AU6305199A

AU6305199A - Small molecule mimetics of erythropoietin

Info

Publication number: AU6305199A
Application number: AU63051/99A
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: 1999-12-02
Publication date: 2000-03-16

Description

AUSTRALIA

Patents Act 1990 COMPLETE SPECIFICATION STANDARD PATENT Applicant: THE SCRIPPS RESEARCH INSTITUTE Invention Title: SMALL MOLECULE MIMETICS OF ERYTHROPOIETIN

S

S.

The following statement is a full description of this invention, including the best method of performing it known to 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 i "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 15s 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 is 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 s 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.

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 s 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 derived from x-ray crystallographic studies of the extracellular domain of EPO receptor (amino acids 1 to 225) complexed with a peptide, EMPI (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 similar to some or all of these contact i atoms are likely to be capable of acting as an EPO mimetic. Moreover, one can use the structural information to design or identify molecules having even more EPO activitythan the peptide mimetic described herein.

2o 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 DESCREMTON OF THE DRAWINGS FIGURE 1 is a flowchart showing a first method for identifying potential niimetics of erythropoietin using a computer system.

FIGURE 2 is a flowchart showing a second method for identifying potential iietics of ezythropoietin using a computer system.

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

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, EMPI (GGTYSCHFGPLTWVCKPQGG; SEQ ID NO:1), is characterized by an intramolecular disulfide bridge. Several lines of evidence suggest that EMP1 can act as an EPO mimetic.

For example, EMPI competes with EPO in receptor binding assays and induces cellular proliferation of cell lines engineered to be responsive to EPO. Both EPO and peptide o1 induce a similar cascade of phosphorylation events and cell cycle progression in EPO responsive cells. Furhter, EMP1 demonstrates significant erythropoietic effects in mice as monitored by two different 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 i15 conformation or assembly of EPO receptor.

Design of small molecule mimetics The structure of the EMPI 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 those involved in contacts between the two EMPI 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"', and Cys"' in each peptide. The following EMPI-EBP hydrophobic interactions are also significant: s Tyr"', Phe", and Trpr 13 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 S* 10o 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 EMP1. 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 threeo. 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 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) 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 s 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 10 relevant portion is referred to a pharmacophore. A pharmacophore then is an arrangement of structural features and functional groups important for biological activity, EPO activity.

Not all identified compounds having the desired pharmacophore will act as an EPO mimetic. The actual activity can be finally determined only by measuring the activity of is the compound in relevant biological assays. However, the methods of the invention are extremely valuable because they can be used to greatly reduce the number of compounds which must be tested to identify an actual mimetic.

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 include 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 three-dimensional structures from twodimensional data include: Concord (Tripos Associated, St. Louis, MO), 3-D Builder (Chemical Design Ltd., Oxford, Catalyst (Bio-CAD 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-3D (Chemical Design Ltd., Oxford, and Sybyl/3DB Unity (Tripos Associates, St. Louis, MO).

s 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, and Chemical Abstracts Service (Columbus, OH).

10 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 a mimetic may require slight structural alteration or adjustment of a chemical structure designed or identified using the methods of the invention.

15 In general, chemical compounds identified or designed using the methods ofthe invention can be sythesized chemically and then tested for EPO activity using any of the methods described below. The methods of the invention are particularly useful because they can be used to greatly decrease the number potential mimetics which must be screened for EPO activity.

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 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 s 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 10o 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 15 described herein.

FIGURE 1 is a flowchart showing a first method for identifying potential mimetics of o"e "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 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 .1 comprising a processor, a data storage system, at least one input device, and at least one S o 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 vive assays of EPO activity should be performed. For example, mimetic molecules should be able to stimulate proliferation of TF-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 of Mo7e 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 of EPO. 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 administered to a conditioned m ouse. Incorporation of "Fe into blood serves as a m easure of see. erythropoiesis. This erythropoiesis can be attributed to the candidate mimetic.

The assays described above are exam ples 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 m easure biological activity at several concentrations of candidate m im etic. The activity a t a g iv e n c o n c e n tr a ti o n o f c a n d id a te m im e tic c a n b e c o m p a r e d to th e a c tiv ity o f E P O itself.

4 Structural Data The coordinates for amino acids I to 225 of the human EPO receptor bound to peptide EMP1 are presented in the attached appendix in standard Brookhaven database format.

Also included in this appendix is a fist 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-EMPI Complex The extracellular fragment of human EPO receptor (EPO binding protein, EBP), consisting of residues 1-225, was expressed in PEghia coli and purified as described (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 V.=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 10 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 P-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 s15 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, 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-mII (FBN-fl) domains than to Ig domains (Bork et al., J. Mol. Biol., 242:309, 1994).

The FBN-Ul 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 D1 and D2 domains of the a chain ofinterferon-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 lo (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-III 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 s1 C' strand. Superposition of equivalent P-sheet core residues of the Dl 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 D1, a short a-helix (residues 10-20), precedes the first P-sandwich that is better 20 described as a hybrid of the FBN-ffI fold with an Ig fold (residues 24-114), rather than strict FBN-ll topology. In this h-type fold (Wang et al., Nature 348:411, 1990; Ryu et al, 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. Dl contains the two conserved disulfide bridges linking Cys (PA) to Cys N (PB) and Cys" (PC) to Cys" 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" 2 side chain could easily accommodate a carbohydrate moiety.

A helical linker (residues 115-118) connects D to D2 (The torsion angles for the interdomain helical linker for Asn"', Glu'" and Val" are -50° -760, -21, 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 (Connoly, 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 for the two domains.

D2 (residues 119-220) folds into the standard FBN-l (s-type) topology with one free 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 Prom 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 n U which has a positive 4) Y 520,400) consistent with the equivalent Ala'" and Ala' 1 0 torsion angles in hGHbp 63 ,680) and PRLR TY The Pro 2 4 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 Dl domains are only 0.8 A apart, sufficient to perturb perfect two-fold symmetry.

10 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 D1 Ca pairs) and 0.47 A (93 D2 Ca pairs).

The cyclic EMPI contains a single disulfide bridge between CysN and Cys", which links two short P-strands (residues 4-7 and 13-16) that are connected by a slightly distorted type 1 P-tum [Pron" and Leuar of the P-tur have <0,T -38° and -99°, is respectively. The carbonyl oxygen ofLeu 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". 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 (Conneily, J. Appl. Crystallog. 16:439, 1983; Davies et 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 of Tyr,Phe n and TrpF'. The construction of each hydrophobic core resembles a box which places the aromatic rings ofPhe",Trp" 3 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, L5, 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 0 polar areas. A hydrophobic core is formed between the peptide and receptor and comprises Phe",Met'" and Phe" from one EBP molecule and the peptide hydrophobic box consisting ofPhe

P

and Trp" 3 from one peptide and Tyr" and Cys" 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 mainchain of the P-turn residues Gly",Pro e and LeL" from one peptide with the 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 .I surprisingly minor contribution to the overall stability of the complex where the interooo receptor buried molecular surface is only 75 A 2 contributed by Leu and Arg' from 20 each receptor molecule.

EMP1 is one of a family of sequences that contain several conserved residues, besides the cysteines -A.NN 4 M ,a The most structurally significant of these consensus residues appear to be Tye' and Trp'", which along with the disulfide bridge have a major contribution to the hydrophobic core of the peptide-peptide 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 EMPI 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 10 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 EMPI that demonstrates increased biological potency (Johnson et al, in preparation). The Cys"' is 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 EMPI mediates formation of a soluble EBP dimer complex in solution consistent with the crystal structure.

The WSXWS motif 20 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 p-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 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 TrpP 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 Sert 2 and Sert2 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 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 of Arg'" 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 of Trp2, the Ne of the Arg'" and the center of the benzene ring of Trp 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 t 1 side chain has hydrophobic interactions with the indole ring of Trp", completing the alternating stacking of two is aromatic and two positively-charged amino acid residues. The side chain of Glu'" forms a hydrogen bond with Arg' 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 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 P-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 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 x-cation interactions. The i-cation system is extended in hGHbp and PRLR to include an additional aromatic residue (Trp'" for hGHbp and Trp 5 6 for PRLR) from the loop region s that links PC and PC' in D2 and a positively-charged residue (Arg 2 for hGHbp and Arg" 47 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 1 or from PC as in PRLR (Arg' 4 7 the glutamine residue that hydrogen bonds and orients the arginine also switches strands. Sequence alignments suggest that this Arg-Gln switch 10o could be common to other members of the class-i 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 of Lys 2 Tyrm, Arg 2 Phem, Arg, Trp'", Lys'" for hGHbp and Lys'", Trp' 91 Arg'", Trp'", Arg", Trp'", Lys'" for PRLR.' The first aromatic-Arg-aromatic trio are approximately 4A apart, S i15 as in EBP, but the second system is stacked closer together at approximately 3.6 A spacings consistent with Tx- 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.

o Based on sequence alignments with other members of the class-1 cytokine receptor 20 superfamily, such structurally extended x-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 motif 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 SerZ still maintains the equivalent interaction. A Ser 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 10 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 1 to Glu mutation in the WSAWS sequence resulted in better transportation from the ER to is 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.

CellBiol. 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' 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 (L1-L6), three to of which (L1-L3) come from one end of the P-sandwich structure in D1, 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 Ll to L6 for the hGHbp. A nonactive PRLR, complexed with only one molecule of hGH, also uses the same contact loops (LI to L6) (Somerset aL, Nature 372:478, 1994). Based on similarity of the ligand S 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 2o 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, LI, 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 3 Glu", Ile'~, Trp'" 0 Ile' 05 Pro' 0 6 Asp", and Trp o 6 which are located in contact loops Ll, L3 and L5 with the most significant contribution kcal/mol) coming from two aromatic residues (Trp'" and Trl") 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 04 '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 1 in the shorter L5 loop. In the i 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 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 5 In these three class-1 receptor structures, some loops are disordered which are in D2 for EBP for EBP (residues 164-166 in EBP1 and 133-135 in EBP2) and in Dl 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; DI 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 LI-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, Dl and D2 are related by a s 125 degree angle, which elongates the receptor and restricts the binding determinants that can be used for interaction with hormone; the L1 loop now becomes buried in the D1-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 is5 the wild-type by a factor of approximately 1000, whereas other mutants (Ser91Ala, Ser92Ala, Val94Ala, MetlSOAla 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 S*.i Trpl04Ala mutation results in an increase in the Kd by a factor of more than 2,500 a 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-1 cytokine receptor complexes, whose structures have been determined so far, suggests that when the natural EPO hormone, which is -24proposed 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 (Ile 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°N in human and 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 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 oligomerication plays a key role in activation of the receptor, and that the main functional S 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; Quelle 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-EMPI 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.

Towards design of small molecule mimetics 0 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 15 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 (lBa), contrbutes mos of the binding energy and strongly implied that a "minimized" hormone designed to interact 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 EUiott 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 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 of the 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 diffracted to 3.3A resolution, that in difference Fourier (F-Fcto gave a dear 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 te lerature 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 DI, 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 S. hydrogen bond interactions were analyzed using HBPLUS (McDonald et al., J. Mol. Biol.

lo 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 will 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.

28 all.con Thu Apr 25 15:08:07 1996 1 EBP1-PEPTIDE1 VDW 1 LEU 33 CB 4 PHE 308 CE1 1 3.95 VDW 1 LEU 33 CB 4 PEE 308 CD1 1 4.11 VDW 1 PEE 93 CE1 4 TRP 313 CH2 1 3.74 VDW 1 PHE 93 CZ* 4 TRP 313 CH2 1 3.98 VDW 1 PHE 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 PRE 308 CD2 1 3.52 Vw 1 MET 150 SD 4 THR 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 TPP 313 CZ2 1 4.10 VDW 1 MET 150 C 4 LEU 311 0 1 3.41 VDW 1 TR 151 N 4 LEU 311 0 1 3.45 VDW 1 THR 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 OGI1 4 LEU 311 CD2 1 3.43 SVDW 1 TER 151 OG1 4 LEU 311 CA 1 3.91 VDW 1 TER 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 SSHORTVDW 1 HIS 153 CE1 4 TER 312 0G1 1 2.87 VDW 1 BIS 153 CE1 4 TER 312 CB 1 3.48 VW 1 BIS 153 CE1 4 TER 312 CA 1 3.76 VDW 1 HIS 153 NE2 4 TER 312 OG1 1 3.57 VDW 1 PRE 205 CE2 4 PEE 308 CZ 1 3.90 VDW 1 PEE 205 CZ 4 PHE 308 CE2 1 3.40 VDW 1 PEE 205 CZ 4 PEE 308 CZ 1 3.53 EBP2-PEP1 VDW .2 SER 591 CA 4 TYR 304 H08 1 3.44 VDW 2 SER 591 CB 4 TYR 304 H08 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 H08 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 OH 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 PEE 593 CB 4 CYS 315 0 1 3.74 VDW 2 PEE 593 CD1 4 CYS 315 CB 1 3.55 VDW 2 PEE 593 CD1 4 TYR 304 CD2 1 3.72 -29all.con Thu Apr 25 15:08:07 1996 2 VDW 2 PRE 593 CD1 4 TYR 304 CE2 1 3.90 VDW 2 PEE 593 CEl 4 CYS 315 CB 1 3.71 SEORTVDW 2 VAL 594 CG1. 4 PRO 317 CG 1 3.17 SaORTVDW 2 VAL 594 CG1 4 PRO 317 CD 1 3.23 EBP1-PEPTIDE2 VDW I SER 91 CB 4 PRO 417 CB 1 3.84 VDW 1 SER 91 CB 4 PRO 417 CG 1 3.90 VDW 1 SER 91 OG 4 PRO 417 CE 1 3.90 VDW 1 SER 92 N 4 TYR 404 CE2 1 3.82 VDW 1 SER 92 CA 4 TYR 404 OH 1 3.85 VDW 1 SER 92 CE 4 TYR 404 OH 1 3.42 VDW I SER 92 CE 4 TYR 404 CZ 1 4.04 VDW 1 SER 92 CE 4 TYR 404 CE2 1 4.09 VDW 1 PHE 93 CE 4 CYS 415 0 1 3.43 VDW 1 PEE 93 CD1 4 TYR 404 CE2 1 3.71 VDW 1 PEE 93 CD1 4 TYR 404 CD2 1 3.83 VDW 1 PHE 93 CDl 4 CYS 415 CE 1 3.92 VDW I PEE 93 CEl 4 CYS 415 CB 1 4.09 VDW 1 PEE 93 CEI 4 TYR 404 CE2 1 4.09 VDW 1VAL 94 CG1 4 PRO 417 CG 1 3.54 VDW I VAL 94 CG1 4 PRO 417 CD 1 3.54 VDW 1 VAL 94 CG2 4 PRO 417 CG 1 4.11 EBP2-PEPTIDE2 .SEORTVDw 2 LEU 533 CE 4 PEE 408 i 1 3 VDW 2 LEU 533 CE 4 PEE 408 CD1 1 3.77 VDW 2 LEU 533 CE 4 PRE 408 CZ 1 4.00 VDW 2 LEU 533 CG 4 PEE 408 CEl 1 4.05 VDW 2 LEU 533 CD1 4 PEE 408 CE1 1 3.75 VDW 2 LEU 533 CD1 4 PEE 408 CZ 1 3.92 VDW 2 LEU 533 0 4 PEE 408 CE1 1 3.67 VDW 2 PEE 593 CE1 4 TRP 413 CE2 1 3.34 VDW 2 PEE 593 CE1 14 TRP 413 CZ2 1 3.41 VDW 2 PEE 593 CZ 4 TRP 413 CZ2 1 3.67 VDW 2 PEE 593 CZ 4 TRP 413 CE2 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 1 3.72 VDW 2 MET 650' CA 4 PRO 410 0 1 3.59 VtW 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 PHE 408 CD2 1 3.80 VDW 2 MET 650 CG 4 PHE 408 CG 1 3.92 VDW 2 MET 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 THR 412 C 1 3.75 VDW 2 MET 650 SD 4 PHE 408 CD2 1 3.76 VDW .2 MET 650 SD 4 THR 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 2 MET 650 CE 4 TRP 413 CD2 1 3.76 VDW 2 MET 650 CE 4 PEE 408 CD2 1 3.83 VDW 2 MET 650 CE 4 TRP 413 C1 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 TER 651 N 4 LEU 411 0 1 3.56 VDW 2 TER 651 N 4 PRO 410 C 1 3.77 VDW 2 TER 651 CA 4 PRO 410 0 1 3.41 SBORTVDW 2 TER 651 CB 4 PRO 410 0 1 3.03 VDW 2 TER 651 CE 4 PRO 410 C 1 3.98 VDW 2 TSP 651 CE 4 LEU 411 CA 1 4.02 VDW 2 TER 651 OG1 4 PRO 410 C 1 3.62 all, con

VDW

SHORTVDW

VDW

Thu Apr 25 15:08:07 1996

SEP

SER

HIS

N

CA

CB

0G- .CE1 CE1

LEU

LE

TER

PEPTIDE1-PEPTIDE2 r r r

SHORTVDW

VDW

SHORTVDW

VDW

TER 303 TER 303 TYR 304 TYR 304 TYR 304 TYR 304 TYR 304 TYR 304 SER 305 SER 305 CYS 306 CYS 306 CYS 306 CYS 306 CYS 306 CYS 306 CYS 306 PRE 308 PEE 308 TRP 313 TRP 313 TRP 313 TRP 313 1 TRP 313 1 TRP 313 TRP 313 CYS 315 S CYS 315 CYS 315 3 GN 318 3 GN 318 OGi OG1

CB

CD1 CD1 0 0 0

CA

C

0 0 0 0

CB

SG

CE1 CR1

CG

CD1 CD1 CD 1

NEI

CZ2 CR2

SG

CD

OE1 HIS 4 HIS 4 CYS 4 TRP 4 TRP 4 cyS 4 CYS 4

SER

TYR

TER

TYR

CYS

TYR

TYP

TRP

cys

CYS

TRP

ITRP

I GLN I SER 07 07 106 113 113 106 106 105 404 404 403 404 404 404 406 406 406 404 404 413 413 413 413 413 415 415 413 413 413 418 405

C

0 0

C

CB

OG1

CB

CA

0 CZ3 CR2

N

0

CA

0 0

CB

CD1

CA

SG

CB

OH

CR1 CD1 CD1 NE1

CG

CDX

SG

CZ2 CE2 CH2 NE2

CB

3.83 3.51 3.18 4.09 3.73 3.00 3.91 2.94 3.61 3.86 3.81 3.94 3.33 3.47 3.57 3.51 3.77 3.50 3.54 3.59 3.75 3.81 3.75 4.06 3.93 4.08 3.85 3.04 3.37 4.09 3.31 3.84 3.83 3.59 3.95 4.00 3.28 3.80 bret2lc.pdb Thu Apr 25 12:27:47 1996 a a.

a

REMARK

ATOM

AND PEPTIDE (P.ESIDUES 303-318, 403 418) 1 N LYS 2 CA LYS 3 CB LYS 4 CG LYS 5 CD LYS 6 CE LYS 7 NZ LYS 8 C LYS 9 0 LYS 10 N PHE 11 CA PHE 12 CB PHE 13 CG PRE 14 CD1 PHE :5 CD2 PHE 16 CE1 PHE 17 CE2 PHE 19 :Z PHE 19 C PHE 20 C PHE 21 N GLU 22 CA GLU 23 CB GLU 24 CG GLO 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 SE 34 C SER 35 0 SEF.

36 N LYS 31 CA LYe 36 CD LYS 39 CG 40 CD LYS 41 CE LY 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 N LED 56 CA LEZ: s! CLP LE'- 58 CG LEU 59 CD1 LED 60 CD2 LE'" 61 C LEAJ 62 LE'- 63 N LEU 64 CA LEU 65 C? 66 CG LE:' 75 CDI LE'-' 68 CD2 LE;: 9 C LE; 10 -0 LE; 10 10 10 10 10 10 10 1n 11 11 11 1i 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 1C 16 16 16 1"

I-

17 1i 17 1 18 40.090 29 39.634 3C 38.153 29 38.334 3( 38.119 2! 31.165 21 35.685 21 30.921 3: 39.589 3; 37.602 3 36.868 3 35.549 3 34.497 3 34.862 3 33.142 3 33.910 3 32.180 3 32.566 3 37.644 3 31.71E 3 38.181 3 38.905 3 39.253 3 40.185 3 39.455 3 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 38.566 39.191 38.193 39.586 39.782 38.920 38.375 37.571 39.592 "'9.683 40.560 41.792 42.711 42.361 42.624 42.444 43.001 43.012 44.204 45.414 44.360 42.3714 42.985 41.136 40.434 38.999 28.72! 37.235 39.422 40.393 39.876 9.25' 0.133 9.361 0.155 9.212 8.015 3.367 1.427 2.442 1.386 2.588 2.257 3.362 4.717 3.038 5.728 4.041 5.395 3.567 ,4.740 13.106 14.036 3.423 34.309 35.301 36.411 34.952 34.539 35.703 33.687 34.094 32.898 32.959 35.202 36.249 34. 355 35.912 25.287 34.366 33.862 33.270 32.142 37.198 38.290 37.053 38.18i 31. 69 38.961 40.18 38.20 38.19 371.11 39.56 40.15 38.89 39.46 38.42 371.48 38.29 36.46 40.14 41.4.

41.01 42.21 41.31 41.2 41.2 42.1 43.2 44.3

MOLECULE;.

22.042 1.00 22.51 20.962 00 23.48 13.979 i.00 22.87 18.735 1.00 22.92 17.552 1.00 24.27 17.890 1.00 26.55 17.998 1.00 26.18 21.420 1.00 22.91 21.636 1.00 24.11 21.640 1.00 21.40 22.026 1.00 13.56 22.725 1.00 19.01 22.609 1.00 20.24 22.610 1.00 19.49 22.400 1.00 19.51 22.5271 '.00 19.64 22.2517 .00 20.10 22.321 00 19.48 22.881 30 19.32 22.516 1.00 18.89 ;4.016 00 20.71 24.886 1.00 20.59 26.246 L.00 21.48 27.123 1.00 23.60 23.056 1.00 25.09 28.215 1.00 23.07 28.589 1.00 21.05 24.172 l.00"19.22 24.334 1.00 18.49 23.341 1.00 11.67 22.571 1.00 16.71 21.851 1.00 18.51 20.459 1.00 23.19 21.554 1.00 15.57 21.546 00 15.13 20.698 ;.00 12.00 13.675 i.00 8.51 18.169 1.00 5.06 S 1.714 L.00 2.36 1 .161 00 2.00 15.496 00 2.27 14.528 1.00 2.00 1 20.295 1.00 1.05 0 19.155 1.00 7.15 1 21.442 1.00 11.98 8 22.194 1.00 12.13 7 23.318 1.00 11.49 0 22.666 1.00 12.49 9 22.535 13.58 7 23.161 1.30 13.91 6 23.615 00 14.31 0 24.052 00 14.76 7 22.426 1.00 15.45 22.537 7.00 15.35 6 21.214 :.00 16.12 7 20.042 O 15.32 3 13.910 0 1'5.72 5 13.662 1.00 17.46 4 18.506 ".00 16.45 2 1 ).774 .00 16.32 I1 19.512 1.00 15.04 3 18.711 00 15.31 1l 11.908 1.00 17.34 1- 13.443 .00 15.72 67 022 .C 13.2 63 17.640 00 9."6 60 17.329 17 16.625 00C 10.13 84 20.500 .00 17.38 20.257 00 13.32 THE COMPLEX BETWEEN THE EXTRACELLULAR DOMAIN OF ERYTHROPOIETI' RECEPTOR (EBP) AND AN AGONIST EPO MIMETIC PEPTID1: 1 (EMHI) WARNING RESIDUES 21-23 (521-522) and 164-166, 633t HAVE WEAK OP. NO ELECTRON DENSITY MAP AND HAVE BEEN MODELED INTO THE STRUCTURE. THESE RESIDUES HAVE A HIGH 8 OF ,0.

THE STR.UCTURE CONSISTS OF TWO RECEPTOR (F.ESICUES :0-220, 510-;2.) -32bref21c.pdb Thu Apr 25 12:27:47 1996 2 ATOM 71 N ALA 19 40.921 42.981 21.680 1.00 19.88 ATOM 72 CA ALA 19 40.925 43.941 22.789 1.00 22.64 ATOM 73 CB ALA 19 41.560 43.331 24.041 1.00 22.75 6 ATOM 74 C ALA 19 41.601 45.273 12.445 1.00 25.13 6 ATOM 75 0 ALA 19 42.026 45.499 21.294 1.00 25.03 3 ATOM 76 N ALA 20 41.649 46.164 23.453 1.00 28.71 ATOM 77 CA ALA 20 42.246 47.514 23.323 1.00 28.51 6 ATOM 78 CB ALA 20 41.529 48.505 24.310 1.00 28.93 6 ATOM 79 C ALA 20 43.770 47.526 23.562 1.00 27.54 ATOM 80 0 ALA 20 44.438 46.484 23.505 1.00 27.85 ATOM 81 N ARG 21 44.326 48.699 23.848 1.00 90.00 ATOM 82 CA ARC 2: 45.765 48.784 24.075 1.00 90.00 6 ATOM 83 CB ARC 21 46.562 48.353 22.819 1.00 90.00 6 ATOM 84 CG ARG 21 45.827 48.428 21.446 1.00 90.00 s ATOM 85 CD ARG 21 45.719 49.838 20.863 1.00 90.00 6 ATOM 86 NE ARG 21 44.765 50.675 21.591 1.00 90.00 ATOM 87 CZ ARG 21 43.448 50.471 21.610 1.00 90.00 6 ATOM 88 NH1 ARG 21 42.915 49.448 20.926 1.00 90.00 7 ATOM 89 NH2 ARG 21 42.669 51.270 22.350 1.00 90.00 ATOM 90 C ARG 21 46.298 50.118 24.590 1.00 90.00 6 ATOM 91 0 ARG 21 45.875 51.199 24.132 1.00 90.00 3 ATOM 92 N GLY 22 47.158 50.016 25.614 1.00 90.00 ATOM 92 CA GLY 22 47.824 51.171 26.193 1.00 90.00 ATOM 94 C GLY 22 49.053 51.371 25.314 1.00 90.00 6 ATOM 95 0 GLY 22 48.939 51.174 24.089 1.00 90.00 ATOM 96 N PRO 23 50.230 51.765 25.872 1.00 90.00 ATOM 97 CD PRO 23 50.318 52.564 27.119 1.00 90.00 ATOM 98 CA PRO 23 51.451 51.971 25.062 1.00 90.00 i ATOM 99 CB PP.0 23 51.713 53.452 25.287 1.00 90.00 6 ATOM 100 CG PRO 23 51.527 53.511 26.850 1.00 90.00 6 ATOM 101 C PRO 23 52.681 51.167 15.544 1.00 90.00 6 ATOM 102 0 PRO 23 52.560 50.067 26.123 1.00 90.00 ATOM 103 N GLU 24 53.863 51.758 25.308 1.00 28.27 7 ATOM 104 CA GLU 24 !5.136 51.178 25.741 1.00 24.32 6 ATOM 105 CB GLU 24 56.332 52.009 25.238 1.00 24.01 6 ATOM 106 CG GLU 24 56.479 52.149 23.723 1.00- 25.03 6 ATOM 107 CD GLU 24 56.710 50.822 22.959 1.00 24.22 6 ATCH 108 OE1 GLU 24 57.171 50.954 21.793 1.00 23,14 S ATOM 109 OE2 GLU 24 56.430 49.692 23.478 1.00 18.50 ATOM 110 C GLU 24 55.117 51.264 27.268 1.00 23.39 6 ATOM 111 0 GLU 24 54.874 52.365 27.829 1.00 24.36 4 ATOM 112 N GLU 25 55.342 50.124 27.925 1.00 18.35 ATOM 113 CA GLU 25 55.371 5C.058 29.377 1.00 14.09 6 ATOM 114 CB GLU 25 53.962 49.818 29.907 1.00 17.09 ATOM CG GLU 25 53.789 49.985 31.410 1.00 22.21 ATOM 116 CD GLU 25 53.199 51.348 21.799 1.00 27.17 ATOM "17 OE1 CLU 25 53.461 52.355 21.057 1.00 27.15 ATOM e18 OE2 GL. 25 52.461 5:.401 22.937 1.00 26.11 ATOM 119 C GLG 25 56.249 48.872 29.725 1.00 11.99 ATOM 120 0 GLU 25 56.056 47.779 29.181 1.00 14.30 3 ATOM 121 N LEO 26 57.246 49.098 20.512 1.00 8.48 ATOM 122 CA LEU 26 58.147 48.034 21.001 1.00 5.93 6 ATOM 123 CB LEC 26 59.396 48.624 21.652 1.00 4.03 ATCM 124 CG LE3 26 60.719 47.880 21.488 1.00 2.00 4 ATOM 125 CDI LEV 26 61.53"7 48.145 22.704 1.00 4.41 ATOM :26 CD2 LE- 26 60.535 46.401 21.317 1.00 2.00 ATOM 127 C LZ3 26 57.409 47.188 22.030 1.00 6.68 ATOM 128 *O LZC 26 56.951 47.72. 23.041 1.00 9.43 3 ATOM 129 N LE- 27 57.31C 45.880 21.791 1.00 5.11 ATOM 130 CA 2' 56.612 44.996 22.719 1.00 5.71 ATOM 131 CB LZ 2- 55.428 44.334 22.035 1.00 6.50 ATOM 122 CG 2- 54.281 45.269 21.673 1.00 10.34 ATOM 122 CD1 2- 53.101 44.423 21.125 1.00 10.81 ATOM 134 C02 LE 2' 53.871 46.133 22.906 1.00 7.08 ATOM 135 2- 5'.454 43.)22 2-397 .00 .11 ATOM 136 0 LZE 2' 58.002 43.037 22.742 1.00 7.62 ATOM 127 N 2S 57.46C 43.964 2.726 1.00 7.42 ATOM 128 CA 28 58.206 43.027 25.554 00 4.67 ATOM 139 "YS 28 57.246 42.359 26.529 1.00 4.38 ATOM 140 0 28 56.211; 42.345 2i.861 1.00 2.56 ATOM 141 CB CY 2E 59.26( 43.791 26.357 1.00 3.64 ATOM 142 SC :Y3 28 60.429 44.763 25.358 1.00 4.37 1; ATOM 143 ;4 2 5-.99 26.977 1.00 2.00 ATOM 144 CA ?E 21* 56.817 40.402 27.942 .OC 2.00 ATOM 145 CB ?HE 2- 55.474 39.899 17.322 1.00 4.36 ATOM 146 CG ?.HE 29 L8 38.642 26.427 OC 43 ATOM 147 CDI ?u!E 29 5!-.492 37.36 i4.99C :.0C 2.00 ATOM 148 CD2 Pu- 219 51.79C 38.747 2..058 00C 2.30 -33bretf2lc.pdb Thu Apr 25 12:27:47 1996

ATCOM

ATOM

ATCH

ATOM

ATCH

ATOM

ATCM

ATOM

ATCH

ATOM

ATCM

ATOM

ATOMH

ATOM

ATCM

ATOM

L49 150, 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 113 174 175 176 177 178 179 180 181 182 183 184 185 186 181 18 18 19 19 19 19 19 19 19 19 19 19 20 20 20 20 20 20 20 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 CE1 PHE CE2 PHE cZ PHE c PHE 0 PHE N THR CA THP.

cB THE 001 THP.

CG2 THP.

C THR O THR N CLU CA GLU CB GLU CG CLU CD GLO OEl GLU OE2 GLU C GLU O CL N ARGC CA ARC CB ARG CG ARGC CD ARGC NE ARC CZ A.RG ARC NH1 ARC NH2 ARC C ARC O ARC N LEU CA LEU CB LEU CC LEU CD1 LEU CD2 LEU C LE SO LEU 9 N GL 0 CA CLU I CB CLU 2 CG GCLU 3 CD GLU 4 OE1 GLU 5 OE2 GLU 6 C CLU 7 C GLU 8 N *ASP 9 CA ASP 0 CB ASP 1 CC ASP 2 301 ASP 3 002 ASP 4 C ASP 5 0 ASP 6 *N LEC 07 CA LED 08 CB LEU 09 CG LEU 10 CD1 LEU 11 CD2 LEC 12 L 14 N ;AL 15 CA VAL 16 CE BIAL 17 CGl VAL 13 CG2 VAL 19 c VAL 20 C VALt 21 N s 22 CA CYS 23 :s 224 C 225 CB CYS 226 SC CYS 29 29 29 29 29 30 30 30' 30 30 30 30 31 31 31 31 31 31 31 31 31 32 32 32 32 2 32 32 32 32 32 32 33 33 33 33 33 33 33 33 34 34 34 34 34 34 34 34 34 35 35 35 35 35 35 35 35 36 36 36 36 36 36 3' 3, 3- 3- 3, 38 38 38 38 38 30 55.605 55.906 55.815 57.678 58.702 57.340 58.021 58.720 59.337 57.763 56.951 55.774 57.342 56.378 56.5771 56.490 56.651 57.538 55.916 56.453 55.437 57.678 58.006 58.844 58.284 58.376 57.070 56.328 56.763 55.145 58.834 59.004 59.382 60.084 59.536 58.323 57.061 58.38 :61.61 62.26 62.13 63.53 64.31 63.51 62.75 61.81 63.08 63.67 64.41 62.97 62.98 62.21 60.61 60.05 60.1 62.3: '1.5 62.6 62.0 62.9 62.2 60.9 63.1 62.1 i3.0 61.0 60.9 59.8 60.0 59.

60.

59.

61.

60.

61.

36.243 26.

37.616 24.

36.365 34.

39.260 23.

38.897 21.

38.814 29.

37.694 43.

38.116 41.

36.982 42.

36.661 42.

36.601 40.

36.924 40.

35.326 40.

34.219 40.

33.240 39 33.821 38.

32.750 371 32.875 36 31.7153 37 33.432 42 32.940 42 33.064 42 32.390 43 31.154 43 30.364 42 28.894 42 2e.271 42 28.350 41 29.036 43 27.734 43 33.536 44 34.526 4 33.499 4 34.736 4 35.403 4 36.310 4 35.584 4 1 37.604 4 0 34.893 4 9 35.702 4 0 34.174 4 9 34.210 4 5 33.005 4 8 31.931 4 4 30.858 4 O 3C.224 4 2 3C.645 8 34.239 4 3 33.459 8 35.150 1 35.244 S34.034 8 34.189 5 34.542 02 33.911 36 36.566 63 37.153 77 37.046 98 38.272 02 39.484 16 40.825 94 40.9'7 84 41.343 19 39.170 71 37.640 3E 38.589 60 38.559 66 37.575 07 37.337 957 36.271 55S 39.970 738 40.553 204 40.557 831 41.886 '62 41.816 592 41.143 808 42.975 860 43.383 266 843 543 957 766 463 820 408 827 614 814 665 .786 .650 .286 .248 .395 .302 .079 .582 .416 .670 .4C5 .261 .469 .295 187 .128 .128 4.224 3.520 5.416 5.716 6.986 6.699 7.032 7.464 5.506 6.168 4.516 4.144 4.73: 5.54 4.69 5.25 3.49 2.59 :2.01 41.93 40.48 29.89 39.95 38. 91 41.02 40.01 40.73 33.83 23.31 33.4 23.3 13.7 36.8 34.7 -4.2 22.6 24.9 34.3 35.0 -3.3 22.3 2i.

23.

2-1.

1.00 2.00 1.00 2.00 1,00 3.80 L.00 2.00 1.00 4.11 1.00 3.12 1.00 2.00 1.00 2.00 L.00 2.00 1.00 6.81 6 1.00 8.70 3 1.00 7.95 1.00 8.18 1.00 7.89 i 1.00 8.99 6 1.00 10.58 6 1.00 13.03 i 1.00 14.01 3 1.00 8.38 6 1.00 9.78 1.00 7.19 1.00 8.64 :.00 9.16 6 1.00 10.75 i 1.00 11.21 .00 13.52 :.00 16.55 1.00 17.12 1.00 17.61 1.00, 9.21 1.00 13.37 1.00 7.72 1.00 8.01 1.00 7.85 1.00* 2.00 1.00 3.91 1.00 3.00 L.00 8.52 1.00 10.67 1.00 6.25 1.00 8.09 1.00 10.89 1 1.00 18.21 9 1.00 21.61 1 L.00 22.26 4 1.00 22.29 4 1.00 7.89 i *.00 10.91 3 1.00 6.40 3 1.00 4.88 5 1.00 5.00 7 1.00 6.69 2 1.00 6.86 5 1.00 2.00 6 1.00 3.42 1 1.00 4.41 4 1.00 2.00 1.00 2.00 45 1.00 2.00 S0 1.00 2.40 65 1.00 2.31 62 1.00 2.00 C3 1.00 3.03 41 1.00 3.E5 !1 1.00 3.46 07 1.00 2.00 Ci 1.00 2.00 S9 t.00 2.00 42 1.00 2.30 29 1.00 3.99 42 00 5.63 11 .0 2.00 12 00 4.35 124 1.00 5.14 1.00 8.41 213 1.00 2.98 972 1.00 3.22 6 6 6 6 6 6

C

4 6 6 1 6 1 i 5 3 i r i i i 6i

I'

206 1.00 2.00 -34bref2lc.pdb ATOM 227 N PHE ATOM 228 CA PHE ATOM 229 CB PHE ATOH 230 CG PHE ATOM 231 CD1 PP.E ATOM 232 CD2 PHIE ATOM 233 CEl PHE ATOM 234 CE2 PHL ATOM 235 CZ PHE ATOM 236 PHE ATOM 237 O PHE ATOM 238 N TRP ATOM 239 CA TRP ATOM 240 CB TRP ATOM 241 CO TRP ATOM 242 CD2 TRP ATOM 243 CE2 TRP ATOM 244 CE3 TRP ATOM 245 C1 TRF ATOM 246 NEL TPP ATOM 247 CZ2 ThP ATOM 248 CZ3 TRP ATOM 249 CH2 TP.P ATOM 250 C TRP ATOM 251 0 TRP ATOM 252 N GLJ ATOM 253 CA GLU ATOM 254 CB CLU ATOM 255 CC GL' ATOM 256 CD CLU ATOM 257 OE1 GLU ATOM 258 OE2 GLU ATOM 259 C GLU ATOM 260 0 GLU ATOM 261 N GLU ATOM 262 CA GLU ATOM 263 CB GLU ATOM 264 CC GLU ATOM 265 CD CLC ATOM 266 OE1 GLC ATOM 267 OE2 GL ATOM 268 C CLU' ATOM 269 0 CGL ATOM 270 N ALA ATOM 271 CA ALA ATOM 272 CS ALA ATOM 273 C ALA ATOM 274 0 ALA ATOM 275 N ALA ATOM 276 CA ALA ATOM 277 CB ALA ATOM 279 C ALA ATOM 279 0 ALA ATOM 280 N SEr ATOM 281 CA SER ATOM 282 CB SER ATOM 283 00 SET ATOM 284 C SEAR ATCOM 285 0 SEF ATOM 286 N ALA ATOM 287 CA ALA ATOM 288 CB ALA ATOM 289 C ALA ATOM 290 -1 ALA ATOM 291 :4 GL ATOM 292 CA GLY ATOM 293 C GLY ATOM 234 0 G: ATOM 295 N VAL ATOM 296 CA VA: ATOM 297 Ci VA.

ATOM 298 ClI VAI ATOM 299 CC2 VA:L ATOM 300 C VAL ATOM 301 Q VA ATOM 302 N CGLY ATOM 333 CA GLY ATOM -04 C CLY 39 39 29 29 39 19 39 39 29 39 29 39 40 40 40 40 40 40 40 40 40 40 40 40 40 40 41 41 41 41 41 41 41 41 41 42 42 42 42 42 42 42 42 42 43 43 43 43 43 44 44 44 44 44 45 45 45 45 45 45 46 46 46 46 46 47 47 48 46 48 42 48 46' 49 49 59.811 59.621 58.865 57.461 56.416 57.190 55.123 55.896 54.868 58.826 50.262 58.837 58.084 58.826 60.014 61.386 62.143 62.049 60.003 61.277 63.527 63.431 64.152 57.785 58.530 56.625 56.267 54.898 54.860 53.619 53.418 52.843 56.335 56.456 56.403 56.426 57.1729 58.974 60.242 61.019 60.470 56.1671 55.880 56.243 55.988 55. 513 57.164 58.309 56. 878 57.928 57.326 58.828 58.401 60.08 60.96 61.61 61.47 61.99 62.59 62.11 63.04 62.81 64.37 64.65 45.14 66.45 66.55 67.22 65.87 55.95 64.82 64.5 65.21 5.90 65.0 66.8 66.9 67.1 42.540 30 42.507 29 41.225 28 41.198 29 41.686 29 40.807 20 41.795 2 40.917 3 41.411 2 43.713 2 44.451 2 43.926 2 44.996 2 46.352 2 46.517 2 46.185 2 46.555 2 45.595 2 47.056 2 47.087 2 46.358 2 45.395 2 45.780 2 44.538 2 43.761 2 44.914 2 44.533 2 43.940 2 42.586 2 41.687 2 40.748 2 41.891 2 45.715 2 46.888 45.389 46.399 47.207 46.393 47.114 46.519 48.271 45.73' 44.332 46.314 46.007 47.145 45.291 45.583 44.282 43.514 42.507 S44.442 45.534 6 44.068 2 44.326 e 46.002 9 47.244 6 44.207 9 43.221 2 44.471 1 44.134 0 44.781 9 44.538 S45.746 0 4!.!25 0 43.762 8 44.415 1 45.457 2 43.843 0 44.302 5 45.230 2 45.071 46.656 4 43.060 62 42.183 82 42.34i 48 41.79 99 42.211 .742 .286 .900 .411 .636 1.709 9.153 1.228 0.451 3.794 9.580 7.490 6.846 6.872 5.928 6.200 5.062 7.294 4.661 4.144 4.989 7.217 6.068 5.418 4.824 4.914 3.556 3.555 4.450 4.254 5.055 3.301 !2.558 22.956 21.271 20.211 20.227 20.511 20.115 19.371 20.519 18.853 18.795 17.771 16.400 15.515 15.731 15.930 14.903 14.208 13.263 13.438 13.047 13.275 12.508 13. 354 12.69 11.68 12.12 10.43 1.46 8.12 10.02 10.20 10.43 11.00 12.40 12.54 13.39 14.79 1.23 16.70 14.96 15.64 15.44 1.52 1 8 Thu Apr 25 12:27:47 1996 4 1.00 i.00 5.3 1.00 4.80 1.00 7.ZP 1.00 8.61 1.00 1.97 1.00 3.47 .00 3.13 00 2.72 1.00 3. s 1.00 4.23 1.00 3.45 1.00 4.71 1.00 4.45 :.00 7.44 1.00 9.31 1.00 8.04 1.00 10.26 1.00 8.12 1.00 6.99 1.00 10.83 1.00 10.61 1.00 11.42 .00 00 4.51 1.00 1.'s9 .00 3.!4 1.00 7.9i 00 11.7- 00 13.6 >.00-15..1 00 17.90 1.00 9.08 1.00 8.71 1.00 8.40 1.00 8.64 1.00 6.56 1.00 :5.'3 1.00 .1 i.00 9.43 1.00 6.1 1.00 9.90 1.00 9.53 1.00 10.9i 1.00 12.:.7 i.00 12.56 1.00 1.00 12.4.

00 3. 2 1.00 B.:2 .00 1.00 1.00 3.

S1.00 10.3: I 1.00 11.24 5 1.00 3 1.00 13.!Z 4 1.00 5 1.00 14.3.

9 1.00 4.

7 1.00 8 1.00 3 .00 1 3 0 o2 9 1.00 0 1.00 15.13 6 1.00 1. 9 1.00 .3.

9 1.00.

1 00 1 .00 4 1.00 2 00 3 1.00 21 >.00 93 00 29 OC 1.1; bref2l1c.pdb Thu Apr 25 12:21:47 1996 ATOM 305 0 GLY 49 67.294 42.396 13.152 :.00 3.06 ATOM 306 N PRO 50 61.214 41.234 19.732 1.00 4.49 ATOM 301 CD PRO 50 61.104 39.790 19.536 1.00 2.00 ATOM 308 CA PRO 1C 67.519 41.540 21.125 1.00 2.?9 ATOM 309 CB PRO 50 61.545 40.158 21.162 1.00 3.91 ATOM 210 CG PP.0R 50 67.935 39.264 20.622 1.00 2.00 ATOM 211 C PRO 10 68.831 42.301 21.315 1.00 4.81 ATOM 212 0 PRO !0C 68.962 43.122 22.21"; 1.00 1.36 ATOM 313 N GLY 5; 69.781 42.100 20.403 1.00 5.60 7 ATOM 314 CA GLY I, 11.059 42.792 20.471 .00 2.8) ATOM 315 C GLY 1, 10.991 44.263 20.103 1.00 3.26 ATOM 316 0 GLY 51 12.025 44.910 19.956 1.00 5.85 ATOM 311 N ASN 52 69.192 44.815 19.968 1.00 2.00 ATOM 318 CA ASN 52 69.670 46.211 19.604 1.00 2.00 ATOM 219 CB ASN '2 68.527 46.401 18.633 1.00 3.33 ATOM 320 CG ASN 52 68.768 47.534 11.666 1.00 1.97 ATOM 321 OD1 ASN 52 69.233 47.311 16.538 1.00 12.55 ATOM 322 ND2 ASN 52 68.442 48.753 18.019 1.00 10.05 ATOM 323 C ASN 52 69.505 41.144 20.797 1.00 3.59 s ATOM 324 0 ASN 52 69.524 48.359 20.638 1.00 2.00 3 ATOM 325 N TYR 53 69.286 46.513 21.985 1.00 5.10 ATOM 326 CA TYP. 53 69.148 41.350 23.229 1.00 5.58 oATOM 321 CB TYP. 53 61.7107 471.412 23.710 1.00 5.70 ATOM 328 CG TYP. 513 66.615 47.547 22.768 1.00 4.84 ATOM 329 CD1 TYF. -3 66.061 46.414 22.188 1.00 6.02 ATOM 220 CE1 TYP. 3 65.080 46.495 21.282 1.00 5.48 ATOM 331 CD2 TYP. 52 66.123 4e.789 22.405 1.00 5.30 ATOM 332 CE2 TYP. 53 65.112 48.891 21.495 1.00 6.56 V,060 ATOM 333 CZ TYP. 53 64.598 41.729 20.929 1.00 8.11 ATOM 334 OH TYF. 53 63.590 41.767 19.987 1.00 12.54 ATOM 335 C TYR 53 69.943 46.667 24.308 1.00 .3.83 SATOM 336 0 TYR 53 70.116 45.465 24.245 1.00 4.09 3 ATOM 331 N SEP. 54 10.251 41.428 25.346 1.00 3.81 ATOM 338 CA SEP. 54 70.977 46.921 26.501 1.00 6.59 ATOM 339 CB SER 54 12.296 47.682 26.710 1.00 8.72 ATOM 340 OG SEP 54 13.405 46.8671 26.341 1.00- 13.32 ATOM 341 C SEE 54 10.071 41.035 21.126 1.00 4.52 ATOM 342 0 SER 54 69.495 48.089 21.982 1.00 5.58 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 44.676 29.514 1.00 6.11 ATOM 346 CG PHE 55 61.052 44.700 30.596 1.00 6.96 'i SATOM 347 CDI PHE 55 65.141 44.865 20.214 1.00 10.11.

,ATOM 248 CD2 PHE 55 67.330 44.5471 31.929 1.00 8.73 ATOM 349 CE1 PRE 15 64.713 44.879 31.154 :.00 12.64 ATOM 250 CE2 PHE 55 66.317; 44.561 22.874 1.00 8.02 ATOM 351 C2 PHE ;5 65.00- 44.728 32.490 1.00 8.93 ATOM 352 C PRE 15 69.942 45.179 30.891 1.00 2.90 ATOM 253 0 PHE 15 10.476 44.710 21.200 1.00 2.00 ATOM 354 N SER 56 10.083 46.892 21.595 1.00 2.00 ATOM 255 CA SER 56 10.854 46.862 32.818 1.00 5.40 ATOM 356 CB SER 56 12.159 41.651 22.681 1.00 6.39 ATOM 351 OG SER 56 71.950 48.939 22.162 1.00 9.05 3 ATOM 358 C SER 56 10.089 47.214 34.108 1.00 8.43 ATOM 359 0 SER 56 69.080 47.943 34.098 1.00 7.21 ATOM 360 N TYR 10.548 46.635 25.213 1.00 7.52 ATOM 361 CA TYR 69.915 46.856 36.495 1.00 8.61 ATOM 362 "CB TYR 57 69.091 45.621 26.883 1.00 3.65 ATOM 363 CG TYR 69.863 44.334 27.004 1.00 4.11 ATOM 364 CD1 TYR 5" 70.254 43.835 28.254 1.00 2.00 ATOM 365 CE1 TYR 5' 10.865 42.587 28.384 1.00 2.00 ATOM 366 CD2 TYR 5- 10.11- 43.560 !5.894 1.00 4.11 ATOM 267 CE2 TYR 70.729 42.316 326.020 1.00 2.48 ATOM 268 CZ TYR t- '1.094 41.834 27;.260 1.00 2.00 ATOM 3-9 TY? 1.672 40.591 27.334 1..00 2.00 ATOM 270 C TYR 70.885 47.253 417.616 1.00 10.04 ATOM 271 TYR 12.092 47.181 31.466 1.00 11.91 ATOM 312 N GL L 70.353 47.181 38.105 i.00 11.02 ATOM 213 CA GL, "6 11.18. 48.143 39.832 1.00 9.11 ATOM 374 CS CL\ 5. 71.613 49.592 39.154 1.00 10.64 ATOM 315 CG CL: 56 72.167 50.091 41.062 :.00 13.28 ATOM 3216 CD GLN !E 12.821 51.436 40.954 1.00 13.51.

ATOM 211 .E l Ie ?2.165 52.472 40.844 1.:C 15.62 ATOM 31a NE2 GLN 16 74.141 51.435 41.026 1..00 14.36 ATOM 3279 C GLN 16 70.430 41.886 41.123 1.00 8.05 ATOM 380 0 GLN 1.E 59.48.9 48.583 41.468 :.OC ATOM 281 N LEU 1 7C. '7'1 46.19E 41.169 !.00 e.41 ATOM 28-2 CA LEU 59 ;0.183 46.43! 42.038 CC 6.43 -36bref21c.pdb Thu Apr 25 12:27:47 1996 6 ATOM 383 CS LEU 59 10.534 44.993 43.313 1.00 4.10 ATOM 3684 CC LEU 59 69.811 44.344 44.446 1.00 2.46 ATOM 385 CO1 LEU 59 68.343 44.461 44.221 1.00 3.98 ATOM 386 CD2 LEU 59 70.246 42.909 44.462 1.00 6.03 ATOM 387 C LEU 59 70.926 47.335 43.995 1.00 9.36 6 ATOM 388 0 LEU 59 72.'125 47.210 44.085 1.00 9.93 ATOM 389 N GLU 60 70.227 48.253 44.667 L.00 11.94 1 ATOM 390 CA GLU 60 7C.844 49.221 45.603 1.00 13.27 ATOM 391 CB GLU 60 69.852 49.691 46.643 i.00 14.05 4 ATOM 392 CG GLU 60 70.448 50.769 47.531 1.00 15.91 ATOM 393 CD GLU 60 69.443 51.351 48.510 i.00 16.83 3 ATOM 394 OE1 GLU 60 69.263 50.755 49.601 1.00 16.52 3 ATOM 395 OE2 GLU 60 68.852 52.410 48.181 1.00 15.71 ATOM 396 C GLU 60 72.159 48.859 46.315 1.00 14.73 6 ATOM 397 0 GLU 60 12.200 47.971 47.189 1.00 14.00 8 ATOM 398 N ASP 61 13.193 49.638 45.913 1.00 16.22 1 ATOM 399 CA ASP 61 74.569 49.501 46.452 1.00 17.32 6 ATOM 400. CB ASP 61 74.624 49.151 47.930 1.00 22.61 4 ATOM 401 CG ASP 61 14.2871 50.345 48.814 1.00 26.60 6 ATOM 402 001 ASP 61 74.262 50.144 50.054 1.00 30.15 8 ATOM 403 OD2 ASP 61 14.036 51.470 48.211 1.00 21.62 3 ATOM 404 C ASP 61 15.390 48.539 45.610 1.00 16.14 6 ATOM 405 0 ASP 6: 76.582 48.742 45.423 1.00 16.58 3 ATOM 406 N GLU 62 14.758 47.416 45.130 1.00 14.78 7 ATOM 407 CA GLU 62 15.402 46.524 44.223 1.00 13.68 4 ATOM 408 CB GLU 62 14.418 45.359 43.931 1.00 15.90 6 ATOM 409 C: GL; 62 74.592 44.612 42.585 1.00 20.15 ATOM 410 CD GLU 62 72.574 44.998 41.452 1.00 18.81 6 ATOM 411 OEI GLU 62 73.324 46.202 41.202 1.00 19.09 a ATOM 412 GE2 GLU 62 73.041 44.078 40.788 1.00 17.28 ATOM 413 C GLU 62 75.709 47.363 42.941 1.00.10.99 6 ATOM 414 0 GLU 62 75.069 48.402 42.704 1.00 11.23 3 ATOM 415 N PRO 63 -6.744 46.984 42.173 1.00 9.01 7 ATOM 416 CD PRO 63 77.785 45.913 42.435 1.00 9.66 6 ATOM 417 CA PRO 63 77.069 47.740 40.959 1.00 8.47 6 ATOM 418 CB PRO 63 78.517 41.322 40.691 1.00 5.33 6 ATOM 419 CC PRO 63 78.504 45.895 41.103 1.00 7.09 6 ATOM 420 C PRO 63 76.146 41.407 29.779 1.00 ;6.19 ATOM 421 0 PRO 63 15.413 46.366 29.7715 1.00 4.91 a ATOM 422 N TPP 64 76.119 48.300 38.788 1.00 3.37 1 SATOM 423 CA TPP 64 75.298 48.092 37.613 1.00 2.00 4 ATOM 424 C3 TP.P 64 75.441 49.259 26.645 1.00 2.40 4 ATOM 425 CG TP.P 64 14.591 50.490 26.923 1.00 2.00 ATOM 426 CD2 TP.? 64 13.181 50.651 36.618 1.00 2.00 i ATOM 427 CE2 TPP 44 72.845 51.972 27.050 1.00 2.28 4 ATOM 428 CE3 TP. 64 72.114 49.811 26.186 1.00 2.18 4 ATOM 429 CD1 TP.P 44 7-.027 .51.682 "7.410 1.00 2.00 4 ATOM 430 NEl TP.R 54 72.995 52.573 37.4871 .00 2.00 7 ATOM 431 Z22 TP.P 64 71.537 52.416 26.950 00 2.00 4 ATOM 432 CZ3 TP 64 70.878 50.314 36.081 1.00 2.49 6 ATOM 433 :H2 TRF 64 70.515 51.636 26.471 1.00 2.00 4 ATOM 434 C TP.F 64 75.100 46.815 26.903 1.00 2.00 6 ATOM 435 3 TP.P 64 16.877 46.528 36.736 1.00 2.00 3 ATOM 436 N LYS 65 74.704 46.036 26.524 1.00 2.00 1 ATOM 437 CA LY! 45 74.909 44.793 35.803 1.00 2.00 4 ATOM 438 CB LYS 65 74.603 43.597 26.668 1.00 2.61 4 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 55 76.204 41.795 29.488 1.00 10.13 ATOM 442 NZ LY" 45 76.452 43.031 40.293 1.00 15.09 7 ATOM 443 C L'YS 65 74.017 44.725 24.584 1.00 2.00 ATOM '444 2 Y-S 45 71.125 45.534 24.416 1.00 2.81 i ATOM 445 N LEZ 46 17.201 43.692 233.780 i.3G 2.51 ATOM 446 CA L- 66 '2.421 43.532 22.558 OC 3.38 4 ATOM 447 3 4 -4.242 43.528 21.340 3C 2.07 ATOM 448 CG L- 4 66 -1.135 44.851 21.138 0C 2.42 ATOM 449 CD1 Ll-: .6 -4.363 44.485 20.416 5.47 ATOM 450 :D2 4;6 74.221 45.880 20.383 1..C 2.99 ATOM 451 L-V 4 -2.651 42.23, 22.492 '.00 3.16 AT.Z 452 6 11.125 41.19; 22.943 1.OC 2.56 ATOM 453 N 4 71.471 42.286 21.385 :.00 4.64 ATOM 454 :A 4 -7C..686 41.090 21.108 1.00 8.30 ATOM 455 4 4i.J52 2. 19l "1 ?.34 4 ATOM 456 W:S 4- .006 41.96:. 2'.512 00 11.12 ATOM 457 :C C 4 31 41.271: 22.363 9.68 ATOM 453 SC CYS 6- 6.2;:97 39.18. 22.300 00 9.98 1A ATOM 459 AP.C 12 2.67 29.72- 2.649 10.38 ATOM 460 CA ARG 6: 70.561 29.532 2:s.181 0OC 11.77 -37bref21c.pdb Thu Apr 25 12:27:47 1996 7 ATOM 461 CB ARC 68 71.380 38.359 27.627 1.00 15.15 ATOM 462 CG 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 21.17 ATOM 464 NE ARG 68 71.010 35.943 25.653 1.00 25.20 ATOH 465 CZ ARG 68 71.437 34.837 26.288 1.00 27.66 ATOM 466 NH1 ARG 68 72.710 34.732 26.7C5 1.00 28.62 ATOM 467 NH2 ARG 68 70.601 33.818 26.498 00 27.68 ATOM 468 C ARG 68 69.142 39.327 27.751 1.00 .76 ATOM 469 O ARG 68 68.449 38.504 28.317 1.00 3.75 ATOM 470 N LEO 69 68.762 40.027 26.684 1.CO 8.1k ATOM 471 CA LEU 69 67.428 39.983 26.131 1.00 5.24 ATOM 472 C3 LEU 69 67.137 41.247 25.328 1.00 4.64 ATOM 473 CC LEU 69 67.431 42.587 25.980 1.00 5.82 ATOM 474 CD1 LEU 69 67.302 43.727 25.026 1.00 9.48 ATOM 475 CD2 LEU 69 66.498 42.773 21.111 1.00 9.06 ATOM 476 C LED 69 67.222 38.794 25.221 1.00 6.45 ATOM 477 C LEO 69 68.175 38.217 24.655 1.00 6.60 ATOH 478 N RIS 70 65.947 38.430 25.133 1.00 6.17 ATOM 479 CA MIS 70 65.448 31.374 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 70 65.759 35.494 25.871 1.00 4.94 ATOM 482 CD2 HIS 70 66.779 34.706 25.460 1.00 7.46 ATOM 483 ND1 lHIS 70 65.759 35.444 27.243 1.00 8.83 ATOM 484 Z11 HIS 70 66.738 34.653 27.650 1.00 7.22 SATOM 485 NE2 HIS 10 67.372 34.193 26.586 :.00 6.78 ATOM 486 C HIS 70 64.40 38.097 23.546 1.00 6.62 '29 39.240 23.862 30 '.62 S...ATOM 487 3 HIS 70 64.129 39.240 23.83 .00 '.2 ATOM 488 N CLN 71 63.871 37.453 22.520 .0C :3.06 ATOM 489 CA GLN 71 62.828 38.038 21.676 1.00 12.44 ATOM 490 CB CLN 71 63.449 38.691 20.442 1.0C 12.64 ATOM 491 CC CLN 71 62.523 39.628 19.675 1.00 12.33 ATOM 492 CD CLN 71 63.193 40.157 18.423 1.00 11.98 ATOM 493 OE1 GLN 71 63.256 41.364 18.185 1.00 14.18 ATOM 494 NE2 GLN 71 63.741 39.254 17.638 1.00 13.04 ATOM 495 C CLN 71 61.867 36.915 21.278 1.00 14.54 ATOM 496 O GLN 71 62.293 35.846 20.828 1.0-13.15 ATOM 497 N ALA 72 60.576 37.148 21.510 1.00 16.60 ATOM 498 CA ALA 72 19.540 36.163 21.222 1.00 17129 ATOM 499 CB ALA 72 59.106 35.462 22.513 1.00 18.25 SATOM 500 C ALA 72 58.339 36.816 20.552 1.00 17.09 ATOM 501 o ALA 72 57.962 37.949 20.890 1.00 17.99 SATOM 502 N PRO 73 57.770 36.140 19.535 1.00 15.10 *690: ATOIH 503 CD PRO 73 58.266 34.944 18.833 .00 15.56 ATOM 504 CA PRO 73 56.618 36.681 18.835 1.O 14.26 ATOM 505 CB PRO 73 56.539 35.789 17.608 l.OC 14.62 ATOM 506 CC PRO 73 57.057 34.500 18.096 1.OC 14.52 ATOM 507 PRO 73 55.392 36.586 19.701 32.69 as ATOM 508 3 PRO 73 55.295 35.678 20.522 3C 16.10 ATOM 509 N THR 74 54.568 37.632 19.628 1.OC 12.65 ATOM 510 CA THR 74 53.304 37.789 20.338 .C 11.59 ATOM 511 CB TRR 74 52.987 39.276 20.518 1.2: 3.94 ATOM 512 CGI THR 74 54.100 39.935 21.092 .OC 12.22 ATOH 513 C02 THER 74 51.790 39.404 21.423 1.0t 13.10 ATOM 514 C TER 74 52.216 37.289 19.382 .OC 13.56 ATOM !15 TRR 74 52.234 37.637 la.198 1.0C 16.99 ATOM 516 V ALA 75 51.237 36.542 19.885 1.LC 12.64 ATOM- 17 CA ALA 75 30..31 36.076 19.045 ATOM 518 CD ALA 75 48.995 35.578 19.905 .0C 10.80 ATOM 519 ALA 75 49.612 37.152 18.102 3.70 ATOM 520 3 ALA 75 49.256 36.837 16.987 1. 12.33 ATOM 521 N ARC 76 49..583 38.410 18.545 .12 ATOMH 22 CA ARG 7 49.107 39.552 17.744 10.3 ATOM 523 C ARG 76 48.870 40.786 33.605 1. 3.98 ATOM 524 C ARC 76 47.709 40.722 19.529 1:i.38 ATOM 525 CD ARG 76 47.936 41.676 20.73 .2 ATOM 526 NE ARG 76 47.296 41.163 21.951 1.11 23.03 ATOM t27 C. ARG 76 47.70C 40.066 22.60! 25.34 ATOM 525 N1 ARGC 76 48.745 39.355 22.!61 25.68 ATOM 529 4H2 ARG 76 47.065 39.679 23.71-2 28.25 ATOMH 530 ARG 76 50.026 40.042 16.64; 12.35 ATOM 531 0 ARC 76 49.680 41.002 15.961 :C 15.69 ATOM 532 N GLY 7! 51.223 39.489 16.508 01 12.27 ATOM 533 CA CLY 52.'21 29.982 15.471.. 3 ATOM 534 C GLY 71 51.079 41.083 15.902 12.38 ATOM 535 GLY 17 53.633 41.814 15.1C2 c: 1-58 ATOM 536 sN ALA 7i 53.242 41.226 17.20S 12.04 ATOM 531 CA ALA 1? 54.158 42.21) 1-.75? 1 0 ATOM 538 CD ALA 78 53.465 43.041 1j.83! 10.28 -38-

S

0 *90r S@ *r S 0 0O 55.0 bref2lc.pdb ATOM 539 C ATOM 540 0 ATOM 541 N ATOM 542 CJ ATOM 543 C ATOM 544 C ATOM 545 Cc ATOM 546 C ATOM 547 0 ATOM 548 N ATOM 549 C ATOM 550 C ATOM 551 C ATOM 552 C ATOM 553 N ATOM 554 C ATOM 555 ATOM 556 N ATOM 557 C ATOM 558 0 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 510 ATOM 571 ATOM 5172 ATOM 573 ATOM 574 ATOM 515 ATOM 576 ATOM 5177 ATOM 518 ATOM 519 ATOM 580 ATOM 581 ATOM 582 ATOM 583 ATOM 584 ATOM 5 ATOM 586 ATOM 5871 ATOM 588 ATOM 589 ATOM 590 ATOM 591 ATOM 592 ATOM 593 ATOM 594 ATOM 595 ATOM 596 ATOM 5971 ATOM 598 ATOM 599 ATOM 600 ATOM -601 ATOM 602 ATOM 603 ATOM 604 ATOM 605 ATOM 606 ATOM 6071 ATOH 608 ATOM 609 ATOM 610 ATOM 611 ATOM 612 ATOM 613 ATOM 614 ATOM t15 ATOM 616

ALA

VAL

A VAL B VAL G1 VAL G2 VAL

VAL

ARC

A ARC B ARC G ARC D ARG E ARC Z ARC H1 ARG H2 ARC

ARC

PRE

A PHE B PHE G PHE D1 PHE :D2 PHE :E1 PHE :E2 PHE :Z PRE

PRE

S PHE N TRP CA TRP CB TRP CC TRP CD2 TRP CE2 TRP CE3 TRFP CD1 TRP NEt TRP CZ2 TP.

CZ3 TRP CH2 TRP C TP O TPP N CYS CA CYS O CYS CB Crs SC CYS N SEA CA SER CB SEP.

OC. SEP C SER O SER N LEU CA LEU CB LED CC LEU CD1 LED CD2 LE"'

LEU

LEt N PP.C CO PRAc CA PP.C Cb PROC CC P.C C PP.C 0 PP.

N THR CA THR CB TER OC1 TPR CG2 THP C THR l8 19 79 19 19 79 To 19 is 89 80 80 80 80so 80 80 80so so so so 91 31 91 0.

81.

a'a.

ai 81 31 82 at 82 82 82 82 82 32 32 32 32 82 82 32 !3 33 83 33 33 84 i4 34 84 34 35 25 :t.

C..

36 if.

if 9' se f 55.263 55.080 56.418 57.546 58.844 .8.106 59.135 57.786 51.633 '8.207 58.420 57.507 57.465 56.674 55.272 54.415 54.829 53.142 59.846 60.466 60.346 61.688 62.385 62.744 61.861 63.941 62.164 64.275 63.3714 61.546 60.725 62.301 62.263 61.253 61.585 62.234 62.328 62.744 S61.304 61.750 62.919 63.333 63.415 63.656 64.606 63.169 65.024 64 .63 63.13 66.02 66.43 65.24 64.90 64.39 65.09 66.12 67.17 66.00 67.11 66.67 66.73 67.01 67.84 61.70 6'.00 69.02 69.95 69.74 71.2 71.2 69.3 69.1 69.2 68.7 68.9 68.4 68.1 69.3 41.329 18 40.106 18 41.923 18 41.178 19 41.391 19 40.141 11 42.848 18 41.500 20 42.637 21 40.491 21 40.648 22 39.672 23 39.838 25 38.710 25 38.809 25 37.809 25 36.631 25 38.011 25 40.484 2 39.434 2 41.519 2: 41.481 2 42.814 2 43.102 2 43.181 2 42.670 2 44.030 2 42.908 2 43.594 2 41.209 2 41.848 2 40.240 2 39.911 2 38.189 2 31.412 2 36.372 2 35.248 2 36.277 2 36.888 2 35.581 2 34.048 35.071 33.980 39.561 39.733 39.156 1 38.149 2 38.3713 S38.969 6 39.909 5 40.538 1 31.353 4 36.980 6 35.555 5 34.752 4 37.135 2 36.544 2 37.940 5 38.209 7 39.160 2 40.624 3 41.388 0C 40.844 9 36.991 2 36.023 7 37.017 3 38.092 60 35.313 12 36.361 31 37.343 33 35.832 43 36.847 27 34.622 92 34.39; 63 32. 94; 97 32.183 49 22.599 52 35.26" .357 .495 .640 .192 .354 .024 .111 .672 .125 .403 .813 .550 .052 .630 .2371 .313 .743 *.063 1.297 1.114 1.951 4.488 4.305 2.915 2.091 2.409 0.763 1.086 0.251 5.955 6.604 6.469 1.891 a.199 7.697 8.428 7.577 9.722 6.453 6.378 7.9871 0.1371 19.212 18.371 27.623 29.635 30.282 21.702 22.271 20.319 31.992 22.258 33.610 33.658 32.13 -4.48 24.19 25.54 26.45 27.54 7.19 28.48 25.23 27.11 27.35 27.38 26.98 33.03 37.92 39.51 40.16 40.0 4.3 41.7 40.6 42.9 42.5 Thu Apr 25 12:27:47 1996 8 L.00 11.11 6 L.00 13.01 1.00 9.69 1.00 1.22 S 1.00 6.05 6 1.00 6.29 t 1.00 5.80 1.00 5.75 6 1.00 4.15 1.00 4.34 1.00 7.09 6 1.00 8.65 1.00 1.34 1.00 6.89 1.00 6.67 1.00 4.11 1.00 5.04 1.00 2.00 L.00 5.10 1.00 3.871 1.00 4.32 1.00 5.56 1.00 4.971 1.00 5.07 1.00 6.98 1.00 7.11 1.00 7.58 1.00 10.89 1.00 1^.08 1.00 7.23 1.00 8.68 1.00 7.82 1.00 8.83 1.00 9.85 1.00 12.09 1.00 11.52 1.00 13.271 1.00 15.01 1.00 14.64 1.00 12.57 1.00 17.05 1.00 16.175 1.00 17.82 1.00 a.c-S 1.00 7.22 1.00 7.16 1.00 6.S2 1.00 4.93 1.00 5.96 1.00 7.73 1.00 15.35 1.00 3.11 S1.00 4.32 1.00 5.70 1 i.00 12.40 3 1.00 '.36 0 1.00 11.62 6 1.00 671 7 1.00 4.38 6 1.00 3.56 7 1.00 5.43 2 1.00 2 1.00 S.46 0 1.00 2 .00 3.2: 8 '.00C 9 1.00 6 4 1 .O 2 :.0o 5 1.00 .)i9 7 1.00 4.26 29 94 00 i. 27 ,.00 017 O0 o .2Z 75 00 1.!3 31 L.00. .7s

I

6 6 9 6 6 6

I,

6 6

C

1 6 6 6 6 i 16 6

I,

6 i 7 i .4 6 i 6 6

I

i

I

i i S s 0c -39bref21c.pdb Thu Apr 25 12:27:47 1996 9 ATOM 611 0 THR 81 68.606 35.730 43.384 .00 9.13 ATOM 618 N ALA 88 70.661 35.474 42.541 30 8.99 ATOM 619 CA ALA 88 71.313 36.286 43.568 :0 8.39 ATOM 620 CB ALA 38 72.812 36.176 43.419 1.00 3.06 ATOM 621 C ALA 88 70.922 37.752 43.497 30 8.97 ATOM 622 0 ALA 98 71.441 38.573 44.247 i.00 10.83 ATOM 623 N ASP 3S 70.030 36.090 42.578 .30 8.36 ATOM 624 CA ASP 39 69.633 39.470 42.397 00 8.96 ATOM 625 CB ASP 29 70.041 39.911 40.992 1.00 7.68 ATOM 626 CG ASP 89 71.563 39.915 40.788 .00 6.7 ATOM 627 ODI1 ASP a9 72.319 40.224 41.720 30 3.92 ATOM 628 OD2 ASP 89 72.012 39.646 ?9.667 1.00 6.25 ATOM 629 C ASP 89 68.141 39.746 42.654 1.00 9.65 ATOM 630 0 ASP 89 67.668 40.880 42.522 1.00 9.22 ATOM 631 N THRP. 90 67.420 38.724 43.094 1.00 7.69 ATOM 632 CA THRP. 90 66.010 38.866 43.359 '.00 5.03 4 ATOM 633 CB THR 90 65.298 37.603 42.898 1.00 3.78 6 ATOM 634 OG1 THR 90 65.905 36.466 43.495 '.00 2.00 z ATOM 635 CG2 THR 90 65.464 37.445 41.430 ".00 3.18 t ATOM 636 C TRR 90 65.667 39.219 44.823 1.00 8.87 ATOM 637 0 THP. 90 64.634 38.790 45.335 1.00 11.62 ATOM 638 N SEP 9! 66.492 40.043 45.479 :.00 7.49 ATOM 639 CA SER 91 66.264 40.434 46.877 1.00 7.31 ATOM 640 CB SEP. 9 67.470 41.178 47.448 1..00 9.23 ATOM 641 OG SEP. 91 68.619 40.343 41.478 1.00 9.38 ATOM 642 C SER 91 65.008 41.265 47.033 1.30 8.55 ATOM 643 0 SEP. 91 64.779 42.197 46.263 1.30 9.92 ATOM 644 N SER 92 64.281 41.029 48.125 1.30 8.2 ATOM 645 CA SEP. 92 63.000 41.671 48.328 1.30 6.55 ATOM 646 CB SEP. ?2 62.022 40.702 49.003 1.00 7.73 ATOM 647 OG SER 92 61.127 40.120 48.085 1.00 9.02 ATOM 648 C SER 92 62.732 42.992 48.963 1.00 6.08 6 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 -1 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 6 ATOM 655 CD2 PEE 93 .60.475 43.884 52.232 1.00 2.00 6 ATOM 656 CE1 PHE 93 61.260 41.265 52.689 1.00 2.00 6 ATOM 651 CE2 PHE 93 59.520 42.881 52.478 00 2.00 ATOM 658 CZ PE 93 59.922 41.573 12.704 00 2.00 ATOM 659 C PHE 93 63.923 46.107 50.035 -1.00 5.65 ATOM 660 0 PHE 93 63.753 47.156 :.3.657 1.00 5.71 1 ATOM 661 N VAL 94 64.611 46.008 48.938 1.00 5.76 ATOM 662 CA VAL 94 65.542 47.054 48.410 1.00 4.07 ATOM 663 CB VAL 94 66.969 46.501 49.238 1.00 3.20 ATO 664 CGI VAL 94 67.600 46.310 49.571 00 6.25 ATOM 665 CG2 VAL 94 66.935 45.177 47.522 1.30 2.00 ATOM 666 C VAL 94 65.042 47.525 47.040 1.00 6.50 i.

ATOM 667 0 VAL 94 64.317 46.793 46.368 00 6.26 ATOM 668 N PRO 95 65.364 48.780 46.648 00 4.63 SATOM 669 CD PRO 95 65.947 49.823 47.507 00 5.07 ATOM 670 CA PRO 95 64.960 49.357 45.365 2.90 ATOM 61i CB PRO 95 65.316 50.826 45.530 1.00 2.93 ATOM 672 CG PRO 95 65.261 51.036 47.004 1.00 4.40 ATOM 673 C PRO i5 B5.783 48.756 44.248 00 SATOM 674 *O PRO 95 66.985 48.592 44.399 00 7.49 ATOM 675 N LEU 96 65.128 48.419 43.141 1.00 6.65 ATOM 76 CA LEO 16 65.776 47.852 41.957 1.30 5.19 ATOM 677 CB LEU ?6 65.088 46.531 41.543 .00 3.04 ATOM 67, CG LEU 96 65.571 45.607 40.411 1.00 2.00 ATOM 679 CDI LEO t6 E6.945 45.060 40.642 1.30 2.00 ATOM 680 CD2 LEU ?6 64.648 44.446 40.215 00 2.00 A7CM 681 f LEU 65.112 48.886 43.81 1.230 A.21 ATOM i82 LEU ?6 64.639 49.309 40.36( 00 5.C2 ATOM 683 N GLU 9' 66.881 49.355 40.416 1.00 3.18 ATC 684 A GL" 67.000 50.324 2.326 1.30 3.49 ATOM 685 CB GLU 9' 68.315 51.069 23.476 1.30 10.17 ATCM 666 CG SLU 7" 68.162 52.499 2).849 1.3C0 10.56 ATOM 687 CD GLU 67.806 53.335 23.676 1.30 12.04 ATOM 686 OE1I GLU 68.087 54.545 23.734 1.30 14.20 A7O:; 6sq 0E2 GLU 67.252 52.7a7 2:.691 1..3 1-.32 ATOM 690 C GLU 2' 66.95S 49.61-3 2.-387 30 8.11 ATOM 691 0 GLU 67.-35 48.689 27.741 1.30 ?.01 ATOM 92 N LEV 38 66.083 50.053 27.101 :.00 3.76 ATOM ;93 -A LEV ?8 65.954 49.400 25.821 50 .3.77 ATOM 694 CB LEV 98 64.592 48.695 23.754 00 3.21 bre 21c.pdb Thu Apr 25 12:27:47 1996 ATOM 695 CC LEU 98 64.366 41.487 26.686 1.00 3.91 ATOM 696 CD1 LEU 98 62.912 47.080 25.121 t.00 9.15 ATOM 691 CD2 LEU 98 65.202 46.309 25.266 1.00 3.89 ATOM 698 C LED 98 66.141 50.388 24.616 30 9.74 ATOM 699 0 LEU 98 65.751 51.556 24.781 1.00 11.17 ATOM 700 N ARC 99 66.814 49.945 23.621 '.00 7.82 ATOM 101 CA ARG )9 61.050 50.799 22.467 1.:C 3.42 ATOM 702 CB ARG 99 68.265 51.101 22.680 1.30 9.99 ATOM 703 CG ARG 99 68.319 52.571 23.915 1.30 13.57 ATOM 704 CD ARG 99 69.548 53.483 23.822 1.30 15.6 ATOM 705 NE ARG 99 70.198 52.717 23.766 1.00 21.42 ATOM 706 CZ ARG 99 11.623 52.634 22.709 1.00 23.75 i ATOM 707 NH1 ARG 99 71.364 53.271 21.557 1.00 25.09 ATOM 708 NH2 ARG 99 72.747 51.921 22.818 1.00 24.11 ATOM 109 C ARG 99 61.294 50.002 21.174 1.00 7.84 i ATOM 710 0 ARG 99 68.179 49.159 21.118 1.00 8.53 1 ATOM 711 N VAL 100 66.528 50.307 20.136 1.00 5.56 7 ATOM 712 CA VAL 100 66.670 49.664 28.852 1.00 5.54 i ATOM 713 CB VAL 100 65.321 49.097 23.391 1.00 a.61 ATOMH 714 CGC1 VAL 100 65.446 48.461 27.008 1.00 1.63 f 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 7711 0 VAL 100 66.556 51.831 21.819 1.C0 3.63 ATOM 718 N THR 10: 68.236 50.490 27.156 1.00 7.98 ATOM 719 CA THP. 101 68.768 51.483 25.193 1.0 10.18 6 ATOM 720 CB THP. 101 70.000 52.277 26.748 1.00 8.43 ATOM 721 OCG1 THP 101 70.526 51.629 27.809 00 13.91 ATOM 722 CG2 THP. 10.- 69.603 52.663 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 49.750 24.645 1.00 11.61 ATOM 725 N ALA 102 68.915 51.752 23.767 1.00 12.50 ATOM 126 CA ALA 102 69.216 51.369 22.366 1.00 14.07 ATOM 727 CB ALA 102 68.735 52.465 21.399 1.00 14.73 ATOM 128 C ALA 102 70.721 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 71.111 50.332 21.270 1.00 12.13 7 ATOM 731 CA ALA 103 12.520 50.004 21.021 1.00 13.74 ATOM 732 CB ALA 103 72.631 48.712 20.183 1.00 153,06 6 ATOM 733 C ALA 103 73.250 51.173 20.338 1.00 14.07 s ATOM 734 0 ALA 103 73.958 51.013 19.345 1.00 16.53 i ATOM 735 N SER 104 73.105 52.341 20.931 00 12.51 1 ATOM 736 CA SEP 104 73.673 53.569 20.440 1.00 10.25 ATOM 731 CB SEP. 104 72.834 54.066 13.266 1.00 9.41 ATOM 138 OG SEP. 104 71.434 54.033 19.565 1.00 8.41 ATOM 739 C SER 104 73.507 54.528 21.600 1.00 11.58 ATOM 140 0 SEP. 104 73.557 55.746 21.412 1.20 11.80 ATOM 741 N GLY 105 73.1871 53.964 22.770 1.30 11.41 ATOM 742 CA GLY 73.002 54.147 23.976 1.:0 12.64 ATOM 743 C SLY 135 71.737 55.568 23.980 1.30 13.51 ATOM 144 3 SLY 105 171.507 56.335 24.921 !.00 15.64 ATCM 745 N ALA 106 10.929 55.433 22.930 1.30 12.54 ATOM 146 CA ALA 106 69.668 56,166 22.837 1.00 11.65 S* ATOH 747 CS ALA 106 69.068 56.040 21.444 1.00 13.177 ATOM 748 C ALA 136 68.752 55.553 23.84 1.30 11.28 ATOM 749 0 ALA 106 68.501 54.338 23.899 1.00 10.70 i ATOM 750 N PP.0 107 68.239 56. 392 24.779 1.3C 8.60 ATOM 751 CD PP.0 1o 68.390 57.855 24.686 :C 9.28 ATOM 752 CA PRO 107 67.354 56.019 25.882 1..0 7.17 ATOM 753 CB PP.C. 107 67.282 51.314 26.683 1.30 8.42 6 oo.* ATOM 754 CG PP.0 107 67.302 58.358 25.605 '.00 9.15 ATOM 755 C PRO 17 65.964 55.459 25.552 7.66 4 ATOM 156 O PRO 107 65.224 56.048 24.181 1..C 8.78 ATOM 75 N AP.G 108 65.595 54.353 26.196 7.20 ATOM 758 CA AP.G 64.290 53.751 25.993 C 4.63 ATOM 759 CB AP.G 18 64.439 52.415 25.2E8 7.43 ATOM 160 CG AP.C 1,38 63.168 51.302 24.695 30 10.88 ATOM 161 CD AP.G 108 62.182 52.688 23.460 0C 14.12 ATOM 762 NE AP.G .1S 61.461 52.313 22.3M4 C 16.25 ATOM 163 CZ A?.G 1-8 61.086 51.084 22.650 O 15.01 ATOM 764 NH1 AP.G o10 61.911 50.067 22.764 :C 18.31 ATOM 765 NH2 ARCG 10 59.858 50.867 22.236 1.3; 11.47 ATOM 766 C ARG 108 6:.45! 53.624 27.283 00 5.36 ATOM 767 ARPCG .i 62.42C 54.259 27.404 i.36:: .6 ATOM 168 N TYR -199 63.883 52.8!7 2a.263 i- .12 ATOM 169 CA TYR 109 53.102 52.711 2.509 .712 ATOM 770 CB TYR 109 62.41S 51.250 2).631 .62 ATOM 771_ CG Y? 1-09 61.45! 51.024 23.544 3.20 ATOM 772 CD1 TYR 109 61.7175 50.089 2-.565 1 i .38 -41bref21lc.pdb Thu Apt.25 12:27:47 1996 a a

ATOM

173 71174 7715 776 777 7.79 780 781 782 783 784 785 786 787 788 789 790 791 792 793 794 795 796 797 798 799 800 801 802 803 804 805 806 807 808 809 810 811 812 813 814 815 816 81"7 81 281 S2( 82 82: 82.

82 82 82 82 82 82 83 83 83 83 8i 83 8.

3 8 8 8 8 8 8 9 8 8 8 CE1 TYR 1C CD2 TYR 1C CE2 TYR 10 CZ TYR 10 OH TYR I1 C TYR 1I O TYR I1 N HIS 1 CA HIS 1 CB HIS 1 CG HIS 1 CD2 HIS 1 ND1 HIS 1 CEI HIS 1 NE2 HIS 1 C HIS 1 O HIS 1 N ARC 1 CA ARG 1 CB ARC 1 CC ARG 1 CD ARG 1 HE ARG CZ ARG NH1 ARG NH2 ARG C ARG 0 ARG

VAL

CA VAL CB VAL CGI VAL CG2 VAL C VAL O VAL N ILE CA ILE CB ILE CG2 ILE CGI ILE CD1 ILE I C ILE 0 ILE N HIS 1 CA HIS 8 CB HIS 9 CG HIS 0 CD2 HI8 1 ND1 HIS 2 CE1 HIS 3 HE2 HIS 4 C HIS 5 0 HIS 6 N ILE 7 CA ILE 8 CB ILE 9 CG2 ILE 0 *CG1 ILE 1 CD1 ILE 2 C ILE 3 0 ILE 74 NI ASN s5 :A ASN 36 CB ASN 17 CG ASN 39 ODI ASN 39 ND2 ASN 40 C ASN 41 0 ASN 42 N SLU 43 CA GL;C 44 CB GLU 45 CC SLCU 46 CD GL;: 47 OEI GLC 48 OE2 GL 149 C GLU 50 0 GLU 19 09 09 09 09 09 09 1L0 10 10 10 10 10 10 10 10 10 11 112 112 .11 111 111 112 111 111 111 111 112 112 112 112 112 112 113 113 113 113 113 113 113 113 114 114 114 114 114 114 114 114 114 114 115 115 115 115 115 115 115 115 116 116 116 116 116 116 116 116 116 11" 11" 11" 11' 11" 60.897 60.230 59.337 59.670 58.777 63.911 65.124 63.198 63.760 64.468 65.167 66.383 64.623 65.476 66.553 62.628 61.740 62.693 61.716 60.878 59.700 58.370 57.828 57.096 56.822 56.585 62.546 63.176 61.877 62.493 62. 882 63.003 64.235 61.398 60.268 61.709 60.692 60.223 '59.680 61.39( 61.012 61.10: 62.14 60.26 60.50 59.79 60.55 61.33 60.58 61.36 61.83 59.90 58.70 60.74 60.26 61.4: '60.95 62.3 63.7 59.1' 58.2 59.0 57-.9 58.3 58.5 59.4 57.8 56.5 55.5 56.6 55.4 55.

55.9 56.: 56.

55.

54.

49.788 26.

51.642 28.

51.347 27.

50.421 26.

50.152 25.

52.909 20.

52.737 10.

53.259 11 52.467 23 54.830 13 55.029 14 54.616 15 55.764 35 55.803 26 55.114 36 53.380 24 54.224 14 52.361 15 52.116 36 50.881 35 50.590 36 50.465 25 49.099 !5 48.521 26 49.182 3 47.308 51.350 51.808 2 51.758 2 51.471 2 52.803 4 52.545 4 53.354 4 50.668 4 1 51.105 4 1 49.480 4 48.638 4 I 47.527 4 0 48.130 2 6 46.623 4 2 45.471 3 5 47.931 4 1 48.234 4 7 47.000 3 46.181 4 3 46.758 4 47.821 7 47.787 9 49.130 8 49.850 5 49.057 7 44.830 15 44.688 1 43.820 61 42.495 39 41.480 53 40.049 33 41.672 31 42.190 07- 42.012 94 41.21"7 12 42.492 36 42.066 11 42.342 82 43.223 70 44.421 06 44.414 89 42.1'2 12 42.223 664 43.858 480 44.614 732 46.113 958 46.606 160 48.090 648 48.601 816 48. *5 116 44.321 440 45.12.: 557 480 476 511 481 774 .794 .825 .174 .296 .613 .048 .652 .662 .321 .214 .240 .062 .112 .742 .641 .862 .183 6.730 1.840 6.550 1.369 7.306 9.510 9.822 0.601 2.094 0.093 0.542 0.581 1.049 1.686 0.688 9.426 0.315 9.468 3.001 43.572 43.463 44.645 45.860 46.555 ;7.65 46.1 C 46.89 47.93 44.33 44.22 44.2C 43.81 43.88 43.98 42.65 42.9f 44.75 44.3C 45.9i 46.8' 43.3 43.6 48.0 4).5 46.5 46.8 45.8 45.4 45.5 46.9 48.0 44.0 43.

1.00 12.39 00 10.61 00 12.42 00 12.48 00 14.44 c 00 8.52 6 00 9.59 i.00 10.99 1.00 14.45 00 16.0 00 21.12 i '.00 21.71 00 24.07 00 23.40 6 00 22.60 :.00 12.21 6 :.00 13.06 8 :.00 11.08 00 10.30 6 00 9.90 6 00 8.05 6 1.00 8.40 6 i.00 8.93 i.00 8.80 00 10.13 *.00 10.84 1.00 11.2 00 13.11 1.00 11.16 :.00 11.15 1.00 12.50 1.00 13.08 1.00 12.31 1.00 7.17 00 8.50 1.00 5.20 1.00 6.80 00 x. 60 00 6.45 L.00 1.39 00 9.87 00 7.16 1.00 9.02 1 .00 2.78 1.00 2.00 0 '.00 2.00 5 00 2.00 2 :.00 4.22 6 00 4.03 1 1.00 2.34 8 1.00 8.21 0 00 2.00 1 1.00 2.00 1 1.00 2.00 1 00 2.00 3 00 3.64 4 1.00 4.23 .0 00 2.00 6 00 2.23 1.30 3.56 2 00 6.91 87 .50 4.63 9! 00 5.21 iC .C00 5.33 5: i..0 5.Q4 •0 .00 3.06 51 L.00 8.46 4" C 5.S2 79 00 4.52 41 20 8.36 36 00 7.65 34 00 6.11 3- 'C 12.42 02 :0 15.01 54 )0 18.35 702 i.00 11.7.

2; OC 42E .30 9.90 3 6 6 6 6 7 6 6 3 s: -42brf2le Pdb Thu Apr 25 12:27:47 1996

S.

o. .o *o *oo

ATOM

ATCHM

ATCH

ATOM

ATOMCH

ATOM

ATHOM

ATCOM

ATOM

ATCH

ATOMH

ATOM

ATHOM

ATOM

ATOMH

ATOM

ATCOM

ATOM

ATCHOM

ATOM

851 852 853 854 855 856 857 858 859 860 861 862 863 864 865 866 867 868 869 870 871 872 873 874 875 876 877 878 879 880 881 882 883 884 885 886 887 888 889 890 891 892 893 894 895 896 891 898 899 900 901 902 903 904 90: 90 90 90 90 91 91 91 91 91 91 91 91 91 91 92 92 92 92 92 92 9: 9.

N VAL I CA VAL I CB VAL 1 CG1 VAL 1 CG2 VAL I C VAL I 0 VAL I N VAL 1 CA VAL I CB VAL CG1 VAL CG2 VAL C VAL 0 VAL N LEU CA LEU -CB LEO CC LEU CD1 LEU CD2 LEO C LEO 0 LEU N LEU CA LEU CB LEU CG LEU CDI LEU CD2 LEU C LEU 0 LEU N ASP CA ASP CB ASP CG ASP OD1 ASP OD2 ASP C ASP 0 ASP N ALA CA ALA CB ALA C ALA 0 ALA N PP.RO CD PRO CA PP.C CB PRO I CG PP. C 9 C PPRO 0 PRO N VAL CA VAL 3 CB VAL 4 CC1 VAL 5 CG2 VAL 6 C VAL 7 0 VAL 8 *N SLY 9 CA GLY 0 C GLY 1 0 SLY 2 N LEU 3 CA .EU 4 CB LEU 5 CC 6 CD1 LEC 7 CD2 LE: 8 C LEC .9 3 LEL 0 N VAL 1 CA VAL 22 CB VAL i3 CC! VAL 24 CG2 VAL 25 C 'VAL 26 0 VAL 21 N ALA 28 CA ALA 18 18 18 18 18 18 18 119 .19 119 119 119 119 119 120 120 120 120 120 120 120 120 121 121 121 121 121 121 121 122 122 122 122 122 122 122 122 123 123 123 123 123 124 124 124 124 124 124 124 125 125 125 125 125 125 125 126 126 126 12i 127 12- 12- 12" 128 12- 12- 12- 12- 125 128 128 129 12S 126 129 12if 55.477 43, 55.226 42 56.313 43 57.484 42 55.828 44 55.060 41 55.453 40 54.404 40 54.155 39 53.778 38 53.749 37 54.735 39 52.998 38 52.007 39 53.171 37 52.175 37 52.446 31 51.496 31 50.125 31 52.053 31 52.289 3: 52.985 3; 51.600 3' 51.629 3 51.063 3: 52.050 3 52.939 3 52.944 3 50.974 3 50.256 3 51.279 3 50.687 3 51.493 2 52.701 2 52.927 3 53.411 2 49.292 3 48.957 3 48.464 2 47.107 2 46.187 46.981 47.826 45.979 45.216 45.652 44.362 44.602 45.451 45.289 45.524 45.345 46.724 47.474 47.504 44.436 44. 002 44.068 43.230 41.939 41.588 41.246 39.971 39.594 38.17'- 37.954 37.942 38.846 38.585 38.177 37.087 37.485 37.999 38.521 35.862 35.973 34.691 33.430 .151 .839 .488 .519 .165 .334 .755 .716 .276 .736 .267 .231 .960 .674 .919 '.411 .894 .332 1.938 1.605 1.887 5.241 5.340 3.924 3.689 3.227 2.076 4.328 2.995 3.420 1.709 0.726 9.421 9.437 0.429 '8.405 0.494 0.954 9.813 29.562 29.374 28.398 27.484 28.490 29.731 27.47 28.02: 29.48 26.11 26.02 25.04 23.71 23.00 23.80 22.77 22.83 23.28 21.66 20.73 21.26 20.98 22.11 22.6 23.9 24.5 25.3 25.5 21.6 21.0 21.3 20.4 19.1 18.0 19.4 21.0 21.7 20.5 21.0 43.523 1.4 42.137 1.0 41.261 1.

40.942 1.' 40.062 1.1 41.948 1.1 40.936 1.1 42.919 1.

42.896 1.

44.305 1.

44.292 1.

45.352 1.

41.945 1.

41.932 1.

41.132 1.

40.174 1.

38.745 1.

37.614 1.

37.790 1.

26.306 1.

40.262 1.

39.487 1.

41.250 1.

41.552. 1 42.964 1 44.062 1 43.550 1 44.501 1 40.554 1 29.654 1 40.672 1 39.782 1 39.773 1 38.795 1 38.066 1 38.748 1 40.343 1 41.453 1 29.568 1 40.010 1 1 38.839 1 1 40.954 I 40.971 1 0 41.846 1 6 42.096 8 42.845 2 43.436 5 43.432 1 42.172 2 40.966 2 42.944 5 42.381 6 42.025 6 40.974 6 43.256 8 43.267 1 44.316 1 42.768 5 43.494 13 44.035 1 45.170 13 43.268 67 43.118 49 42.935 13 43.071 22 44.424 16 41.892 23 43.612 83 42.538 61 44.737 06 44.815 47 45.616 8'J 44.701 77 44.659 01 45.470 I95 44.374 174 45.031 061 45.579 10 o0 00 0 0 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 .00 L.00 L.00 1.00 1.0O 1.01 1.01 1.01 1.0 1.0 1.0 1.0 1.0 1.0 ".0 1.0 1.0 1.0 1.0 1.0 1.0 1.( 1.'

I.

1.

3.55 2.91 2.00 2.85 2.00 2.18 3. S- 2.71 3.05 2.4 2.00 2.00 2.00 2.00 3.02 2.95 5.65 11.07 9.95 11.67 2.40 2.00 2.39 2.7- 4.51 10.24 14.' 9.4! 5.4.

7.90 8.57 6.90 7.74 9.54 9.98 10.20 7.04 5.*44 6.22 4.14 1 4 3.93 5.3- 0 2.90 0 2.9- 0 0 0 o 0 2.2.

0 4.04 0 0 0 2.01 0 0 6.23 '0 5.21 10 4..2 0 10 8.- 0 0 7.3 00 00 11.:.

00 7.;4 00 10.2" oC 6.

00 00 7..

00 6. 12 00 0c O0 00 00 00 7 00 4.6.

U

I

2 2 7 -43brtf21c.pdb Thu Apr 25 12:27:47 1996 13 ATOM 929 CS ALA 129 32.585 21.680 44.477 1.00 4.36 6 ATOM 930 C ALA 129 32.693 19.876 46.202 1.00 9.11 6 ATOM 931 0 ALA 129 32.130 18.760 45.655 1.00 9.32 1 ATOM 932 N ARG 130 32.018 20.106 47.329 1.00 9.76 7 ATOM 933 CA ARG 130 31.288 12.020 41.990 1.00 10.55 s ATOM 934 CB ARG 130 32.220 18.310 48.961 1.00 11.88 A ATOM 935 cG ARG 130 31.165 .6.979 49.486 1.00 11.87 6 ATOM 936 CD ARG 130 32.108 16.811 50.963 1.00 15.61 ATOM 937 NE ARG 130 33.351 17.567 11.252 1.00 15.76 1 ATOM 938 CZ ARG 130 33.669 13.135 52.414 1.00 20.41 ATOM 939 NH1 ARG 130 32.818 18.092 13.449 1.00 1a.08 7 ATOM 940 NH2 ARG 130 34.840 18.791 !2.514 1.00 21.04 ATOM 941 C ARG 130 30.028 19.479 48.721 1.00 10.90 6 ATOM 942 0 ARG 130 29.932 20.593 49.250 1.00 10.77 8 ATOM 943 N LEU 131 29.065 18.582 48.792 1.00 12.00 7 ATOM 944 CA LEO 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 LEU 131 25.035 20.002 49.487 1.00 10.47 6 ATCH 948 CD2 LEU 131 24.252 17.783 48.531 1.00 11.69 6 ATOM 949 C LEU 131 27.199 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 21.968 19.328 11.834 1.00 14.88 7 ATOM 952 CA ALA 132 27.964 19.982 53.249 1.00 16.22 6 ATOM 953 CB ALA 132 28.212 20.228 14.122 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 132 25.719 19.000 54.109 1.00 16.97 a ATOM 956 N ASP 133 26.553 11.009 !3.411 1.00 20.15 ATOM 957 CA ASP 133 25.397 !6.156 53.729 1.00 22.27 6 ATOM 958 CB ASP 122 25.868 14.755 54.193 1.00 23.23 6 ATOM 959 CG ASP 133 26.187 12.783 13.024 00 25.12 ATOM 960 OD1 ASP 133 25.704 14.012 51.671 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 23.515 17.415 54.715 1.00 24.05 8 ATOM 964 N GLU 134 25.310 16.802 56.037 1.0 19.91 7 ATOM 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 6 ATOM 967 CC GLU 134 26.589 15.897 58.281 1.00 17.83 S ATOM 968 CD CL 134 28.003 16.514 58.153 1.00 20.37 6 ATOM 969 OE1 GLO 134 28.980 15.726 58.020 1.00 19.82 c ATOM 970 OE2 GLU 134 28.136 11.775 58.183 1.00 18.81 1 ATOM 971 C GLU 134 24.784 18.933 57.068 1.00 17.19 i ATOM 972 0 GLU 134 25.842 19.534 57.197 1.00 18.37 3 ATOM 973 N SER 135 23.648 19.496 56.651 1.00 16.42 1 ATOM 974 CA SEP. 135 23.315 20.938 56.510 1.00 17.66 ATOM 975 CB SEP 125 24.435 21.857 51.166 1.00 17.67 s ATOM 976 OG SER 135 25.623 21.981 !6.400 1.00 19.35 ATOM 9117 SER 125 22.990 21.443 55.124 1.00 18.19 6 ATOM 978 0 SEP. 135 22.366 22.501 54.991 1.00 17.96 3 ATOMH 99 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 ATCHOM 981 Z GLY 136 23.165 22.335 52.312 1.00 22.07 6 ATOM 982 0 GLY 136 23.225 23.345 51.910 1.00 22.69 6 ATOM 983 N HIS 131 25.071 22.258 12.622 1.00 21.69 1 ATOM 984 CA HIS 131 25.992 23.332 52.301 1.00 19.69 6 ATOM 985 CB HIS 123 '26.594 23.884 53.590 1.00 22.11 4 ATOM 986 CG HIS 137 25.768 24.968 54.204 1.00 25.43 4 ATOM 987 CD2 HIS 131 26.049 25.862 !5.183 1.00 27.18 6 ****ATCHOM 988 ND1 HIS 121 24.484 25.256 !3.711 1.00 26.89 7 ATOM 989 CEI HIS 131 24.014 26.287 54.465 1.00 26.67 4 ATOM 990 NE2 HIS 132 24.944 26.674 15.325 1.00 26.59 ATOM 991 HIS 12' 27.081 22.363 51.329 '.00 19.46 ATOM 992 0 HIS 123 27.428 21.666 11.301 1.00 20.08 ATOM 993 N 'IAL 138 21.547 23.171 !0.468 1.00 16.09 ATOM 994 CA VAL 128 28.598 22.427 49.526 1.00 12.40 4 ATOM 995 CS VAL 128 28.391 24.107 43.143 1.00 12.43 4 ATOM )96 CC1 VAL 29.125 24.286 47.390 00 10.78 ATOM 997 CG2 VAL 123 27.444 23.253 47.290 1.00 12.93 ATOM 998 C 'IAL 13P. 29.891 22.987 20.156 1.00 11.10 ATOM 999 0 VAL 138 29.96C 24.376 10.7C5 00 11.62 ATOM 1000 1t 'VAL 139 30.812 22.982 50.111 1.00 9.36 ATOM 1001 CA VAL 129 32.194 22.269 '?.7124 OC 10.38 ATOM 1002 Cb VAL 139 32.53S 22.371 11.949 1.00 6.78 4 ATOM 1003 =C1 VAL '.19 33.781 22.87? 52.620 00 7.80 4 ATOM 1004 CG2 VAL 139 31.415 22.393 52.946 1.00 6.80 ATOM 4005 C VAL 139 33.249 23.095 43.615 '.00 10.04 ATOM 1006 3 VAL L29 33.33: 22.026 43.961 00 10.34 -44bref21c.pdb Thu Apr 25 12:27:47 1996 14 *t a 4

ATOM

ATCM

ATOM

ATCOM

ATOM

ATCHM

ATOM

ATOMH

ATOM

ATOH

ATO

ATOM

ATO

ATOI

ATO

1007 N LEO 14 1008 CA LEO 14 1009 CB LEO 14 1010 CG LEO 1< 1011 CD1 LEU 1 1012 CD2 LEU 1 1013 C LEU 1 1014 C LEU 1.

1015 ARG 1 1016 CA ARG 1 101i CB ARCG 1018 CG ARG 1 1019 CD ARG 1 1020 NE ARG 1 1021 CZ ARG 1 1022 NH1 ARG 1 1023. NH2 ARG 1 1024 C ARG 1 1025 0 ARG 1 1026 N TRP 1 1027 CA TRP 1 1028 CB TRP 1 1029 CG TRP I 1030 CD2 TPP 1 1031 CE2 TRP 1032 CE3 TRP 1033 CM TRP 1034 ME1 TRP 1035 CZ2 TRP 1036 CZ3 TRP 1031 CH2 TRP 1038 C TRP 1039 0 TRP 1040 N LEO 1041 CA LEO 1042 CB LEO 1043 CG LEO 1044 CDI LEO 1045 CD2 LEO 1046 C LEO 1041 0 LEO 1048 N PRO 1049 CD PRO 1050 CA PRO 1051 CB PRO 1052 CG PRO 1053 C PRO 1054 0 PRO 1055 1 PRO 1056 CD PRO 1051 CA PRO 1058 CB PRO 1059 CG PRO 1060 C PRO 1061 0 PRO 1062 M PRO 1063 CD PRO 1064 CA PRO 1065 CB PRO 1066 CG PRO 10.7 C PRO 1068 1 PRO 1069 N GL 1070 CA GLC .:31 :3 G L'- 1012 CG GL; :013 CD GL'; 1014 OE1 GL' 1015 :E2 GL'! 1016 CL: 1011 3 GLU 101S N THR S101) A T H 1080 CB THE 1081 31G THR N 1082 :G2 THR -1013 C THR M 1084 3 THR 40 40 40 40 40 40 40 40 41 41 41 41 41 41 41 41 41 41 41 42 42 142 142 142 1 4 2 142 142 142 142 142 142 142 142 143 143 143 143 143 143 143 143 144 144 144 144 144 144 144 145 145 145 145 145 145 145 146 146 146 146 146 146 146 141 141 147 14' 147 14- 148 148 148 148 146 148 148 33.975 24.194 49.312 1.0 35.027 24.306 43.384 1.0 34.966 25.613 47.761 1.0 33.126 25.968 47.000 C 33.806 27.395 46.505 L.C 33.594 24.972 45.869 l.C 36.354 24.170 49.069 I.

36.366 24.7714 !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 1.1 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.

42.727 22.282 53.773 1.

39.632 23.383 47.804 1.

39.289 23.227 46.639 1.

40.871 23.715 48.154 1.

41.941 23.846 47.182 1.

41.754 25.101 46.354 1.

41.661 26.356 47.155 1.

40.482 26.905 417.749 1.

40.852 28.094 48.397 1.

29.145 26.508 41.188 1.

42.611 21.216 41.456 42.196 28.261 48.209 1 39.93' 28.885 43.072 1 38.245 21.296 43.454 1 38.645 28.414 49.089 1 43.288 23.851 47.877 1 43.380 23.103 49.076 1 44.349 23.995 47.109 1 45.700 24.039 417.656 1 46.520 22.816 47.123 1 46.031 21.414 47.408 1 46.832 20.483 46.601 1 46.182 21.223 43.862 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 1 48.021 26.996 47.295 1 48.955 27.359 48.445 1 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 51.118 26.696 44.455 51.815 26.999 45.448 51.396 25.652 43.639 50.138 25.412 42.347 52.462 24.665 43.851 52.358 23.778 42.622 50.912 23.951 42.161 53.863 25.273 43.967 54.272 26.087 43.135 54.604 24.825 44.975 55.959 25.281 45.248 56.894 24.258 44.077 56.133 23.566 43.456 57.471 22.401 44.166 58.335 22.639 45.061 57.201 21.215 43.789 56.052 26.173 45.624 57.099 21.403 45.453 54.915 21.364 46.124 55.048 29.11776 4-.541 53.71E 29.551 46.118 53.589 29.464 44.765 53.881 31.014 44.621 55.212 28.981 43.048 54.609 29.080 43.789 0 3.25 0 6.26 0 2.05 0 2. SO 10 2.00 00 2.00 00 3.88 00 10.60 30 11.4 7 0 12.16 6 00 16.99 00 21.35 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 .00 5.00 .00 6.66 .00 5.41 .00 3.56 .00 2.35 .00 2.00 .00 2.00 .00 2.00 .00 2.00 .00 4.81 .00 2.00 L.00 2.00 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 2.72 L.00 2.80 1.00 2.95 00 4.11 .00 3.80 00 9.22 00 5.90 1.00 6.83 1.CO 7.88 1.00 6.28 1.00 3.28 1.00 10.56 1.00 10.54 1.00 3.65 1.30 1.00 18.10 1.00 22.16 1.00 24.12 1.30 23.13 1.00 10.12 1.00 12.66 1.00 10.44 1.00 31 1.30 4.74 1.00 2.30 30 4.00 1.00 4.53 6 6 3 6 6 6 3 6

I

6 3

I

7 5

X

4 4 bref21c.pdb Thu Apr 25 12:27:47 1996 a.

a. a a.

a a ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM I

ATOM

085 086 081 088 089 090 091 092 093 094 095 096 ,091 1098 1099 1100 1101 1102 1103 1104 1105 1106 1101 1108 1109 1110 1111 1112 1113 1114 1115 1116 1117 1118 1119 1120 1121 1122 1123 1124 1125 1126 1127 1128 1129 1130 1131 1132 113: 113' 113; 113 113 113 113 114 114 114 114 114 1.14 114 114 114 114 115 11! 115 11: 11: 11: 11 11 11 11 11 11 11 N PRO 1 CD PRO 1 CA PRO 1 CS PRO 1 CG PRO I C PRO 1 0 PRO 1 N MET 1 CA MET 1 CB MET 1 CG MET 1 SD MET 1 CE MET 1 C MET 1 0 MET 1 N THR I CA THR CB THR OG1 THR CG2 TR C THR 0 THP.

N SER CA SER CB SER OG SER C SER 0 SER N HIS CA HIS CB HIS CG HIS CD2 HIS ND1 HIS CEl HIS NE2 HIS C HIS 0 HIS N ILE CA ILE CB ILE CC2 ILE CG1 ILE CDI ILE 9 C ILE 0 ILE N ARG CA ARG 3 CB ARC 4 CG ARG 5 CD ARG 6 NE ARG 7 CZ ARG 8 NR1 ARC 9 NH2 ARC 0 C ARC 1 0 ARG 2 "N TYR 3 CA TYR 4 CB TYR 5 CG TYR 6 CDI TYF.

7 CEI TYR 18 CD2 TYF.

9 CE2 TYF.

i0 CZ TYF.

1 OH T'Y.

52 C TYR, 53 0 TYR 54 N GL'' 55 CA GLU 56 CB GLU 57 CG GL' 58 CD GLU 59 D3E1 GLJ 60 OE2 GLU 61 C GLU 62 0 GLU 49 49 49 49 49 49 49 50 50 50 50 50 .50 .50 .50 151 151 151 151 151 151 151 152 152 152 152 152 152 153 153 153 153 153 153 153 153 153 153 154 154 154 154 154 154 154 154 155 155 155 155 155 155 1355 155 155 155 155 156 156 156 156 156 156 156 156 156 156 156 156c 151 151 151 157 157 157 157 157 15.

56.219 29.605 43.503 51.156 30.451 47.666 56.623 29.151 49.926 58.014 30.190 49.860 58.050 31.144 48.698 55.142 30.869 50.498 55.080 31.600 49.737 55.727 31.012 51.814 54.916 32.048 52.464 55.415 33.469 52.109 56.864 33.812 52.512 57.164 33.918 54.292 57.009 35.706 54.546 53.411 31.927 52.169 52.749 32.952 52.002 52.818 30.696 52.239 51.464 30.405 51.963 51.157 28.902 51.199 51.581 28.183 52.955 51.821 28.341 50.609 50.403 30.920 52.922 49.218 30.919 52.583 50.114 31.331 54.123 49.755 31.831 55.041 50.178 31.598 56.416 51.027 32.645 56.893 49.563 33.321 54.842 48.982 33.976 55.681 50.148 33.866 53.180 50.010 35.291 53.485 51.479 35.883 53.275 52.310 35.915 54.526 52.810 37.048 55.182 52.781 34.868 55.191 53.540 35.254 56.204 53.513 36.510 56.215 49.275 35.491 52.221 49.013 36.614 51.811 48.931 34.385 :1.603 48.201 34.412 50.311 48.493 33.116 49.523 41.906 33.208 48.126 49.982 32.883 49.376 50.301 31.727 48.512 46.103 34.532 50.665 46.165 33.891 51.564 46.068 35.391 49.88! 44.638 35.649 49.91( 44.372 31.149 49.811 44.596 31.920 51.09' 44.382 39.399 50.841 44.206 40.104 52.11 44.832 41.229 52.49 45.11e 41.848 51.69 44.600 41.707 53.12 44.067 34.962 48.66 44.800 34.760 47.67 42.783 34.596 48.73 42.077 33.921 47.65 41.11774 32.414 43.01 42.978 31.665 48.33 43.447 31.591 49.65 44.624 30.889 49.96 43.10C 31.012 47.34 44.89S 30.283 47.64 45.34( 30.240 48.91 46.495 29.56' 49.21 40.'3' 34.600 47.3 40.152 35.204 48.2 40.286 34.521 46.1 38.919 35.038 45.1 39.036 36.256 44.8 37.622 36.826 44.6 37.577 38.030 43.7 37.566 39.171 44.2 37.486 37.826 42.5 28.254 33.920 44.9 38.799 33.290 44.1 1.00 7.6 1.00 4.62 1.00 5.20 1.00 2.62 1.00 2.00 1.00 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.

1.00 2.48 1.00 5.15 1.00 4.08 1.00 3.72 1.00 3.59 1.00 2.22 1.00 8.69 1.00 3.84 1.00 5.68 1.00 7.24 1.00 6.42 1.00 6.44 1.00 6.46 1.00 5.8 1..30 1..0 10.00 00 7.22 30 5.i6 1.00" 4.92 1.00 4.69 1.00 3.84 1.00 6.02 1.00 3.19 1.00 2.00 1.00 2.14 4 1.00 "6.78 1.00 2.00 1.00 2.00 1.00 2.00 1.00 2.06 1.00 2.GC 1.00 2.00 1 L.00 2.05 1 1.00 2.30 S.OC 4.56 30 5.2 8 1..3 5.20 I 1.00 8.42 38 .00 14.35 9 1.00 24.48 6 1.00 27.35 s 9 1.30 25.45 5 1.00 28.94 8 8 1.30 5.2 9 1.00 5.21 I 1.3C 5.2, 1 1.00 i9 1.30 1 13.-- 8 30 16.2i 1 C 1 4 16 o60 1 .2 19 12.2 65 2! 56 S. S 07 4..

20 1.:C 4. 13 4. .3: 1 26 i.l 32 14 1.: 97 :o 1 02 1..0 10.4 a. a a a a.

a a. a a.

a 46 kb.rf21c.pdb Thu Apr 25 12:27:47 1996 16 ATCOM 1163 N VAL 158 31.022 33.675 45.406 1.00 5.40 ATOM 1164 CA VAL 158 36.196 32.621 44.842 1.00 6.15 ATOM 1165 CD VAL 158 35.459 31.871 45.954 1.00 3.03 ATOM 1166 CC1 VAL 158 34.655 30.759 45.391 1.00 4.03 ATOM 1167 CG2 VAL 158 36.429 31.369 46.962 1.00 3.63 ATOM 1168 C VAL 158 35.154 33.186 43.878 1.00 9.07 ATOM 1169 0 VAL 158 34.400 34.103 44.208 1.00 10.93 ATOM 1170 r ASP 157 35.114 32.622 42.681 1.00 10.57 ATOM 1171 CA ASP 159 34.147 33.012 41.672 1.00 10.09 ATCHOM 1172 CB ASP 159 34.828 33.112 40.327 1.00 11.17 ATOM 1173 CG ASP 159 33.873 33.473 29.256 1.00 13.89 ATOM 1174 OD1 ASP 159 33.863 32.822 28.172 1.00 13.65 ATOM 1175 OD2 ASP 159 33.093 34.407 39.547 1.00 15.65 ATOM4 1176 C ASP 159 32.997 31.985 41.575 1.00 9.91 ATOM 1177 0 ASP 159 33.227 30.761 41.474 1.00 11.09 ATOM 1178 N VAL 160 31.766 32.485 41.637 1.00 7.83 ATCOM 1179 CA VAL 160 30.582 31.642 41.535 1.00 5.49 ATOM 1180 CB VAL 160 29.637 21.774 42.755 1.00 3.19 i ATCHOM 1181 CG1 VAL 160 28.512 30.738 42.742 1.00 3.00 1 ATOM 1182 CG2 VAL 160 30.362 31.602 44.091 1.00 2.00 i ATOM 1183 C VAL 160 29.842 32.132 40.286 1.00 6.19 s ATOM 1184 0 VAL 160 29.364 33.280 40.238 1.00 8.22 ATOM 1185 N SER 161 29.835 31.272 23.300 1.00 7.72 ATOM 1186 CA SEP 161 29.104 31.475 38.046 1.00 8.29 ATOM 1187 CB SER 161 30.094 31.628 26.a91 1.00 10.26 ATOM 1188 OG SER 161 30.637 32.951 26.934 1.00 13.94 ATOM 1189 C SER 161 28.161 30.275 -7.938 1.00 7.24 ATOM 1190 0 SER 161 28.601 29.117 28.024. 1.00 7.94 ATOM 1191 N ALA 162 26.885 30.605 27.791 1.00 9.16 ATOM 1192 CA ALA 162 25.793 29.612 27.784 1.30 12.39 ATHM 1193 CB ALA 162 24.689 30.055 28.736 1.00 1.5.24 ATOM 1194 C ALA 162 25.199 29.394 36.379 1.00 14.12 i ATOM 1195 0 ALA 162 25.593 30.044 35.406 1.00 13.91 S ATOM 1196 N GLY 163 24.220 28.499 36.369 1.00 15.85 7 ATOM 1197 CA GLY 163 23.598 27.913 35.150 1.00 16.65 ATOM 1198 C CLY 163 22.561 28.761 34.370 1.00 18.26 i ATOM 1199 0 CLY 163 21.996 29.729 34.897 1.00 18.80 S ATOM 1200 N ASN 164 22.416 28.231 33.146 1.00 90.00 7 ATOM 1201 CA ASN 164 21.568 28.664 21.994 1.00 90.00 i ATOM 1202 CB ASN 164 20.505 27.625 31.685 1.00 90.00 ATOM 1203 CC ASN 164 19.337 27.730 32.702 1.00 90.00 ATOM 1204 D001 ASN 164 19.322 27.033 33.726 1.00 90.00 ATOM 1205 ND2 ASN 164 18.334 28.580 32.511 1.00 90.00 S* ATOM 1206 C ASN 164 20.728 29.929 22.186 1.00 90.00 s ATOM 1207 ASN 164 19.665 29.874 22.817 1.00 90.00 ATOM 1208 N CLY 165 21.227 31.004 21.601 1.00 90.00 ATOM 1209 CA CLY 165 20.544 32.321 21.514 1.00 90.00 ATOM 1210 C CLY 165 20.214 33.048 22.859 1.00 90.00 ATOM 1.211 0 GLY 165 19.470 33.987 22.927 1.00 90.00 ATOM 1212 N ALA 166 20.941 32.706 33.967 1.00 90.00 ATOM 1213 CA ALA 166 20.602 33.406 35.242 1.00 90.00 ATCHOM 1214 CB ALA 166 19.550 32.609 35.015 1.00 90.00 ATOM 1215 C ALA 166 21.795 33.647 36.188 1.00 90.00 ATOM 1216 C ALA 166 21.646 33.653 37.421 1.00 90.00 ATOM 1217 N GLY 167' 22.964 33.851 35.614 1.00 11.62 ATOM 1218 CA GLY 167 24.167 34.185 36.400 1.00 13.44 ATOM 1219 C GLY 147 24.11C 35.688 354.704 1.00 15.68 ATOM 1220 *0 GLY 16' 23.701 36.494 25.863 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 37.545 38.252 1.00 18.83 ATOM 1223 CD SER 168 23.543 37.788 29.465 1.00 21.81 ATOM 1224 0C SER 148 22.556 38.750 39.118 00 23.47 ATOM 1225 C SER 168 25.820 38.200 28.537 1.00 18.61 ATOM 1226 SER 168 25.961 39.425 38.506 1.00 18.81 ATOM 1227 4 VAL 169 26.806 37.379 28.789 :.0C 18.64 ATOM 1228 CA VAL 169 28.218 37.762 39.149 1.00 17.78 z ATOM 1229 CB VAL 169 28.719 39.141 38.657 1.00 19.01 ATOM 1230 CC1 VAL 169 30.262 39.261 38.769 .00G 16.57 ATOM 1231 CG2 VAL 169 28.407 39.441 37.197 1.00 18.24 ATOM 1232 C VAL 169 28.387 37.796 40.666 1.O0 17.25 ATOM 1233 0 VAL 169 28.222 38.841 41.313 1.00 15.44 ATCHOM 1234 N GLN 170 28.725 36.631 41.201 1.00 15.91 ATOM 1235 CA CLN 170 28.90! 26.474 42.647 1.C 17.12 ATOM 1236 CS GLN 10 2-4 8 25.459 43.231 1.00 19.39 ATOM 1237 CC CLN 170 2;.21 35.468 44.766 1.00 24.35 ATOM 1238 CD GLN 170 28.202 34.091 4,.365 1.00 26.34 ATOM 1239 OEI GLN 170 27.369 23.192 4..247 1.0OC 27.24 ATOM 1240 NE2 GLN 170 29.335 33.868 46.004 1.00 28.12 -47bref21c.pdb ATOM 1241 C GLN ATOM 1242 0 GLN ATOM 1243 N ARC ATOM 1244 CA ARC ATOM 1245 CB ARC ATOM 1246 CG ARC ATOM 1247 CD ARC ATOM 1248 NE ARC ATOM 1249 CZ ARG ATOM 1250 NH1 ARG ATOM 1251 NH2 ARG ATOM 1252 C ARG ATOM 1253 0 ARCG ATOM 1254 N VAL ATOM 1255 CA VAL ATOM 1256 CB VAL ATOM 1257 CG1 VAL ATOM 1258 CG2 VAL ATOM 1259 C VAL ATOM 1260 0 VAL ATOM 1261 N CLU ATOM 1262 CA GLU ATOM 1263 CB GLU ATOM 1264 CG GLU ATOM 1265 CD GLU ATOM 1266 OE1 GLU ATOM 1267 OE2 GLU ATOM 1268 C GLU ATOM 1269 0 GLU ATOM 1270 N ILE ATOM 1271 CA ILE ATOM 1272 CB ILE ATOM 1273 CG2 ILE ATOM 1274 CGC1 ILE ATOM 1275 CD1 ILE ATOM 1276 C ILE ATOM 1277 0 ILE ATOM 1278 N LEO ATOM 1279 CA LEU ATOM 1280 CB LEU ATOM 1281 CC LEU ATOM 1282 CDl LEU ATOM 1283 CD2 LEU ATOM 1284 C LEU ATOM 1285 0 LEU ATOM 1286 N CLU ATOM 128-, CA GLU ATOM 1288 CS GLU ATOM 1289 CG GLU ATOM 1290 CD GLU ATOM 1291 OE1 GLU ATOM 1292 OE2 GLO ATOM 1293 C GLD ATOM 1294 0 GLU ATOM 1295 N GLY ATOM 1296 CA GLY ATOM 1297 C GLY ATOM 1298 *0 CLY ATOM 1299 N ARG ATOM 1300 CA ARC ATOM 1231 CB ARG ATOM 1202 CG ARG ATOM 122 CD ARG ATOM 1204 NE ARG A-CM 12T! CZ ARG ATOM 1306 NH1 ARG ATOM 1307 MH2 ARG ATOM 1205 C ARG ATOM 1309 0 ARG ATOM 1I2: THF.

ATOM 13:1 CA THR ATOM 1312 CB THR ATOM i.2 1 OC1 THR ATOM 114 CG2 THR ATOM 1215 C THR ATOM 1316 0 THR ATOM 1317 N GLU ATOM 1313 CA GLU 170 170 171 171 171 171 171 171 171 171 171 171 172 172 172 172 172 172 172 173 173 173 173 173 173 173 172 173 173 174 174 174 174 174 174 174 174 175 175 175 175 175 175 175 17) 176 176 176 176 176 176 176 176 176 177 177 177 177 178 178 178 178 178 178 '.79 178 178 178 17B 179 179 179 179 179 179 179 180 180 30.344 36.030 43.047 1.00 14.76 30.735 34.892 42.819 1.00 10.49 21.101 36.932 43.674 1.00 13.88 32.47 36.643 44.094 1.00 13.53 33.441 37.718 43.573 1.00 13.16 23.545 37.814 42.049 1.00 12.56 34.460 26.758 41.425 1.00 13.31 24.628 26.922 29.969 1.00 10.48 25.274 37.932 29.376 1.00 8.84 25.841 28.899 43.105 1.00 4.3? 25.304 38.000 28.045 1.00 6.87 22.581 26.543 45.630 1.00 15.23 21.706 27.062 46.350 1.00 17.57 33.651 35.916 46.131 1.00 11.99 33.816 35.727 47.565 1.00 9.19 33.473 34.260 48.000 1.00 10.74 33.300 24.155 49.521 1.00 5.41 32.236 33.745 47.262 1.00 11.43 25.216 25.966 48.031 1.00 9.92 36.134 35.398 47.507 1.00 10.28 35.365 36.778 49.062 1.00 14.35 36.671 27.041 49.657 1.00 14.21 36.760 38.463 50.218 1.00 17.07 36.591 29.569 49.173 1.00 21.96 37.267 40.903 49.573 1.00 25.14 27.709 41.647 48.649 1.00 23.21 37.359 41.206 !0.803 1.00 26.88 26.910 36.016 50.779 1.00 13.64 36.017 25.720 51.592 1.00 13.24 28.087 35.403 50.719 1.00 14.30 38.557 34.406 51.669 1.00 14.95 38.915 33.088 50.966 1.00 12.11 40.014 32.388 51.689 1.00 13.06 37.679 32.182 50.893 1.00 13.75 36.625 32.629 49.917 1.00 12.34 39.802 35.051 52.250 1.00' 15.60 40.563 35.693 51.532 1.00 17.19 39.982 34.956 53.558 1.00 16.67 41.138 35.582 54.166 1.00 16.56 40.838 35.972 55.609 1.00 15.47 40.467 37.466 55.733 1.00 16.91 40.100 38.112 54.394 1.00 14;03 39.345 37.623 56.733 1.00 16.66 42.394 24.753 54.031 1.00 16.41 42.322 33.535 53.838 :.00 17.23 43.542 35.431 54.084 1.00 17.18 44.842 34.765 53.946 1.00 16.66 46.000 35.733 54.145 1.00 21.33 45.963 36.472 55.432 1.00 20.62 46.145 37.925 55.180 1.00 22.84 47.330 38.343 55.218 1.00 23.62 45.117 38.626 54.911 1.00 23.22 45.068 33.602 54.852 1.00 12.93 44.875 33.686 56.062 1.00 16.37 45.574 32.545 54.259 i.00 9.95 45.839 31.341 55.001 1.00 8.11 14.73E 20.340 54.827 1.00 7.43 44.990 29.169 54.962 1.00 9.00 43.534 30.787 54.493 1.00 7.50 42.398 29.882 54.316 1.00 8.26 41.11( 30.660 54.477 1.00 10.81 41.154 31.621 55.616 1.00 14.76 40.911 30.920 56.950 i.00 20.12 41.904 21.285 57.960 1.00 24.00 42.4CC 22.509 58.135 1.00 26.21 42.004 33.543 57.381 1.00 27.32 43.35C 32.681 53.043 1.00 26.51 42.27! 29.216 52.954 !.OC 7.67 42.486 29.881 !1.938 1.00 8.54 42.20! 27.906 !2.934 1.00 7.97 42.14! 27.157 51.689 1.00 9.51 43.37 26.310 51.542 1.00 9.72 43.655 25.7C3 !2.318 1.00 12.75 44.55 27.162 51.073 1.00 6.02 40.872 26.265 51.641 1.00 14.19 40.892 25.102 51.155 1.00 15.46 29.7C 26.831 52.151 1.00 13.36 38.469 26.188 52.162 1.00 12.94 Thu Apr 25 12:27:47 1996 -48braf21c.pdb Thu Apr 25 12:27:47 1996 18

S.

S

ATOM

ATOHM

ATOM

ATCHOM

ATOM

S"ATCHOM

ATOM

ATO

1319 CB GLU 1 1320 CG GLO 1 1321 CD CLU 1 1322 OE1 GLO 1 1323 OE2 GLU 1 1324 C GLU 1 1325 0 GLU 1 1326 N CYS 1 1321 CA CYS 1 1328 C3 CYS 1 1329 SG CYS 1 1330 C CYS 1331 0 CYS 1332 N VAL 1333 CA VAL 1334 CB VAL 1335 CG1 VAL 1336 -CG2 VAL 1331 C VAL 1338 0 VAL 1339 N LEO 1340 CA LEO 1341 CB LEU 1342 CG LEO 1343 CD1 LEU 1344 CD2 LEO 1345 C LEO 1346 0 LEU 1341 0 SER 1348 CA SER 1349 CS SER 1350 OG SER 1351 C SER 1352 0 SER 1353 N ASN 1354 CA ASN 1355 CB ASN 1356 CG ASN 1357 OD1 ASN 1350 ND2 ASN 1359 C ASN 1360 0 ASN 1361 N LEU 1362 CA LEU 1363 CB LEO 1364 CG LEO 1365 CD1 LEU 1366 CD2 LEU 1361 C LEO 1368 0 LEO 1369 N ARG 1370 CA ARG 1371 CB ARG 1372 CG ARG 1313 CD ARG 1314 NE ARG 1375 CZ ARG 1316 NH1 ARG 1377 NH2 ARG 1318 C ARG 1319 0 ARG 1380 N GLY 1381 CA GLY 1382 C GLY 1383 GLY 1384 N ARG 1385 CA ARG 1386 CB ARG 139187 CG ARG 1388 CD AP.G 1369 NE AP.G 1390 CZ ARG 1391 NH1 AP.G 1392 NH2 ARG 1393 C ARG H 1394 0 ARG 4 1395 N THR 1H 396 CA THR 80 80 80 80 80 80 80 er 81" 81 ,81 181 181 182 182 182 182 182 182 182 183 183 183 183 183 183 163 183 184 184 184 184 184 184 185 185 185 185 185 185 185 185 186 186 186 196 laE 136 186 186 187 187 187 181 187 187 187 137 187 181 131 138 188 188 139 189 139 189 189 139 189 189 189 189 199 10 190 38.329 25.242 !3.340 37.418 24.052 !3.048 37.112 23.255 14.299 36.526 23.871 15.216 37.413 22.045 54.387 31.442 21.288 12.301 37.742 28.385 52.782 36.209 26.986 11.934 35.149 27.967 12.034 35.382 28.990 13.936 33.911 29.643 13.288 33.166 21.287 51.905 33.606 26.383 11.086 32.790 21.639 12.743 31.478 26.985 12.613 31.093 26.072 13.820 32.003 26.307 !5.003 29.669 26.255 14.193 30.353 27.910 12.171 29.930 28.828 52.872 29.954 27.715 !0.930 28.921 28.515 13.338 29.052 28.500 48.811 30.193 29.380 43.350 20.636 28.956 46.970 29.734 30.852 43.398 27.564 28.027 1:.778 27.139 26.a87 1:.514 26.891 28.909 21.486 25.583 28.642 !1.998 25.558 29.046 13.461 26.601 28.369 14.144 24.671 29.537 11.208 25.115 30.545 13.679 23.422 29.140 !1.048 22.479 29.998 13.338 22.463 31.389 51.008 22.274 31.330 52.546 Z2.899 32.131 ±3.270 21.392 30.414 !3.050 22.641 30.149 49.194 22.967 31.228 43.263 22.329 29.062 43.093 22.384 28.972 44.635 23.632 28.110 46.201 25.006 28.318 44.924 25.951 21.112 46.540 25.689 29.663 .6.631 21.06? 29.230 44.261 20.449 21.566 47.114 20.611 28.382 45.01! 19.311 21.749 44.571 18.045 28.415 43.32' 19.153 29.870 43.26: 18.525 30.512 42.05, 19.21E 30.197 43.90: 18.997 29.109 40.06, 18.110 28.181 43.43 19.594 29.001 25.87 19.528 26.264 44.29 20.606 25.788 43.81 18.412 25.551 44.48 18.369 24.124 44.29 18.304 23.695 42.84 11.160 24.421 4i.01 18.822 22.492 42.5f 18.891 21.885 41.23 17.491 21.501 4:.7 17.450 20.203 2.3- 1-.'80 20.447 2'.31 18.510 19.373 27.7! 18.018 19.215 27.21 16.76E 17.337 .;41 18.88E 17.342 '.61 19.610 22.11773 .2 19.406 22.605 ;i.3 20.432 23.119 ;4.6 21.195 24.611 2.3 1.00 14.42 1.00 18.37 1.00 19.86 i 1.00 21.21 1.00 18.58 i 1.00 14.56 1.00 14.76 1.00 13.82 00 12.64 '.00 12.66 1.00 13.38 16 1.00 13.84 1.00 15.56 8 1.00 13.12 7 1.00 11.97 6 1.00 9.54 6 1.00 10.81 6 1.00 8.15 6 1.00 12.84 6 1.00 13.90 1 1.00 11.79 7 1.00 12.16 i 1.00 13.26 1.00 11.81 6 1.00 9.24 1.00 13.01 1.00 14.24 1.00 15.09 1.00 14.69 1.00 16.60 6 1.00 11.40 6 1.00 18.19 a 1.00 17.61 6 1.00 18.84 3 1.00 18.50 1 1.00 21.04 6 1.00 21.82 6 1.00 33.52 6 1.00 36.61 3 1.00 36.25 1 1.00 19.48 6 1.00 18.46 6 1.00 17153 1.00 15.82 1 1.00 14.99 6 1.00 15.24 6 1.00 13.51 t S 1.00 14.02 1.00 16.15 6 i 1.00 16.68 1 1.00 15.66 1 1 1.00 14.27 4 1 1.00 14.63 6 13 .00 19.73 4 4 1.00 23.14 5 1.00 26.90 1 0 1.00 2).017 0 1.00 29.72 1 4 1.00 21.36 7 8 1.00 16.01 2 1.00 14.20 2 00 11.94 1 1.00 1-.35 2 1.00 19.74 6 6 OC 20.69 i3 1.00 23.12 1 19 1.OC 20.15 i 1.30 22.54 1 1.00 26.04 6 8C 1.OC 26.32 S6 00 21.40 99 1.00 29.60 05 1.CC 23.45 86 0GC 29.39 13 OC 20.12 17 *.OC 21.60 93 1.00 '3.12 12 1.00 1-.35 -49b-f2lc.pdb Thu Apr 25 12:27:47 1996 a a ATOM 13 ATOM 13 ATOM 1: ATOM 14 ATOM 14 ATOM 1 ATOM 1' ATOM 1 ATOM 1I ATOM 1I ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM 1 ATOM I ATOM 1

ATOM

91 198 199 100 101 102 403 404 405 406 401 408 409 410 411 412 413.

414 ,415 .416 1411 1418 1419 L420 1421 1422 1423 1424 1425 1426 1421 1428 1429 1430 1431 1432 1433 1434 1435 1431 143 143 143 144 144 144 144 144 144 144 144 144 144 145 14: 14: 14 14: 14 14 14 14 1-4 14 14 14 14 14 14 1 1 1 1 CB THR 19 OGi THP. 19 CG2 THR 19 C THR 19 o THR 19 N ARC 19 C. ARC 19 CB ARC 1I CG ARC 1 CD ARC I! HE ARC 1 CZ ARC 1 HH1 ARG 1 NH2 ARC 1 C ARC 1 0 ARC 1 N TYR 1 CA TYR 1 CB TYRP. 1 CG TYR 1 CD1 TYR 1 CE1 TYR 1 CD2 TYP I CE2 TYR I CZ TYR OH TYP.R C TYR 0 TYP.R N THR CA THR CB TRR OCI TRR SCG2 THR C TR.

I 0 THR 2 N PRE I CA PHE I CB PHE 5 CG PHE 6 CDI PHE 7 CD2 PHE 8 CEI PHE 9 CE2 PHE 0 CZ PHE 1 C PHE 2 0 PHE 3 N ALA 4 CA ALA 5 CB ALA 6 C ALA .1 0 ALA 8 H VAL 19 CA VAL 50 CB VAL 51 CG1 VAL 52 CG2 VAL 53 C VAL 54 '0 VAL 55 N ARG 56 CA ARC 51 CB ARG 58 CG ARG 59 CD ARCG 60 NE ARC 61 CZ ARC 62 NH1 ARC 63 NH2 ARG 464 C ARG 165 ARG 166 N ALA 461 CA ALA 468 CB ALA 469 C AL.A 0 0 10 10 10 9or 91 91 91" 91 91 91 91 91 91 91 91 92 92 92 92 92 .92 192 192 192 192 192 192 193 193 193 193 193 193 193 194 194 194 194 194 194 194 194 194 194 194 195 195 195 195 195 196 196 196 196 196 196 196 197 191 19-' 191 19-' 19' 19- 196 19' 19- 1i" 198 19 198 199 199 199 21.494 20.310 21.869 22.516 23.024 23.262 24.621 24.183 26.243 26.802 26.824 2'.611 28.650 21.562 25.411 25.114 26.495 21.380 21.283 26.063 26.105 24.949 24.831 23.610 23.145 22.618 28.159 29.134 29.511 30.815 31.036 30.030 32.399 31.681 31.311 32.68 33.48 33.42 S32.03 31.53 31.22 30.21 29.95 29.48 34.92 35.36 35.64 31.05 31. 1 31.11 39.0: 39.8 40.5 40.2 40.1 41.0 41.4 41.5 42.6 42.2 41.3 41.0 40.: 40.: 40.1 39.

43.

42.

44.

45.

46.

41.

46 46 25.944 40.4 26.366 41.2 26.984 29.3 24.011 2 .6 23.222 40.4 24.460 238.

24.018 38.2 23.686 25.

23.411 26.

22.032 2.2 21.206 25.: 21.329 24.

22.261 24.

20.481 33.

25.213 38.

26.344 28.

24.950 39.

25.911 39.

26.021 41.

26.159 41.

28.138 42.

28.861 42.

26.111 42.

26.840 42.

28.211 42.

28.912 42 25.551 23 24.402 29 26.491 23 5 26.230 28 S26.551 21 0 25.849 26 9 26.130 36 8 21.182 39 0 28.369 39 5 26.682 40 1 21.511 4C 1 21.133 42 0 26.118 42 1 25.492 4; 2 21.135 4: 3 25.110 4: 1 21.412 4: .2 26.129 4 2 21.565 4 1 26.594 46 29.633 4 51 28.185 4 73 29.298 2 11 29.159 4 31 30.692 4 39 Z9.539 4 39 30.398 4 22 29.609 4 31 30.216 11 28.113 00 31.085 18 30.661 31 32.121 ,81 32.860 219 33.902 184 35.010 062 36.000 345 31.124 269 38.323 846 38.550 163 39.339 314 33.489 685 33.926 710 33.490 415 33.996 420 22.901 241 !5.326 614 35.112 .542 35.901 .250 31.111 .226 38.304 .184 39.66' 60 26 90 12 128 63 53 146 218 502 214 236 198 210 621 233 411 901 411 890 101 435 039 .311 .554 .155 .508 .680 .954 .535 .028 .283 .529 .383 1.425 .113 1.96- 2.421 !.900 2.12: 3.51 3.15 3.94 3.16 0.52 9.93 0.84 0.49 3.04 1.46 1.92 1.71 12.68 13.86 15.2: 13.8 41.9 40.9 42.6 42.1 41.0 41.5 40.5 41.C 40.5 33.: 41.

43.: 44.*: 43.

44.

45.

44.

43.

45.

19 1.00 15.30 1.00 18.33 1.00 10.48 1.00 11.91 1.00 1i7.12 I.00 18.62 1.00 18.64 1.00 23.05 1.00 28.15 1.00 29.31 1..00 31.41 1.00 30.19 '.00 30.54 1.00 30.20 1.00 15.56 i 1.00 14.09 1.00 12.55 1.00 11.03 1.00 10.18 1.00 13.18 1.00 14.11 1.00 14.60 1.00 14.10 1.00 15.93 1.00 13.34 1.00 14.24 1.00 12.33 1.00 12.al31 '.00 10.45 1.00 1.01 1.00 7.66 1.00 5.14 S 1.00 1.11 S1.00 1.05 S1.00 1.20 3 1.00r 8.39 1 1 1.00 5.90 i 1.00 6.91 0 1.00 8.68 3 1.00 5.81 9 1.00 8.15 o 1.00 a.14 6 1.00 5.23 3 1.00 '.24 4 1.00 5.55 4 1.00 6.55 9 1.00 5.34 4 1.00 4.51 17 1..00 5.31 1 1.00 3.32 1 1.00 2.19 43 1.00 2.16 19 1.00 2.18 59 1.00 2.00 L4 1.00 2.00 69 1.00 .04 95 1.00 2.01 31 1.00 5.91 29 1.00 2.00 29 1.00 2.00 69 1.00 2.30 .14 1.00 2.30 04 1.00 2.00 13 1.00 2.41 11 1.00 2.30 151 1.00 2.00 193 1.00 4.02 362 1.00 2.09 280 1.00 2.19 399 1.3C 2.

1 3 550 1.OC 2.41 012 1.00 2.30 442 1.CC :.39 340 1.00 2.1S 612 1.00 2.12 694 1.00 2.38 512 i.00 2.20 .210 1..00 S.61

I

1 3 .1

ATOM

1410 1411 1412 1413 1414

.LA

iRG

LRG

6%G

LRG

a. a.

bref2:

ATOM

ATOf

ATOI

ATO

ATC

lc.pdb 40.

1475 CD ARC 199 1476 NE ARC *99 1477 CZ ARC :99 1478 NH1 ARC ?99 1479 NH2 ARC 199 1480 C ARC :99 1481 0 ARC *99 1482 N MET 230 1483 CA MET 200 1484 CB MET 200 1485 CG MET 200 1486 SD MET 200 1487 CE MET 200 1488 C MET 200 1489 0 MET 200 1490 N ALA 201 1491 CA ALA 201 1492 CB ALA 201 1493 C ALA 201 1494 0 ALA 201 1495 N GLO 202 1496 CA GLO 202 1497 CB GLU 202 1498 CG GLU 202 1499 CD GLU 202 1500 OE1 GLU 202 1501 OE2 GLU 202 1502 C GLU 202 1503 0 GLU 202 1504 N PRO 203 1505 CD PRO 23 1506 CA PRO 203 1507 CB PRO 203 1508 CG PRO 203 1509 C PRO 203 1510 0 PRO 203 1511 N SEP. 204 1512 CA SEP. 204 1513 CB SEP. 204 1514 OG SEP. 204 1515 C SEP. 204 1516 0 SER 204 1517 N PHE 205 1518 CA PHE 235 1519 CB PRE 205 1520 CG PRE 205 1521 CD1 PHE 225 1522 CD2 PRE 23! 1523 CE1 PHE 235 1524 CE2 PHE 235 1525 CZ PHE 235 1526 C PHE 205 1527 0 PHE 205 1528 N GLY 206 1529 CA GLY 236 1530 C GLY 206 1531 0 GLY 206 S1532 'N GLY 207 S1533 CA CLY 237 1534 C SLY 23' 1 1535 0 GLY 237 1536 N PHE 2C8 1537 CA PHE 238 S1535 CB PRE 238 '539 CG PRE 238 S1540 CD1 PHE 258 4 1541 CD2 PHE 208 S1542 CE1 PHE 238 1543 CE2 PHE 208 1544 CZ PHE 238 S1545 C PHE 20P.

S1546 0 ?HE 20e M 11l N T.P 2c;9 S1548 CA TPP 239 M 1549 CB TP 20S M 1550 CG TPP 209 M 1551 CD2 TP.P 209 1552 CE2 TPP 209 45.938 46.306 46.187 45.738 46.417 48.030 47.555 49.243 50.015 51.484 52.311 t3.261 52.284 49.340 49. 074 49.050 48.369 41.633 49.261 50.488 48.622 49.336 48.428 41.650 48.360 49.466 47.174 49.7185 49.394 50.696 51.150 51.322 51.339 51.846 52.740 53.531 53.073 54.420 P4.614 55.093 54.686 55.632 53.818 53.901 53.911 55.01: 54.85 56.381 55.92 57.45 57.21 52.74 51.75 52.91 51.89 52.00 *52.95 51.02 51.12 49.82 48.85 49.71 48.6: 49.0: 50.1: 49.9 51.4 51.0 52.5 52.2 47.8 48.4 46.6 45.7 44.3 43.5 41.

42.: 40.

1737 45.915 1.00 9.17 6 42.120 45.579 42.662 44.363 41.950 43.329 43.954 44.181 37.321 47.023 36.916 48.058 37.864 46.984 38.096 48.197 38.423 47.891 37.271 47.346 36.286 48.538 34.975 48.812 39.289 48.814 40.314 48.228 39.126 50.167 40.140 50.962 39.414 52.117 41.285 51.464 41.204 51.453 42.360 51.901 43.521 52.421 44.756 52.276 44.796 50.914 45.575 49.7157 46.164 49.968 45.613 48.634 43.317 53.903 42.321 54.561 44.173 54.411 44.143 55.820 45.290 53.714 46.367 54.782 45.538 55.984 44.892 53.356 45.743 52.985 43.623 53.540 43.146 53.222 41.764 53.868 S41.356 55.224 S43.060 51.696 S43.660 51.152 I 42.309 51.031 1 42.014 49.624 S40.513 49.39C 3 39.862 :0.05; 4 38.885 !1.02! B 40.136 49.661 1 38.198 51.591 2 39.449 50.23' 5 38.480 51.20: 3 42.728 48.901 6 43.147 49.50 3 42.864 47.59 2 43.459 46.75 1 42.855 45.36 6 42.124 45.08 0 43.080 44.52 !2 42.534 43.17 25 42.355 42.43 7 43.048 42.65 84 41.332 41.6C 21 41.069 40.8( 34 41.071 29.3; 58 42.013 29.0; 56 43.311 39.01 41 41.530 9.7 22 44.253 2.7 06 42.393 28.5 92 43.756 23.5 96 39.767 41.1 62 38.823 41.7 02 39.780 40.8 66 38.625 41.0 102 38.979 40.8 05 39.319 42.C IS( 38.550 42.1 341 39.314 43.! I1.00 13.78 1.00 15.94 s 1.00 18.32 1.00 18.45 1.00 5.53 1.00 8.08 1.00 5.53 1.00 4.85 1.00 3.73 1.00 4.67 1.00 9.73 1.00 2.41 1.00 1.02 s 1.00 6.42 1.00 7.96 1.00 10.65 6 1.00 4.85 6 1.00 12.36 1.00 13.02 3 1.00 15.12 1.00 19.04 1.00 23.13 6 1.00 28.94 1.00 31.22 1.00 32.80 1.00 30.41 1.00 19.11 1.00 20.41 1.00 16.25 1.00 15.32 1.00 14.26 1.00 13.02 1.00 16.38 1.00 12.03 1.00' 15.28 1.00 8.98 1.00 11.79 1.00 11. 87 1.00 12.48 1.00 11.88 1.00 11.24 i.00 10.89 S1.00 8.76 1 1.00 8.10 1.00 12.81 9 1.00 11.19 1 1.00 11.00 1.00 1.25 1 1.00 11.11 2 .00oo 8.98 D 1.00 8.87 8 1.00 9.29 2 1.00 8.57 1 1.00 8.14 1 1.00 7.24 1 1.00 8.58 0 1.00 1.18 6 1.00 7.-9 10 1.00 4.80 i6 5.05 18 1.00 3.71 5 00 3.73 12 1.00 6.46 LI 00 6.52 4 1.00 6.75 93 1.00 9.68 90 ;.00 i.99 79 1.00 8.12 80 1.00 6.95 49 1.00 2.2: 04 1.00 2.77 78 1.00 2.3C 173 .00 2.1: 11 1.00 4.79 i11 1.00 4.76 .04 1.00 2.6- 159 1.00 2.97 6 6 6 6 i 3 6

I

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

ATOM

ATOt ATOt ATOf

ATOC

ATC

ATCI

ATe

ATC

ATZ

ATO

AT

ATC

AT

1553 CE3 TRP 20 1554 CD1 TPP 20 1555 NE1 TP.P 20 1556 CZ2 TPP 20 1557 CZ3 TRF 20 :558 CH2 TPP 20 1559 C TRP 20 1560 TRP 20 1561 N SEP. 21 1562 CA SEP. 21 1563 CB SEP 2 1564 OC SEP. 2 1565 C SER 2 1566 0 SER 2 1561 N ALA 2 1568 CA ALA 2 1569 -CB ALA 2 1570 C ALA 2 1571 0 ALA 2 1572 N TP.P 2 1573 CA TP.P 2 1574 CB TP.P 2 i515 CG TP.P 2 1576 CD2 TRP 2 15177 CE2 TP.P 2 1578 CE3 TP.P 1579 CDI TP.P :580 NE1 TPP 2 1581 CZ2 TPP 1582 CZ3 TRP 1583 CH2 TRP 1584 C TRP 1585 0 TRP 1586 N SE,.

1587 CA SEP.

1588 CB SER 1589 OG SEP.

1590 C SEP.

1591 0 SER 1592 N CLU 1593 CA GL'I 1594 CB GLU 1595 CC GLU 1596 CD GLU 1597 OEl GLU 1598 OE2 GCLU 1599 C CLU 1600 '3 CLU 1601 N PP.0 1602 CD PP.RO 1603 CA PP.0 1604 CB PRO 1605 CC PP.0 1606 C PRO 1607 0 PP.0 1608 N VA.

S1609 CA VAL I 1610 'CB VAL 1611 CC1 VAL S1612 CG2 VAL 1613 C :AL 1 14 ';L m "615 N SEF.

S 1616 CA 3EP.

'617 C 3 E.- 1618 DC !EPR 1619 C ;Z t: ii2O Z 1621 N EC .4 1623 CB LE 1624 CC LEU 1625 CDI LE' M 1626 CD2 S 1621 C EEC M 628 p EC t 1629 N LCC M 1630 CA LE 9 9 9 9 9 9 9 P9 .3 10

LO

10 10 10 i0 11 11 12 12 12 12 12 12 212 212 212 212 212 212 212 213 212 213 213 213 213 214 214 214 214 214 214 214 214 214 215 215 215 215 215 215 215 216 216 216 216 216 216 214 211 211 2.7 21' 211 2.-i 218 21:8 218 218 218 218 28 9 219 219 43.445 42.908 42.211 41.825 42.933 42.131 46.222 46.556 46.235 46.650 46.903 45.683 45.571 44.564 45.832 44.895 45.639 43.893 44.160 42.736 41.791 40.4471 39.723 39.061 38.529 28.8671 29.566 28.850 31.811 28.162 21.640 42.340 43.262 41.771 42.222 42.04 40.66 91.30 0.26 41.64 40.69 41.30 42.10 41.24 41.62 40.21 39.55 29.79 38.30 37.95 31.0 26.1 36.4 36.3 26.6 35.4 24.6 24.7 25.5 25.2 32.2 23.0 22.3 10.9 30.5 29.

3C.

29.

2.

28.

21.

28.

26.

28.

26.

25.

24.

31.234 43.

40.586 42.

40.554 43.

36.309 45.

36.729 44.

317.513 45.

37.604 40.

31.)69 33.

36.335 43.

3-.269 33.

34.002 40.

32.363 40.

34.968 3.

35.689 3 33.924 7.

33.423 36 32.571 25 32.558 1 32.175 z8 32.263 37 31.433 27 31.434 36 32.765 14 33.399 23 34.597 31 33.063 3 33.576 2! 34.680 25 35.470 1 3.92i 35.111 30.012 29.696 29.145 3 21.747 1 1 27.183 4 7 21.131 4 3 26.959 3 5 27.471 4 25.718 4 24.911 2 1 23.662 2 1 22.191 2 9 24.291 2 7 25.3371 8 23.631 O 24.814 3 24.625 1 25.031 9 25.363 58 24i965 55 235.896 30 25.447 I8 23.609 64 22.654 40 22.553 69 22.346 40 21.829 69 20.568 26 22.929 61 22.334 01 24.039 5 21.913 52 22.241 49 21.1!- 610 23.1 127 21.282 424 2C.38*1 06' 21.791 222 2C.)E.

605 21.295 991 20.615 2c- 2CT 11.:.12 64. 21.135 727 21.206 306 22.35 958 2C.114 486 20.164 446 240 396 14B 616 461 023 920 412 533 3317 660 515 .398 .135 .751 .768 .5671 .106 .014 .134 .993 .942 .030 .541 347 .861 .219 .259 1.1671 9.671 7.111 7.043 8.598 3.642 0.04! 0.391 7.73 1.29 7.44 6.66 6.19 4.87 3.64 :3.00 :3.30 17.68 13.86 17.2! -5.86 23.0! 21.2 25.9 23.2 21.5 39.1 -3.4 43.9 41.0 1.9 39.2 33.

33.4 2.0 43.

.3.

4).

4 3.

4).

,.00 2.00 00 2.25 1.00 2.00 i.00 4.70 30 4.-1 1.00 4.6 1.30 3.11 00 3.26 00 4.99 1.00 5.2i 1.03 4.60 1.00 3.40 1.00 9.36 1.00 13.86 00 10.41 1.00 10.20 1.00 10.37 1 1.00 11.25 ,.00 14.78 1.00 9.47 1.00 7.14 1.00 3.05 1.00 4.98 1.00 2.00 1.00 2.33 1.00 2.00CO L.00 2.00 1.30 2.00 1.00 4.55 1.00 2.47 1.00 2.13 1.00 8.93 1.00 8.63 1.00 11.16 1.00 11.60 1.00 12.78 S1.00 13.18 8 1.00 12*.671 3 1.00 14.82 1 1.00 12.59 o 1.00 12.29 8 1.00 16.21 3 1.00 23.12 0 00 27.82 1 1.00 29.07 1 1.00 27.91 0 10 11.51 4 1.00 11.96 8 1.00 11.02 8 1.00 12.53 9 1.00 11.49 90 1.00 9.49 31 1.00 12.12 31 1.00 9.78 25 .00 12.44 i2 30 1.47 34 *.00 7.05 24 1.00 8.24 16 :3 9.46 18 1.00 6.68 59 .00 9.31 45 1.0 11.20 21 00 8.41 66 .00 9.61 C2 0 13.

04 O0 13.22 601 30 10.91 641 10 9.60 224 00 10.92 1C2 11 1- 566 :.00 9.62 7e9 )30 i.92 626 053 ;o0 3.s 903 30 11.91 693 00 12.22 87 30 14.15 160 .00 13.92 j j i

I.

C

o -52brmf2lc.pdb Thu Apr 25 12:27:47 1996

ATOM

ATCM

ATOM

1631 CB LEU 1632 CG LEV 1633 C1 LEU 1634 C72 LEU 1635 C LEU 1636 O LEU 1637 N THP.

1638 CA THP.

1639 C THP.

1640 G001 TPP.

1641 CGC2 THP.

1642 C THR 1643 THP.

1644 N THP.

1645 CA THP.

1646 CS THP.

1647 001 THP.

1648 CG2 THF.

1649 C TEHR 1650 0 THP.

1651 N TYP.

1652 CA TYP 1653 CB TYP.

1654 CC TYP.

1655 COI3 TY? 1656 ':71 TYR 1657 CD2 TYf 1658 CE2 TYR.

1659 CZ TYP.

1660 CH TY? 1661 C TYP.

1662 O TYP.

1663 N SEP.

1664 CA SEP.

1665 CS SEF 1666 OG SEP 1661 C SE?.

1668 0 SE.

1669 CYS 1610 CA CYs 1671 C CYS 1672 C CY! 16713 C3 CY 1674 3G C0 1675 N HIS 1616 CA H:T 161177 3 II 1618 Ss K:: 1679 =32 HI: 1660 RHIS 1681 :71 :-s 1682 NE2 RIS 1683 C HIS 1684 H I 1695 PRE 1686 :A Pe 1687 CB PEE 1611 P E 1689 :31 PET 1690 C=2 P.E 1691 1:i PET 1692 CT2 PEE 1693 :Z PE 1694 PE 169± 1696 N LY 1697 1698 S 1699 S LY i700 N P: 1731 :D Pn: 1702 CA P.: :72 :t PT*: 1704 C P.: 1705 r: 1106 P1: 1707 N 1708 CA LE: 219 219 219 219 219 219 220 220 220 220 220 220 220 303 203 303 303 3033 303 303 304 304 304 304 304 304 304 304 304 304 304 304 305 305 305 305 305 305 306 306 306 306 306 306 307 301 30' 20, 2" 307 307 301 3071 309 308 308 308 3 39 308 308 308 308 308 "28 309 239 310 310 310 210 !1(1 21i 311 23.86; 15.3-2 40.209 23.819 18.429 23.736 22.857 19.303 317.941 25.208 1.412 23.096 24.080 20.226 42.248 1.

24.3718 19.295 42.986 23.501 21.329 42.692 23.057 21.472 44.068 22.289 22.1;4 44.250 1 22.030 23.232 42.967 23.076 23.704 45.099 22.111 20.325 44.368 21.196 20.3!3 43.582 67.975 42.354 64.372 1 67.750 41.634 65.591 66.400 42.008 66.344 1 65.988 43.329 65.963 66.595 42.023 67.861 1 67.737 40.103 65.280 1 68.525 39.342 65.838 66.882 39.690 64.343 1 66.756 38.28. 63.973 1 65.306 21.326 64.148 1 64.839 37.i27 65.585 64.311 29.123 66.072 E4.00 3S.24a E7.3e9 65.030 66.486 64.721 37. 22 61.809 64.208 38.2:: 68.261 63.886 32.35? 69.598 67.182 38.065 62.554 67.277 39.024 61.804 67.474 36.819 62.201 67.856 36.442 60.843 69.204 35.705 60.838 70.226 36.516 61.427 66.736 35.557 60.213 66.490 34.433 (.0.754 '66.093 36.051 19.218 64.968 35.364 18.619 64.970 35.329 51.131 65.609 35.702 56.302 63.738 36. 3 18.889 63.703 36.826 60.556 64.186 34.026 ±6.808 64.01± 22.6C4 !5.459 65.03e 32.3:? :5.083 64.853 21.13 15.746 64'.068 3C.i24 15.420 65.704 30.723 !5.734 65.467 29.443 6.976 64.478 29.056 !6.192 62.576 33.6 5.236 61.811 32.?93 16.188 62.167 33.-26 !3.980 60.81: '2.21 3.6471 50.491 223. 2 2.167 60.530 34.n' 51.891 S1.140 35.216 !0.747 ±9.935 35.ZZ2 52.738 61.152 36.4:2 !0.448 59.942 3f.-:2 12.445 60.541 31.224 !1.3071 60.689 3:.2:7 t3.849 1.489 20.424 !3.322 !9.146 'C.-32 14.691 59.517 29.23: 14.922 58.2* 23.3i ±-.098 57.806 29.755 !3.3.6 L1.'91 27.7x6 !4.222 58.486 2f.2. 14.1742 56.64E 27.42) !3.354 16.581 2± 440 57.'J5 25.-7 12.857 1.?95 26.'2 '3.909 L4.281 28.241 13.132 55. 22 28.:12 IS.±F.

54.145 !!.756 22 Co 13.95 30 16.51 00 18.05 30 15.67 00 12.96 00 12.64 00 12.!2 00 10.21 .30 10.53 .00 14.4) .30 13.55 .00 11.61 .00 13.03 .00 11.41 .00 9.49 .00 10.05 .00 12.85 .00 12.80 .30 9.93 .00 9.31 .00 10.11 .00 9.53 .30 7.06 .30 7.97 .30 4.80 .00 3.80 .3C 6.93 .00 4.43 .00 4.88 .00 10.24 0 8.33 .00 11.69 00 8.34 .00 9.43 1.00 13.12 1.00O 18.03 1.00 10.05 1.00 10.34 :.oo 9.05 :.00 5.32 1.30 6.70 00 6.69 :.00 6.36 .00 8.87 >.00 6.09 :.3C 7.!0 30 11.44 14.32 .00 16.07 16.54 .30 14.82 1.00 17.24 1.00 9.06 .00 11.93 00 3.50 30 6.63 30 7.92 30 5.48 .2 6.64 1.20 9.42 1.30 3.48 .30 6.33 >30 5.44

C.-C

5.25 1.OC 5.53 t G. 57 .00 3.19 >2C 9.04 u 9.55 32 30 10.2! "1.38 !.53 ~1 5 i i 7 r r 6 9 o r i j z

II.

r s r r 1 -53bref2lc.pdb Thu Apr 25 12:27:47 1996 23 ATOM 1709 C3 LEU 311 53.834 28.437 !7.060 1.00 4.'4 ATOM 1110 :C LEU 311 52.037 27.211 517.12 1.00 1. 4 ATOM 1711 Cn1 LEUt 311 51.524 21.802 117.619 1.00 1.24 ATOM 1712 =22 LEU 311 52.694 26.580 !5.181 1.00 :.t2 ATOM 1713 C LEU 311 54.346 30.580 '6.002 1.00 4.35 ATOM 1714 C LEU 311 53.586 31.41: 55.540 1.00 4.1 ATOM 1715 THP. 212 55.390 30.898 16.741 1.00 1 ATOM 1716 A THR 212 55.680 32.285 57.015 1.00 .i2 ATOM 1111 CB THP. 312 54.1772 32.732 18.256 00 ATOM 1718 Cz1 THR 212 54.998 34.144 19.416 1.00 12.16 ATOM 1119 CC2 THP 312 !5.115 31.95: 59.526 1.00 1.36 ATOM 1120 C THR 312 57.168 32.342 51.444 1.00 i.58 ATOM 1121 THR 312 57.868 31.352 57.215 1.00 1.15 ATOM 1722 N TRP 313 51.641 33.4711 17.979 1.00 5.?6 ATOM 1723 CA TRP 313 59.050 33.653 13.382 1..00 6.32 ATOM 1724 C TRP 313 59.294 35.032 58.992 1.00 2.13 ATOM 1725 Cc TRP 313 58.937 36.213 58.158 1.00 5.28 ATOM 1726 C32 TRP 313 59.685 36.779 57.066 1.00 6.34 ATOM 1127 C2 TRP 313 59.026 37.968 56.682 1.00 4.38 ATOM 1728 CL3 TRP 313 60.845 36.403 !6.392 00 3.66 ATOM 1129 CD1 TRP 313 57.883 31.044 58.359 1.00 4.69 ATOM 1730 Bl1 TRP 313 51.933 38.103 57.488 1.00 5.20 ATOM 17131 Z2 TRP 313 59.484 38.784 15.656 1.00 4.75 ATOM 1732 273 TRP 313 61.301 37.222 :5.350 1.00 1.62 ATOM 1733 H2 TRP 313 60.618 38.398 55.004 1.00 5.-2 ATOM 1734 TRP 313 59.605 32.519 53.389 1.30 3.28 ATOM 1735 TRP 313 58.931 32.186 k3.359 1.00 1.40 ATOM 1736 N VAL 314 60.847 32.216 19.139 '.CO .C *ATOM 11737 CA VAL 314 61.533 31.286 60.013 1.00 ATOM 1738 CB VAL 314 62.145 20.110 19.249 :.00 .IZ *ATOM 1739 ccI VAL 314 62.868 29.204 60.190 1.00 2.24 ATOM 1740 222 VAL 314 61.099 29.333 18.536 1.00 3.95 ATOM 1141 C VAL 314 62.637 32.192 60.499 :.00 3.62 ATOM 1142 0 VAL 314 63.512 32.562 53.730 1.00 11.C3 ATOM 1743 N CYS 315 62.516 32.672 61.724 1.00 9.61 ATOM 1144 CA CYS 315 63.524 33.56 62.250 1.00' 13.57 SATOM 1745 2 CYS 315 64.417 32.948 63.293 1.00 13..0 ATOM 1746 0 CYS 315 64.191 31.825 63.748 1.00 11.89 ATOM 1747 n CYS 315 62.905 34.861 62.757 1.00 12:12 ATOM 1148 SC CYS 315 62.176 35.824 (1.399 1.00 .24 1 ATOM 1749 14 LYS 316 65.402 33.724 63.715 1.00 13.33 S ATOM 1750 ZA LYS 316 66.381 33.242 64.650 1.30 i.33 SATOM 1151 C3 LYS 316 67.301 32.320 63.860 1.00 12.47 ATOM 1752 CG LYS 316 68.200 31.444 64.637 1.00 :2.22 ATOM 1753 CD LYS 316 69.242 30.818 63.708 :.00 1-.2 ATOM 1754 CE LYS 316 10.213 31.865 63.178 1.00 1.2: SATOM 1755 NZ LYS 316 71.029 !2.46? (4.288 1.0C .4 ATOM 1756 LYS 316 67.141 34.462 65.092 C ATOM 1751 2 LYS 316 67.192 35.468 64.359 OC ATOM 1158 N PRO 31' 67.592 34.516 65.355 1.00 2.25 ATOM 1759 CD PP.0 317 67.284 33.517 67.471 1.00 .8 ATOM 1760 SA PRO 317 68.344 35.662 66.855 1.00 12.51 ATOM 1761 CB PRO 317 68.365 35.412 68.349 1.00 4.33 ATOM 1162 !c PRO 317 68.381 33.979 68.426 1.00 4.27 ATOM 1763 C PP.0RO 317 69.773 35.714 64.285 1.00 3 ATOM 1764 PRO 31 70.532 34.732 66.339 ATOM 1765 ::GLN 318 70.105 36.867 65.711 00 1.4.2 ATOM 1766 CA GL 318 71.418 37.:37 65.144 1.00 15.?3 ATOM 1167 CB GLN 318 71.369 38.436 64.326 .00 ATOM 1168 Cc CLN 318 12.01C 38.335 62.946 !.00 15.24 ATOM 1169 C3 GLN 318 71.602 39.462 C2.064 1.00 ATOM 171C -11 GL\ 319 70.734 39.341 61.189 1.00 !:.i0 ATOM 1Y71 :72 GLN 318 12.199 40.642 12.305 1.00 11.42 ATOM 1712 2 GLN 318 12.213 37.325 61.360 1.00 .i.2S ATOM 73 LN 219 11.901 38.227 E2.174 1.0c ':.24 ATOM 1714 TE 403 10.252 35.791 55.614 1.OC ATOM 1715 CA THR 403 69.393 36.053 54.455 !.00 ATOM 111776 CB THF 403 68.Z36 34.931 54.252 l.C .1 ATOM 1771 G1 THRi 403 68.911 33.651 '4.627 1.00 ATCOM 1713 22 TER 402 i2.869 24.332 12.148 1.0 2 ATO 1719 THR 402 66.251 37.471 54.551 1.OC 1 ATOM 1780 THR 402 69.149 38.341 53.751 :.OC ATOM 1181 TY? 404 .a C5.4 ATOM 1782 CA TYP 404 6.195 29.04: 55.682 OC ATOM 1793 '9 TY. 404 65.698 39.11: 51..366 2.26 ATOM 1784 CZ TYR 404 6.133 38.96 52.910 C .42 ATOM 1785 CC1 TYR 404 65.036 37.70 12.377 .3C .2 ATOM 1786 CE1 TYR 404 64..23 37.54: 12.042 OC -54bzr*21c.pdb Thu Apr 25 12:27:47 1996 a a a a.

a. 9a

ATCHM

ATOM

ATCOM

ATOM

ATCOM

ATOHM

ATOM

1787 CD2 TYP j188 CE2 TYF 1189 CZ TYP 17190 OH TYR 1791 C TYP.

1792 0 TYP.

1193 N SER 1794 CA SEP.

17195 C3 SEP.

1796 00 SEP.

17197 C SEE.

1798 0 SER 1799 N CYS 1800 CA CYS 1801 C CYS 1802 0 CYS 1803 CB CYS 1804 SG CYS 1805 N HIS 1806 CA HIS 1807 CB HIS 1808 CG HIS 1809 CD2 HIS 1810 ND1 HIS 1811 CEl HIS 1812 NE2 HIS 1813 S "is 1814 3 HIS 1815 N PHE 1816 CA PHE 1817 CB PHE 1818 CG PHE 1819 CD1 PHE 1820 CD2 PHE 1821 CE1 PHE 1822 CE2 PHE 1823 CZ PHE 1824 C PHE 1825 0 PHE 1826 N SLY 1827 CA GLY 1828 C GLY 1829 0 SLY 1830 N PP.ROC 1831 CD PRO 1832 CA PP.0 1833 CS PP?? 1834 CG PRO 1835 PRO 1836 0 PP.C 1837 N *.EU 1838 CA LZU 1839 CB LEU 1840 CG LEU 1841 CDI LEU 1842 C02 LE: 1843 C LEO 1844 0 LEU 1845 N THR 1846 CA -HR 1847 CB TSR 1848 .01 THPR 1849 CG2 THR 1850 C TER 1851 1852 N RP.

1953 CA TP? 1854 CS 1855 CG MPP 1856 CC2 1857 CE2 TP.? 1858 CEZ TCP 1859 CC1 TP? 1860 NE1 77?.

1861 CZ2 1862 CZ2 TP.P 1863 Cr.2 F.? 1864 C T p 434 404 404 304 404 404 405 405 "05 405 405 406 406 406 406 406 406 407 401 407 4017 407 42? 401 407 407 4.78 408 438 408 408 40R 408 408 408 408 408 409 409 409 409 4' 9 410 410 410 410 410 410 411 411 411 411 411 411 411 412 412 4.2 412 412 :12 412 41, 1 2 41" 41r 65.

64.

67.

61.

67.

68.

69.

66.

65.

64 64.

64 63 63 63 63 64 63 64 62 63 63 61 61 61 59 59 59 59 59 59 59 5i 51 6 58 5 5.

5 5 5 5 5 5 5 5 5 5 5 5 5 5 299 40.071 !3.050 1.

992 39.918 !1.710 1.

109 38.650 51.219 1.

441 28.463 49.891 374 39.313 !7.169 1.

459 38.471' 19.006 1.

453 40.653 57.500 1, 581 41.068 58.894 1, 842 41.887 19.094 1 985 41.082 !3.888 I 332 41.863 59.305 1 .154 43.047 !8.975 1 .466 41.198 60.046 1 .220 41.789 60.452 1 .192 42.035 61.938 1 .900 41.386 62.709 1 .096 40.827 60.107 1 .277 39.951 !8.514 1 .363 42.987 62.332 1 .162 43.317 63.721 1 .001 44.542 64.165 1 .179 45.803 63.370 1 .324 46.233 62.204 1 .968 46.832 63.812 1 .025 47.837 62.954 1 .840 47.499 61.969 1 .687 42.614 E3.801 .078 43.935 62.789 1 .099 43.443 64.976 .690 43.146 65.168 1.281 43.636 66.643 1 .441 42.260 67.218 1 1.675 42.125 68.562 1.411 41.158 66.409 I.888 40.882 69.095 1.626 39.885 66.935 9.866 39.751 68.282 9.459 45.185 64.136 0.370 46.018 64.744 8.231 45.463 64.347 7.868 46.791 63.936 6.494 46.954 64.509 5.996 46.065 (.5.196 5.879 48.100 64.299 6.497 49.286 63.693 4.544 48.391 64.788 4.276 49.754 64.166 5.623 50.390 64.195 3.52t 47.367 64.313 2.831 46.752 65.137 3.471 47.165 62.981 2.544 46.233 (2.329 2.254 46.614 60.898 1.310 47.803 (0.553 0.007 47.519 61.244 1.888 49.156 60.961 3.052 44.831 62.192 2.365 43.870 62.481 54.231 44.705 61.643 ;4.749 43.388 61.431 53.985 42.829 60.244 54.152 41.413 60.166 54.417 43.523 18.976 56.252 43.565 61.220 1.722 44.671 E1.376 57.003 42.490 60.964 58.468 42.57 60.747 59.002 41.293 60.115 58.912 40.017 60.909 59.722 39.7134 (2.023 59.314 38.413 62.398 60.?12 40.409 62.745 58.12: 39.011 E0.667 58.395 37.998 (1.546 19.97' 37.766 63.459 61.212 39.764 63.801 60.941 38.451 64.152 58.960 43.720 59.832 00 2.00 00 2.00 00 2.53 00 6.21 .00 6.871 .00 5.71 .00 7.44 .00 7.96 .00 9.81 .00 14.61 .00 10.09 .00 10.03 .00 10.45 .00 10.00 .00 10.98 .00 12.25 .00 12.32 .00 12.21 .00 10.98 .00 8.89 .00 11.52 .00 12.77 .00 11.11 .00 10.97 .00 10.32 .00 10.00 .00 3.26 .00 10.54 30 7.42 00 6.36 1.00 5.63 1.00 3.30 L.00 4.11 1.00 4.22 L.00 2.80 1.00 4.80 1.00 4.71 1.00 1.02 1.00 8.84 1.00 4.91 1.00 2.33 1.00 2.02 1.00 4.33 1.00 2.00 1.00 2.98 1.00 3.12 .30 4.67 1.00 6.29 1.00 7.04 1.30 8.58 1.00 6.97 1.00 5.66 1.00 8.28 1.00 11.17 1.00 15.07 1.00 14.05 1.00 4.04 1.00 2.78 1.00 3.16 1.00 2.09 1.00 2.00 1.00 4.34 1.00. 2.00 1.0G 2.54 1.00 3.36 0O 4.26 1.0C 3.65 1.00 2.26 1.3C 4.36 1.0oc .99 1.00 5.87 .;oG 2.3 0 .00- 2.14 1. OC .oc .O0

S

6

S

brof2lc.pdb Thu Apr 25 12:27:47 1996 a a a.

ATOM

ATO

ATO1

ATO

ATOa

ATO

AT

ATC

AT(

ATO

1865 1 TRP 41 1866 N VAL 41 1861 CA VAL 41 1868 CS VAL 41 1869 CG1 VAL 41 e180 C=2 VAL 41 1811 VAL 41 1812 VAL 4 1813 CYS 4 1814 CA CYS 4 1875 CYS 4 1916 C CYS 4 1977 C3 CYS 4 :178 SG CYS 4 1879 N LYS 4 1880 CA LYS 4 1381 -C3 LYS 4 1882 CS LYS 4 1883 CD LYS 4 1884 CT LYS 4 1885 NZ LYS 4 1886 1 LYS 4 1887 1 LYS 4 1888 PRO 1889 PRO i890 A PRO 1891 :3 PRO 1892 PRO 1893 PRO 1894 C PRO 1895 N GLN 1896 CA GLN 1891 C3 GLN 1898 C3 GLN 1899 :D GLN 1900 OZ1 GLN 1901 NE2 GLN 1902 Z GLN 1903 C GLN 1904 N LYS 1905 :A LYS i906 :3 LYS 1901 :C LYS 1908 LYS 1909 :Z LYS 191C NZ LYS 1911 3 LYS :912 LYS i93 PHE 1914 :A PHE 1915 :3 PHE 1916 :3 PRE 1911 :31 PRE 1918 32 PHE 1919 Z1I PRE 1920 :E2 PRE :921 :z PRE '922 PHE 1923 PHE .924 GLO :925 -A GLU *926 GLU 3GLU M 921 :z CLII 9.29 1 GLC 9 GL;: 93C :2 GLU M i 31 GLU :?32 L M 93 SER M 4 2 SE.

:935 SER H '-36 1=SER M -3 SER *i 929 5CSET 4 :939 LYS M 1940 LYS OM 1941 LYS OM 1942 LYS 3 4 14 14 14 14 4 14' 15 15 15 15 15 15 16 16 16 16 16 16 16 16 416 417 411 417 411 4171 411 411 418 418 418 418 418 418 418 418 418 510 510 510 510 510 510 510 510 510 511 511 511 511 511 511 511 511 511 311 511 512 512 512 512 512 512 512 512 512 512 112 !13 514 514 514 514 58 60 60 61 62 19 62 63 62 63 64 63 63 62 65 66 67 6 6 6 6 6 6 6 6

I

6 1 1 1 .*81 44.350 19.115 !.0 .27a 43.923 59.813 .0 .904 44.921 18.951 1.0 1 46.289 19.660 3 .:93 47.012 59.029 1.0 .189 41.111 !9.541 1.0 .242 44.340 18.533 1.3 82 44.296 19.303 1.0 .296 43.820 17.314 1.0 42.222 !6.809 1.0 .238 44.001 15.161 .0 .114 44.949 55.189 1.3 .207 41.882 56.222 '.C .061 41.071 51.341 1.C .484 43.622 t5.581 1.

.341 44.191 54.585 >1.

.176 45.349 !5.135 1.

6.482 46.235 56.144 6.618 45.629 57.541 1.

5.851 46.404 !8.599 1.

6.292 45.888 59.931 1.

1.234 43.008 14.2-78 1.

1.523 42.181 15.175 1.

1.,573 42.817 12.990 1.

1.231 43.561 51.7 "71 6.434 41.684 12.611 1.

8.394 41.641 11.144 1.

8.247 43.041 !0.780 1.

9.845 41.868 '3.221 0.361 42.990 13.325 1.

0.400 40.762 '3.100 1.

1.153 40.741 54.209 1 1.933 39.562 !5.165 1 1.948 39.963 56.620 1 1.580 38.823 57.530 1 71.37 37.668 517.098 1 11.478 39.131 58.801 1 12.660 40.583 52.990 1 12.410 39.656 52.112 1 36.636 45.141 96.455 1 36.983 44.821 97.554 1 31.004 45.503 8.958 1 31.194 44.129 100.099 1 39.382 44.786 99.984 40.149 44.388 101.309 40.281 42.907 101.710 36.039 43.642 11.542 26.117 42.7-? S3.413 35.089 43.650 96.604 34.207 42.501 96.453 32.903 42.833 95.120 31.969 41.646 95.592 32.470 40.353 95.362 30.594 41.a806 95.735 31.630 39.235 95.219 29.739 40.690 95.653 C.271 39.394 95.424 35.064 41.629 95.554 !5.406 40.483 95.913 3!.416 42.200 94.392 36.244 41.509 93.406 36.523 42.391 92.112 37.498 41.754 91.015 36.951 40.687 90.101 346 40.30' 13.936 25.869 40.011 90.501 37.f01 41.161 94.162 40.02" S4.161 27.984 42.16. 94.930 39.1i4 42.001 S5.745 -9.534 43.314 96.443 40.319 43.054 S1.594 29.122 40.87. S '5 40(1.041 40.02. 96.846 28.C56 40.844 1.513 3 4.902 39.192 9,4.5689 G36.839 40.12. S0.605 3-.256 41.165 103.621 0 1.06 0 6.50 0 6.63 0 .88 0 6.16 0 3.31 0 3.59 0 11.73 0 3.15 0 9.1% 0 3.05 0 a.16 00 9-11 0 14.11 o0 7.88 30 3.50 6 00 14.11 30 19.54 00 23.24 6 00 23.14 o 00 21.C8 30 12.10 00 10.95 00 12.45 00 11.38 00 11.16 30 10.58 00 11.41 00 14.43 00 14.95 00 15.69 .30 16.01 .00 15.85 .00 13.51 .00 16.21 .00" 16.54 .00 16.18 .00 17.;91 .00 20.26 .00 20.08 .00 22.39 .00 22.50 .30 24.41 .30 24.33 .30 23.09 .30 21.46 1.30 21.11 .30 20.11 30 20.62 .00 18.81 1.30 11.03 1.00oo 11.36 1.00 11.10 1.30 19.23 31 16.04 1.30 20.47 1.30C 17.16 .C 17.52 1.:0 16.93 1.0 171.14 C a18.20 1.3 20.3 28.00 1.2c 20.11 29.86 1.13 30.21 >2C 15.96 ;C 16.76 1.3: 13.11 1.'C 12.12 I.)C 12.170 1.2. 13.01 12.51 C 14.35 1.94 .59 .7 -56bref21c.pdb Thu Apr 25 12:27:47 1996 000000 @0 0 O 00 0* 0* 0 0* 0 00 0 0*00

ATOM

ATOHM

ATOM

ATOHM

ATOM

ATCOM

ATOM

ATOMN

ATOM

ATOt ATOt

ATOI

1943 CD LYS 5 1944 CZ LYS 5 1945 NZ LYS 5 1946 C LYS 5 1947 0 LYS 5 1948 N ALA S 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 LEO 1959 CA LEU 1960 C3 LEU 1961 CC LEU 1962 CD1 LEU 1963 CD2 LEU 1964 C LEU 1965 0 LEU 1966 N LEU 1967 CA LE 1968 C3 LE 1969 C LEU 1970 CDI LEU 1971 CD2 LEU 1972 C LEU 1973 O LEU 1974 N ALA 1975 CA ALA 1976 CB ALA 1977 C ALA 1978 0 ALA 1979 N ALA 1980 CA ALA 1981 CB ALA 1982 C ALA 1983 0 ALA 1984 N AP.G 1985 CA ARC 1986 C3 AP.CG 1987 CCG ARC 1988 C ARC 1989 NE ARC 1990 CZ ARP.G 1991 NH1 ARC 1992 NH2 ARG 1993 Z ARG 1994 0 ARC 1995 N GLY 1996 CA GLY 1997 C GLY 1998 0 GLY 1999 N PRO 2000' CD PRCO 2001 CA PRCO 2002 C3 PRO 2003 CO PRO 2004 S PRO 2005 3 PRO 2006 N SLE 2007 L 2003 SF GL 2009 CC CLZ 2013 CD GL 2011 :El GL.

2012 CL 2013 C GL 2014 GLU 2015 N CIZ 2016 CA CL* 2017 CE C L 4 2018 CC GL 4 2019 CD GLZ S 2020 OE1 CLU 14 14 14 14 14 15 15 I e $16 516 516 516 517 517 517 517 511 517 tie 517 :181 518 518 518 518 518 518 518 519 519 519 519 519 520 520 520 520 520 521 521 521 521' 52; 5 2.

521 52: 521 521 521 522 522 522 522 523 523 523 523 523 523 524 !2- 524 524 524 524 524 524 524 t2, '2: 121 52L 521 525- 36.388 41.093 101.842 36.374 42.393 102.539 1.

35.661 42.215 103.798 37.621 38.443 97.959 37.841 37.435 98.620 37.132 38.401 96.716 36.876 37.117 96.038 36.187 37.366 94.719 38.165 36.299 95.806 1.

38.176 35.069 95.920 1.

39.241 37.026 95.494 1.

40.562 36.478 95.204 41.457 37.533 94.614 41.205 35.872 96.419 41.690 34.751 96.353 41.226 36.599 97.530 41.809 36.040 98.743 1 41.445 36.874 99.947 1 42.141 38.193 100.158 41.717 39.177 99.108 1 41.754 38.683 101.519 41.271 34.634 98.992 42.009 33.751 99.437 39.997 34.433 98.648 39.291 33.177 96.857 1 37.84t 33.467 99.273 1 21.614 32.731 100.773 1 26.802 34.965 100.936 36.951 32.519 101.495 39.339 32.158 97.733 39.185 30.955 97.979 39.557 32.623 96.505 39.603 31.726 95.342 39.310 32.481 94.072 40.908 30.949 95.209 41.733 31.215 94.311 41.047 29.935 96.068 42.228 29.064 96.115 !42.169 28.165 97.371 42.579 28.212 94.865 41.764 27.430 94.339 43.834 28.352 94.449 44.407 27.633 53.322 45.499 28.484 S2.652 45.117 29.950 92.441 45.751 30.a71 93.500 45.5!2 30.373 94.854 46.279 29.452 95.464 47.351 28.957 94.843 45.888 28.889 96.620 45.o018e 26.343 93.866 44.842 26.022 95.032 45.710 2!.592 93.022 46.336 24.375 93.500 47.851 24.578 93.549 48.288 25.677 93.891 18.672 23.333 93.225 48.070 22.203 92.929 50.157 23.469 93.185 50.429 22.304 92.201 49.277 21.315 92.486 50.96E 24.731 2.741 50.499. 25.617 91.984 52.222 24.761 93.180 53.121 25.851 z2.829 54.289 25.979 93.857 55.487 24.958 93.730 55.207 23.507 94.250 54.91C 22.603 93.413 1.343 23.263 ?w.484 53.672 25.532 91.428 53.705 24.359 91.016 61 6 26.564 3.747 22 26.411 89.427 53.557 26.334 38.442 53.857 25.543 6';.149 52.595 25.16 -2.35' 52.474 23.956 61.991 26 0 00 30 3.28 00 11.13 00 13.26 00 13.10 30 9.iS 00 13. 00 i.E3 00 7.7a 00 8.76 00 7.65 00 6.46 00 7.37 00 8.55 00 8.04 00 5.52 .00 3.15 .00 4.53 .00 9.66 .00 4.29 .00 1.29 .00 10.33 .30 3.49 .00 '.25 .00 !.25 .30 1.53 .30 2.48 .30 ?.17 .00 2.11 .00 8.:0 .00 11.23 .00 13.55 .00 12.74 .00 15.14 0 15. 00 17.93 i.00 19..E1 00 2d.83 00 13.53 1.00 13.39 1.00 90.0O 1.00 90.20 00 90.00 30 90. 0 :.00 90.30 00 Cc 1.00 .00 9. 2 1.00

C

1.00 90.:3 .00 90.:0 00 9. :0 ;0 .3 -:0 1.00 9.1c 30 :.00 9'.C .0O 9. :c :.00 90. :0 1.20 9C.: 1.20 00 1.OC .00 24. 2C 2 3 00 27.? .00 23.' :C 2:.5 1.30 21.10 2C 21.2.

:.00 2..22 1.00 21.22 2c iz.! C 2C :2.i3 .oc 3".1 .00 3C.i4 0C 3:.25 7 7 i,

I

i i i i

I

i i i -57-

S

0 0* 0 0 *0O 0 0 *0 00 @0 0

OS

S 0 bret21c.pdb ATOM 2021 OE2 GLU 5; ATOM 2022 C GLU 5 ATOM 2023 o GLU 5; ATOM 2024 N LEU ATOM 2025 CA LEU 5: ATOM 2026 CB LEU 5; ATOM 2027 CC LEU 5 ATOM 2028 CC1 -EU 1 ATOM 2029 CD2 LEU S ATOM 2030 C LEU 5 ATOM 2031 0 LEU 5 ATOM 2032 N LEU 5 ATOM 2033 CA LEU 5 ATOM 2034 CB LEU S ATOM 2035 CG LEU 5 ATOM 2036 CD1 LEO 5 ATOM 2031 CD2 LEU 5 ATOM 2038 C LEU 5 ATOM 2039 0 LEU ATOM 2040 N CYS ATOM 2041 CA CYS ATOM 2042 C CYS ATOM 2043 0 CYS ATOM 2044 CB CYS ATOM 2045 SG CYS ATOM 2046 N PE ATOM 2047 CA PHE ATOM 2048 CB PHE ATOM 2049 CC PHE ATOM 2050 CD1 PHE ATOM 2051 CD2 PHE ATOM 2052 CE1 PHE ATOM 2053 CE2 PHE ATOM 2054 CZ PHE ATOM 2055 C PHE ATOM 2056 0 PHE ATOM 2051 N THR ATOM 2058 CA THP.

ATOM 2059 CB THR ATOM 2060 OG1 THF.

ATOM 2061 CCG2 THP.

ATOM 2062 C THRP ATOM 2063 0 THP.

ATOM 2064 N GLU ATOM 2065 CA GLU ATOM 2066 CB GLU ATOM 2067 CC GLU ATOM 2068 CD GLU ATOM 2069 OE1 CLU ATOM 2070 OE2 GLU ATOM 2071 C GLU ATOM 2072 0 GLU ATOM 2073 N ARC ATOM 2014 CA ARC ATOM 2075 CB ARC ATOM 2016 CC ARC ATOM 2077 CD ARC ATOM 20-78 "NE ARC ATOM 2019 CZ ARC ATOM 2080 NH1 ARC ATOM 2081 NH2 ARC ATOM 2082 C ARG ATOM 2093 ARC ATOM 2084 N -EU ATOM 2085 C.A LE' ATOM 2086 CB LEU ATOM 2087 CC LEU ATOM 2088 :CD: LEC ATOM 2089 CD2 LEU ATOM 2090 C ATOM 2091 0 LE' ATOM 2092 N GL; ATOM 2093 ATOM 2094 CB L ATOM 2095 CG CLI ATOM 2096 CD GL'.

ATOM 2091 OE1 SL- ATOM 2098 OE2 GL 25 25 25 26 26 26 26 26' 26 26 26 27 271 21 27 221 27 521 27 21 528 528 528 ;28 528 529 529 529 529 529 529 .29 529 529 529 529 530 .30 530 530 530 530 530 531 532 532 532 532 532 522 532 522 523 523 534 52 524 522 53- 51- 51.731 26.066 E8 .119 1.00 34.52 55.512 27.633 89.150 30 8.91 55.306 28.676 6).723 1.00 9.70 56.619 21.495 63.331 30 5.52 57.455 28.638 81.940 30 4.14 58.859 28.182 81.485 1.30 4.80 60.103 29.082 87.590 1.00 2.00 61.166 28.501 E6.706 1.30 2.00 59.856 30.499 61.193 00 2.00 56.688 29.248 86.751 00 2.64 56.521 28.601 85.733 CO 2.30 56.209 30.474 86.892 1.00 2.00 55.415 31.107 85.854 1.00 2.00 54.115 31.638 86.441 1.00 4.05 53.035 30.653 86.824 30 2.65 51.951 31.429 87.441 30 2.00 52.541 29.889 85.620 1.00 2.00 56.110 32.256 85.116 1.00 4.04 56.413 33.252 85.836 1.00 5.30 56.234 32.176 83.844 1.00 3.62 56.929 33.199 83.051 '.00 2.91 55.981 33.810 82.044 :.00 2.18 55.081 33.121 81.560 1.30 2.61 58.132 22.593 62.282 >.30 2.00 59.491 31.832 83.234 00 2.00 1 56.197 35.088 E1.743 1.00 2.00 55.397 35.792 60.758 C0 4.16 54.008 36.143 Z1.303 030 3.88 53.980 37.215 82.231 >.20 2.00 53.958 38.611 81.733 00 2.00 53.912 37.123 E3.611 1.00 2.00 53.868 39.691 62.590 00 2.00 53.822 36.201 84.471 1.00 2.00 53.801 39.490 63.961 1.00 2.00 56.100 37.031 80.200 1.00 5.11 57.018 37.511 80.185 :.00 6.52 55.665 37.471 79.018 1.00 2.84 5,6.225 38.655 78.311 00 2.00 5'1.228 38.280 77.232 1.00 2.00 57.683 39.460 16.579 1.00 2.64 56.631 37.355 16.234 00 2.96 55.016 39.582 177.948 1.0C 2.59 53.999 39.124 ;1.611 1.00 4.31 55.215 40.882 3.076 .00 2.29 54.246 41.854 117.747 1.00 5.46 54.178 42.919 7~.836 1.30 10.50 54.046 42.346 e0.257 1.3 12.93 53.771 43.413 i1.298 14.12 54.085 44.606 El.079 1.03 15.54 53.221 43.052 E2.355 00 18.13 54.462 42.489 76.382 1.00 6.42 53.505 42;'685 75.650 1.00 9.10 55.659 43.021 76.152 1.00 5.91 56.039 43.529 -4.832 1.00 6.83 56.900 44.195 14.890 .30 6.46 56.141 46.059 75.094 1.00 4.16 '55.682 46.070 -6.483 00 6.94 54.531 46.930 16.696 1.00 14.70 54.158 47.395 71.8990 1.00 11.72 54.817 41.096 -3.975 1.00 13.74 52.998 48.056 13.017 00 18.08 56.934 42.364 -4.434 .20 3.63 56.904 41.310 75.052 .0 12.29 57.767 42.502 73.436 :.o3 10.64 59.606 41.256 72.195 ZC 12.12 58.326 40.790 71.821 l.'C 13.12 56.984 40.298 71.741 .0C 10.95 56.531 39.7113 0.348 11. 9 56.1772 39.204 72.754 1.3C 12.40 60.064 41.723 73.430 3 11.> 60.891 41.6903 2.535 0O 12.1; 60.365 42.115 14.666 C 12.95 61.122 42.523 7'5.003 13.:Z 61.999 43.332 14.365 C 1 .;4 61.006 44.974 '4.791 >0 23.:E 60.768 46.010 17.684 20 26.3.

59.849 46.860 13.862 :C 26.36 61.461 45.933 72.625 62 25.33 hu Apr 25 12:27:47 1996 50 **«50 -58bref2lc.db Thu Apr 25 12:27:47 1996

S

*5 S. S

S

ATOM

A Tom

ATOM

ATC4M

ATOM

2099 C GLU 5 2100 GLU 5 2101 N ASP 2102 CA ASP 2103 CS ASP 2104 CC ASP 2105 301 ASP 2106 302 ASP 2107 Z ASP 2108 C ASP 2109 N LEU 2110 CA LEU 2111 CS LEU 2112 C LEU 2113 CDI LEU 2114 CD2 LEU 2115 C LEU 2116 0 LEU 2117 N VAL 2118 CA VAL 2119 CS VAL 2120 CG1 VAL 2121 CG2 VAL 2122 C VAL 2123 0 VAL 2:24 N CYS 2125 CA CYS 2126 C CYS 2121 O CYS 2128 CB CYS 2129 SC CYS 2130 N PHE 2131 CA PHE 2132 C3 PHE 2133 CG PHE 2134 CDI PHE 2135 CD2 PHE 2136 CE1 PHE 2131 CE2 PHE 2138 CZ PHE 2139 C PHE 2140 C PHE 2141 N TFF 2142 CA TPP 2143 CB TRP 2144 CC TP.P 2145 CD2 T.P 2146 CE2 TP.P 2147 CE3 TP.P 2148 CDI TRP 2149 E1 TP.P 2150 CE2 TPP 2151 CZ3 TPP 2152 CR2 TPP 2153 C TP 2154 0 TP.P 2.55 N GLU 2156 CA CLC 2157 CB GL; 2158 C GL 2;59 CD GLU 2160 -EL CGL 2.61 -E2 GLU' 2162 GLC 2:63 L 2164 N GLU 2:65 CA GL 2-66 7b GL.

2167 CC GL;, 2168 CD CZ 2169 *3E1 CL: 2'70 3E2 CL: 2:71 C GLU 2;72 GL 2172 ALA 2'14 CA ALA *275 Cz ALA S2:16 C ALA 24 24 .35 i~S 525 125 !25 525 !35 536 536 536 536 536 536 536 536 537 537 537 531 537 521 537 538 5328 538 538 538 538 539 539 539 539 539 539 539 539 539 539 539 540 540 540 540 540 540 140 540 540 540 540 540 540 540 541 541 541 541 541 541 541 541 542 542 542 542 542 542 542 542 542 !42 142 61.892 42.579 76.527 62.651 42.380 7".066 61.251 41.637 77.194 61.247 41.519 78.638 60.188 42.544 7).128 58.848 42.334 78.430 58.020 41.541 73.913 58.635 42.949 71.372 60.793 40.201 72.033 60.062 39.577 13.295 61.176 39.731 60.204 60.117 38.436 80.651 61.614 37.315 80.149 61.012 35.958 80.495 59.697 35.789 .1.782 61.955 34.853 80.152 60.725 38.468 62.154 61.701 38.896 82.751 59.606 38.093 62.7671 59.514 38.050 84.219 58.439 39.006 84.161 58.391 z8.900 86.262 58.754 40.434 64.386 59.111 36.652 84.604 58.232 36.096 83.911 59.812 36.048 65.553 59.452 34.711 86.055 59.375 34.771 27.597 60.165 35.457 E3.251 60.438 33.619 E5.600 60.634 33.421 83.795 58.426 34.059 68.178 58.267 34.099 89.621 57.295 35.232 89.997 55.852 35.009 89.515 54.835 34.690 90.420 55.519 35.104 88.147 53.540 34.410 89.986 54.201 34.878 87.706 53.223 34.562 68.630 57.689 32.8017 90.123 57.391 31.913 89.352 57.606 32.696 91.436 56.965 31.575 92.102 57.859 30.331 92.252 58.890 30.380 93.315 60.250 30.807 93.175 60.861 20.65 94.430C 61.008 31.299 92.11C 58.738 29.995 94.61( 59.914 30.161 95.28 62.208 30.984 94.65' 62.336 31.623 92.321 62.921 31.465 93.59 56.504 32.199 93.41 56.-74 33.366 93.66 55.698 31.467 94.18 55.187 31.999 95.45 53.768 32.565 95.27 53.592 33.523 94.07 52.202 34.134 93.99 52.094 25.229 93.41 51.219 33.553 94.51 55.148 30.925 9i.50 54.-44 29.811 94.22 55.552 31.242 97.72 55.521 30.222 93.7f 56.311 29.482 ?98.8 58.122 30.359 98.71 59.40 29.571 99.01 59.711 29.256 100.11 60.095 29.263 98.0; 55.CS2 20.763 100.1 54.741 31.94 100.2 55.051 29.889 101.1 54.652 30.25E 102.4 54.466 29.038 102.3 55.716 31.141 103.1 1.00 10.95 1.00 10.92 1.00 9.01 1.00 6.92 1.00 8.31 1.00 8.75 L.00 11.89 L.00 15.77 1.00 6.27 1.00 6.6 1.00 5.28 1.00 4.48 A 1.00 2.00 1.00 2.00 1.00 2.00 1.00 2.00 1.00 5.42 1.00 5.81 L.00 6.59 7 1.00 4.71 6 1.00 3.90 6 1.00 7.66 1.00 6.66 A 1.00 2.70 1.30 5.62 1.00 3.31 1.00 4.7 1.)1 5.86 00 6.30 L.00 2.00 L.00 3.19 14 1.00 3.78 7 1.00 4.15 6 1.00 4.88 6 1.00 7.86 6 1.00 5.60 6 1.00 9.65 A 1.30 ;4.81 1.00 7.22 1.00 5.52 1.00 3.30 4 1.00 5.07 3 1.00 2.62 7 1.00 5.41 4 1.00 5.13 1.00 7.06 4 1.;0 4.64 I 1.3C 5.72 4 S1.00 5.86 S1.50 8.29 6 1..0 8.36 1 1 1.00 8.15 4 8 1.00 7.58 6 1.00 8.06 7 1.00 6.24 8 1.300 7.32 3 6 8.81 7 2 1.00 10.45 4 0 00 11.89 4 0 1.00 14.89 1 1.00 16.24 4 5 .o 17.33 1 6 1.30 16.64 i 7 1.c 10.33 2 1.00C 10.32 4 1.30 10.91 i6 10.78 13 .2 10.24 i 38 .0 14.40 4 )6 1.2 15.17 4 38 1.00 17.03 26 17.30 28 66 48 1.70 9.88 93 .0 7.10 25 4.26 4 08 1.C 8.66 4 -59brf2lc.pdb Thu Apr 25 12:27:47 1996 a a a

ATOM

ATOHM

ATOM

ATOHM

ATOM

ATCOM

ATOM

ATOHM

ATOM

ATOI

ATOt ATOt

ATOI

ATO

ATOI

ATO

AT

2177 O ALA 5 2178 N ALA 5 2179 CA ALA 5 2180 CB ALA 5 2181 C ALA 5 2182 O ALA 5 2183 N SER 2184 CA SER 2185 CB SER 5 2186 C00 SER 5 2187 C SEP. 1 2188 C SER 5 2189 N ALA 5 2190 CA ALA 5 2191 CB ALA 5 2192 C ALA 5 2193 -0 ALA 5 2194 N GLY 5 2195 CA GLY 2196 C GLY 2191 O GLY 2198 N VAL 2199 CA VAL 2200 CS VAL 2201 CC1 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 C PRO 2214 C PRO 2215 0 PRO 2216 N CLY 2217 CA GLY 2218 C GLY 2219 3 GLY 2220 N ASN 2221 CA ASN 2222 CS ASN 2223 CG ASN 2224 301 ASN 2225 ND2 ASH 2226 C ASN 2227 C ASN 2228 N TYR 2229 CA TYR 2230 CB TYP.

2231 C TYF.

2232 CD1 TYP.

2233 CE TYP 2234 CD2 TYR 2235 CE2 TYF.

2236 CZ TYF.

2237 2) TYF.

2238 C TYR 2239 TYR 2240 N 5SE.

2241i :A SER S2242 SR SER 2243 V- sl;.

2244 C SE; H 2245 SEP.

S 2246 N PHI S 2247 CA PHE S 2248 CB PHE 2249 CG PHE n 2250 C31 PHE n 2251 C02 PHE H 2252 CE1 PHE H 2253 CE2 PHE M 2254 CZ PHE 43 44 44 44 44 44 45 45 45 45 45 45 46 46 46 46 46 47 47 '47 541 548 148 '48 548 489 548 ,48 549 549 549 549 550 550 550 550 550 550 550 551 551 551 551 552 552 352 552 552 552 552 552 553 553 !53 553 ss3 553 553 553 553 553 !!3 554 554 554 (555 155.

155 555 56.911 30.849 1C2.998 55.286 32.253 103.695 56.199 33.185 104.325 55.425 34.374 104.890 56.861 32.397 105.438 56.169 31.144 106.216 58.204 32.393 135.456 58.992 31.669 106.453 59.335 30.251 105.980 60.291 29.628 IC6.827 60.245 32.440 1C6.891 60.865 33.184 106.117 60.557 32.271 lCS.114 61.639 32.942 1C.882 61.927 32.215 110.200 62.928 33.213 108.143 63.651 32.291 101.15 63.212 34.495 107.965 64.438 34.889 107.300 64.841 34.140 106.032 66.045 34.046 IC5.1739 63.867 33.560 C105.322 64.111 32.882 10G4.048 63.115 31.749 1C3.826, 63.134 31.309 102.363 63.450 30.579 1:4.756 63.874 33.371 1:2.995 62.721 34.309 102.114 64.954 34.612 IC2.541 64.852 35.667 101.551 65.4713 35.180 1CO.263 65.765 33.991 100.117 65.666 36.066 99.283 65.213 37.459 S9.186 66.271 35.639 98.017 66.333 36.943 97.199 66.201 38.019 98.199 §7.647 34.964 58.1571 7.991 34.066 97.311 68.384 35.340 99.204 69.714 34.791 99.442 69.776 33.300 93.601 70.854 32.736 93.581 68.62! 32.555 1-3.721 68.573 31.215 93.881 67.510 30.851 1C0.90 .1.197 31.449 1-2.22 68.789 31.112 102.85 66.991 32.411 1C2.63 68.287 30.504 98.59 68.176 29.265 98.58 68.157 31.278 97.50 67.867 30.738 94.18 66.432 31.08 95.77 65.367 30.341 96.52 64.491 31.001 17.37 63.574 30.290 -3.11 65.280 28.253 64.355 28.243 17.14 63.516 29.914 ?.0 62.65C 28.183 1.3.7 68.191 31.287 69.432 32.306 15.2 68.845 30.612 -3.9 69.622 21.109 70.999 30.456 12.3 70.954 29.192 12.2 68.800 30.783 'i.6 68.289 29.584 i.5 S8.574 :1.751 12.1 67.811 31.643 1.5 66.734 22.730 1.4 65.72C -2.51 i.

64.422 32.509 51.3 56.242 32.554 ;7.

63.541 32.382 2 f.7 9 32.427 00 10.83 .00 9.48 .00 10.43 00 1.53 I.00 11.84 .00 13.61 00 12.11 00 13.08 00 12.9Z 1.00 14.06 1.00 14.68 00 15.67 .00 17.50 :.00 17.93 00 11.18 1.00 18.94 1.00 19.69 1.00 19.34 00 20.46 1.00 20.86 1.00 23.71 5.00 18.62 1.00 14.08 .00 12.11 1.00 13.62 1.00 11.28 1.00 15.33 1.00 16.13 1.00 15.42 1.00 12.34 1.00 12.73 s 1.00 11.82 .00 12.01 1.00 12.99 1.00 13.59 1.0w 9.83 1.00 10.09 1.00 13.;34 1.00 14.83 i 1.00 13.58 1 1.00 11.00 1.00 9.01 1 1.00 11.57 5 !.00 6.84 3 1.00 6.10 4 1.00 4.38 6 !.00 6.^3 0 1.00 7.24 1 1.00 3.39 0 00 7.54 0 1.00 1.91 6 1.00 5.28 6 1.00 4.43 9 1.00 4.87 0 1.00 4.46 3 1.30 3.71 1.00 3.40 !3 .00 3.40 7 1.C 3.44 12 00 2.00 18 1.30 3.67 14 1.00 5.08 99 1.00 4.35 80 1.30 5.81 3 3 32 30 3.42 4 00 11.53 21 00 6.33 02 00 .3 -3 30 1.43 36 OC 5.32 84 .0!7 84 .03 5.15 67 1.00 396 i9 1.00 4.43 50 .29 ?63 .00 2.?2 64.030 32.339 ii-.196 .00 5.62 a.

bref2lc.pdb ATOM 2255 C PHE S ATOM 2256 0 PHE 5 ATOH 2251 N SER 5 ATOM 2258 CA SER 5 ATOM 2259 CB SER 5 ATOM 2260 OC SER 5 ATOM 2261 SER 5 ATOM 2262 0 SER 5 ATOM 2263 N TYR 5 ATOM 2264 CA TYP. 5 ATOM 2265 CB TYP.

ATOM 2266 CG TYP.

ATOM 2267 CD1 TYP.

ATOM 2268 CE1 TYP.

ATOM 2269 CD2 TYR ATOM 2270 CE2 TYR ATOM 2211 CZ TYR ATOM 2212 OH TYR ATOM 2213 C TYR ATOM 2214 0 TYR ATOM 2215 N GLN ATOM 2276 CA GLN ATOM 2277 CS GLN ATOM 2218 CC GLN ATOM 2279 CD GLN ATOM 2280 OE1 GLN ATOM 2281 KE2 GL1; ATOM 2282 S GLN ATOM 2283 0 GLN ATOM 2284 N LEU ATOM 2285 CA LEU ATOM 2286 CB LEU ATOM 2287 CG LEU ATOM 2288 CDI LEU ATOM 2289 CD2 LEU ATOM 2290 C LEU ATOM 2291 0 LEU ATOM 2292 N GLU ATOM 2293 CA GLU ATOM 2294 CB GLU ATOM 2295 CG GLC ATOM 2296 CD GLU ATOM 2291 OE1 GLU ATOM 2298 OE2 GL:: ATOM 2299 C GLU ATOM 2300 0 GLZ ATOM 2301 N AS? ATOM 2302 CA AS? ATOM 2303 CB ASP ATOM 2304 CG ASP ATOM 2305 001DI ASP ATOM 2306 OD2 ASP ATOM 2307 C ASP ATOM 2308 0 ASP ATOM 2309 N GLCU ATOM 2310 CA GL.

ATOM 2311 CB GL ATOM 2312 'CG GLC ATOM 2313 CD GL' ATOM 2314 OEI GL: ATOM 2315 OE2 GL ATOM 2316 GL: ATOM 2317 30 SL' ATOM 2318 N PPRO ATOM 2319 ;D ATOM 2320 PP.

ATOM 2321 C? PP.R ATOM 2322 CG PFE: ATOM 2323 C PPF.

ATOM 2324 .3 P.C ATOM 2325 N TP? ATOM 2326 CA TP ATCOM 2327 CB T7?; ATOM 2328 CG TR? ATOM 2329 CD2 TR.P ATOM 2330 CE2 TR? ATOM 2331 CE2 TP.P ATOM 2332 CD1 TP.F 55 55 56 56 56 56 56 56 5-1 51 57 i57 i5' 557 55, 551 557 551 551 551 558 558 558 558 558 558 558 558 558 558 559 559 559 559 559 559 559 559 560 560 560 560 560 560 560 560 560 561 561 561 561 561 561 561 561 562 562 562 562 562 562 562 562 562 563 563 563 563 563 :63 564 564 56, 564 564 564 564 564 68.779 31.759 E8.337 69.184 32.858 87.945 69.095 30.616 67.740 70.019 20.503 E6.619 70.969 29.315 86.879 71.922 29.58' 87.891 69.335 30.298 85.257 68.535 29.389 85.111 69.682 31.102 84.255 69.123 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 E1.023 68.737 34.368 83.434 69.184 35.667 83.260 69.734 36.047 82.051 70.124 31.356 81.865 70.191 30.834 81.870 71.316 31.196 82.090 69.839 30.360 80.695 70.831 30.227 79.648 71.603 28.925 79.828 72.506 23.598 i8.648 73.171 21.282 73.780 12.552 26.320 -3.183 74.447 27.229 73.477 70.204 30.208 13.279 69.420 29.309 77.977 70.518 31.189 77.445 69.945 31.139 76.120 70.036 32.487 75.399 68.975 33.527 75.792 69.103 34.810 75.005 67.612 32.955 75.564 10.764 30.060 75.441 71.951 29.947 75.728 70.091 29.169 14.718 90.737 28.064 73.997 69.787 21.517 12.938 70.290 26.305 72.163 69.701 26.201 10.738 69.790 27.202 69.983 69.200 25.130 70.346 71.995 28.572 13.310 11.919 29.491 72.505 13.140 27.970 -3.64e 14.460 28.346 13.11i 74.418 28.398 71.581 14.440 27.038 70.961 74.530 26.039 71.72! 74.296 26.963 69.72! 74.995 29.667 73.66 175.663 30.426 72.93 74.714 29.972 74.92 75.22C 31.218 75.50 )4.093 32.235 75.65 73.224 32.450 74.40 73.909 33.234 73.28 74.330 34.407 73.51 73.981 32.610 72.16 75.764 30.841 87 75.431 29.759 77-.3 16.662 31.681 77.4f 7.20C 23.000 7.03 77.156 31.287 13.79 78.186 32.376 7).1" 7?.65! 33.548 17..4( 75.96: 31.277 73.71 74.981 32.001 75.995 30.362 80.7' 74.945 30.255 81.81 75.204 29.19' 62.8 74.650 27.88S E2.7 72.217 21.585 82.9 73.116 26.18a 82.7 72.156 28.35 8E2.2 75.25C 26.70'1 82.3 Thu Apr 25 12:27:47 1996 00 6.86 1.00 a.43 i.00 1.22 1.00 6.83 1.00 4.30 1.00 8.78 1.00 5.62 1.00 8.35 1.00 3.o 3.30 1.00 2.00 1.00 2.00 1.00 2.00 1.00 2.56 1.00 2.00 1.00 2.00 1.00 3.10 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 30 2.96 :.00 2.00 1.00 2.89 1.00 2.00 1.00 2.00 6 1.00 2.00

A

1.00 2.00 6 1.00- 5.30 6 1.00 4.67 1.00 6.97 1 1.00 11'.03 1.00 14.40 i 1.00 19.08 i '1.0 20.20 4 1.00 25.39 1.00 21.83 I 1.30 11.71 S .00 10.88 I 1.3C 12.36 1 1.30 13.20 S 1..30 11.29 1 1.00 13.29 5 30 14.53 9 '.30 11.84 1 1.00 17.27 1 1.00 21.21 6 1.30 11.40 4 1.30 16.45 2 00 20.22 8 00 23.17 9 1..C 23.82 1 20 22.18 9 :C 27.47 1 14.28 3 :C 16.04 65 2 11.29 i4 24 14 3 11.69 .1 :C 7.10 04 1.1 4.79 88 1..G 10.73 58 C 11.36 72 1.:C 8.20 06 1..2C 5.30 45 2.55 00 1C 1.38 41 4.62 61 3Z 6.36 96 8.59 87 ;C 4.26 -61bref2lc.pdb

T

ATOM 2333 NE1 TRF 56 ATOM 2334 CZ2 TP.P 56 ATOM 2335 C23 TRP 5E ATOM 2336 CH2 TRP 5 ATOM 2337 C TRP 5 ATOM 2338 0 TP.P 5 ATOM 2339 N LYS 5 ATOM 2340 CA L'YS 5 ATOM 2341 CE LYS 5 ATOM 2342 CC LYS 5 ATOM 2343 CD LYE 5 ATOM 2344 CE LYS 5 ATOM 2345 NZ LYS 5 ATOM 2346 C LYS 5 ATOM 2347 0 LYS 5 ATOM 2348 N LE 5 ATOM 2349 CA LEU 5 ATOM 2350 CB LE 5 ATOM 2351 CC LED 5 ATOM 2352 CD1 LEU 5 ATOM 2353 CD2 LE 5 ATOM 2354 C LEO ATOM 2355 C LEU O ATOM 2356 N CYS ATOM 2357 CA CYS ATOM 2358 C CYS ATOM 2359 O CYS ATOM 2360 CB CYS ATOM 2361 SG CYS ATOM 2362 N ARG ATOM 2363 CA ARC ATOM 2364 CB ARG ATOM 2365 CC ARG ATOM 2366 CD ARG ATOM 2367 NE ARC ATOH 2368 CZ ARC ATOM 2369 NH1 ARG ATOM 2370 NH2 ARG ATOH 2371 C ARG ATOM 2312 3 ARC ATOM 2373 N LEU ATOM 2374 CA LEU ATOM 2375 CB LEU ATOM 2376 CC LEO ATOM 2377 CDI LEC ATOM 2378 CD2 LEU ATOM 2379 C LEU ATOM 2380 0 LEU ATOM 2381 N HIS ATOM 2392 CA HIS ATOM 2383 CS HIS ATOM 2384 CC HIS ATOM 2385 CD2 HIS ATOM 2386 ND1 HIS ATOM 2387 CEI HIS ATOM 2388 NE2 P.IS ATOM 2399 C HIS ATOM 2390 '0 HIS ATOM 2391 N GLN ATOM 2392 CA SLN ATOM 2393 CE GLN ATOM 2394 C SLN ATOM 2395 CD GLN ATOM 2396 f1l SLN ATOtI 2297 NE2 SLN ATOM 2398 C GLN ATOM 2399 G CLN ATOM 2400 K ALA ATOM 2401 CA ALA ATOM 2402 C? ALA ATOM 2403 ALP.

ATOM 2404 Z ALA ATOM 2405 N C ATOM 2406 CD PFC- ATOM 2407 CA PP.0 ATOH 2408 CE PPC ATOM 2409 C0 PP.0 ATOM 2410 C PRO hu Apr 25 12:27:47 1996 4 64 55 64 64 64 65 65 65 65 66 66 66 66 66 65 66 66 61 567 567 61 566 566 568 561 568 5687 569 568 568 568 568 568 566 568 569 560 569 568 569 569 569 569 56970 56970 !69 569 570 570 570 510 570 571 370 570 571 571 511 5." S71 511 571 !1 571 511 572 572 512 572 571.

sl2 573 513 57 74.338 25.675 82.422 L.0 71.880 25.546 62.929 L.0 10.928 21.123 83.461 L.0 70.801 26.328 83.279 1.C 74.880 31.597 62.525 1.0 75.908 32.259 82.740 1.0 73.690 31.997 82.921 1.0 73.542 32.256 83.612 L.

73.099 34.332 62.625 1.

74.242 34.886 81.791 1.

73.827 35.197 E0.371 i.

74.814 36.116 79.711 1.

74.856 37.374 80.497 1.

72.669 33.171 84.878 1.

71.856 32.270 85.043 1.

72.863 34.113 85.783 1.

72.160 34.100 87.042 1.

73.187 33.857 88.143 1.

12.902 33.890 89.641 1.

14.121 33.292 90.343 1.

12.660 35.299 90.155 1.

71.505 35.418 87.265 1.

72.175 36.430 87.315 i.

70.199 35.446 87.406 1.

69.636 36.738 67.658 1.

69.245 27.013 69.124 69.271 36.113 89.983 68.506 37.017 66.701 1 67.190 35.797 86.808 69.009 38.293 89.405 1 68.626 38.177 90.727 1 68.781 40.310 90.798 1 70.037 40.829 91.510 1 71.329 40.711 90.681 1 72.045 41.996 90.624 1 72.587 42.642 91.671 1 72.531 42.151 92.918 1 73.191 43.816 91.465 1 67.185 38.399 91.086 1 66.247 36.690 90.329 1 67.046 37.752 92.248 65.782 37.304 92.807 1 66.005 36.101 93.715 65.069 34.917 93.607 64.374 34.905 92.287 (5.852 23.675 93.759 65.318 36.461 93.637 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 41.541 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 39.076 95.393 62.098 37.884 95.284 61.-2t 39.869 96.246 60.655 39.363 97.063 61.18! 38.806 98.371 60.150 38.01' 99.168 60.187 38.342 100.666 61.169 39.03' 101.358 59.11- 38.962 IC1.170 59.712 40.504 91.308 60.098 41.656 97.285 58.445 40.152 91.419 51.348 41.021 97.656 56.920 41.77- 95.356 56.211 40.214 946.195 56.26C 38.974 98.057 55.212 40.32' 2..864 55.084 42.102 99.602 54.205 29.86? S).323 53.7609 40.437 14.696 54.78! 41.599 10,.984 53.044 39.12: 3.311 31 0 5. 6 0 6.49 0 6.19 0 3.18 0 5.66 00 3.22 00 3.69 00 2.20 00 2.00 00 2. 30 3.81 30 3. co00 6.31 00 3.24 00 2.93 00 3.46 30 6.16 00 7.13 00 11.34 00 13.73 00 11.29 00 6.69 00 6.50 00 1.27 .00 10.28 .00 13.50 .00 13.64 12.37 .00 17.22 .00 15.13 .00 14.78 .00o 17.37 .00 20.45 .00 20.67 .00 22.26 .07 22.85 .00 20.25 .00 24.23 .00 14.39 .00 15.75 .00 11.39 00 6.i2 1.00 2.00CO L.O0O 3.41 *.0O 3.80 1.00 2.00 1.00 S.24 '.4 1.00 10.84 o.00 u. :4 i.00 10.31 1.00 13. :0 00 1. .0 1.00 14.17 t.00 12.6 ).92 1.00 14.44 1.00 ?.24 i.00 8.37 0O 11.43 :.00 1.

30 21-13 .00 23.69 :.OC 22.! 3C 26 :.O0 1.22 .0 :.OC 8.45 00 >8 OL T.33 i i

I

i i i i i i

I

-62-

S.

bref21c.pdb ATOM 2411 0 PRO ATOM 2412 N THR ATOM 2413 CA THR ATOM 2414 C3 THP.

ATOM 2415 OGI THF.

ATOM 2416 CG2 THR ATOM 2417 C THR ATOM 2418 0 THR ATOM 2419 N ALA ATOM 2420 CA ALA ATOM 2421 CB ALA ATOM 2422 C ALA ATOM 2423 0 ALA ATOM 2424 N ARG ATOM 2425 CA ARG ATOM 2426 CB ARG ATOM 2427 CG ARG ATOM 2428 CD ARG ATOM 2429 NE ARG ATOM 2430 CZ ARG ATOM 2431 NHI ARG ATOM 2432 NH2 ARG ATOM 2433 C ARG ATOM 2434 0 ARG ATOM 2435 N CLY ATOM 2436 CA CLY ATOM 2431 C G.Y ATOM 2438 0 GLY ATOM 2439 N ALA ATOM 2440 CA ALA ATOM 2441 CB ALA ATOM 2442 C ALA ATOM 2443 0 ALA ATOM 2444 N VAL ATOM 2445 CA VAL ATOM 2446 CB VAL ATOM 2447 CG1 VAL ATOM 2448 CG2 VAL ATOM 2449 C VAL ATOM 2450 0 VAL ATOM 2451 N ARG ATOM 2452 CA ARG ATOM 2453 CB ARG ATOM 2454 CG ARG ATOM 2455 CD ARG ATOM 2456 NE ARG ATOM 2451 CZ ARG ATOM 2458 NHl ARG ATOM 2459 NH2 ARG ATOM 2460 C ARG ATOM 2461 0 ARG ATOM 2462 N PHE ATOM 2463 CA PRE ATOM 2464 CB PHE ATOM 2465 CG PHE ATOM 2466 CD1 PHE ATOM 2467 CD2 PHE ATOM 2468 'CE1 PHE ATOM 2469 CE2 PHE ATOM 2410 CZ PHE ATOM 2471 Z PHE ATOM 2472 PHE ATOM 2473 N TPP ATOM 2474 CA TP.P ATCE 2475 C3 ?.P ATOM 2476 :C T.P ATOM 2477 CD2 TP ATOM 2478 CE2 TP ATOM 2479 CE2 TP.P ATOM 2480 :01 TP.? ATOM 2481 NE1 TP.P ATOM 2482 CZ2 TP.P ATOM 2483 :Z2 TRF ATOM 2484 CH2 TP.P ATOM 2485 "7 ATOM 2486 TPP ATOM 2487 N -Y5 ATOM 2488 CA CYS 573 174 74 574 174 574 574 !74 575 575 S75 576 576 576 576 576 576 576 576 576 576 577 577 578 578 578 578 578 579 579 579 579 579 579 579 580 550 580 590 580 5380 580 530 saO 580 581 581 51al 581 531 !31 531 531 531 1,,1 32 5322 562 532 532 532 582 532 532 532 582 5 32 532 58".

533 52.76e 52.428 51.255 51.075 52.135 49.712 50.119 50.163 49.08' 47.934 46.9332 47.282 46.480 47.663 47.178 46.877 45.534 45.633 44.350 44.171 45.188 42.979 48.090 47.843 49.167 50.066 1.201 51.959 51.263 52.332 51.842 53.443 53.278 54.597 55.673 56.957 56.734 57.363 "55.922 55.599 56.460 56.721 55.769 55.926 55.080 53.652 52.71' 53.05( 51.47( 58.15 5S.66.

58.82 60.20 60.98 61.27 60.51 62.37 60.63 62.69 61.92 60.28 59.68 61.03 61.12 59.86 59.46 59.91 59.31 60.17 58.6 58.6 59.6 61.0 60.4 62.4 63.2 62.5 63.6 40.608 97.552 38.574 98.416 1.

38.232 97.727 1.

36.738 97.733 1.

36.153 96.980 1.

36.324 91.115 1.

36.852 98.515 1.

38.814 99.752 1.

29.324 97.812 1 39.946 98.467 1 40.433 91.439 1.

38.960 99.443 1.

29.355 100.286 1 37.695 99.344 1.

36.637 100.189 1.

35.414 99.328 1 35.451 98.604 1 34.631 97.302 1 34.081 96.848 i 33.438 95.6867 1 33.261 94.833 1 32.928 95.391 1 26.216 101.251 1 25.177 101.972 1 36.963 101.606 1 36.615 102.7C5 25.638 102.425 23.280 C13.356 1 21.140 101.193 1 34.245 100.720 1 332.360 99.617 1 35.158 100.212 1 36.384 100.128 1 34.593 99.905 1 35.431 99.406 1 25.294 100.247 1 35.863 101.618 33.860 100.30 35.128 97.929 34.044 97.452 36.104 97.229 35.911 95.816 4 36.792 94.991 36.721 93.503 4 37.813 92.844 37.511 92.913 9 35.362 93.341 S329.581 93.721 0 37.952 93.466 9 36.282 95.523 4 37.321 95.954 7 35.387 94.827 0 35.596 94.458 2 34.355 94.803 4 34.214 96.250 C 23.372 97.045 1 34.883 96.822 5 33.191 98.390 4 34.700 98.165 f 33.854 98.944 35.39 92.961 6 35.101 92.194 26.844 92.525 9 37.054 91.090 61 27.773 90.589 12 38.933 91.423 16 40.268 41.280 66 41.017 92.359 44 40.906 90.356 6i 28.915 92.533 04 40.165 93.1C5 1, 42.365 92.538 01 ;2.24- 90.524 3E 42.973 91.617 09 37.i22 90.429 19 38.299 91.041 5( 27.312 6).150 56 27.766 E3.334 00 7.72 00 8.95 00 10.96 00 10.37 00 14.24 00 13.72 00 12.85 00 14.59 00 14.8 00 14.50 00 14.72 00 14.38 .00 15.91 .00 12.79 .00 11.82 .00 15.95 .00 20.92 .00 24.61 .00 27.37 .00 28.99 .00 29.46 .00 27.90 .30 9.90 .00 8.14 .00 10.36 .00 9.18 .00 11.02 .00 10.42 .00 11.51 .00 10.32 .00. 6.95 .00 10.21 00 9.88 1.00 9.95 00 10.55 00 9.32 1.00 8.45 L.00 11.44 1.00 9.09 00 8.40 1.30 7.06 ;.oc 7.86 1.00 8.84 1.00 7.88 1.00 8.78 1.00 6.85 1.50 5.69 1.00 5.12 i.00 2.00 1.00 1.72 1.00 1.66 1.00 6.07 1.00 5.52 1.00 4.84 1.00 4.90 1.00 3.60 00 5.69 1.00 4.44 1.30 5.88 00 3.43 00 5.46 .30 6.33 30 6.16 1.SC 7.26 ,C 9.34 00 10.74 30 11.49 .G00 11.22 1.30 11.65 30 14.19 .OC 12.18 00 12.31 3: 15.91 1.00 16.33 c 94 1.0C0 .37 3C C( 6 3 6 6 6 6 6 6 6 6 b a 6 0 6 6 8 6 6.

6 -6 i, Thu Apr 25 12:27:47 1996 32 -63braf21c.pdb Thu Apr 25 12:27:47 1996

S

*5 *5

S..

S

ATOM

.;TOM

ATOM

2489 C CS 2490 0 CYS 2491 CB CYS 2492 SG CYS 2493 N SER 2494 CA SER 2495 SB SEP.

2496 :G SEP.

2497 SEP.

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

2!16 CB THF.

2517 OG1 THR 2518 CG2 THP.

2519 C THR 2520 C THF.

2521 N ALA 2522 CA ALA 2523 CB ALA 2524 C ALA 2525 0 ALA 2526 N ASP 2521 CA ASP 2529 CB ASP 2529 CG ASP 2520 OD1 ASP 2131 CD2 ASF 2532 ASP 2533 3 ASP 2534 N THF.

2535 CA THF.

2536 C3 THP 2537 ?C1 THF.

2538 CC2 TF.

2539 C THR 2540 0 THE 2541 N SEP.

2542 CA SER 2543 CS SER 2544 OG SEP.

2545 C SEP.

2546 -0 SEP.

2541 N SEP.

2549 CA SEP.

2549 C3 SEF.

25C CG SER 2'51 C: F.

2552 C SEF.

2553 PHE 2555 3CS PHE 2556 CC FFE 2557 PHE 25!' PHE 2559 C51 PHE 252 C:E2 PH 2:51 Pf 2562 PHE 25462 PE 2564 N VAL 2565 CA VAL 2566 Ci. VAL 593 583 583 583 584 584 564 584- 584 584 585 585 585 585 585 585 585 585 586 586 586 586 596 586 586 587 581 587 581 581 581 587 588 588 588 588 588 589 589 589 589 589 589 539 589 590 590 590 590 590 590 590 591 591 591 591 591 591 592 592 532 592 592 592 593 59?.

593 5337 593 594 594 594 594 63.154 62.143 64.501 65.603 63.895 63.556 63.210 62.296 64.819 65.874 64.743 65.889 65.638 65.265 65.929 65.633 66.134 65.188 67.410 68.622 67.746 69.251 69.505 67.416 67.834 66.691 66.261 66.168 65.921 65.049 67.182 66.739 68.472 69.512 10.896 69.435 69.025 68.877 68.745 69.173 70.673 71.088 71.422 67.341 67.080 66.435 65.040 64.118 64.496 64.269 64.696 63.610 65.592 65.317 66.69: 61.041 '64.40: 64.45 63.58: 62.60 61.39 60.19 63.21 64.38 62.38 62.71 62.86 61. '4 62.04 50.39 61.02 59.38 59.68 63.84 64. 3 64.2 65.21 38.449 E7.073 1.

38.055 26.520 1.

36.591 21.876 1.

36.996 25.410 39.453 E6.606 40.150 E5.315 1.

41.612 E5.649 1.

42.141 Z4.680 1.

40.052 54.531 1.

40.485 E4.990 1.

39.3517 3.390 1.

39.214 62.500 1.

38.192 81.374 1.

36.731 B1.541 1.

35.888 80.486 1 36.271 E2.912 1 40.562 81.832 1 41.282 21.508 1 40.929 81.637 1 40.279 E2.160 1 42.202 80.993 42.304 61.191 1 41.470 82.416 1 42.019 13.520 1 41.019 13.912 1 42.985 ,3.9517 42.949 :1.569 1 44.355 -6.969 t 45.330 -3.002 L 44.408 -5.929 1 42.186 15.657 1 41.308 15.948 1 42.530 16.700 1 41.927 15.849 1 42.342 76.320 40.425 15.700 39.894 14.681 39.147 76.693 38.300 16.651 37.684 71.976 37.683 73.168 38.045 79.298 37.299 -7.230 37.845 -5.376 36.659 -5.383 38.780 14.133 38.451 "5.899 39.571 -5.426 40.806 -5.845 I 39.728 :7.928 38.106 14.465 38.414 -4.001 37.405 -3.783 37.022 72.391 2 36.681 -1.696 6 37.115 13.790 5 35.867 :2.177 6 34.847 -2.882 5 35.999 -1.135 7 34.988 10.803 5 35.633 70.1:9 5 36.638 -0.916 6 33.945 *:.889 6 22.914 03.563 8 32.980 :3.527 5 31.900 '3.622 6 32.414 7.189 4 33.45a (5.7S9.

1 34.679 -5.1 7 99 33.162 E.343 C 35.584 -5.866 8C 34.054 8 35.262 ii.12.

8S 30.94: i).00o: 02 30.17'7 ".151 22 30.95a '.291 84 30.11:'3 .991 00 8.52 00 3.13 00 11.02 00 12.88 1.

00 11.08 00 11.13 00 14.00 00 22.72 00 11.03 00 14.11 00 8.82 00 i.31 .00 5.24 .00 2.00 .00 2.00 .00 5.67 .00 8.19 .00 1.56 .30 10.50 .00 12.29 .00 11.85 .00 11.45 .00 13.83 .00 14.14 .00 14.11 .00 13.17 .00 12.49 .00 15.11 .00 18.67 .00 17.05 .00 12.00 .00 11.83 L.00 11.51 1.00 7.86 .00 8.95 .OC 71.36 1.00 8.37 1.00 7.82 1.00 7.85 1.00 5.24 1.00 5.26 00 6.38 00 2.00 1.00 '.96 7.86 1.00 8.88 00 10.02 1.00 8.46 1.00 7.66 1.00 10.59 1.00 10.88 1.00 15.28 1.00 11.68 '.00 11.91 1.00 13.98 1.00 16.79 1.00 11.64 1.00 12.56 9.34 1.00 5.84 .030 6.26 00 5.45 1.00 5.25 00 4.72 C 5.79 1.00 .33 1.3C 7.57 00 6.76 L.O0 3.27 cI 21 1.00 9.60 1. 30 .0 1.0: 1-44 i.OC 9.34 ".OC 11.09 3 32 0(4 ~.29 0 0 9. 17

S

1 6

S

s 6 3 1 6 e 6 2 c 6 6 a 7 6 c 6 3 3

C

8 7 e

"I

s 66.:.88 30.109 1.155 -64a a.

bxaf2lc.pdb ATOM 2567 CC1 VAL 5 ATOM 2568 CG2 VAL 5 ATOM 2569 C VAL S ATOM 2570 0 VAL ATOM 2571 N PRO ATOM 2572 CD PRO ATOM 2573 CA P.0O ATOM 2574 CB PP.0 ATOH 2575 CG PRO ATOM 2516 C PRO ATOM 2577 0 PRO ATOM 2578 N LEU ATOM 2579 CA LE3 ATOM 2580 CB .U ATOM 2581 C. LEU ATOM 2582 CDI LEU ATOM 2583 CD2 LEO ATOM 2584 C LEO ATOM 2585 0 LEU ATOM 2586 N GLD ATOM 2587 CA GLU ATOM 2588 CB GLO ATOM 2589 CG GLU ATOM 2590 CD GLU ATOM 2591 OE1 GLU ATOM 2592 OE2 GLU ATOM 2593 C 01.0 ATOM 2594 0 GLU ATOM 2595 N LEU ATOM 2596 CA LEU ATOM 2597 CB LEG ATOM 2598 CG LEU ATOM 2599 CDI LEO ATOM 2600 CD2 LEU ATOM 2601 C LEU ATOM 2602 0 LEU ATOM 2603 N ARG ATOM 2604 CA ARG ATOM 2605 CB ARC ATOM 2606 CC ARG ATOM 2607 CD ARG ATOM 2608 NE ARG ATOM 2609 CZ ARG ATOM 2610 NH1 AP.G ATOM 2611 NH2 ARG ATOM 2612 C ARG ATOM 2613 0 ARG ATOM 2614 N 7AL ATOM 2615 CA ATOM 2616 C3B VAL ATOM 2617 CG1 VAL ATOM 2618 CG2 VAL ATOM 2619 C VAL ATOM 2620 0 *;AL ATOM 2621 N T£.

ATOM 2622 CA T?.

ATOM 2623 CB TE=?.

ATOM 2624 "OGI TFP.

ATOM 2625 CG2 TH.

ATOM 2626 C T-1.

ATOM 2627 0 ATOM 2628 N ALA ATOM 2629 CA ALA ATOM 2630 CE ALA ATOM 2631 ALA ATOM 2632 C ALA ATOM 2633 N AL.A ATOM 2634 CA ;LA ATOM 2635 CB ;A.A ATOM 2636 A.A ATOM 2637 3 ALA ATOM 2638 N SER ATOM 263:- CA S- ATOM 2640 CB SER ATOM 2641 0G S3E ATOM 2642 C EAr ATOM 264-3 SEP ATOM 2644 N '94 >94 '94 '94 595 595 595 595- 595 595 595 596 596 596 596 596 596 596 596 597 591 591 591 597 597 597) 597 597 598 598 598 598 598 598 598 599 599 599 599 599 599 599 599 599 599 599 599 600 600 600 600 600 600 600 601 601 601 601 601 601 601 602 602 602 602 602 603 603 603 603 603 604 604 604 604 604 604 605 67.086 21.490 49.894 1.I 66.35? 32.005 72.175 1.1 64.874 29.552 72.261 1.1 64.201 3C.239 73.037 L.

65.287 28.308 72.572 1.

65.910 27.414 71.592 1.

65.040 27.558 73.802 L.

65.623 26.185 73.468 1.

65.442 26.084 12.064 1.

65.728 26.142 75.048 1.

66.955 28.077 75.180 1.

64.923 28.692 75.955 1.

65.420 29.282 77.199 1.

64.610 30.596 77.561 1.

65.384 21.870 78.068 1.

64.500 32.639 19.002 1.

66.646 31.534 78.783 1.

65.252 28.293 78.347 1.

64.121 27.938 73.121 1.

66.384 27.861 78.900 1.

66.406 26.943 80.031 1.

67.566 25.980 79.909 1 67.699 25.125 81.113 1 68.548 23.955 80.855 L 69.206 23.971 79.805 1 68.562 22.014 81.675 1 66.483 27.704 81.361 1 67.322 28.596 81.536 1 65.590 27.358 82.296 1 65.519 28.001 83.600 1 64.159 28.670 83.777 1 63.756 29.657 82.681 1 62.279 29.702 82.601 1 64.368 31.021 82.888 1 65.761 26.988 64.100 1 65.337 25.833 84.605 1 66.462 27.428 85.736 1 66.804 26.580 86.862 1 48.254 26.115 86.710 1 68.479 24.611 86.512 1 69.385 24.359 85.308 1 69.658 22.945 £5.047 10.176 22.100 65.942 70.472 22.515 87.182 70.452 20.845 65.580 66.717 27.367 68.150 67.394 28.364 i8.259 65.843 26.379 89.081 65.756 27.644 90.381 64.322 28.001 90.825 64.336 28.512 92.248 63.737 29.035 69.917 66.273 26.622 91.371 65.744 25.525 91.426 67.309 26.963 92.124 67.891 2i.043 93.098 69.296 25.601 52.688 69.228 24.939 91.430 69.890 24.631 93.684 67.995 26.634 94.481 68.267 27.822 S4.637 67.788 25.792 95.484 67.915 26.196 96.877 67.254 25.191 97.745 69.404 26.180 97.153 10.101 25.324 96.613 69.872 27.069 93.036 71.292 27.162 98.415 71.517 28.370 99.300 71.871 25.882 ?9.070 73.066 25.785 S9.320 71.026 24.892 91.324 71.497 23.629 9'.897 10.409 22.980 1C0.140 69.?02 22.024 99.997 11.914 22.6e9 98.777 12.462 21.61' 91.042 71.604 23.070' 97.535 00 11.21 00 8.98 00 6.86 00 9.44 00 4.06 00 4.50 00 4.23 00 4.01 00 2.00 30 00 3.03 00 3.21 00 4.16 00 3.29 00 2.00 00 3.47 00 2.16 00 4.67 0 2.22 .00 4.53 .00 3.76 .00 2.00 .00 2.00 .00 5.62 .00 10.01 .00 6.65 .30 2.57 3.19 .00 3.03 .00 2.16 .00 -2.00 .00 2.00 .00 2.00 .00 2.00 .00 2.92 .00 2.64 .00 2.34 00 3,62 .00 6.78 00 10.90 1.00 14.84 1.CO 17.19 L.00 17.80 1.30 17.23 1.00 15.10 1.00 3.41 1.Z; 4.23 2.27 2.32 2.2 .2C 2.02 1.30 1.00 2.30 1.3C 3.23 1.30 1.30 5.21 :.CC 6.14 1.30 12.7- 30 8.70 1.3C S.74 2^ 10.2 11.56 9.735 2: 1.2

C

Thu Apr 25 12:27:47 1996 34 bref21c.pdb Thu Apr 25 12:27:47 1996

S

ATOM

ATOt 2645 CA GLY 6 2646 C GLY 26417 GLY 2648 N ALA 2649 CA ALA 2650 CB ALA 2651 C ALA 2652 0 ALA 2653 N PRO 2654 CD PRO 2655 CA PRO 2656 CB PRO 2651 CG PRO 2658 C PRO 2659 C PRO 2660 N ARG 2661 CA ARG 2662 CB ARG 2663 CG ARG 2664 CD ARG 2665 NE ARG 2666 CZ ARG 2661 NH1 ARG 2668 NH2 ARG 2669 C ARC 2610 0 ARG 2671 1 TYP.

2612 CA TYP.

2613 CS TYP.

2614 CG TYP.

2615 CD1 TYP.

2616 CE1 TYR 2611 CD2 TYP.

2618 CE2 TYRP.

2619 CZ TYRP.

2680 OH TYF.

2681 C TYP.

2682 0 TYR 2683 N HIS 2684 CA HIS 2685 CB HIS 2686 CG HIS 2687 CD2 HIS 2688 ND1 HIS 2689 CE1 HIS 2690 NE2 HIS 2691 C HIS 2692 HIS 2693 N ARG 2694 CA ARG 2695 CB ARG 2696 CG ARG 2697 CD ARC 2698 NE ARG 2699 CZ ARG 2100 NH1 ARC 2701 NH2 ARC 2102 C ARG 2103 0 ARG 2104 N VAL 2105 CA VAL 2106 VAL 2701 :C1 VAL 2106 CG2 'JAL 2109 VAL 2110 VAL 21"1 N I.£ 2712 IL- 2712 Cb ILE 2714 'C2 IL" 2115 CC1 I.LE 2716 CD1 ILE 2711 ;-E 2711a3 EL I 2119 N H.T 2120 CA HIS 2121 Cb 2122 CC HIS 05 605 605 606 606 606 606 606' 601 601 601 601 601 601 608 608 608 608 608 608 608 608 608 608 608 608 609 609 609 609 609 609 609 609 609 609 609 609 610 610 610 610 610 610 610 610 610 610 611 611 611 611 611 611 611 611 611 611 612 612 612 612 612 612 612 613 613 613 613 613 61:1 614 614 614 614 71.944 22.262 96.318 1.1 10.109 21.620 95.185 10.111 21.198 94.631 1.

69.639 21.606 96.512 68.376 21.001 96.194 1.

61.492 20.885 91.381 1.

61.665 21.110 95.113 L.

67.450 22.914 95.234 1.

61.222 21.063 94.014 1.

61.457 15.636 93.821 L.

66.520 21.660 92.950 I.

66.656 20.581 91.845 1.

61.655 19.620 92.355 1.

65.046 21.969 93.220 1.

64.281 21.084 93.599 1.

64.656 23.215 92.953 1.

63.284 23.658 93.095 1.

63.198 25.105 93.591 1.

63.510 25.320 95.066 I.

62.608 24.414 95.992 1.

61.169 24.119 95.820 1.

60.530 25.828 96.200 61.193 26.811 96.113 1 59.216 25.936 96.048 62.586 23.548 91.139 (1.613 22.836 91.612 63.095 24.194 90.100 62.405 24.140 69.406 1 61.532 25.394 89.203 60.543 25.684 90.298 L 60.700 26.198 91.131 1 59.166 21.078 92.156 1 59.434 24.852 90.499 1 58.494 25.120 91.506 1 58.664 26.235 92.326 1 51.689 26.529 93.255 L 63.316 24.032 88.193 1 64.448 24.514 88.207 1 62.803 23.416 87.137 63.536 22.308 85.886 64.306 21.995 85.715 65.112 21.883 84.524 65.692 22.830 83.153 65.346 20.681 83.896 66.030 20.893 62.186 66.250 22.189 82.616 42.50C 22.456 84.114 E1.459 22.824 64.194 62.190 24.306 E3.801 61.858 24.561 82.756 60.946 25.103 83.222 59.416 2 5.513 82.826 58.101 26.890 82.920 57.501 26.833 82.093 56.64- 21.834 81.931 56.85C 28.913 E2.542 '5.605 27.111 81.138 -2.657 24.994 81.558 3.80C 25.350 81.680 i2.014 24.333 60.388 62.66? 25.256 1I.119 ;3.056 24.068 78.198 '3.80.6 24.561 16.961 63.917 23.089 18.935 .490 25.9656 3.464 0.382 25.436 18.481 61.614 27.181 7.968 60.557 27.374 17.340 59.889 28.933 18.210 19.24; 28.219 -).471 60.89C 30.015 13.669 60.267 31.241 ').182 60.99E 28.501 7-;.094 62.164 28.553 713.109 60.012 29.113 75.412 60.252 30.007 14.241 59.604 29.42' 72.910 (..441 28.410 12.211 00 4.1 00 1.43 00 9.81 30 '.11 00 6.20 00 2.64 30 6.88 D0 1.80 C0 6.21 30 6.18 00 1.15 00 1.21 00 5.40 CO 6.86 00 6.25 00 6.55 00 6.82 00 1.55 .00 11.99 .00 14.22 .00 14.28 .00 14.39 .00 15.96 .00 13.38 .00 6.91 .00 9.99 .00 1.03 .00 1.82 .00 9.92 .00 11.15 .00 12.36 .00 13.98 .00 13.86 .00 13.63 .00 15.21 .00" 11.36 .00 1.45 .00 10.10 1.00 4.17 00 3.51 00 2.85 1.00oo 2.00 1.00 2.00 00 2.00 :.00 2.00 00 2.00 00 3.94 ;.OC 4.31 1.00 4.10 1.00 2.00 00 2.00 1.00 5.34 1.00 2.76 1.00 4.99 1.00 4.31 .OC 9.01 1.00 2.00 1.00 2.00 00 3.11 1.30 2.16 1.00 5.11 :.0o 5.26 1.00 6.96 1.00 9.61 tc. 4.40 0 5.91 00 2.39 2.00 00 2.00 2.1l, OC 2.00 00 2.00 00 2.06 00 0C 63 0( c. 2.10 -66brt21lc.pdb Thu Apr 25 12:27:47 1996 *0

S.

S S *5*S S. S. S S

S

ATOM

ATOFM

ATOM

ATCl

ATOM

2723 CD2 HIS 6 2724 ND1 HIS 6 2725 CE1 HIS 6 2726 4E2 HIS 2727 C HIS 2728 HIS 2729 N ILE 2730 CA ILE 2731 CB ILE 2732 CG2 ILE 2733 CCI ILE 2734 CD1 ILE 2735 C ILE 2736 0 ILE 2731 N ASN 2738 CA ASH 2739 CB ASN 2140 CG ASN 2741 ODI ASN 2742 ND2 ASN 2743 C ASN 2744 0 ASH 2745 N GLU 2746 CA GLO 2741 CB GLU 2748 CG GLU 2749 CD GLU 2750 E1 GLU 2751 0E2 GLO 2752 C GLU 2753 0 GLU 2754 N VAL 2755 CA VAL 2756 CB VAL 2751 CG1 VAL 2758 CG2 VAL 2759 C VAL 2760 0 VAL 2761 N VAL 2762 CA VAL 2763 C3 VAL 2764 CGC VAL 2765 CG2 VAL 2766 C VAL 2767 0 VAL 2768 N LEU 2769 CA LE' 277110 CS LEU 2771 CG LEU 2712 CD1 LEV 2773 CD2 LEU 2714 C LEO 277115 0 LEU 2776 N LED 2777 CA LE5 2778 :B LEU 2779 C3 LEO 2780 *CD1 LEU 2781 C02 LEU 2782 C LEU 2783 LEU 2784 N ASP 2185 CA ASF 2186 :C ASP 27i7 C= ASP 2188 ?D1 AS? 2789 :D2 AS; 2790 ASP? 2791 AS? 2792 N ALA 2793 CA ALA I 294 CD ALA 2795 ALA S296 ALA 2791

PP.C.

2198 CD PRPC 2799 CA PP.C 2800 CB PP.C 14 14 14 614 614 614 615 615' 615 615 615 615 615 615 616 616 616 616 616 616 616 616 617 611 611 611 611 617 511 618 611 618 618 618 618 618 618 619 619 619 619 619 619 619 620 620 620 620 620 620 620 620 621 621 621 621 621 621 621 621 622 622 622 422 622 622 622 622 623 623 623 623 624 624 624 624 61.353 28.536 11.281 60.442 21.075 12.609 61.310 26.419 71.865 61.875 27.294 11.051 59.580 31.311 14.664 58.419 31.306 75.046 60.315 32.412 14.674 19.717 33.661 15.108 60.770 34.168 75.221 60.102 36.115 15.501 61.185 34.387 76.301 63.067 35.246 16.351 58.569 34.019 14.205 57.609 34.687 74.651 58.639 33.673 72.943 57.618 34.015 71.945 58.205 33.893 70.513 58.860 32.539 10.236 56.410 31.767 69.399 59.954 32.213 70.910 56.281 33.241 72.124 55.265 33.632 71.581 56.280 32.240 72.989 55.088 31.444 13.242 55.424 29.951 13.185 56.381 29.633 72.086 !6.432 28.180 11.104 56.653 21.922 70.498 16.276 21.297 72.575 54.438 31.744 74.587 53.440 21.127 14.930 !4.995 32.667 75.354 54.433 32.988 16.655 55.365 32.566 77.870 55.666 31.109 77.938 56.651 33.3317 1.890 54.119 34.459 16.727 54.600 35.167 17.616 !53.333 34.937 75.778 12.910 36.345 15.792 12.765 36.886 14.401 52.741 38.409 14.449 53.884 36.412 13.519 51.700 36.581 76.589 50.817 35.731 76.61C 51.639 37.734 77.26E 50.492 28.143 78.08C 50.702 31.790 7.554 49.613 31.183 80.431 50.233 31.141 81.77' 48.306 31.985 80.521 50.382 39.654 77.921 50.858 40.437 78.73 49.739 40.044 76.83 49.549 41.432 76.46 48.832 41.498 75.11 49.469 40.971 13.84 48.395 40.832 12.83 50.545 41.903 73.31 48.130 42.253 77.42 4-.941 41.728 79.19 48.918 42.565 77.35 48.148 44.513 18.12 48.678 45.938 77.34 1.1746 46.300 ,3.9( 10.398 41.342 13.7; 49.921 45.580 13.9' 46.855 44.429 77.3: 46.861 44.015 71.1l ,5.7'54 .4.803 717.91 44.452 44.764 77.3: 43.317 44.723 13.41 j2 61 45. 15 -4.3 13 46.953 76.4 43.311 45.890 15.4 42.601 4.628 75.1 42.969 46.928 14.4 41.933 46.241 7'.6 1.00 2.96 1.00 4.63 1 1.00 2.00 1.00 6.31 1.00 3.58 1.00 2.50 1.00 2.76 1 1.00 2.55 1.00 2.49 1.00 2.9 1.00 2.00 i 1.00 2.00 1.00 3.27 1.00 5.04 3 1.00 5.73 7 1.00 4.76 1.00 2.00 6 1.00 2.00 1.00 2.00 3 1.00 2.00 7 1.00 4.60 6 1.00 6.70 3 1.00 4.63 1 1.00 5.16 1.00 4.92 1.00 8.53 1.00 11.83 1.00 15.40 00 14.68 3 1.00 4.18 4 1.00 7.74 3 1.00 3.63 7 1.00 2.00 6 1.00 2.00 6 1.00 2.00 6 1.00 2.00 6 1.00 2.00 6 1.00 2,77 a 1.00 2.00 1 1.00 3.10 6 1.00 2.32 6 1.00 2.43 i 1.00 7.61 6 1.00 4.11 i 1.00 6.41 3 i 1.00 2.53 1 1.00 3. 37 1 1.00 3.39 4 S'..00 3.95 6 5 1.00 5.62 9 1.00 3.21 1.00 5.44 4 6 1.00 7.07 a 4 1.00 7.07 7 5 1.00 5.70 4 1 1.00 5.58 6 5 1.00 2.00 1 1.00 2.42 4 7 1.00 2.00 4 7 1.00 ?.59 4 8 1.00 8.04 i 5 1.00 11.43 7 8 .OC 10.55 4 18 1.00 9.98 i .3 OC 11.16 !4 OC 12.42 16 1.00 11.12 3 16 OC 10.98 12 1.00 11.16 3 55 *.00 13..11 26 1.00 12.49 02 1.00 13.24 i 99 00 10.77 89 1.00 11.45 3 62 1.00 ".62 7 75 1.0C 1.09 1 86 1.20 6.69 32 .00 6.32 -67bruf2lc.pdb Thu Apr 25 12:27:47 1996 9 9 *99 9 9 *99* .9 9.

99 9 *9 9 *99* 9*fr* C. 9.

.9 .9 99*99* 99 9* 99 9**9 9

ATOM

ATOH

ATOM

ATCH

ATOM

ATOHM

ATOM

ATOI

ATO

ATOM

ATO

ATOI

ATOC

ATO

ATC

2801 C3 PRO 62 2802 C PRO 6 2803 3 PRO 6 2804 N VAL 6 2805 CA VAL 6 2806 :3 VAL 6 2801 CG1 VAL 6 2808 CG2 VAL 6 2809 VAL 6 2810 3 VAL 6 2811 N GLY 6 2812 :A GLY 6 2813 GLY 6 2814 GLY 6 2815 LEU 6 2816 CA LEO 6 2811- LEU 6 2818 CG LEO 2819 COl LEU 2820 CD2 LEU I 2821 C LEU 2822 0 LEU 2823 N VAL 2824 CA VAL 2825 CB VAL 2826 CG1 VAL 2821 CG2 VAL 2828 VAL 2829 3 VAL 2830 N ALA 2831 CA ALA 2832 CB ALA 2833 C ALA 2034 3 ALA 2835 N ARG 2836 CA ARC 2831 CB ARG 2838 CC ARG 2839 CD ARC 2840 NE ARC 2841 CZ ARG 2842 NH1 ARG 2843 NH2 ARG 2844 C ARG 2845 2 ARG 2846 H LEU 2841 :A LEO 2848 :B LEU 2849 CC LEU 2850 CDI LEU 2851 C02 LEU 2852 C LEU 2853 3 LEO 2854 N ALA 2855 CA ALA 2956 CB ALA 2851 ALA 2858 "0 ALA 2859 :1 ASP 2860 CA ASP S28.61 CS ASP 2862 :G ASP 2863 D1 ASP 2864 2OD2 ASP 2865 ASP 2866 2 ASP 28617 GLU 4 2868 CA GLU H 2869 CB GLU 4 2810 C2 GLU 2811 CD GLU 2812 E1 GLU H 2313 OE2 GLU H 2814 GLU M 2815 GLU M 2816 N SER M 2811 CA SER 44 2818 CB SER 24 24 24 25 25 25 25 25' 25 25 26 26 26 26 21 21 21 621 i21 621 621 621 628 628 628 628 628 628 628 629 629 629 629 629 630 630 630 630 630 630 630 630 630 630 630 631 631 631 631 631 631 631 631 632 632 632 632 632 633 633 633 632 633 633 233 62233 634 634 634 634 634 634 634 634 634 635 635 635 42.334 44.150 13.736 L.0 42.366 48.198 15.095 1.0 41.591 48.139 16.056 1.0 42.693 49.352 14.518 1.0 42.152 50.638 14.969 1.C 43.254 51.616 75.160 1.C 44.097 51.324 76.386 L-.

44.116 51.144 13.933 1.

41.136 51.193 13.95C 1.

40.119 50.513 12.970 1.

40.629 52.392 14.243 l.

39.683 53.098 13.389 1.

38.396 52.482 12.843 1.1 31.906 52.901 1.7115 1.

37.819 51.522 13.565 1.

36.576 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 14.740 1.

35.415 51.869 12.928 1.

35.001 52.548 73.881 1.

34.954 52.005 71.682 1.

23.814 52.862 71.355 1.

34.166 54.119 10.490 1.

34.935 55.151 71.318 1.

34.942 !3.723 69.244 1 32.787 52.009 10.609 1 33.146 51.111 69.143 1 31.528 52.157 11.036 1 30.393 51.453 10.440 1 29.532 50.850 11.531 1 29.593 52.496 69.664 1 29.684 53.693 69.980 1 28.823 52.061 66.659 1 28.014 52.979 61.845 1 28.813 53.103 66.809 1 29.081 55.154 61.175 1 29.565 56.016 65.999 1 29.366 51.461 66.223 1 29.621 58.112 67.368 1 30.108 51.460 68.455 1 29.421 59.440 61.426 1 26.861 52.308 67.125 1 26.945 51.133 66.744 25.787 53.049 66.944 24.650 52.498 66.238 23.379 53.267 66.603 22.269 52.408 67.214 22.275 50.961 66.711 22.351 52.322 68.140 24.826 52.170 64.791 24.739 53.915 64.341 25.094 51.758 64.027 25.170 51.915 62.641 25.601 50.699 61.943 13.711 52.420 62.235 22.964 51.604 61.190 23.542 53.100 62.434 22.239 54.366 62.2C3 22.438 55.880 62.0:2 22.352 56.115 63.272 21.718 56.363 64.347 22.852 57.911 63.227 21.466 53.894 60.52: 20.252 53.666 60.941 22.131 53.747 59.712 21.428 53.465 22.349 53.156 51.325 22.841 55.203 517.22 23.66 55.525 56.15: 24.012 54.625 55.2!: 24.295 '6.691 56.34: 2.911 52.021 58.272 20.024 51.126 51.!!2 21.465 51.135 59.163 21.062 49.120 59.1.! 22.288 48.820 56.S4 37 0 9.96 .0 10. 38 0 13. 0 0 11.2 1 00 8.571 00 8.1'7 00 10. I i 00 6.41 00 11. :0 00 11.2 00 10. 2 00 12.'1 00 14.18 00 14.32 00 16.6 00 11. 3 00 13.89 00 13.26 00 15.73 00 12.93 6 00 18.21 6 00 17.62 3 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 25.97 .00 22.67 .00 23.69 .00 22.36 .00" 19.90 .00 19.83 .00 22.67 .00 24;86 .00 26.19 .00 28.04 1.00 26.18 1.00 26.18 L.00 1).38 1.00 19.93 1.00 18.11 1.00 13.38 1.00 18.29 1.00 1..24 1.00 18.31 1.00 18.38 1.00 21.32 1.00 23.22 1.00 21.42 1.00 22.038 1.30 22.?1 1.00 24.54 1.00 25.46 1.00 90.30 1.00 90.30 1.00 9C0.30 1.00 9C.30 00 90.30 1.00 9C. :0 i.00 90. :0 ".00 9:.30 1.00 9C.30 1.c0 1.00 1.CO :3 9C.30 1.00 9c. )0 1.c0 92..3 .0C :.OC 31.o

S

1 3 4 1 6 1 4 4 4 i 1 4 7 6 3 .4 .1 11 0 -68- 0 0s S S

S

5505 S. Of 0 0 0

S.

0 0 0045 0e 000 00 0 0* 00 000000 0e 0 06 000* 0 brauf2

ATOM

Lc.pdb Thu Apr 25 12:27:47 1996 2879 OG SER 2890 C SER 2881 0 SER 2882 N GLY 2883 CA GLY 2884 C GLY 2885 0 GLY 2886 N HIS 2887 CA HIS 2888 CB HIS 2889 CG HIS 2890 CD2 HIS 2991 ND01 HIS 2892 CEI HIS 2893 NE2 HIS 2894 C HIS 2895 0 HIS 2096 N VAL 2897 CA VAL 2898 CB VAL 2899 CG1 VAL 2900 CG2 VAL 2901 C VAL 2902 0 VAL 2903 N VAL 2904 CA VAL 2905 CB VAL 2906 CGI VAL 2907 CG2 VAL 2908 C VAL 2909 0 VAL 2910 N LEU 2911 CA LEU 2912 CB LEO 2913 CG LEO 2914 CDI LEO 2915 CD2 LEO 2916 C LEO 2917 0 LEO 2918 N ARC 2919 CA ARC 2920 CB ARC 2921 CG ARC 2922 CD ARCG 2923 NE ARC 2924 CZ AP.G 2925 NHI ARC 2926 NH2 ARC 2927 C ARC 2928 0 ARC 2929 N TP 2930 CA TRP 2931 CB TRP 2932 CG TPP 2933 CD2 TRP 2934 CE2 TP.P 2935 CE3 TPP 2936 CDI TPS 2937 NEI TP? 2938 C22 T.P 2939 CZ3 TP.P 2940 CR2 TP.F 2941 C TPRF 2942 0 TP.P 2943 M N 2944 CA LEr 2945 CB LE'- 2946 CG LE.

2947 CD1 LE' 2948 CD2 LEW- 2949 C LEW 2950 O LE 2951 N PP: 2952 CD PM 2953 CA 2954 CB PP.C 2955 CC PR.: 2956 C PP.R 635 635 635 536 636 636 636 637 637 637 637 637 637 637 637 637 637 638 638 638 638 638 638 638 639 639 639 639 639 639 639 640 640 640 640 640 640 640 640 641 641 641 641 641.

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 64 643 643 644 644 644 644 644 644 23.189 49.037 60.063 1.

20.328 49.370 60.435 1.

19.394 48.552 60.427 1.

20.780 50.010 61.488 1.

20.217 49.834 62.821 1, 20.996 48.771 63.586 1 20.541 47.640 63.790 1 22.203 49.107 64.010 1 22.920 48.155 64.847 1 23.190 46.817 64.148 1 23.915 46.854 62.796 1 25.124 47.337 62.400 1 23.338 46.289 61.665 1 24.176 46.428 60.659 1 25.247 47.050 61.079 1 24.223 48.651 65.427 1 24.505 49.862 65.432 1 24.921 47.631 65.968 1 26.119 47.770 66.646 1 26.169 46.693 67.730 1 26.966 47.127 68.963 1 24.781 46.310 68.2!1 1 27.422 47.694 65.877 1 27.763 46.687 65.236 1 28.129 48.808 65.940 29.41' 48.927 65.309 29.362 49.967 64.127 1 30.383 51.140 64.296 29.531 49.189 62.796 30.503 49.131 66.402 30.569 50.164 67.103 31.245 48.035 66.588 32.312 47.853 67.561 32.296 46.385 68.002 31.948 45.925 69.398 30.755 46.635 69.940 31.703 44.456 69.328 33.727 48.158 67.106 S34.319 47.345 66.393 34.320 49.236 67.616 35.717 49.564 67.269 35.744 50.820 66.406 36.505 50.608 65.100 35.742 51.114 63.884 34.649 50.212 63.502 33.446 50.620 63.085 33.173 51.335 63.013 22.538 49.716 62.685 36.638 49.707 68.527 36.119 49.879 69.635 37.972 49.398 68.366 38.925 49.123 69.515 38.765 48.534 70.453 39.106 47.243 63.819 38.203 46.359 69.133 38.926 45.195 68.814 "36.855 46.438 68.760 40.304 46.612 69.860 40.208 45.377 69.267 38.345 44.116 68.150 36.289 45.374 68.098 37.03! 44.225 67.a03 40.424 49.824 69.178 40.79E 49.704 68.006 41.275 49.382 0.2C7 42.741 50.063 70.039 43.31C 51.312 70.676 42.887 52.62? 70.081 43.784 53.715 70.583 43.012 52.525 68.601 43.506 48.891 70.662 43.096 48.351 71.697 44.645 48.49a 70.059 45.206 49.056 68.317 45.481 47.381 70.556 46.485 47.175 6).412 46.642 48.57. 64.867 4b.192 47.79. '1.a5l 38 00 90.00 .00 90.00 .00 90.00 00 90.00 .00 90.00 .00 90.00 .00 90.00 .00 29.39 .00 28.30 .00 27.4" .00 26.32 .00 26.14 .00 26.56 .00 26.93 .00 26.35 .00 217.39 .00 27.46 .00 25.98 .00 22.67 .00 23.93 .00 24.68 .00 23.20 .00 21.16 00 17.80 .00 19.71 *.00 21.49 1.00 22.97 00 22.32 L.00 21.09 1.00 18.72 L.00 15.61 l.OD 17.29 1.00 15.07 1.00 11.06 1.00 9.33 1.00 6.96 1.00 7.60 1.00 1-3.19 1.00 13.52 1.00 16.40 1.00 18.02 1.00 18.96 1.00 23.80 1.00 25.92 1.00 26.12 1.00 27.21 1.00 24.02 1.00 23.76 1.00 17.87 1.00 13.51 1.00 16.84 1.00 14.61 1.00 13.71 1.00 3.75 1.00 10.16 1.00 10.08 1.00 8.27 1.00 7.42 1.00 10.16 1.00 8.53 1.00 ".26 OC ".13 1.OC 15.14 i.OC 1.51 :2.07 :.OC "2.34 1..OC .27 0C 2.05 l.OC ".00 ).98 00 15.42 00 19.66 :.Cc 1.98 :.OC 15.21 1.OC .1.66 1.0c 15.17 oc :-5.08 1.OC -1.57 4 6 3

S

6 6 6 4.

4 4 -69bz-f2le.pdb Thu Apr 25 12:27:47 1996 39 *6

ATOM

ATCH

ATOM

2951 0 PRO 6 2958 N PRO 6 2959 CD PRO 2960 CA PRO 2961 CB PRO 2962 CG PRO 6 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 2972 N GLD 2913- CA GLU 2914 CD GLU 2915 CG GLU 2916 CD GLU 2911 OE1 GLU 2918 0E2 GLU 2919 C GLU 2990 0 GLU 2981 N THR 2982 CA TSP.

2983 CB THR 2984 0G1 THR 2985 CG2 THR 2906 C THR 2907 0 THR 2988 N PRO 2999 CD PRO 2990 CA PRO 2991 CB PRO 2992 CG PRO 2993 C PRO 2994 0 PRO 2995 N MET 2996 CA MET 2997 CB MET 2998 CG MET 2999 SD MET 3000 CE MET 3001 C MET 3002 0 MET 3003 N THR 3004 CA THR 3005 CB TRF 3006 OGI THR 3001 C62 TR 3008 C TER 3009 0 THR 3010 N SEP 3011 CA SER 3012 CB SER 3013 OG SER 3014 "C SER 3015 0 SER 3016 N HIS 3011 CA HIS 3018 CB HIS 3019 CG HIS 3020 CD2 HIS 3021 NDI HIS 3022 CEl HIS 3023 NE2 HIS 3024 C HIS 3025 0 HIS 3026 N ILE 3021 CA ILE 3028 CB ILE 3029 CG2 ILE 3030 CGI ILE 3031 CD1 ILE 3032 C ILE -3033 0 ILE 3034 N ARG '44 i45 645 45 645 :45 645 645* 646 646 646 646 646 646 646 641 641 64'1 641 641 641 641 641 641 648 E48 648 648 f48 648 648 649 649 649 649 649 649 649 650 650 650 650 650 650 650 650 M51 651 651 651 651 651 651 652 452 652 652 652 652 523 653 6.53 553 053 653 453 653 653 654 654 654 654 654 654 654 654 655 46.148 48.918 12.209 1.

46.806 46.824 12.588 1.

46.832 45.392 12.229 1.

41.530 41.049 73.851 1.

48.219 45.146 14.038 1.

41.321 44.142 13.302 1.

48.415 48.118 13.512 1.

49.211 48.142 72.605 1.

48.433 49.229 74.315 1.

41.682 49.431 15.618 1.

49.334 50.350 14.105 1.

49.004 51.345 15.217 1 41.619 50.941 75.614 1 50.809 49.956 74.116 1 51.204 48.918 14.679 1 51.620 50.186 13.410 1 53.043 50.546 73.383 1 53.753 51.217 14.552 1 53.188 52.131 14.380 1 54.239 53.410 15.640 1 53.641 53.215 16.115 1 55.175 54.305 15.563 1 53.485 49.082 13.218 1 54.508 48.691 13.195 1 52.735 48.316 12.384 1 53.029 46.899 12.062 1 51.832 45.984 12.452 1 51.552 46.119 )3.852 52.134 44.533 12.141 1 53.295 46.161 10.534 1 52.584 41.310 69.715 1 54.320 45.968 10.131 1 55.333 45.245 70.941 54.610 45.819 68.713 56.106 45.495 68.711 56.233 44.592 69.819 53.827 44.101 68.015 52.95 1 44.106 68.705 !4.224 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 56.511 40.141 64.031 52.112 43.354 65.975 51.478 42.289 65.991 51.581 44.546 65.891 50.136 44.808 65.906 49.858 46.198 65.323 50.419 41.191 66.162 48.364 46.502 65.181 49.353 43.14 C5.039 48.309 43.264 65.454 49.866 43.418 63.929 49.110 42.623 62.863 49.510 42.949 61.416 '50.405 41.990 60.995 49.235 41.114 63.151 49.034 40.261 62.214 49.521 40.795 64.390 49.584 39.399 64.805 50.991 39.011 65.253 51.892 38.953 64.029 52.285 31.884 63.288 52.411 40.011 C3.438 53.111 39.668 62.395 53.011 38.36' 62.291 48.4'16 39.163 65.830 41.989 38.044 65.994 48.046 40.234 66.410 41.012 40.145 67.580 41.059 41.456 f8.355 46.252 41.368 6).653 48.469 41.891 (8.163 48.560 43.36? 69.131 45.633 39.187 61.156 44.981 40.508 66.395 45.214 38.661 C7.7:3 00 12.33 00 10.61 00 10.41 00 1.59 00 10.22 00 9.51 00 9.51 00 11.11 .00 9.63 00 9.61 .00 9.90 .00 9.95 .00 11.92 .00 13.01 .00 14.24 .00 13.38 .00 14.59 .00 15.62 .00 19.18 .00 20.10 .00 22.18 .00 19.41 .00 14.31 .00 18.36 .00 11.24 .30 9.00 .00 9.19 .00 10.10 .00 8.04 .00 9.21 00 9.52 .00 1.20 1.00 6.54 1.00 6.88 1.00 5.46 1. 0r 3.39 1.00 8.17 1.00 9;10 1.00 9.01 1.00 9.79 1.00 8.66 1.00 1.85 1.00 1.28 1.00 2.00 i.00 11.50 1.00 13.41 '.00 11.63 !.00 12.15 1.00 13.04 1.00 14.61 1.00 15.14 1.00 12.51 1.00 16.15 1.00 11.13 1.00 6.89 1.00 5.16 1.00 4.04 1.00 1.54 1.00 9.34 1.00 1.1 1.00 6.49 1.00 6.61 1.00 9.19 1.00 9.28 00 10.33 1.00 5.42 1.00 '.91 00 4.62 1.00 5.90 1.00 5. 1 1.o0 4.75 1.00 3.95 30 5.93 1.00 3.24 1.00 2.00 1.00 1.10 .00 39 1.00 5.10 4 6 1 3 '1 6 6 4 1" bref21c.pdb Thu Apr 25 12:27:47 1996

ATOM

ATCOM

ATOM

ATCOM

ATOM

ATCOM

ATOM

3035 CA ARG 3036 CB ARG 3031 CG ARG 3038 CD ARG 3039 NE ARG 3040 CZ ARG 3041 NHI ARG 3042 NH2 ARG 3043 C ARG 3044 0 ARG 3045 N TYR 3046 CA TYR 3047 CB TYR 3048 CG TYR 3049 CD1 TYP.

3050 CE1 TYR 3051 CD2 TYR 3052 CE2 TYR 3053 CZ TYR 3054 OH TYR 3055 C TYR 3056 0 TYR 3057 N GLO 3058 CA GLU 3059 CB GLU 3060 CC GLO 3061 CD GLU 3062 O1 GLU 3063 OE2 GLU 3064 C GLU 3065 0 GLD 3066 N VAL 3061 CA VAL 3068 CB VAL 3069 CG1 VAL 3070 CG2 VAL 3071 C VAL 3072 0 VAL 3073 N ASP 3074 CA ASP 3075 CB ASP 3076 CG ASP 3077 ODI ASP 3078 OD2 ASP 3079 C ASP 3080 0 ASP 3081 N VAL 3082 CA VAL 3083 CB VAL 3084 CGI VAL 3005 CG2 VAL 3086 C VAL 3087 0 VAL 3089 N SER 3099 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 CE ASN 3106 CG ASN 3107 0D1 ASN 3108 ND2 ASN 3109 C ASN 3110 0 ASN 31L1 N GLY 3112 CA GLY 655 655 655 655 655 655 655 655' 655 655 656 656 656 656 656 656 656 656 656 656 656 656 657 657 651 657 6571 651 651 657 657 658 658 658 658 658 658 658 659 659 659 659 659 659 659 659 460 660 660 660 660 660 660 661 661 661 661 661 661 662 662 662 662 662 643 663 663 663 664 664 664 664 664 664 664 664 66 665 43.856 38.107 67.582 I.

43.947 36.608 61.851 1.

42.732 35.835 61.393 1I 42.923 35.234 66.013 1 41.690 35.243 65.243 1 41.487 34.509 64.1!5 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 69.706 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 70.366 1 42.779 43.407 10.461 1 43.422 43.826 69.307 1 44.498 44.701 69.373 1 39.693 38.646 69.848 1 39.504 37.608 69.210 1 38.967 39.048 70.905 1 31.776 38.359 11.431 1 38.109 37.385 12.555 1 36.874 36.766 73.2171 1 36.755 35.254 72.9711 1 36.157 34.838 :1.945 37.245 34.472 -3.826 36.827 39.366 72.006 37.163 40.033 72.985 35.635 39.428 71.412 34.550 40.334 11.819 33.826 40.908 70.578 32.355 41.228 70.903 34.552 42.151 70.055 33.518 39.602 72.697 33.025 38.519 72.336 133.168 40.225 73.818 32.217 39.660 14.762 32.857 39.583 16.152 31.841 39.320 177.262 31.708 40.220 78.127 31.191 38.238 17.248 30.959 40.488 14.877 30.946 41.480 15.641 29.924 40.096 74.127 28.623 40.775 74.150 27.835 40.550 72.851 28.760 40.397 11.683 26.931 39.368 72.990 27.768 49.299 75.335 27.719 39.092 75.635 27.018 41.218 75.943 26.210 40.865 77.104 27.146 40.683 78.308 18.007 39.569 71.169 25.132 41.882 77.544 24.814 42.901 76.839 24.676 41.596 18.784 23.690 42.325 79.598 23.909 43.856 79.493 22.242 41.933 73.339 21.935 40.739 79.266 21.367 42.948 79.300 19.936 42.775 79.041 19.124 41.953 80.038 18.542 40.929 -9.649 19.032 42.453 81.277 18.317 41.81S 82.410 17.157 42.106 82.938 15.907 42.725 82.013 15.-91 43.57 81.:14 14.939 41.852 82.294 11.831 40.352 82.334 16.976 39.992 e..488 18.250 39.511 8:.243 11.918 38.122 82.294 .00 4.10 6 .00 6.54 6 .00 12.78 .00 19.16 .00 25.22 .00 28.18 .00 29.93 .00 30.11 .00 4.93 .00 4.71 .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 00 9.06 1.00 11.39 1.00 14.16 L.00 17.29 1.00 19.32 1.00 18.57 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 15.57 1.00 16.39 1.00 15.s80 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 :.00 22.72 1.00 24.09 1.00 25.i A 1.00 27.33 1.00 28.05 1.00 29.36 1.00 26.86 1.00 25.-8 1.00 32 OC 24.45 :.00 24.29 6 6 6 7 6 8 6 6 6 6 6 6 6 -7 6 6 6 6 6 8 6 6 6 6 6 a 4 8 6 6 1 .3 .4 4 43 1 1 4 4 :1

I

*i *i

II

-71bret21c.pdb Thu Apr 25 12:27:47 1996 41

ATO

ATC

ATO

ATC

ATO

AT<

AT(

AT4

AT

ATI

AT

A1

AT

A1

A;

A1

A

A1

A

H 3113 C GLY 6 1 3114 0 GLY 6 H 3115 N ALA 6 v 3116 CA ALA 6 )M 3117 CB ALA 6 )M 3118 C ALA 6 )M 3119 0 ALA 6 M 3120 N GLY 6 )H 3121 CA GLY 6 H 3122 C GLY 6 OH 3123 0 GLY 6 OM 3124 N SER 6 OH 3125 CA SER 6 CH 3126 CB SER 6 DH 3127 OG SER 6 OH 3128 C SER 0H 3129- 0 SER OH 3130 N VAL OH 3131 CA VAL C4 3132 CB VAL CH 3133 CG1 VAL OH 3134 CG2 VAL OM 3135 C VAL OM 3136 0 VAL OM 3131 N GLN OCH 3138 CA GLN 'O4 3139 CB GLN 0OH 3140 CG GLN *OH 3141 CD GLN O4 3142 OE1 GLN OM 3143 NE2 GLN OC 3144 C GLN OM 3145 0 GLN OH 3146 N ARC TOM 3147 CA ARC CMH 3148 CB ARG TCM 3149 CG ARC COH 3150 CD ARG TOM 3151 NE ARG TOM 3152 CZ ARG TOM 3153 NH1 ARG TOM 3154 NH2 ARC TOM 3155 C ARG TOM 3156 0 ARG TOH 3157 N VAL TOM 3158 CA VAL TOM 3159 CB VAL TOM 3160 CG1 VAL TW 3161 CG2 VAL TOM 3162 C VAL TCW 3163 0 VAL TCH 3164 N GLO kTCH 3165 CA GLO LTCH 3166 CB GLU TOM 3167 CG GLU TOM 3168 CD GLU kTOM 3169 OE1 GLU ATCH 3170 OE2 GLO ATOM 3171 C GLU ATOM 3172 0 GLU ATOM 3173 N ILE ATOM 3174 CA ILE ATOM 3175 CB ILE ATOM 3116 CC2 ILE ATOMH 177 CG1 ILE ATOM 3172 CDI ILE ATOM 3179 C ILE ATOM 3180 0 ILE ATOM 3181 N LEU ATOM 3182 CA LEU ATOM 3183 CB LED ATOM 3184 CG LEU ATOM 3185 CD1 LEU ATOM 3186 CD2 LEO ATOM 3187 C LEU ATOM 3188 0 LED ATOM 3189 N CLU ATOM 3190 CA GLU 65 65 66 66 66 66 66 67T 67 67 67 68 68 68 668 i68 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 67'.

675 675.

675 675 675 675 676 676 18.560 37.239 82.235 1.0 18.754 36.011 82.454 1.0 18.161 37.805 81.047 1.C 19.457 37.054 80.035 1.C 19.331 37.724 78.693 1.C 20.893 37.166 80.577 1.c 21.300 38.225 61.075 1.

21.579 36.036 80.672 1.

22.941 36.058 8L.159 1.

23.838 35.946 79.949 24.789 35.145 79.937 1.1 23.483 36.689 78.896 1.

24.256 36.669 77.641 1.

23.634 37.605 76.547 1.

24.312 37.574 75.278 1.

25.597 37.209 78.057 1.

25.647 38.220 78.798 1.

26.623 36.397 77.762 1.

28.049 36.715 77.987 1.

28.665 35.974 79.266 1.

28.460 34.484 79.178 1.

30.175 36.316 79.456 1.

28.668 36.266 76.644 1.

29.846 35.888 76.545 1.

27.845 36.409 75.59i 1.

28.193 36.009 74.245 27.005 36.236 73.312 I.

27.182 35.569 71.935 1 27.933 36.432 70.902 1 28.500 37.485 71.234 1 27.912 35.995 69.634 1 29.519 36.583 73.696 1 29.792 37.782 73.770 1 30.332 35.679 73.157 1 31.631 36.013 72.639 1 32.678 35.334 73.517 1 32.946 36.061 74.887 1 32.493 35.269 76.139 1 32.986 35.894 77.368 1 33.863 35.344 78.218 1 34.370 34.124 78.021 1 34.304 36.062 79.241 1 31.869 35.669 71.158 31.425 34.618 70.645 1 32.576 36.556 70.460 32.879 36.337 69.049 32.079 37.317 68.160 30.649 37.440 68.682 32.728 38.702 68.133 34.379 36.538 68.849 34.964 37.495 69.358 35.011 35.587 68.184 36.437 35.666 67.911 36.902 34.409 67.150 36.621 34.525 65.601 36.996 33.299 64.759 '36.964 32.153 65.300 37.279 33.501 63.537 36.645 36.859 66.978 35.688 37.420 66.456 37.899 37.192 66.108 38.224 38.270 65.790 38.340 39.659 66.498 38.785 40.718 65.483 37.060 40.044 67.289 35.824 40.386 66.489 39.596 37.922 65.198 40.511 37.502 65.909 39.722 38.012 63.884 41.000 37.737 63.251 40.846 37.553 61.744 40.335 36.155 61.359 38.786 36.050 61.326 40.961 35.743 60.014 41.944 38.895 63.585 41.500 40.013 63.920 43.240 38.587 63.521 44.316 39.514 63.829 '0 23.94 A 0 24.01 0 22.31 7 00 22.71 30 21.95 s 00 24.38 4 00 25.18 8 00 25.52 7 00 26.48 s 00 28.11

A

00 29.47 00 28.73 7 00 28.04 6 00 28.80 6 00 24.54 8 00 27.60 6 00 27.37 8 00 26.59 7 00 23.08 00 20.59 6 00 19.42 00 20.06 00 21.55 00 20.19 00 20.21 .00 18.75 .00 17.59 .00 22.13 .00 22.70 .00 24.66 .00 23.69 .00 17.46 .00 15.56 .00 13.69 .00 16.60 .00" 17.57 .00 19.96 .00 18073 .00 19.78 .00 19.40 .00 17.08 .00 17.95 00 18.54 1.00 20.62 00 18.18 i.00 15.30 1.00 15.97 1.00 17.58 1.00 17.86 1.00 14.22 14.18 1.00 13.30 1.00 14.85 17.98 00 21.07 00 22.50 ;.00 20.19 00 23.59 :.00 14.79 1.00 15.66 00 15.73 00 15.34 :.00 16.72 :.00 15.50 00 15.11 00 12.07 L.00 16.94 1.00 15.56 ".00 18.65 00 16.13 ".00 16.02 :.00 17.94 OC 13.53 ".00 18.65 :.00 16.58 :.00 16.45 00 14.67 00 12.70 6 6

I

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a 7 6 8 6 6 6 6 6 7 6 8 7 6 1 6 6 7 6 6 4 6 7 7 6 9 1 6 6 4

S

8 7 6 6 4 4 9 6 9 7 o 6 3 4 3 7 4 4 s 3

I

4 -72bref2lc.pdb Thu Apt 25 12:27:47 1996

ATOM

ATCHO

ATOM

ATCHOM

ATOM

ATCOM

ATOM

ATCHOM

ATOM

ATCHOM

ATOM

ATCHM

ATOM

ATCHM

ATOM

ATCHOM

ATOM

ATCHOM

ATOM

ATCHOM

ATOM

ATCHOM

ATOM

ATCHOM

ATOM

ATCHOM

ATOM

ATCHOM

ATOM

ATCHOM

ATOM

ATCHOM

ATOM

ATCHOM

ATOM

ATCHOM

ATOM

ATOMH

ATCHOM

ATOM

ATCHOM

ATOM

3191 C GL0 3192 CG GLU 3193 CD GLD 3194 OEI GLU 3195 OE2 GLS 3196 C GLU 3197 0 GLU 3198 N GLY 3199 CA GLY 3200 C GLY 3201 0 SLY 3202 N ARG 3203 CA ARG 3204 CB ARG 3205 CG ARG 3206 CD ARC 3207 NE ARG 3208 CZ ARG 3209 H1 ARG 3210 NR2 ARG 3211 C ARG 3212 0 ARC 3213 N THP.

3214 CA BP..

3215 CB TIP.

3216 001 7TP.

3217 CC2 3218 C 7HP.

3219 0 7?.

3220 N C:L 3221 CA GL3 3222 CB GLU 3223 CG GLU 3224 CD GLU 3225 OE1 GLU 3226 OE2 GLU 3227 C GLO 3228 0 GLU 3229 N CYS 3230 CA CYS 3231 CB CY 3232 SG CtS 3233 C CS' 3234 0 ~S 3235 N ';AL 3236 CA *AL 3237 CB 7AL 3238 CG1 *;kL 3239 CG2 ';AL 3240 C "AL 3241 0 .7-L 3242 N :L= 3243 CA "L.

3244 CB .r 3245 CG 3246 CD1 I"- 3247 CD2 L.: 3248 *C LX- 3249 0 3250 N ZER 3251 CA :.7 3252 CB 5Z; 3253- OG SE 3254 C 3255 0 3256 N A:N 3257 CA A: 3258 CB 3259 CG As 3260 OD1 Z 3261 ND2 ;,3X 3262 C AS 3263 0 3264 N :Z- 3265 CA 3266 CB 3267- CG L:r 3268 CD1 616 676 676 676 6176 676 676 677 671 677 677 678 678 678 678 678 678 678 678 678 678 678 679 679 679 679 679 679 679 680 680 680 680 680 680 680 680 680 681 681 681 681 681 681 682 682 682 682 682 682 682 683 683 683 683 683 683 683 683 684 684 684 684 684 684 684 685 685 685 685 685 685 685 685 686 686 686 686 686 45.667 38 45.627 31 45.494 36 46.538 36 44.367 35 44.268 4C 43.569 41 45.030 41 45.121 43 43.796 43 43.770 44 42.700 4: 41.387 4 40.342 4: 39.529 4: 40.401 4; 41.014 4 41.887 4 42.214 4 42.380 3 41.001 4 41.199 4 40.462 4 40.027 4 40.996 4 41.204 4 42.332 4 38.637 4 38.393 4 37.732 4 36.358 4 36.289 4 36.140 4 35.086 4 34.342 4 33.019 4 35.489 35.887 34.299 33.382 33.617 32.134 31.958 31.5179 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 26.081 25.003 25.222 26.502 23.614 22.800 23.397 22.049 21.716 22.993 23.994 22.972 21.748 22.271 20.099 20.583 21.779 22.718 23.700 .907 63 .882 62 .518 63 .007 63 .967 63 0.836 63 1.007 62 1.772 6 3.103 6 3.794 6 4.949 6 3.134 6 3.743 6 2.666 6 2.932 6 2.681 6 1.368 6 0.845 5 1.525 5 9.631 6 4.532 6 4.034 6 5.743 6 6.552 6 7.685 6 8.405 6 7.148 6 7.171 6 18.336 6.384 6.812 1.765 4 17.101 4 17.782 17.032 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 44.318 43.294 43.584 43.127 43.741 41.638 43.730 44.610 43.161 43.521 42.906 43.25'? 43.199 44.106 41.945 41.496 40.428 39.749 40.433 38.406 40.9718 39.905 41.704 41.260 41.525 42.760 42.840 .526 .478 .080 1.546 .108 3.146 2.159 3.699 3.145 2.961 2.323 3.329 3.174 2.927 1.695 0.504 0.643 9.187 8.700 0.037 4.420 5.529 4.249 5.390 5.669 4.448 6.229 5.182 .5.540 4.604 54.332 63.128 61.755 60.847 60.138 60.825 64.076 63.364 64.654 64.498 63.603 66.606 64.540 635.448 63.517 63.511 62.131 60.969 61.867 64.001 63.342 65.258 65.859 67.348 68.299 69.661 68.381 65.104 65.544 63.914 63.02 61.629 61.06' 63.49: 63.69 63.82 64.13 63.08 62.50 62.18 62.40 65.53 (5.92 66.28 671.64 68.58 68.41 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 11.52 1.00 11.01 1.00 11.91 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 19.04 1.00 18.69 1.00 18.32 1.00 18.05 1.00 16.53 1.00 14.40 1.00 21.29 1.00 22..4 1.00 22.91 1.00 24.61 1.00 26.42 1.00 26.71 1.00 24.30 1.00 23.64 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 1.00 17.50 1 1.00 13.82 1.00 13.45 1.00 15.36 1.00 24.03 1.00 24.27 4 1.00 25.99 8 1.00 26.98 9 1.00 31.20 7 1.00 36.99 1 1.00 26.69 9 1.00 27.76 6 1.00 24.94 1 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 21.14 7 1.00 23.95 19 1.00 24.26 14 1.00 22.44 14 1.00 23.417 08 00 21.84 -73bref21c.pdb Thu Apr 25 12:27:47 1996 43 *4 4

ATOM

ATCH

ATOM

ATCH

ATOM

ATCHOM

ATOM

ATCHOM

ATOM

ATCO

ATOM

ATOH

ATOt ATOt

ATO

ATOt

ATOI

ATO

3269 CD2 LEU 61 3210 C LED 61 3211 0 LEO 61 3272 N ARG 6 3213 CA ARC 6 3214 CB ARG 6 3275 CC ARG 6 3216 CD ARC 6 321177 NE ARG 6 3218 CZ ARG 6 3279 NH1 ARG 6 3280 NH2 ARG 6 3281 C ARG 6 3282 0 ARG 6 3283 N GLY 6 3284 CA GLY 6 3285 C GLY 4 3286 0 GLY 6 3287 N ARG 3288 CA ARG 3289 CB ARG 3290 CG ARG 3291 CD ARG 3292 NE ARG 3293 CZ ARG 3294 N1 ARG 3295 NH2 ARG 3296 C ARG 3291 0 ARG 3298 N THR 3299 CA THR 3300 CB THR 3301 OG1 THP.

3302 CG2 THR 3303 C THRR 3304 0 TRR 3305 N ARG 3306 CA ARG 3307 CB ARG 3308 CG ARG 3309 CD ARG 3310 NE ARG 3311 CZ ARG 3312 HH1 ARG 3313 NH2 ARG 3314 C ARG 3315 0 ARG 3316 N TYR 3317 CA TYR 3318 CB TYR 3319 CG TYR 3320 CDI TTR 3321 CEI TYR 3322 CD2 TYR 3323 CE2 TYR 3324 CZ TYR 3325 OH TYR 3326 *C TYR 3321 0 TYR 3328 N TRR 3329 CA THR 3330 CB THR 3331 OG1 THR 3332 CG2 THR 3333 C THP.

3334 0 THR 3335 N PHE 3336 CA PHE 1 3331 CB PHE 3338 CC PHE H 3339 CD1 PRE 4 3340 C02 PHE M 3341 CE1 PHE 1 3342 CE2 PHE M 3343 CZ PHE M 3344 C PHRE S.3345 0 PHE H 3346 N ALA 86 86 86 87 al 87 87- 87 87 81 87 871 .88 88 88 688 689 689 689 689 689 689 689 689 689 689 689 690 690 690 690 690 690 690 691 691 691 691 691 691 691 691 691 691 691 692 692 692 692 692 692 692 692 692 692 692 692 693 693 692 692 693 69 692 694 694 694 694 694 694 694 694 694 694 694 69 23.563 42.742 67.173 1.C 19.233 41.566 68.375 1.C 18.361 40.669 68.478 1.C 19.035 42.801 68.858 1.0 17.838 43.147 69.636 1.

18.117 42.901 71.113 1.

17.254 41.847 11.745 1.4 17.778 40.471 11.410 1.4 16.883 39.426 71.911 L.1 16.832 38.188 71.416 1.1 17.636 37.837 10.405 1.

15.969 37.303 11.908 1.

17.358 44.587 69.517 1.

17.863 45.369 68.695 1.

16.420 44.939 10.401 1.

15.825 46.263 10.434 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 13.902 1.

13.543 49.819 74.581 1.

13.398 50.988 13.575 1.

14.071 52.266 73.908 1.

14.201 52.828 75.121 1.

13.738 52.253 16.250 1.

14.704 54.066 75.213 1 16.425 41.958 74.648 1 16.512 48.542 15.756 1 17.153 46.887 74.313 1 18.053 46.127 75.182 1 18.530 44.902 14.403 1 17.550 44.550 13.405 1 18.808 43.136 15.355 1 19.337 46.821 75.661 1 20.052 47.436 74.841 1 19.653 46.704 76.966 1 20.920 47.275 77.514 1 '20.908 41.426 79.055 1 21.668 46.303 19.660 1 21.736 46.597 81.403 1 22.360 45.549 82.240 1 21.681 44.632 82.957 1 20.331 44.612 82.931 1 22.337 43.77115 83.768 22.024 46.269 77.114 21.863 45.028 17.231 23.157 46.781 16.682 24.2:3 45.893 76.256 24.237 45.885 74.744 23.317 44.905 74.100 23.303 43.575 14.501 22.544 42.636 13.833 22.535 45.283 73.014 21.755 44.345 12.325 21.772 43.022 12.745 21.021 42.086 12.059 25.534 46.436 76.739 25.776 47.643 76.606 26.382 45.567 77.302 27.711 45.989 77.758 27.877 45.985 79.301 26.746 46.642 19.909 29.155 46.745 19.685 28.-73 45.070 11.062 28.450 43.870 76.926 29.811 45.661 76.604 30.841 44.969 75.845 30.833 45.501 14.405 29.451 45.682 13.816 28.740 46.060 14.043 28.882 44.679 73.015 27.430 41.035 73.481 27.617 44.854 12.450 26.919 46.024 12.679 32.137 45.210 76.374 32.!33 46.304 76.835 33.112 44.227 16.155 40 20.88 i 00 26.62 6 00 27.06 8 o0 25.21 00 21.90 00 21.00 6 00 18.87 6 00 20.25 00 23.51 7 00 24.71 00 25.89 00 23.14 7 00 23.317 00 24.06 3 00 23.19 7 00 22.75 6 00 23.19 6 00 21.67 8 00 23.01 1 00 23.10 6 00 22.81 6 00 20.45 00 18.41 .00 17.79 .00 19.24 .00 12.88 .00 18.11 .00 25.87 .00 25.28 .00 25.78 .00-23.94 .00 24.95 .00 24.96 .00 24.38 .00 27.33 .00 25.88 .00 28.66 .00 21.60 .00 28.38 .00 30.17 .00 30.51 .00 29.33 1.00 31.23 1.00 32.13 1.00 26.34 1.00 27.81 1.00 28.65 1.00 27.19 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 00 19.71 1.00 16.44 1.00 16.79 1.00 14.83 1.00 14.75 1.00 14.22

I

1

U

6 8 4 1 8 1 7 6 4 8 6 1 8 7 6 6 4 6 8 1 1 1 4 4 8 6 4 4 4 6 6 4 8 4 8 .9

A

7 o 3 4

R

6 6 6 6 6 8 8 4.4444 4. 4 -74bref21c.pdb Thu Apr 25 12:27:47 1996 44 a.

S

ATOM

ATCOM

ATOM

ATCOM

ATOM

334"1 CA ALA 3348 CB ALA 3349 C ALA 3350 0 ALA 3351 N VAL 3352 CA VAL 3353 CB VAL 2354 CG1 VAL 3335 CG2 VAL 3356 C VAL 3357 0 VAL 3358 N ARC 3359 CA ARC 3360 CB ARC 3361 CG ARC 3362 CD ARC 3363 NE ARC 3364 CZ ARC 3365 NR1 ARC 3366 NH2 ARG 3367 C ARC 3368 0 ARC 3369 N ALA 3310 CA ALA 3371 CB ALA 3312 C ALA 3373 0 ALA 3374 N ARC 3375 CA ARC 3376 CB ARG 3377 CG ARC 33178 CD ARC 3379 NE ARC 3300 CZ ARG 3381 NHIl ARC 3382 NH2 ARC 3383 C ARG 3384 0 ARG 3385 N MET 3386 CA MET 3387 CB MET 33988 CG MET 3389 SD MET 3390 CE MET 3391 C MET 3392 0 MET 3393 N ALA 3394 CA ALA 3395 CB ALA 3396 C ALA 3397 0 ALA 3396 N GLO 3399 CA GLO 3400 CB GLD 3401 CG GLU 3402 CD GLU 3403 0E1 GLO 3404 -OE2 GLO 3405 C GLU 3406 0 GLO 3407 N PRO 3408 CD PP.0RO 3409 CA PRO 3410 CB PRO 2411 Cc PRO 3412 C PRO 3413 1 PRCO 3414 N SER 3415 CA SEP 3416 CS SER 3417 ,C SER 3418 C SER Z.19 SEB 3420 N PHE 3421 CA PHE 3422 CB PHE 3423 CG PRE 3424 CC1 PHE 695 695 695 695 696 696 696 696 696 696 696 697 691 69? 691 691 691 691 691 691 691 697 698 698 696 698 698 699 699 699 699 699 699 699 699 699 699 699 700 700 700 700 700 700 700 700 701 701 701 701 701 702 702 702 702 702 702 702 702 702 703 703 703 703 703 703 103 704 704 704 704 104 704 701 015 105 70! 705 34.532 44.271 .6.533 1.00 14.58 34.704 43.821 17.959 1.00 15.52 35.331 43.352 15.579 1.00 16.59 34.739 42.503 74.883 1.00 16.711 36.663 43.475 75.554 1.00 18.89 37.475 42.631 14.640 1.00 18.54 31.455 43.242 13.198 1.00 19.19 31.867 44.705 73.223 1.00 17.15 38.335 42.446 72.255 1.00 20.60 38.923 42.284 75.047 1.00 18.61 39.654 43.093 75.631 1.00 18.43 39.321 41.055 14.738 1.00 18.97 40.675 40.563 75.050 1.00 18.67 40.593 39.173 75.664 1.00 17.03 39.72 39.078 76.889 1.00 15.40 39.842 37.650 1177.417 1.00 18.07 39.071 36.676 76.632 1.00 17.47 38.722 35.467 77.081 1.00 19.24 39.061 35.070 78.309 1.00 20.70 38.014 34.643 76.318 1.00 18.93 41.625 40.494 73.818 1.00 18.98 41.180 40.255 72.617 1.00 19.20 42.926 40.660 74.077 1.00 17.10 43.973 40.609 73.057 1.00 14.99 44.816 41.858 13.146 1.00 15.98 44.838 39.366 13.296 1.00 14.49 45.073 38.999 14.432 1.00 16.90 45.349 38.753 12.234 1.00 13.57 46.174 37.540 12.325 1.00 10.72 45.229 36.331 72.392 1.00 12.04 45.692 35.014 71.1794 1.00 12.63 46.738 34.349 72.665 1.00 20.39 46.913 32.910 72.399 1.00 21.37 46.119 31.955 72.895 1.00 21.92 45.069 32.257 73.672 1.00 21.47 46.442 30.682 72.710 1.00- 22.33 47.090 37.470 71.094 1.00 9.38 46.680 37.820 69.991 1.00 10;.96 48.355 37.109 11.282 1.00 8.21 49.263 37.029 10.140 1.00 7.21 50.724 36.955 70.551 1.00 6.01 51.322 38.292 10.963 1.00 5.33 52.092 39.250 69.678 1.00 9.84 51.368 40.792 69.955 1.00 8.49 48.875 35.808 69.375 1.00 6.64 48.609 34.755 69.939 1.00 6.32 48.849 35.943 68.069 1.00 7.50 48.425 34.837 67.250 1.00 8.94 47.605 35.361 66.065 1.00 7.41 49.483 33.855 66.779 1.00 9.12 50.679 34.165 66.639 1.00 9.86 48.980 32.669 66.491 1.00 10.01 49.763 31.574 65.987 1.00 13.16 48.971 30.275 66.108 1.00 15.92 48.724 29.784 67.501 1.00 18.17 48.597 28.284 67.507 1.00 21.01 4"7.904 27.731 66.611 1.00 22.10 49.233 27.652 68.377 1.00 24.81 50.126 31.770 64.510 1.00 13.07 49.560 32.617 63.802 1.00 12.10 51.106 30.986 64.037 1.00 14.95 51.501 30.820 62.625 1.00 17.31 51.783 30.001 64.899 1.00 14.84 51.896 28.794 63.999 1.00 14.77 52.253 29.467 62.635 1.00 19.35 53.150 30.488 65.409 1.00 13.50 53.801 29.774 66.157 1.00 15.09 53.587 31.681 65.002 1.00 11.82 54.873 32.218 65.461 1.00 9.78 55.156 33.574 64.798 1.00 9.23 55.301 33.474 63.394 1.00 8.65 54.860 32.386 61.003 1.00 11.09 55.621 31.729 61;.736 ".00 12.01 53.937 33.229 61.468 1.00 8.75 53.761 33.532 68.857 1.00 3.52 5!.323 34.973 68.988 1.00 :.-09 54.159 35.924 68.184 1.OC 7.49 53.696 36.417 66.957 1.OC 8.92 bref2lc.pdb Thu Apr 25 12:27:47 1996 r rr r i r rr r r r ATOM 3 ATCM 3 ATOM 3 ATOM 3 ATOM 3 ATOM 3 ATOH 3 ATOM 3 ATOM 3 ATOH 3 ATCOM 3 AT0 3

ATOM

ATOm

ATOM

ATCH

ATOM

ATCH

ATOM

ATON

ATOM

ATCHo

ATOM

ATCH

ATOCM

ATCH

ATOM

ATCM

ATOM

ATCH

ATOM

ATCOM

ATOM

ATCHm

ATOM

ATOC

ATOM

ATCOM

ATOM

ATCHM

ATOM

ATOHM

ATOM

ATOm

ATOM

425 426 427 428 429 430 431 432 433 434 435 436 4437 3438 1439 3440 3441- 1(- 3442 3443 3444 3445 3446 3447 3448 3449 3450 3451 3452 3453 3454 3455 3456 3457 3458 3459 3460 3461 3462 3463 3464 3465 3466 3461 346 346 347 347 347: 347 347 347 347 347 347 347 348 34' 348 348 34B 348 34' 34 34 34 34 34 34 34 34 34 34 34 34 34 35 -35 CD2 PRE 70 CE1 PRE 70 CE2 PHE 70 cz PHE 70 C PRE 7 0 PEE 7 N CLY 7 CA GLY 7 S GLY 7 0 CLY 7 N GLY 7 CA GLY 7 C GLY 7 0 GLY I N PHE 7 CA PRE 7 CB PBE I CG PRE 7 CD1 PRE 1 CD2 PRE 7 CE1 PHE 1 CE2 PRE 1 CZ PHE C PE 0 PRE N TP CA TPP CB TRP CG TRP CD2 TRP CE2 TRP CL3 TRP CD1 TRP NEI TR CZ2 TRP CZ3 TRP CH2 TRP C TRP O TRP N SER CA SER CB SER G00 SEP 6 C SER 9 O SER 0 N ALA L CA ALA 2 CB ALA 3 C ALA 4 0 ALA 5 N TRP 6 CA TRP 7 CB TRP 8 CG TRP 9 CD2 TRP 0 CE2 TRP 1 CE3 TRP 2 CD1 TRP 3 NEl TRP 4 CZ2 TRP 5 CZ3 TRP 6 CH2 TRP 97 C TRP 8 -O TRP 89 N SEP.

90 CA SER 91 CS SER 92 G00 SEP.

93 C SER 94 O SER 95 N GLO 96 CA GLC 97 CB GL 98 CG GLC 99 CD GLU 00 OE1 GLC 01 OE2 GLC 02 C GLU 05 45 45 75 05 05 076 06 06 06 01 07 07 0-7 08 08 08 08 08 08 108 08 709 408 708 709 709 709 709 709 709 709 709 709 709 709 709 709 709 7109 710 710 710 710 710 710 711 712 711 711 112 712 712 712 712 712 712 712 712 712 712 712 7123 712 713 713 713 713 713 713 714 714 j14 714 714 714 714 714 55.446 36.

54.512 37.

56.270 37.

55.804 37.

52.783 32.

52.257 31.

52.634 32.

51.728 31.

51.661 32 52.345 33 50.829 32 50.738 32 49.465 32 48.894 31 48.993 33 47.801 33 48.171 33 49.358 33 49.196 31 50.638 33 50.296 31 51.730 32 51.370 31 46.846 35 47.260 36 45.562 34 44.475 35 43.114 3 42.417 3 42.098 3 41.465 3 42.283 3 41.971 3 41.398 3 41.018 3 41.838 3 41.214 3 ,44.635 3 44.770 3 44.620 3 44.765 3 45.040 4 43.847 4 43.522 42.531 43.580 42.435 42.855 41.432 41.810 40.155 39.159 31.751 37.202 36.1796 36.416 36.718 37.037 36.574 35.969 36.279 35.908 39.498 40.124 .9.174 39.366 39.294 37.973 38.161 37.081 38.309 37.163 -7.524 38.4170 38.699 39.860 37.'35 35. 885 284 68.

252 66.

115 67.

598 66.

591 69.

697 68.

.751 70.

.956 71.

.726 72.

.739 73 .295 73 .990 73 .823 75 .731 76 .927 76 .911 7 .981 78 .126 79 .787 79 .679 19 .016 79 .912 79 .587 80 .066 77 6.187 76 .77' 7 1.752 7 5.083 7 4.592 7 5.354 7 4.481 7 6.687 7 3.326 7 3.250 7 4.897 7 7.103 7 6.209 7 6.973 7 6.823 7 68.177 7 9.350 1 0.594 7 41.238 1 49.567 1 38.832 40.563 40.867 41.817 41.560 42.073 41.558 42.251 42.031 40.647 40.091 38.745 40.600 39.647 38.499 37.906 39.776 38.434 43.747 44.269 44.385 45.819 46.108 45.899 46.480 45.908 47.705 48.391 49.80s 49.836 51.236 51.479 52.074 48.366 611 163 833 606 505 878 .809 622 .932 .069 .878 .162 .977 .063 .540 .372 .874 .277 .592 .352 .974 .731 .040 .077 6.72i 4.285 4.119 7.396 6.165 4.999 4.092 4.634 5.929 4.689 2.841 3.399 2.513 8.056 9.268 7.508 8.351 7.501 7.15 49.21 49.13 80.01 80.89 81.99 79.96 78.91 80.32 79.52 80.09 79.84 78.51 78.80 71.27 80.7 80.1 77.7 76.2 76.5 79.5 80.4 18.3 78.1 76.6 76.1 18.1 78.1 79.2 19.8 81.

81.

82.

81.

79.

1.00 8.54 1.00 7.44 1.00 4.91 1.00 5.19 1.00 5.11 1.00 4.57 1.00 8.69 1.00 7.99 1.00 9.39 1.00 1.00 10.91 1.00 9.87 1.00 7.80 1.00 7.37 3 1.00 7.59 1.00 8.42 i 1.00 9.14 i 1.00 8.19 1.00 5.98 i 1.00 6.32 1.00 8.74 1.00 5.05 1.00 4.00 1.00 7.99 1.00 6.94 1.00 9.09 1.00 12.14 1.00 11.59 1.00 12.07 1.00 9.80 1.00 9.82 1.00 9.79 1.00 11.53 1.00 12.13 1.00 9.03 1.00 11.59 1.00 10.54 1.00 10.56 1.00 12.13 S1.00 11.52 1.00 12.14 1.00 9.78 7 1.00 10.05 6 1.00 12.22 9 1.00 17.16 6 1.00 12.01 4 1.00 12.49 3 1.00 12.98 5 1.00 13.23 5 1.00 14.99 6 1.00 13.85 7 1.00 12.59 2 1.00 8.73 5 1.00 8.57 6 1.00 8.04 9 1.00 8.30 0 1.00 4.78 19 1.00 8.29 50 1.00 8.70 83 1.00 8.46 62 1.00 7.52 20 1.00 9.00 20 :.30 12.59 60 12.C30 95 OC 15.!2 66 2.30 15.45 59 00 14.50 49 3C 11.86 99 1.00 15.88 64 2.30 18.64 79 1.00 17.04 88 1.00 20.29 76 21.4 447 1.00 24.61 978 2.00 24.4 420 1.00 27.8.

957 :.0c 25.69 027 1.OC 21.46 7 4 3

I

-76br2l1c.pdb ATCHOM 3303 0 GLO ATOM 3504 N PRO ATCH 3505 CD PRO ATOM 3506 CA PRO ATOM 3507 CB PRO ATOM 3508 CG PRO ATOM 3509 C PRO ATOM 3510 0 PRO ATOM 3511 N VAL ATOMH 3512 CA VAL ATOM 3513 CB VAL ATCH 3514 CG1 VAL ATCHOM 3515 CG2 VAL ATCH 3516 C VAL ATCM 3511 0 VAL ATOM 3518 N SER ATOM 3519 CA SER ATOM 3520 CB SER ATOM 3321 OG SER ATOM 3522 C SER ATOM 3523 0 SER ATOM 3524 N LED ATOM 3525 CA LED ATCM 3526 CB LED ATCH 3521 CG LEO ATOM 3528 CD1 LED ATCHM 3529 CD2 LEO ATOM 3530 C LEO ATOM 3531 0 LEO ATCH 3332 N LED ATOM 3533 CA LED ATOM 3534 CB LEO ATCM 3335 CG LED ATOM 3536 CD1 LED ATOM 3537 CD2 LEO ATOMC 3538 C LEO ATCH 3539 0 LEO ATOM 3540 N THR ATOM 3341 CA TRP.

ATOM 3542 CB TERP ATCH 3543 OG1 THR ATOM 3544 CC2 THP ATOM 3545 C TRP.

ATCOM 3546 0 THP.

Thu Apr 25 12:27:47 1996 714 715 115 715 115 715 715 7516 716 716 716 116 716 116 716 711 7111 7171 711 717 718 718 118 118 718 718 718 718 719 719 719 719 719 719 719 719 719 120 120 120 720 720 720 120 120 120 35.861 48.844 11.886 1.00 21.24 34.787 41.852 19.611 1.00 20.46 34.703 47.167 81.090 1.00 21.13 33.460 41.694 "9.015 1.00 19.23 32.621 41.183 80.182 1.00 21.32 33.226 41.974 81.352 1.00 19.98 32.814 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 16.910 1.00 19.79 31.769 50.100 15.440 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 16.900 1.00 21.79 29.515 48.182 16.624 1.00 20.72 28.859 50.269 77.264 1.00 22.27 21.439 49.911 77.331 1.00 21.09 26.920 50.181 78.164 1.00 23.89 27.182 49.064 19.601 1.00 24.17 26.552 50.748 76.315 1.00 20.65 26.541 51.970 76.394 1.00 19.78 25.838 50.014 75.523 1.00 21.29 24.666 50.583 14.385 1.00 21.71 25.009 49.949 73.188 1.00 17.72 24.502 50.860 72.051 1.00 15.29 25.271 52.1917 2.069 1.00 11.08 24.631 50.165 70.733 1.00 11.73 23.4711 50.236 75.183 1.00 22.58 23.399 49.506 -6.191 1.00 24.55 22.392 50.723 14.564 1.00 23.55 21.023 50.470 15.054 1.00 23.37 20.632 51.586 76.069 1.00 23.00 21.540 51.746 77.325 1.00 22.19 21.290 53.039 78.004 1.00 19.79 21.416 50.545 78.254 1.00 20.88 19.986 50.393 13.904 1.00 23.18 18.886 50.958 74.036 1.00 24.17 20.325 49.6517 72.828 1.00 22.42 19.498 49.515 11.597 1.00 21.89 19.038 48.042 71.295 1.00 22.41 18.198 41.332 12.513 1.00 24.25 20.042 41.288 70.444 1.00 20.14 18.263 50.417 71.492 1.00 22.94 17.140 49.941 71.240 1.00 22.69

S..

S

*5

S

*5 *SS S

S

S S *5 55 S S. S S S S S S S S S5 5 55 .55 Table I Data Set Resolution Reflections Completeness RZY Site@ 1A) 09(.10 00 Native 25.0-2.8 14158 .30 1) .0- R R Phasing Power RCullis RKrout, Phasing Powerl HgAc 2 25.0-3.0 1 1496 0.9) (0.91) 0.10 2 0.102 0.56 0.1141 Iso 1.87 13.lA) 0.008 no 1.3S 14.OA) U0 2 (140 3 25.0-3.0 11931 0.96 (0.94) 0.14 4 0.116 0.62 0.1371 iso 1.95 (3.1k) 2 )20.114 Ana 1.72 (3.9k) Refinement Statistics: RHS'"from ideal values Average B Value (A 2 Resolution RelflectLoflB Total Number R-vaiue Bond Length Bond Angle EBPl EBP2 Peptides F>1a of atoms 8.0-2.8 13894 3462 0.21 0.0161A) 2.1* 10.5 12.3 10.7 tR4Isor FPH-Fpl /EFp.

IR .lisEI Fpm±FdJ -FX~c~c)I /FN-Fpl for all centric ref lectionaS.

IR Kraut=El FPH(obs)_F~pl(C&1c) 4 F'PM(obsr-F*Ph(CAC) I I/E 1 ,b,+FPH(b) for all acentric relfections (anamalous case).

SPhase Power-(EIF FP~aI 2 /EI FPHobfsrFPC&1c) 12 )1/2 ;1 FPKC6s )_FPCaC)1 is the lack of closure error to maximum resolution Indicated.

Mean Figure of Merit-l P(a)e 1 4/Ep(a)l where P(a) is the phase probability.

'Comfpleteness of data in the outer shell, (2.9-2.8A) for the native and (3.1-3.0k) for both derivatives.

9 9 9 S. S S SS *9 55 9. 5.

SS 555 5 *55 S 95.. 9.

55 9

S

5 S S S S5 9 S 55 5 99 9SS Table 2 Peptidel-EBPl paptidelIESP2 paptid*el-BP2 Paptide2-EDP1 paptidel-Paptido2 Gl 1y9O-Het 5 0

N

Pro PIOO-Thr

ISN

Pro PIOO-Thr 15107 Leupl 1O.SerlSN Tyrp'OH-Ser 9 2

N

GlyP 9 O-Het 5 0 t'I P ro~ 10 0-Th r 151

N

Proplo-Thr ~15V Le uplIO-Ser 15 2

N

Tyr P'OH-Ser 9 2 H Tyrp4O- CYaP6" Tyrp'N-CYS

P

6 0 cys P 6 OTyr P4N Cys 6N -Tyr P 4 0 LsuplloSI 5 2 0Yf Leu PlO-SerZO 150fI

Claims

1. A computer-assisted method for identifyig potential mimetics of erythropoietin, usn a programmed computer comprising a processor, a data storage system, an input device, and an output device, comprising the steps of:. inputting into the programmed computer through said input device data comprising the three-dimensional coordinates of a subset of the atoms in the peptide GGTYSCHIFGPLTWVCKCPQGG when said peptide is co- crystallized with a portion of the erythropoietin receptor comprising amino acids I to 225 of said receptor, thereby generating a criteria data set; E. 10 comparing, using said processor, said criteria data set to a computer database of chemical structures stored in said computer data storage system; selecting from said database, using computer methods, chemiucal structures OV having a portion that is structurally similar to said criteria data set; outputting to said output device the selected chemical structures having a portion similar to said criteria data set. omputer-assisted method for identifying potential mnimetics of erythropoietin, ig a programmed computer comprising a processor, a data storage system, an it device, and an output device, comprising the steps of: inputting into the programmed computer through said input device data comprising the three-dimensional coordinates of a subset of the atoms in the peptide GGTYSCIFGPLTWVCKPQGG when said peptide is co- crystallized with a portion of the erythropoietin receptor comprising amino acids I to 225 of said receptor, thereby generating a criteria data set; constructing, using computer methods, a model of a chemical structure having a portion that is structurally similar to said criteria data set; outputting to said output device the constructed model. :ompound having a chemical structure selected using the method of claim 1, "compound being an EPO mimetic. compound of claim 3 wherein said compound is not a peptide. compound of claim 3 wherein said compound is a peptide. "'".!compound of claims 5 wherein said peptide has 15 of fewer amino acids. is 2nd day of December 1999 g* PPS RESEARCH INSTITUTE atent Attorneys HACK