCH INSTITUTE Invention Title: SMALL MOLECULE MIMETICS OF ERYTHROPOIETIN The following statement is a full description of this invention, including the best method of performing it known to me/us: la SMALL MOLECULE MIMETICS OF ERYTHROPOIETIN BACKGROUND OF THE INVENTION 1. Field of the Invention This invention relates to computer-assisted methods for identifying and designing small s molecule mimetics of erythropoietin.

2. Description of Related Art Erythropoietin (EPO) is the primary regulator of the proliferation and differentiation of immature erythroid cells. EPO is produced in the fetal liver and in the adult kidney in response to hypoxia (low oxygen levels in blood or tissue). It circulates in the blood 10 stream where it targets the EPO receptor (EPOR) on committed progenitor cells in the bone marrow and other hematopoietic tissues. Recombinant human erythropoietin (rHuEPO) is widely used in therapy of patients with anaemia due to chronic renal failure, cancer chemotherapy and AZT treatment.

The EPO receptor belongs to the cytokine receptor superfamily which includes receptors for other hematopoietic growth factors such as interleukins (ILs), colony stimulating factors (CSFs) as well as growth hormone prolactin and ciliary neurotrophic factor (CNTF). The structural architecture of this family of receptors consists of three modules: a ligand binding extracellular domain, a short trans membrane region and a large cytoplasmic domain. It has been proposed that the extracellular domain of this superfamily comprises two discrete domains each containing approximately 100 residues that fold into a sandwich consisting of 7 antiparallel P-strands with the topology of an Ig constant domain. Members of the family share two characteristic motifs in their extracellular domain: a pair of conserved disulfide bridges in the N-terminal domain, and a WSXWS box (where X is any amino acid residue) in the C-terminal domain. For most members of this receptor superfamily, oligomerization of one or more polypeptide chains -2is essential for forming high affinity receptor complexes. A homodimer complex has been demonstrated to be the active form ofhGHR and a similar model has been suggested for G-CSF, prolactin and EPO receptors.

Erythropoietin induces dimerization of two EPO receptor molecules, which results in subsequent phosphorylation of the cytoplasmic domains by the association with two tyrosine kinase (JAK2) molecules to initiate a cascade of events that leads to the relevant biological.

Given the importance of erythropoietin, it would be very desirable to be able to identify molecules capable of binding the EPO receptor and eliciting the response normally 10 elicited by EPO.

3 SUMMARY OF THE INVENTION The invention features methods for identifying molecules which will bind to the EPO receptor and act as a EPO mimetic. Preferred EPO mimetics identified using the method of the invention act as agonists of the EPO receptor in one or more in vitro or in vivo biological assays of EPO activity. Preferred mimetics are molecules lacking peptide bonds, are non peptidic mimetics.

Preferred peptide mimetics have 15 or fewer, more preferably 10 or fewer amino acids.

The methods of the invention entail identification and design of molecules having a particular structure. The methods rely on the use of precise structural information o 15 derived from x-ray crystallographic studies of the :extracellular domain of EPO receptor (amino acids 1 to 225) complexed with a peptide, EMP1 (EPO Mimetic Peptide 1; described below), which acts as an EPO mimetic. This crystallographic data permits the identification of atoms in the peptide mimetic that are important for EPO receptor binding and dimerization. More importantly, this data defines a three dimensional array of the important contact atoms. Other molecules which include a portion in which the atoms have a similar three dimensional arrangement 25 similar to some or all of these contact atoms are likely to be capable of acting as an EPO mimetic. Moreover, one Scan use the structural information to design or identify S* molecules having even more EPO activity than the peptide mimetic described herein.

According to a first aspect of the present invention there is provided a method for identifying mimetics of erythropoietin, comprising the steps of: inputting into a programmed computer through an input device data comprising the three-dimensional coordinates of a subset of the atoms in the peptide GGTYSCHFGPLTWVCKPQGG when the peptide is co-crystallized H: \MaraR\Keep\Speci\P36307.doc 22/02/00 4 with a portion of the erythropoietin receptor comprising amino acids 1 to 225 of the receptor, thereby generating a criteria data set; comparing, using a processor, the criteria data set to a computer database of chemical structures stored in a computer data storage system; selecting from the database, using computer methods, chemical structures having a portion that is structurally similar to the criteria data set; outputting to an output device the selected chemical structures having a portion similar to the criteria data set; providing a compound having a structure outputted in step and 15 selecting from the compounds provided in step a compound which increases erythropoiesis in vivo.

According to a second aspect of the present invention there is provided the use of an EPO mimetic identified by the method described above in the manufacture of a medicament for increasing erythropoiesis in a patient in need thereof.

According to a third aspect of the present invention there is provided a method for increasing erythropoiesis in a patient in need thereof comprising administering to said patient an effective amount of an EPO mimetic identified using the method described above.

According to a fourth aspect of the present invention there is provided a pharmaceutical composition comprising an EPO mimetic identified using the method described above together with a pharmaceutically acceptable salt.

According to a fifth aspect of the present invention there is provided the use of an EPO mimetic identified using the method described above for increasing erythropoiesis in a patient in need thereof.

H:\MaraR\Keep\Speci\P36307.doc 22/02/00 4A According to a sixth aspect of the present invention there is provided a pharmaceutical composition comprising an EPO mimetic identified using the method described above together with a pharmaceutically acceptable salt, when used for increasing erythropoiesis in a patient in need thereof.

The details of the preferred embodiment of the present invention are set forth in the accompanying drawings and the description below. Once the details of the invention are known, numerous additional innovations and changes will become obvious to one skilled in the art.

BRIEF DESCRIPTION OF THE DRAWINS FIGURE 1 is a flowchart showing a first method for identifying potential mimetics of erythropoietin using a computer system.

e FIGURE 2 is a flowchart showing a second method for identifying potential mimetics of erythropoietin using a computer system.

Like reference numbers and designations in the various 25 drawings indicate like elements.

e H:\MaraR\Keep\Speci\P36307.doc 22/02/00 DETAILED DESCRIPTION OF THE INVENTION Throughout this description, the preferred embodiment and examples shown should be considered as exemplars, rather than as limitations on the present invention.

Described below is the crystal structure of a small peptide mimetic of EPO bound to an s extracellular portion of the EPO receptor. The peptide, EMP1 (GGTYSCHFGPLTWVCKPQGG; SEQ ID NO: is characterized by an intramolecular disulfide bridge. Several lines of evidence suggest that EMP1 can act as an EPO mimetic.

For example, EMP1 competes with EPO in receptor binding assays and induces cellular proliferation of cell lines engineered to be responsive to EPO. Both EPO and peptide 1o induce a similar cascade of phosphorylation events and cell cycle progression in EPO responsive cells. Furhter, EMP demonstrates significant erythropoietic effects in mice as monitored by two diferent in vivo assays of nascent red blood cell production. This "data, when combined, strongly supports the notion that the peptide ligand, which has a sequence unrelated to that of EPO, is capable of binding to and inducing an agonist is conformation or assembly of EPO receptor.

Design of small molecule mimetics The structure of the EMP1 dimer demonstrates that a molecule substantially smaller than the natural hormone can act as an agonist and induce the appropriate biological response.

The peptide is assumed to have a substantially smaller contact interface with the receptor than its natural hormone. The binding determinants in the EPO receptor form an almost flat surface which is mainly hydrophobic in nature, without any cavities or charged residues that may help in design of a small molecule ligand to interact with the receptor.

This simplified framework of interactions revealed by the structural data presented herein can be used to identify additional EPO mimetics. The atoms of EMPI which are important for binding to the EPO receptor and forming dimeric EPO receptor include those involved in the contact between the EMP1 (peptide) and EBP (EPO receptor) and -6those involved in contacts between the two EMP1 molecules in the dimeric complex (peptide-peptide contacts). In addition to the contacts listed in Table 2, the following EMPI-EMPI hydrophobic contacts are significant: Tyr"', Cys", Phe", Trp

P

M

3 and Cys'" in each peptide. The following EMPI-EBP hydrophobic interactions are also significant: s Tyr", Phe", and Trp P 1 in each peptide. It will be understood by those skilled in the art that not all of the atoms present in a significant contact residue need be present in a mimetic. In fact, it is only those few atoms which actually from important contacts with the EPO receptor which are likely to be important for mimetic activity. Those skilled in the art will be able to identify these important atoms based on the model of the dimeric EMPI-EPO complex which can be constructed using the structural data herein.

Preferred mimetics will include atoms at postions similar to those of the EPO receptor contacting atoms of EMP 1. Even more preferred mimetics will be structurally similar to the dimer of EMP1 found in the structure described below. This is because the dimerization of EMP1 is an important factor in the diemerization of the EPO receptor.

is The methods of the invention employ a computer-based methods for identifying :compounds having a desired structure. More specifically, the invention uses the threedimensional coordinates of a subset of the atoms in the peptide GGTYSCHFGPLTWVCKPQGG when the peptide is co-crystallized with a portion of the erythropoietin receptor comprising amino acids 1 to 225 of the human EPO receptor, to determine peptide and non-peptide mimetic candidates by means of computer methods.

These computer-based methods fall into two broad classes: database methods and de novo design methods. In database methods the compound of interest is compared to all compounds present in a database of chemical structures and compounds whose structure is in some way similar to the compound of interest are identified. The structures in the database are based on either experimental data, generated by NMR or x-ray crystallography, or modeled three-dimensional structures based on two-dimensional sequence) 7 data. In de novo design methods, models of compounds whose structure is in some way similar to the compound of interest are generated by a computer program using information derived from known structures, data generated by x-ray crystallography and/or theoretical rules. Such design methods can build a compound having a desired structure in either an atom-by-atom manner or by assembling stored small molecular fragments.

The success of both database and de novo methods in identifying compounds with activities similar to the compound of interest depends on the identification of the functionally relevant portion of the compound of interest.

For drugs, the functionally relevant portion is referred 15 to a pharmacophore. A pharmacophore then is an arrangement of structural features and functional groups important for biological activity, EPO activity.

Not all of the compounds identified in steps to (d) having the desired pharmacophore will act as an EPO mimetic. The actual activity can be finally determined .°o only by measuring the activity of the compound in relevant biological assays and selecting those compounds which show S. an increase in erythropoiesis in vivo.

Dimerization of the EPO receptor is important for activity. Accordingly, preferred mimetics will be based on the structure of the EMP1 dimer as it is bound to the EPO receptor dimer. Thus, preferred mimetics have included important contacts from both of the RWJ 61233 peptides present in the structure described below. Such mimetics will favor dimerization of the EPO receptor.

Programs suitable for generating predicted threedimensional structures from two-dimensional data include: Concord (Tripos Associated, St. Louis, MO), 3-D Builder (Chemical Design Ltd., Oxford, Catalyst (Bio-CAD H:\MaraR\Keep\Speci\P36307.doc 22/02/00 8 Corp., Mountain View, CA), and Daylight (Abbott Laboratories, Abbott Park, IL).

Programs suitable for searching three-dimensional databases to identify molecules bearing a desired pharmacophore include: MACCS-3D and ISIS/3D (Molecular Design Ltd., San Leandro, CA), ChemDBS-D (Chemical Design Ltd., Oxford, and Sybyl/3DB Unity (Tripos Associates, St. Louis, MO).

Programs suitable for pharmacophore selection and design include: DISCO (Abbott Laboratories, Abbott Park, IL), Catalyst (Bio-CAD Corp., Mountain View, CA), and ChemDBS- 3D (Chemical Design Ltd., Oxford, Databases of chemical structures are available from Cambridge Crystallographic Data Centre (Cambridge, U.K.) and Chemical Abstracts Service (Columbus, OH).

De novo design programs include Ludi (Biosym Technologies Inc., San Diego, CA) and Aladdin (Daylight Chemical Information Systems, Irvine CA).

Those skilled in the art will recognize that the design of 25 a mimetic may require slight structural alteration or adjustment of a chemical structure designed or identified S* using the methods of the invention.

In general, chemical compounds identified using steps (a) to of the present invention can be synthesized chemically and then tested for EPO activity using any of the methods described below. The method of the invention is particularly useful because it can be used to greatly decrease the number of potential mimetics which must be screened for EPO activity.

H:\MaraR\Keep\Speci\P36 3 07.doc 22/02/00 8A The invention may be implemented in hardware or software, or a combination of both. However, preferably, the invention is implemented in computer programs executing on programmable computers each comprising a processor, a data storage system (including volatile and non-volatile memory and/or storage elements), at least one input device, and at least one output device. Program code is applied to input data to perform the functions t:oo..

4* H:\MaraR\Keep\Speci\P36307.doC 22/02/00 described above and generate output information. The output information is applied to one or more output devices, in known fashion. The computer may be, for example, a personal computer, microcomputer, or workstation of conventional design.

Each program is preferably implemented in a high level procedural or object oriented programming language to communicate with a computer system. However, the programs can be implemented in assembly or machine language, if desired. In any case, the language may be a compiled or interpreted language.

Each such computer program is preferably stored on a storage media or device ROM or magnetic diskette) readable by a general or special purpose programmable 10 computer, for configuring and operating the computer when the storage media or device :is read by the computer to perform the procedures described herein. The inventive system may also be considered to be implemented as a computer-readable storage medium, configured with a computer program, where the storage medium so configured causes a computer to operate in a specific and predefined manner to perform the functions described herein.

FIGURE 1 is a flowchart showing a first method for identifying potential mimetics of erythropoietin using a computer system. The method uses a programmed computer Scomprising a processor, a data storage system, at least one input device, and at least one .output device, and comprises the steps of.

inputting into the programmed computer through an input device data comprising the three-dimensional coordinates of a subset of the atoms in the peptide GGTYSCHFGPLTWVCKPQGG when the peptide is co-crystallized with a portion of the erythropoietin receptor comprising amino acids 1 to 225 of the receptor, thereby generating a criteria data set (STEP 100); comparing, using the processor, the criteria data set to a computer database of chemical structures stored in the computer data storage system (STEP 102); selecting from the database, using a program suitable for searching threedimensional databases to identify molecules bearing a desired pharmacophore (such as those described above or equivalents), chemical structures having a portion that is structurally similar to the criteria data set (STEP 104); s .outputting to an output device the selected chemical structures having a portion similar to the criteria data set (STEP 106).

FIGURE 2 is a flowchart showing a second method for identifying potential mimetics of erythropoietin using a computer system. The method uses a programmed computer comprising a processor, a data storage system, at least one input device, and at least one S. o10 output device, and comprises the steps of: inputting into the programmed computer through an input device data comprising the three-dimensional coordinates of a subset of the atoms in the peptide GGTYSCHFGPLTWVCKPQGG when the peptide is co-crystallized with a portion of the erythropoietin receptor comprising amino acids 1 to 225 of the is receptor, thereby generating a criteria data set (STEP 200); constructing, using a program suitable for generating chemical structure models (such as those described above or equivalents), a model of a chemical structure having a portion that is structurally similar to the criteria data set (STEP 202); outputting to the output device the constructed model (STEP 204).

Confirmation of Biological Activity In order to determine whether a molecule identified using the methods of the invention can act as an EPO mimetic, one or more in vitro or in vivo assays of EPO activity should be performed. For example, mimetic molecules should be able to stimulate proliferation ofTF-1 cells (Kitamura et al., J. Cell Physiol. 140:323, 1985) or B6Sut cells (Greenberger et al., Proc. Natl. Acad. Sci. USA 80:2931, 1983), but preferably do not stimulate proliferation of cells which do not bear the EPO receptor.

Thus, preferred mimetics do not stimulate proliferation ofMo7e cells (Avanzi et al., Br.

J. Haematol. 69:359, 1988).

-11- Potential mimetics can also be tested in a murine model of erythropoiesis. In this assay a potential mimetic is administered to normal mice which express endogenous basal levels ofEPO. Reticulocytes are counted, preferably by flow cytometry, to determine whether the candidate mimetic increases reticulocyte levels. An increase in reticulocyte levels indicates that the candidate mimetic is stimulating erythropoiesis. Because the mice used in this assay already express EPO, this assay may be relatively insensitive. As an alternative, candidate mimetics can be assayed in the exhypoxic-polycythemic mouse bioassay. In this assay polycythemia is induced by conditioning mice in a hypobaric chamber to reduce endogenous EPO levels. A potential EPO mimetic can be adminiso10 tered to a conditioned mouse. Incorporation of "Fe into blood serves as a measure of erythropoiesis. This erythropoiesis can be attributed to the candidate mimetic.

The assays described above are examples of suitable assays. Other assays for EPO activity known to those skilled in the art are also useful.

In order to determine the biological activity of a candidate mimetic it is preferable to 1is measure biological activity at several concentrations of candidate mimetic. The activity at a given concentration of candidate mimetic can be compared to the activity of EPO itself.

S" Structural Data The coordinates for amino acids 1 to 225 of the human EPO receptor bound to peptide EMPI are presented in the attached appendix in standard Brookhaven database format.

Also included in this appendix is a list of van der Waals interactions. These coordinates can be used in the design and identification of EPO mimetics according to the methods of the invention.

Structure of EBP-EMP1 Complex The extracellular fragment of human EPO receptor (EPO binding protein, EBP), consisting of residues 1-225, was expressed in Escherichili and purified as described -12- (Johnson et al., Protein Express. Purif. 7:104, 1996). Rhomboidal-shaped crystals of an EBP complex with EMPI were obtained in orthorhombic space group P2,2,2,, with cell parameters a=59.2A, b=75.5A, c=132.2A, with two EBP and two peptide molecules in the asymmetric unit and a VM=2.8 A/dalton (Matthews, J. Mol. Biol. 33:491, 1968). The crystal structure was determined by multiple isomorphous replacement (MIR) using two heavy atom derivatives (Table Residues 1-2 and 19-20 of each peptide as well as residues 1-9, 21-23, 164-166, 221-225 of receptor molecule I, and residues 1-9, 21-23, 133-135, 221-225 of receptor molecule II had poor or no electron density and are excluded from the structure analyses S* t10 An important break in the electron density that affects the structure interpretation occurs for the three residues (Arg" -Gly" -Pro") that link the amino terminal a-helix to the first -strand in Dl of both receptor molecules. A molecular packing diagram shows the proximity of a second nbn-crystallographically related dimer in the crystal that gives two possibilities of how this three-residue linker may be connected. The current choice of is linker connectivity is based on a structure of another independent EBP-peptide complex at higher resolution (2.5 which shares a similar molecular packing, but for which the electron density is clear for these three residues. At present there are no experimental data to verify whether this N-terminal a-helix exists in solution or is a crystallization packing artifact. Notably, this helical region is not observed in the published structures 20 ofhGHbp (begins at residue 32; deVos et al., Science 255:306, 1992), PRLR (begins at residue 2, without any defined secondary structure until the first P-strand, residue 6; Somers et al., Nature 372:478, 1994), the INF-yRa (begins at residue 17; Walter et al., Nature 376:230, 1995) or the tissue factor (begins at residue 3 without any defined secondary structure until the first P-strand, residue 11; Muller et al., Nature 370:662, 2s 1994).

The EBP monomer folds into two domains, Dl and D2, that form an L-shape with the long axis of each domain aligned at approximately 90° to each other, the overall molecular dimensions are 45 A x 52 A x 62 A The N-terminal domain (DI, residues -13- 114) and C-terminal domain (D2, residues 119-220) are connected by a short four residue a-helix linker. Both domains are more closely related in overall topology to Fibronectin type-ln (FBN-II) domains than to Ig domains (Bork et al., J. Mol. Biol., 242:309, 1994).

The FBN-ll fold is composed of two antiparallel P-pleated sheets, consisting of strands A, B, E and strands G, F, C and and is found in the two domains of the human growth hormone (de Vos et al., Science 255:306, 1992) and prolactin (Somers et al., Nature 372:478, 1994) receptors, the DI and D2 domains of the a chain of interferon-y receptor (IFN-yRa) (Walter et al., Nature 376:230, 1995), the D2 domain of CD4 (Wang et al, Nature 348:411, 1990; Ryu et al., Nature 348:419, 1990), the two domains of tissue factor o10 (Muller et al., Biochemistry 33:10864, 1994; Harlos et al., Nature 370:662, 1994), the third fibronectin-type repeat oftenacin (Leagy et al., Science 258:987, 1992) and the D2 domain of the chaperone protein PapD (Holmgren et al., Nature 342:248, 1989). The FBN-m topology differs from an Ig constant domain by a shift of strand D from one Psheet (strands A, B, E and D) to the other (strands G, F, C, where it is defined as the 15 C strand. Superposition of equivalent P-sheet core residues of the D1 and D2 domains in EBP gives an r.m.s. deviation of 2.3 A for 77 Ca pairs, which is significantly larger than the corresponding domain overlaps for hGHbp (1.1A) and PRLR and reflects a difference in the subclass of fold between the two EBP domains.

In Dl, a short a-helix (residues 10-20), precedes the first P-sandwich that is better 2o described as a hybrid of the FBN-III fold with an Ig fold (residues 24-114), rather than strict FBN-Ul topology. In this h-type fold (Wang et al., Nature 348:411, 1990; Ryu et a, Nature 348:419, 1990), the C strand is long and interacts first with strand C and then switches to interact with strand E (where C changes its designation to strand D) forming a four-on-four strand P-sandwich. DI contains the two conserved disulfide bridges linking Cys (PA) to Cys N (PB) and Cys" (PC) to CysP The number of residues between the cysteine pairs that form the two disulfide bridges are 9 and 15 for EBP, compared to 9 and 10 in both GHR and PRLR. The longer connection between strands C and E enables the second half of strand C to become strand D. This h-type topology is not found in either of the two s-type GHR domains. A potential glycoylation site exists -14on residue Asn" 2 which is located towards the end of the loop region connecting the PB and PC strands. Although Asn" is not glycosylated in this bacterially expressed protein, an external cavity around the Asn 52 side chain could easily accommodate a carbohydrate moiety.

A helical linker (residues 115-118) connects Dl to D2 (The torsion angles for the interdomain helical linker for Asn"', Glu" 7 and Val" are -50* 99°, 26°, and -151 38* respectively.) and has been observed in other members of this receptor family, hGHbp, PRLR, IFN-yRa and tissue factor. In EBP, the domain association is further restricted by a mixed assortment of hydrogen bonding, hydrophobic o10 interactions and one salt bridge (between Arg" and Asp'") from 11 residues of Dl and 12 residues of D2 with a total buried surface [The molecular surface areas buried by interaction were calculated using the program MS (Connolly, J. Appl. Crystallog, 16:439, 1983) using a 1.7A probe sphere and standard atomic radii (as described in Davies, et al, Ann. Rev. Biochem. 59:439, 1990). There may be some discrepancies between values is reported here and other (deVos et al., Scince 255:306, 1992) published values due to use ofa different algorithm (Connolly) vs. Lee et al., J. Mol. BioL, 55: 379, 1971) and probe radii. For clarity all values reported here have been calculated in the same way for better comparison between the receptors] of 950 A 2 for the two domains.

D2 (residues 119-220) folds into the standard FBN-lll (s-type) topology with one free 2 cysteine and no disulfide bridges, consistent with GHR and PRLR that have three and two disulfide bridges, respectively, in Dl but none in D2. After the a-helix linker, D2 begins with an irregular coil (residues 118-126) that contains Pro" 4 which is conserved in the structures of hGHbp, PRLR, tissue factor and IFNy-Ra, and based on sequence alignment, in most class-1 and class-2 cytokine receptors (Bazan, Proc. Natl. Acad. Sci.

USA 87:6934, 1990). This short coil ends with Gly which has a positive 4 520,40°) consistent with the equivalent Ala'" and Ala" torsion angles in hGHbp T a 63°,68 0 and PRLR 'Y 580,38"). The Pro 2 region forms an analogous extended bulge conformation adjacent and parallel to a corresponding bulge containing the WSXWS motif. The WSAWS sequence forms a modified wide P-bulge (Richardson, Adv. Prot. Chem. 34:167, 1981) and is located in an extended chain region immediately preceding the PG strand that would normally connect to the membrane spanning region of the EPOR.

s The quaternary structure of the complex is composed of two peptides and two receptors that form a T-shapes assembly. A noncovalent peptide dimer interacts with two receptor molecules to generate an almost perfect 2-fold symmetrical arrangement. After superposition of D2 of the two EBP molecules in the dimer, the centers of mass of the two DI domains are only 0.8 A apart, sufficient to perturb perfect two-fold symmetry.

so Separate superposition of the corresponding Dl and D2 of each receptor in the dimer results in r.m.s. deviations of 0.53 A (105 DI Ca pairs) and 0.47 A (93 D2 Ca pairs).

The cyclic EMPI contains a single disulfide bridge between Cys" and Cys r which links two short P-strands (residues 4-7 and 13-16) that are connected by a slightly distorted type 1 p-tum [Pro 0 and Leu n of the P-turn have 1<,f -38* and -99", s respectively. The carbonyl oxygen of Leu r has a hydrogen bond to EBP distorting the value from its normal 0*30 in a standard type I P-turn.] consisting of residues Gly"-ProO-Leu"'-Thr" 2 Each peptide has a very close association with its other peptide partner and buries 320 A of its 1220 A 2 molecular surface in this interaction (Connelly, J. Appl. Crystallog. 16:439, 1983; Davies et al., Ann. Rev. Biochem. 59:439, 1990; Richards, J. Mol. Biol. 55:379, 1971). Four hydrogen bonds between the mainchains of the two peptides results in formation of a four-stranded anti-parallel Ppleated sheet (Table Two symmetric hyrdophobic cores are assembled by peptide dimerization and are comprised of the disulfide bridges and the side chains ofTyr",Phe" and Trpe'. The construction of each hydrophobic core resembles a box which places the aromatic rings ofPhe7,Trp

P

and Tyr" (from the other peptide) and the disulfide bridge (Cys"-Cys' 5 at the corers. The two glycine residues at either end of the peptide are not structured.

-16- The peptide dimer is embedded in a deep crevice between two EBP receptor molecules.

A portion of each peptide monomer interacts with both receptor molecules. The binding sites of each EBP are practically identical due to the 2-fold symmetric interactions imposed on binding the peptide dimer. The four major contact areas on EBP come from s segments on four loop regions (L1, L3, LS, L6) that connect strands A to B (LI residues 33-34) and F to G (L6 residues 90-94) in DI and strands B to C (L5 residues 148-153) and F to G (L6 residues 203-205) in D2. The total buried molecular surfaces in the peptide-EBP assembly are 840 A 2 and 880 A 2 for the two peptides and EBP's, respectively. The peptide-EBP interaction can be separated into distinct hydrophobic and 10o polar areas. A hydrophobic core is formed between the peptide and receptor and comprises Phe,Met'" and Phe 20 from one EBP molecule and the peptide hydrophobic box consisting of Phe" and Trp"' from one peptide and Tyr and Cys r from the other peptide. The polar interactions are located mainly at the bottom of the binding crevice and are mainly with lo6p L5 in D2. Five of the six hydrogen bonds are between the s15 mainchain of the P-turn residues Gly",Pro r 0 and Led" from one peptide with the oo mainchain and sidechain hydroxyl of conserved Tyr", which crosses over its other peptide partner, to interact with loop L3 (Table The EBP-EBP interaction makes a surprisingly minor contribution to the overall stability of the complex where the interreceptor buried molecular surface is only 75 A 2 contributed by Leu' 1 and Arg 1 7 from 20 each receptor molecule.

EMPI is one of a family of sequences that contain several conserved residues, besides the cysteines ,.aNiI02-- 1;9-.91 MiSG. The most structurally significant of these consensus residues appear to be Tyr" and Trp", which along with the disulfide bridge have a major contribution to the hydrophobic core of the peptide-peptide 2 interaction. Moreover, these two aromatic residues play a pivotal role in peptide-receptor interaction and in receptor dimerization.

Dimerization of EBP in Solution -17- To explore the interaction of EMP1 with EBP in solution we employed a bifunctionalsulphydryl reactive crosslinker DPDPB, [1,4-di-(2'-pyridyldithio propionamido) butane], in an attempt to stabilize a peptide-dependent dimeric structure.

The choice of crosslinker was based on previous experiments with amine-reactive s crosslinkers that were found to inactivate EBP. EBP contains a single free sulphydryl in D2 which is potentially reactive to crosslinking reagents (The DPDPB crosslinker itself does not inactivate the EPO binding potential of EBP nor the proliferative properties of EMP1). A dimeric EBP product is formed by co-incubation of EMPI, DPDPB and EBP. The amount of dimeric product increases with peptide 10o concentration and no significant dimer product is observed in the absence of peptide.

DPDPB-crosslinked products formed through disulfide-exchange reactions should be readily reversible by reduction as is seen for the covalently-linked EMP 1-mediated dimer.

Furthermore, we have constructed a covalently-linked dimeric form of EMP1 that demonstrates increased biological potency (Johnson et al, in preparation). The Cys"' 15 residues in D2 of the EBP dimer are 20.7 A apart (Sy-Sy distance) which approximates the 16 A length (and approximately 2 A in bond length at each end) of the DPDPB crosslinker. Thus EMPl mediates formation of a soluble EBP dimer complex in solution consistent with the crystal structure.

The WSXWS motif 2 The WSAWS sequence (residues 209-213) corresponding to the WSXWS box occurs in a P-bulge (Richardson, Adv. Prot. Chem. 34:167, 1981; Chan et al., Protein Science, 2:1574, 1993) immediately preceding -strand G in D2. Residues in this motif do not interact with ligand, have no role in receptor-receptor interactions and are located on the opposite side of the receptor-receptor and receptor-ligand interface. The WSAWS box 2s represents only a segment of a complex array of interactions that involves several other conserved side chains from the four-stranded P-sheet in D2. The indole ring systems of Trp 2 09 and TrpU 2 point toward an external concave surface of the P-sheet and are only partially solvent exposed, whereas the Ala 2 side chain points directly out into solution.

The amides and hydroxyls of both Ser 1 0 and Ser 2 3 form hydrogen bonds with the main -18chain of residues 198 and 196 of adjacent strand F in a pseudo P-sheet type interaction that resembles a modified wide P-bulge (Richardson, Adv. Prot. Chem. 34:167, 1981; Chan et al., Protein Science, 2:1574, 1993) where the sidechain hydroxyl rather than the carbonyl oxygen makes the P-sheet interaction. The P-bulge architecture places the two s Trp-residues, which are spread four residues apart, on the same side of the P-sheet and not on opposite sides as in normal P-sheet or extended chain structures. The guanidinum group ofArg" from Strand F, the central residue (Richardson, Adv. Prot. Chem. 34: 167, 1981; Chan et al., Protein Science, 2:1574, 1993) in the bulge, is positioned exactly between the two Trp indole rings to form an extended i-cation system (Kumpf et al., 10 Science 261:1708, 1993. The center of the pyrrole ring ofTrp" 2 the Nc of the Arg'" and S" the center of the benzene ring of Trp 1 2 are positioned on a straight line with the three planes of the conjugated systems stacked parallel to each other at approximately 4 A spacing. In addition, the aliphatic portion of the Arg 1 side chain has hydrophobic interactions with the indole ring of Trp 2 completing the alternating stacking of two aromatic and two positively-charged amino acid residues. The side chain of Glu'" forms a hydrogen bond with Arg 9 7 s presumably to help orient the guanidinium group and add some specificity and stabilization to the system.

It appears then that the linear WSXWS motif identified from sequence alignments of i cytokine receptors represents only a component of a more complex conformational unit 20 that contributes a significant structural feature to D2. Aromatic residues have previously been suggested to have a stabilizing effect and play a role as a folding nuclei in structures of antiparallel -sandwiches (Finkelstein et al., Protein Eng. 6:367, 1993). The aminoaromatic parallel stacking between the guanidinium group of arginine and the aromatic rings is a common feature in protein structures (Burley et al., Adv. Prot. Chem., 39:125, 1988; Flocco et aL, J. MoL Biol., 235:709, 1994), but a parallel triple stacking of n-cation systems is rare (Kim et al., Biochemistry 32:8465, 1993) although observed in other class-1 cytokine receptors, hGHbp and PRLR.

The structural equivalents of the WSXWS motif in hGHbp (YGEFS) and PRLR (WSAWS) are involved in an even more intricate and complex array of 7-cation interactions. The it-cation system is extended in hGHbp and PRLR to include an additional aromatic residue (Trp'" for hGHbp and Trp' m for PRLR) from the loop region that links PC and PC in D2 and a positively-charged residue (Arg 2 for hGHbp and Arg 4 7 for PRLR) that stacks between the Trp and the second aromatic residue. The additional Arg residue is contributed either from the PF strand as in hGHbp (Arg 2 1 or from PC as in PRLR (Arg 47 the glutamine residue that hydrogen bonds and orients the arginine also switches strands. Sequence alignments suggest that this Arg-Gln switch o10 could be common to other members of the class-1 cytokine receptor family. The extended n-cation system in hGHbp and PRLR consists of five positively charged and three aromatic residues stacked in an alternating order which comprises ofLys 2 Tyrm, 0 Arg 2 Phe m Arg 2 Trp 1 Lys 1 9 for hGHbp and Lys"s, Trp 9 1 Arg 1 Trp"', Arg 1 4 7 Trp" Lys'" for PRLR. The first aromatic-Arg-aromatic trio are approximately 4A apart, 15 as in EBP, but the second system is stacked closer together at approximately 3.6 A spacings consistent with It-n interaction (Burley et al., Adv. Prot. Chem., 39:125, 1988; Flocco et al., J. Mol. Biol., 235:709, 1994). The outer lysines also use the aliphatic ~portions of their side chains to form hydrophobic interactions with the aromatic rings.

Based on sequence alignments with other members of the class-I cytokine receptor 20 superfamily, such structurally extended n-cation systems could exist in human thrombopietin, IL-6 and ciliary neurotrophic factor receptors, and in human IL-4 receptor based on structural modeling (Gustchina et al., Proteins 21:140, 1995). Although IFNyRa and tissue factor do not have a WSXWS moti the corresponding sequences TTEKS (residues 213-217) for IFN-yRa (Walter et al., Nature 376:230, 1995) and KSTDS (residues 201-205) for tissue factor (Muller et al., Biochemistry 33:10864, 1994; Harlos et al., Nature 370:662, 1994), maintain a very similar P-bulge. The consensus sequence among these five x-ray structures indicates that a serine or threonine in positions 2 and maintain a common set of hydrogen bonds between their side chain hydroxyls and the mainchain of the neighboring strand. Only in hGHbp is there no hydroxyl-containing residue in position 2, but Ser m still maintains the equivalent interaction. A Ser 2 6 to Ala mutation abrogates hGHR binding to hGH, and its expression on the cell surface is drastically reduced (Baumgartner et al., J. Biol. Chem., 269: 29094, 1994). In GM- CSFRa and IL-2RP, point mutations of the serine residues cause a substantial decrease in cell surface expression but little or no effect on ligand binding (Ronco et al., J. Biol.

s Chem. 269:277, 1994; Miyazaki et al., EMBO Journal 10:3191, 1991).

Conservation of the WSXWS motif in EPOR or its equivalent in other members of the class 1 cytokine receptors has been proposed to be essential for biological activity and was thus assumed to be part of the receptor binding site (Yoshimura et al., J. Biol. Chem.

267:11619, 1992; Quelle, MoL Cell Biol. 12:4553 1992). For EPOR, a systematic study of 100 mutations of the WSAWS sequence demonstrates that most of the mutations of the two tryptophan and serine resulted in molecules that did not reach the cell surface but were retained in the endoplasmatic reticulum (Hilton et al., Proc. Natl. Acad. Sci. USA 92:190, 1995; Hilton et al., J. Biol. Chem. 271:4699, 1996). Furthermore, an Ala 21 to Glu mutation in the WSAWS sequence resulted in better transportation from the ER to 15 the Golgi and a 3-5 fold increase of the number of EPOR molecules on the cell surface compared to the wild-type (Hilton et al, Proc. Natl. Acad. Sci. USA 92:190, 1995; Hilton et al., J. BioL Chem. 271:4699, 1996). These results support our conclusion that the WSXWS sequence plays an important role in the structure and folding ofD2 in EPOR and other related receptors.

Comparison with other cytokine-receptor complex structures The overall quaternary structure of the peptide-EBP complex substantially from the equivalent arrangement in the hGH-hGHR complex. The non-symmetric nature of the single four-helix-bundle structure of the growth hormone ligand results in an asymmetric homo-dimerization of the receptor that corresponds to a 159" rotation between receptors compared to the almost perfect 2-fold (180*) rotation for the EBP-peptide complex. The tertiary arrangement of domains within EBP and hGHbp is also somewhat different.

When the equivalent EBP and hGHbp D2 domains are superimposed on each other, their corresponding Dl domains differ by a 12" rotation and a 4.3A translation.

-21- The mechanism of hGH binding to its receptor has been well studied (Wells, Curr. Opin.

Cell Biol. 6:163, 1994; Clackson et al., Science 267:383, 1995) and is sequential. Initial high affinity (nM) binding of the hormone with one receptor results is a buried surface of 1130 A 2 on the receptor. The second hGHbp2 has a substantially smaller interface s (deVos et al., Science 255:306, 1992) with the second binding site on hGH and interacts only with the preformed 1:1 complex to generate buried surface areas of 740 A 2 with hGH and 440 A 2 with the first hGHbpl (deVos et al., Science 255:306, 1992; (Wells, Curr.

Opin. Cell Biol. 6:163, 1994; Clackson et al., Science 267:383, 1995). The binding determinants of each hGHbp are comprised of the six recognition loops (L 1-L6), three 0o of which (L1-L3) come from one end of the P-sandwich structure in DI, one from the interdomain linker and two from D2.

Although these two receptor complexes, EBP-EMP1 and hGH-hGHbp, have different dimeric arrangements, which probably in this case represent differences in the size and shape of the natural versus synthetic ligand, both receptors share equivalent ligand is recognition loops, L1, L3, L5 and L6 for the EBP and LI to L6 for the hGHbp. A nonactive PRLR, complexed with only one molecule of hGH, also uses the same contact loops (LI to L6) (Somers et aL, Nature 372:478, 1994). Based on similarity of the ligand recognition sites in hGHbp and PRLR, one would expect that the binding site of EBP, when its natural EPO ligand is bound, would extend to include two additional loops, L2 20 and L4, that comprise residues 59-63 (L2) between strands C to C, and residues 110-118 (L4) from the carboxyl end of PG in D and the interdomain linker. These six loops in EBP, hGHbp and PRLR area in structurally equivalent positions but vary in size, amino acid composition and conformation although the interacting portions of each loop (side or tip) remain similar, L1, L2, L3, L5 interact mainly with their tips and L6 with its side.

In EBP, the L5 loop is three residues shorter than in hGHbp and PRLR, where the L6 loop is three and four residues longer than in hGHbp and PRLR, respectively. The L2 loop also varies (6 to 10 residues) among the three receptors but in EBP does not participate in peptide binding, and in hGHbp is partially disordered, although it does contact the hormone. In one respect, this situation is similar to the complementarity- -22determining regions (CDR's) in antibodies, where changes in length and sequence of the six binding loops impose specificity for different antigens, whereas the framework itself remains constant (Wilson et al., Ciba Foundation Symposium. Wiley, Chichester, 1991, Vol. 159, p. 13).

s It has been shown for the hGH-hGHbp complex that only a subset of 9 out of 33 interacting residues that make up the structural epitope of the receptor constitute a functional epitope or hot spot (Wells, Curr. Opin. Cell Biol. 6:163, 1994; Clackson et al., Science 267:383, 1995) where high affinity binding interaction takes place. This reduced epitope is substantially smaller than the structural epitope and is comprised from residues (Arg 0 Glu", Ile'0, Trp'", Ile' 0 s Pro 6 Asp'", and Trp' which are located in contact loops LI, L3 and L5 with the most significant contribution kcal/mol) coming from two aromatic residues (Trp'" and TrIp") in L3 and L5 (Wells, Curr. Opin. Cell Biol.

6:163, 1994; Clackson-et al., Science 267:383, 1995; Wells, Proc. Natl Acad. Sci. USA 93:1, 1996). In EBP, Phe" is equivalent to Trp' 4 in hGHbp, as suggested previously is (Wells, Curr. Opin Cell Biol. 6:163, 1994; Clackson et al., Science 267:383, 1995; Wells, Proc. Natl Acad. Sci. USA 93:1, 1996; Jolliffe et al., Nephrol. Dial Trans. 10:suppl. 2, 28, 1995), but there is no homologous residue to Trp' in the shorter L5 loop. In the EBP-EMP1 complex, the Phe" peptide aromatic side chain occupies the equivalent position of the Trp'" side chain in hGHbp. One can assume that when EPO binds to its S2 receptor, the hormone may provide an aromatic residue to the hydrophobic core of the binding interface and/or the L6 loop in EBP may play a more significant role in the hormone binding than in hGHbp, since it is 3 residues longer and contains the aromatic Phe 2 In these three class-1 receptor structures, some loops are disordered which are in D2 for EBP for EBP (residues 164-166 in EBPI and 133-135 in EBP2) and in DI for both hGHbp (residues 55-58, 73-78 for hGHbpl and 54-60, 73-75 for hGHbp2) and PRLR (residues 31-33, 84-86). Otherwise, these three class-1 cytokine receptors do not differ greatly in their over all tertiary structures; Dl and D2 have broadly similar general arrangement in all three receptors such that the angle between the long axes of the two domains is approximately 90 degrees. I tis this arrangement of domains that allow these particular L1-L6 loops to be available for the recognition and binding ofligands. In a 2:2 complex between IFN-y and its class-2 receptor IFN-yRa, DI and D2 are related by a 125 degree angle, which elongates the receptor and restricts the binding determinants that can be used for interaction with hormone; the L loop now becomes buried in the DI-D2 interface, although the other five loops (L2-L6) are still available for ligand interaction.

This elongated interdomain arrangement is also observed in tissue factor (Muller et al., Biochemistry 33:10864, 1994; Harlos et al., Nature 370:662, 1994) which has a distant 0o relationship to the cytokine receptor superfamily.

A mutational analysis of the EBP molecule indicates that the most crucial amino acid residue for binding EPO is Phe" in the L3 loop (Jolliffe et al., Nephrol. Dial. Trans.

10:suppl 2,28, 1995). 'The Phe93Ala mutant shows an increase int he ICs compared to is the wild-type by a factor of approximately 1000, whereas other mutants (Ser91Ala, Ser92Ala, Val94Ala, Metl50Ala and Hisl53Ala) show small relative increases in teh ICo of only 2.5-12.5 fold). The side chain of Phe" buries 66 A 2 of molecular surface, which is the highest among interacting side chains. In hGHbp, the corresponding Trpl04Ala mutation results in an increase in the Kd by a factor of more than 2,500 compared to the wild-type indicating the equivalent importance of this residue in hGH binding and its key contribution to the hydrophobic core of the functional epitope (Wells, Curr. Opin. Cell Biol. 6:163, 1994; Clackson et al., Science 267:383, 1995; Bass et al.

Proc. Natl. Acad. Sci. USA 88:4498, 1991).

The role of dimerization on signal transduction In the EBP-EMP1 complex structure, we surprisingly observe that a peptide, unrelated in sequence and probably in structure, to the natural ligand, can induce a biologically active dimerization of EPO receptor that promotes signal transduction and cell proliferation. Comparison of three class-I cytokine receptor complexes, whose structures have been determined so far, suggests that when the natural EPO hormone, which is proposed to have a structure of a four-helix bundle (Boissel et al., J. Biol. Chem.

268:15983, 1993), induces receptor dimerization, it is more likely to resemble the hGHhGHbp assemblage. This would suggest that more than one mode of productive extracellular dimerization is permissive for intracellular dimerization of the cytoplasmic s domains with two JAK2 molecules in order to initialize the cascade of events that produces the biologically relevant signal (Ihle et al., Seminars in Immunology 5:375, 1993; Klingmuller et al., Cell 80:729, 1995). The peptide-EBP structure would then represent only one possible dimeric arrangement that promotes signal transduction.

Mutant EPOR molecules, containing a single Arg to Cys mutation (Arg'" in human and 10 Arg'" in murine), have been shown to form biologically active dimers in the absence of EPO (Yoshimura et al., J. Biol. Chem. 267:11619, 1992); Watowich et al., Proc. Natl.

Acad. Sci. USA 89:2140, 1992; Watowich et al., Mol. Cell. Biol. 14:3535, 1994), suggesting that extracellular recptor homo-dimerization may be sufficient in itself for signal transduction. It has been shown in another system (Spencer et al., Science is 262:1019, 1993) that activation of a specific set of trasncription factors can be induced by the chemical crosslinking of cytoplasmic domains of modified cell membrane receptors that do not contain the extracellular and transmembrane domains. These receptors are not related to the cytokine receptor superfamily but illustrate that oligomeication plays a key role in activation of the receptor, and that the main functional 20 role of the extracellular, ligand-binding domain is to allow (in the presence of ligand) dimerization or oligomerization and induce similar association of the cytoplasmic domains.

Mutageneses experiments originally suggested a role for the WSXWS motif in this cell signalling process (Yoshimura et al., J. BioL Chem. 267:11619, 1992; Quele et al. Mol.

Cell. Biol. 12:4553, 1992; Chiba et al., Biochem. Biophys. Res. Comm. 184:485, 1992) possibly by promoting receptor homo-dimerization. However, truncation mutants of EPOR (Miura et al., Arch. Biochem. Biophys. 306:200, 1993) do not confirm this role for the WSXWS motif. The EBP-EMP1 complex structure shows that the WSXWS motif of the EPOR, as for the hGH-hGHbp complex (deVos et al., Science 255:306, 1992) is located on the opposite face of the molecule from the receptor dimerization. In the absence of unliganded structures for the extracellular domains of EPOR, hGHR and PRLR, it is not possible to determine whether any conformation change occurs on ligand s binding that would involve the WSXWS box. Apart from being a striking structural feature in D2, and its obvious proximity to the membrane spanning domain, one cannot rule out possible interactions of this region with some other cell surface molecules that are involved somehow in the signal transduction process.

STowards design of small molecule mimetics The structure of the EMP1 dimer demonstrates that a peptide considerably smaller than the natural hormone can act as an agonist and induce the appropriate biological response.

The peptide can be assumed to form a substantially smaller contact interface than the "natural hormone with the receptor. The peptide binding site in EBP forms an almost flat surface, which is mainly hydrophobic in nature, without any cavities or charged residues 1s that are normally essential for the specific targeting of small molecule ligands to a receptor binding site. The hGHbp study (Wells et al., Science 267:383, 1995; Wells, Proc. Natl. Acad. Sci. USA 93:1, 1996) shows that only a small part of the observed structural binding site, the so-called functional epitope (subra), contributes most of the binding energy and strongly implied that a "minimized" hormone designed to interact S. 20 with this site could form sufficient interactions to activate the receptor. Furthermore, the limited site of interaction of the small agonist peptide with the EBP corresponds almost exactly to the smaller functional epitope derived from alanine scanning of hGH and hGHbp. Thus, by a different approach, we have arrived at the similar conclusion that a small number of key interactions can contribute to a functional epitope on a receptor.

Understanding of this simplified interaction surface can be now combined with further mutational studies to assist in identifying the most crucial residues in the functional epitope, and consequently provide a more practical target for drug design.

Data Collection, MIR and Refinement Statistics -26- The crystallographic data is summarized in Table 1. Native crystallographic data were collected on a Siemens multiwire area detector mounted on an Elliott GX-18 generator, operating at 40kV and 55mA, with a crystal-to-detector distance of 120mm. Two derivative data sets were collected on a MAR image plate mounted on a Siemens s generator operating at 50kV and 80mA, with crystal-to-image plate distance of 150mm.

Data were integrated, scaled and reduced using the programs XENGEN (Howard et al., J. App. Cryst. 20:383, 1987) for the native data and DENZO/SCALEPACK (Otwinowski et al., SERC Darsbury Laboratory, Warrington, 1993) for the derivative data. Initial multiple isomorphous replacement anomalous scattering (MIRAS) phases were calculated o1 to 3.1 A using the program package PHASES (Furey, American Crystallographic Association Fortieth Anniversary Meeting, New Orleans, LA, 1990) with a mean figure of merit of 0.64 (25.0-3.1 Phases were refined in PHASES using the solvent flattening protocol to a mean figure of merit of 0.92 (25.0-3.1 The quality of the map was generally good and most of the complex structure could be fitted using the graphics program O (Jone et al., Acta Crystallogr A47:110, 1991). The register of the amino acid residues was verified from the positions ofthe two disulfide bridges in DI, and the positions of the two Hg's from the mercury acetate derivative that were correctly assumed to bind to the free Cys"' residue, the peptide interpretation was verified from another data set from a complex between EBP and an iodinated peptide (Tyr' was substituted forp-iodo-Phe), which diffacted to 3.3A resolution, that in difference Fourier (F-F)al gave a cear indication of the location of the iodine atoms. The structure was refined using the slow-cooling protocol in X-PLOR 3.1(Brunger et al., Acta Crystallogr A46:585, 1990; Brunger, X-PLOR, Version 3.1: A System for X-ray and NMR, Yale Univ. Press, New Haven, CT, 1992) and rebuilt using Fo-Fc, 3Fo-2Fc and SIGMAA(Read Acta Crystallogr. A42:140, 1986) weighted electron density maps. After every two cycles of refinement, a set of simulated annealing omit maps to reduce model bias was calculated and the entire structure rebuilt. After several cycles of refinement, individual tet4erature factors were calculated and after 10 cycles of refinement and model building, the R-value was 0.21 for 8.0-2.8 A data with F>lo (13,984 reflections). The average thermal parameters for receptor I, receptor II and the -27peptides are 10.5A 2 12.3A and 10.7A respectively. Only one non-glycine residue [Asn' in EBP2], located in a loop region in Dl, is in a disallowed region in the Ramachandran plot. No solvent molecules were included in the model due to the moderate resolution (2.8 A) of the structure determination.

s Binding Contacts Binding contacts are summarized, in part, in Table 2: Hydrogen bond interactions in the binding site of the EBP-EMPI complex. Due to the symmetrical nature of the complex, peptide-1 and peptide-2 have equivalent interactions with the two EBP molecules. The hydrogen bond interactions were analyzed using HBPLUS (McDonald et al., J. Mol. Biol.

10 238:777, 1994), based upon both distance (3.9 A cutoff) and geometrical considerations.

A number of embodiments of the present invention have been described. Nevertheless, it wil be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, it is to be understood that the invention is not to be limited by the specific illustrated embodiment, but only by the scope of the is appended claims.

e 28 all.con Thu Apr 25 15:08:07 1996 1 EBP1-PEPTIDE1 VDW 1 LEU 33 CB 4 PEE 308 CE1 1 3.95 VDW 1 LEU 33 CB 4 PRE 308 CD1 1 4.11 VDW 1 PEE 93 CE1 4 TRP 313 CR2 1 3.74 VDW 1 PEE 93 CZ- 4 TRP 313 CR2 1 3.98 VDW 1 PEE 93 .CZ 4 TRP 313 CZ2 1 4.08 VDW 1 PRO 149 CA 4 GLY 309 0 1 3.59 VDW 1 PRO 149 CB 4 GLY 309 0 1 3.49 VDW 1 PRO 149 C 4 GLY 309 0 1 3.66 VDW 1 MET 150 N 4 PRO 310 0 1 3.35 VDW 1 MET 150 N 4 PRO 310 C 1 3.62 VDW 1 MET 150 CA 4 LEU 311 0 1 3.41 VDW 1 MET 150 CA 4 GLY 309 0 1 3.78 VDW 1 MET 150 CA 4 LEU 311 C 1 3.87 VDW 1 MET 150 CG 4 PRE 308 CD2 1 3.50 VDW 1 MET 150 CG 4 PRE 308 CB 1 3.70 VDW 1 MET 150 CG 4 PHE 308 CG 1 3.79 VDW 1 MET 150 SD 4 PEE 308 CD2 1 3.52 VDW 1 MET 150 SD 4 TER 312 C 1 3.55 VDW 1 MET 150 SD 4 TER 312 CA 1 3.58 VDW 1 MET 150 SD 4 TRP 313 N 1 3.75 VDW 1 MET 150 SD 4 PRE 308 CA 1 3.91 VDW 1 MET 150 SD 4 PEE 308 CB 1 4.03 VDW 1 MET 150 CE 4 PRE 308 CD2 1 3.45 VDW 1 MET 150 CE 4 TRP 313 CE2 1 3.71 VDW 1 MET 150 CE 4 PEE 308 CE2 1 3.79 VDW 1 MET 150 CE 4 TRP 313 CD2 1 3.83 VDW 1 MET 150 CE 4 TRP 313 NE1 1 3.91 VDW 1 MET 150 CE 4 TRP 313 CZ2 1 4.10 VDW 1 MET 150 C 4 LEU 311 0 1 3.41 VDW 1 TER 151 N 4 LEU 311 0 1 3.45 VDW 1 TER 151 CA 4 PRO 310 0 1 3.82 VDW 1 TER 151 CB 4 PRO 310 0 1 3.56 VDW 1 TER 151 OG1 4 LEU 311 CD2 1 3.43 VDW 1 TER 151 OG1 4 LEU 311 CA 1 3.91 VDW 1 THR 151 CG2 4 PRO 310 0 1 3.60 VDW 1 SER 152 CB 4 LEU 311 0 1 3.54 VDW 1 HIS 153 ND1 4 LEU 311 0 1 3.57 SHORTVDW 1 HIS 153 CE1 4 TER 312 OG1 1 2.87 VDW 1 HIS 153 CE1 4 TBR 312 CB 1 3.48 TVDW 1 BIS 153 CE1 4 TBR 312 CA 1 3.76 VDW 1 BIS 153 NE2 4 THR 312 OGI1 1 3.57 o. VDW 1 PE 205 CE2 4 PEE 308 CZ 1 3.90 VDW 1 PHE 205 CZ 4 PRE 308 CE2 1 3.40 VDW 1 PEE 205 CZ 4 PRE 308 CZ 1 3.53 EP2-PEP1 VDW .2 SER 591 CA 4 TYR 304 08 1 3.44 VDW 2 SER 591 CB 4 TYR 304 08 1 3.88 VDW 2 SER 591 CB 4 PRO 317 CB 1 3.95 VDW 2 SER 591 OG 4 TYR 304 H08 1 3.44 VDW 2 SER 591 OG 4 PRO 317 CB 1 3.61 VDW 2 SER 591 OG 4 TYR 304 CZ 1 3.83 VDW 2 SER 591 OG 4 TYR 304 CE2 1 3.84 VDW 2 SER 591 C 4 TYR 304 08 1 3.62 VDW 2 SER 592 N 4 TYR 304 CE2 1 3.66 VDW 2 SER 592 N 4 TYR 304 CZ 1 3.68 VDW 2 SER 592 CA 4 TYR 304 H08 1 3.80 VDW 2 SER 592 CB 4 TYR 304 OH 1 3.73 VDW 2 SER 592 C 4 TYR 304 CE2 1 4.00 VDW 2 SER 592 O 4 TYR 304 CE2 1 3.53 VDW 2 SER 592 O 4 PRO 317 CD 1 3.59 VDW 2 PHE 593 CB 4 CYS 315 0 1 3.74 VDW 2 PEE 593 CDl 4 CYS 315 CB 1 3.55 VDW 2 PEE 593 CD1 4 TYR 304 CD2 1 3.72 -29afl.con Thu Apr 25 15:08:07 1996 2 VDW 2 PEE 593 CD1 4 TYR 304 CE2 1 3.90 VDW 2 PEE 593 CE1 4 CYS 315 CE 1 3.71 SaORTVDW 2 VAL 594 CG1. 4 PRO 317 CG 1 3.17 SaORTVDW 2 VAL 594 CG1 4 PRO 317 CD 1 3.23 EEPB1-PEPTIDE2 VDW 1 SER 91 .CB 4 PRO 417 C 1 3.84 VDW 1 SER 91 CB 4 PRO 417 CG 1 3.90 VDW 1 SER 91 OG 4 PRO 417 C 1 3.90 VDW 1 SER 92 N 4 TYR 404 CE2 1 3.82 VDW 1 SER 92 CA 4 TYR 404 OR 3.85 VDW 1 SER 92 CB 4 TYR 404 08 1 3.42 VDW 1 SER 92 CB 4 TYR 404 CZ 1 4.04 VDW 1 SER 92 CE 4 TYR 404 CE2 1 4.09 VDW -iPEE 93 CB 4 CYS 415 0 1 3.43 VDW 1 PRE 93 CD1 4 TYR 404 c2 1 3.71 VDW 1 PEE 93 CD1 4 TYR 404 CD2 1 3.83 VDW 1 PEE 93 CD1 4 CYS 415 CE 1 3.92 VDW 1 PEE 93 CEl 4 CYS 415 C 1 4.08 VDW 1 PE 93 CE1 4 TYR404 CE2 1 4.09 VDW 1 VAL 94 CG1 4 PRO 417 CG 1 3.54 VDW 1 VAL 94 CG1 4 PRO 417 CD 1 3.54 VDW 1 VAL 94 CG2 4 PRO 417 CG 1 4.11 EBP2-PEPTIDE2 :SHORTVDW 2 LEU 533 4 PE 408 CR1 1 3.1 VDWR VD 2 LEU 533 CB4 0 *i vDw 2 LEt1533 CE 4 PE 408 CD1 1 3.77 VDW 2 LEU 533 CE 4 PEE 408 CZ 1 4.00 VDW 2 LEU 533 CG 4 PEE 408 CEI 1 4.05 VDW 2 LEU 533 CD1 4 PHE 408 CE1 1 VDW 2 LEU 533 CD1 4 PEE 408 CZ 1 3.92 VDW 2 LEU 533 0 4PEE 408 C1 1 3.67 VDW 2 PEE 593 CE1 4 TPP 413 CR2 1 3.34 VDW 2 PEE 593 CE1 4 TRP 413 CZ2 1 3.41 VDW 2 PEE 593 CZ 4 TRP 413 CZ2 1 3.67 VDW 2 PEE 593 CZ 4 ThP 413 CR2 1 3.96 VDW 2 PRO 649 CA 4 GLY 409 0 1 3.79 VDW 2 PRO 649 CE 4 GLY 409 0 1 3.56 VDW 2 PRO 649 C 4 PRO 410 0 3.72 VDW 2 MET 650* CA 4 PRO 410 0 1 3.59 VDW 2 MET 650 CA 4 GLY 409 0 1 3.67 VDW 2 MET 650 CA 4 LEU 411 0 1 3.77 VDW 2 MET 650 CG 4 PRE 408 CD2 3.80 VDW 2 MET 650 CG 4 PE 408 CG 1 3.92 VDW 2MET 650 CG 4 PEE 408 CE 1 4.05 VDW 2 MET 650 SD 4 TRP 413 N 1 3.72 VDW 2 MET 650 SD 4 TER 412 C 3.75 VDW 2 MET 650 SD 4 PE 408 CD2 1 3.76 VDW .2 MET 650 SD 4 TER 412 CA 1 3.78 VDW 2 MET 650 SD 4 PEE 408 CA 1 4.02 VDW 2 MET 650 CE 4 TRP 413 CE2 1 3.67 VDW 2 MET 650 CE 4 TPP 413 NEl 1 3.76 VDW 2MET 650 CE 4 TRP 413 CD2 1 3.76 VDW 2 MET 650 CE 4 PE 408 CD2 1 3.83 VDW 2 MET 650 CE 4 TPP 413 CD1 1 3.88 VDW 2 MET 650 CE 4 TRP 413 N 1 3.89 VDW 2 MET 650 CE 4 TRP 413 CG 1 3.90 VDW 2 MET 650 C 4 LEU 411 0 1 3.54 VDW 2 MET 650 C 4 PRO 410 0 1 3.57 VDW 2 THR 651 N 4 LEU 411 0 1 3.56 VDW 2 TaR 651 N 4 PRO 410 C 1 3.77 VDW 2 TER 651 CA 4 PRO 410 0 1 3.41 SHORTVDW 2 TER 651 CE 4 PRO 410 0 1 3.03 VDW 2 TER 651 CE 4 PRO 410 C 1 3.98 VDW 2 THR 651 CE 4 LE] 411 CA 1 4.02 VDW 2 TaP 651 OG1 4 PRO 410 C 1 3.62 all.cn Thu Apr 25 15:08:07 1996 3 VDW 2 SER 652 N 4 LEU 411 C 1 3.83 VDW 2 SER 652 CA 4 LEU 411 0 1 3.51 VDW 2 SER 652 CB 4 LEU 411 0 1 3.18 VDW 2 SER 652 CE 4 LEU 411 C 1 4.09 VDW 2 SER 652 OG- 4 THR 412 CE 1 3.73 SHORTVDW 2 HIS 653 .CE1 4 TER 412 OGI 1 3.00 VDW 2 HIS 653 CEl 4 TEA 412 CB 1 3.91 PEPTIDE1-PEPTIDE2 SHORTVDW 3 THR 303 OGI 4 HIS 407 CE 1 2.94 VDW 3 THR 303 OG1 4 HIS 407 CA 1 3.61 VOW 3TR 304 CE 4 CYS 406 0 1 3.86 VDW 3 TYR 304 CD1 4 TRP 413 CZ3 1 3.81 VDW 3 TYR 304 CD1 4 TRP 413 CE2 1 3.94 VDW 3 TYR 304 0 4 CYS 406 N 1 3.33 VDW 3 TYR 304 0 4 CYS 406 0 1 3.47 .VDW 3 TYR 304 0 4 SER 405 CA 1 3.57 VDW 3 SER 305 CA 4TYR 404 0 1 3.51 VDW 3 SER 305 C 4 TYR 404 0 1 3.77 VDW 3 CYS 306 0 4 TER 403 CB 1 3.50 VDW 3 CYS 306 0 4 TYR 404 CE 1 3.54 VDW 3 CYS 306 0 4 TYR 404 CD1 1 3.59 VDW 3 CYS 306 0 4TYR 404 CA 1 3.75 VDW 3 CYS 306 CE 4 CYS 406 SG 1 3.81 V VOW 3 CYS 306 SG 4 CYS 406 SG 1 3.75 VOW 3 CYS 306 SG 4 CYS 406 CE 1 4.06 VDW 3 PHE 308 CE. 4 TYR 404 OH 1 3.93 VOW 3 PEE 308 CEl 4 TYR 404 CEL 1 4.08 VDW 3 TRP 313 CG 4 TRP 413 CD1 1 3.85 SHORTVDW 3 TRP 313 CD1 4 TPP 413 CD1 1 3.04 VDW 3 ThP 313 CD1 4 TRP 413 NEl 1 3.37 VDW 3 TRP 313 CD1 4 TRP 413 CG 1 4.09 VDW 3 TRP 313 NEl 4 TRP 413 CD1 1 3.31 VDW 3 TBP 313 CZ2 4 CYS 415 SG 1 3.84 VDW 3 TPP 313 CR2 4 CYS 415 SG 1 3.83 VDW 3 CYS 315 SG 4 TRP 413 CZ2 1 3.59 VDW 3 CYS 315 SG 4 TPP 413 CE2 1 3.95 VoW 3 CYS 315 SG 4 TRP 413 CR2 1 4.00 VoW 3 GN 318 CD 4 GLN 418 NE2 1 3.28 VOW 3 GLN 318 OE1 4 SER 405 CE 1 3.80 -31bref21c.pdb Thu Apr 25 12:27:47 1996 REMARK THE COHPLEX BETWEEN THE EXTRACELLULAR DOMAIN OF ERYTHROPOIETI REMARK RECEPTOR (EBP) AND AN AGONIST EPO MINETIC PEPTID): 1 (iEMl) REMAR HANING RESIDUES 21-23 (521-522) and 164-166. 433-E<.

REMARK HAVE WEAK OP. NO ELECTRGN DENSITY MAP AND HAVE BEEN MODELED REMARK INTO THE STP.UCTURE. THESE RESIDUES HAVE A HIGH B OF

REMARK

REMARK THE STRUCTURE CONSISTS OF TWO RECEPTOR (F.ESICUES :0-220. .EMARK AND PEPTIDE (P.ESIDUES 303-318, 403 418) MOLECULE..

ATOM 1 N LYS 10 40.090 29.25' 22.042

S

S S o f

*S

**2

ATOM

ATOHM

ATOM

2 CA LYS 3 CB LYS 4 CG LYS 5 CD LYS 6 CE LYS 7 NZ LYS 8 C LYS 9. O LYS 10 N PHE 11 CA PHE 12 CB PHE 13 CG PRE 14 CD1 PRE :5 CD2 PHE 16 CE1 PHE 17 CE2 PHE 18 CZ PHE 19 C PHE 20 0 PRE 21 N GLU 22 CA GLU 23 CB GLU 24 CC GLU 25 CD GLU 26 OE1 GLU 27 OE2 GLU 28 C GLU 29 0 GLU 30 N SER 31 CA SEF.

32 CB SER 33 OG SEA 34 C SER 35 0 SEP.

36 N LYS 37 CA LYS 38 CB LYS 39 CG L-1 40 CD LYS 41 CE LYI 42 NZ LYS 43 C LYS 44 0 LYS 45 N ALA 46 CA ALA 47 CB ALA 48 C ALA 49 0 ALA 50 'N ALA 51 CA ALA 52 CB ALA 53 C ALA 54 0 ALA -55 N LEU 54 CA LEW; 51 CP LV-' 58 CG LEZ 59 CDI LE 60 CD2 LZ'- 61 C LEU 62 LE7' 63 N LEU 64 CA LEU 65 CS .4-E- 66 CC LW'- 47 CD1 LEU 68 CD2 LEt 69 C LE'; 10 0 LE;' 10 10 10 10 10 10 10 1(2 11 11 11 11 11 11 11 12 11 11 11 12 12 12 12 12 12 12 12 12 13 13 13 13 13 13 14 14 14 14 14 14 14 14 14 15 15 15 15.

15 16 16 16 16 1" i- 1" 18 18 18 1P 18 18 39.634 38.753 38.334 38.119 37.165 35.685 38.921 39.589 37.602 36.868 35.549 34.497 34.862 33.142 33.910 32.180 32.566 27.644 31.77 11 38.181 38.905 39.253 40.185 39.455 40.024 38.356 40.131 40.513 40.730 *41.903 42.522 42.256 41.570 42.239 40.563 40.117 39.063 39.629 38.5t6 39.191 38.193 39.586 39.782 38.920 38.375 37.571 39.592 '39. 683 40.560 41.792 42.771 42.361 42.624 42.444 43.007 43.01: 44.20.

45.41.

44.36 42.37 42.98 41.13 40.43 38.99 28.72 31.23 39.42 40.39 39.81 30.133 2 29.361 1 30.155 1 29.212 1 28.015 1 28.367 1 31.427 2 32.442 2 31.386 2 32.588 2 32.257 2 33.362 2 34.717 2 33.038 2 35.728 2 34.041 2 35.395 2 33.567 2 34.740 2 33.106 34.036 2 32.423 34.309 35.301 36.417 34.952 34.539 35.703 33.687 34.094 32.898 32.959 35.202 36.249 34.355 35.912 35.287 34.366 33.862 33.270 32.742 37.198 38.290 37.053 38.188 38.960 40.189 38.207 38.196 1 37.710 39.56' 4 40.75 9 4 38.896 7 39.46? 2 32.423 4 31.48', 4 38.294 0 36.462 4 40.741 5 41.433 6 41.013 4 42.210 9 41.367 5 41.262 5 41.260 2 42.117 3 43.28, 6 44.3175 0.962 9.979 8.735 7.552 7.890 7.998 1.420 1.636 1.640 2.026 2.725 2.609 2.670 2.400 2.527 2.257 2.321 ;2.881 :2.516 4.016 24.886 26.246 27.123 23.056 28.275 2a.589 24.172 24.334 23.341 22.571 21.851 20.459 21.554 21.546 20.698 13.675 13.769 17.714 16.761 15.496 14.528 20.295 19.755 21.442 22.194 23.378 22.666 22.535 23.167 23.615 24.052 22.426 22.537 21.274 20.042 13.910 662 18.501 1 77 1'.51 18.71: 11.90' 19.44 1 02 17.64 17.32 1i.62 20.50 20.25 1.00 22.57 00 23.48 1.00 22.87 1.00 22.92 1.00 24.27 1.00 26.55 1.00 26.18 1.00 22.91 1.00 24.17 1.00 21.40 '.00 18.56 1.00 19.07 1.00 20.24 1.00 19.49 1.00 19.51 *.00 19.64 L.00 20.10 00 19.48 I.00 19.32 1.00 18.89 00 20.71 1.00 20.59 1.00 21.48 1.00 23.60 1.00 25.09 1.00 23.07 1.00 21.05 .0(T 19.22 1.00 18.49 1.00 17.67 1.00 16.71 1.00 18.51 1.00 23.19 1.00 15.51 00 15.13 i.00 12.00 1.00 8.51 00 5.06 1.00 2.36 00 2.00 00 2.27 1.00 2.00 1.00 3.05 1.00 7.15 1.00 11.98 1.00 12.13 1.00 11.49 1.00 12.49 1.00 13.58 1.30 13.91 00 14.37 00 14.76 S1.0 15.45 00 15.35 S1.S0 16.12 0G 15.32 15.72 S-.00 17.46 6 14.45 4 00 16.32 2 1.00 15.04 1 .00 15. 31 a8 .00 1-.34 3 .00 15.72 2 .CC 1 '2 0 00C 9. 6 9 1.0C0 5.61 5 OC 10. 13 0 .00 17.38 7 .00 11.32

T

-32bref2lc.pdb Thu Apr 25 12:27:47 1996 **o of g 0

ATOM

71 N ALA 72 CA ALA 73 CB ALA 74 C ALA 75 0 ALA 76 N ALA 77 CA ALA 79 CB ALA 79 C ALA 80 0 ALA 81 N ARG 82 CA ARG 83 CB ARG 84 CG ARC 85 CD ARG 86 NE ARG 87 CZ ARC 88 NR1 ARG 89 NH2 ARG 90 C ARG 91 0 ARC 92 N GLY 92 CA GLY 94 C GLY 95 0 GLY 96 N PRO 97 CD PRO 98 CA PRO 99 CB PP.0 100 CG PRO 101 C PRO 102 0 PRO 103 N CLU 104 CA GLU 105 CB GLU 106 CG GLU 107 CD GLU 108 OE1 GLU 109 OE2 GLU 110 C GLU 111 0 GLU 112 N GLU 113 CA GLU 114 CB GLU 115 CC GLU 116 CD GLU 1i7 OE1 CLU 118 OE2 GL*.' 119 C GLZ 120 0 GLU 121 N LEO 122 CA LEU 123 CB LEC 124 CC LEV 125 CDI LEV :26 CD2 LE: 127 C LZE 128 '0 LEC 129 N LZC 130 CA LE" 131 CB LE 132 CC LE'-: 132 CD1 LZ: 134 CD2 LEU 135 -E: 136 0 LE"- 137 N C6YS 138 CA :s3 139 C YS 140 0 141 CB CY.T 142 SC SYS 143 H ?.6 144 CA ?HE 145 CB ?HE 146 CG ?PE 147 CDl ?H£ 148 CD2 PH! 19 19 19 19 19 20 20 20" 20 20 2: 2: 21 21 21 21 21 21 21 21 21 22 22 22 22 23 23 23 23 23 23 23 24 24 24 24 24 2 24 2: 2.

2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 40.921 42 40.925 43 41.560 43 41.601 45 42.026 45 41.649 46 42.246 41 41.529 44 43.770 4 44.438 44 44.326 41 45.765 41 46.362 41 45.921 41 45.719 4 44.765 5 43.448 5 42.915 4 42.669 5 46.298 5 45.875 5 47.158 5 47.824 5 49.053 5 48.939 5 50.230 5 50.318 3 51.451 5 51.713 5 51.527 5 52.661 52.560 53.863 35.136 56.332 56.479 56.710 4 51.171 4 56.430 4 55.117 4 54.874 5 55.342 5 55.371 5 53.962 5 53.789 5 53.199 5 53.461 5 52.461 5 56.249 5 56.056 6 57.246 6 58.147.

6 59.396 6 60.719 6 61.537 26 60.535 26 57.409 26 56.951 27 57.31C 27 56.613 2- 55.428 2- 54.281 2- 53.101 2' 53.871 2- 57.454 27 58.002 23 57.46C 28 58.206 28 57.246 28 56.2171 28 59.266 28 60.429 2. 57.59s 2i* 56.817 29 55.474 29 55.158 29 5!..493 29 51.79C .981 1.941 .331 5.273 5.499 6.164 7.514 8.505 7.526 6.484 8.699 8.704 8.353 8.420 9.838 0.675 0.471 9.448 1.270 0.118 1.199 0.016 1.171 1.371 1.174 1.765 2.564 i1.971 53.452 i3.517 51.167 50.067 51.758 51.178 52.009 52.149 50.822 50.954 49.692 51.264 52.365 50.124 5C.058 49.818 49.985 51.340 52.355 51.401 48.872 4 7.779 49.098 48.03 48.62 47.881 48.14 46.40 47.18 47.72 45.88 44.99 44.33 45.26 44.42 46.13 43.32 43.03 43.96 43.02 42.35 42.3 43.7 44.7 41.1 40.4 39.8 38.6 31.3 38.7 21.680 1.

22.789 1.

24.041 1.

12.445 1.

21.294 1.

23.453 1.

23.333 1.

24.310 1.

23.562 1.

23.505 1.

23.848 1.

24.075 1.

22.819 1.

21.446 1.

20.863 1 21.591 1 21.610 1 20.926 1 22.350 1 24.590 1 24.132 1 25.614 1 26.193 1 25.314 1 24.089 1 25.872 1 27.119 1 25.062 1 25.287 1 26.850 1 15.544 1 26.123 1 25.308 1 25.741 25.238 23.723 22.959 21.793 23.478 27.268 27.829 27.925 29.377 29.907 31.410 1 21.799 S21.0517 22.937 2 29.125 9 29.181 8 20.572 4 21.001 4 21.652 0 21.488 5 22.704 1 21.317 8 22.030 7 23.041 0 21.797 6 22.719 4 22.035 8 21.673 3 21.125 i3 22.906 2 :3.3 2c 1 22.742 64 24.726 27 25.554 59 26.529 45 24.861 91 26.357 63 25.358 15 24.97~ 02 27.943 99 27.322 43 21.437 6 234.990 47 25.050 00 19.88 00 22.64 6 00 22.75 6 00 25.13 00 25.03 3 00 28.77 7 00 28.51 6 00 28.93 6 00 27.54 6 00 27.85 .00 90.00 .00 90.00 6 .00 90.00 6 .00 90.00 6 .00 90.00 6 .00 90.00 .00 90.00 6 .00 90.00 7 .00 90.00 i .00 90.00 6 .00 90.00 3 .00 90.00 .00 90.00 i .00 90.00 6 .00 90.00 3 .00 90.00 .00 90.00 6 .00 90.00 6 .00 90.00 6 00 90.00 i 00 90.00 00 90.00 3 00 28.27 7 1.00 24.32 6 1.00 24.01 6 1.00 25.03 6 1.00 24.22 6 1.00 23.14 S 1.00 18.50 1.00 23.39 i 1.00 24.36 1.00 18.35 1.00 14.09 s 1.00 17.09 s 22.21 i 1.00 27.11 1.00 27.15 1.00 26.11 1.00 11.99 1.00 14.38 1.00 8.48 1.00 5.93 s 1.00 4.03 1.00 2.00 1.00 4.41 6 1.00 2.00 4 1.00 6.68 1.00 9.43 3 1.00 5.17 1.00 5.71 1.00 6.50 1.00 10.34 1.00 10.81 1.00 7.08 00 .41 1.00 7.62 1.00 7.42 00 4.67 1.00 4.38 1.00 2.56 1.00 3.64 ".00 4.31 1i 0C 0c 2.00 4 00 4.36 .C0 2.43 :.0C 2.00 00 2.30 -33br.f21c.pdb Thu Apr 25 12:27:47 1996 3 ATOM 149 CE1 PHE 29 55.605 36.243 26.206 1.00 2.00 ATOM 150, CE2 PHE 29 55.906 37.616 24.266 1.00 2.00 ATOM 151 CZ PHE 29 55.015 36.365 34.843 1.00 2.00 ATOMH 152 C PHE 29 57.618 39.260 13.543 1.00 3.80 ATOM 153 0 PHE 29 58.702 38.89' 27.957 1.00 2.00 ATOM 154 N THR 30 57.340 38.814 29.766 1.00 4.11 ATOM 155 CA THP. 30 58.021 37.694 43.463 1.00 3.12 ATOM 156 CB THP 30" 58.720 38.116 41.820 1.00 2.00 ATOM 151 OC1 THP. 30 59.331 36.982 42.408 1.00 2.00 ATOM 158 CG2 THP. 30 51.163 36.661 42.827 1.00 2.00 ATOM 159 C THR 30 56.951 36.601 40.614 1.00 6.81 e ATOM 160 0 THR 30 5.77114 36.924 40.814 1.00 8.70 3 ATOM 161 N GLU 31 51.342 35.326 40.665 1.00 1.95 ATOM 162 CA GLU 31 56.318 34.219 40.786 1.00 8.18 6 ATOM 163 CB GLU 31 56.577 33.240 39.650 1.00 7.89 ATHOM 164 CG GLU 31 56.490 33.821 38.286 1.00 8.99 6 ATOM 165 CD GLO 31 56.651 32.150 37.248 1.00 10.58 6 ATOM 166 OE1 GLU 31 57.538 32.815 36.395 1.00 13.03 ATOH 167 0E2 GLU 31 55.916 31.753 37.302 1.00 14.01 3 ATOM 168 C GLU 31 56.453 33.432 42.019 1.00 8.38 6 ATOM 169 0 GLU 31 55.431 32.940 42.582 1.00 9.178 ATOM 170 N ARG 32 57.678 33.064 42.416 1.00 1.19 7 ATOM 171 CA ARG 32 58.006 32.390 43.610 1.00 8.64 4 ATOM 172 CB ARG 32 58.844 31.154 43.4C5 L.00 9.16 6 ATOM 113 CG ARG 32 S8.284 30.364 42.261 1.00 10.75 i ATOM 174 CD ARG 32 58.316 28.894 42.469 1.00 11.21 ATOM 175 E ARCG 32 57.010 28.271 42.295 1.00 13.52 ATOM 176 .CZ ARG 32 56.328 28.350 41.1E7 1.00 16.55 ATOM 177 NH1 ARG 32 56.763 29.036 40.128 1.00 17.12 1 ATOM 178 NH2 ARG 32 55.145 27.734 41.128 1.00 11.617 ATOM 179 C ARC 32 58.834 33.536 44.224 1.00- 9.21 6 ATOM 180 0 ARG 32 59.004 34.326 43.520 1.00 13.37 3 ATOM 181 N LEU 33 59.382 33.499 45.416 1.00 7.12 1 ATOM 182 CA LEU 33 60.084 34.736 45.716 1.00 8.01 6 ATOM 183 CB LEU 33 59.536 35.403 46.986 1.00 1.85 6 ATOM 184 CC LEU 33 58.323 36.310 46.699 1.00- 2.00 6 ATOM 185 CD1 LEU 33 57.061 35.584 41.032 1.00 3.91 6 ATOM 186 CD2 LEU 33 58.381 37.604 47.464 1.00 2.00 6 ATOM 181 C LEU 33 :61.610 34.893 45.506 1.00 8.52 6 ATOM 188 0 LEU 33 62.269 35.102 46.168 1.00 10.67 3 ATOM 189 N GLU 34 62.130 34.114 44.516 1.00 6.25 1 ATOM 190 CA GLU 34 63.539 34.210 44.144 1.00 8.09 ,1 ATOM 191 CB GLU 34 64.315 32.005 44.723 1.00 10.89 6 ATOM 192 CC GLU 34 63.518 31.931 45.541 1.00 18.21 6 ATOH 193 CD GLU 34 62.754 30.858 44.699 1.00 21.41 6 ATOM 194 OE1 GLU 34 61.810 3C.224 45.251 1.00 22.26 3 ATOM 195 0E2 GLU 34 63.082 3C.645 43.494 1.00 22.29 ATHOM 196 C GLU 34 63.618 34.239 42.594 1.00 7.89 6 ATOMH 1917 GLU 34 64.413 33.459 42.01- 00 10.91 ATOM 198 N -ASP 35 62.978 35.150 41.933 1.00 6.40 ATOM 199 CA ASP 35 62.981 35.244 40.483 1.00 4.88 S ATOMH 200 CB ASP 35 62.215 3.4.034 29.895 1.00 5.00 ATOM 201 CG ASP 35 60.6178 34.189 29.9517 .00 6.69 6 S* ATOM 202 OD1 ASP 35 60.055 34.542 3.912 1.00 6.86 ATOM 203 OD2 ASP 35 60.102 33.911 41.025 1.00 2.00 0 ATOM 204 C ASP 35 62.336 36.566 40.016 1.00 3.42 ATOMH 205 0 ASP 35 '1.563 37.153 40.131 :.00 4.41 1 ATOM 206 "N LEC 36 62.61177 37.046 33.834 1.00 2.00 7 ATOM 207 CA LEO 36 62.098 38.272 33.317 1.00 2.00 1 ATOM 208 CB LEU 36 62.902 39.484 23.745 1.00 2.00 ATOM 209 CG ,LE 36 62.219 40.825 23.490 00 2.40 ATOM 210 CD1 LEU 36 60.994 40.997 2?.3-5 1.00 2.31 4 ATOM 211 C22 LEC 36 63.184 41.343 33.762 00 2.00 4 ATOMH 212 LE 36 62.119 39.170 26.8C3 1.00 3.03 ATOM 212 36 63.011 31.640 34.241 00 ATOH 214 N 'VAL 37 61.038 38.589 :.00 3.46 ATHOM 215 CA VAL 31 60.960 38.559 34.101 00 2.00 ATOM 216 'VAL 231 59.866 37.515 34.2C6 00 2.00 ATOM 217 CG1 VAL 3' 60.007 37.337 22.699 1.00 2.00 4 ATOM 213 CG2 VAL 3- 59.951 36.271 24.942 ".00 2.00 4 ATOM 219 S VAL 3" 60.555 39.970 34.329 i.00 3.99 4 ATOM 220 C VAL 37 59.138 40.553 25.043 1.00 5.63 ATOM 221 :4 2Y 38 61.204 40.551 33.33 2.00 ATOM 222 CA CYS 38 60.831 41.886 22.322 00 4.35 ATOMCH 223 s: C. 38 60.762 41.816 !1.224 00 5.14 ATOM 224 CYS 38 61.592 41.143 00 8.41 ATOM 225 CB CY 38 61.808 42.975 23.2:2 :.00 2.98 1 ATOM 226 SC CYS 38 61.860 43.383 34.972 1.00 3.22 1A -34brf21c.pdb Thu Apr 25 12:27:47 1996 4 ATOM 227 N PHE 39 59.811 42.540 30.742 1.00 4. 9 ATOM 228 CA PHE 39 59.621 42.507 29.286 i.00 5.3 ATOM 229 CB PHE 39 58.865 41.225 28.900 1.00 4.80 ATOM 230 CG PHE 39 57.461 41.198 29.411 1.00 7.S ATOM 231 CD1 PPE 39 56.416 41.686 28.636 1.00 8.61 ATOM 232 CD2 PHE 29 57.190 40.807 20.709 1.00 7.97 ATOM 223 CE1 PHE 39 55.123 41.795 29.153 1.00 9.47 ATOM 234 CE2 PRE 29 55.896 40.911 31.228 1.00 9.23 ATOM 235 CZ PHE 29 54.868 41.411 30.451 :.00 8.72 ATOM 236 C PHE 39 58.826 43.713 23.794 1.00 3., ATOM 237 0 PHE 39 58.262 44.451 29.580 1.00 4.23 ATOM 238 N TRP 40 58.837 43.926 27.490 1.00 3.45 ATOM 239 CA TRP 40 58.084 44.996 26.846 1.00 4.71 ATOM 240 CB TRP 40 58.826 46.352 26.872 1.00 4.45 ATOM 241 CG TRP 40 60.014 46.517 25.928 1.00 7.44 ATOM 242 CD2 TRP 40 61.386 46.185 26.200 1.00 9.31 ATOM 243 CE2 TRP 40 62.143 46.555 25.062 1.00 6.04 ATOM 244 CE3 TRP 40 62.049 45.595 27.294 1.00 10.246 ATOM 245 CD1 TRF 40 60.003 47.056 24.661 1.00 8.12 6 ATOM 246 NE1 TP.P 40 61.277 47.087 24.144 1.00 6.99 ATOM 247 CZ2 TRP 40 63.527 46.358 24.989 1.00 10.83 ATOM 248 CZ3 TRP 40 63.431 45.395 27.217 1.00 10.6: ATOM 249 CH2 TRP 40 64.152 45.780 26.068 1.00 11.4. ATOM 250 C TRP 40 57.785 44.538 25.418 :.00 s ATOM 251 0 TRP 40 58.530 43.761 24.824 1.00 4. ATOM 252 N GLU 41 56.625 44.314 24.914 1.00 7.?9 ATOM 253 CA GLU 41 56.267 44.533 23.556 :.00 a.54 4 ATOM 254 CB GLU 41 54.898 43.940 23.555 00 7.91 ATOM 255 CG GLL 41 54.860 42.586 24.450 00 11.7 ATOM 256 CD GLU 41 53.619 41.687 24.254 00 13.67- ATOM 257 OE1 GLU 41 53.418 40.748 25.055 1.00-15.11 3 ATOM 258 OE2 GLU 41 52.843 41.891 23.301 1.00 11.90 ATOM 259 C GLU 41 56.335 45.715 22.558 1.00 9.08 6 ATOM 260 0 GLU 41 56.456 46.888 22.956 1.00 8.71 ATOM 261 N GLU- 42 56.403 45.389 21.271 1.00 8.40 7 ATOM 262 CA GLU 42 56.426 46.399 20.211 1.0& 9.64 ATOM 263 CB GLU 42 57.729 47.207 20.227 1.00 6.56 4 ATOM 264 CG GLU 42 58.974 46.393 20.511 1.00 5.?32 ATOM 265 CD GLI 42 60.242 47.114 20.115 1.00 ATOM 266 OE1 GLU 42 61.019 46.519 19.371 1.00 9.43 1 ATOM 267 OE2 GLU 42 60.470 48.271 20.519 1.00 6.1. ATOM 268 C GLU 42 56.167 45.737 18.853 :.00 9.90 4 ATOM 269 0 GLU 42 55.880 44.532 18.795 1.00 9.59 4 ATOM 270 N ALA 43 56.243 46.514 17.771 1.00 10.968 ATOM 271 CA ALA 43 55.988 46.007 16.400 1.00 i ATOM 272 CB ALA 43 55.513 47.145 15.515 1.00 12.5 4 ATOM 273 C ALA 43 57.164 45.291 15.731 1.00 ATOM 274 0 ALA 43 58.309 45.683 15.930 1.00 12...

ATOM 275 N ALA 44 56.878 44.282 14.903 :.00 ATOM 276 CA ALA 44 57.928 43.514 14.208 1.00 3.:2 ATOM 277 CB ALA 44 57.326 42.507 13.263 1.00 4.9- ATOM 278 C ALA 44 58.828 44.442 13.438 1.00 ATOM 279 0 ALA 44 58.407 45.534 13.047 1.00 i.i: ATOM 280 N SER 45 60.086 44.068 13.275 1.00 3.2: ATOM 281 CA SER 45 60.962 44.326 12.508 1.00 10.3: ATOM 282 CB SEA 45 61.618 46.002 12.354 1.00 11.34 ATOM 283 OG SER 45 61.479 47.244 12.695 1.00 ATOM 284 *C SER 45 61.996 44.207 11.683 ".00 13.S2 ATOM 285 0 SE 45 62.599 43.221 12.124 1.00 15.-2 ATOM 286 N ALA 46 62.112 44.471 10.435 1.00 14.3 ATOM 287 CA ALA 46 63.041 44.134 9.469 1.00 14.4.

ATOM 288 CB ALA 46 62.810 44.781 8.127 1.00 ATOM .289 C ALA 46 64.379 44.538 10.028 :.00 ATOM 290 0 ALA 46 64.657 45.746 10.203 :.00 1-.

ATOM 291 N GLY- 4 55.140 42.2:. 10.433 :.00 ATOM 292 CA GLY 4. 66.450 43.762 11.009 00 1." ATOM 293 C GLY 47 66.558 44.415 12.400 1.00 ATOM 234 0 GL- 4- 67.221 45.457 12.546 1.00 1.

ATOM 295 N VAL 48 65.8732 43.843 13.399 :.00 13.: ATOM 296 CA VA: 46 45:.950 44.202 14.799 :.00 ATOM 297 Cl' VA'. 46 64.825 45.230 15.231 00 ATOM 298 CG1 VAI 48 64.572 45.071 16.701 1.00 ATOM 299 CC2 VA; 46 65.21 6 44.56C 14.964 .00 ATOM 200 C VAL 48 65.904 42.060 15.642 1.00 ATOM 301 0 VA- 48. 65.062 42.183 15.443 1.00 ATOM 302 N GLY 49 66.882 42.343 I.521 '.00 3.4- ATOM 33 CA GLY 49 66.948 1.79. 17:. 393 00 ATOM 304 C CLY 49 6'.199 42.211 13.829 OC bref2lc.pdb Thu Apr 25 12:27:47 1996 ATOM 305 0 GLY 49 61.294 43.396 10.152 :.00 3.06 3 ATOM 306 N PRO 50 61.214 41.234 19.1732 1.00 4.49 ATOM 301 CD PRO so50 617.104 39.790 19.536 1.00 2.00 9, ATOM 308 CA PRO !0 67.519 41.540 21.125 1.00 2.99 ATOM 309 CB PRO 50 61.545 40.158 21.762 1.00 3.91 ATOM 210 CG PRO 50 67.935 39.264 20.622 1.00 2.00 6 ATOM 311 C PRO 10 68.837 42.301 21.315 1..00 4.871 ATOM 312 0 PRO 68.962 43.122 22.217 1.00 1.36 ATOM 313 N CLY 51 69.781 42.100 20.403 1.00 5.60 ATOM 314 CA GLY 5 7 ?1.059 42.192 20.417 1.00 2.8 ATOM 315 C GLY 70.991 44.263 20.103 1.00 3.36 ATOM 316 0 GLY 51 72.025 44.910 19.956 1.00 5.85 ATOM 317 N ASN 52 69.1792 44.815 19.968 1.00 2.00 ATOM 318 CA ASN 52 69.670 46.211 19.604 1.00 2.00 6 ATOM 219 CB ASN 52 68.521 46.401 18.633 1.00 3.33 6 ATOM 320 CG ASN 52 68.768 47.534 17.666 1.00 1.91 6 ATOM 321 OD1 ASN 52 69.233 47.311 16.538 1.00 12.55 ATOM 322 ND2 ASN 52 68.442 48.753 18.079 1.00 10.05 ATOM 323 C ASN 52 69.505 47.144 20.191 1.00 3.59 6 ATOM 324 0 ASN 52 69.524 48.359 20.638 1.00 2.00 3 ATOM 325 N TYR 53 69.286 46.573 21.985 1.00 5.70 ATOM 326 CA TYP. 53 69.148 47.350 23.229 1.00 5.58 ATOM 321 CB TYP. 3 61.101 47.412 23.110 1.00 5.10 6 ATOM 328 CC TYP. 53 66.615 47.547 22.768 1.00 4.84 ATOM 329 CDl TYF. 53 66.067 46.414 22.188 ".00 6.02 f ATOM 230 CE1 TYR !3 65.080 46.495 21.282 :.00 5.48 ATOM 331 CD2 TYPR 53 66.123 48.789 22.405 1.00 5.30 ATOM 332 CE2 TYP. 53 65.112 48.891 21.495 1.00 6.56 ATOM 333 CZ TYP. 53 64.598 47.729 20.929 1.00 8.17 ATOM 334 OH TYR. 53 63.590 47.167 19.987 1.00 12.54 3 ATOM 335 C TYR 53 69.943 46.661 24.308 1.00 .3.83 6 ATOM 336 0 TYR 53 70.116 45.465 24.245 1.00" 4.09 3 ATOM 337 N SEP. 54 10.251 47.428 25.346 1.00 3.81 1 ATOM 338 CA SEP. 54 10.911 46.921 26.501 1.00 6.59 ATOM 339 CB SER 54 12.296 47.682 26.710 1.00 8.72 i ATOM 340 OG SEP. 54 13.405 46.861 26.341 1.00- 13.32 3 S* ATOM 341 C SER 54 70.0711 417.035 21.726 1.00 4.52 ATOM 342 0 SER 54 69.495 48.089 21.982 1.00 5.58 3 ATOM 343 N PHE 55 ;69.931 45.926 28.443 1.00 3.52 ATOM 344 CA PHE 55 69.095 45.818 29.641 1.00 3.38 ATOM 345 CB PHE 55 68.141 44.616 29.514 1.00 6.11 ATOM 346 CG PHE 55 617.052 44.700 30.596 1.00 6.96 i ATOM 341 CDI PHE 55 65.741 44.865 30.214 1.00 10.17 1 ATOM 248 CD2 PHE 55 67.330 44.5417 31.929 1.00 8.13 A ATOM 349 CE1 PHE 55 64.113 44.819 31.154 :.00 12.64 ATOM 250 CE2 PHRE 55 66.31; 44.561 22.874 1.00 8.02 ATCM 251 CZ PHE 55 65.00" 44.728 32.490 1.00 8.93 ATOM 352 C PHE !5 69.942 45.719 30.891 1.00 2.90 S* ATOM 253 0 PHE 15 10.416 44.710 21.200 1.00 2.00 ATOM 354 N SER 56 170.083 46.892 31.595 1.00 2.00 ATOM 255 CA SER 56 70.854 46.862 32.818 1.00 5.40 ATOM 356 CB SER 56 72.159 41.651 22.681 1.00 6.39 ATOM 351 OG SER 56 171.950 48.939 22.162 1.00 9.05 3 ***ATOM 358 C SER 56 170.089 47.214 34.108 1.00 8.43 SATOM 359 0 SEA 56 69.080 417.943 34.098 1.00 1.21 ATOM 360 N TYR 70.548 46.635 25.213 1.00 7.52 SATOM 261 CA TYR 69.915 46.856 36.495 1.00 8.61 ATOM 362 'CB TYR 5' 69.091 45.621 26.883 1.00 3.65 A ATOM 363 CC TYR V? 69.863 44.334 231.004 1.00 4.11 ATOM 364 CDI TYR 5- 70.254 43.835 28.254 1.00 2.00 ATOM 365 CE1 TYR 5' 1 70.865 42.581 28.384 1..00 2.00 ATOM 366 CD2 TYR 5- 70.11! 43.560 25.894 1.00 ,4.11 ATOM 367 CE2 TYR 70.729 42.316 36.020 1.00 2.48 ATOM Y68 CZ TYR 71.096 41.834 37.260 1.00 2.30 ATOM 3-39 TY?. 1.672 40.591 27.334 :.00 2.00 ATOM 2170 C TYR 70.885 47.253 37.616 :.00 10.04 ATOM 211 TYR 12.092 47.181 37.466 1.00 11.91 ATOM 312 N GLN i. 10.353 47.1781 38.705 1.0C 11.02 ATOM 373 CA GLN 58 e 1.181 48.143 39.832 1.00 9.11 ATOM 374 CS GL, 5. 71.613 49.592 39.754 ".00 10.64 ATOM 315 CG GLN 58 72.167 50.091 41.062 1.00 13.28 4 ATOM 2316 CD GLN 5E 72.821 51.436 40.954 1.00 13.57 ATOM 277 OEI GI: 5e 72.165 52.472 40.844 15.62 ATOM 318 NE2 GLN !E 74.147 51.4352 41.026 .00 14.36 ATOM 319 C GLN 56 10.430 47.886 41.123 1.00 8.05 ATOM 380 0 CLN 5e 69.48.9 48.582 41.468 .OC ATOM 381 N LEU I 7C.771 46.79e 41.169 1.00 e.41 ATOM -28F2 CA LEU 59 70.183 46.43! 43.038 :.CC 6.43 -36brf21c.pdb Thu Apr 25 12:27T:4 7"1996 6 ATOM 383 CS LEU 59 70.534 44.993 43.313 1.00 4.10 ATOM 364 CC LEU 59 69.811 44.344 44.446 1.00 2.46 ATOM 385 CD1 LEU 59 68.343 44.461 44.227 1.00 3.98 ATOM 386 CD2 LEU 59 70.246 42.909 44.462 1.00 6.03 ATOM 387 C LEO 59 70.926 47.335 43.995 1.00 9.36 i ATOM 388 0 LEU 59 72.1'.5 47.210 44.085 1.00 9.93 ATOM 389 N GCLU 60 70.221 48.253 44.667 1.00 11.94 ATOM 390 CA GLU 60 7C.844 49.221 45.603 1.00 13.27 i ATOM 391 CS GLU 60 69.852 49.697 46.643 1.00 14.05 i ATOM 392 CG GLU 60 70.448 50.769 47.531 1.00 15.91 ATOM 393 CD CLU 60 69.443 51.351 48.510 1.00 16.83 ATOM 394 OE1 CLU 60 69.263 50.755 49.607 1.00 16.52 ATOM 395 OE2 GLU 60 68.852 52.410 48.181 1.00 15.17 a ATOM 396 C GLU 60 72.159 48.859 46.315 1.00 14.73 6 ATOM 397 0 GLU 60 72.200 47.971 47.189 1.00 14.00 8 ATOM 398 N ASP 61 73.193 49.638 45.973 1.00 16.22 7 ATOM 399 CA ASP 61 74.569 49.501 46.452 1.00 17.32 6 ATCHM 400. CB ASP 61 74.624 49.151 47.930 1.00 22.61 ATOM 401 CC ASP 61 74.287 50.345 48.814 1.00 26.60 6 ATOM 402 OD1 ASP 61 74.262 50.144 50.054 1.00 30.15 8 ATOM 403 OD2 ASP 61 74.036 51.470 48.271 1.00 27.62 3 ATOM 404 C ASP 61 75.390 48.539 45.610 1.00 16.14 6 ATOM 405 0 ASP 6: 76.562 48.742 45.423 1.00 16.58 3 ATOM 406 N GLU 62 74.758 47.476 45.130 1.00 14.78 7 ATOM 407 CA GLU 62 75.402 46.524 44.223 1.00 13.68 6 ATOM 408 C3 CLU 62 74.418 45.359 43.931 1.00 15.90 ATOM 409 CS GLU 62 74.592 44.612 42.585 1.00 20.15 A ATOM 410 CD GLU 62 13.574 44.998 41.452 18.81 6 ATOM 411 OE1 GLU 62 73.324 46.202 41.202 1.00 19.09 a ATOM 412 GE2 GLU 62 73.047 44.078 40.788 1.00 17.28 ATOM 413 C GLU 62 75.709 47.363 42.947 1.00.10.99 6 ATOM 414 0 GLU 62 75.069 48.402 42.704 1.00 11.23 9 ATOM 415 N PRO 63 76.744 46.984 42.173 1.00 9.01 7 ATOM 416 CD PRO 63 77.785 45.973 42.435 1.00 9.66 6 ATOM 417 CA PRO 63 77.069 47.740 40.959 1.00 8.41 6 ATOM 418 CB PRO 63 78.517 47.322 40.691 1.00 5.33 6 ATOM 419 CG PRO 63 78.504 45.895 41.103 1.00 7.09 6 ATOM 420 C PRO 63 76.146 47.407 29.779 1.00 6.19 6 ATOM 421 0 PRO 63 75.473 46.366 29.775 1.00 4.91 3 ATOM 422 N TP.P 64 76.119 48.300 38.788 1.00 3.37 7 ATOM 423 CA TP.P 64 75.298 48.092 37.613 1.00 2.00 4 ATOM 424 CS TP.P 64 75.441 49.259 26.645 1.00 2.40 ATOM 425 CG TRP 64 74.591 50.490 26.923 1.00 2.00 6 ATOM 426 C02 TP.? 64 73.181 50.651 36.678 1.00 2.00 ATOM 427 CE2 TPJP 64 72.845 51.972 27.050 1.00 2.28 i ATOM 428 CE3 TP.P 64 72.174 49.811 36.186 1.00 2.18 ATOM 429 CD1 TP.P 64 -5.027 51.682 27.410 1.00 2.00 ATOM 430 NE1 T.F 54 73.995 52.573 27.487 .300 2.00 7 ATOM 431 22 TP.P 64 "1.537 52.476 36.950 ".00 2.00 6 ATOM 432 :23 T?.F 54 70.878 50.314 36.087 1.00 2.49 6 ATOM 433 :H2 TR.F 64 70.575 51.636 36.471 1.00 2.00 6 ATOM 434 C TP.F 64 75.700 46.815 36.903 1.00 2.00 6 ATOM 435 3 TRP 64 76.877 46.528 36.736 1.00 2.00 3 ATOM 436 .3 LYS 65 74.704 46.036 36.524 1.00 2.00 7 ATOM 437 CA LYS 65 74.909 44.793 35.803 1.00 2.00 6 ATOM 438 CB LYS 55 74.603 43.597 26.668 1.00 2.61 ATOM 439 CG LYS 65 :5.611 43.306 27.673 1.00 3.35 4 ATOM 440 CD LYS 65 75.207 42.082 38.401 1.00 4.33 4 ATOM 441 CE LYS S5 76.204 41.795 39.488 '1.00 10.13 ATOM 442 NZ LYS i5 76.452 43.031 40.293 1.00 15.09 7 ATOM 443 C LYS 55 -4.017 44.725 24.584 1.00 2.00 ATOM 444 LYS i 5 71.125 45.534 24.416 1.00 2.81 ATOM 445 LE: 56 74.201 43.692 23.780 i.30 2.51 ATOM 446 CA LEr 66 '2.421 43.532 22.558 !.0C 3.38 4 ATOM 44,1 CS 66 -4.342 43.586 21.340 3C 2.07 ATOM 448 CG 46 -1.135 44.851 :1.138 1.00 2.42 4 ATOM 449 CDI LEU i6 -4.363 44.485 20.416 1.00 5.47 ATOM 450 :D2 L- 56 -4.327 45.880 20.383 L.OC 2.99 ATOM 451 C L-z -5 .2.651 42.234 22.492 1.00 3.16 ATC. 452 t: .6 1.125 41.19. 22.943 OC 2.56 ATOM 453 N C"3 5 1.479 42.28. 2!1.385 1.00 4.64 ATOM 454 CA CYS 75. C..686 41.090 21.708 00 8.30 ATOM 5 7: 56 40.J52 191 1.0 ?.34 ATOM 456 CYS .0 06 41.96:. ;2.512 00 11.12 1 ATOM 457 CS CYS 5- 41.27. 232.363 OC 9.68 ATOM 453 SG CYS 5- Sa.297 39.78:. 22.300 1.00 ).98 1 A ATOM 4359 N c P.C .b v..672 39.72- 2. 649 .OC 10.38 ATOM 460 CA AP.C 6: 70.561 39.534 187 0( 11.77 -37bref21c.pdb Thu Apr 25 12:27:47 1996 7 ATOM 461 CB ARC 68 71.380 38.359 27.621 1.00 15.15 ATOM 462 CC ARC 68 71.366 38.376 26.053 1.00 20.38 ATOM 463 CD ARC 68 71.858 37.102 25.359 1.00 21.11 ATOM 464 NE ARC 68 11.010 35.943 25.653 1.00 25.20 ATOM 465 CZ ARG 68 71.437 34.837 26.288 1.00 21.66 ATOM 466 "H21 ARG 68 72.710 34.732 26.7C5 1.00 28.62 ATOM 467 NH2 ARG 68 10.601 33.818 26.498 1.00 27.68 ATOM 468 ARG 68 69.143 39.327 27.751 1.00 9.76 ATOM 469 C ARG 68 68.449 38.504 28.317 1.00 9.75 ATOM 470 N LED 69 68.7'2 40.021 26.684 .C00 8.1Z ATOM 471 CA LEU 69 67.428 39.983 26.131 1.00 5.24 ATOM 472 C3 LEU 69 67.137 41.241 25.328 1.00 4.64 ATOM 473 CG LED 69 67.431 42.581 25.980 1.00 5.82 ATOM 474 CD1 LEU 69 67.302 43.127 25.026 1.00 9.48 ATOM 415 CD2 LEU 69 66.498 42.7713 21.111 1.00 9.06 ATOM 476 C LEO 69 61.222 38.794 25.221 1.00 6.45 ATOM 477 LED 69 68.175 38.217 24.655 1.00 6.60 ATOM 478 N RIS 70 65.947 38.430 25.133 1.00 6.11 ATOM 479 CA HIS 70 65.448 37.374 24.296 1.00 4.34 ATOM 480 C3 HIS 70 64.792 36.308 25.103 1.00 3.32 ATOM 481 CC HIS 10 65.759 35.494 25.871 1.00 4.94 ATOM 482 CD2 HIS 10 66.779 34.106 25.460 1.00 1.46 ATOM 483 1D41 HIS 10 65.159 35.444 27.243 1.00 8.83 ATOM 484 C1 HIS 10 66.738 34.653 27.650 1.00 9.22 ATOM 485 NE2 HIS 10 61.212 34.193 26.586 ".00 6.78 ATOM 486 C HIS 70 64.407 38.097 23.546 :.00 6.62 ATOM 487 3 HIS 70 64.129 39.240 23.862 :.00 '.62 ATOM 488 N GLN 71 63.871 31.453 22.520 :.OC 13.06 ATOM 489 CA GLN 71 62.828 36.022 21.676 :.00 12.44 ATOM 490 CB GLN 71 63.449 38.691 20.442 1.00 12.64 ATOM 491 CG GLN 01 62.523 39.628 19.675 1.00 A2.33 ATOM 492 CD GLN 71 63.193 40.151 18.423 1.00 11.98 ATOM 493 OEI GLN 71 63.256 41.364 18.185 1.00 14.18 ATOM 494 NE2 GLN 71 63.141 39.254 17.638 1.00 13.04 ATOM 495 C GLN 71 61.867 36.915 21.218 1.00 14.54 ATOM 496 0 GLN 71 62.293 35.846 20.828 1.00"13.15 ATOM 491 N ALA 72 60.576 31.148 21.510 1.00 16.60 ATOM 498 CA ALA 72 19.540 36.163 21.222 1.00 17.29 ATOM 499 CB ALA 72 59.106 35.462 22.513 1.00 18.25 ATOM 500 C ALA 12 58.339 36.816 20.552 1.00 11.09 ATOM 501 0 ALA 12 51.962 31.949 20.890 1.00 17.99 ATOM 502 N PRO 73 51.110 36.140 19.535 1.0C 15.70 7 ATOM 503 CD PRO 73 58.266 34.944 18.833 1.00 15.56 ATOM 504 CA PRO 73 56.618 36.681 18.835 00 14.26 ATOM 505 CB PRO 73 56.539 35.789 17.608 1.00 14.62 ATOM 506 CC PRO 73 57.057 34.500 18.096 ".0C 14.52 ATOM 507 PRO 73 55.292 36.586 19.7107 12.69 ATOM 508 3 PRO 73 55.295 35.678 20.522 .3C 16.10 ATOM 509 2N TRR 74 54.568 31.632 19.628 ".0C 12.65 ATOM 510 CA THR 74 53.304 37.789 20.338 1.3C 11.59 ATOM 511 CB TRR 74 52.987 39.216 20.518 2: 3.94 ATOM 512 CG1 THR 74 54.100 39.935 21.092 12.22 ATOM 513 CG2 THR 74 51.790 39.484 21.423 0C 13.10 ATOM 514 C TBR 74 52.216 31.289 19.382 1.0C 13.56 ATOM 515 0 THR 74 52.234 31.637 18.198 1.0C 16.99 ATOM 516 N ALA 15 51.237 26.542 19.885 CC 12.64 ATOM- 517 CA ALA 15 50.131 36.016 19.045 2.0C .0.05 ATOM 518 'CB ALA 75 48.995 35.518 19.905 OC 10.80 ATOM 519 ALA 15 49.612 31.152 18.102 8.70 ATOM 520 3 ALA 15 49.256 36.837 16.987 0 12.33 ATOM 521 N ARC 71 49...83 38.410 18.545 9.12 ATOM 522 CA ARC 16 49.10" 39.552 17.144 10.37 ATOM 523 CE ARG 76 48.870 40.186 13.60! .0.98 ATOM 524 CG ARG 76 47.709 40.722 19.529 .6.38 ATOM 525 CD ARG 16 4:'.930 41.676 20.713- 2.12 ATOM 526 NE ARG 76 47.29E 41.163, 21.957 2: 23.32 ATOM 5271 ARG 76 47.700 40.066 22.605 25.34 ATOM 52S .H1 ARG 76 48.745 39.355 22.16: 25.68 ATOM 529 NK2 ARG 76 47.065 39.619 23.712 23.25 ATOM 530 C ARG 76 50.026 40.042 16.641 "2.35 ATOM 531 ARC 16 49.680 41.002 15.961 :C "5.69 ATOM 532 N GLY 7- 51.223 39.489 1I.508 1.0: .2.71 ATOM 533 CA GLY 52.21 29.982 15.47-2 .1.3? ATOM 534 C GLY 7 52.079 41.083 15.90 .38 ATOM 535 GLY 7 53.633 41.814 15.1C2 C: "..58 ATOM 536 N ALA 1p. 5..242 41.226 17.20B :2.04 ATOM CA ALA 54.15E 42.21) 17.75? 11.0 ATOM 538 CB ALA 78' 53.465 43.041 13.83! -0.28 -38bef2lc.pdb ATOM 539 C ATOM 540 0 ATOM 541 N ATOM 542 C ATOM 543 C ATOM 544 C ATOM 545 C ATOM 546 C ATOM 547 0 ATOM 540 N ATOM 549 C ATOM 550 C ATOM 551 C ATOM 552 C ATOM 553 N ATOM 554 C ATOM 555 N ATOM 556 N ATOM 557 C ATOM 558 C ATOM 559 N ATOM 560 C ATOM 561 C ATOM 562 C ATOM 563 C ATOM 564 C ATOM 565 ATOM 566 ATOM 567 ATOM 568 ATOM 569 ATOM 570 ATOM 571 ATOM 572 ATOM 573 ATOM 574 ATOM 75 ATOM 576 ATOM 577 ATOM 578 ATOM 579 ATOM 580 ATOM 581 ATOM 582 ATOM 583 ATOM 584 ATOM 585 ATOM 586 ATOM 587 ATOM 588 ATOM 589 ATOM 590 ATOM 591 ATOM 592 ATOM 593 ATOM 594 ATOM 595 ATOM 596 ATOM 597 ATOM 598 ATOM 599 ATOM 600 ATOM -601 ATOM 602 ATOM 603 ATOM 604 ATOM 605 ATOM 606 ATOM 601 ATOM 608 ATOM 609 ATOM 610 ATOM 611 ATOM 612 ATOM 613 ATOM 614 ATOM 615 ATOM 616

ALA

VAL

A VAL B VAL G1 VAL G2 VAL

VAL

ARG

A ARG B ARG G ARG D ARG E ARG Z ARG IH1 ARG H2 ARG

ARG

I PBE A PHE :B PHE :CG PHE D1i PHE :D2 PHE :E1 PHE CE2 PHE :CZ PHE C PHE 0 PHE N TRP CA TRP CB TRP CG TRP CD2 TRP CE2 TRP CE3 TRF CDI TRP NEI TRP CZ2 TP.F CZ3 TRP CH2 TRF C TP.P 0 TRP N CYS CA CYS c CYS O CYS CB CYS SG CYS N SER CA SER CB SEP.

OG SEP.

C SER 0 SER N LEO CA LEU CB LEO CG LEU CDI LEU CD2 LEU S LEU 0 LE: N PRO CD PRC' CA PP.C Cb PRO C P.C C PP.0 0 PRO N TP.R CA ThR CB THR OGI THR CG2 THE C THR 7e 78 19 19 19 19 79

SC

8C 80 80 80 8C 80 80 80 80 80 80 91 81 91 a 8.

8: 9: 82 82 8e2 62 82 82 82 32 32 32 82 82 32 82 32 a23 82 842 34 34 23 33 35 34 33 34 34 845 35 35 if.

s

S-

55.263 4: 55.080 41 56.418 4: 57.546 4 58.844 4 !8.706 4 19.135 4 57.786 4 57.633 4 18.207 4 58.420 4 57.507 3 57.465 3 56.674 3 55.272 3 54.415 3 54.829 3 53.142 3 59.846 4 60.466 3 60.346 4 61.688 4 62.385 4 62.744 4 61.861 4 63.947: 62.164 64.275 63.374 61.546 60.725 62.301 62.263 61.253 61.585 62.234 62.328 62.744 61.304 61.750 62.919 63.333 63.415 63.656 64.606 63.769 65.024 64.632 63.737 66.026 66.435 65.241 64.904 64.396 65.095 66.124 67.113 66.002 67.115 66.677 66.132 67.013 67.840 67.709 67.002 69.027 69.953 69.760 71.212 -1.201 69.332 69.142 69.227 68. 79 i 68.963 68.491 68.149 69.352 1.329 1i 0.106 1, 1.923 1 1.118 1 1.391 1 0.741 1 2.848 1 1.500 2 2.631 2 0.491 2 0.648 2 9.672 2 9.838 2 8.710 2 8.809 2 7.809 2 6.631 2 8.017 2 0.484 2 >9.434 2 1.519 2 1.481 12.814 3.102 2 43.781 42.670 44.030 42.908 43.594 41.209 41.848 40.240 39.911 38.789 37.412 36.372 35.248 36.277 36.888 35.581 34.048 35.011 33.980 39.561 39.733 39.156 38.749 38.373 38.969 39.909 40.538 .37.353 36.980 35.555 34.752 37.135 36.544 37.940 38.209 39.160 40.624 41.388 40.844 36.991 36.021 37.017 38.092 35.313 36.361 37.343 35.832 36.847 34.622 34.399 32.949 32.183 22.599' 35.262.

8.351 8.495 9.640 9.192 9.354 7.024 8.171 0.672 1.125 1.403 2.813 3.550 5.052 5.630 5.237 5.313 5.743 5.063 :3.297 3.114 3.951 24.488 24.305 22.915 22.091 22.409 20.763 21.086 20.251 25.955 26.604 26.469 27.891 28.199 27.697 28.428 27.577 29.722 26.453 26.318 27.987 20.137 29.272 28.371 27.623 29.635 20.282 21.702 22.271 20.319 31.992 22.258 33.610 33.658 32.731 34.483 24.190 25.546 26.451 27.546 27.197 28.48; 25.23; 27.111 2 35; 27.38 2. 98 33.03 37.92 77 39.51 40.18 40.02 41.39 41.72 40.60 42.91 42.53 Thu Apr 25 12:27:47 1996 8 1.00 11.11 1.00 13.01 1.00 9.69 1.00 7.32 1.00 6.05 1.00 6.29 1.00 5.80 1.00 5.75 1.00 4.75 1.00 4.34 1.00 7.09 1.00 8.65 1.00 7.34 1.00 6.89 1.00 6.67 1.00 4.11 1.00 5.04 1.00 2.00 1.00 5.10 1.00 3.87 1.00 4.32 1.00 5.56 1.00 4.97 1.00 5.07 1.00 6.98 1.00 ".17 1.00 7'.8 1.00 10.89 L.00 10.08 1.00 7.23 1.0" 8.68 1.00 7.82 1.00 8.83 1.00 9.85 1.00 12.09 1.00 11.'12 1.00 13.27 1.00 15.01 1.00 14.64 1.00 12.57 1.00 17.05 1.00 16.715 1.00 17.82 1.00 8. 05 1.00 7.22 L.00 7.16 1.00 6.S2 1.00 4.93 1.00 5.96 1.00 7.713 1.00 15.35 1.00 3.11 1.00 4.32 1.00 5.70 1.00 12.40 1.00 ".36 0 00 11. 92 1.00 67 I1.00 4.58 6 1.00 3.56 7 1.00 5.43 2 1.00 2 1.00 5.,6 0 1.O0 6.,0 2 .0OC 2.2: 8 1.00 5.

9 1.00 6.

6 .0.C .34 1 1.0C 2..

2 1.00C 5 1.00 39 1 1.00 4.26 9 OC 4.1; 4 00 *7 00 .:2 7 2..3 15 oC 1 .0.0 9 6 6 6 6 7 6 6 6 6 6 7 6 7 6 9 6 6 6 6 6 6 6 6 16 6 1 3

*J

:l -39bz.£21c.pdb Thu Apr 25 12:27:47 1996 9 ATOM 617 0 THR 87 68.606 35.730 43.384 00 9.13 ATOM 618 N ALA e8s 70.661 35.474 42.541 0 8.99 ATOM 619 CA ALA e88 71.313 36.286 43.568 20 8.39 ATOM 620 CB ALA 38 72.812 36.176 43.419 .0O0 9.06 ATOM 621 C ALA 88 70.922 37.752 43.497 :.30 8.97 ATOM 622 0 ALA 88 71.441 38.573 44.247' 1.00 10.83 ATOM 623 N ASP 39 70.030 38.090 42.578 :.30 8.36 ATOM 624 CA ASP 89" 69.633 39.470 42.391 :.00 8.96 ATOM 625 CB ASP 89 70.047 39.911 40.992 1.00 7.68 ATOM 626 CG ASP 89 71.563 39.915 40.788 :.00 6.71 ATOM 627 ODI1 ASP 89 72.319 40.224 41.720 00 3.92 ATOM 628 OD2 ASP 89 72.012 39.646 29.667 1.00 6.25 1 ATOM 629 C ASP 89 68.141 39.746 42.654 ".00 9.65 ATOM 630 0 ASP 89 67.668 40.880 42.522 1.00 9.22 ATOM 631 N THP 90 67.420 38.724 43.094 :.00 7.69 ATOM 632 CA THR 90 66.010 38.866 43.359 1.00 5.03 6 ATOM 633 CB THR 90 65.298 37.603 42.898 1.00 3.78 ATOM 634' OG1 THR 90 65.905 36.466 43.495 1.00 2.00 ATOM 635 CG2 THR 90 65.464 37.445 41.430 :.00 3.18 ATOM 636 C THR 90 65.667 39.219 44.823 1.00 8.87 ATOM 637 0 TH. 90 64.634 38.790 45.335 1.00 11.62 1 ATOM 638 N SEP. 91 66.492 40.043 45.479 :.00 7.49 ATOM 639 CA SER 91 66.264 40.434 46.877 ".00 7.31 ATOM 640 CS SEP. 9: 67.470 41.178 47.448 1.00 9.23 ATOM 641 OG SEP. 91 68.619 40.343 47.478 :.00 9.38 3 ATOM 642 C SER 9" 65.008 41.265 47.033 ".00 8.55 ATOM 643 0 SEP. 9 64.779 42.197 46.263 .30 9.92 ATOM 644 N SER 92 64.287 41.029 4a.125 1.30 8.52 ATOM 645 CA SEP. 92 63.000 41.671 48.328 ".00 6.55 i ATOM 646 CB SEP ?2 62.022 40.702 49.003 :.00 7.73 6 ATOM 647 OG SEP 92 61.127 40.120 48.085 :.00 9.02 ATOM 648 C SER 92 62.732 42.992 48.963 1.00 6.08 6 S* ATOM 649 0 SER 92 61.652 43.499 48.744 1.00 10.02 a ATOM 650 N PHE 93 63.600 43.581 49.764 1.00 5.40 ATOM 651 CA PHE 92 63.132 44.847 50.366 1.00 3.55 6 ATOM 652 CB PHE 93 62.881 44.663 51.879 1.00- 2.38 6 ATOM 653 CG PHE 93 61.836 43.585 52.207 1.00 2.00 6 ATOM 654 CD1 PHE 93 62.214 42.264 52.444 1.00 2.00 o ATOM 655 CD2 PHE 93 .:60.475 43.884 52.232 1.00 2.00 ATOM 656 CE1 PHE 93 61.260 41.265 52.689 :.00 2.00 6 ATOM 657 CE2 PHE 93 59.520 42.881 52.478 1.00 2.00 t ATOM 658 CZ PHE 93 59.922 41.573 !2.704 :.00 2.00 ATOM 659 C PHE 93 63.923 46.107 50.035 :.00 5.65 ATOM 660 0 PHE 93 63.753 47.156 ".657 1.30 5.77 ATOM 661 N VAL 94 64.671 46.008 48.938 ".00 5.76 ATOM 662 CA VAL 94 65.542 47.054 48.410 :.00 4.07 ATOM 663 C3 VAL 94 66.969 46.501 49.238 :.00 3.20 A* ATOM 664 CG1 VAL 94 67.600 46.310 49.571 ".00 6.25 ATOM 665 CG2 VAL 94 66.935 45.1177 47.522 :.00 2.00 ATOM 666 C VAL 94 65.042 47.525 47.040 :.00 6.50 ATOM 667 0 VAL 94 64.317 46.793 46.368 1.CO 6.26 ATOM 668 N PRO 95 65.364 48.780 46.648 :.00 4.63 ATOM 669 CD PRO 95 65.947 49.823 47.507 1.00 5.07 ATOM 670 CA PRO 95 64.960 49.357 45.365 1.00 2.90 ATOM 671 CB PRO 95 65.316 50.826 45.530 1.00 2.93 ATOM 672 CC PRO 95 65.261 51.036 47.004 :.00 4.40 A* TOM 673 C PRO ;5 65.783 48.756 44.248 ".00 5.0 7 ATOM 674 O-0 PRO 95 66.985 48.592 44.399 1.00 7.49 ATOM 675 N LEU 96 65.128 48.419 43.14'1 1.00 6.65 ATOM 676 CA LEO 96 65.776 47.852 41.9!7 ".00 5.19 ATOM 677 CB LEU ?6 65.088 46.531 41.543 00 3.04 ATOM 676 CG LEO 96 65.571 45.607 40.411 :.00 2.00 ATOM 679 CD1 LEU 96 66.945 45.060 40.642 1.30 2.00 ATOM 680 CD2 LEU 96 64.648 44.446 40.215 00 2.00 ATCM 681 C LEO 65.711 48.886 43.8 1. 20 6.21 ATOM 482 9 LE f 94 64.639 49.309 40.36' 00 5.C2 ATOM 683 N GLU 66.881 49.355 40.416 00 8.18 ATOM 684 CA GLL 67.000 50.324 2.326 1.00 3.49 ATOM 685 CB CLO 9' 68.311 51.069 29.476 1.30 10.17 ATCM 666 :CC SLU 68.162 52.499 23.349 .3C 10.56 ATOM 687 CD GLU 9" 67.806 53.335 23.676 1.30 12.04 ATOM 686 OE1 GL 68.087 54.545 23.734 1.30 14.20 AWO 65? OE2 GLL 67.252 52.787 27-.691 :.3C 17.32 ATOM 690 C GL 66.95S. 49.610 2-.)87 :.30 8.71 ATOM 691 0 GLL i' 6?.'35 48.689 27.741 .3C 9. 01 ATOM 692 N LEU 38 66.083 50.053 27".101 :.30 3.76 ATOM i93 .A LEL 98 65.954 49.400 2-5.821 3.77 ATOM 694 CB LEU 98 64.592 48.695 25.754 .00 3.21 bzf21c.pdb Thu Apr 25 12:27:47 1996 ATOM 695 CG LEO 98 64.366 41.487 26.686 1.00 9.91 ATOM 696 CD1 LEU 98 62.912 47.080 25.721 i.00 3.15 ATOM 691 CD2 LEU 98 65.203 46.309 25.266 1.00 3.89 ATOM 698 C LEO 98 66.141 50.388 24.676 30 9.14 ATCH 699 0 LEO 98 65.751 51.556 24.781 1..00 11.17 ATOM 700 N ARC 99 66.814 49.945 23.621' 1.00 1.82 ATOM 701 CA ARC )9 67.050 50.799 22.467 1. 38.42 ATOM 102 CB ARG 99 68.265 51.101 22.680 '.30 9.99 ATOM 703 CG ARG 99 68.319 52.571 23.915 1.30 13.57 ATOM 704 CD ARC 99 69.548 53.483 22.832 1.00 15.6~ ATOM 705 NE ARC 99 10.198 52.717 23.166 L.00 21.42 ATOM 706 CZ ARG 99 71.623 52.634 22.709 1.00 23.75 ATOM 107 NHI ARG 99 11.364 53.271 21.551 1.00 25.09 ATOM 108 NH2 ARG 99 72.747 51.921 22.818 1.00 24.11 1 ATOM 109 C ARG 99 67.294 50.002 21.114 1.00 7.84 ATOM 710 0 ARG 99 68.119 49.159 21.118 1.00 8.53 2 ATOM 711 N VAL 100 66.528 50.307 20.136 1.00 5.56 ATOM 112 CA VAL 100 66.670 49.664 28.852 1.00 5.54 i ATOM 713 CB VAL 100 65.321 49.097 2a.391 1.00 8.61 s ATOM 114 CC1 VAL 100 65.446 48.461 27.008 1.00 1.63 6 ATOM 715 CG2 VAL 100 64.821 48.100 29.419 1.00 7.70 6 ATOM 716 C VAL 100 67.146 50.745 27.877 1.00 6.61 ATOM 711 0 VAL 100 66.556 51.831 27.819 1.C0 3.63 ATOM 718 N THR 10: 68.236 50.490 27.156 1.00 7.98 ATOM 719 CA THR 101 68.768 51.483 26.193 1.00 10.18 6 ATOM 720 CB THP. 101- 70.000 52.277 26.748 1.00 8.43 ATOM 721 OC1 THP. 101 70.526 51.629 27.3 08 .00 13.91 ATOM 722 CG2 THP. 10: 69.603 53.663 21.148 1.30 11.20 ATOM 723 C THR 101 69.115 50.926 24.792 1.00 11.66 ATOM 724 0 THR 101 69.483 49.758 24.645 1.00 11.61 ATOM 725 N ALA 102 68.915 51.752 23.767 1.00 12.50 ATOM 726 CA ALA 102 69.216 51.369 22.386 1.00 14.07 s ATOM 127 CB ALA 102 68.735 52.465 21.399 1.00 14.73 i ATOM 728 C ALA 102 70.121 51.154 22.249 1.00 13.24 6 ATOM 729 0 ALA 102 71.511 51.752 23.012 1.00 12.22 8 ATOM 730 N ALA 103 11.111 50.332 21.270 1.00 12.73 1 ATOM 731 CA ALA 103 72.520 50.004 21.021 1.00 13.74 ATOM 732 CB ALA 103 72.631 48.712 20.183 1.00 15.06 ATOM 733 C ALA 103 1'3.250 51.113 20.338 1.00 14.01 6 ATOM 134 0 ALA 103 13.958 51.013 19.345 1.00 16.53 ATOM 135 N SER 104 73.105 52.341 20.931 1.00 12.51 7 ATOM 736 CA SEP. 104 73.673 53.569 20.440 :.30 10.25 i ATOM 737 CB SEP. 104 72.834 54.066 .3.266 1.00 ).41 ATOM 738 OG SEP. 104 71.434 54.033 19.565 1.00 8.47 ATOM 739 C SER 104 73.507 54.528 21.600 1.00 11.58 ATOM 7400 SEP 134 73.551 55.746 21.412 1.00 11.80 ATOM *41 N GLY 105 13.18;. 53.964 22.770 :.30 11.41 ATOM -42 CA GLY 125 3.002 54.747 22.916 0 12.64 ATOM 743 C SLY 105 11.731 55.568 23.980 :.30 13.51 A ATOM 144 0 3LY 105 71.507 56.335 24.921 00 15.64 ATOM 745 N ALA 106 70.929 55.433 22.930 1.30 12.54 ATCM 746 CA ALA 106 69.668 56,166 22.831 1.00 11.65 ATCHOM 14 CS ALA 106 69.068 56.040 21.444 ".00 13.77 ATOM 748 C ALA 106 68.752 55.553 23.884 1.30 11.28 ATOM 749 0 ALA 106 68.501 54.338 23.899 :.00 10.10 ATOM -50 N PRO 107 68.239 56. 392 24.779 1.30 8.60 ATOM 751 CD PROP. 10' "68.390 57.855 24.686 1.;0 9.28 ATOM 752 *CA PRO 101 67.354 56.019 25.882 :.30 7.17 ATOM 753 CB PRO 101 67.282 57.314 26.683 1.30 8.42 ATOM 754 CG PRO 107 67.302 58.358 25.605 00 9.15 ATOM 755 C PP.0 1C7 65.964 55.45) 25.552 1.;0 7.66 ATOM -56 0 PRO 1i0 65.224 56.048 24.181 8.78 ATOM 757 N A.G 108 65.595 54.353 24.196 ATOM 758 CA ARG 108 64.290 53.751 25.993 4.63 ATOM '59 CS AP. 1038 64.439 52.411 25.2E8 7.42 ATOM 160 CG AP.G 106 63.168 51.302 24.695 n..0 10.88 ATOM 161 CD ARG 108 62.782 52.688 23.460 1.:C 14.12 ATOM 762 NE AP.0 18: 61.461 52.313 22.964 'C 16.25 ATOM 763 CZ AP.G 1I8 61.086 51.084 22.650 15.01 ATOM 764 NH1 AP.C: 10S 61.911 50.067 22.764 :C 18.31 ATOM 165 NH2 ARG 108 59.858 50.867 22.236 3; 19.47 ATOM '66 C ARG 108 63.455 53.624 27.253 00 5.36 ATOM 767 AP.G 1.8 62.420 54.259 27.404 4.86 ATOM 768 N TYR 109 63.882 52.823 2a.263 .12 ATOM 169 CA TYP. 109 63.102 52.111 29.509 4.72 ATOM 70 CE TYR 109 62.415 51.350 2).631 7.62 ATOM 771 CG 139 41.45! 51.024 23.544 3.20 ATOM 772 CD1 TYR 109 61.775 50.089 21.565 :C 11.38 -41bref21c.pdb Thu Apt 25 12:27:47 1996 11 ATOM 773 CE1 TYR 109 60.897 49.788 26.557 :.00 12.39 ATOM 774 CD2 TYP. 109 60.230 51.642 28.480 ".00 10.61 i.

ATOM 775 CE2 TYR 109 59.337 51.347 27.476 :.00 12.42 4 ATCOM 776 CZ TYR 109 59.670 50.421 26.511 ".00 12.48 ATOM 777 OH TYR 109 58.777 50.152 25.481 ".00 14.44 a ATOM -78 C TYR 109 63.911 52.909 20.714 :.00 8.52 s ATOM 779 0 TYR 109 65.124 52.737 30.794 00 9.59 3 ATOM 790 N HIS 11O0 63.198 53.259 21.825 :.00 10.99 1 ATOM 781 CA HIS 110 63.760 52.467 23.174 :.00 14.45 ATOM 782 CB HIS 110 64.468 54.830 33.296 00 16.C0 ATOM 783 CG HIS 11C 65.167 55.029 24.613 :.00 21.12 6 ATOM 784 CD2 HIS 110 66.383 54.616 25.048 00 21.71 3 ATOM 785 ND1 HIS 110 64.623 55.764 35.652 1.00 24.07 7 ATOM 786 CE1 HIS 110 65.476 55.803 26.662 :.00 23.40 6 ATOM 787 NE2 HIS 110 66.553 55.114 26.321 :.00 22.60 7 ATOM 788 C HIS 110 62.628 53.380 24.214 1.00 12.21 6 ATOM 789 0 BIS 110 61.740 54.224 34.240 1.00 13.06 8 ATOM 790 N ARG 111 62.693 52.361 35.062 1.00 11.08 ATOM 791 CA ARG 111 61.716 52.116 36.112 1.00 10.30 6 ATOM 792 CB ARG 111 60.878 50.881 35.742 :.00 9.90 6 ATOM 793 CG ARG 111 59.700 50.590 36.641 00 8.05 6 ATOM 794 CD ARG 111 58.370 50.465 25.862 :.00 8.40 6 ATOM 795 hE ARG 111 57.828 49.099 35.783 *.00 8.93 ATOM 796 CZ ARG 11; 57.096 48.521 26.730 00 8.80 ATOM 797 NH1 ARG 111 56.822 49.182 317.840 1.00 10.13 ATOM 798 NH2 ARG 111 56.585 47.308 36.55C ".00 10.84 ATOM 799 C ARG 111 62.546 51.950 27.369 00 11.27 s ATOM 800 0 ARG 111 63.776 51.808 27.306 :.00 13.11 3 ATOM 801 N VAL 112 61.877 51.758 29.510 1.00 11.16 1 ATOM 802 CA VAL 112 62.493 51.471 29.822 :.00 11.15 6 ATOM 803 CB VAL 112 62.882 52.803 40.601 1.00 12.50 6 ATOM 804 CG1 VAL 112 63.003 52.545 42.094 1.00 13.08 6 ATOM 805 CG2 VAL 112 64.235 53.354 40.093 1.00 12.31 6 ATOM 806 C VAL 112 61.398 50.668 40.542 1.00 7.77 6 ATOM 807 0 VAL 112 60.268 51.105 40.581 ".00 8.50 3 ATOM 808 N ILE 113 61.709 49.480 41.049 1.00 5.20 7 ATOM 809 CA ILE 113 60.692 48.638 41.686 1.00 6.80 6 ATOM 810 CB ILE 113 60.223 47.527 40.688 1.00 5.60 6 SATOM 811 CG2 ILE 113 :59.680 48.130 29.426 1.00 6.45 s ATOM 812 CG1I ILE 113 61.396 46.623 40.315 1.00 7.39 i ATOM 813 CDI ILE 113 61.012 45.471 39.468 :.00 9.87 6 ATOM 814 C ILE 113 61.105 47.931 43.001 1.00 7.16 ATOM 815 0 ILE 113 62.141 48.234 43.572 1.00 9.02 ATOM 816 N HIS 114 60.267 47.000 43.463 1.00 2.78 1 ATOM 817 CA HIS 114 60.503 46.187 44.645 1.00 2.00 6 ATOM 818 CB HIS 114 59.793 46.758 45.860 1.00 2.00 ATOM 819 CG HIS 114 60.554 47.82' 46.555 00 2.00 SATOM 20 CD2 HIS 114 61.337 47.787 47.652 :.00 4.22 ATHOM 821 ND1 HIS 114 60.589 49.130 46.1C0 1.00 4.03 ATCHOM 822 CE1 HIS 114 61.368 49.850 46.891 00 2.34 ATOM 823 NE2 HIS 114 61.835 49.057 47.938 1.00 8.21 ATOM 824 C HIS 114 59.907 44.830 44.330 :.00 2.00 ATOM 825 0 HIS 114 58.705 44.688 44.221 1.00 2.00 ATOM 826 N ILE 115 60.741 43.820 44.201 :.00 2.00 ATOM 827 CA ILE 115 60.261 42.495 43.871 :.00 2.00 i ATOM 828 CS ILE 115 61.439 41.480 43.883 1.00 3.64 ATOM 829 CG2 ILE 115 -60.953 40.049 43.984 :.00 4.23 ATOM 830 *CG1 ILE 115 62.333 41.672 42.650 00 2.00 ATOM 831 CD1 ILE 115 63.731 42.190 42.966 *.00 2.23 ATOM 832 C ILE 115 59.107 42.012 44.751. .00 3.56 4 ATOM 833 0 ILE 115 58.294 41.217 44.3C2 1.0 6.91 ATOM 834 9 ASN 116 59.012 42.492 45.98! 1.00 4.63 7 ATOM 835 :A ASN 116 57.936 42.066 46.895 1.00 5.21 ATOM 836 CB ASN 116 58.317 42.342 43.31C ".00 5.23 ATOM 337 CG ASN 116 58.582 43.823 43.'55 20 5.54 ATOM 339 OD1 ASN 116 59.470 44.421 48.07 00 3.06 ATOM 839 ND2 ASN 116 57.806 44.414 4).551 1.00 8.46 1 ATOM 840 C ASN 116 56.589 42.722 46.54- C 5.i2 ATOM 841 0 ASN 116 55.512 42.223 45.899 1.00 4.52 ATOM 942 N LC 11 56.664 43.858 45.841 20 8.36 ATOM 643 CA GLU 11- 55.480 44.614 45.436 00 7.65 ATOM 844 CB GLU 11- 55.732 46.113 45.534 00 6.11 ATOM 845 CG LU 11 55.958 46.560 46.93" .00C. 12.42 ATOM 946 CD 3L 11- 56.160 48.095 47.0C2 :0 15.0': ATOM 847 OE1 GLU 11 56.648 48.601 48.054 30 18.5 ATOM 848 OE2 GL- 11- 55.816 48.757 44.002 1.00 11.7': ATOM 849 C GLU 11- 55.116 44.321 44.025 OC 6.25 ATOM 350 0 GLU 117 54.440 45.12:. 43.42i 30 9.90 -42bxhf21c.pdb Thu Apr 25 12:27:47 1996 12 ATOM 851 N VAL 118 55.477 43.151 43.523 1.00 3.55 ATOM 852 CA VAL 11 55.226 42.839 42.137 1.00 ATOMH 853 CB VAL 118 56.373 43.488 41.261 1.00 2.CO ATOM 854 CG1 VAL 118 57.484 42.519 40.942 1.00 2.85 ATOM 855 CG2 VAL 118 55.828 44.165 40.062 1.00 2.00 ATOM 856 C VAL 118 55.060 41.334 41.948 1.00 2.18 ATOM 857 0 VAL 118 55.453 40.755 40.936 1.00 3.!C ATOM 858 N VAL 119 54.404 40.716 42.919 1.00 2.7 ATOM 859 CA VAL 119 54.155 39.276 42.896 1.00 3.05 ATOM 860 CB VAL 119 53.778 38.736 44.305 1.00 2.4"5 ATOM 861 CG1 VAL 119 53.749 31.267 44.292 1.00 2.00 ATOM 862 CG2 VAL 119 54.735 39.231 45.352 1.00 2.00 ATOM 863 C VAL 119 52.998 38.960 41.945 1.00 2.00 ATCHM 864 0 VAL 119 52.007 39.674 41.932 1.00 2.00 ATCM 865 N LEV 120 53.171 37.919 41.132 1.00 3.02 ATOM 866 CA LEU 120 52.175 37.411 40.174 1.00 2.95 ATOM 867 -CB LED 120 52.446 37.894 38.745 1.00 5.65 ATOM 868 CC LEU 120 51.496 37.332 37.674 1.00 11.07 ATHOM 869 C01 LEU 120 50.125 37.938 37.790 1.00 9.95 ATOM 870 CD2 LEO 120 52.053 31.605 36.306 1.00 11.67 ATCOM 811 C LEO 120 52.289 35.887 40.262 1.00 2.40 ATOM 872 0 LEU 120 52.985 35.241 39.487 1.00 2.00 ATOMH 873 N LEU 121 51.600 35.340 41.250 1.00 2.39 ATOM 874 CA LEU 121 51.629 33.924 41.552 1.00 2.7- ATOM 875 CB LEO 121 51.063 33.689 42.964 1.00 4.57 ATOM 876 CG LEU 121 52.050 33.22' 44.062 1.00 10.24 ATOM 877 CD1 LEU 121 52.939 32.076 43.550 1.00 14.E- ATOM 978 CD2 LED 121 52.944 34.328 44.501 1.00 9.45 ATOM 879 C LEU 121 50.974 32.995 40.554 1.00 5.4" ATCHOM 880 0 LEU 121 50.256 33.420 39.654 1.00 7.90 ATMCH 881 N ASP 122 51.279 31.709 40.672 1.00 6.57 ATOM 882 CA ASP 122 50.687 30.726 39.782 1.00 6.90 ATCHM 883 CB ASP 122 51.493 29.421 39.773 1.00 7.76 ATOMH 884 CG ASP 122 52.701 29.431 38.795 1.00 9.54 ATOM 885 OD1 ASP 122 52.927 30.429 38.066 1.00 9.98 ATOMH 886 OD2 ASP 122 53.411 28.405 38.748 1.0* 10.20 ATOM 887 C ASP 122 49.292 30.494 40.343 1.00 7.04 ATOM 888 O ASP 122 48.957 30.954 41.453 1.00 5.44 ATOM 889 N ALA 123 48.464 29.813 29.568 1.00 6.22 7 ATOM 890 CA ALA 123 47.107 29.562 40.010 1.00 4.1 ATOMH 891 CB ALA 123 46.187 29.374 38.839 1.00 ATOM 092 C ALA 123 46.981 28.398 40.954 1.00 3.93 ATOM 893 0 ALA 123 47.826 27.484 40.971 1.00 5.37- ATCHOM 894 N PP.C 124 45.979 28.490 41.846 1.00 ATOM 895 CD PRO 124 45.216 29.736 42.096 1.00 2.90 ATOM 896 CA PP.R 124 45.652 21.478 42.845 1.00 2.91 ATOM 897 CB PRO 124 44.362 28.022 43.436 1.00 ATOM 898 CG PP.0 124 44.602 29.485 43.432 1.00 ATCHM 899 C PP.R 124 45.451 26.111 42.172 1.00 2.: ATOM 900 0 PRO 124 45.289 26.022 40.966 1.00 ATOM 901 N VAL 125 45.524 25.042 42.944 1.00 2.21 ATOM 902 CA VAL 125 45.345 23:715 42.381 1.00 4.06c ATCHM 903 CB VAL 125 46.724 23.006 42.025 1.00 2.S" ATOM 904 CC1 VAL 125 47.474 23.806 40.974 1.00 o• ATOM 905 CC2 VAL 125 47.584 22.776 43.256 1.00 2.C: ATOM 906 C VAL 125 44.436 22.838 43.261 1.00 ATOM 907 0 VAL 125 "44.002 23.281 44.316 1.00 6.3- ATOM 908 N GLY 126 44.068 21.661 42.768 1.00 5.2 ATOM 909 CA GLY 126 43.230 20.735 43.494 1.00 4.1-.

ATOM 910 C GLY 126 41.939 21.283 44.035 1.00 ATOM 911 0 SLY 12i 41.588 20.981 45.170 1.00 8." ATOM 912 N LEU 12- 41.246 22.113 43.268 1.00 ATOM 913 CA LEU 12- 39.971 22.667 43.718 1.00 7.2" ATOM 914 CB LEG 12- 39.594 23.949 42.935 l.00 3.2 ATOM 915 CC 'E 12- 38.175 24.573 43.071 0C 11.:; ATOM 916 CD1 LE 12" 37.954 25.322 44.424 1.00 ATOM 917 CD2 LE: 12- 37.942 25.516 41.892 1.00 10.2- ATOM 918 C LEC 12- 38.846 21.623 43.612 6.1: ATOM 919 0 LE 12- 38.585 21.083 42.538 1.00 6.-t ATOM 920 N VAL 12" 38.177 21.36? 44.737 1-.00 ATOM 921 CA VAL 128 37.087 20.406 44.815 1.00 6. 2 ATOM 922 CE VAL 128 37.485 19.147 45.616 1.00 ATOM 923 CC1 VAL 12S. 37.999 18.08e 44.701 C0 ATOM 924 CG2 VAL 129 38.521 19.477 46.659 1.00 9..

ATOM 925 VAL 12S 35.862 21.001 45.470 00 ATOM 926 0 :VAL 126 35.973 21.795 44.314 1.00 4. ATOM 127 N ALA 129 34.691 20.574 45.031 1.00 7.

ATOM 928 CA ALA 129 33.430 21.061 45.579 1.00 6.4.

-43brf21c.pdb Thu Apr 25 12:27:47 1996 13 ATOM 929 CS ALA 129 32.585 21.680 44.4771 1.00 4.36 i ATOM 930 C ALA 129 32.693 19.8676 46.202 1.00 9.11 6 ATOM 931 0 ALA 129 32.730 18.760 45.655 1.00 9.32 a ATOM 932 N ARG 130 32.018 20.106 47.329 1.00 9.76 7 ATOM 933 CA ARG 130 31.288 13.020 47.990, 1.00 10.55 6 ATOM 934 CB ARG 130 32.220 18.310 48.967 1.00 11.88 4 ATOM 935 CG ARG 130 31.165 .6.979 49.486 1.00 11.87 4 ATOM 936 CD ARG 130 32.108 16.871 50.963 1.00 15.67 ATOM 937 NE ARG 130 33.351 17.5617 1.252 1.00 15.76 1 ATOM 938 CZ ARG 130 33.669 13.135 52.414 00 20.46 ATOM 939 NH1 ARG 130 32.818 18.092 53.449 1.00 18.08 ATOM 940 NH2 ARG 130 34.840 18.791 52.514 1.00 21.04 ATOM 941 C ARG 130 30.028 19.479 48.121 1.00 10.90 6 ATOM 942 0 ARG 130 29.932 20.593 49.250 1.00 10.7711 ATOM 943 N LEU 131 29.065 18.582 48.792 1.00 12.00 7 ATOM 944 CA LEU 131 27.813 18.909 49.460 1.00 13.66 6 ATOM 945. CB LEU 131 26.640 18.313 48.688 1.00 12.73 6 ATOM 946 CG LEO 131 25.301 18.511 49.353 1.00 11.96 6 ATOM 947 CD1 LEO 131 25.035 20.002 49.487 1.00 10.47 6 ATCH 948 CD2 LEO 131 24.252 17.783 48.531 1.00 11.69 6 ATOM 949 C LEU 131 27.799 18.409 50.892 1.00 13.46 6 ATOM 950 0 LEO 131 27.702 17.204 51.128 1.00 12.81 8 ATOM 951 N ALA 132 27.968 19.328 51.834 1.00 14.88 1 ATOM 952 CA ALA 132 27.964 19.982 13.249 1.00 16.22 6 ATOM 953 CB ALA 132 28.272 20.228 :4.122 1.00 14.91 6 ATOM 954 C ALA 132 26.638 18.324 53.656 1.00 16.51 6 ATOM 955 0 ALA 122 25.719 19.000 54.109 1.00 16.97 ATOM 956 N ASP 133 26.553 17.009 !3.411 1.00 20.15 ATOM 957 CA ASP 123 25.397 15.156 53.729 1.00 22.27 6 ATOM 958 CB ASP 123 25.868 14.755 54.193 1.00 23.23 6 S. ATOM 959 CG ASP 133 26.187 12.783 13.024 1.00 25.12 ATOM 960 001 ASP 133 25.704 14.012 51.871 1.00 26.91 3 ATOM 961 OD2 ASP 133 26.894 12.758 53.284 1.00 25.03 3 ATOM 962 C ASP 133 24.655 16.814 54.885 1.00 22.10 6 ATOM 963 0 ASP 133 23.575 17.415 54.715 1.00 24.05 8 ATOM 964 N GLU 134 25.310 16.802 56.031 1.00 19.91 7 ATCH 965 CA GLU 134 24.742 11.410 57.211 1.00 18.60 6 ATOM 966 CB GLU 134 25.418 16.953 58.482 1.00 17.36 ATOM 967 CG GLU 134 26.589 15.897 58.281 1.00 11.83 6 ATOM 968 CD GLO 134 28.003 16.514 58.153 1.00 20.37 ATOM 969 OE1 GLO 134 28.980 15.726 58.020 1.00 19.82 a ATOM 970 OE2 GLU 134 28.136 11.175 58.183 1.00 18.81 3 ATOM 911 C GLU 134 24.784 18.933 57.068 1.00 17.19 S *o0. ATOM 912 0 GLU 134 25.842 19.534 57.197 1.00 18.37 3 ATOM 973 N SER 135 23.648 19.496 56.657 1.00 16.42 7 ATOM 974 CA SEP. 135 23.375 20.938 56.510 1.00 17.66 A ATOM 975 CB SEP. 135 24.435 21.857 57.166 1.00 11.67 4 ATOM 976 OG SER 135 25.623 21.981 56.400 1.00 19.35 ATOH 917 SER 135 22.990 21.443 55.124 1.00 18.19 4 006, ATOM 978 0 SEP. 135 22.366 22.501 54.991 1.00 17.96 8 ATHOM 919 N GLY 136 23.287 20.665 54.095 1.00 19.82 7 ATOM 980 CA GLY 136 22.945 21.109 52.753 1.00 21.54 6 ATOM 981 C GLY 136 23.765 22.335 52.312 1.00 22.07 6 ATOM 982 0 GLY 136 23.225 23.345 51.910 1.00 22.69 3 ATOM 983 N HIS 131 25.071 22.258 52.622 1.00 21.69 ATOM 984 CA HIS 131 25.992 23.332 12.301 1.00 19.69 6 ATOM 985 CB HIS 131 26.594 23.884 53.590 1.00 22.11 6 ATOM 986 CG HIS 131 25.168 24.968 !4.204 1.00 25.43 4 ATOM 987 CD2 HIS 131 26.049 25.862 55.183 1.00 27.18 6 ATCH 988 ND1 HIS 127 24.484 25.256 !3.7717 1.00 26.89 7 ATOM 989 CEI HIS 131 24.014 26.287 !4.465 1.00 26.67 A ATOM 990 NE2 HIS 137 24.944 26.674 15.325 1.00 26.59 7 ATOM 991 HIS 12' 27.081 22.363 1L.329 1.00 19.46 ATOM 992 0 HIS 137 27.428 21.666 11.301 1.00 20.08 i ATOM 993 N 'IAL -13 27.547 22.171 ;3.418 1.00 16.09 7 ATOM 994 CA VAL 128 28.598 23.427 49.526 1.00 12.40 i ATOM 995 CB VAL 12a 28.391 24.107 43.143 1.00 12.43 4 ATOM )96 CC1 VAL 13?. 29.725 24.286 47.390 1.00 10.78 4 ATOM 997 CC2 VAL 283 27.444 23.258 47.290 00 12.93 ATOM 998 C 'VAL 12P 29.891 23.

7 7 156 00 11.10 ATOM 999 0 VAL 13 29.960 24.316 50.705 00 11.62 ATOM 1000 1 VAL 139 30.872 22.982 50.171 1.00 9.36 I ATOM 1001 CA VAL 129 32.194 22.269 10.724 L.OC 10.38 ATOM 1002 Cb VAL 139 32.53S 22.371 51.949 00 6.78 ATOM 1003 -01 VAL 139 33.781 22.877 12.620 00 7.80 ATOM 1004 CG2 VAL 139 31.415 22.393 52.946 1.00 6.80 ATOM -1005 C VAL 139 33.249 23.095 4).615 '.00 10.04 4 ATOM 1006 0 VAL 139 33.333 22.026 43.961 00 10.34 -44bref21c.pdb Thu Apr 25 12:27:47 1996 14 OO *eee t e e C S 0 S 0 C 0 50

ATOM

ATO

ATOM

1001 N LEDO 1008 CA LEO 1 1009 CB LED 1 1010 CG LEO 1 1011 CD1 LEU 1 1012 CD2 LEO 1 1013 C LEU 1 1014 0 LEU 1 1015 ARC 1 1016 CA ARG C 1011 CB ARG I 1018 CG ARG 1 1019 CD ARG 1020 NE ARG 1021 CZ ARG 1022 NH1 ARG 1023. NH2 ARG 1024 C ARG 1025 0 ARG 1026 N TRP 1021 CA TRP 1028 CB TRP 1029 CG TRP 1030 CD2 TPP 1031 CE2 TRP 1032 CE3 TRP 1033 CD1 TRF 1034 EI TRP 1035 CZ2 TRP 1036 CZ3 TRP 1031 CH2 TRP 1038 C TRP 1039 0 TRP 1040 N LEO 1041 CA LEU 1042 CB LEU 1043 CG LEO 1044 CD1 LEO 1045 CD2 LEO 1046 C LEU 1041 0 LED 1048 N PRO 1049 CD PRO 1050 CA PRO 1051 CB PRO 1052 CG PRO 1053 C PRO 1054 0 PRO 1055 N PRO 1056 CD PRO 1051 CA PRO 1058 CB PRO 1059 CG PRO 1060 C PRO 1061 0 PRO 1062 N PRO 1063 CD PRO 1064 CA PRO 1065 CB PRO 1066 CG PRO 10.6 C PRO 1068 7 PRO 1069 N GLU 1010 CA GL: 1II7 =C GLU 1012 CG GLU :013 CD GLZ 1014 OE1 GL* 1071 OE2 GL: 1016 CL: 1011 3 GLt 10879 N THR 1019 :A TER 1080 :B THR 1081 3G1 TER 1082 CG2 THR S-013 C THR 4 1084 0 THR 40 40 40 40 40 40 40 40 .41 .41 141 141 141 141 141 141 141 141 141 142 142 142 142 142 142 142 142 142 142 142 142 142 142 143 143 143 143 143 143 143 143 144 144 144 144 144 144 144 145 145 145 145 145 145 145 146 146 146 146 146 146 146 147 141 147 147 147 141 141 148 148 148 148 148 140 33.975 24.194 49.312 1.

35.021 24.306 43.384 1.1 34.966 25.673 417.761 1.

33.126 25.968 47.000 33.806 27.395 46.505 L.1 33.594 24.912 45.869 1.

36.354 24.170 49.069 1.

36.566 24.774 !0.115 1.

31.218 23.481 48.409 1.

38.618 23.235 48.929 1.

38.682 21.805 49.446 1.

39.347 21.645 50.793 1.

40.849 21.410 50.691 1.

41.431 21.433 52.042 1.

42.344 22.314 52.482 1.

42.821 23.266 51.673 1.

42.127 22.282 53.7713 1.

39.632 23.383 41.804 1.

39.289 23.227 46.639 1.

40.811 23.715 48.154 1.

41.941 23.846 47.182 1.

41.154 25.101 46.354 1.

41.661 26.356 47.155 1.

40.482 26.905 417.749 1 40.852 28.094 48.391 1 29.145 26.508 47.7188 1 42.671 21.216 471.456 1 42.196 28.261 48.209 1 39.937 28.885 43.012 1 38.245 27.296 43.454 1 38.645 28.474 49.089 1 43.288 23.85 41.81177 1 43.380 23.703 49.076 1 44.349 23.995 47.109 1 45.100 24.039 47.656 1 46.520 22.876 41.123 1 46.031 21.414 47.408 1 46.832 20.483 46.601 1 '46.182 21.223 48.862 1 46.310 25.326 47.158 1 45.765 25.910 46.214 1 47.411 25.759 47.762 1 48.003 25.321 49.030 48.021 26.996 47.295 48.955 21.359 48.445 48.442 26.605 49.601 48.821 26.750 46.011 48.999 25.611 45.580 49.249 21.823 45.342 49.058 29.249 45.645 50.022 27.643 44.113 50.532 29.053 43.839 49.467 29.898 44.312 51.178 26.696 44.455 51.8715 26.899 45.448 51.396 25.652 43.639 50.138 25.412 42.341 52.462 24.665 43.857 52.358 23.1778 42.622 50.912 23.951 42.167 53.863 25.273 43.961 54.212 26.0871 43.135 54.604 24.825 44.915 55.959 25.281 45.248 56.894 24.253 44.011 56.733 23.566 43.456 57.4711 22.401 44.166 58.335 22.639 45.0e1 57.201 21.215 43.789 56.052 26.1773 45.624 57.099 21.403 45.453 54.975 21.364 46.124 55.048 29.116 4-;.541 53.71E 29.551 56.178 53.589 29.464 44.765 53.881 31.014 44.621 55.217 28.818 43.048 54.609 28.080 43.789 00 3.25 00 6.26 00 2.05 00 2.00S 00 2.00 00 2.00 00 3.88 00 10.60 00 11.4 00 12.16 6 00 16.99 1 00 21.35 6 00 24.13 6 00 29.12 00 30.00 6 00 30.75 00 29.95 00 13.10 6 00 13.55 00 11.10 .00 6.61 .00 6.92 .00 9.55 .00 9.85 .00 9.31 .00 10.67 .00 10.90 .00 11.52 .00 11.31 .00 11.65 .00 *9.80 .CO 5.00 .00 6.66 .00 5.41 .00 3.56 .00 2.35 .00 2.00 .00 2.00 .00 2.00 1.00 2.00 1.00 4.81 1.00 2.00 1.00 2.00 L.00 2.00 L.00 2.00 L.00 2.00 1.00 2.00 1.00 2.00 1.00 2.00 1.00 2.00 1.00 2.72 1.OO 2.80 1.00 2.95 1.00 4.11 1.00 3.80 00 9.22 1.00 5.90 .00 6.83 1.00 7.88 1.00 6.28 3.00 3.28 1.00 10.56 1.00 10.54 1.00 3.65 .00 ?.95 1.00 18.10 .00 22.76 1.00 26.12 1.30 23.73 1.00 10.12 1.00 12.66 1.00 10.44 1.00 7.31 1.00 5.61 30 4.14 :.00 2.30 00 4.00 1.00 4.53

S

6

I

4

I

6 3 5 4 6 6 6 3 1 4 4 6 6 4 6

I

7 6

X

4 i i i bref2lc.pd ATOM 1085 ATOM 1096 ATOM 1087 ATOM 1088 ATOM 1089 ATOM 1090 ATOM 1091 ATOM 1092 ATOM 1093 ATOM 1094 ATOM 1095 ATOM 1096 ATOM 1091 ATOM 1098 ATOM 1099 ATOM 1100 ATOM 1101 ATOM 1102 ATOM 1103 ATOM 1104 ATOM 1105 ATOM 1106 ATOM 1107 ATOM 1108 ATOM 1109 ATOM 1110 ATOM 1111 ATOM 1112 ATOM 1113 ATOM 1114 ATOM 1115 ATOM 1116 ATOM 1117 ATOM 1118 ATOM 1119 ATOM 1120 ATOM 1121 ATOM 1122 ATOM 1123 ATOM 1124 ATOM 1125 ATOM 1126 ATOM 1127 ATOM 1126 ATOM 1129 ATOM 113C ATOM 1131 ATOM 1132 ATOM 113: ATOM 1134 ATOM 113; ATOM 113' ATOM 113 ATOM 113 ATOM 113 ATOM 114 ATOM 114 ATOM4 114 ATOM 114 ATOM 114 ATOM 1.14 ATOM 114 ATOM 114 ATOM 114 ATOM 114 ATOM 115 ATOM 11: ATOM 11; ATOM 115 ATOM 11: ATOM 11: ATOM 11 ATOM 11: ATOM 11 ATOM 11 ATOM 11 ATOM 11 ATOM 11 s 1 2 3 4 3 6 7 8

S

Q

b 5 5 5 5 N PRO 1 CD PRO I CA PRO I CB PRO 1 CG PRO I C PRO 1 0 PRO I N MET I CA MET 1 CB MET 1 .G MET I SD MET 1 CE MET I C MET 1 O MET 1 N THR 1 CA THR I CB THR O01 THR CG2 THR C THR 0 THR N SER CA SER CB SER OG SER

SER

o SER N HIS CA HIS CB HIS CG HIS CD2 HIS NDI HIS CEl HIS NE2 HIS C HIS 0 HIS N ILE CA ILE CB ILE CG2 ILE CGI ILE CD1 ILE SC ILE 0 ILE N ARC SCA ARC SCB ARC I CG ARC 5 CD ARC 6 NE ARC 7 CZ ARC B NHI1 ARC 9 NH2 ARC 0 C ARC 1 0 ARC 2 N TYR.

3 CA TYR 4 CB TYR 5 CG TYR 6 CDI TYF.

I CEl TYR 8 CD2 TYF.

9 CE2 TYF.

0 CZ TYF.

,1 OH TY.

i2 C TYR 3 0 TYR 54 N GL'-' 55 CA GL: 56 CD GLU 51 CC GL' 58 CD GLU 59 OEl CLU 60 OE2 GLU 61 C GLU 62 0 GLU 49 49 49 49 49 49 49 50 50 50 50 50 50 50 ,50 .51 .51 .51 151 151 151 151 152 152 152 152 152 152 153 153 153 153 153 153 153 153 153 153 154 154 154 154 154 154 154 154 155 155 155 155 155 155 155 15 135 155 155 156 156 156 156 156 156 156 156 156 156 156 15G 151 151 151 15- 151 157 15' 151 15-1 56.

51.

56.' 58.1 58.1 55.

55.

54.

55.

56.

51.

53.

52.

51.

50.

49.

50.

49.

50.

51 49 48 50 50 51 52 52 52 53 53 49 49 S48 48 48 41 4! 50 46 41 41 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4' 219 29.605 48.

156 30.451 47, 623 29.157 49 014 30.190 49 050 31.144 48 742 30.869 50 080 31.600 49 127 31.012 51 916 32.048 52 415 33.469 !2 864 33.812 !2 164 33.91e 54 009 35.706 54 411 31.921 52 149 32.952 52 818 30.696 52 464 30.405 51 151 28.902 51 581 28.183 52 821 28.341 50C 403 30.920 52 .218 30.919 52 .114 31.331 54 .155 31.831 5; .118 31.598 51 .027 32.645 51 .563 33.321 t .982 33.976 5: .148 33.866 .010 35.291 5 .419 35.883 5 .310 35.915 5 .810 31.048 5 .181 34.868 5 .540 35.254 5 .513 36.510 5 .275 35.491 5 1.013 36.614 5 1.931 34.385 .201 34.412 1.493 33.116 4 P.906 33.208 4 9.982 32.883 4 0.301 31.121 6.103 34.532 6.165 33.891 6.068 35.391 4.638 35.649 4.312 31.149 4.596 31.920 4.382 39.399 4.206 40.104 4.832 41.229 5.118 41.848 4.600 41.101 4.067 34.962 4.800 34.760 12.183 34.596 12.011 33.921 41.174 32.414 12.918 31.665 13.447 31.591 14.624 30.889 43.10C 31.012 44.899 30.283 45.34( 30.240 46.495 29.561 40.136 34.600 40.152 35.204 40.28A 34.531 38.919 35.038 39.036 36.256 37.622 36.826 37.511 38.030 37.566 39.111 31.486 31.826 28.254 33.920 38.'99 33.290 .503 .666 .926 .860 .698 .490 .131 .814 .464 .109 .512 .292 .546 .169 .002 .239 .963 .799 !.955 609 '.922 2.583 1.123 5.041 6.476 6.893 4.842 5.697 3.780 3.485 3.215 4.526 5.182 5.191 6.204 6.215 2.221 1.811 1.603 0.371 9.523 18.126 19. 316 48.512 50.669 51.564 49.88; 49.911 49.811 51.09 50.84 52.11 52.49 51.69 53.12 48.66 47.67 48.73 47.65 48.01 48.33 49.65 49.9< 47.3' 41.6 48.91 49.2 47.3 48.2 46.1 45.1 44.8 44.6 43.7 44.2 42.5 44.9 44.1 Thu Apr 25 12:27:47 1996 1.00 7.63 1.00 4.62 1.00 5.20 1.00 2.62 1.00 2.00 1.033 7.00 1.00 10.83 1.00 1.26 1.00 5.41 1.00 5.16 1.00 2.00 1.00 8.51 1.00 2.48 1.00 5.15 1.00 4.08 1.00 3.'2 1.00 3.59 1.00 2.22 1.00 8.69 1.00 3.84 1.00 5.68 1.00 1.24 1.00 6.42 1.00 6.44 1.00 6.46 .00 5.38 ".0C '.14 .3O 10.-G =0 lO. G i.oo .23 1.30 1.00 4.92 i.00 4.89 1.00 3.84 1.00 6.02 1.00 3.19 1.00 2.00CO 1.00 2.54 1.00 6.78 1.00 2.00 1.00 2.00 .00 2.CO 1.00 2.06 1.00 2.CC 2 1.00 2.00 9 1.00 2.05 4 1.00 2.30 5 0oc 4.56 0 1.00 3.23 B 0 5.20 4 1.00 8.42 8 1.00 14.?5 9 1.00 24.48 6 1.00 27.35 9 1.30 25.45 5 1.00 28.94 8 5.0 8 1.30 5.12 9 1.00 5.^8 .1 1.30 5.24 .1 1.00 5.-3 19 1.30 10.34 1 :0 13. 68 1.30 16.23 41 :C 14.4- 46 14.-1 60 14.2:} 09 12.24 65 2 56 C 8.1S 0 0C 4.

20 1.ZC 4.; 13 1.01 4.31 14 26 32 1 194 1 9102 10. .02 .010.:.

46 b.f2lc.pdb Tbu Apr 25 12:27:47 1996 16 ATOM 1163 N VAL 158 37.022 33.675 45.406 1.00 5.40 ATOM 1164 CA VAL 158 36.196 32.627 44.842 1.00 6.15 ATCOM 1165 CB VAL 158 35.459 31.871 45.954 1.00 3.03 ATCH 1166 CG1 VAL 158 34.655 30.159 45.391 1.00 4.03 ATOM 1161 CG2 VAL 158 36.429 31.369 46.962 1.00 3.63 ATCHOM 1168 C VAL 158 35.154 33.186 43.819 1.00 9.01 ATOM 1169 0 VAL 158 34.400 34.103 44.208 1.00 10.93 ATOM 1110 K ASP 159" 35.114 32.622 42.681 1.00 10.51 ATOM 1171 CA ASP 159 34.147 33.012 41.612 1.00 10.09 ATCOM 1172 CB ASP 159 34.828 33.112 40.327 1.00 11.10 ATOM 1173 CG ASP 159 33.813 33.413 29.256 1.00 13.83 ATOM 1174 OD1 ASP 159 33.863 32.822 38.172 1.00 13.65 ATCHOM 1175 OD2 ASP 159 33.093 34.407 39.547 1.00 15.65 ATOM 1176 C ASP 159 32.991 31.985 41.575 1.00 9.91 ATOM 1177 0 ASP 159 33.221 30.761 41.474 1.00 11.09 ATOM 1178 N VAL 160 31.766 32.485 41.631 1.00 1.83 ATCM 1179 CA VAL 160 30.582 31.642 41.535 1.00 5.49 ATCH 1180 CB VAL 160 29.637 31.174 42.755 1.00 3.19 ATCHOM 1181 CG1 VAL 160 28.512 30.139 42.142 1.00 3.00 ATOM 1182 CG2 VAL 160 30.362 31.602 44.091 1.00 2.00 ATCOM 1183 C VAL 160 29.842 32.132 40.286 1.00 6.19 ATOM 1184 0 VAL 160 29.364 33.280 40.238 1.00 8.22 ATOM 1185 N SER 161 29.835 31.272 29.300 1.00 1.12 ATCH 1186 CA SEP. 161 29.104 31.415 28.046 1.00 8.29 ATOM 1187 CB SER 161 30.094 31.628 26.891 1.00 10.26 ATOM 1188 OG SER 161 30.631 32.951 26.934 1.00 13.94 ATOM 1189 C SER 161 28.161 30.215 27.1938 1.00 1.24 ATOM 1190 0 SER 161 28.601 29.117 28.024 1.00 ?.94 ATOM 1191 N ALA 162 26.885 30.605 231.191 1.00 9.16 ATOM 1192 CA ALA 162 25.793 29.612 21.184 1.00 12.39 ATC 1193 CB ALA 162 24.689 30.055 28.736 1.00 1.5.24 ATOM 1194 C ALA 162 25.199 29.394 36.319 1.00 14.12 ATOM 1195 0 ALA 162 25.593 30.044 35.406 1.00 13.91 SATOM 1196 N GLY 163 24.220 28.499 36.369 1.00 15.85 *ATOM 1197 CA GLY 163 23.598 27.913 35.150 1.00 16.65 o ATOM 1198 C GLY 163 22.561 28.761 34.370 1.00" 18.26 ATOM 1199 0 GLY 163 21.996 29.729 34.891 1.00 18.80 3 ATCOM 1200 N ASN 164 22.416 28.231 33.146 1.00 90.00 ATOM 1201 CA ASN 164 21.568 28.664 21.994 1.00 90.00 ATOM 1202 CB ASN 164 20.505 21.625 31.685 1.00 90.00 ATOM 1203 CC ASN '164 19.337 217.730 32.702 1.00 90.00 ATOM 1204 OD1 ASN 164 19.322 27.033 33.726 1.00 90.00 SATOM 1205 ND2 ASN 164 18.334 28.580 32.511 1.00 90.00 ATOM 1206 C ASN 164 20.728 29.929 32.186 1.00 90.00 ATOM 1207 0 ASN 164 19.665 29.8974 32.811 1.00 90.00 ATCO4 1208 N CLY 165 21.227 31.004 21.601 1.00 90.00 ATCOM 1209 CA GLY 165 20.544 32.321 31.514 1.00 90.00 ATOM 1210 C GLY 165 20.214 33.048 32.859 1.00 90.00 :ATOM 1211 0 GLY 165 19.410 33.98? 22.927 1.00 90.00 ATOM 1212 N ALA 166 20.941 32.706 23.961 1.00 90.00 SATOM 1213 CA ALA 166 20.602 33.406 35.242 1.00 90.00 ATOM 1214 CB ALA 166 19.550 32.609 36.015 1.00 90.00 ATOM 1215 C ALA 166 21.7195 33.647 36.188 1.00 90.00 ATOH 1216 ALA 166 21.646 33.653 31.421 1.00 90.00 ATOM 1217 N GLY 167 22.964 33.851 35.614 1.00 11.62 SATOMH 1218 CA GLY 161 24.161 34.185 36.400 1.00 13.44 ATOM 1219 C GLY 167 "24.11C 35.688 36.104 1.00 15.68 A TOM 1220 0 GLY 161 23.701 36.494 35.863 1.00 15.58 ATOM 1221 N SER 168 24.504 36.099 37.909 1.00 17.86 ATOM 1222 CA SER 168 24.434 31.545 38.252 1.00 18.83 ATOM 1223 CB SER 168 23.543 31.788 39.465 1.00 21.8: ATOM 1224 OG SER 168 22.558 38.750 39.118 00 23.471 ATOM 1225 C SEA 168 25.820 38.200 38.531 1.00 18.61 ATOM 1226 SER 168 25.961 39.425 38.506 1.00 18.81 ATOM 1221 4 VAL 169 26.808 31.379 28.789 1.,0 18.64 ATOM 1228 CA VAL 169 28.218 37.762 39.149 1.00 11.18 ATOM 1229 CB VAL 169 29.719 39.141 38.651 1.00 19.01 ATOM 1230 CG1 VAL 169 30.262 39.261 38.769 :.GO 16.57 ATCOM 1231 CG2 VAL 169 28.401 39.441 '31.191 1.00 18.24 ATOM 1232 C VAL 169 28.381 31.796 40.666 1.00 17.25 ATOM 1233 0 VAL 169 28.222 38.845 41.313 1.00 15.44 ATHOM 1234 N GLN 170 28.-25 36.631 41.201 1.00 15.91 ATOM 1235 CA GLN 170 28.905 26.476 42.641 1-.12 ATOM 1236 CS GLN 170 21q 8 35.459 43.231 1.00 19.39 ATOM 1237 CG GLN 170 2.21 35.468 44.766 1.00 24.35 ATOM 1238 CD GLN 170 28.202 34.091 45.365 1.00 26.34 ATOM 1239 OE1 GLN 170 27.369 33.192 4.5.247 1.OC 27.24 ATOM 1240 NE2 GLN 170 29.335 33.868 46.004 1.00 28.12 -47- *9 a a a bref2

ATOM

SATOM

ATCH

ATCOM

ATCM

ATOM

SATOM

ATOM

ATOH

ATOM

ATOM ATOM

ATOM

Lc.pdb 1241 C GLN 1 1242 0 GLN 1 1243 N ARG 1 1244 CA ARG 1 1245 CB ARG 1 1246 CG ARG 1 1241 CD ARG 1248 NE ARG 1249 CZ ARG 1250 NH1 ARG 1251 NH2 ARG 1252 C ARG 1233 0 ARG 1254 N VAL 1255 CA VAL 1256 CB VAL 12517 CGI VAL 125B CG2 VAL 1259 C VAL 1260 0 VAL 1261 N GLU 1262 CA GLU 1263 CB GLU 1264 CG GLU 1265 CD GLU 1266 OE1 GLU 1267 OE2 GLU 1268 C GLU 1269 0 GLU 1270 N ILE 1211 CA ILE 1212 CB ILE 1273 CG2 ILE 1274 CGI ILE 1275 CD1 ILE 1276 C ILE 1277 0 ILE 1278 N LED 1219 CA LEO 1280 CB LEU 1281 CG LEU 1292 CDI LEO 1283 CD2 LEU 1284 C LEOU 1285 0 LEOU 1286 N GLU 1287 CA GLO 1288 C9 GLU 1289 CG GLU 1290 CD GLO 1291 OE1 GLU 1292 0E2 GLU 1293 C GLO 1294 0 GLU 1295 N GLY 1296 CA GLY 1297 C GLY 1298 *0 GLY 1299 N ARG 1300 CA ARG 1301 CB ARG 1302 CG ARG 1303 CD ARG 1304 NE ARG 1302 CZ ARG 1306 NH1 ARG 1301 MH2 ARG 130S C ARG 1309 0 ARG 13 M THE.

1311 CA THR 1312 CB THR 13 3 1 THR 1314 CC2 THR 1213 C THR 1316 0 THR 1317 N GLU 1318 CA GLU 70 70 71 71 71 71 171 .71" 171 111 171 171 172 172 1172 172 172 172 172 113 173 173 173 173 173 173 173 173 174 174 174 174 174 174 174 174 175 175 1715 175 175 175 175 176 116 176 116 176 1716 176 176 176 1176 117 177 171 177 178 178 178 178 178 178 178 178 178 1178 178 179 17s 179 179 179 179 179 119 180 180 30.344 36.030 43.047 30.735 34.892 42.819 31.101 36.932 43.674 32.47' 36.643 44.094 33.441 31.718 43.573 23.545 31.814 42.049 34.460 26.758 41.425 34.628 26.922 29.969 25.214 37.932 39.316 35.841 28.899 40.105 25.304 38.000 38.045 22.581 36.543 45.630 31.106 31.062 46.350 33.651 35.916 46.131 33.816 35.727 41.563 33.473 34.260 48.000 33.300 34.155 49.521 32.236 33.145 41.262 25.216 35.966 48.031 36.134 35.398 47.507 35.365 36.778 49.062 36.671 37.041 49.651 36.760 38.463 50.218 36.591 39.569 49.173 37.267 40.903 49.513 2 .709 41.647 48.649 37.359 41.206 50.803 26.910 36.016 50.119 36.017 35.720 51.592 38.087 35.403 50.719 38.557 34.406 51.669 38.915 33.088 50.966 40.014 32.388 51.689 37.679 32.182 50.893 36.625 32.629 49.917 39.802 35.051 52.250 40.563 35.693 51.332 39.982 34.956 53.558 '41.138 35.582 54.166 40.838 35.912 55.609 40.467 31.466 55.733 40.100 38.112 54.394 39.345 37.623 56.733 42.394 34.753 54.031 42.322 33.535 53.838 43.542 35.431 54.084 44.842 34.765 53.946 46.000 35.733 54.145 45.963 36.472 55.432 46.145 37.925 55.180 47.330 38.343 55.210 45.117 38.626 54.911 45.068 33.602 54.853 44.875 33.686 56.06; 45.574 32.545 54.25 45.939 31.341 55.00 44.738 30.340 54.82 44.990 29.169 54.96 43.534 30.787 54.49 42.398 29.882 54.31 41.11( 30.660 54.41 41.154 31.621 55.61 40.911 30.920 56.95 41.904 31.285 51.96 42.4CC 22.509 58.13 42.004 33.543 51.38 43.35C 32.68? 59.04 42.37 29.216 52.95 42.486 29.881 !1.9 42.20; 27.906 52.9 42.145 27.157 51.61 43.316 26.310 51.5 43.659 '25.C3 !2.3: 44.559 27.162 51.0 40.873 26.265 51.6 40.892 23.102 51.1 29.71C 26.831 52.1 38.469 26.188 52.1 Thu Apr 25 12:27:47 1996 17 1.00 14.16 s 1.00 10.49 1.00 13.88 7 1.00 13.53 1.00 13.16 6 1.00 12.56 i 1.00 13.31 4 1.00 10.48 1.00 8.84 1.00 4.3 7 1.00 6.87 1.00 15.23 1.00 11.537 1.00 11.99 1.00 9.19 1.00 10.74 1.00 5.41 1.00 11.43 1.00 9.92 1.00 10.28 1.00 14.35 1.00 14.21 1.00 17.07 1.00 21.96 1.00 25.14 1.00 23.21 1.00 26.88 1.00 13.64 1.00 13.24 1.00 14.30 1.00 14.95 1.00 12.11 1.00 13.06 1.00 13.75 1.00 12.34 1.00, 15.60 1.00 17.19 1.00 16.671 1.00 16.56 1.00 15.47 1.00 16.91 1.00 14.03 1.00 16.66 1.00 16.41 :.00 11.23 1.00 11.18 1.00 16.66 1.00 21.33 1.00 20.62 1.00 22.84 1 1.00 23.62 1 1.00 23.22 2 1.00 12.93 2 1.00 16.371 9 1.00 9.95 1 1.00 8.11 7 1.00 7.43 2 1.00 9.00 3 1.00 7.50 6 1.00 8.26 1 1.00 10.81 6 1.00 14.76 0 i.00 20.12 0 1.00 24.00 35 '.00 26.21 1 1.00 27.32 13 1.00 26.51 14 1.00 7.67 38 1.00 8.54 34 1.00 '.97 89 1.00 9.51 42 1.00 9.12 18 1.00 12.75 13 1.00 6.02 41 1.00 14.19 35 1.00 15.46 51 1.00 13.36 62 1.00 12.84

S

6 6 6 3 7 6 6 6 6 3 6 6 6 6 3 3 .7 6 6 6 6 6 6 6 8 7 6 o 6 6 6 4 a 3 3 7 6 7 2 7 3 3 1 7 5 5 1 3 7 4 1 3 3 s, -48bhtf21c.pdb Thu Apr 25 12:27:47 1996 18 4 a

ATOM

ATOH

ATOM

ATCH

ATOM

ATOH

ATCM

ATCH

ATOM

ATCM

ATOM

ATCH

ATOM

ATCH

ATOM

ATCH

ATCM

ATCH

ATOM

ATCH

ATOM

ATCM

ATOM

ATCH

ATOM

ATCM

ATOM

ATCM

ATOM

ATCM

ATOM

ATCM

ATOM

ATCM

ATOM

ATCH

ATOM

ATOH

ATOM

1319 CB GLU 1 1320 CC GL 1 1321 CD GLU 1 1322 OE1 GLO 1 1323 0E2 GLO 1 1324 C GLU 1 1325 0 GLU 1326 N CYS 1327 CA CYS 1328 C CYS 1329 SG CYS 1330 C CYS 1331 0 CYS 1332 N VAL 1333 CA VAL 1334 C VAL 1335 CG1 VAL 1336 -CG2 VAL 1331 C VAL 1338 0 VAL.

1339 N LED 1340 CA LEO 1341 CB LEU 1342 CG LEU 1343 CD1 LEU 1344 CD2 LED 1345 C LED 1346 0 LED 1347 tN SER 1348 CA SER 1349 C SER 1350 G00 SER 1351 C SER 1352 0 SER 1353 N ASN 1334 CA ASM 1355 CB ASN 1356 CG ASN 1357 OD1 ASN 1358 ND2 ASN 1359 C ASN 1360 0 ASN 1361 N LED 1362 CA LED 1363 CB LED 1364 CG LED 1365 CD1 LEU 1366 CD2 LED 1367 C LED 1368 0 LED 1369 N ARG 1370 CA ARG 1371 C AR 1372 CG ARG 1373 CD ARC 1374 NE ARG 1375 CZ AR 1316 NH AR 1317 NHIl2 ARGC 1371 C ARG 1379 0 AR 130 N CGLY 1381 CA CLY 1382 C GLY 1383 GLY 1394 N ARC 1385 CA ARG 1386 CB ARC 1357 CG ARG 1388 CD ARG 1399 NE ARGC 1390 CZ ARG 1391 %H1 A.G 1392 NH2 ARGC 1393 C ARG 1394 0 ARG 4 1395 N THR 1396 CA THR 80 80 80 80 .80 .80 .90 so .81 LSX L81 1 181 181 182 182 182 182 182 192 1823 183 183 183 183 183 183 153 183 184 184 184 194 194 185 185 1835 185 185 185 185 186 1846 186 196 136 136 196 186 187 187 187 181 187 187 187 187 187 131 137 1387 128 188 189 las '.8A :39 139 189 189 139 189 189 1&9 129 189 199 130 190 38.329 25.242 !3.340 37.418 24.052 !3.048 37.112 23.255 Z4.299 36.526 23.077 !5.216 37.473 22.045 !4.387 37.442 27.288 12.301 37.742 28.385 52.782 36.209 26.986 51.934 35.149 27.967 !2.034 35.382 28.990 !3.936 33.911 29.643 -3.288 33.766 27.287 51.905 33.606 26.383 11.086 32.790 27.639 22.743 31.478 26.985 !2.613 31.093 26.072 53.820 32.003 26.307 !5.003 29.669 26.255 54.193 30.353 27.910 !2.171 29.930 28.928 52.872 29.954 27.715 50.930 28.921 28.515 53.338 29.052 28.500 48.817 30.193 29.380 43.350 30.636 28.956 46.970 29.734 30.852 43.398 27.564 28.027 !..778 27.139 26.887 !3.514 26.897 28.909 !1.487 25.583 28.642 !1.998 25.558 29.046 !3.461 26.601 28.369 54.144 24.671 29.5317 51.208 25.115 30.545 :3.679 23.422 29.140 51.048 22.479 29.998 53.338 22.463 31.389 51.009 22.274 31.330 52.546 Z2.999 32.131 53.270 11.392 30.414 53.050 22.641 30.149 49.794 22.967 31.228 43.263 22.329 29.062 43.093 22.384 28.912 46.63! 23.632 28.170 46.201 25.006 28.318 46.924 25.951 27.172 45.54( 25.689 29.663 46.63' 21.06? 28.230 46.261 20.449 27.566 47.11 20.611 28.382 45.01 19.371 27.749 44.51 18.845 289.415 43.32 19.153 29.870 43.26 19.525 30.512 42.05 19.21E 30.197 43.90 *18.997 29.109 43.06 18.110 29.181 43.43 19.594 29.001 33.87 19.528 26.264 44.29 20.608 25.788 43.87 19.413 25.557 44.41 18.369 24.124 44.29 19.304 23.695 42.84 17.760 24.421 42.0' 18.822 22.492 42.51 18.891 21.885 41.2: 17.495 21.501 47.7 17.450 20.203 21.9 1.'80 20.447 -3.3 18.570 19.373 7.7 18.078 18.215 27.2 16.76E 17.337 7.4 18.888 17.342 34.6 19.610 22.773 41.2 19.406 22.605 3).3 20.432 23.719 41.6 21.195 24.411 2t.3 1.00 14.42 1.00 18.37 1.00 19.86 i 1.00 21.31 1.00 18.58 i *.00 14.56 1.00 14.76 4 00 13.82 00 12.64 00 12.6 00 13.38 14 1.00 13.84 1.00 15.56 3 1.00 13.12 17 1.00 11.97 6 1.00 9.54 6 i.00 10.81 6 i.00 8.15 6 00 12.84 6 1.00 13.90 S 1.00 11.79 7 1.00 12.76 i 00 13.26 6 00 11.81 6 1.00 9.24 i 1.00 13.01 00 14.24 6 1.00 15.09 1.00 14.69 1.00 16.60 6 1.00 17.40 6 1.00 19.79 a 1.00 17.61 6 1.00 18.84 3 1.00 18.50 7 1.00 21.04 6 1.00 27.82 6 1.00 33.52 6 1.00 36.61 3 1.00 36.25 7 1.00 19.48 6 1.00 18.46 a 1.00 17.53 1 1.00 15.82 1.00 14.99 6 1.00 15.24 S 1 .00 13.51 7 1.00 14.02 L 1.00 16.15 5 1.00 16.68 3 9 1.00 15.66 1 6 1.00 14.27 S 7 1.00 14.63 6 3 1.00 19.73 4 4 1.00 23.74 6 5 1.00 24.90 I 0 1.00 29.07 6 0 1.00 29.72 1 4 1.00 21.36 1 '8 1.00 16.07 2 1.00 14.20 13 00 15.94 1 .00 17.35 A 12 1.00 19.74 i .6 .Oc 20.69 53 .00 23.12 19 20.15 S1.30 22.54 71 .00 26.04 6 8C .OC 26.2 56 1.00 27.40 99 1.00 29.60 05 :.CC -3.45 7 86 0C 29.39 7 12 .3C 20.12 4 17 :.OC 21.60 93 00 1.).12 12 1.00 17.35 4 -49- .9* bnf2

ATOM

ATOH

ATet4

ATOI

ATOP

ATOM

ATCO

ATOM

ATOI

ATd

ATO

ATOI

ATO

ATO ATC

ATC

Lc.pdb 1397 CB THR I 1398 O1 THRP 1 1399 CG2 THR 1 1400 C THR 1 1401 0 THR 1 1402 N ARC 1 1403 CA ARG 1 1404 CB ARC 1 1405 CC ARG 1 1406 CD ARG 1 1401 NE ARG 1 1408 CZ ARG 1 1409 NHI ARG 1 1410 NH2 ARG 1 1411 C ARG 1412 0 ARC 1 1413 N TYR 1 1414 CA TYR 1415 CB TYP.

1416 CG TYR 1411 CDl TYR 1418 CE1 TYR 1419 C02 TYP 1420 CE2 TYR 1421 CZ TYR 1422 OH TYP.

1423 C TYP.

1424 0 TYP.

1425 N THR 1426 CA THR 1421 CB THR 1428 O1 THR 1429 CG2 THR 1430 C THP.

1431 0 THR 1432 N PHE 1433 CA PHE 1434 CB PHE 1435 CG PHE 1436 CD1 PHE 1437 CD2 PHE 1438 CEl PHE 1439 CE2 PHE 1440 CZ PRE 1441 C PHE 1442 0 PHE 1443 N ALA 1444 CA ALA 1445 CB ALA 1446 C ALA 1441 0 ALA 1448 N VAL 1449 CA VAL 1450 CB VAL 1451 CG1 VAL 1452 CG2 VAL 1453 C VAL 1454 0 VAL S1455 N ARG 1456 CA ARC 1451 CB ARG 1458 CC ARG 1-459 CO ARG 1460 NE ARG 1461 CZ ARG S1462 NHI ARG S1463 NH2 ARC 4 1464 C ARG 4 1465 0 ARG 4 1466 N ALA 4 1461 CA ALA S1468 CP ALA S1469 C ALA H 1410 0 ALA M 1411 N ARG H. 1412 CA ARG M 1413 CB ARC 4 1414 CG ARG 90 90 90 90 90 91 91 91" 91 91 91 91 91 91 ,91 .91 92 192 192 192 192 L92 192 192 132 192 192 192 193 193 193 193 193 193 193 194 194 194 194 194 194 194 194 194 194 194 195 195 195 195 195 196 196 196 196 196 196 196 191 191 19' 19" .9? 197 197 19- 19' 19" 19- 19B 198 199 196 1)s 192 199 199 199 21.494 25.944 40.460 1.00 15.30 20.310 26.366 41.226 1.00 18.33 21.869 26.984 29.390 1.00 10.48 22.516 24.011 3).612 1.00 17.97 23.024 23.222 40.428 1.00 17.12 23.262 24.460 28.563 1.00 18.62 24.621 24.018 28.253 1.00 18.64 24.183 23.686 26.746 1.00 23.05 26.243 23.417 25.218 1.00 28.15 26.802 22.032 25.502 1.00 29.3; 26.824 21.206 25.274 1.00 31.41 27.617 21.329 34.236 1.00 30.19 28.650 22.261 24.198 1.00 30.54 27.562 20.481 23.210 1.00 30.20 25.411 25.213 38.621 1.00 15.56 25.174 26.344 38.233 1.00 14.09 26.495 24.950 39.417 1.00 12.55 27.380 25.911 39.901 1.00 11.03 27.283 26.027 41.411 1.00 10.18 26.063 26.159 41.890 1.00 13.18 6 26.105 28.138 42.101 1.00 14.17 24.949 28.861 42.435 1.00 14.60 24.837 26.111 42.039 1.00 14.10 23.670 26.840 42.311 1.00 15.93 23.145 28.211 42.554 1.00 13.34 22.618 28.912 42.755 1.00 14.24 28.159 25.557 23.508 :.00 12.33 29.134 24.402 29.680 1.90 12.31 29.511 26.491 23.954 :.00 10.45 30.815 26.230 38.535 1.00 1.07 31.036 26.551 317.028 1.00 7.66 4 30.030 25.849 26.283 1.00- 5.4 32.399 26.130 36.529 1.00 7.11 31.688 27.182 39.383 1.00 1.05 4 31.370 28.369 39.425 1.00 7.20 3 32.685 26.682 40.113 1.00 8.39 1 33.487 27.511 40.961 1.00 5.90 S 33.421 21.133 42.421 1.00 6.97 4 :32.030 26.178 42.900 1.00 8.68 31.531 25.492 42.723 1.00 5.81 A 31.222 21.135 43.519 1.00 8.15 30.273 25.110 43.150 1.00 8.14 4 29.951 27.412 43.946 1.00 5.23 i 29.482 26.129 43.763 1.00 7.24 34.922 27.565 40.524 1.00 5.55 35.361 26.594 29.934 1.00 6.55 2 35.646 28.633 40.849 1.00 5.34 31.051 28.785 40.494 1.00 4.51 37.173 29.298 23.041 1.00 5.31 A 37.141 29.759 41.461 1.00 3.32 31.101 30.692 41.921 1.00 2.19 1 39.039 29.539 41.773 1.00 2.16 7 39.839 30.398 42.689 1.00 3.78 40.522 29.609 43.869 1.00 2.00 40.237 30.216 45.214 1.00 2.00 40.111 28.173 43.869 1.00 .304 '41.000 31.085 41.995 1.00 2.01 41.418 30.661 40.931 1.00 5.91 3 41.531 32.121 42.629 1.00 2.00 42.681 32.860 42.129 1.00 2.00 4 42.279 33.902 41.069 1.00 2.30 41.384 35.010 41.514 :.00 2.30 41.062 36.000 40.504 1.00 2.00 40.345 37.124 41.013 .00 2.41 40.269 38.323 40.517 1.00 2.30 40.846 38.550 29.351 :.00 2.00 39.163 39.339 41.193 1.00 4.02 43.374 33.489 43.362 1.00C 2.09 42.685 33.926 44.280 1.00 2.19 A 44.'10 33.490 43.399 :.OC 2. 03 45.415 33.996 44.550 1.OC 23 .41 46.420 22.903 45.072 1.00 2.30 46.241 25.326 44.442 1.CC 9 46.614 35.112 43.340 1.00 2.19 46.542 35.901 45.612 1.00 2.72 47.250 37.111 45.694 0C 3.38 46.226 38.304 45.572 !.OC 46.784 39.66 45.20 0 6.61 Thu Apr 25 12:27:47 1996 brf2lc .Pdb Thu AJpr 25 12:27:47 1996

ATOM

ATCOM

ATOM

ATCHOM

ATOM

ATCHOM

ATOM

ATCOM

ATOM

1475 CD ARC 1476 NE ARCG 1477 CZ ARCG 1418 NR1 ARCG 1479 NH2 ARG 1480 C ARC 1481 0 ARC 1482 N MET 1483 CA MET 1484 CB MET 1485 CG MET 1486 SD MET 1481 CE MET 1488 C MET 1489 0 MET 1490 N ALA 1491 CA ALA 1492- CB ALA 1493 C ALA 1494 0 ALA 1495 M GLU 1496 CA GLO 1497 CB GLU 1498 CG GLU 1499 CD GLU 1500 OEI GLU 1501 OE2 GLU 1502 C GLU 1503 0 GLU 1504 N PRO 1505 CD PRO 1506 CA PRO 1507 CB PRO 1508 CG PRO 1509 C PRO 1510 0 PRO 1511 N SEP.

1512 CA SEP.

1513 CB SEP.

1514 OG SEP.

1515 C SEP.

1516 0 SER 1511 N PHE 1518 CA PHE 1519 CB PRE 1520 CG PHE 1521 CD1 PHE 1522 CD2 PRE 1523 CE1 PHE 1524 CE2 PHE 1525 CZ PRE 1526 C PHE 1527 0 PRE 1528 N GLY 1529 CA GLY 1530 C CLYI 1531 0 CLY 1532 'N GLY 1533 .CA GLY 1534 C CLY 1535 0 GLY 1536 H PRE 1531 CA PRE 1535 CB PHE 1539 CG PHE 1540 CDI PHE 1541 CD2 PHE 1542 CEI PHE 1543 CE2 PRE 1544 CZ PRE 1545 C PHE 1546 0 PHE 1547 TP.P 1548 CA TP 1549 CB TRP 1550 CG TPP 1551 CD2 TP.P I 1552 CE2 TP.P 99 99 !99 1?9 .99 :99 199 230 200 200 200 200 200 200 200 201 201 201 201 201 202 202 202 202 202 202 202 202 202 203 23 203 203 203 203 203 204 204 204 204 204 204 205 205 205 205 225 235 205 235 205 205 205 206 206 206 206 2031 201 20i 201 209 208 238 208 2:8 208 238 208 238 20P 208 209 239 205 209 209 209 45.938 40.731 45.915 1.

46.306 42.120 45.519 46.187 42.662 44.363 1.

45.738 41.950 43.329 1.

46.417 43.954 44.181 1.

48.030 37.321 41.023 1.

47.555 36.916 48.058 1.

49.243 37.864 46.984 1.

50.015 38.096 48.191 1.

51.484 38.423 41.891 1.

52.311 37.271 41.346 1.

53.261 36.286 48.538 1.

52.284 34.915 48.812 1.

49.340 39.289 48.814 1.

49.074 40.314 48.228 1.

49.050 39.126 50.161 1 48.369 40.140 50.962 1 41.633 39.414 52.117 1 49.261 41.285 51.464 1 50.488 41.204 51.453 1 48.622 42.360 51.901 1 49.336 43.527 52.421 1 48.428 44.756 52.216 1 41.650 44.796 50.914 1 48.360 45.575 49.157 1 49.466 46.164 49.968 1 41.114 45.613 48.634 1 49.185 43.311 53.903 1 49.394 42.321 54.561 1 50.696 44.173 54.411 1 51.150 44.143 55.820 1 51.322 45.290 53.714 1 51.339 46.367 54.782 1 51.846 45.538 55.984 1 52.740 44.892 53.356 1 53.537 45.743 52.985 1 53.073 43.623 53.540 1 54.420 43.146 53.222 A4.674 41.764 53.868 55.093 41.356 55.224 54.686 43.060 51.696 55.632 43.660 51.152 53.818 42.309 51.031 53.901 42.014 49.624 53.911 40.573 49.390 55.073 39.862 !0.052 54.854 38.885 51.029 56.388 40.136 49.668 55.921 38.198 51.599 51.452 39.449 50.237 57.215 38.480 51.202 52.143 42.728 48.900 51.156 43.147 49.508 52.913 42.864 47.592 51.892 43.459 46.751 52.001 42.8355 45.367 *52.956 42.124 45.081 51.020 43.080 44.520 51.122 42.534 43.176 49.825 42.355 42.430 48.857 43.048 42.656 49.784 41.332 41.608 48.621 41.069 40.805 49.034 41.011 29.322 50.158 42.013 39.011 49.956 43.377 39.004 51.441 41.530 28.793 51.022 44.253 33.790 52.506 42.393 28.579 52.292 43.756 23.580 47.896 39.767 41.149 48.462 38.823 41.704 46.603 .39.780 40.878 45.766 38.625 41.073 44.302 38.919 40.811 43.505 39.313 42.011 43.15( 38.550 43.104 42.341 39.316 43.959 00 9.17 00 13.78 00 15.94 00 18.32 00 18. 00 5.53 00 8.08 00 5.53 00 4.85 00 3.13 00 4.67 00 9.73 00 2.41 .00 1.02 .00 6.42 .00 7.96 .00 10.65 .00 4.85 .00 12.36 .00 13.02 .00 15.12 .00 19.04 .00 23.13 .00 28.94 .00 31.22 .00 32.80 .00 30.41 .00 19.11 .00 20.41 .00 16.25 .00 15.32 .00 14.26 .00 13.02 .00 16.38 .00 12.03 .0O 15.28 00 8.98 1.00 11.79 1.00 11.87 1.00 12.48 1.00 11.88 1.00 11.24 1.00 10.89 1.00 8.76 1.00 8.70 1.00 12.81 1.00 11.19 i.00 11.00 :.oo 7.35 1.00 11.11 1.00 8.98 1.00 8.81 1.00 9.29 1.00 8.51 1.00 8.14 1.00 7.24 1.00 8.58 1.00 7.18 1.00 7.59 1.00 4.80 1.00 5.05 1.00 3.11 1.00 3.73 00 6.46 00 6.52 1.00 6.15 1-.00 9.68 ;.00 i.99 1.00 8.12 1.00 6.95 1.00 2.21 1.00 2.71 i.00 2.3C 00 00 4.79 1.00 4.76 00 2.6: 1.00 2.97 g 6 3 6 6 6 3 i 6 6 6 3 6 6

I

L

-51bref2lc.pdb Thu Apr 25 12:27:47 1996 a.

ATOM

ATOHM

ATOM

ATOHM

ATOM

ATCH

ATOM

ATcOM

ATCM

AT".2 AT~t

ATCM

AT&

ATCK

ATM

ATMO

ATM

AOM

ATC.

ATOI

AO

ATC

1553 CE3 TRP 2 1554 CD1 TP.P 2 1555 NE1 TRP 2 1556 CZ2 TPP 2 1557 CZ3 TRF 2 1558 CH2 TP.P 2 1559 C TRP 2 1560 TRP 2 1561 N SEP. 2 1562 CA SEP. 2 1563 CB SEP. 2 1564 00 SEP. 2 1565 C SER 2 1566 0 SER 2 1567 N ALA 2 1568 CA ALA 2 1569- CB ALA 1510 C ALA 1571 0 ALA 1572 N T.P 1573 CA T.P 1574 CB TP.P 1515 CG TP.P 1576 C02 TRP 1577 CE2 TP.P 1578 CE3 TP.P 1579 CD1 TP.P 1580 NE1 TP.P 1581 CZ2 TP.P 1582 CZ3 TRP 1583 CR2 TRP 1584 C TRP 1585 0 TRP 1586 N SEP 1587 CA SEP.

1588 CB SER 1589 00 SEP.

1590 C SEP.

1591 0 SER 1592 N GLU 1593 CA GLJ 1594 CB GLU 1595 CG GLU 1596 CD GLU 1591 OZl GLU 1598 OE2 GLU 1599 C GLU 1600 0 GLU 1601 N PP.0 1602 CD PRO 1603 CA PRO 1604 CB PRO 1605 CG PP.0 1606 C PRO 1607 0 PP.0 1608 N VAL 1609 CA VAL 1610 *CB VAL 1611 CGI VAL 1612 CG2 VAL 1613 C VAL 1614 C VAL 1615 N SEP.

1616 CA SEP.

1617 CE SEP.

1618 MG SEP.

1619 C SE? 1420 0 SE.

1621 N LWEU 1422 CA LE) 1623 CB LE'- 1624 CC LEU 1625 CD LE: 1626 CD2 LEt 1621? LEE: 1628 0 LEU -1629 N Lzu 1630 CA LEW 39 09 39 09 09 09 09 09' 10 10 10 i 0 10 1.0 I.0 211 211 212 212 212 212 212 212 212 212 212 212 212 212 212 212 212 213 212 213 213 214 214 214 2134 214 214 214 214 214 214 215 214 214 215 215 215 216 216 216 216 216 216 216 216 21C 21' 216 217 218 218 218 218 2.7 218 218 218 218 213 218 218 219 219 43.4 42.

42.2 41.

42.

46.

45.

44.

45.

44.

45.

43.

44.

42.

41.

40.

29.

39.

38 28 29 28 !1 28 21 42 43 41 42 42 40 41 42 4; 3 41 40 41 42 4 4 4 3 3 45 37.234 43.446 1.0 908 40.586 42.240 '.C 11 40.554 43.396 '.0 825 36.309 45.148 i.0 933 36.129 44.616 1.

131 31.513 45.461 222 31.604 40.033 1.

556 31.)69 23.920 1.

235 36.335 43.412 650 2!.269 !3.533 1.

903 34.002 43.337 1.

683 33.363 40.660 1.

511 34.966 33.515 1.

564 35.689 23.398 832 32.924 17.735 895 33.423 26.757 1.

639 32.571 35.768 1.

893 32.558 37.567 1.

160 32.175 38.106 1.

736 32.263 37.014 1.

191 31.433 27.134 1.

441 31.434 36.993 1.

123 32.165 36.942 061 33.399 33.030 1.

.529 34.597 37.547 1.

.867 32.063 33.37 .566 33.576 15.867 1 .850 34.680 .5.219 1 .811 35.470 %3.259 1 .162 33.921 43.167 1 .640 35.111 13.671 1 .340 30.012 21.771 1 .262 29.696 -7.043 1 .771 29.145 -8.598 1 .222 27.747 3.642 1 .041 27.183 40.045 1 .661 27.131 40.391 1 .303 26.959 27.738 1 .265 21.471 37.293 1 .644 25.118 37.441 1 .694 24.911 25.660 1 .307 23.662 36.198 1 .101 23.79 34.813 1.249 24.291 33.640 1.627 25.337 23.001 0.218 23.631 23.301 9.550 24.814 27.680 9.793 24.625 33.864 8.301 25.031 21.258 7.959 25.363 .5.868 7.068 24;965 33.059 6.155 25.896 21.290 6.430 25.44' 35.937 6.37E 23.609 23.231 6.664 22.654 21.525 5.440 22.553 33.172 4.669 22.346 1).434 4.740 21.829 43.924 5.569 20.568 41.016 5.226 22.929 41.918 3.261 22.334 3.259 3.001 24.039 3).445 22.25 21.913 33.937 20.952 22.247 23.766 2C.549 22.1! 3".3C2 29.61C 22.170 3'.004 !C.127 21.282 39.6C1 !C.424 2C.081 "?.641 29.067 21.791 43.224 28.222 2C.fl. 41.1C2 28.605 21.295 42.566 21.991. 20.615 43.789 23.2C: 4,3. 1 3.696 28.64- 23.135 "5.053 26.12': 2.208 43.903 26.306 22.335 43.693 25.958 2C.114 4).870 24.486 20.164 4.760 21 0 2.00 00 2.25 20 2.00 00 4.70 o0 !7 )0 4.57 30 4.74 00 3.11 00 3.26 30 4.92 00 5.26 00 4.60 00 3.40 00 9.36 00 13.86 00 10.41 00 10.30 30 10.37 i 00 11.25 00 14.78 00 9.47 00 7.74 00 3.05 00 4.98 00 2.00 .00 2.33 00 2.00 .00 2.00 .00 2.00 .00 4.55 .00 2.47 .00 2.13 .00 8.93 .00 8.63 .00 11.16 .00 11.60 .0O 12.78 .00 13.18 .00 12.67 .00 14.82 .00 12.59 .00 12.29 .00 16.31 .00 23.12 .00 27.82 00 29.07 .00 27.91 00 11.86 00 11.26 1.00 11.02 1.00 12.93 .00 11.49 1.00 9.49 .00 12.12 1.00 ).78 1.00 12.44 1.30 7.47 1.00 7.0C5 1.00 8.24 1.33 9.46 :.00 6.68 1.0 9.31 0 10.20 1.00 8.41 1.00 9.41 0.CO 13.1 00 13.22 30 10.91 10 3.60 30 10.92 30 11.2 00 .2 3.D0 6.92 ;0 3.18 30 1..91 .00 12.22 30 14.15 30 13.92 i i i .3 4 s i i 3 6 6 i 6 3

A

I

i -52bref2lc.pdb Thu Apr 25 12:27:47 1996 22

S

a *5

ATOM

ATOHM

ATCM

ATOM

ATOHM

ATOM

ATOCM

ATCM

ATCK

ATOM

ATCM

ATOM

ATCOM

ATCHO

ATOM

ATCH

ATOM

ATCM

ATOM

ATOMn 1631 CB LEU 1632 CG LEU 1633 C1 LEU 1634 C;2 LEU 1635 C LEU 1636 O LEU 1637 N THP.

1638 CA THP.

1639 CB THP.

1640 OC1 TP.

1641 CC2 TRPH.

1642 C THR 1643 0 THP.

1644 N THP.

1645 CA TH.

1646 CS THP.

1647 OC1 THP.

1648 CG2 TH.

1649 C THR 1650 0 THR 1651 N TYP 1652 CA TYP.

1653 CS TYP 1654 CC TYP 1655 C01 TYR 1656 CE1 TYF.

1657 CD2 TYF.

1658 CE2 TYF 1659 CZ TY 1660 CH. TY? 1661 C TYP.

1662 0 TYP.

1663 N SEP.

1664 CA SEP.

1665 C3 SEP 1666 OG SEP.

1661 C SEP.

1668 SER 1669 N CYS 1670 CA CYS 1671 C CYS 1672 S CY 1673 C3 CY: 1674 SG CYS 1675 N HIS 1676 CA HI:s 1677 3 H:3 1678 SG H1: 1679 :02 H:- 1680 D sRI:s 1681 r1 aI-s 1682 NE2 RIS 1683 C RIHS 1694 RS 1685 N PF.

1686 CA PH' 1687 C3 PH.E 1688 C PE 1689 :D1 PH! 1690 ZD2 PFE 1491 C1 PE 1692 :r2 PH! 1693 PHE 1694 P-I 169! F-- 1696 N 1697 CA 1698 L 1699 SL 1700 N P.R: 101 CD PP: 1702 CA P.: 1::2 '5 P: 1104 CC P.: 1105 F P 1703 F.: 1706 1101 N 1708 CA LE 219 219 219 219 219 219 220 220 220 220 220 220 220 303 303 303 303 303 303 303 304 304 304 304 304 304 304 304 304 304 304 304 305 305 305 305 305 305 306 306 306 306 306 306 301 307 307 301 30? 308 308 308 3038 308 308 300 308 308

Z

309 138 309 !10 30 3' 310 211 )l9 310 210 31i 31) 23.861 23.819 22.857 25.208 24.080 24.378 23.501 23.057 22.289 22.030 23.076 22.111 21.196 67.975 67.750 66.400 65.988 66.595 67.7371 68.525 66.882 66.756 65.306 64.839 64.311 E4.002 65.030 64.721 64.208 63.886 67.182 67.271 61.474 67.856 69.204 70.226 66.736 66.490 66.093 64.968 64.970 65.609 63.738 63.103 64.186 64.015 65.038 64.853 44*.068 65.704 65.467 64.478 62.576 61.811 62.161 60.81± 50.481 60.530 51.140 59.935 61.152 59.942 60.54 60.68 E1.48 !9.14 59.51 58.21 57.80 57.'9 58.48 56.64 16.58 95 5.29 54.38 55..2 54.14 18.372 40.209 18.429 23.736 19.303 37.941 23.096 20.226 42.248 1.

19.295 42.986 21.329 42.692 21.472 44.068 1.

22.744 44.250 23.33, 42.9671 23.C704 45.099 1 20.325 44.368 1 ZC.053 43.582 42.354 64.372 1 41.634 65.597 1 42.008 66.344 43.329 65.963 1 42.033 67.861 1 40.103 65.280 1 39.342 65.838 39.690 64.343 38.22. 63.973 1 27.526 64.148 31.*-37 65.585 39.123 66.072 39.24 671.389 36.-2: 66.486 37.-1 7.809 38.21:: 68.261 3a.359 69.598 38.065 62.554 39.024 61.804 36.819 62.201 36.442 60.843 35.705 60.838 36.516 61.4271 35.557 60.273 34.433 60.754 36.051 59.218 35.364 58.619 35.039 57.131 35.702 56.302 36.5.33 8.889 36.836 60.556 34.026 56.808 22.604 !5.459 32.5:? !5.083 21.13 55.746 3C.

1 24 !5.420 30.723 56.734 29.443 5.976 29.956 !6.192 33.V-6 55.236 32.93 56.188 33.36 53.980 22.2! 53.6471 33.3*93 !2.161 34.55' 51.891 35.C:6 50.147 35.482 52.738 36.422 50.448 3f.-T: 52.445 7 317.224 1.307 9 31.2:- '3.849 3G.;424 !3.32 6 3C.33 34.691 7 29.23: !4.922 23.)-4 !4.098 6 29.765 53.3:6 1 27.C;6 54.233 6 26.5l2 '4.742 E 27.41 !3.354 !3.449 6 25.47 ±3.857 5 28.C' 53.909 S28.241 !3.13t 2 28.1:! 55.16: 5 '5..756 00 13.95 00 16.57 00 18.05 00 15.67 00 12.96 .00 12.64 .00 12.52 .00 10.21 .00 10.53 .00 14.4' .00 13.55 .00 11.61 .00 13.03 .00 11.41 .00 9.49 .00 10.05 .00 12.85 .00 12.80 .00 9.93 .00 9.371 .00 10.11 .00 3.53 .30 7.06 .30 7.97 .30 4.80 .00 3.80 .OC 6.93 .00 4.43 .00 4.88 .00 10.24 00- 8.33 00 11.69 00 8.34 00 9.43 1.00 13.12 00 18.03 L.00 10.05 L.00 10.34 1.00 8.05 00 5.52 :.0O 6.70 i.00 6.69 :.00 6.36 .00 8.87 !.00 6.09 0C 7.50 30 11.44 14.32 00 16.017 00 16.54 0o 14.82 1.00 17.24 1.00 9.06 .00 11.93 :.00 3.50 1.00 6.63 1.30 1.92 1.3C 5.48 1.2 6.64 1.20 9.42 1. 0 3.48 0 3.15 6.33 1.0 5.44 50 ).1

N.~C

.C 5.25 1.0C 5.33 .t 6 .57 1.00 8.19 C 460 2.?C 3.i4 8.55 .32 3 10.25 .53 i0 12.27 .58 1 6 i i 7 r i r r r

S

o t i j r

Z

3 1 0 1 6 i i -53brf£2lc.pdb Thu Apr 25 12:27:47 1996 23 ATOM 1709 C3 LEU 311 53.834 28.437 !7.080 1.00 4.94 ATOM 1710 CC LEU 311 52.837 21.2771 57.127 1.00 5.,4 ATOM 1711 C31 LEU 311 51.524 27.802 51.619 '.00 .26 ATOM 1712 C32 LEU 311 52.684 26.580 !5.781 1.00 5.12 ATOM 1713 C LEU 311 54.346 30.580 56.002 1.00 ATOM 1714 C LEU 311 53.586 31.411 55.540 1.00 4.76 ATOM 1715 THP. 212 55.390 30.898 16.141 1.00 !.21 ATOM 1716 CA THR 212 !5.680 32.285 51.015 1.00 7.42 ATOM 1717 CB THP. 212 54.712 32.732 58.256 1.00 7.> ATOM 1718 CG1 THR 312 54.898 34.144 58.416 1.00 1:.16 ATOM 1719 CC2 THP. 312 !5.115 31.95: 59.526 1.00 6 ATOM 1720 C THR 312 57.168 32.342 57.444 1.00 6.58 ATOM 1721 0 THR 312 57.868 31.352 51.215 1.00 7.15 ATOM 1722 N TRP 313 51.641 33.477 17.979 1.00 5.?6 ATOM 1723 CA TRP 313 59.050 33.653 58.382 00 4.32 ATOM 1724 C3 TRP 313 59.294 35.032 58.992 1.00 2.13 ATOM 1725 CG TRP 313 58.931 36.213 58.158 1.00 5.28 ATOM 1726 CD2 TRP 313 59.685 36.779 57.066 1.00 6.34 ATOM 1727 CE2 TRP 313 59.026 31.968 56.682 1.00 4.38 ATOM 1728 CZ3 TRP 313 60.845 36.403 56.382 1.00 3.66 ATOM 1729 CD1 TRP 313 57.883 37.044 58.359 1.00 4.69 ATOM 1730 NE1 TRP 313 51.933 38.103 51.488 1.00 .C0 ATOM 1731 CZ2 TRP 313 59.484 38.784 55.656 1.00 4.75 ATOM 1732 CZ3 TRP 313 61.301 237.222 !5.350 1.00 i.62 ATOM 1733 CH2 TRP 313 60.618 38.398 55.004 1.00 5.-2 ATOM 1734 TRP 313 59.605 32.519 59.389 30 5.38 ATOM 1735 TRP 313 58.931 32.186 (0.359 1.00 ATOM 1736 N VAL 314 60.841 32.216 59.139 '.CO ATOM 1737 CA VAL 314 61.533 31.286 60.013 1.00 6..7 ATOM 1738 C3 VAL 314 62.145 30.110 19.249 1.00 4.B2 ATOM 1739 CCI1 VAL 314 62.868 29.204 60.190 1.00 S.24 ATOM 1740 C2 VAL 314 61.099 29.333 58.536 1.00 3.95 ATOM 1741 C VAL 314 62.637 32.192 60.499 1.00 3.62 ATOM 1742 0 VAL 314 63.512 32.562 53.730 1.00 11.03 ATOM 1743 N CYS 315 62.516 32.672 61.124 1.00 9.61 ATOM 1744 CA CYS 315 63.524 33.567 62.250 1.00 13.57 ATOM 1745 C CYS 315 64.417 32.948 63.293 1.00 10.10 ATOM 1746 0 CYS 315 64.191 31.825 63.748 1.00 11.89 ATOM 1747 C3 CYS 315 t2.905 34.861 62.757 1.00 13.12 ATOM 1748 SG CYS 315 62.116 35.824 (1.399 1.00 34 ATOM 1749 N LYS 316 65.402 33.724 63.715 1.00 :1.33 ATOM 1750 CA LYS 316 66.381 33.242 64.650 1.00 1.93 ATOM 1751 C3 LYS 316 67.301 32.320 63.860 1.00 1'.41 ATOM 1752 CG LYS 316 68.200 31.444 64.631 1.00 12.22 ATOM 1753 CD LYS 316 69.242 30.818 63.708 1.00 13.2 ATOM 1754 CE LYS 316 10.213 31.865 63.178 1.00 17.21 ATOM 1755 NZ LYS 316 71.029- 22.461 (4.288 1.0C ATOM 1156 C LYS 316 67.141 34.482 65.092 3C ATOM 1757 LYS 316 67.192 35.463 (4.359 1.00 ATOM 1758 N PRO 311 67.592 34.516 6S.355 1.00 1.25 ATOM 1159 CD PRO 317 67.284 33.517 67.471 1.00 ".28 ATOM 1760 CA PRO 317 68.344 35.662 66.855 1.00 1:.51 ATOM 1761 CB PRO 317 68.365 35.412 68.348 1.00 4.33 ATOM 1762 CG PRO 317 68.381 33.979 68.426 00 1.21 ATOM 1763 C PRO 317 69.773 35.714 66.285 1.00 14.13 ATOM 1764 PRO 31- 70.532 34.732 66.339 1.00 .4.11 S* ATOM 1765 GLN 318 "0.105 36.867 65.111 00 1-.42 ATOM 1766 'CA GLN 318 71.418 37.137 65.144 1.00 ATOM 1767 CS GLN 318 71.369 38.436 64.326 1.00 1.12 ATOM 1768 CC GLN 318 72.01C 39.335 62.946 1.00 1.24 ATOM 1169 CD GL% 318 71.602 39.462 (2.064 0 ATOM 177"0 5-1 GLS 319 "0.734 39.341 61.189 1.00 ATOM 1771 :2 GLN 318 12.199 40.642 62.305 1.00 -1.42 ATOM 11772 C GLN 318 72.273 37.386 66.360 1.00 2S ATOM ^173 CL% 21, 71.906 38.22 7';.114 1.0c 24 ATOM 11774 TlP. 403 70.252 35.791 55.614 1.0OC ".il ATOM 1775 CA THR 403 69.393 36.052 54.455 1.00 12.-S ATOM 1776 C5 TE? 403 68.336 34.931 54.252 1.0C ATOM 1177 301 THR 403 68.911 33.651 54.627 1.00 1..i ATOM 178 C=2 TR 402 67.869 .4.381 !2.148 1.0 1:.25 ATOM 1119 C TH? 40. 68.751 31.411 54.551 1.0C .1.12 ATOM 1780 THR 402 69.149 38.341 53.757 1.00 I:.

3 ATOM 1-81 TY? 404 6.-8 3-.0)4 55.454 CC ATOM 1-82 CA TYP. 404 67.195 39.04: 55.682 .00 13 ATOM 17S3 C5 TYP. 404 65.698 39.11:. 55.366 C 2.26 ATOM 1784 C. TYR 404 65.333 38.96. 52.910 1.0CC .42 ATOM 1785 CCI TYR 404 65.036 37.17 52.377 3C 2:.2 ATOM 1766 CEI TYR 404 64.723 37.54. 12.042 1.OC 1.00 -54brzf21c.pdb Thu Apr 25 12:27:47 1996 24 ATOM 1781 CD2 TYR 404 65.299 40.071 !3.050 1.00 2.00 ATOM 1798 CE2 TYP. 404 64.992 39.918 1L.710 1.00 2.00 ATOM 1789 CZ TYP. 404 64.709 38.650 51.219 1.00 2.53 ATOM 1790 OH TYR 404 64.447 38.463 49.891 ;.00 6.21 ATOM 1791 C TYP. 404 67.374 39.373 !7.169 L.00 6.87 ATOM 1792 0 TYP. 404 61.459 38.47 15.006 1.00 5.71 ATOM 1793 N SER 405 67.453 40.653 57.500 1.00 7.44 ATOM 1794 CA SEP 405 67.581 41.068 18.894 1.00 7.96 ATOM 1195 C3 SEP. 405 68.842 41.887 19.094 1.00 9.81 ATOMC 1796 OG SEP. 405 69.985 41.082 !3.888 1.00 14.61 ATOM 1797 C SEF. 405 66.332 41.863 19.305 1.00 10.09 ATOM 1798 0 SER 405 66.154 43.047 58.975 1.00 10.03 ATOM 1799 N CYS 406 65.466 41.198 60.046 1.00 10.45 ATCM 1800 CA CYS 406 64.220 41.789 60.452 1.00 10.00 ATOM 1801 C CYS 406 64.192 42.035 61.938 1.00 10.98 ATCM 1802 0 CYS 406 64.900 41.386 62.709 1.00 12.25 ATOM 1803 CB CYS 406 63.096 40.827 60.107 1.00 12.32 6 ATCH 1804 SG CYS 406 63.277 39.951 58.514 1.00 12.21 ATOM 1805 N HIS 407 63.363 42.987 62.332 1.00 10.98 ATOM 1806 CA HIS 407 63.162 43.317 63.721 1.00 8.89 6 ATOM 1807 CB HIS 407 64.007 44.542 64.165 1.00 11.52 6 ATOM 1808 CG HIS 407 63.719 45.803 63.370 1.00 12.77 ATOM 1809 CD2 HIS 407 64.324 46.233 62.204 1.00 11.11 ATOM 1810 ND1 HIS 437 62.968 46.832 63.812 1.30 10.97 ATOM 1811 CE1 HIS 407 63.025 41.837 62.954 1.00 10.32 ATOM 1812 NE2 K S 407 63.840 47.499 61.969 1.00 10.00 ATOM 1813 C H.IS 407 61.687 43.614 63.801 :.00 3.26 ATOM 1814 0 HIS 407 61.078 43.935 62.789 1.00 10.54 ATOM 1815 N PHE 438 61.099 43.443 64.976 1.30 7.42 ATCOM 1816 CA PHE 408 59.690 43.746 65.168 1.00 6.36 ATCHOM 1817 CB PHE 408 59.281 43.636 66.643 1.00 5.63 ATOM 1818 CG PHE 408 59.441 42.280 67.218 1.00 3.30 TOM 1819 CD1 PHE 408 59.675 42.125 68.562 1.00 4.11 s SATOMCH 1820 CD2 PHE 408 59.411 41.158 66.409 1.00 4.22 A ATOM 1821 CE1 PHE 408 59.888 40.882 69.095 1.00 2.80 4 ATOM 1822 CE2 PHE 408 59.626 39.885 66.935 1.00 4.80 A ATOM 1823 CZ PHE 408 59.866 39.151 68.282 1.00 4.71 i ATOM 1824 C PHE 408 59.459 45.185 64.736 1.00 6.02 A ATOM 1825 0 PHE 408 '60.370 46.018 64.744 1.00 8.84 ATOM 1826 N GLY 409 58.231 45.463 64.347 1.00 4.91 1 ATOM 1827 CA GLY 409 57.868 46.791 63.936 1.00 2.33 ATOM 1828 C GLY 409 56.494 46.954 64.509 1.00 2.02 ATOM 1829 0 GLY 409 55.996 46.065 (.5.196 1.00 4.33 6 ATOM 1830 N PRO 410 55.879 48.100 64.299 1.00 2.00 ATOM 1831 CD PRO 410 56.497 49.286 63.693 1.00 2.98 z ATOM 1832 CA PRP.0 410 54.544 48.397 64.188 1.00 3.72 z ATOM 1833 C2 410 54.276 49.754 64.166 1..30 6.67 ATOM 1834 CG PP. 410 55.623 50.390 64.195 1.00 6.29 ATOM 1835 PP.0 410 53.521 47.367 64.313 1.00 7.04 ATOM 1836 0 PP.0 410 52.831 46.752 65.137 1.00 8.58 ATOM 1837 N LEU 411 53.471 47.165 62.987 1.00 6.97 7 ATCHM 1838 CA LEO 411 52.544 46.233 62.329 1.00 5.66 ATCHM 1839 CB LEU 411 52.254 46.674 60.898 1.00 8.28 a ATOM 1840 CG LEZ 411 51.310 47.803 (0.553 :.00 11.17 1 ATOM 1841 CD1 LEU 411 50.007 47.519 61.244 1.00 15.07 ATOM 1842 CD2 LE3 4:1 51.888 49.156 60.961 1.00 14.05 z ATOM 1843 C LEO 411 "53.052 44.831 62.192 1.00 4.04 ATOM 1844 "0 LEV 411 52.365 43.870 62.481 1.00 2.78 ATOM 1845 N THR 412 54.231 44.705 61.643 1.00 3.16 7 ATOM 1846 CA THR 412 54.749 43.388 61.431 1.00 2.09 ATOM 18.47 CB THR 412 53.985 42.829 60.244 :.00 2.00 ATOM 1848 G01 THR 412 54.152 41.413 60.166 1.00 4.34 ATOM 1849 CG2 THR 412 54.411 43.523 58.916 2.00 ATOM 1850 C T.R 412 56.252 43.565 61.220 :.30 2.54 ATOM 1851 412 16.722 44.67. .1.376 1.SC 2.1l ATOM 1852 TP.?P 413 57.002 42.490 60.964 1.OC 3.36 ATOM 1953 CA 7P.? 412 58.468 42.57) 60.747 0 4.26 ATOM 1854 CB 412 59.002 41.293 60.115 1.OC 3.65 ATOM 1855 CG TP.P 412 58.912 40.078 60.909 00 2.26 6 ATOM 1856 CC2 T.P? 41 59.722 39.734 (2.023 :.3C 4.36 ATOM 1857 CE2 TP.? 413 59.314 38.413 62.398 1.00 1.99 ATOM 1858 CE! TP. 413 60.?12 40.409 62.745 1.00 5.37 ATOM 1859 CC1 TR? 412 5. 12: 39.011 60.667 :.oC 2.3 ATOM 1860 NEl 412 58.395 37.998 (1.546 0C 2.14 ATOM 1861 C22 TP.? 59.975 37.766 63.459 1.0C 7.15 ATOM 1862 CZ3 TP.? 412 61.312 39.764 6:3.801 1.0C 7.56 ATCHOM 1863 C2 TP.? 412 60.941 38.451 6.1.152 ,C 11 ATOH 1864 C TRP. 412 58.960 43.720 59.832 1.00 5.50 br=f21c.pdb Thu Apr 25 12:27:47 1996

ATOM

ATOt ATOt

ATO

ATOI

1865 TRF 4 1866 N VAL 4 1867 CA VAL 4 1868 C3 VAL 4 1869 CG1 VAL 4 1870 CG2 VAL 4 1811 1 VAL 4 1812 VAL 4 1873 CYS 4 1874 CA CYS 4 1875 CYS 4 1976 C CYS 4 1977 C3 CYS 4 1978 SG CYS 4 1879 N LYS 4 1880 CA LYS 1381 -C3 LYS 1882 CS LYS 1883 CD LYS 1884 CZ LYS 1885 NZ LYS 1886 LYS :887 1 LYS 1888 PRO 1989 PRO 1890 :A PRO 1891 :3 PRO 1892 C: PRO 1993 PRO 1894 O PRO 1895 GLN 1896 CA GLN 1897 C3 GLN 1898 CG GLN 1899 CD GLN 1900 OE1 GLN 1901 t-E2 GLN 1902 C GLN 1903 T GLN 1904 N LYS 1905 :A LYS 1906 :3 LYS 1907 :3 LYS 1908 LYE 1909 :T LYS 191C NZ LYS 1911 LYS :912 LYS 1913 PHE 1914 :A PHE 1915 :3 PHE 1916 :3 PHE 1917 1:1 PRE 1918 :32 PHE 1919 =I PEE 1920 1:2 PHE *921 :Z PHE 1922 "C PRE 1923 PHE 1924 GLU 925 :A GLU' -926 :3 GLU 1927 :3 GLu 1529 GL: 193C :12 GLU S131 GLG .132 GLJ 933 SER 534 SER :935 :3 SER :936 SER S -33 3SER 4 .233 SER 4 ?39 LYS M "940 LYS 1 19-1 LYS 1942 LYS 13 14 14 14 14 14 14 14" 15 15 15 15 415 415 116 416 416 416 416 416 416 416 416 417 411 417 417 417 411 411 418 418 418 418 418 418 418 418 418 510 510 510 510 510 510 510 510 510 511 511 511 511 511 511 511 511 511 511 512 512 512 512 512 512 512 512 512 51.

513 113 513 514 514 514 514 58.:87 44.350 19.115 1.

60.273 43.923 59.813 60.904 44.921 18.957 1 61.31 46.289 59.660 1.

62.:93 41.012 59.029 1.

!9.789 41.111 59.547 1.

62.242 44.340 18.533 63.183 44.296 19.303 1.

62.296 43.820 17.314 63.513 43.222 16.809 1.

64.238 44.007 15.767 L.

63.114 44.949 55.189 1.

63.207 41.882 56.222 62.067 41.071 57.341 1.

65.484 43.622 55.581 1.

66.341 44.197 54.585 1.

67.176 45.349 55.135 1.

66.482 46.235 56.144 1.

66.618 45.629 57.541 1.

65.851 46.404 58.599 1.

66.292 45.888 19.937 1.

67.234 43.008 54.218 I, 67.523 42.187 55.175 1 67.573 42.817 52.990 67.231 43.561 51.771 1 66.434 41.684 52.671 1 68.394 41.6471 1.144 1 48.247 43.047 50.780 69.845 41.868 53.221 1 10.361 42.990 53.325 1 70.400 40.762 53.100 1 11.753 40.741 54.209 1 71.933 39.562 55.165 1 71.948 39.963 56.620 I 71.580 38.823 57.530 1 71.377 37.668 57.098 1 11.478 39.131 58.807 1 12.660 40.583 52.990 1 12.470 39.656 !2.172 36.636 45.747 96.455 36.983 44.821 97.554 37.004 45.503 S8.958 37.194 44.729 100.099 39.382 44.7086 99.984 40.149 44.388 101.309 40.281 42.907 101.710 36.039 43.642 S7.542 26.117 42.117 93.413 3!.089 43.650 96.604 34.201 42.501 96.453 32.903 42.833 95.120 31.969 41i646 95.592 32.410 40.353 95.362 30.594 41.a06 95.735 31.630 39.235 95.279 29.738 40.690 95.653 3C.271 39.394 95.424 35.064 41.629 95.554 35.406 40.483 95.913 35.416 42.200 94.392 36.244 41.509 93.406 36.536 42.391 92.172 37.498 41.754 91.075 36.851 40.687 90.101 40.50- :3.936 35.865 40.011 90.501 3 .5.01 41.181 94.162 17.536 40.023 S4.161 31.984 42.161 94.930 -9.134 42.00C. 5.745 39.534 43.314 96.443 40.319 43.054 91.594 2".122 43.817 -I.775 -0.041 40.023 3.8346 28.C56 40.844 17.573 37.02- 39.792 83.568 36.839 40.12: 9~.605 3 .25E 41.16'5 100.627 00 i.06 0 6.50 00 6.63 00 '.88 00 6.76 00 3.37 30 9.59 00 11.73 00 9.75 00 9.15 00 1 00 9.05 00 8.76 00 3.11 00 14.13 1- 00 7.88 30 3.50 o 00 14.71 00 19.54 S 00 23.24 6 00 23.14 4 .00 21.08 .00 12.10 .00 10.95 .00 12.45 .00 11.38 .00 11.76 .30 10.58 .00 11.41 .00 14.43 .00 14.95 .00 15.69 .00 16.01 .00 15.85 .00 13.51 .00 16.21 .00 16.54 .00 16.18 00 17.91 1.00 20.26 1.00 20.08 1.00 22.39 00 22.50 i.30 24.41 1.00 24.33 1.00 25.09 1.00 21.46 30 21.11 30 20.71 .0 20.62 00 18.81 1.00 17.03 1.00 17.36 1.00 17.10 30 19.23 :.00 16.04 1.3C 20.41 1.00 11.16 1.oC 11.52 .3 16.93 i.00 17.14 .2C 18.20 1.31 20.73 ;0 28.00 1.32 20.11 :c 29.86 30.21 1.C 15.96 ;C 16.76 13.17 :C 12.13 30 12.70 13.07 12. :C 14.35 XL 11.94 7.59 OC .11 1 9 *9 -56breD: ATOH ATOM

ATCH

ATOM

ATOHM

ATOM

ATOH

ATOM

ATCH

ATOM

ATCM

ATOM

ATCM

ATOM

ATCH

ATOM

ATCM

ATOM

AOM

Lc.pdb 1943 CD LYS 1944 CE LYS 1945 NZ LYS 1946 C LYS 1947 O LYS 1948 N ALA 1949 CA ALA 1950 CB ALA 1951 C ALA 1952 0 ALA 1953 N ALA 1954 CA ALA 1955 CB ALA 1956 C ALA 1957 0 ALA 1958 N LE 1959 CA LEU 1960 -CB LEU 1961 CG LEU 1962 CD1 LEU 1963 CD2 LE 1964 C LEU 1965 0 LEUO 1966 N LEU 1961 CA LE 1968 CB LEO 1969 CC LEU 1970 CD1 LEU 19171 CD2 LEO 1972 C LEU 1913 O LEU 1974 N ALA 1975 CA ALA 1976 CB ALA 191177 C ALA 1978 0 ALA 1979 N ALA 1980 CA ALA 1981 CB ALA 1982 C ALA 1983 0 ALA 1984 N ARG 1985 CA ARG 1986 C AP.CG 1987 CG ARG 1988 C) ARGC 1989 NE ARC 1990 CZ AP.G 1991 N141 ARG 1992 NN2 ARC 1993 C ARG 1994 0 ARG 1995 N CLY 1996 CA LY 1997 C CLY 1998 O CLY 1999 N PRO 2000 *CO PRO 2001 CA PRCO 2002 CS PRO 2003 CC PRO 2004 C PRC* 2005 3 PRO 2006 N SLU 2007 A GL 2009 CS GL' 2009 CS GLZ 2010 CD GL' 2011 -E1 GL 2012 CL' 2012 C GLU 2014 GL 2015 N GL 2016 CA CL' 2017 CS GL C 2018 CG CGL 2019 CD GLZ 2020 OE1 GCL i14 514 114 314 514 515 .15 515 516 516 516 516 516 511 511 517 511 517 511 5?1 518 518 518 518 518 518 516 518 !18 519 319 519 519 519 519 3520 520 520 520 520 521 521 521 52 521 521 521 521 521 521 522 522 522 522 523 523 523 523 523 523 523 524 524 524 524 524 524 524 524 524 525 121 525 52.- 52!.

36.388 41 36.314 42 35.665 42 37.621 38 31.841 31 37.138 38 36.816 3 36.181 3 38.165 3 38.176 3 39.241 3 40.562 3 41.457 3 41.205 3 41.690 3 41.226 3 41.809 3 41.445 3 42.141 3 41.717 3 41.754 3 41.271 3 42.009 3 39.997 3 39.297 3 731.845 3 37.614 3 36.802 36.951 39.339 39.185 39.5571 39.603 39.310 40.908 41.733 41.0471 42.228 !42.169 42.579 41.764 43.834 44.407 45.499 45. 1. 7 45.51' 45.512 46.279 47. 251 45.888 45.018 44.0842 45.710 46.33E 47.851 48.288 18.6712 48.070 50. Zs 50.429 49.27 50.96E 50.499.

52.222 53.121 54.289 55.4871 55.201 54. 91C 55.343 53.672 53.705 .W6S- 22 53.557 53.851 52.595 52.474 .093 ICL.842 .393 102.539 .215 103.798 8.443 97.959 1.435 98.620 8.401 96.716 7.117 96.038 1.366 94.719 6.299 95.806 068 95.920 7.026 95.494 6.478 95.204 7.533 94.614 5.872 96.419 4.751 96.353 6.399 97.530 6.040 98.743 6.874 99.947 8.193 100.158 9.171 99.108 8.683 101.519 4.634 98.992 3.751 99.4371 4.433 93.648 3.177 98.8571 3.467 99.213 2.131 100.7713 14.965 100.936 32.519 10 12.158 9 10.955 9 32.623 9 31.726 9 32.481 9 30.949 9 31.215 29.935 9 29.064 28.165 28.212 27.430 28.352 27.633 29.484 29.950 30.871 30.373 29.452 28.957 28.889 26.343 26.022 25.592 24.315 24.378 25.6771 23.533 22.203 23.469 22.304 21.315 24.731 25.61? 24.161 25.85± 25.979 24.958 23.507 22.603 23.263 25.532 .24.359 25.564 26.411 26.334 25.543 25.162 23.956 1.495 7.733 1.9719 6.505 5.342 4.0712 5.209 94.311 .6.068 '6.115 97.31 94.865 94.339 94.449 53.322 S2.652 92.441 93.500 ?4.854 95.464 94.843 96.620 93.866 95.032 93.022 93.500 93.549 93.891 93.225 92.92 93.18 92.20 92.48 92.74 91.98 93.18 a2.82 93.85 93.73 94.25 93.41 91.42 91.01 S3.74 89.44 86.44 6';.14 5.3 8:.9! Thu Apr 25 12:27:47 1996 26 00 .00 30 3.28 00 1 .1 .00 13.26 >.00 10.10 030 9.26 >.00 10.3? 00 a.Z3 00 7.78 :.00 8.76 :.00 1.65 00 f.46 :.00 1.97 !.00 8. 2 :.oo a.04 .0 5.52 1.00 3.15 00 4.:3 :.00 9.66 .00 4.29 .00 7.?9 00 10.33 00 3.49 .00 .00 00 5.53 30 2.48 .30 00 8.37 1.00 .1U !.00 11.23 *.00 13.55 !.00 12.14 1.00 15.14 :.00 15.55 00 17.93 .00 1.21 1.00 20.83 .00 19.53 .00 13.29 00 90.0 1.00 90. :0 .00 90. 0 9. :2 .00 93.10 .00 90. 0 1.00 1.00 90.:0 00 92. 0 00 90.:0 >oo0 :0 .00 93.:C 9 30 9;.,C 5 00 9 :.C 9 1.00 93.10 6 00 90. I 6 9:.2: .30 4 1.C00 0 1.00 24.- 9 22.I 1:.oo 2>6~1 0 00 23-.1 0 00 2:.29 0 G 3 -00 2-..C 4 :C 32. A 8 00 21.22 6 *.00 21.22 .00 2.: 1 .C 12.25 2 9 OC 2-.12 5' .00 3.;4 91 00 3*.25 -57- S S

S*

bref2

ATOM

ATO+

ATOM

ATOH

ATOM

ATOH

ATOt

ATOC

ATOI

ic.pdb 2021 OE2 GLU 5 2022 C GLU 5 2023 C GLU 5 2024 N LEU 2025 CA LEU 5 2026 CB LEU S 2027 CC LEU 2028 CD1 LEU 2029 CD2 LEU 2030 C LEU 5 2031 0 LEU 2032 N LEU 2033 CA LEU 2034 CB LEU 2035 CG LEU 2036 CD1 LEU 2037 CD2 LEU 2038 C LEU 2039 0 LEU 2040 N CYS 2041 CA CYS 2042 C CYS 2043 0 CYS 2044 CB CYS 2045 SC CYS 2046 N PHE 2047 CA PHE 2048 CB PHE 2049 CC PHE 2050 C01 PHE 2051 CD2 PHE 2052 CE1 PHE 2053 CE2 PHE 2054 CZ PHE 2055 C PHE 2056 0 PHE 2057 N THR 2058 CA THP.

2059 CB THR 2060 OC1 THP.

2061 CG2 THP.

2062 C THP.

2063 0 THP 2064 N GLU 2065 CA GLU 2066 CB GLU 2061 CG GLU 2068 CD GLU 2069 OE1 GLU 2010 0E2 GLU 2011 C GLU 2072 0 GLU 2073 N ARG 2014 CA ARG 2075 CB ARG 2016 CC ARG 2077 CD ARG 2018 "NE ARG 2079 CZ ARG 2080 NH1 ARC 2081 NH2 ARC 2082 C ARG 2093 ARG 2084 N IEU 2085 C:A i'* 2086 CB LEU 2081 CC LEWU 208 CDi LEL 2089 CD2 LEU 2090 C LE.' 2091 0 LZE 2092 N CL 2093 C. L: 1 2094 CB SL'C 4 2095 CG GL;: 4 2096 CD GL-- 4 2091 OEI GL; H 2098 OE2 GL; 25 25 25 26 26 26 26 26' 26 26 526 527 521 "21 i21 527 527 521 521 529 528 !28 528 128 128 528 529 !29 !29 529 529 529 529 529 529 529 529 530 !30 530 530 530 '30 530 531 532 !32 21 532-. 531 132 '.52 i32 22 !32 532 12 !!22 !'2 523 534 534 53- 51.131 26.066 65.119 55.512 27.633 89.150 55.306 28.676 69.733 56.619 27.495 68.331 57.455 28.638 87.940 58.859 28.182 81.485 60.103 29.082 87.590 61.166 28.501 86.706 59.856 30.499 67.193 56.688 29.248 86.-51 56.521 28.607 e5.133 56.209 30.474 86.892 55.415 31.101 85.954 54.115 31.638 86.441 53.035 30.653 86.824 51.951 31.429 87.441 52.541 29.889 85.620 56.110 32.256 85.176 56.413 33.252 85.836 56.234 32.176 83.844 56.929 33.199 83.051 55.987 33.810 82.044 55.087 33.121 81.560 58.132 22.593 62.282 59.491 31.832 83.234 56.191 35.088 81.143 55.397 35.792 60.758 54.008 36.143 Z1.303 53.980 31.315 82.231 53.958 38.611 E1.733 53.912 31.123 83.611 53.868 39.691 82.590 53.822 38.201 84.411 53.801 39.490 63.961 56.100 37.031 80.200 57.018 37.511 80.185 55.665 31.471 19.018 5.6.225 38.655 78.3177 57.228 38.280 71.232 57.683 39.460 76.519 56.637 37.355 76.234 55.016 39.582 77.948 53.999 39.124 17.611 55.215 40.a82 :3.0o7l 54.246 41.854 17.741 54.178 42.919 11.834 54.046 42.346 80.25' 53.7711 43.413 E1.291 54.085 44.606 61.07' 53.227 43.052 62.35! 54.462 42.489 76.38: 53.505 42.685 75.65 55.659 43.021 -6.15 56.039 43.529 -4.83 56.900 44.795 74.89 56.141 46.059 -5.09 '5.682 46.010 -6.48 54.531 46.930 76.69 54.158 41.395 77.89 54.877 41.096 -3.91 52.998 48.056 13.01 56.934 42.364 74.42 56.904 41.310 "5.0.

51.161 42.502 -3.41 59.606 41.256 13.1 58.326 40.790 71.8; 56.884 40.298 11.7.

56.531 39.773 70.31 56.1723 39.204 72.7: 60.064 41.723 3.4 60.891 41.490 12.5 60.365 42.115 14.6 61.722 42.522 i5.0 61.999 43.882 14.3 61.006 44.97 60.768 46.010 13.6 59.849 46.860 73.8 61.461 45.33 -2.6 Thu Apr 25 12:27:47 1996 27 00 34.53 30 8.91 1.00 9.70 30 5.52 30 4.14 30 4.80 00 2.00 1.30 2.00 00 2.00 00 2.64 CO 2.30 00 2.00 1.30 2.00 00 4.05 1.30 2.65 30 2.00 1.00 2.00 1.00 4.04 1.00 5.30 1.00 3.62 00 2.97 00 2.18 30 2.61 30 2.00 00 2.00 00 2.00 ^0 4.15 00 3.88 1..0 2.00 00 2.00 1.00 2.00 00 2.00 1.00 2.00 1.00 2.00 00 5.77 1.00 6.52 1.00 2.84 .00oo 2.00 1.00 2.00 1.00 2.64 00 2.96 OC 2.59 .00 4.31 i 1.

0 0 2.29 F 1.00 5.46 i 1.30 10.50 1. 0 12.93 I ;0 14.12 S1.300 15.54 5 00 la.13 2 1.00 6.42 0 00 9.10 2 1.00 5.91 2 1.00 6.83 0 1.00 6.46 4 1.00 4.16 3 30 6.94 6 00 14.70 0 1.00 17.'2 5 i.00 13.7; 7 00 13.08 14 .0 7.63 i2 00 12.29 16 1.0o 10.64 95 1: 12.12 21 C 13.12 41 1.00 48 :1.69 54 1.30 12.40 30 3, 11..£ 35 _.00 12.7 66 C 12.95 03 13.30 65 C 1-.94 91 :C 23.:S 84 20 26.3- 62 26.36 25 25.33 -58-

*S.S

S brat2

ATOM

ATOHM

ATOM

ATOHM

ATOM

ATC

ATOM

ATC'M

ATOM

A T om

ATOM

ATCM

ATOM

ATCIM

ATOM

1c.pdb 2099 C CLU 2100 CGLU 2101 N ASP 2:02 CA ASP 2103 CB ASP 2104 CC ASP 2105 001 ASP 2106 OD2 ASP 2107 C ASP 2108 C ASP 2109 N LEU 2110 CA LEU 2111 CS LEU 2112 CG LEU 2113 CD1 LEU 2114 CD2 LEU 2115 .7 LEU 2116 O LEU 2117 N VAL 2118 CA VAL 2119 CB VAL 2120 CG1 VAL 2121 CG2 VAL 2122 C VAL 2123 0 VAL 2124 N CIS 2125 CA CYS 2126 C CYS 2127 0 CYS 2128 CB CYS 2129 SC CYS 2130 N PHE 2131 CA PRE 2132 CB PHE 2133 CC PHE 2134 CD1 PE 2135 CD2 PHE 2136 CE1 PHE 2137 CE2 PHE 2138 CZ PHE 2139 C PHE 2140 0 PHE 2141 N TFF 2142 CA TP.P 2143 CB TRP 2144 CC TP.P 2:45 CD2 TPP 2146 CE2 TP.P 2147 CE3 TP.P 2148 CDl TRP 2149 NEl TP.P 2150 CZ2 TP.P 2151 CZ3 TPP 2152 CR2 TP 2153 C TP.P 2154 0 TP.P 215 N GCLU 2:56 'CA GLU 2157 CB CL; 2158 CC GLU 2759 CD GLU 2:60 3E1 GLU 2-.61 0E2 CLU 2:62 C GLL 2:53 3 2164 N CLC 2:65 CA CLZ 2166 Cb GL- 2167 CS GL 2:68 CD CL 2169 OE1 CLI 21:0 CE2 GLZ 2:i c GLUC 2-72 CL: 2:73 :.'ALA 2:174 CA ALA -Z-5 CS ALA 2i76 C ALA 534 534 535 535 525 525 525 535 135 536 536 536 536 536 536 536 536 537 537 537 537 537 537 137 538 538 538 538 538 538 539 539 539 539 539 539 539 539 539 539 539 540 540 540 540 .40 540 140 540 540 540 540 540 540 540 541 541 141 541 141 541 541 541 !42 542 142 542 542 542 542 542 543 542 542 61 62 61 61 60 50 58 58 60 60 61 60 61 61 59 61 60 61 59 59 56 5 5 5 5 5 5 5 6 6 6 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 6 6 .892 42.579 76.527 1.

.651 42.380 -'.066 1.

.251 41.637 77.194 1.

.247 41.579 78.638 1.

.188 42.544 73.128 1.

.848 42.334 78.430 1 .020 41.541 73.913 1.

.635 42.949 77.372 1 .793 40.201 79.033 1 .063 39.577 13.295 1 .176 39.731 80.204 1 .717 38.436 80.651 1 .614 37.315 80.149 1 .012 35.958 80.495 1 .697 35.789 79.782 1 .955 34.853 80.152 1 .725 38.468 62.154 1 .701 38.896 82.751 1 .606 38.093 62.767 1 .514 38.050 84.219 1 .439 39.006 84.761 1 1.391 38.900 86.262 1 8.754 40.434 64.386 1 9.1:1 36.652 84.604 1 8.232 36.096 83.971 1 9.812 36.048 65.553 1 9.452 34.711 86.05 1 9.375 34.771 87.597 1 0.165 35.457 63.257 0.438 33.619 ES.600 0.634 33.421 83.795 8.426 34.059 88.178 1 8.267 34.099 89.621 1 7.295 35.232 89.997 5.852 35.009 89.515 4.835 34.690 90.420 5.519 35.104 88.147 3.540 34.470 89.986 4.201 34.878 87.706 3.223 34.562 68.630 7.689 32.807 90.123 7.397 31.913 29.352 7.606 32.696 91.436 6.965 31.575 92.102 7.859 30.331 92.252 8.890 30.380 93.315 0.250 30.807 93.175 0.861 30.657 94.430 61.008 21.299 92.110 18.738 29.995 94.610 59.914 30.161 95.286 52.206 30.984 94.657 62.336 31.623 92.328 62.927 31.465 93.596 56.504 32.189 93.417 56.-74 33.366 93.668 55.698 31.467 94.186 55.187 31.999 95.452 53.768 32.565 95.270 53.592 33.523 94.070 52.202 34.134 93.991 52.094 35.229 93.415 51.219 33.550 94.516 55.148 30.925 94.507 54.244 29.811 9S.232 55.552 31.242 97.724 55.521 30.222 93.766 56.871 29.482 98.833 58.122 30.359 98.138 59.40 29.571 99.006 59.711 29.256 100,).188 60.095 29.263 98.026 _.C382 20.763 :00.128 54.741 31.947 100.248 55.051 29.889 101.135 54.652 30.258 102.493 54.466 29.038 103.325 55.-16 31.141 103.108 00 10.95 00 10.92 00 9.01 .006 6.92 .00 8.31 .00 8.75 .00 11.89 .00 15.77 .00 6.27 .00 6.6t .00 5.28 .00 4.48 .00 2.00 .00 2.00 .00 2.00 .00 2.00 .00 5.42 .00 5.81 .00 6.59 .00 4.71 .00 3.90 .00 7.66 .00 6.66 .00 2.70 .00 5.62 .00 3.31 .00 4.73 .30 5.86 .00 6.30 .00 2.00 0Q 3.79 1.00 3.78 1.00 4.15 1.00 4.88 L.00 7.86 L.00 5.60 L.00 9.65 L.00 4.81 1.00C 7.22 1.00 5.52 1.00 3.30 1.00 5.07 1.00 2.62 1.00 5.41 1.00 5.13 1.00 7.06 .;G0 4.64 3.0C 5.73 .C 5.86 1.0 8.29 1.06 8.36 1.00 8.15 1.00 7.58 1.OC 8.06 1.00 6.24 1.G0 7.32 1.0 8.81 1.00 10.45 1.00 11.89 1.00 14.89 1.0 16.24 .C 1-.33 :.oc 16.64 10.3 1.00 10.32 1.5C 10.91 1.:c 10.78 C 10.24 .20 14.40 1.27 15.97 1.00 17.03 :.ZG 17.30 .66 9.88 .c CG .66 6 7 4 7 6 4 4 0 3 .7 7 3 3 1 5 r.

3 7 i i r r 3 1 7i i Thu Apr 25 12:27:47 1996 28 S.

S

*5 5 S S S -59betf2lc.pdb Thu Apr 25 12:27:47 1996 e I to o 0 0**00

S

ATOM

ATOHM

ATOM

ATCH

ATOHM

ATOM

ATCM

ATCH

ATOM

ATCH

ATOM

ATCOM

ATOM

ATOMH

ATOM

ATCH

ATCM

ATOM

ATCH

ATOM

AT0M

ATOM

ATO

ATOM

ATM

ATOM

21117 0 ALA 5 2178 N ALA 2179 CA ALA 5 2180 CB ALA 5 2181 C ALA 2182 O ALA 2183 N SER 2184 CA SER 2185 CB SER 2186 00 SER 2187 C SEP.

2188 C SER 2189 N ALA 2190 CA ALA 2191 CB ALA 2192 C ALA 2193 -0 ALA 2194 N CGLY 2195 CA GLY 2196 C GLY 2197 0 CLY 2198 N VAL 2199 CA VAL 2200 CB VAL 2201 CGI VAL 2202 CG2 VAL 2203 C VAL 2204 03 VAL 2205 N GLY 2206 CA GLY 2207 C CLY 2208 0 GLY 2209 N PRO 2210 CD PRO 2211 CA PRO 2212 CB PRO 2213 CC PRO 2214 C PRO 2215 0 PRO 2216 N GLY 2217 CA CGLY 2218 C GLY 2219 3 CGLY 2220 N ASN 2221 CA ASN 2222 CE ASN 2223 CC ASN 2224 001 ASN 2225 ND2 ASN 2226 C ASN 2217 C ASN 2228 N TYR 2229 CA TYR 2230 CB TyP.

2231 CG TYF.

2232 CDL TYP.

2233 CEl TYP.

2234 'CD2 TYr, 2235 CE2 TYR 2236 CZ TYR.

223. OH TYF.

2238 C TYR 2239 C TYR 2240 N SEP.

2241 CA SER 2242 C SEP.

2243 3V sE; 2244 C SE 2245 3 SEF.

2246 N PNE 2247 CA PHE 2248 CB P.E 2249 CC PHE 2230 1DI PHE 2251 CD2 P.E 2252 CE1 PHE 2253 CE2 PHE S2254 CL PHE 43 44 44 44 '44 .44 .45 )45 145 54 1 145 545 546 546 546 546 546 541 547 5471 541 548 548 548 548 548 548 548 549 549 549 549 550 550 550 550 550 550 550 55: 551 551 5512 552 '52 552 552 552 552 552 553 553 33 553 ss:3 553 553 553 553 !!3 553 5:3 554 !54 !54 (555 5 55:.

555 56.911 30.849 1C2.998 55.286 32.253 103.695 1.

56.199 33.185 104.325 55.425 34.374 1C4.890 1.

56.861 32.397 105.438.

56.169 31.744 1C6.216 !8.204 32.393 105.456 58.993 31.669 :06.453 1.

59.335 30.251 105.980 60.291 29.628 106.827 1.

60.245 32.440 C106.891 1.

60.865 33.184 106.111 60.557 32.271 108.174 1.

61.639 32.942 1C8.882 61.927 32.215 110.200 62.928 33.213 108.143 1 63.651 32.297 101.751 1.

63.212 34.495 107.965 64.438 34.889 107.300 1 64.841 34.140 106.032 1 66.045 34.046 IC5.739 1 63.867 33.560 1CS.322 64.111 32.882 104.048 1 63.115 31.749 103.826 63.134 31.309 102.363 1 63.450 30.519 1:4.7156 63.814 33.91 102.995 62.721 34.309 102.714 1 64.954 34.612 142.541 64.852 35.667 101.551 65.473 35.180 IC0.263 65.765 33.991 10.117 1 65.666 36.066 99.283 65.213 31.459 93.186 66.271 35.639 98.0171 66.333 36.943 97.199 66.201 38.019 98.199 §7.647 34.964 5.151 01.991 34.066 97.371 68.384 35.340 99.204 69.714 34.797 93.443 69.11776 33.300 99.601 10.854 32.736 93.588 68.625 32.655 13.726 68.573 31.215 9.888 67.510 30.851 1C0.904 61.797 31.449 1I2.226 68.789 31.112 102.850 66.991 32.411 1C2.631 68.287 30.304 98.590 68.176 29.265 99.580 68.157 31 218 91.506 67.867 30.738 95.186 66.432 31.0898 95.7119 65.367 30.341 95.520 64.491 31.001 57.373 63.574 30.290 33.117 65.280 28.953 53.423 64.355 28.243 27.167 63.516 28.914 93.012 62.65C 28.188 i8.719 68.791 31.287 5.14 69.432 32.306 *5.298 68.845 30.612 33.980 S9.622 2i.:09 i2.afs 70.999 30.456 12.332 70.954 29.192 i2.2.4 68.800 30.183 11.621 68.289 29.484 :-1.502 95.574 11.7a3 3.7f? 67.811 31.640 Fi.536 66.734 32.730 1*.484 65.12C J2.52:1 1.33 64.422 32.509 -5.567 66.242 32.554 57.319 53.541 32.382 i7.501 5!.379 32.427 S5.962 64.030 32.339 E4.196 29 00 10.83 00 9.48 00 10.43 00 11.53 00 11.84 00 13.61 00 12.17 00 13.08 00 12.9t 00 14.06 00 14.68 00 15.67 00 17.50 .00 17.93 00 17.78 .00 18.94 .00 19.69 .00 19.34 .00 20.46 .00 20.86 .00 23.71 .00 18.62 .00 14.08 .00 12.71 .00 13.62 .00 11.28 .00 15.33 .00 16.13 .00 15.42 .00 12.34 .00 12.73 .00 11.82.

.00 12.01 .00 12.99 .00 13.59 0(r 9.83 .00 10.09 .00 13.34 1.00 14.83 1.00 13.58 1.00 11.00 i.00 9.01 1.00 11.57 1.00 6.84 1.00 6.10 1.00 4.08 1.00 6.03 00 7.24 1.00 3.39 .00 7.54 L.00 1.91 5.00 5.28 1.00 4.43 1.00 4.87 *.00 4.46 1.00 3.71 1.00 3.40 00 3.40 .0C 3.44 1.00 2.00 1.30 3.67 1.00 5.08 00 4.85 .30 5.81 1.30 670 .c0 3.42 1.00 11.53 00 6.93 .00 7.33 OC 4.43 0C 5.32 00 5.15 38 1.Dc 3.96 1.00 .4.43 .C 1.29 O..C X)2 00 5.62 r i

I

r 3 i 3 i r i i i i

I

i i i i i

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0 0@ 0 0 0* brf21c.pdb Thu Apr 25 12:27:47 1996 **0 0.°ooo e *00 g 0

ATOM

ATCH

ATOM

ATOMH

ATOM

ATO

2255 C PHE 2256 0 PHE 2257 N SER 2258 CA SER 2259 CB SER 2260 OG SER 2261 SER 2262 0 SER 2263 N TYR 2264 CA TYP.

2265 CB TYP.

2266 CG TYR 2267 CD1 TYP.

2268 CE1 TYP.

2269 CD2 TYR 2270 CE2 TYR 2271 CZ TYR 2272 OH TYR 2273 C TYR 2274 0 TYR 2275 N GLN 2276 CA GLN 2277 CB GLN 2278 CG GLN 2279 CD GLN 2280 OE1 GLN 2281 tE2 GLN 2282 C GLN 2283 0 GLN 2284 N LED 2285 CA LEU 2286 CB LEU 2287 CG LEU 2288 CD1 LEU 2289 CD2 LEU 2290 C LEU 2291 0 LEU 2292 N GLU 2293 CA GLU 2294 CB GLU 2295 CG GLC 2296 CD GLU 2291 OE1 GLU 2298 OE2 GLU 2299 C GLU 2300 0 GL 2301 N ASP 2302 CA ASP 2303 CB ASP 2304 CG ASP 2305 OD1 ASP 2306 OD2 ASP 2307 C ASP 2308 0 ASP 2309 N GLC 2310 CA GL- 2311 CB GLC 2312 'CG GLC 2313 CD GLi 2314 OE1 GL: 2315 OE2 GL 2316 C GL 2311 0 'L 2318 N PRO 2319 CD PP.: 2320 CA PP.C 2321 CB PPC 2322 CG Pp.: 2323 C PP.C 2324 PP.C 2325 N TP.? 2326 CA TP.? 2321 CB TP.7 2328 CC TR? 2329 CD2 TR? 2330 CE2 TRF 2331 CE3 TRP 2332 CDI TP.P 555 555 556 556 556 556 556 556 557 557 551 551 551 557 551 551 551 551 551 557 558 558 558 558 558 558 558 558 558 559 559 559 559 559 559 559 560 560 560 560 560 560 560 560 560 561 561 561 561 561 561 561 561 562 562 562 562 562 562 562 562 562 563 563 563 563 563 563 563 564 564 564 564 564 564 564 564 68.119 31.759 88.337 69.184 32.858 87.945 69.095 30.616 67.740 70.019 30.503 E6.619 70.969 29.315 86.879 71.922 29.58? 87.891 69.336 30.298 65.251 68.535 29.389 85.117 69.682 31.102 84.255 69.122 30.943 82.924 68.198 32.089 82.569 68.832 33.434 82.422 69.405 33.825 81.218 69.851 35.126 81.023 68.737 34.368 83.434 69.184 35.667 83.260 69.734 36.047 82.051 70.124 37.356 81.865 10.191 30.834 81.870 11.316 31.196 82.090 69.839 30.360 80.695 70.831 30.221 79.648 71.603 28.925 19.828 72.506 28.598 18.648 13.171 21.282 13.788 72.552 26.320 93.183 14.447 21.229 73.477 70.204 30.208 73.279 69.420 29.309 7.977 70.518 31.109 11.445 69.945 31.139 76.120 10.036 32.487 15.399 68.975 33.521 75.792 69.103 34.810 15.005 67.612 32.955 15.564 10.764 30.060 15.447 11.951 29.947 15.728 70.091 29.169 74.718 70.137 28.064 13.997 69.787 27.517 72.938 10.290 26.305 72.163 69.701 26.207 10.738 69.790 27.202 69.983 69.200 25.130 70.341 71.995 28.572 73.31C 71.919 29.491 -2.50! 73.140 27.970 -3.641 14.460 28.346 .3.11i 14.478 23.398 71.58! 14.440 21.038 70.961 74.530 26.039 71.72! 14.296 26.963 69.72' 74.995 29.667 73.66 75.663 30.426 12.93 74.114 29.972 74.92 75.22C 31.218 75.50 '4.093 32.235 75.65 73.224 32.450 14.40 13.909 33.234 13.28 74.330 34.401 73.51 73.981 32.670 72.16 15.764 30.8417 5.87 75.431 29.159 77.37 76.662 31.681 77.4( 20C 22.000 77.03 77.156 31.287 13.7 78.186 22.376 7).1; 77.655 23.5438 7..4C 75.96: 31.217 7.71 74.981 22.00' 75.995 30.362 80.17 74.945 30.255 E1.31 75.304 '29.19? 82.8, 74.65C 27.886 E2.7 73.27( 27.585 82.9 .3.116 26.188 82.1 72.15e 28.357 E2.2 17.25C 26. 70' 82.3 00 6.86 1.00 8.43 00 7.22 00 6.3 3 1.00 .4.30 1.00 8.78 00 5.62 L.00 8.35 1.00 3. 0o 1.00 3.30 1.00 2.00 1.00 2.00 1.00 2.00 1.00 2.56 1.00 2.00 6 1.00 2.00

A

1.00 3.10 i 1.00 3.23 1.00 3.33 1.00 4.25 1.00 3.52 1.00 3.20 1.00 3.66 1.30 6.55 30 5.14 1.00 6.68 1.00 7.23 1.00 3.24 1.00 2.96 00 2.00 1.00 2.39 1.00 2.00 i 1.00 2.00 6 1.00 2.00 1.00 2.00 6 1.00r 5.30 6 1.00 4.67 1.00 6.97 1.00 11.03 1.00 14.40 1.00 19.08 i .CO0 20.20 1.00 25.39 1.00 21.83 1.00 11.71 S .00 10.88 I 3C 12.36 1 30 13.20 9 30 11.29 8 1.00 13.29 5 1.30 14.53 9 '.30 11.84 1 1.00 17.27 1 1.00 21.27 6 1.30 17.40 4 *.30 16.45 2 00 20.22 8 00 23.17 6 9 00 23.82 1 20 22.18 9 3C 27.47 3 I 14.20 8 3 :C 16.04 ,5 2C 11.29 4 5.24 14 3. 11.69 .1 C 7.10 04 6.79 18 10.73 8 C 11.36 72 1.:0 8.20 06 5.30 45 2.55 Do ,C 5.38 41 i: 6.62 61 ZC 6.86 96 8.59 87 6.26 -61bref21c.pdb Thu Apr 25 12:27:47 1996

ATOM

ATOH

ATOM

ATOH

ATO

ATOP

ATO

AT01

ATO

2333 NE1 TRP 5 2334 CZ2 TPP 5 2335 CZ3 TRP 5 2336 CH2 TRP 5 2337 C TRP 5 2338 0 TP.P 5 2339 N LYS 5 2340 CA LYS 5 2341 CB LYS 5 2342 CG LYS 5 2343 CD LYS 5 2344 CE LYS 5 2345 NZ LYS 5 2346 C LYS 5 2341 0 LYS 2348 N LEO 2349 CA LEU 2350 CB LEO 2351 CG LED 2352 CD1 LEO 2353 CD2 LEO 2354 C LED 2355 C LEO 2356 N CYS 2357 CA CYS 2358 C CYS 2359 0 CYS 2360 C3 CYS 2361 SG CYS 2362 N ARG 2363 CA ARG 2364 CB ARG 2365 CC ARG 2366 CD ARG 2367 NE ARG 2368 CZ ARG 2369 NH1 ARG 2370 NH2 ARG 2371 C ARG 2372 3 ARG 2373 N LEU 2374 CA LEO 2375 CB LEU 2376 CG LED 2377 CD1 LEG 2318 CD2 LEO 2379 C LEU 2380 0 LEO 2381 N HIS 2382 CA HIS 2383 CB HIS 2384 CG HIS 2385 CD2 HIS 2386 ND1 HIS 2381 CE1 HIS 2388 NE2 HIS 2389 C HIS 2390 *0 HIS 2391 N GLN 2392 CA GLN 2393 CS GLN I 2394 CG GLK 2395 CD GLN 2396 OE1 3LN 2291 NE2 3LK 2398 GLN 2399 0 SLN 2400 N ALA M 2401 CA ALA 4 2402 C? ALA 4 2403 ALA 1 2404 C- ALA 4 2405 N 4 2406 CD PF.C M 2407 CA PP.R- M 2408 CB PP.C' H 2409 CC PP.C M 2410 C PRC 64 64 64 64 64 64 65 65 65 65 65 65 65 .65 565 566 566 566 566 566 566 566 566 561 567 567 561 561 567 568 568 568 568 568 568 568 568 568 569 568 569 569 569 569 569 569 !69 569 570 570 570 570 570 570 570 5170 570 570 571 571 571 571 571 571 5711 572 572 572 512 5?; 5%, 53 5-3 57.

57?.

14.338 25.675 82.422 1.

11.880 25.546 62.929 L.

70.928 27.723 83.461 1.

10.801 26.328 e3.279 1.

14.880 31.591 62.525 1.1 15.908 32.259 82.740 1.1 73.690 31.991 82.921 1.

73.542 33.256 83.612 L.

73.099 34.332 62.625 1.

14.242 34.886 81.791 I.

73.821 35.191 60.371 L.

74.814 36.116 79.711 1.

74.856 37.314 80.497 1.

12.669 33.111 84.878 1.

71.856 32.270 85.043 1.

72.863 34.113 85.783 1.

72.160 34.100 81.042 1.

73.18- 33.957 88.143 1.

72.902 33.890 89.641 1.

14.121 33.292 90.343 1.

12.660 35.299 90.155 1.

11.505 35.418 87.265 1.

72.175 36.430 87.315 1 70.199 35.446 81.406 1 69.636 36.738 61.658 1 69.245 21.013 89.124 1 69.271 36.113 89.983 1 68.506 37.017 66.701 1 67.190 35.791 86.808 69.009 38.293 89.405 1 68.626 38.777 90.727 1 68.781 40.310 90.798 1 70.037 40.829 91.510 1 11.329 40.111 90.681 1 72.045 41.996 90.624 1 72.581 42.642 91.671 1 12.531 42.151 92.918 1 ,73.191 43.816 91.465 1 67.185 38.399 91.086 66.241 38.690 90.329 1 67.046 37.752 92.248 65.782 37.304 92.807 66.005 36.101 93.715 65.069 34.911 93.607 64.374 34.905 92.287 65.852 33.615 93.759 65.318 36.461 93.631 66.121 29.228 94.131 64.015 38.644 93.719 63.454 39.712 94.531 62.841 40.811 93.655 63.820 41.547 92.802 64.739 42.492 93.108 63.845 41.421 91.431 64.728 42.263 90.925 65.285 42.925 91.924 62.359 39.016 95.393 62.098 37.384 95.284 61.125 39.869 96.246 60.655 39.363 9?.063 61.181 38.806 98.371 60.15C 38.017 S9.168 60.181 38.342 100.666 61.169 39.037 101.358 59.113 38.362 IC1.170 59.712 40.504 97.308 60.098 41.656 97.285 58.445 40.152 9?.419 57.348 41.081 97.656 56.92C 41.774 94.356 56.217 40.214 98.195 56.260 38.974 98.053 55.213 40.32' 94.4 55.084 42.102 99.602 54.205 39.863 S).323 53.169 40.43' IC0.696 54.78! 41.599 101).984 5:.044 39.7134 3.377 31 00 5.;6 00 6.49 0 6.79 00 3.18 00 5.66 00 9.22 00 3.69 00 2.30 00 2.00 00 2. :0 00 3.81 00 3.15 00 6.31 00 3.24 00 2.93 00 3.46 30 6.16 00 7.13 00 11.04 00 13.73 .00 11.29 .00 6.69 .00 6.50 .00 1.27 .00 10.289 .00 13.50 .00 13.64 0 12.37 .00 17.22 .00 15.13 .00 14.78 .00 17.31 .00 20.45 .00 20.61 .00 22.26 .0(0 22.85 .00 20.25 .00 24.23 00 14.39 1.00 15.75 _.00 11.39 1.00 6. 2 1.00 2.C00 1.00 3.41 1.00 3.80 1.00 2.00 00 4 .O0 8.24 D3 9.65 1.00 10.84 00 :1.:4 1.00 10.31 1.00 13.10 1.00 14.:0 1.00 14.17 1.00 12. 1.00 ).92 1.00 14.44 1.00 ?.24 1.00 A.31 1.00 11.43 1.00 13.:7 00 2.53 i.00 22.69 *.oc 22.'6 1.00 2.52 00 2. :0 .ODC 26 1.00 5 2 3.or 0N .2* L.0(c '.362 0 0 7.,33 -62brf2:

ATOM

ATCt.

ATOM

Lc.pdb 2411 0 PRO 2412 N THR 2413 CA THR 2414 C3 THP.

2415 OG1 THP.

2416 CG2 THR 2411 C THR 2418 0 THR 2419 N ALA 2420 CA ALA 2421 CB ALA 2422 C ALA 2423 0 ALA 2424 N ARG 2425 CA ARG 2426 CB ARG 2421 CG ARG 2428 CD ARG 2429 NE ARG 2430 CZ ARG 2431 NH1 ARG 2432 NHH2 ARG 2433 C ARG 2434 0 ARG 2435 N GLY 2436 CA GLY 2437 C GLY 2438 0 GLY 2439 N ALA 2440 CA ALA 2441 CB ALA 2442 C ALA 2443 0 ALA 2444 N VAL 2445 CA VAL 2446 CS VAL 2447 CG1 VAL 2448 CG2 VAL 2449 C VAL 2450 0 VAL 2451 N ARG 2452 CA ARG 2453 CB ARG 2454 CG ARG 2455 CD ARG 2456 NE ARG 2457 CZ ARG 2458 NH1 ARG 2459 NH2 ARG 2460 C ARG 2461 0 ARG 2462 N PHE 2463 CA PRE 2464 CB PHE 2465 CG PHE 2466 CD1 PHE 2467 CD2 PRE 2468 "CE1 PRE 2469 CE2 PRE 2470 CZ PRE 2471 C PHE 2472 3 PHE 2473 N TP.P 2474 CA TP 2475 C3 T?.P 2476 :C TP.P 2477 CD2 TP 2478 CE2 TPP 2479 CE3 TP.P 2480 CD1 P.? 2481 NEI TPP 2482 CZ2 TP.P 2483 CZ3 TP.

2484 CH2 TRP 2485 0 T?.P 2486 0 TRP 2487 N !Ys 2488 CA CYS 573 174 574 574 174 174 174 174 515 575 575 !76 S76 576 576 !16 576 516 5716 576 576 !76 571 57 S l 77 178 578 578 578 578 579 579 579 579 579 -79 580 590 580 580 580 580 530 580 i90 "aO 580 581 581 381 531 531 531 581 531 'i2 512 582 532 532 532 582 532 582 532 532 532 532 5833 5 a3 52.768 4C.608 97.552 1.00 7.72 52.428 38.514 98.416 1.00 8.95 51.255 38.232 91.727 1.00 10.96 51.075 36.738 91.733 1.00 10.37 52.135 36.153 96.980 1.00 14.24 49.712 36.324 97.15 1.00 13.72 50.119 36.852 98.515 1.00 12.85 50.163 38.814 99.752 1.00 14.59 49.087 29.324 97.812 1.00 14.8 47.934 39.946 98.467 1.00 14.50 46.922 40.433 97.439 1.00 14.72 47.282 28.960 99.443 1.00 14.38 46.480 39.355 100.286 1.00 15.91 47.683 37.695 99.344 1.00 12.79 47.118 36.637 100.189 1.00 11.82 46.877 35.414 99.328 1.00 15.95 45.534 35.451 98.604 1.00 20.92 45.633 34.631 97.302 1.00 24.61 44.350 34.081 96.848 1.00 27.37 44.171 33.438 95.681 1.00 28.99 45.188 33.261 94.833 1.00 29.46 42.979 32.928 95.391 1.00 27.90 48.090 36.216 101.251 1.00 9.90 47.843 3!.177 101.972 1.00 8.14 49.167 36.963 101.606 1.00 10.36 50.066 36.615 102.7C5 00 9.58 51.201 32.638 102.425 1.00 11.02 51.959 25.280 1C3.356 1.00 10.42 51.263 25.140 IC1.193 1.00 11.51 52.332 34.245 100.720 1.00 10.32 51.842 33.360 99.617 1.00. 6.95 53.443 33.158 100.212 1.00 10.21 53.278 36.384 100.138 1.00 9.88 54.597 34.593 99.905 1.00 9.95 55.673 35.431 99.406 1.00 10.55 56.957 35.294 100.247 1.0T 9.32 56.734 35.863 101.618 1.00 8.45 57.363 33.860 100.350 1.00 11.44 '55.923 35.128 91.929 1.00 9.09 55.599 34.044 97.452 1.00 9.40 56.460 36.104 917.229 1.00 7.06 56.721 35.917 95.816 .0OC 1.86 55.769 36.792 94.991 1.00 8.84 55.926 36.721 93.503 1.00 1.88 55.080 37.813 92.844 '.00 8.78 53.652 37.511 92.913 1.00 6.85 !2.71' 36.362 93.341 00 5.69 53.05C 39.581 93.721 :.00 5.12 51.410 37.952 93.466 1.00 2.00 58.159 36.282 95.523 1.00 1.72 58.664 37.321 95.954 1.00 1.66 58.827 35.387 94.827 1.00 6.07 60.200 35.596 94.458 1.00 5.52 60.982 34.355 94.803 1.00 4.84 61.274 34.214 96.250 1.00 4.90 60.510 33.372 7.045 :.00 3.60 '2.371 34.883 96.822 1.00 5.69 60.835 33.191 98.390 1.00 4.44 62.694 34.700 98.165 1.30 5.88 61.92f 33.854 98.944 1.00 3.43 60.287 35.839 92.961 1.00 5.46 59.686 35.101 92.194 :.30 6.33 61.03: 26.844 92.525 30 6.16 61.129 37.054 91.090 1.CC 7.26 59.861 21.773 90.589 C~ 9.34 59.462 38.933 91.423 :.00 10.14 59.916 40.268 91.280 :.00 11.49 59.366 41.017 92.359 1.00 11.22 60.744 40.906 90.356 1.00 11.65 58.662 28.915 92.530 :.30 14.19 58.604 40.165 93.1C5 1.3C 12.18 59.615 42.365 92.538 00 12.31 61.001 '42.24' 90.524 15.91 60.436 42.913 91.611 1:.O 16.33 62.409 37.622 90.429 7.94 63.21"9 38.299 S1.041 :.00 6.37 62.55( 27.312 6).150 OC 7.90 63.656 27.766 63.334 3C 9.15 Thu Apr 25 12:27:47 1996 32 -63o bref2

ATOM

Lc.pdb 2489 C CYS 2490 0 CYS 2491 CB CYS 2492 SG CYS 2493 N SER 2494 CA SER 2495 :B SEP.

2496 :G SEP.

2497 SEP.

2498 C SER 2499 N LEU 2500 CA LEU 2501 CB LEU 2502 CC LEU 2503 C31 LEU 2504 CD2 LEO 2505 C LEU 2506 0 LEU 2507 N PRO 2508 CD PRO 2509 CA PRO 2510 CB PRO 2511 CG PRO 2512 C PRO 2513 0 PP.0 2514 N THR 2515 CA THP.

2116 C3 THF.

2517 OG1 THR 2518 CG2 THR 2519 C THR 2520 0 THP.

2521 N ALA 2522 CA ALA 2523 CB ALA 2524 C ALA 2525 0 ALA 2526 N ASP 2527 CA ASP 2529 CB ASP 2529 CG ASP 2530 OD1 ASP 2131 OD2 ASF 2532 C ASP 2533 3 ASP 2534 N THE.

2535 CA THF.

2536 C3 THP.

2523 Gl THF.

2538 CG2 THR.

2539 C THR 2540 0 TH.

2541 N SEP.

2542 CA SER 2543 C3 SER 2544 OG SEP.

2545 C SEP 2546 *0 SER 2547? SER 2548 CA SEP.

2549 C3 SEP.

252 CG SER 2551 C SZP.

2552 C SEF.

2!52 PHE 2554 CA PHE 2555 C3 P.E 2156 F FE.

255 PHE 255: :32 PP.E 2559 C1 PHE 2561 CE2 PHE 2!61 :2 PRE 2562 PHE 2563 PHE 2564 S VAL 2565 CA VAL.

2566 C. VAL SS3 583 583 583 584 584 564 584- 584 584 585 535 585 585 585 585 585 585 586 586 586 586 596 586 586 58' 581 58' 587 581 581 581 588 588 588 588 588 589 589 589 589 589 589 589 589 590 590 590 590 590 590 590 591 591 591 591 591 591 592 592 532 592 592 592 59' 593 593 593 532 5933 593 594 594 594 63.154 38.449 E? 62.143 38.055 81 64.50? 36.591 0- 65.603 36.996 c 63.895 39.453 0E 63.556 40.150 E8 63.210 41.612 1E 62.296 42.141 E 64.819 40.052 E 65.814 40.485 E 64.143 39.357 E6 65.889 39.214 E 65.638 38.192 E 65.265 36.131 B 65.929 35.888 8 65.633 36.211 E 66.134 40.562 8 65.188 41.282 2 61.410 40.929 8 68.622 40.279 6 61.746 42.202 8 69.257 42.304 6 69.505 41.410 8 61.416 42.019 1 61.834 41.019 7 66.691 42.985 66.261 42.949 66.168 44.355 65.921 45.330 65.049 44.408 61.182 42.186 66.739 41.308 68.412 42.530 69.513 41.921 10.896 42.342 69.435 40.425 69.825 39.894 68.811 39.141 68.145 38.300 69.173 37.684 10.613 31.683 71.088 38.045 11.422 31.299 61.341 31.845 61.080 36.659 66.4325 38.180 65.040 38.451 64.118 39.571 64.496 40.806 64.269 39.128 64.696 38.106 63.610 38.414 65.592 31.405 65.312 31.022 66.692 36.681 61.046 31.115 64.405 35.861 64.456 34.847 63.585 35.999 62.601 34.988 61.395 35.633 60.195 36.638 63.216 33.945 64.386 33.914 62.388 32.980 62.115 31.900 62.866 32.474 61.'44 33.45a 62.041 34.679 60.399 22.162 61.020 35.584 59.38C 34.054 59.68 35.262 43.848 30.947 64.302 30.117 64.222 30.958 65.284 20.113 66.1>88 30.109 7.013 6.520 7.816 S.410 6.606 5.315 5.649 4.680 4.531 4.990 3.390 2.500 1.374 1.541 0.486 2.912 1.832 1.508 1.631 2.160 0.993 1.191 2.416 9.520 3.912 '3.957 17.569 -6.969 "3.002 75.929 :6.651 ;5.948 76.700 75.849 76.320 15.700 ,4.681 16.693 76.651 71.976 -3.168 19.298 71.230 76.316 -5.383 74.133 "5.899 -S.426 -5.845 .1.928 -4.465 74.001 -3.183 -2.391 -1.696 )3.190 ,2.177 -2.88; 71.132 .0.80 -3.91 .886 63.56 :?.52 '3.62 41.18 '5.19 '-.04 f5.86 '5.1_ .).00 71.2 "0.9 11.i Thu Apr 25 12:27:47 1996 33 1.00 8.52 1.00 8.13 1.00 11.02 :.00 12.88 1.00 11.08 1.00 11.13 1.00 14.00 1.00 22.72 1.00 11.03 1.00 14.1 1.00 8.82 1.00 7.21 1.00 5.24 1.00 2.00 1.00 2.00 1.00 5.61 1.00 8.79 1.00 7.56 1.00 10.50 1.00 12.29 1.00 11.85 1.00 11.45 1.00 13.83 1.00 14.14 1.00 14.11 00 13.11 1.00 12.49 1.00 15.11 i.00 18.61 00 17.05 1.00 12.00 1.00 11.83 1.00 11.51 1.00 7.86 1.00 8.95 I.OC 7.36 1.00 8.31 1.00 7.82 1.00 1.85 1.00 5.24 1.00 5.26 6.38 00 2.00 1.00 96 00 7.86 00 8.88 00 10.02 1.00 8.46 1.00 1.66 1.00 10.59 S1.00 10.88 1.00 15.28 1.00 11.68 1.00 11.91 1.00 13.98 0 16.79 7 1.00 11.64 2 1.00 12.56 5 1.30 9.34 3 1.00 5.84 9 00 6.26 6 .00 5.45 9 1.00 5.25 3 00 4.12 oC S 00 .33 9 3C 57 .00 6.16 3.21 3 L .0 5.21 6 1.OC 9.60 2 .30 0: 44 i.00 i.34 i 1.3c 11.09 91 32 91 .29 55 01' 9.L1 4 4 2 6 1 6 4 0 6 6 6 2 1 7 6 6 6 2 4 0 6 6 3 6 6 3 6 6 4 4 1 -64bx-f21c.pdb Thu Apr 25 12:27:47 1996

ATOM

ATCM

ATOM

ATCM

ATOM

2567 CC1 VAL 5 2568 CG2 VAL 5 2569 C VAL 5 2570 0 VAL 5 2571 N PRO 5 2572 CD PRO 5 2573 CA PP.0 5 2574 CB PP.0 5 2575 CG PRO 5 2576 C PRO 5 2577 0 PRO 5 2578 N LED 5 2579 CA LED 5 2580 CB LEU 2581 CG LEO 2582 CDI LEO 2583 CD2 LEO 2584 *C LEO 2585 0 LEO 2586 N GLO 2587 CA GLU 2588 CB GLO 2589 CG GLU 2590 CD GLU 2591 OE1 GLU 2592 OE2 GLU 2593 C 3LU 2594 0 GLU 2595 N LEU 2596 CA LEO 2597 CD LEC 2598 CG LEU 2599 CD1 LED 2600 CD2 LEU 2601 C LEU 2602 0 LEU 2603 N ARC 2604 CA ARG 2605 CB ARG 2606 CC ARG 2607 CD ARG 2608 NE ARC 2609 CZ ARG 2610 NHI AP.G 2611 NH2 ARG 2612 C ARG 2613 3 ARC 2614 N *;AL 2615 CA 2616 C3B AL 2617 CGI VIAL 2618 CG2 VAL 2619 C VIAL 2620 0 *;AL 2621 N TH.

2622 CA TE?.

2623 C3 TH-?.

2624 *OGI THP.

2625 CG2 THE.

2626 C THF.

2627 7 2628 N ALA 2629 CA ALA 2630 CE ALA 2631 ALA 2632 0 ALA 2633 N ALA 2634 CA ALA 2635 CB ALA 2636 AA 2637 3 kLA 2638 N SEA 2633 CA 2640 CB SER 2641 OG 3ZSA 2642 C S.ER 264-3 0 3SE? 2644 N 94 94 94 94 95 95 95 95- 95 '95 '95 96 96 596 596 596 596 596 596 597 591 59"7 597 597 597 597 5971 597 598 598 598 598 598 598 598 598 599 599 599 599 599 599 599 599 599 599 599 600 600 600 600 600 600 600 601 601 601 601 601 601 601 602 602 602 602 602 603 i03 603 603 603 604 604 604 604 604 604 605.

67.086 31.490 69.894 1.00 11.27 66.359 32.005 72.175 1.00 8.98 64.874 29.552 12.261 1.00 6.86 64.201 30.239 73.037 L.00 9.44 65.287 28.308 72.572 1.00 4.06 65.910 27.414 11.592 1.00 4.50 65.040 27.558 13.802 L.00 4.33 65.623 26.185 -3.468 1.00 4.0C7 65.442 26.084 72.064 1.00 2.00 65.728 26.142 75.048 1.30 3. 66.955 28.077 75.180 1.00 3.03 64.923 28.692 75.955 1.00 3.21 65.420 29.282 77.199 1.00 4.16 64.610 30.596 77.561 1.00 3.29 65.384 31.870 78.068 1.00 2.00 64.500 32.639 79.002 1.00 3.47 66.646 31.534 78.783 1.00 2.16 65.252 28.293 78.347 1.00 4.67 64.121 27.938 73.721 1.00 2.!2 66.384 27.861 78.900 1.00 4.53 66.406 26.943 80.031 1.00 3.76 67.566 25.980 79.909 1.00 2.00 67.699 25.125 81.113 1.00 2.00 68.548 23.955 80.855 1.00 5.62 69.206 23.971 79.805 1.00 10.01 68.562 22.014 81.675 1.00 6.65 66.483 27.704 81.367 1.00 2.57 67.322 28.596 81.536 1.00 3.19 65.590 27.358 82.296 1.00 3.03 65.519 28.001 63.600 1.30 2.16 64.159 28.670 83.777 1.00 -2.00 63.756 29.657 82.681 1.00 2.00 62.279 29.702 82.601 1.00 2.00 64.368 31.021 82.888 1.00 2.00 65.761 26.988 64.700 1.00 2.92 65.337 25.833 84.605 1.00- 2.64 66.462 27.428 85.736 1.00 2.34 66.904 26.580 86.862 1.00 3.62 «8.254 26.115 86.710 1.00 6.78 68.479 24.611 86.512 1.00 10.90 69.385 24.359 85.308 1.00 14.84 69.658 22.945 85.047 1.00CO 17.19 70.176 22.100 65.942 1.00 17.80 70.472 22.515 £7.182 1.30 17.23 70.452 20.845 65.580 1.00 15.70 66.711 27.367 68.150 1.00 3.41 67.394 28.364 68.259 1.0 4.23 65.843 26.979 89.081 2. 7 65.756 27.644 90.387 2. :7 64.322 28.001 90.825 :.OC 2.02 64.336 28.512 92.248 l.00 63.737 29.035 69.917 1.0C 2.00 66.273 26.622 91.371 1.30 3.23 65.744 25.525 91.426 1.30 4.11 67.309 26.963 92.124 1.00 5.21 67.881 2S.043 93.098 1. C 6.14 69.296 25.601 92.688 C- 69.228 24.939 91.430 1.00 12.77' 69.890 24.631 93.684 1.30 8.70 67.995 26.634 94.481 1.3C 8.74 68.267 27.822 94.637 2: 11.77 67.788 2S.792 95.484 67.915 26.196 96.877 6.2 67.254 25.191 97.745 3.1 69.404 26.180 97.153 3 10.107 25.324 96.613 11.56 69.872 27.069 93.036 9.7'3 71.292 27.162 98.415 22 71.517 28.370 99.300 i. 71.871 25.882 99.070 .:23 73.066 25.785 99.320 71.026 24.892 9".324 71.491 23.639 99.897 44 10.409 22.980 1C0.740 2 69.702 22.024 99.997 5.42 71.914 22.689 98.77- 72.462 21.61' 9).042 11.6, 71.604 23.070 97.535 .29 br f2lc .pdb ATOM 2645 CA GLY ATOM 2646 C GLY ATOM 2647 0 GLY ATOM 2648 N ALA ATOM 2649 CA ALA ATOM 2650 CB ALA ATOM 2651 C ALA ATOM 2652 0 ALA ATOM 2653 N PRO ATOM 2654 CD PRO ATOM 2655 CA PRO ATOM 2656 CB PRO ATOM 2651 CG PRO ATOM 2658 C PRO ATOM 2659 0 PRO ATOM 2660 N ARC ATOM 2661. CA ARG ATOM 2662 CB ARG ATOM 2663 CG ARC ATOM 2664 CD ARG ATOM 2665 NE ARG ATOM 2666 CZ ARG ATOM 2667 NH1 ARC ATOM 2668 NH2 ARC ATOM 2669 C ARC ATOM 2610 0 ARG ATOM 2671 1 TYP.

ATOM 2672 CA TYP.

ATOM 2673 CS TYR ATOM 2674 CC TYR ATOM 2675 CD1 TYR ATOM 2676 CE1 TYR ATOM 2677 C02 TYP.

ATOM 2678 CE2 TYP.

ATCH 2679 CZ TYP.

ATOM 2680 OH TYR ATOM 2681 C TYP.

ATOM 2682 0 TYR ATOM 2683 N HIS ATOM 2684 CA HIS ATOM 2685 CB HIS ATOM 2686 CG HI! ATOM 2687 CD2 HI! ATOM 2688 ND1 H:! ATOM 2689 CEI HIS ATOM 2690 NE2 HI! ATOM 2691 C HIS ATOM 2692 HIS ATOM 2693 N ARG ATOM 2694 CA ARG ATOM 2695 CB ARG ATOM 2696 CG ARG ATOM 2697 CD ARG ATOM 2698 NE ARG ATOM 2699 CZ ARG ATOM 2700 NHI ARG ATOM 2701 NH2 ARG ATOM 2702 C ARG ATOM 2703 0 ARC ATOM 2704 N VAL ATOM 2705 'A VAL ATOM 2706 :B VAL ATOM 2707 CCI VAL ATOM 2706 CG2 VAL ATOM 2709 C VAL ATOM 2710 V AL ATOM 2711 N ATOM 2712 CA ILE ATOM 2712 Cb ILE ATOM 2714 SC2 ILt ATOM 2715 CCI ILE ATOM 2716 CD1 ILE ATOM 2717 ILE ATOM 2718 1 3 L- ATOM 2719 N H:i ATOM 2720 CA HIS ATOM 2721 Cb P'- ATOM 2722 CC H:S 605 605 605 606 606 606 606 606" 607 607 607 607 607 607 607 608 608 608 608 608 608 608 608 608 608 608 609 609 609 609 609 609 609 609 609 609 609 609 610 610 610 610 610 610 610 610 610 610 611 611 611 611 611 611 611 611 611 611 611 612 ;12 612 612 612 612 612 613 A13 613 61? 613 613 413 614 614 614 614 71.944 22.262 96.378 1.00 17 70.709 21.620 95.785 1.00 '.43 70.711 21.198 94.631 1.00 8.81 69.639 21.606 S6.573 00 7.11 68.376 21.001 96.194 1.00 6.20 67.492 20.885 97.387 i.30 2.64 617.665 21.770 95.11; ".30 6.88 67.450 22.974 95.234 1.30 7.80 67.222 21.063 94.074 I.0CO 6.21 67.45"; 19.636 93.821 1.30 6.78 66.520 21.660 92.950 i.00 7.75 66.656 20.587 91.845 1.00 7.27 67.655 19.620 92.355 1.00 5.40 65.046 21.969 93.220 1.C0O 6.86 64.287 21.084 93.599 1.00 6.25 64.656 23.215 92.953 1.00 6.55 63.284 23.658 93.095 1.00 6.82 63.198 25.105 93.591 1.00 7.55 63.510 25.320 95.066 1.00 11.99 62.608 24.474 95.992 1.00 14.22 61.169 24.719 95.820 1.00 14.28 60.530 25.828 96.200 1.00 14.39 61.193 26.817 96.773 1.00 15.96 59.216 25.936 96.048 00 13.38 62.586 23.548 91.739 1.00 6.91 61.613 22.836 91.612 00 9.99 63.095 24.194 90.700 1.00 7.03 62.405 24.140 89.406 1.00 7.82 S1.532 25.394 89.203 1.00 9.92 60.543 25.684 90.298 1.00 11.75 60.700 26.798 91.137 1.00 12.36 59.768 27.078 92.156 1.00 13.98 !9.434 24.852 90.499 1.00 13.86 58.494 25.120 91.506 1.00 13.63 58.664 26.235 92.326 1.00 15.21 !7.689 26.529 93.255 1.00- 17.36 63.316 24.032 88.193 1.00 7.45 64.448 24.514 88.207 1.00 10.10 :62.803 23.416 87.137 1.00 4.17 63.536 22.308 85.886 1.00 3.51 64.306 21.995 85.775 00 2.85 65.112 21.883 84.524 1.00 2.00 65.692 22.830 83.753 1.00 2.00 65.346 20.681 83.896 00 2.00 66.030 20.893 82.786 1.00 2.00 6.250 22.189 82.676 1.00 2.00 i2.500 22.456 t4.774 00 3.94 £1.459 22.824 84.794 .00O 4.37 62.790 24.306 E3.807 1.00 4.10 61.858 24.561 82.756 1.00 2.00 60.946 25.703 83.222 1.00 2.00 59.476 23.573 82.826 1.00 5.34 58.701 26.890 82.920 1.00 2.76 57.501 26.833 82.093 1..00 4.99 56.647 27.834 81.931 1.00 4.31 !6.85C 28.973 E2.542 :.00 9.07 !5.605 27.711 f1.138 .00 2.00 .2.657 24.994 81.558 1.00 2.00 63.800 25.350 81.680 1.00 3.11 i2.074 24.333 60.388 1.00 2.76 25.256 7.ll9 1.00 5.17 .3.056 24.068 78.198 1.0O 5.26 .3.806 24.56' 76.967 1.00 6.96 63.917 23.089 78.935 00 9.67 ';.490 25.968 -3.464 2C- 4.40 "0.382 25.436 78.481 1..0 5.97 61.674 27.1897 7.968 1.00 2.39 £0.

5 5 7 27.374 17.340 .30 2.00 !9.889 28.933 78.270 1.00 2.00 !9.244, 28.279 2. 1' 60.89C 30.015 73.669 OC 2.00 60.261 31.241 -).182 .00 2.00 c0.

9 9 i -28.501 .094 i 2'! 62.164 28.553 73.709 .OC0 2.06 60.012 29.173 75.412 00 60.252 30.00? 74.241 OC 63 59.604 29.427 ?2.970 OC 6(..447 28.410 72.271 oC. 2.10 Thu Apr 25 12:27:47 1996 -66brt21c.pdb Thu Apr 25 12:27:47 1996

ATOM

ATCOM

ATOM

ATCH

ATOM

ATCM

ATCH

ATOM

ATOMC

ATOM

2723 CD2 HIS 6 2724 ND1 HIS 6 2725 CE1 HIS 6 2726 NE2 HIS 6 2727 C HIS 6 2728 HIS 2729 N ILE 2730 CA ILE 2731 CB ILE 2732 CG2 ILE 2733 CGI ILE 2734 CD1 ILE 2735 C ILE 2736 0 ILE 2737 N ASN 2738 CA ASN 2739 CB ASH 2740 -CG ASN 2741 001 ASN 2742 ND2 ASN 2743 C ASN 2744 0 ASN 2745 4 GLU 2746 CA GLO 27147 CB GLU 2748 CG GLU 27149 CD GLU 2750 E1 GLO 2751 OE2 GLO 2752 C GLU 2753 0 GLO 2754 N VAL 2755 CA VAL 2756 CB VAL 2757 CGI VAL 2758 CG2 VAL 2759 C VAL 2760 0 VAL 2761 N VAL 2762 CA VAL 2763 C3 VAL 2764 CGC1 VAL 2765 CG2 VAL 2766 C VAL 2767 0 VAL 2768 N LEU 2769 CA LEU 2770 CB LEU 2771 CG LEU 2772 CD1 LEV 2773 CD2 LEU 2774 C LEU 2775 0 LEU 2776 N LEU 2777 CA LEU 2778 CB LEU 2779 C3 LEO 2780 DI LEU 2781 :C2 LEU 2712 C LEU 27832 LEU 2784 ASP 271-85 A ASF 2786 :3 ASP 27' :GC ASP 27188 D1 AS? 2789 :D2 ASP 2790 ASP 2791 1 ASP 2792 -N ALA 2793 CA ALA 2794 CS ALA 27195 ALA 27196 ALA 27971 PRP.

2798 CD PRO 2799 CA PP.C 2800 CE' PP.C- 614 614 614 14 614 614 615 615' 615 615 615 615 615 615 616 616 616 616 616 616 616 616 611 617 611 617 617 617 617 611 618 618 618 618 618 618 618 618 619 619 619 619 619 619 619 620 620 620 620 620 620 620 620 621 621 621 621 621 621 621 621 622 622 622 622 622 622 622 622 622 623 622 623 622 624 624 624 624 61.353 28.536 71.281 1.

60.442 27.015 72.609 1.

61.310 26.419 71.865 1.

61.875 27.284 71.051 1.

59.580 31.311 74.664 1.

58.419 31.306 75.046 1.

60.315 32.412 74.674 1.

59.717 33.661 75.108 1, 60.770 34.768 75.221 1 60.102 36.115 75.507 1 61.785 34.387 76.307 1 63.067 35.246 76.351 1 58.569 34.079 14.205 1 57.609 34.687 14.651 1 58.639 33.673 72.943 1 57.618 34.015 71.945 1 58.205 33.893 70.513 1 58.860 32.539 10.236 1 56.410 31.767 69.399 1 59.954 32.273 70.910 1 56.287 33.247 72.124 1 55.265 33.632 71.581 1 56.280 32.240 72.989 1 !5.088 31.444 73.242 1 55.424 29.951 73.185 1 56.381 29.633 72.086 1 16.433 28.180 71.704 1 56.653 21.922 70.498 i 56.276 27.291 72.575 54.438 31.144 74.587 53.440 21.127 14.930 54.995 32.667 75.354 54.433 32.908 76.655 1 55.365 32.566 77.870 55.666 31.109 77.838 56.651 33.331 77.890 54.119 34.459 76.127 54.600 35.167 77.616 *!3.333 34.937 75.778 52.970 36.345 75.792 52.765 36.886 74.407 52.741 38.409 74.449 53.884 36.412 73.519 51.700 36.587 76.589 50.817 35.731 76.610 51.639 37.734 77.268 50.492 28.143 78.080 50.702 37.790 73.554 49.613 37.183 80.438 50.233 37.141 81.775 48.306 37.985 80.529 50.382 39.654 77.920 50.858 40.437 78.736 49.739 40.044 16.834 49.549 41.432 76.465 48.832 41.498 75.111 49.469 40.971 73.845 48.395 40.832 72.831 50.545 41.903 73.377 48.130 42.253 77.427 47.941 41.728 78.198 48.918 42.565 77.355 48.148. 44.513 73.128 48.6-8 45.938 77.368 47.746 46.300 13.963 50.398 41.342 78.724 49.927 45.580 79.976 46.855 44.429 77.336 46.861 44.075 74.152 ;5.754 44.808 77.965 44.452 44.764 177.326 43.375 44.723 13.402 267 '45.175 74.399 413 46.953 76.489 2.311 45.990 75.462 42.607 44.628 75.175 42.969 46.928 74.486 41.i33 46.241 73.632 00 2.96 00 4.63 00 2.00 00 6.21 00 3.58 .00 2.50 .00 2.76 .00 2.55 .00 2.49 .00 2.99 .00 2.00 .00 2.00 .00 3.27 .00 5.04 .00 5.73 .00 4.76 .00 2.00 .00 2.00 .00 2.00 .00 2.00 .00 4.60 .00 6.70 .00 4.63 .00 5.16 .00 4.92 .00 8.53 .00 11.83 .30 15.40 .00 14.68 ;.00 4.18 1.00 -7.74 1.00 3.63 1.00 2.00 1.00 2.00 1.00 2.00 1.00 2.00 1.00 2.00 1.00 2.77 1.00 2.00 1.00 3.10 1.00 2.32 1.00 2.43 L.00 7.61 1.00 4.11 1.00 6.41 1.00 2.53 1.00 3.37 1.00 3.39 1. 00 3.95 1.00 5.62 1.00 3.31 1.00 5.44 1.00 7.07 1.00 7.07 1.00 5.70 1.00 5.58 1.00 2.00 1.00 2.42 1.00 2.00 1.00 7.59 1.00 8.04 1.00 11.43 OC 10.55 1.00 9.98 1.OC 11.16 OC 12.42 .00 11.12 OC 10.98 1.00 11.16 '.30 12.11 1.00 12.49 1.00 13.24 10.77 1.00 11.45 1.00 7.62 1.0C 7.09 6.69 .00 6.32

I

7 o 3 7 6 6 3 7 6 3 3 7 6 6 6 A 3 6 6 6 3 6 6 4 1 6 6 3 a 7 4 5 4 3 4 6 4 7

*I

-67bm.f2

ATOM

ATCH

ATOM

ATCHOM

ATOM

ATCHOM

ATOM

ATOH

ATOM

ATCH

ATOt Lc.pdb Thu Apr 25 12:27:47 1996 2801 CG PRO 6 2802 C PRO 6 2803 0 PRO 6 2804 N VAL 6 2805 CA VAL 2806 :C VAL 2801 CG1 VAL 2808 CG2 VAL 2809 C VAL 2810 0 VAL 2811 N GLY 2812 CA GLY 2813 C GLY 2814 CLY 2815 N LEO 2816 CA LEO 2811 CB LEU 2818 CG LEO 2819 CD1 LEU 2820 CD2 LEU 2821 LEU 2822 0 LEU 2823 N VAL 2824 CA VAL 2825 CB VAL 2826 CG1 VAL 2821 CG2 VAL 2828 VAL 2829 0 VAL 2830 N ALA 2831 CA ALA 2832 CB ALA 2833 C ALA 2034 0 ALA 2835 N ARG 2836 CA ARC 2831 CB ARG 2938 CC ARG 2839 CD ARG 2840 NE ARG 2841 :Z ARC 2842 NH1 ARC 2843 NH2 ARG 2844 ARC 2845 2 ARC 2846 N LEU 2941 CA LEU 2848 CB LEU 2849 CG LEU 2850 COl LEU 2851 CD2 LEU 2852 C LEU 2853 3 LEU 2854 4 ALA 2855 CA ALA 2956 CB ALA 2951 C ALA 2858 '0 ALA 2859 ASP 2860 CA ASP 28.61 CB ASP 2862 CCG ASP 2863 D1 ASP 2864 *:D2 ASP 2865 ASP 2866 2 ASP 2861 CLU 2868 CA GLU 2869 CB GLU 2910 CG GLU 2911 CC GLU 2812 ?E1 GLU 2813 3E2 GLU 2814 C GLU 2815 GLU 2816 N SER 2811 CA SER 4 2818 CB SER 24 24 24 25 525 625 625 625" 625 625 626 626 626 626 621 621 621 621 621 621 621 621 628 628 628 628 628 628 628 629 629 629 629 629 630 630 630 630 630 630 630 630 630 630 630 631 631 631 631 631 631 631 631 632 632 632 632 632 633 633 633 632 633 633 623 633 634 634 634 634 634 634 634 634 634 635 635 635 42.334 44.150 13.136 L.

42.366 48.198 15.095 1.

41.591 48.139 16.056 1.

42.693 49.352 14.518 1.

42.152 50.638 74.969 1.

43.254 51.616 15.160 1.

44.097 51.324 76.386 1.

44.116 51.744 73.933 1.

41.136 51.193 73.950 1.

40.119 50.513 12.910 1.

40.629 52.392 74.243 1.

39.683 53.098 13.389 1.

38.396 52.482 12.843 1.

31.906 52.901 11.715 1.

31.819 51.522 13.565 1.

36.516 50.879 13.112 1.

36.138 49.789 14.092 1.

34.946 48.955 13.631 1 35.399 48.124 12.461 1 34.421 48.034 14.140 1 35.415 51.869 12.928 1 35.001 52.548 13.881 1 34.954 52.005 11.682 1 23.814 52.862 11.355 1 34.166 54.119 70.490 1 34.935 55.151 11.318 1 34.942 !3.723 69.244 1 32.781 52.009 10.609 1 33.146 51.111 69.143 1 31.528 52.151 11.036 1 30.393 51.453 10.440 1 29.532 50.830 11.531 1 29.593 52.496 69.664 1 29.684 53.693 69.900 1 28.823 52.061 68.659 1 28.014 52.919 67.845 1 28.813 53.103 66.809 1 29.081 55.154 61.115 1 29.565 56.016 65.999 29.366 51.461 66.223 29.621 58.112 67.368 30.108 51.460 68.455 29.421 59.440 61.426 26.861 52.308 61.125 26.945 51.133 66.744 25.181 53.049 66.944 24.650 52.498 66.233 23.319 53.261 66.603 22.269 52.408 67.2:4 22.275 50.961 66.711 22.351 52.322 68.140 24.826 52.110 64.791 24.139 53.915 64.34: 25.094 51.158 64.0!' 25.170 51.915 62.641 25.601 50.699 61.943 23.'11 52.420 62.225 22.964 51.604 61.190 23.542 53.700 62.434 22.239 54.366 62.2C3 22.438 55.880 62.0C: 22.352 56.115 63.272 21.718 56.363 64.3C.

22.852 57.911 63.227 21.466 53.894 60.921 20.2523 53.666 60.941, 22.131 53.741 59.192 21.428 53.465 58.5;4 22.349 53.156 51.325 22.841 55.203 51.322 23.766 55.525 56.15: 24.012 54.625 55.261 24.295 5t.69i 56.34~i 20.911 :2.021 58.372 20.024 51.126 51.553 21.465 51.135 59.163 21.062 49.120 59.145 22.288 48.820 58.694 37 00 9.96 00 10.98 00 13.30 00 11.2 00 8.51 00 8.17 00 10 00 6.41 00 11. :0 00 11.2 00 10.53 00 12.11 00 14.19 00 14.32 00 16.06 .00 17. 3 .00 13.89 .00 13.26 .00 15.13 .00 12.93 6 .00 18.21 4 .00 17.62 .00 19.54 .00 19.16 .00 18.31 .00 19.05 .00 18.46 .00 21. 1 .00 19.35 .00 21.23 .00 21.69 .00 25.91 .00 22.67 .00 23.69 1.00 22.36 1.00" 19.90 1.00 19.83 1.00 22.67 1.00 24.86 1.00 26.19 1.00 28.04 1.00 26.18 1.00 26.18 1.00 13.38 1.00 19.93 1.00 18.71 1.00 13.38 1.30 18.29 1.00 17.34 1.00 18.31 1.00 18.38 1.00 21.32 1.00 23.22 1.00 21.42 1.00 22.08 1.00 22;7 1.00 24.54 1.00 25.46 1.00 90.30 1.00 90.30 1.00 9C.30 1.00 90.30 1.00 9C. 30 1.00 90. :0 1.00 :C ".00 9C. 20 1.00 90.;0 1.00 9:.30 1.00 9C. 30 1.30 :0 1.00 9C.30 1.CO 9C. -0 :3 1.00 9C. i.CC "3 OC :0 ".OC 9C.30 1.00

I

6 6 1 6 9 6 3 6

I

3 1 .9

A

3 6 4 7 1 3 4 5 4 1 3 3 .i n -68-

S.

bret21c.pdb ATCHM 2879 OG SER ATOM 2880 C SER ATOM 2881 0 SER ATOM 2882 N GLY ATOM 2883 CA GLY ATOM 2984 C GLY ATOM 2885 0 GLY ATOM 2886 N HIS ATOM 2887 CA HIS ATOM 2888 CB HIS ATOM 2889 CG HIS ATOM 2890 CD2 HIS ATOM 2891 ND1 HIS ATOM 2892 CE1 HIS ATOM 2893 NE2 HIS ATOH 2894 C HIS ATCM 2895 0 HIS ATOM 2896. N VAL ATOM 2891 CA VAL ATOM 2898 CB VAL ATOM 2899 CG1 VAL ATOM 2900 CG2 VAL ATOM 2901 C VAL ATOM 2902 0 VAL ATOM 2903 N VAL ATOM 2904 CA VAL ATCM 2905 CB VAL ATCM 2906 CG1 VAL ATOM 2907 CG2 VAL ATOM 2908 C VAL ATOM 2909 0 VAL ATOM 2910 N LEU ATCM 2911 CA LEU ATOM 2912 CB LEU ATOM 2913 CG LEU ATOM 2914 CD1 LEU ATCM 2915 CD2 LEU ATMC 2916 C LEU ATOM 2917 0 LEU ATOM 2918 N ARG ATOM 2919 CA ARG ATOM 2920 CB ARG ATOM 2921 CG ARG ATCOM 2922 CD AP.G ATCM 2923 NE ARG ATOM 2924 CZ ARG ATCM 2925 H1 ARP.G ATOM 2926 NH2 ARP.G ATOM 2927 C ARCG ATOM 2928 0 ARG ATOM 2929 N TRP ATOM 2930 CA TRP ATOM 2931 CB TRP ATOMC 2932 CG TRP ATOM 2933 CD2 TPP ATOM 2934 CE2 TRP ATCH 2935 CE3 TP.P ATCM 2936 'CD1 TPF ATOM 2937 NE1 TPP ATCHOM 2938 CZ2 TRP ATOM 2939 CZ3 TP.P ATOM 2940 CH2 TRF ATOMH 2941 C TRF.

ATOM 2942 0 TP.P ATOM 2943 N ATOM 2944 CA LEZ" ATOM 2945 CB LE* ATOM 2946 CC LE"-, ATOM 2947 CD1 LEt' ATOM 2948 CD2 LE' ATOM 2949 C LZ;E ATOM 2950 LEU ATOM 2951 N ATCOM 2952 CD PP.C ATOM 2953 CA PP.: ATOM 2954 CB PP.C ATOM 2955 CC PP.C.

ATOM 2956 C PP.C" 635 635 635 636 636 636 636 637 637 637 637 637 637 631 637 637) 637 638 638 638 638 638 638 638 639 639 639 639 639 639 639 640 640 640 640 640 640 640 640 641 641 641 641 641 641 641 641 641 641 641 642 642 642 642 642 642 642 642 642 642 642 642 642 642 643 643 643 643 643 643 643 643 644 644 644 644 644 644 23.189 49.037 60.063 1.00 90.00 20.328 49.370 60.435 1.00 90.00 19.394 48.552 60.427 1.00 90.00 20.780 50.010 61.488 1.00 90.00 20.217 49.834 62.821 1.00 90.00 20.996 48.771 63.586 1.00 90.00 20.541 47.640 63.790 1.00 90.00 22.203 49.107 64.010 1.00 29.39 22.920 48.155 64.8471 .00 28.30 23.190 46.817 64.148 1.00 27.49 23.915 46.854 62.196 1.00 26.32 25.124 47.337 62.400 1.00 26.14 23.338 46.289 61.665 1.00 26.56 24.176 46.428 60.659 1.00 26.93 25.247 47.050 61.079 1.00 26.35 24.223 48.651 65.427 1.00 21.39 24.505 49.862 65.452 1.00 27.46 24.921 47.631 65.968 1.00 25.98 26.119 47.770 66.646 1.00 22.67 26.169 46.693 67.730 1.00 23.93 26.966 47.127 68.963 1.00 24.68 24.781 46.310 68.2!1 1.00 23.20 27.422 47.694 65.877 1.00 21.16 27.763 46.687 65.236 1.00 17.80 28.129 48.808 65.940 1.00 19.71 29.41' 48.927 65.309 1.00 21.49 29.362 49.967 64.127 1.00 22.971 30.383 51.140 64.296 1.00 22.32 29.531 49.189 62.796 1.00 21.09 30.503 49.131 66.402 1.00 18.72 30.569 50.164 67.103 1.00 15.61 31.245 48.035 66.588 1.01) 17.29 32.312 41.853 67.561 1.00 15.07 32.296 46.385 68.002 1.00 11.06 31.948 45.925 69.398 1.00 9.33 30.755 46.635 69.940 1.00 6.96 31.703 44.456 69.328 1.00 7.60 33.727 48.158 67.106 1.00 15.19 34.319 47.345 66.393 1.00 13.52 34.320 49.236 67.616 1.00 16.40 35.717 49.564 67.269 1.00 18.02 35.744 50.820 66.406 1.00 18.96 36.505 50.600 65.100 1.00 23.80 35.742 51.114 63.884 1.00 25.92 34.649 50.212 63.502 1.00 26.12 33.446 50.620 63.085 1.00 27.21 33.173 51.935 63.013 1.00 24.02 22.538 49.716 62.685 1.00 23.76 36.638 49.707 68.527 1.00 17.87 36.119 49.879 69.655 1.00 19.51 37.972 49.598 68.366 1.00 16.84 38.925 49.723 69.515 1.00 14.61 38.165 48.534 10.453 1.00 13.11 39.106 47.243 69.819 1.00 38.203 46.359 69.133 1.00 10.16 38.926 45.195 68.814 1.00 10.08 "36.855 46.438 68.760 1.00 8.27 40.304 46.612 69.860 1.00 7.42 40.208 45.31177 69.267 1.00 10.16 38.345 44.116 68.150 1.00 8.33 36.289 45.374 68.098 1.00 ".26 37.03" 44.225 67.803 OC 13 40.424 49.824 69.178 1.OC 15.14 40.796 49.704 68.006 1.0C :7.51 41.271 49.982 70.2C7 12.07 42.741 50.063 10.039 00 "3.34 43.31C 51.312 70.616 1.0C 3.27 42.887 52.627 70.081 1.0C 9.05 43.784 53.715 70.583 1.00 7.00 43.012 52.525 68.601 1.00C .98 43.508 48.891 70.662 1.00 15.42 43.096 48.351 71.697 1.00 19.66 44.645, 48.493 70.059 CC 15.88 45.206 49.056 68.817 1.00C '5.21 45.481 47.381 70.556 1.0C 14.66 46.485 47.17!. 61.412 1.00 15.17 46.642 48.573 60.861 1.0C 15.08 46.192 47.793 71.a51 1.00 11.57 Thu Apr 25 12:27:47 1996 -69- *e *e *e brf2:

ATOM

ATCOM

ATOM

ATCOM

ATOM

AT(*

Lc.pdb 2951 0 PRO 2958 N PRO 2959 CD PRO 6 2960 CA PRO 2961 CB PRO 2962 CG PRO 2963 C PRO 2964 0 PRO 2965 N PRO 2966 CD PRO 2961 CA PRO 2968 CB PRO 2969 CG PRO 2910 C PRO 2911 0 PRO 2912 N GLO 2973. CA GLO 2974 CB GLU 2975 CG GLO 2976 CD GLO 2977 OE1 GLU 2918 OE2 GLU 2979 C GLU 2980 0 GLU 2981 N THR 2982 CA THP.

2983 CB THR 2984 OGI1 THR 2985 CC2 THR 2986 C THR 2987 0 THR 2980 H PRO 2989 CD PRO 2990 CA PRO 2991 CB PRO 2992 CG PRO 2993 C PRO 2994 0 PRO 2995 N MET 2996 CA MET 2991 CB MET 2998 CG MET 2999 SD MET 3000 CE MET 3001 C MET 3002 0 MET 3003 N THR 3004 CA THP.

3005 C9 THF.

3006 OGI THR 3001 CG2 THR 3008 C TSR 3009 0 THR 3010 N SEP.

3011 CA SER 3012 CB SEP.

3013 OG SIR 3014 'C SER 3015 0 SER 3016 N HIS 30.11 CA HIS 3018 CB HIS 3019 CG HIS 3020 CD2 HIS 3021 NDI HIS 3022 CE1 HIS 3023 NE2 HIS 3024 C HIS 3025 0 HIS 3026 N ILE S3027 CA ILE S3028 CB ILE S3029 CG2 ILE 3030 CCIG ILE 3031 CDI ILE 3032 C ILE -3033 0 ILE 3034 N ARC 144 '45 645 145 i45 645 645 645' 646 546 646 646 646 646 646 641 647 641 647 641 641 641 6471 641 648 f48 648 648 648 648 648 649 649 649 649 649 649 649 650 650 650 650 650 650 650 650 !51 651 651 651 51 651 651 652 652 652 652 652 652 653 653 4.53 653 653 453 653 653 654 654 654 654 654 654 654 654 655 46.148 48.918 12.209 46.806 46.824 12.588 46.832 45.392 12.229 41.530 47.049 13.851 48.219 45.146 74.038 47.321 44.142 13.502 48.415 48.118 13.512 49.211 48.142 12.605 48.433 49.229 74.315 47.682 49.431 75.618 49.334 50.350 74.105 49.004 51.345 75.211 47.619 50.941 15.674 50.809 49.956 74.116 51.204 48.918 14.679 51.620 50.786 13.410 53.043 50.546 73.383 53.753 51.217 74.552 53.188 52.131 14.380 54.239 53.470 75.640 53.641 53.215 16.715 55.175 54.305 15.563 53.485 49.082 73.218 54.508 48.691 73.195 52.155 48.316 12.384 53.029 46.899 72.062 51.832 45.984 12.452 51.552 46.119 13.852 52.134 44.533 12.141 53.295 46.761 70.534 52.584 41.310 69.115 54.320 45.968 10.131 55.333 45.245 10.941 54.610 45.819 68.713 56.106 45.495 68.11 56.233 44.592 69.879 53.821 44.701 68.015 52.957 44.106 68.705 54.224 44.406 66.838 53.645 43.363 65.981 54.158 41.969 66.310 55.616 41.834 66.230 56.219 41.811 64.535 56.571 40.141 64.031 52.112 43.354 65.915 51.418 42.289 65.991 51.581 44.546 65.891 50.136 44.808 65.90f 49.858 46.198 65.32: 50.419 41.191 66.16; 48.364 46.502 65.18' 49.353 43.184 65.03! 48.309 43.264 65.454 49.866 43.419 63.82! 49.110 42.623 62.86: 49.510 42.949 61.41 '50.405 41.990 60.89 49.235 41.114 63.15 49.034 40.261 62.27 49.523 40.195 64.39 49.584 39.399 64.80 50.991 39.071 65.25 51.892 38.953 64.02 52.285 31.884 63.28 52.411 40.071 63.43 53.171 39.668 62.35 53.011 38.361 62.25 48.416 39.163 65.81 41.989 38.044 65.91 48.046 40.234 66.4' 47.012 40.145 61.51 41.059 41.456 68.3: 46.252 41.36a 6).6! 48.469 41.891 68.1 48.560 43.367 69.1: 45.633 39.187 67.1 44.981 40.508 66.3 45.214 38.661 7.1 1.00 12.33 1.00 10.61 1.00 10.47 1 1.00 3.59 1.00 10.22 1.00 9.51 1.00 9.51 1.00 11.11 1 .00 9.63 1.00 9.62 1.00 9.90 1.00 9.95 1.00 11.92 i 1.00 13.01 1.00 14.24 3 1.00 13.38 1 1.00 14.58 1.00 15.62 i 1.00 19.18 f 1.00 20.10 6 1.00 22.18 1.00 19.41 1.00 14.37 1.00 18.36 1.00 11.24 1 1.00 9.00 1.00 9.18 1.00 10.10 1.00 8.04 1.00 9.21 1.00 9.52 3 1.00 7.20 7 1.00 6.54 1.00 6.88 i 1.00 5.46 6 1.00" 3.39 6 1.00 8.117 1.00 9.10 1.00 9.01 1.00 9.19 1.00 8.66 1.00 7.85 1.00 1.28 14 1.00 2.00 11.50 1.00 13.41 1.00 11.63 1.00 12.15 1 1.00 13.04 1.00 14.67 1 1.00 15.14 9 1.00 12.51 1 1.00 16.135 1.00 11.13 3 1.00 6.89 6 1.00 5.16 4 5 1.00 4.04 1 1.00 1.54 4 1.00 9.34 0 1.00 1.771 5 1.00 6.49 3 1.00 6.61 9 1.00 9.79 8 1.00 9.28 8 1.00 10.33 15 1.00 5.42 41 00 '.91 10 00 4.62 94 1.00 5.90 10 1.00 5.11 10 1.00 4.75 55 1.00 3.95 53 00 5.93 60 1.00 3.24 31 2.00 56 1.00 5.10 95 1.00 ".39 "3 O0 5.10 Thu Apr 25 12:27:47 1996 39 brtc21c.pdb Thu Apr 25 12:27:47 1996 t S. S

S

5555

S

S. S S S

S.

S

*S

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Se S5

ATOM

ATCOM

ATOM

ATCM

ATOM

ATCM

ATOM

ATCH

ATOM

ATCM

ATOM

ATCOM

ATOM

ATCM

ATOM

ATOM.

ATOM

ATCM

ATOM

ATCM

ATOM

ATC.O

ATOM

3035 CA ARG 3036 CB ARG 3031 CG ARG 3038 CD ARG 3039 NE ARG 3040 CZ ARG 3041 NH1 ARG 3042 NH2 ARG 3043 C ARG 3044 0 ARG 3045 N TYR 3046 CA TYR 3047 CB TYR 3048 CG TYR 3049 CDl TYR 3050 CE1 TYR 3051 CD2 TYR 3052 .CE2 TYR 3053 CZ TYR 3054 OH TYR 3055 C TYR 3056 0 TYR 3037 N GLO 3058 CA GLU 3059 CB GLO 3060 CG GLU 3061 CD GLU 3062 OE1 GLU 3063 0O2 GLU 3064 C GLU 3065 0 GLO 3066 N VAL 3067 CA VAL 3068 CB VAL 3069 CG1 VAL 3070 CG2 VAL 3071 C VAL 3072 0 VAL 3073 N ASP 3014 CA ASP 3015 CB ASP 3076 CG ASP 3077 001 ASP 3078 OD2 ASP 3079 C ASP 3080 0 ASP 3081 N VAL 3082 CA VAL 3003 CB VAL 3084 CG1 VAL 3085 CG2 VAL 3086 C VAL 30871 0 VAL 3088 N SER 3089 CA SER 3090 CB SER 3091 OG SER 3092 *C SER 3093 0 SER 3094 N ALA 3095 CA ALA 3096 CB ALA 3097 C ALA 3098 0 ALA 3099 N GLY 3100 CA GLY 3101 C GLY 3102 0 GLY 3103 N ASN 3104 CA ASN 3105 CS ASN 3106 CG ASN 3101 00D1 ASN 3108 ND2 ASN 3109 C ASN 3110 0 ASN 311) N CLY 3112 CA GLY 655 655 635 633 635 655 6355 655 655 655 656 6536 656 656 656 656 656 656 656 656 656 656 656 657 651 651 657 657 6537 657 657 658 650 658 658 658 658 659 659 659 659 659 659 659 639 660 660 660 660 660 660 660 661 661 661 661 661 661 662 662 662 662 662 643 663 663 663 663 664 664 664 664 664 664 664 664 665 665 43.856 38.107 61.582 1 43.941 36.608 67.851 1 42.732 35.835 67.393 1 42.923 35.234 66.013 1 41.690 35.243 65.243 1 41.487 34.509 64.155 1 42.441 33.699 63.683 1 40.343 34.523 63.465 1 43.012 38.786 68.687 1 43.561 39.225 69.106 1 41.706 38.916 68.485 1 40.852 39.533 69.491 1 40.315 40.886 69.041 1 41.339 41.973 69.131 1 41.994 42.423 67.995 1 43.029 43.341 68.077 1 41.736 42.482 10.366 1 42.779 43.407 70.461 1 43.422 43.826 69.301 1 44.498 44.701 69.373 1 39.693 38.646 69.848 1 39.504 37.608 69.210 1 39.967 39.048 10.905 37.776 38.359 11.431 38.109 37.385 12.555 1 36.874 36.766 73.217 36.755 35.254 72.977 36.151 34.838 01.945 37.245 34.472 73.826 36.827 39.366 72.006 37.163 40.033 72.985 35.635 39.429 71.412 34.550 40.334 71.819 33.826 40.908 70.578 32.355 41.228 10.903 34.552 42.151 70.055 33.518 39.602 12.697 33.025 38.519 72.336 t33.168 40.225 73.818 32.217 39.660 14.762 32.857 39.583 16.152 31.841 39.320 17.262 31.108 40.220 78.127 31.191 38.238 77.248 30.959 40.488 14.877 30.946 41.400 75.641 29.924 40.096 74.127 28.623 40.775 74.150 27.835 40.550 72.8351 28.760 40.397 11.683 26.931 39.368 72.990 27.768 40.299 75.335 27.719 39.092 75.635 27.018 41.218 75.943 26.210 40.865 77.104 27.146 40.683 18.308 8.007 39.569 7S.169 25.132 41.882 77.544 24.814 42.901 76.839 24.616 41.596 18.784 23.690 42.325 79.596 23.909 43.8356 79.493 22.242 41.933 13.339 21.935 40.739 79.266 21.367 42.948 79.300 19.936 42.775 79.047 19.124 41.953 80.038 18.542 40.929 -9.649 19.032 42.453 81.277 18.317 41.816 82.410 17.157 42.106 82.938 15.907 42.725 82.013 1!.-91 .43.57 81.114 14.939 41.852 82.294 17.831 40.332 82.334 16.976 39.992 8..488 18.250 39.511 82.243 11.918 38.122 82.294 .00 4.10 6 .00 6.54 6 .00 12.78 6 .00 19.16 .00 25.22 .00 29.18 .00 29.93 .00 30.11 .00 4.93 .00 4.74 s .00 3.05 .00 4.57 .00 5.74 .00 11.08 .00 11.86 .00 13.79 .00 13.83 .00 14.75 .00 14.26 .00 19.33 .00 7.31 .00 1.58 00 9.63 1.00 9.06 1.00 11.39 1.00 14.76 1.00 17.29 1.00 19.32 1.00 18.51 1.00 10.04 1.00 .8.78 1.00 13.32 1.00 15.04 1.00 17.13 1.00 18.15 1.00 15.29 1.00 13.57 1.00 16.39 1.00 15.80 1.00 16.22 1.00 18.33 1.00 17.02 1.00 16.96 1.00 15.05 1.00 17.09 1.00 16.55 1.00 17.40 1.00 18.10 1.00 15.37 1.00 16.34 1.00 15.04 1.00 20.40 1.00 21.69 1.00 22.33 1.00 23.37 1.00 23.56 1.00 25.08 1.00 25.29 1.00 24.51 1.00 26.02 1.00 23.48 1.00 24.66 1.00 22.08 1.00 16.69 1.00 23.15 1.00 24.87 1.00 23.53 1.00 22.72 1.00 24.09 1.00 25.66 1.00 27.33 1.00 28.05 1.00 29.36 1.00 26.86 1.00 2."78 1.00 21. 92 OC 24.4!5 00 24.29

I

6 6 6 6 8 8 7 4 6 6 6 6 a 8 6 8 1 6 6 6 6 8 7 6 6 6 a a 6 3 7 4 4 4 4 8 7 6 6 8 6 8 7 4 *1 ;4 *i 'i

II

*i -71hbr2llc.pdb Thu Apr 25 12:27:47 1996 00Ss as *52 as@*.

s ee s.

o

S

ATCM

ATCH

ATOM

ATCM

ATOM

ATCM

ATOM

ATCM

ATOM

ATCM

ATOM

ATCM

ATOM

ATCM

ATOM

ATCM

ATOM

ATCM

ATOM

ATCM

ATOM

ATCH

ATCM

ATOM

ATom

ATOM

ATCM

ATOM

ATCH

ATCM

ATOM

ATCH

ATCM

ATCH

ATOM

ATCM

ATOM

ATCM

ATOM

ATCH

ATOM

ATCH

ATOM

ATOn

ATCH

ATOM

ATCHo 3113 C GLY 3114 0 GLY 3115 N ALA 3116 CA ALA 3117 CB ALA 3118 C ALA 3119 0 ALA 3120 N GLY 3121 CA GLY 3122 C GLY 3123 O GLY 3124 N SER 3125 CA SE.

3126 CB SER 3127 OG SER 3128 C SER 3129- 0 SER 3130 N VAL 3131 CA VAL 3132 C VAL 3133 CGl VAL 3134 CG2 VAL 3135 C VAL 3136 0 VAL 3131 N GLN 3139 CA GLN 3139 CB GLN 3140 CC GLN 3141 CD GLN 3142 OE GN 3143 NE2 GLN 3144 C GLN 3145 0 GLN 3146 N ARG 3147 CA AR 3148 CB ARG 3149 CG ARG 3150 CD ARG 3151 NE ARG 3152 CZ ARG 3153 NH1 ARG 3154 NH2 ARG 3155 C ARC 3156 0 ARG 3151 N VAL 3158 CA VAL 3159 CB VAL 3160 CGI VAL 3161 CG2 VAL 3162 C VAL 3163 0 VAL 3164 N CGLU 3165 CA LD 3166. C GLO 3167 CC GLD 3168 CD GLU 3169 OEl GLU 3170 '0E2 GLD 3171 C GLU 3172 0 GLU 3173 N ILE 3174 CA ILE 3175 C ILE 3176 CC2 ILE 3171 CG1 ILE 3173 CD1 ILE 3179 C ILE 3180 0 ILE 3181 N LEU 3182 CA LEU 3183 C LEU 3184 C LEU 3185 CDO LEU 3186 CD2 LED 3187 C LEU 3188 0 LED 3189 N GLU 3190 CA GLU 665 665 666 666 666 666 666 667 667 667 661 668 668 668 668 668 668 669 669 669 669 669 669 669 670 670 670 670 670 670 670 670 670 671 671 671 671 671 671 671 671 671 671 671 672 672 672 672 672 672 672 673 673 673 673 673 673 673 673 673 674 674 674 674 674 674 674 674 675 675 675 675 675 675 615 675 676 676 18.560 37.239 82.235 1.00 23.94 18.754 36.011 62.454 1.00 24.01 18.767 37.805 81.047 1.00 22.31 7 19.457 37.054 80.035 1.00 22.71 19.331 37.724 78.693 1.00 21.95 6 20.893 37.166 80.577 1.00 24.38 6 21.300 38.225 81.075 1.00 25.18 a 21.579 36.036 80.672 1.00 25.52 7 22.941 36.058 8L.159 1.00 26.48 i 23.838 35.946 79.949 00 28.11 24.789 35.145 79.937 1.00 29.47 23.483 36.689 78.896 1.00 28.73 7 24.256 36.669 77.641 1.00 28.04 6 23.634 37.605 76.547 1.00 28.80 6 24.312 37.574 75.278 1.00 24.54 8 25.597 37.209 78.057 1.00 27.60 6 25.647 38.220 78.198 1.00 27.37 8 26.623 36.397 77.762 1.00 26.59 7 28.049 36.715 77.987 1.00 23.08 6 28.665 35.974 79.266 1.00 20.59 6 28.460 34.484 79.178 1.00 19.42 6 30.175 36.316 79.456 1.00 20.06 6 28.668 36.266 76.644 1.00 21.55 6 29.846 35.888 76.545 1.00 20.19 9 27.845 36.409 75.598 1.00 20.21 7 28.193 36.009 74.245 1.00 18.75 6 27.005 36.236 73.312 1.00 17.59 6 27.182 35.569 71.935 1.00 22.13 6 27.933 36.432 70.902 1.00 22.70 6 28.500 37.485 71.234 1.00 24.66 a 21.912 35.995 69.634 1.00 23.69 7 29.519 36.583 73.696 1.00 17.46 6 29.792 37.782 73.770 1.00 15.56 8 30.332 35.679 73.157 1.00 15.69 7 31.631 36.013 72.639 1.00 16.60 6 32.678 35.334 73.517 1.00 17.57 6 32.946 36.061 74.887 1.00 19.96 6 32.493 35.269 76.139 1.00 18.73 6 32.986 35.894 77.368 1.00 19.78 7 33.863 35.344 78.218 1.00 19.40 6 34.370 34.124 78.021 1.00 17.08 7 34.304 36.062 79.241 1.00 17.95 7 31.869 35.669 71.158 1.00 18.54 6 31.425 34.618 10.645 1.00 20.62 8 32.576 36.556 70.460 00 18.18 7 32.879 36.337 69.049 1.00 15.30 6 32.079 37.31' 68.160 1.00 15.97 4 30.649 37.440 68.682 1.00 17.58 f 32.728 38.702 68.133 1.00 17.86 4 34.379 36.538 68.849 1.00 14.22 6 34.964 37.495 69.358 1.00 14.18 8 35.011 35.587 68.184 1.00 13.30 7 36.437 35.666 67.911 1.00 14.85 6 36.902 34.409 67.150 1.00 17.98 6 36.621 34.525 65.601 .00 21.07 4 36.996 33.299 64.759 1.00 22.50 4 36.964 32.153 65.300 1.00 20.19 3 37.279 33.501 63.537 00 23.59 9 36.645 36.859 66.978 1.00 14.79 35.688 37.420 66.456 1.00 15.66 9 37.899 37.192 66.708 1.00 15.73 7 38.224 38.270 65.790 1.00 15.34 4 38.340 39.659 66.498 1.00 16.72 4 38.785 40.719 65.483 '.00 15.50 4 37.060 40.044 67.289 1.00 15.11 4 35.824 40.386 66.409 1.00 12.07 A 39.596 37.922 65.198 1.00 16.94 4 40.511 37.502 65.909 1.00 15.56 3 39.722 38.012 63.884 1.00 18.65 41.000 37.73' 63.251 00 16.13 S 40.846 37.553 61.44 1.00 16.02 4 40.335 36.155 61.359 1.00 17.94 4 38.786 36.050 61.326 1.0C 13.53 40.967 35.743 60.014 1.00 18.65 6 41.944 38.895 63.585 1.00 .16.58 6 41.500 40.013 63.920 1.00 16.45 43.240 38.587 63.521 1.00 14.67 7 44.316 39.514 63.829 1.00 12.70 4 06 *00 0 a

S

-72brf2lc.pdb Thu Apr 25 12:27:47 1996

ATOM

ATCH

ATOM

ATCH

ATOM

ATCHM

ATOM

ATCHO

ATOM

ATOM ATOM

ATCH

ATOM

ATCH

ATOM

ATCH

ATOM

ATCH

ATOM

ATCH

ATOM

ATCH

ATOM

ATCH

ATOM

ATCH

ATOM

ATCH

ATOM

ATCH

ATOM

ATCH

ATOM

ATCH

ATOM

ATCH

ATOM

ATOH

ATCH

ATOM

ATOM ATCH

ATOM

ATOH I 3191 CB GLU 3192 CC GLU 3193 CD GLU 3194 OE1 CG.

3195 012 GLU 3196 C CLJ 3197 0 ULD 3198 N SLY 3199 CA GLY 3200 C SLY 3201 0 SLY 3202 N ARG 3203 CA ARC 3204 CB ARC 3205 CC ARC 3206 CD ARGC 3207 NE ARCG 3208 CZ ARC 3209 NIl ARC 3210 NH2 ARG 3211 C ARGC 3212 0 ARC 3213 N P.

3214 CA 7-P.

3215 CB T.P.

3216 OC1 :P.

3217 CC2 T.H.

3218 C THP.

3219 0 3220 N 3221 CA G Z 3222 CB GLU 3223 CC CLU 3224 CD CLU 3225 OE1 GU 3226 0E2 GLU 3227 C GLU 3228 O GLU 3229 N CYS 3230 CA CYS 3231 CB CYS 3232 SC CYS 3233 C 5 3234 O :Y5 3235 N ;AL 3236 CA tAL 3237 CB ,,L 3238 CG1 7AL 3239 CC2 TAL 3240 C *AL 3241 0 7IL 3242 N !-u 3243 CA -w 3244 CB 3245 CG Lr.

3246 CD1I 3247 CD2 LEZ 3248 *C r 3249 0 3250 N !AR 3251 CA T.

3252 CB az;.

3253- OG SI.

3254 C 3255 O 3256 N 3257 CA 3258 CB A:: 3259 CC L:N 3260 OD1 Af: 3261 ND2 kSX 3262 C AS7 3263 3264 N 3265 CA 3266 CB 3267-C C 3268 CD1 U= 676 676 676 676 676 676 676 677 677 677 671 678 678 678 6718 678 678 678 679 678 679 678 679 679 679 679 679 679 679 680 680 680 680 680 680 680 680 680 681 681 681 681 681 681 682 682 682 682 682 682 682 683 683 683 683 683 683 683 683 684 6894 684 684 684 684 685 685 685 685 695 685 685 685 686 686 686 686 686 45.667 45.627 45.494 46.3538 44.367 44.268 43.569 45.030 45.121 43.796 43.770 42.700 41.387 40.342 39.529 40.401 41.014 41.887 42.274 42.300 41.001 41.199 40.462 40.027 40.996 41.204 42.332 38.637 38.393 37.732 36.358 36.289 36.140 35.086 34.342 35.019 35.489 35.887 34.299 33.382 33.617 32.134 31.958 31.579 31.181 29.818 29.433 30.190 27.952 28.861 28.659 28.449 27.485 27.326 28.420 28.201 '28.376 26.228 25.446 26.087 25.003 25.222 26.50, 23.61 22.80 23.39 22.04 21.71 22.99 23.99 22.97 21.74 22.27 20.89 20.58 21.77 22.71 23.70 38.907 6 37.882 6 36.518 6 36.007 6 35.967 6 40.836 6 41.007 6 41.772 6 43.103 6 43.794 6 44.949 6 43.134 6 43.743 6 42.666 6 42.932 6 42.681 6 41.368 6 40.845 5 41.325 5 39.631 6 44.532 6 44.034 6 45.743 46.552 47.685 48.405 47.148 47.171 48.336 46.384 46.812 47.765 47.101 47.782 47.032 49.045 45.579 44.641 45.578 44.462 43.402 42.836 45.006 45.763 44.688 45.174 45.877 45.270 45.785 44.077 43.049 44.;18 43.294 43.584 43.127 43.741 41.638 43.730 S44.610 S43.161 S43.521 42.906 43.257? 4 43.199 0 44.106 7 41.945 9 41.496 6 40.428 3 39.749 4 40.433 2 38.406 8 40.978 1 39.905 9 41.704 3 41.260 9 41.525 8 42.760 0 42.840 3.526 2.478 3.080 3.546 3.108 3.146 2.159 3.699 3.145 2.961 2.523 3.329 3.174 2.927 1.695 0.504 0.643 9.7087 8.700 0.037 4.420 5.529 4.249 65.390 5.669 64.448 16.229 65.182 65.540 14.604 64.332 63.128 61.755 60.847 60.138 60.825 64.076 63.364 64.654 64.498 65.603 66.606 64.540 65.448 63.517 63.511 62.131 60.969 61.867 64.001 63.342 65.258 65.859 67.348 68.299 69.667 68.3817 65.104 65.544 63.914 63.028 61.629 61.067 63.491 63.699 63.824 64.131 63.08 62.50 62.19 62.40 65.53 (5.92 66.28 67.64 68.58 68.47 69.70 1.00 12.08 1.00 11.18 1.00 13.77 1.00 16.32 1.00 13.00 1.00 12.13 1.00 12.89 1.00 11.52i.00 11.07 1.00 11.9'6 1.00 14.32 1.00 12.98 1.00 14.43 1.00 13.34 1.00 15.05 1.00 17.70 1.00 22.61 1.00 23.28 1.00 22.06 1.00 25.26 1.00 14.43 1.00 15.07 1.00 13.15 1.00 14.13 1.00 14.19 1.00 17.57 1.00 13.59 1.00 16.43 1.00 15.23 1.00 18.09 1.00 1.04 1.00 18.69 1.00 18.32 1.00 18.05 1.00 16.53 1.O0 14.40 1.00 21.29 1.00 22.54 1.00 22.91 1.00 24.61 1.00 26.42 1.00 26.71 1.00 24.30 1.00 23.84 1.00 21.58 1.00 20.10 1.00 18.07 1.00 16.40 1.00 17.19 1.00 17.00 1.00 15.10 1.00 17.47 1.00 20.70 1.00 17.50 1.00 13.82 1.00 13.45 1.00 15.36 1.00 24.03 1.00 24.21 1.00 25.99 1.00 26.98 1.00 31.20 1.00 36.99 1.00 26.69 1.00 27.76 1.00 24.94 1.00 25.85 3 1.00 27.66 4 1.00 28.61 6 1.00 26.41 7 1.00 28.57 3 1.00 26.76 3 1.00 27.14 7 :.00 25.95 9 1.00 24.26 4 1.00 22.44 4 1.00 23.41 8 21.84 -73bre2lc.pdb Thu Apr 25 12:27:47 1996 0 e 0 0 **00 o0.oo0 1.

*o *o

ATOM

ATCH

ATCOM

ATOM

ATCHOM

ATOM

ATCHM

ATOM

ATCOM

ATOM

ATCOM

ATCM

ATOM

ATCH

ATOM

ATCHM

ATOM

ATCM

ATOM

ATCOM

ATOM

ATCM

ATOM

ATCOM

ATOM

ATCH

ATCM

ATOM

ATCOM

ATOM

3269 CD2 LEU 3210 C LED 3271 0 LEO 3212 N ARG 3273 CA ARG 3274 CB ARG 3275 CG ARG 3276 CD ARC 3277 NE ARC 3278 CZ ARCG 3279 NH1 ARG 3280 NH2 ARG 3281 C ARG 3282 0 ARG 3283 N GLY 3284 CA GLY 3285. C CLY 3286 0 GLY 3287 N ARCG 32068 CA ARCG 3289 CB ARG 3290 CG ARCG 3291 CD ARG 3292 NE ARG 3293 CZ ARG 3294 NH1 ARG 3295 NH2 ARG 3296 C ARG 3297 0 ARG 3298 N THR 3299 CA THR 3300 CB THR 3301 OG1 THP.

3302 CG2 THR 3303 C THR 3304 0 TRR 3305 N ARG 3306 CA ARG 3307 CB ARC 3308 CG ARG 3309 CD ARG 3310 NE ARG 3311 CZ ARCG 3312 HH1 ARG 3313 NH2 ARG 3314 C ARG 3315 0 ARCG 3316 N TYR 3317 CA TYR 3318 CB TYR 3319 CG TYR 3320 CD1 TYR 3321 CE1 TYR 3322 CD2 TYR 3323 CE2 TYR 3324 CZ TYR 3325 OH TYR 3326 "C TYR 3327 0 TYR 3328 N TRR 3329 CA THR 3330 CS THR 3331 OG1 THR 3332 CC2 THR 3333 C TPRR 3334 0 THR 3335 N PHE 3336 CA PRE 3337 CB PRE 3338 CG PHE 3339 CD1 PRE 3340 CD2 PRE 3341 CE1 PRE I 3342 CE2 PRE 3343 CZ PRE 3344 C PRE .3345 0 PHE 3346 N ALA 686 686 686 687 687 687 687 687- 687 687 687 687 687 687 688 688 688 688 689 689 689 689 689 689 689 689 689 689 689 690 690 690 690 690 690 690 691 691 691 691 691 691 691 691 691 691 691 692 692 692 692 692 692 692 692 692 692 692 692 693 693 693 693 693 692 .693 694 694 694 694 694 694 6)4 694 694 694 694 695 23.563 42.742 67.173 1.

19.233 41.566 68.375 1.

18.361 40.669 68.478 1.

19.035 42.801 6a.858 1.

17.838 43.147 69.636 1.

18.117 42.901 71.113 1.

17.254 41.847 71.745 1.

17.778 40.471 71.410 1.

16.883 39.426 71.911 1.

16.832 38.188 71.416 1.

17.636 37.837 70.405 1 15.969 37.303 71.908 1 17.358 44.587 69.517 1 17.863 45.369 68.695 1 16.420 44.939 70.407 1 15.825 46.263 70.434 1 15.583 46.644 71.874 1 15.359 45.760 72.726 1 15.712 47.944 72.154 1 15.531 48.533 13.500 1 14.034 48.518 73.902 1 13.543 49.819 74.581 1 13.398 50.988 73.575 1 14.071 52.266 73.908 1 14.201 52.828 75.128 1 13.738 52.253 16.250 1 14.704 54.066 75.213 1 16.425 47.958 74.648 1 16.312 48.542 75.756 1 17.153 46.887 74.313 1 18.053 46.127 75.182 18.530 44.902 74.403 17.550 44.550 73.405 18.808 43.136 75.355 19.337 46.821 75.661 20.052 47.436 74.841 19.653 46.704 76.966 20.920 47.275 77.514 !20.908 47.426 79.055 21.668 46.303 79.860 21.736 46.597 81.403 22.360 45.549 82.240 21.681 44.632 82.957 20.331 44.612 82.931 22.337 43.775 83.768 22.024 46.269 77.114 21.863 45.028 77.231 23.157 46.781 76.682 24.2:3 45.893 76.256 24.237 45.885 74.744 23.317 44.905 74.100 23.303 43.575 74.501 22.544 42.636 73.833 22.535 45.283 73.014 21.755 44.345 72.325 21.772 43.022 72.745 21.021 42.086 72.059 25.534 46.436 76.139 25.776 47.643 76.606 26.382 45.567 77.302 27.711 45.989 71.758 27.877 45.985 79.301 26.746 46.642 79.909 29.155 46.745 19.685 28.7Z3 45.070 77.062 28.450 43.870 76.926 29.811 45.661 76.604 30.841 44.969 75.845 30.833 45.501 74.405 29.457 45.682 73.816 28.740 46.860 74.043 28.882 44.619 73.015 27.480 41.035 73.481 27.617 44.854 72.450 26.919 46.024 72.679 32.237 45.210 76.374 32.!33 46.304 76.835 33.112 44.227 76.155 43 00 20.88 6 00 26.62 6 00 27.06 a 00 25.21 00 21.90 i .00 21.00 6 .00 18.87 .00 20.25 1 .00 23.57 .00 24.78 .00 25.69 .00 23.14 .00 23.31 .00 24.06 .00 23.79 .00 22.75 .00 23.19 .00 21.67 .00 23.01 .00 23.70 .00 22.81 .00 20.45 .00 18.41 .00 17.79 .00 19.24 .00 12.88 .00 18.71 .00 25.87 .00 25.28 .00 25.78 1.00-23.94 1.00 24.95 1.00 24.96 1.00 24.38 1.00 27.33 1.00' 25.88 1.00 28.66 1.00 27.60 1.00 28.38 1.00 30.17 1.00 30.51 1.00 29.33 1.00 31.23 1.00 32.13 1.00 28.34 1.00 27.81 1.00 28.65 1.00 27.18 1.00 23.54 1.00 24.61 1.00 23.60 1.00 23.69 1.00 23.82 1.00 24.04 1.00 24.91 1.00 24.40 1.00 27.00 1.00 22.44 1.00 21.10 1.00 19.16 1.00 14.99 1.00 13.81 1.00 14.05 1.00 12.28 1.00 14.45 1.00 11.01 1.00 15.34 1.00 15.68 1.00 18.12 1.00 19.49 00 18.66 1.00 18.42 CO 19.71 1.00 16.44 1.00 16.79 1.00 14.83 1.00 14.75 1.00 14.22

S

6 6 r.7

I

7 6

B

8

I

6 8 6 6 8 7 1 4 6 6 8 6 6 8 7 s 6 6 i 4 6 1 4 7 1 4 6 7 6 6 8 4 6 8 4

R

i

'I

A

6 4 4 6 6 6 6 9 -74- Thu Apr 25 12:27:47 1996 a bref21c.pdb ATOM 3347 CA ALA ATOM 3348 CB ALA ATOM 3349 C ALA ATOM 3350 0 ALA ATOM 3351 N VAL ATOM 3352 CA VAL ATOM 3353 CB VAL ATOM 2354 CG1 VAL ATOM 3355 CG2 VAL ATOM 3356 C VAL ATOM 3357 0 VAL ATCOM 3359 N ARC ATOM 3359 CA ARC ATOM 3360 CB ARC ATOM 3361 CG ARC ATOM 3362 CD ARG ATOM 3363- NE ARC ATOM 3364 CZ ARG ATOM 3365 NHIl ARG ATOM 3366 NH2 ARG ATOM 3361 C ARG ATOM 3368 0 ARG ATOM 3369 N ALA ATOM 3370 CA ALA ATOM 3371 CB ALA ATOM 3372 C ALA ATOM 3313 0 ALA ATOM 3314 N ARC ATOM 3375 CA ARG ATCHOM 3316 CB ARG ATOM 3377 CG ARG ATOM 3378 CD ARG ATHM 3379 NE ARG ATCM 3380 CZ ARG ATCHOM 3381 NH1 ARC ATOM 3382 NH2 ARC ATOM 3383 C ARG ATOM 3384 0 ARG ATOM 3385 N MET ATOM 3386 CA MET ATOM 3387 CB MET ATOM 3388 CG MET ATOM 3389 SD MET ATCHOM 3390 CE MET ATOM 3391 C MET ATOM 3392 0 MET ATOM 3393 N ALA ATOM 3394 CA ALA ATOM 3395 CB ALA ATOM 3396 C ALA ATOM 3397 0 ALA ATOM 3398 N GLO ATOM 3399 CA GLO ATOM 3400 CB GLO ATOM 3401 CG GLU ATCHOM 3402 CD GLU ATOM 3403 OE GLO ATCOM 3404 *OE2 GLO ATOM 3405 C GLO ATOM 3406 0 GLU ATOM 3407 N PRO ATOM 3408 CD PRO.

ATOM 3409 CA PRO ATCOM 3410 CB PRCO ATOM 3411 Cc PRO ATOM 3412 C PRO ATOM 3413 0 PRCO ATOM 3414 N SER ATOM 3415 CA SEP ATOM 3416 CB SER ATOM 3417 O= SER ATOM 3418 C SER ATOM 319 SER ATOM 3420 N PHE ATOM 3421 CA PHE ATOM 3422 CB PHE ATOM 3423 CG PRE ATOM 3424 CC PHE 695 695 695 695 696 696 696 696" 696 696 696 691 691 697 691 697 697 691 697 691 697 691 698 698 698 690 698 699 699 699 699 699 699 699 699 699 699 699 700 700 100 700 700 100 700 700 701 701 7101 701 701 702 702 702 702 702 702 7102 102 702 7103 703 703 703 703 703 703 7104 704 704 704 104 704 705 705 705 70! 705 34.532 44.271 76.533 34.704 43.821 17.959 35.331 43.352 75.579 34.739 42.503 14.883 36.663 43.4715 75.554 37.475 42.631 74.640 37.455 43.242 73.198 37.867 44.705 73.223 38.335 42.446 72.255 38.923 42.284 75.041 39.654 43.093 715.637 39.321 41.055 74.7138 40.675 40.563 75.050 40.593 39.1713 75.664 39.172 39.018 716.89 39.842 37.650 77.417 39.071 36.676 76.632 38.722 35.4671 17.081 39.061 35.078 78.309 38.014 34.643 716.318 41.625 40.494 713.818 41.180 40.255 72.617 42.926 40.660 74.077 43.973 40.609 73.057 44.816 41.858 73.146 44.838 39.366 73.296 45.073 38.999 74.432 45.349 38.753 72.234 46.114 37.540 72.325 45.229 36.331 72.392 45.692 35.014 71.794 46.738 34.349 72.665 46.913 32.910 72.399 46.119 31.955 72.895 45.069 32.2571 73.6712 46.442 30.682 72.7110 47.090 31.470 71.094 46.680 37.820 69.991 48.355 37.109 71.282 49.263 371.029 70.140 50.124 36.955 10.551 51.322 38.292 70.963 52.092 39.250 69.678 51.368 40.7192 69.955 48.875 35.808 69.375 48.609 34.7155 69.939 48.849 35.943 68.069 48.425 34.837 67.250 47.605 35.361 66.065 49.483 33.855 66.779 50.619 34.165 66.639 48.980 32.669 66.491 49.163 31.574 65.987 48.9711 30.275 66.108 48.7124 29.784 67.501 48.591 28.284 67.507 *7.904 27.731 66.611 49.233 271.652 68.377 50.126 31.7170 64.510 49.560 32.617 63.802 51.106 30.986 64.037 51.501 30.820 62.625 51.782 30.007 64.899 51.896 28.794 63.999 52.253 29.467 62.635 53.150 30.488 65.409 53.801 29.7114 66.157 53.581 31.681 65.002 54.873 32.218 65.461 55.15e 33.5714 64.798 55.301 33.474 62.394 54.860 32.386 67.003 55.621 31.729 67.736 53.937 33.229 67.468 53.7671 33.532 68.857 53.323 34.9713 68.988 54.159 35.924 68.184 53.696 36.417 66.951 44 1.00 14.58 1.00 15.52 1.00 16.59 1.00 16.17 1.00 18.89 1.00 18.54 1.00 19.19 1.00 17.15 1.00 20.60 oo1.00 19.6 1.00 18.43 1.00 18.97 1.00 18.67 1.00 17.03 1.00 15.40 1.00 18.07 1.00 17.47 1.00 19.24 1.00 20.70 1.00 18.93 1.00 18.98 1.00 19.20 1.00 17.10 1.00 14.99 1.00 15.98 1.00 14.49 1.00 16.90 1.00 13.51 1.00 10.72 1.00 12.04 1.00 12.63 1.00 20.39 1.00 21.37 1.00 21.92 1.00 21.47 1.00 22.33 1.00 9.38 1.00 10.86 1.00 8.21 1.00 7.21 1.00 6.01 1.00 5.33 1.00 9.84 1.00 8.49 1.00 6.64 1.00 6.32 1.00 7.50 1.00 8.94 1.00 7.41 1.00 9.12 1.00 9.86 1.00 10.01 1.00 13.16 1.00 15.92 1.00 18.11 1.00 21.01 1.00 22.10 1.00 24.81 1.00 13.07 1.00 12.10 1.00 14.95 1.00 171.31 1.00 14.84 1.00 14.71 1.00 19.35 1.00 13.50 1.00 15.09 1.00 11.82 1.00 9.78 1.00 9.23 1.00 8.65 1.00 11.09 00 12.01 1.00 8.75 1.00 3.52 1.00 !.09 1.OC 1.49 1.00 8.92

S

S. S

C

*5 bref2

ATOM

ATOH

ATOM

ATOHM

ATOM

ATOHM

ATOM

ATOHM

ATOM

ATCH

ATCHM

ATOM

ATCOM

ATOM

ATOn

ATCM

ATOM

ATCH

ATOM

ATCH

ATOM

ATCHO

ATCOM

ATCM

ATOM

ATCH

ATCHO

ATCM

ATOM

ATCHO

ATCOM

ATCH

ATOM

ATCHO

ATCH

ATOM

ATCH

ATCM

ATOM

ATCM

ATCH

ATOM

ATCH

ATOM

ATCH

ATOM

ATM

ATOM

ATOI

ATCO

AtO~ 1c.pdb Thu Apr 25 12:27:47 1996 3425 CD2 PRE 3426 CE1 PRE 3421 CE2 PEE 3428 CZ PEE 3429 C PRE 3430 0 PEE 3431 N GLY 3432 CA GLY 3433 C GLY 3434 O GLY 3435 N GLY 3436 CA GLY 3437 C GLY 3439 0 GLY 3439 N PHE 3440 CA PHE 3441- C PBE 3442 CG PRE 3443 CD1 PRE 3444 CD2 PRE 3445 CEI1 PEE 3446 CE2 PRE 3447 CZ PRE 3448 C PEE 3449 0 PHE 3450 N TRP 3451 CA TRP 3452 CB TRP 3453 CO TRP 3454 CD2 TRP 3455 CE2 TRP 3456 CE3 TRP 3457 CD1 TRP 3458 NE1 TRF 3459 CZ2 TRP 3460 CZ3 TRP 3461 CH2 TRP 3462 C TRP 3463 O TRP 3464 N SER 3465 CA SER 3466 CB SER 3467 00 SEP.

3468 C SER 3469 O SE 3470 N ALA 3471 CA ALA 3472 CB ALA 3473 C ALA 34174 0 ALA 3475 N TRP 3416 CA TRP 3477 C TRP 34178 CC TRP 3479 CD2 TRP 3480 CE2 TRP 3481 CE3 TRP 3482 'CD1 TRP 3483 NEI TRP 3484 CZ2 TRP 3485 CZ3 TRP 3486 CH2 TRP 3487 C TRP 3488 0 TRP 3489 N SEP.

3490 CA SER 3491 C3 SEPR 3492 00 SEP.

3493 C SER 3494 O SER 3495 N CL 3496 CA GLC 3497 CB GLC 3498 CC GLU 3499 CD GL 3500 OE GL H 3501 OE2 tGL S 3502 C GLU l0s los 705 705 705 705 105 706 706 706 706 701 701 101 701 700 708 108 708 108 108 708 708 709 709 708 709 109 709 709 709 709 109 709 109 709 709 709 709 7109 710 710 710 710 I11 710 711 iil 112 11 111 712 712 712 712 712 712 712 712 712 112 7112 112 712 7112 713 113 713 113 713 713 114 714 114 714 714 714 114 114 55.446 36.284 69.611 1.

54.512 37.252 66.163 1.

56.270 37.115 67.833 1.

55.804 37.598 66.606 1.

52.783 32.591 69.505 1.

52.257 31.697 68.878 1.

52.634 32.751 70.809 1.

51.728 31.956 71.622 1.

51.661 32.726 72.932 1.

52.345 33.739 73.069 1.

50.829 32.295 73.878 1.

50.738 32.990 15.162 1.

49.465 32.823 15.977 1.

48.894 31.731 76.063 1.

48.993 33.927 76.540 1 47.801 33.911 177.372 1 48.171 33.981 78.874 1 49.358 33.126 19.277 1 49.196 31.1787 79.592 1 50.638 33.679 19.352 1 50.296 31.016 79.974 1 51.730 32.912 79.731 1 51.7510 31.597 80.040 1 46.846 35.066 77.077 1 47.260 36.187 76.721 1 45.562 34.777 7711.285 1 44.475 35.752 177.119 1 43.114 35.083 77.396 1 42.417 34.592 76.165 1 42.098 35.354 74.999 1 41.465 34.481 74.092 1 42.283 36.687 74.634 1 41.971 33.326 15.929 1 41.398 33.250 74.688 1 41.018 34.897 72.841 41.838 37.103 73.399 1 41.214 36.209 72.513 1 ,44.635 36.913 78.056 44.770 36.823 79.268 44.620 38.177 77.5089 44.765 39.350 78.351 45.040 40.594 71.501 43.841 41.258 77.157 43.522 39.567 19.216 42.531 38.832 79.139 43.580 40.563 80.076 42.435 40.867 80.894 42.855 41.811 81.993 41.432 41.560 19.965 41.810 42.073 78.915 40.155 41.558 80.326 39.159 42.251 19.527 31.751 42.031 80.092 37.202 40.647 79.845 36.796 40.091 18.516 36.416 38.745 18.809 36.718 40.600 11.270 37.037 39.647 80.769 36.514 38.499 80.150 35.969 37.906 117.783 36.279 39.176 76.262 35.908 38.434 16.520 39.498 43.741 79.520 40.124 44.269 80.460 19.174 44.385 18.395 39.366 45.819 78.166 39.294 46.108 76.659 37.913 45.899 76.149 38.167 46.480 78.799 37.081 45.908 78.164 38.309 47.705 19.279 37.163 48.391 19.888 :.524 '49.80? 80.276 38.470 49.836 81.4471 38.699 51.236 81.978 39.860 51.479 82.420 37.735 52.014 81.957 35.885 48.366 79.0271 00 8.54 00 7.44 00 4.91 00 5.19 00 5.11 00 4.57 00 8.69 00 7.99 00 9.39 00 00 10.91 00 9.87 1 .00 7.80 .00 7.37 .00 7.59 .00 8.42 .00 9.14 .00 8.19 .00 5.98 .00 6.32 .00 8.74 .00 5.05 .00 4.00 .00 7.99 .00 6.94 .00 9.09 .00 12.14 .00 11.59 .00 12.01 .00 9.80 .00 *9.82 .00 9.79 .00 11.53 .00 12.13 .00 9.03 0u 11.59 1.00 10.54 1.00 10.56 L.00 12.13 L.00 11.52 1.00 12.14 1.00 9.78 1.00 10.05 1.00 12.22 1.00 17.16 1.00 12.01 1.00 12.49 1.00 12.98 1.00 13.23 1.00 14.99 1.00 13.85 1.00 12.59 1.00 8.73 1.00 8.57 1.00 8.04 1.00 8.30 1.00 4.78 1.00 8.29 1.00 8.70 00 8.46 1.00 7.52 1.00 9.00 00 12.39 00 12.30 1.0 15.33 1.30 15.45 .00 .4.50 a.30 11.86 i.00 15.88 30 18.64 1.00 17.04 !.00 20.29 3c 21.i4 1.00 24.61 1.00 26.4! 1.00 2:.81 1.00 25.69 1.00 21.46 i i r 3 r

I

t i r 1 1 t i r r 3 3 r 1 r z 1 i i -76bxsf21c.pdb ATCM 3503 0 GLO ATOM 3504 N PRO ATOM 3505 CD PRO ATCH 3506 CA PRO ATOM 3507 CB PRO ATOM 3508 CG PRO ATOM 3509 C PRO ATOM 3510 0 PRO ATOM 3511 N VAL ATCH 3512 CA VAL ATOM 3513 CB VAL ATCH 3514 CG1 VAL ATOM 3515 CG2 VAL ATCH 3516 C VAL ATCH 3517 0 VAL ATCM 3518 N SER ATCHOM 3519 CA SER ATOM 3520 CB SER ATOM 3521 OG SER ATOM 3522 C SER ATOM 3523 0 SER ATCOM 3524 N LED ATOM 3525 CA LEO ATOM 3526 CB LED ATCM 3527 CG LEO ATOM 3528 CD1 LED ATOM 3529 CD2 LED ATOM 3530 C LED ATOM 3531 0 LEO ATOM 3532 N LED ATOM 3533 CA LED ATOM 3534 CB LED ATOM 3335 CG LEO ATOM 3536 CD1 LEO ATCOM 3537 CD2 LEO ATCH 3338 C LEO ATCOM 3539 0 LED ATOM 3540 N THR ATOM 3541 CA THP ATOM 3542 CB TP.

ATCH 3543 OG1 THP.

ATCOM 3544 CG2 THP.

ATCH 3545 C TP.

ATCH 3546 0 THP.

Thu Apr 25 12:27:47 1996 714 715 715 715 715 715 715 715' 716 716 716 716 716 716 716 717 717 717 717 717 717 718 718 718 718 718 718 718 718 719 719 719 719 719 719 719 719 720 720 720 720 720 720 120 35.867 48.844 77.886 1.00 21.24 34.787 47.852 79.611 1.00 20.46 34.703 47.761 81.090 1.00 21.13 33.460 47.694 79.015 1.00 19.23 32.627 47.183 80.182 1.00 21.32 33.226 47.974 81.332 1.00 19.98 32.874 48.959 78.473 1.00 20.02 33.194 50.060 78.922 1.00 20.10 31.934 48.769 77.562 1.00 20.51 31.229 49.858 76.910 1.00 19.7 31.769 50.100 75.440 1.00 18.56 30.988 49.293 14.396 1.00 18.80 31.749 51.563 75.099 1.00 16.95 29.778 49.366 76.908 1.00 21.79 29.515 48.182 76.624 1.00 20.72 28.859 50.269 77.264 1.00 22.27 27.439 49.971 77.331 1.00 21.09 26.920 50.181 78.764 1.00 23.89 27.182 49.064 79.607 1.00 24.17 26.552 50.748 76.3735 1.00 20.65 26.541 51.970 76.394 1.00 19.78 25.838 50.014 75.523 1.00 21.29 24.866 50.583 74.385 1.00 21.71 25.009 49.949 73.188 1.00 17.72 24.502 50.860 72.057 1.00 15.29 25.271 52.197 72.069 1.00 11.08 24.631 50.165 70.733 1.00 11.73 23.477 50.236 75.183 1.00 22.58 23.399 49.506 76.191 1.00 24.55 22.392 50.723 14.564 1.00 23.355 21.023 50.470 75.054 1.00 33.37 20.632 51.386 76.069 1.00 23.00 21.540 51.746 77.325 1.00 22.19 21.290 53.039 78.084 1.00 19.79 21.416 50.345 78.254 1.00 20.88 19.986 50.393 73.904 1.00-23.18 18.886 50.958 74.036 1.00 24.11 20.325 49.657 72.828 1.00 22.42 19.498 49.515 71.597 1.00 21.89 19.038 48.042 71.295 1.00 22.47 18.798 47.332 72.513 1.00 24.25 20.042 47.288 70.444 1.00 20.74 18.263 50.417 71.492 1.00 22.94 17.140 49.947 71.240 1.00 22.69 S

S

Tal I. 9 Data~ Se Reouto Refecton Copetns Sie .io .9uli I .~at Phsn Pow 1A (if 0 90 9) 0.05 9* 9 9 Naiv 250-. 149 Naie 25.0-2.0 11581 0.963(0.94) 0.05 4 0.1 0.6 0.37

A

UO 2(143)20.114 Ano 1.72 (3.9A) Refinement Statistics: R.145from Ideal values Average B Value 2 Resolution RelflectiOflU Total Number R-value Bond Length Bond Angle EBP1 EBP2 Peptides F>lo of atoms 8.0-2.8 13894 3462 0.21 0.016(A) 2.10 10.5 12.3 10.7 E16r FP"_ Fpi/~ $RCUIIis'E IFpN±FI- FK(caIc) I F for all centric reflections.

IRnatE P(b)F"C1 EIFoSFP(~C)II/ -F FPH~obs) +F.PH(Ob,)for all acentric relfectioli (anamaloui case).

S~huePowr-tIFPNCSC) 2 /EI FpH)p(CIC )1 2)12 ;1 FPH(b)FpCjCaIc is the lack of closure error to maximum reolution indicatqd.

M~ean Figure of IMerit-4C P(a)e 1 4/EP(O)I where P(a) Is the phase probability.

'Completeness of data in the outer shell, (2.9-2.18k) for the native and (3.1-3.0k) for both derivative.

ese 0 000 0 0 0 0 0 0 00 0 000 0 Table 2 Peptidel-ESPl I Pptidel-ESP2 PeptidolBEBP2 Paptida248BP1 Peptidel-Peptide2 Giyp~O-Ket 1 5 0 Pro PIOO-Thr 51

N

PrOP1Oo-ThrillOy Leup 1 10.Serl 5 2 t4 LeuplioSer 1 5 20-f Tyrp'OH-Ser 9 2 4 GlyP 9 O-Ket 15 0

N

P rop 1 0 O-Th r 5 1

N

ProPIOO-ThrisioY 1 LeuP 1 1O-Serl 52

N

Le'? 1 1O..SerlSOy Tyr P4OH-Ser 92 N Tyrp4O-CyU P 6

H

Tyr AN-CYSP 6

O

CYuP 6 O-Tyrp~m CysP 6 N- Tyr P 4 0

Claims

1. A method for identifying mimetics of erythropoietin, comprising the steps of: inputting into a programmed computer through an input device data comprising the three-dimensional coordinates of a subset of the atoms in the peptide GGTYSCHFGPLTWVCKPQGG when the peptide is co-crystallized with a portion of the erythropoietin receptor comprising amino acids 1 to 225 of the receptor, thereby generating a criteria data set; comparing, using a processor, the criteria data set to a computer database of chemical structures stored in a computer data storage system; selecting from the database, using computer methods, chemical structures having a portion that is structurally similar to the criteria data set; outputting to an output device the selected chemical structures having a portion similar to the criteria data set; 20 providing a compound having a structure outputted in step and selecting from the compounds provided in step (e) a compound which increases erythropoiesis in vivo. 25 2. The use of an EPO mimetic identified using the method of claim 1 in the manufacture of a medicament for increasing erythropoiesis in a patient in need thereof.

3. The use of claim 2, wherein the mimetic is not a polypeptide.

4. A method for increasing erythropoiesis in a patient in need thereof comprising administering to said patient an effective amount of an EPO mimetic identified using the method of claim 1. H:\MaraR\Keep\Speci\P36307.doc 22/02/00 80 The method of claim 4, wherein the EPO mimetic is not a polypeptide.

6. A pharmaceutical composition comprising an EPO mimetic identified using the method of claim 1 together with a pharmaceutically acceptable salt.

7. The pharmaceutical composition of claim 6, wherein the EPO mimetic is not a polypeptide.

8. The use of an EPO mimetic identified using the method of claim 1 for increasing erythropoiesis in a patient in need thereof.

9. The use of claim 8, wherein the mimetic is not a polypeptide. A pharmaceutical composition comprising an EPO mimetic identified using the method of claim 1 together with a 20 pharmaceutically acceptable salt, when used for increasing erythropoiesis in a patient in need thereof. 0. 5* o11. The pharmaceutical composition of claim 10, wherein the EPO mimetic is not a polypeptide. Dated this 2 2 nd day of February 2000 THE SCRIPPS RESEARCH INSTITUTE By their Patent Attorneys GRIFFITH HACK Fellows Institute of Patent and Trade Mark Attorneys of Australia H:\MaraR\Keep\Speci\P3630 7 doc 22/02/00