HEADER LIGASE/LIGASE INHIBITOR 28-JUL-13 4LWV
TITLE THE 2.3A CRYSTAL STRUCTURE OF HUMANIZED XENOPUS MDM2 WITH RO5545353
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: E3 UBIQUITIN-PROTEIN LIGASE MDM2;
COMPND 3 CHAIN: A, B, C;
COMPND 4 FRAGMENT: N-TERMINAL DOMAIN (UNP RESIDUES 21-105);
COMPND 5 SYNONYM: DOUBLE MINUTE 2 PROTEIN, XDM2, P53-BINDING PROTEIN MDM2;
COMPND 6 EC: 6.3.2.-;
COMPND 7 ENGINEERED: YES;
COMPND 8 MUTATION: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: XENOPUS LAEVIS;
SOURCE 3 ORGANISM_COMMON: CLAWED FROG,COMMON PLATANNA,PLATANNA;
SOURCE 4 ORGANISM_TAXID: 8355;
SOURCE 5 GENE: MDM2;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 511693;
SOURCE 8 EXPRESSION_SYSTEM_STRAIN: BL21;
SOURCE 9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 10 EXPRESSION_SYSTEM_PLASMID: PUBS 520
KEYWDS MDM2, E3 UBIQUITIN LIGASE, P53, NUCLEUS, LIGASE-LIGASE INHIBITOR
KEYWDS 2 COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR B.J.GRAVES,C.LUKACS,C.A.JANSON
REVDAT 1 02-JUL-14 4LWV 0
JRNL AUTH Z.ZHANG,X.J.CHU,J.J.LIU,Q.DING,J.ZHANG,D.BARTKOVITZ,N.JIANG,
JRNL AUTH 2 P.KARNACHI,S.S.SO,C.TOVAR,Z.M.FILIPOVIC,B.HIGGINS,K.GLENN,
JRNL AUTH 3 K.PACKMAN,L.VASSILEV,B.GRAVES
JRNL TITL DISCOVERY OF POTENT AND ORALLY ACTIVE P53-MDM2 INHIBITORS
JRNL TITL 2 RO5353 AND RO2468 FOR POTENTIAL CLINICAL DEVELOPMENT.
JRNL REF ACS MED.CHEM.LETT. V. 5 124 2014
JRNL REFN ISSN 1948-5875
JRNL PMID 24900784
JRNL DOI 10.1021/ML400359Z
REMARK 2
REMARK 2 RESOLUTION. 2.32 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNX 2005
REMARK 3 AUTHORS : BRUNGER,ADAMS,CLORE,DELANO,GROS,GROSSE-
REMARK 3 : KUNSTLEVE,JIANG,KUSZEWSKI,NILGES,PANNU,
REMARK 3 : READ,RICE,SIMONSON,WARREN,ACCELRYS
REMARK 3 : SOFTWARE INC.(BADGER,BERARD,KUMAR,SZALMA,
REMARK 3 : YIP,DZAKULA)
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.32
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 39.44
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : 1115147.730
REMARK 3 DATA CUTOFF LOW (ABS(F)) : 0.0000
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : 99.6
REMARK 3 NUMBER OF REFLECTIONS : 19022
REMARK 3
REMARK 3 FIT TO DATA USED IN REFINEMENT.
REMARK 3 CROSS-VALIDATION METHOD : THROUGHOUT
REMARK 3 FREE R VALUE TEST SET SELECTION : RANDOM
REMARK 3 R VALUE (WORKING + TEST SET) : 0.233
REMARK 3 R VALUE (WORKING SET) : 0.230
REMARK 3 FREE R VALUE : 0.284
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT : 541
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : 0.012
REMARK 3
REMARK 3 FIT/AGREEMENT OF MODEL WITH ALL DATA.
REMARK 3 R VALUE (WORKING + TEST SET, NO CUTOFF) : 0.2330
REMARK 3 R VALUE (WORKING SET, NO CUTOFF) : 0.2300
REMARK 3 FREE R VALUE (NO CUTOFF) : 0.284
REMARK 3 FREE R VALUE TEST SET SIZE (%, NO CUTOFF) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT (NO CUTOFF) : 541
REMARK 3 ESTIMATED ERROR OF FREE R VALUE (NO CUTOFF) : 0.0120
REMARK 3 TOTAL NUMBER OF REFLECTIONS (NO CUTOFF) : 10923
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 6
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 2.32
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.98
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 99.80
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 1694
REMARK 3 BIN R VALUE (WORKING SET) : 0.3380
REMARK 3 BIN FREE R VALUE : 0.3430
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 4.90
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 87
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : 0.037
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 2070
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 138
REMARK 3 SOLVENT ATOMS : 48
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 67.30
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 38.50
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.00000
REMARK 3 B22 (A**2) : 0.00000
REMARK 3 B33 (A**2) : 0.00000
REMARK 3 B12 (A**2) : 0.00000
REMARK 3 B13 (A**2) : 0.00000
REMARK 3 B23 (A**2) : 0.00000
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.35
REMARK 3 ESD FROM SIGMAA (A) : 0.40
REMARK 3 LOW RESOLUTION CUTOFF (A) : 5.00
REMARK 3
REMARK 3 CROSS-VALIDATED ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM C-V LUZZATI PLOT (A) : 0.44
REMARK 3 ESD FROM C-V SIGMAA (A) : 0.49
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.008
REMARK 3 BOND ANGLES (DEGREES) : 1.800
REMARK 3 DIHEDRAL ANGLES (DEGREES) : 24.300
REMARK 3 IMPROPER ANGLES (DEGREES) : 0.700
REMARK 3
REMARK 3 ISOTROPIC THERMAL MODEL : RESTRAINED
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. RMS SIGMA
REMARK 3 MAIN-CHAIN BOND (A**2) : 1.610 ; 1.500
REMARK 3 MAIN-CHAIN ANGLE (A**2) : 2.870 ; 2.000
REMARK 3 SIDE-CHAIN BOND (A**2) : 2.010 ; 2.000
REMARK 3 SIDE-CHAIN ANGLE (A**2) : 3.240 ; 2.500
REMARK 3
REMARK 3 BULK SOLVENT MODELING.
REMARK 3 METHOD USED : FLAT MODEL
REMARK 3 KSOL : 0.33
REMARK 3 BSOL : 24.94
REMARK 3
REMARK 3 NCS MODEL : NULL
REMARK 3
REMARK 3 PARAMETER FILE 1 : PROTEIN_REP.PARA
REMARK 3 PARAMETER FILE 2 : WATER_REP.PARAM
REMARK 3 PARAMETER FILE 3 : ION.PARAM
REMARK 3 PARAMETER FILE 4 : RO5545353.PRX
REMARK 3 TOPOLOGY FILE 1 : PROTEIN.TOP
REMARK 3 TOPOLOGY FILE 2 : WATER.TOP
REMARK 3 TOPOLOGY FILE 3 : ION.TOP
REMARK 3 TOPOLOGY FILE 4 : RO5545353.TPX
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 4LWV COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 13-AUG-13.
REMARK 100 THE RCSB ID CODE IS RCSB081186.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 15-OCT-10
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 6.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : APS
REMARK 200 BEAMLINE : 31-ID
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 0.99990
REMARK 200 MONOCHROMATOR : DIAMOND
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : AREA DETECTOR
REMARK 200 DETECTOR MANUFACTURER : RAYONIX MX225HE
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : CRYSTALCLEAR
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 19022
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.320
REMARK 200 RESOLUTION RANGE LOW (A) : 44.020
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.9
REMARK 200 DATA REDUNDANCY : 5.700
REMARK 200 R MERGE (I) : 0.12200
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 11.0000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.32
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.45
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.8
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : NULL
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : NULL
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: MOLREP
REMARK 200 STARTING MODEL: NULL
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 65.42
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.56
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 40-50% SATURATED AMMONIUM SULFATE,
REMARK 280 0.1M MES, PH 6.5, 5% PEG200, VAPOR DIFFUSION, HANGING DROP,
REMARK 280 TEMPERATURE 278K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 2
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,-Y,Z
REMARK 290 3555 -X+1/2,Y+1/2,-Z
REMARK 290 4555 X+1/2,-Y+1/2,-Z
REMARK 290
REMARK 290 WHERE NNN -> OPERATOR NUMBER
REMARK 290 MMM -> TRANSLATION VECTOR
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY TRANSFORMATIONS
REMARK 290 THE FOLLOWING TRANSFORMATIONS OPERATE ON THE ATOM/HETATM
REMARK 290 RECORDS IN THIS ENTRY TO PRODUCE CRYSTALLOGRAPHICALLY
REMARK 290 RELATED MOLECULES.
REMARK 290 SMTRY1 1 1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 1 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 1 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 2 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 44.37100
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 66.04650
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 44.37100
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 66.04650
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1, 2, 3
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON
REMARK 300 BURIED SURFACE AREA.
REMARK 350
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS
REMARK 350 GIVEN BELOW. BOTH NON-CRYSTALLOGRAPHIC AND
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.
REMARK 350
REMARK 350 BIOMOLECULE: 1
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A
REMARK 350 BIOMT1 1 1.000000 0.000000 0.000000 0.00000
REMARK 350 BIOMT2 1 0.000000 1.000000 0.000000 0.00000
REMARK 350 BIOMT3 1 0.000000 0.000000 1.000000 0.00000
REMARK 350
REMARK 350 BIOMOLECULE: 2
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC
REMARK 350 APPLY THE FOLLOWING TO CHAINS: B
REMARK 350 BIOMT1 1 1.000000 0.000000 0.000000 0.00000
REMARK 350 BIOMT2 1 0.000000 1.000000 0.000000 0.00000
REMARK 350 BIOMT3 1 0.000000 0.000000 1.000000 0.00000
REMARK 350
REMARK 350 BIOMOLECULE: 3
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC
REMARK 350 APPLY THE FOLLOWING TO CHAINS: C
REMARK 350 BIOMT1 1 1.000000 0.000000 0.000000 0.00000
REMARK 350 BIOMT2 1 0.000000 1.000000 0.000000 0.00000
REMARK 350 BIOMT3 1 0.000000 0.000000 1.000000 0.00000
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: TORSION ANGLES
REMARK 500
REMARK 500 TORSION ANGLES OUTSIDE THE EXPECTED RAMACHANDRAN REGIONS:
REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT:(10X,I3,1X,A3,1X,A1,I4,A1,4X,F7.2,3X,F7.2)
REMARK 500
REMARK 500 EXPECTED VALUES: GJ KLEYWEGT AND TA JONES (1996). PHI/PSI-
REMARK 500 CHOLOGY: RAMACHANDRAN REVISITED. STRUCTURE 4, 1395 - 1400
REMARK 500
REMARK 500 M RES CSSEQI PSI PHI
REMARK 500 LYS A 66 -140.96 63.51
REMARK 500 GLN A 67 -86.51 58.28
REMARK 500 GLN A 68 25.19 143.12
REMARK 500 HIS A 69 56.19 71.74
REMARK 500 LYS B 66 -81.47 95.36
REMARK 500 GLN B 68 -10.83 -158.32
REMARK 500 CYS B 73 31.86 -158.28
REMARK 500 VAL B 104 -72.35 -96.62
REMARK 500 ALA C 59 -73.21 -55.78
REMARK 500 LYS C 60 -19.78 -46.81
REMARK 500 LYS C 66 -84.09 119.70
REMARK 500 GLN C 67 -64.91 -24.22
REMARK 500 GLN C 68 27.12 161.64
REMARK 500 HIS C 69 61.29 72.44
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: NON-CIS, NON-TRANS
REMARK 500
REMARK 500 THE FOLLOWING PEPTIDE BONDS DEVIATE SIGNIFICANTLY FROM BOTH
REMARK 500 CIS AND TRANS CONFORMATION. CIS BONDS, IF ANY, ARE LISTED
REMARK 500 ON CISPEP RECORDS. TRANS IS DEFINED AS 180 +/- 30 AND
REMARK 500 CIS IS DEFINED AS 0 +/- 30 DEGREES.
REMARK 500 MODEL OMEGA
REMARK 500 GLU A 65 LYS A 66 -148.40
REMARK 500
REMARK 500 REMARK: NULL
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 20W A 201
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE SO4 A 202
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE SO4 A 203
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE SO4 A 204
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 20W B 201
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 20W C 201
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 4LWT RELATED DB: PDB
REMARK 900 RELATED ID: 4LWU RELATED DB: PDB
DBREF 4LWV A 21 105 UNP P56273 MDM2_XENLA 21 105
DBREF 4LWV B 21 105 UNP P56273 MDM2_XENLA 21 105
DBREF 4LWV C 21 105 UNP P56273 MDM2_XENLA 21 105
SEQADV 4LWV LEU A 50 UNP P56273 ILE 50 ENGINEERED MUTATION
SEQADV 4LWV HIS A 92 UNP P56273 PRO 92 ENGINEERED MUTATION
SEQADV 4LWV ILE A 95 UNP P56273 LEU 95 ENGINEERED MUTATION
SEQADV 4LWV LEU B 50 UNP P56273 ILE 50 ENGINEERED MUTATION
SEQADV 4LWV HIS B 92 UNP P56273 PRO 92 ENGINEERED MUTATION
SEQADV 4LWV ILE B 95 UNP P56273 LEU 95 ENGINEERED MUTATION
SEQADV 4LWV LEU C 50 UNP P56273 ILE 50 ENGINEERED MUTATION
SEQADV 4LWV HIS C 92 UNP P56273 PRO 92 ENGINEERED MUTATION
SEQADV 4LWV ILE C 95 UNP P56273 LEU 95 ENGINEERED MUTATION
SEQRES 1 A 85 GLU LYS LEU VAL GLN PRO THR PRO LEU LEU LEU SER LEU
SEQRES 2 A 85 LEU LYS SER ALA GLY ALA GLN LYS GLU THR PHE THR MET
SEQRES 3 A 85 LYS GLU VAL LEU TYR HIS LEU GLY GLN TYR ILE MET ALA
SEQRES 4 A 85 LYS GLN LEU TYR ASP GLU LYS GLN GLN HIS ILE VAL HIS
SEQRES 5 A 85 CYS SER ASN ASP PRO LEU GLY GLU LEU PHE GLY VAL GLN
SEQRES 6 A 85 GLU PHE SER VAL LYS GLU HIS ARG ARG ILE TYR ALA MET
SEQRES 7 A 85 ILE SER ARG ASN LEU VAL SER
SEQRES 1 B 85 GLU LYS LEU VAL GLN PRO THR PRO LEU LEU LEU SER LEU
SEQRES 2 B 85 LEU LYS SER ALA GLY ALA GLN LYS GLU THR PHE THR MET
SEQRES 3 B 85 LYS GLU VAL LEU TYR HIS LEU GLY GLN TYR ILE MET ALA
SEQRES 4 B 85 LYS GLN LEU TYR ASP GLU LYS GLN GLN HIS ILE VAL HIS
SEQRES 5 B 85 CYS SER ASN ASP PRO LEU GLY GLU LEU PHE GLY VAL GLN
SEQRES 6 B 85 GLU PHE SER VAL LYS GLU HIS ARG ARG ILE TYR ALA MET
SEQRES 7 B 85 ILE SER ARG ASN LEU VAL SER
SEQRES 1 C 85 GLU LYS LEU VAL GLN PRO THR PRO LEU LEU LEU SER LEU
SEQRES 2 C 85 LEU LYS SER ALA GLY ALA GLN LYS GLU THR PHE THR MET
SEQRES 3 C 85 LYS GLU VAL LEU TYR HIS LEU GLY GLN TYR ILE MET ALA
SEQRES 4 C 85 LYS GLN LEU TYR ASP GLU LYS GLN GLN HIS ILE VAL HIS
SEQRES 5 C 85 CYS SER ASN ASP PRO LEU GLY GLU LEU PHE GLY VAL GLN
SEQRES 6 C 85 GLU PHE SER VAL LYS GLU HIS ARG ARG ILE TYR ALA MET
SEQRES 7 C 85 ILE SER ARG ASN LEU VAL SER
HET 20W A 201 41
HET SO4 A 202 5
HET SO4 A 203 5
HET SO4 A 204 5
HET 20W B 201 41
HET 20W C 201 41
HETNAM 20W (2S,3R,4R,5R)-N-(4-CARBAMOYL-2-METHOXYPHENYL)-2'-
HETNAM 2 20W CHLORO-4-(3-CHLORO-2-FLUOROPHENYL)-2-(2,2-
HETNAM 3 20W DIMETHYLPROPYL)-5'-OXO-4',5'-DIHYDROSPIRO[PYRROLIDINE-
HETNAM 4 20W 3,6'-THIENO[3,2-B]PYRROLE]-5-CARBOXAMIDE
HETNAM SO4 SULFATE ION
FORMUL 4 20W 3(C29 H29 CL2 F N4 O4 S)
FORMUL 5 SO4 3(O4 S 2-)
FORMUL 10 HOH *48(H2 O)
HELIX 1 1 THR A 27 ALA A 37 1 11
HELIX 2 2 THR A 45 LYS A 60 1 16
HELIX 3 3 ASP A 76 GLY A 83 1 8
HELIX 4 4 GLU A 91 ARG A 101 1 11
HELIX 5 5 THR B 27 ALA B 37 1 11
HELIX 6 6 MET B 46 GLN B 61 1 16
HELIX 7 7 ASP B 76 GLY B 83 1 8
HELIX 8 8 GLU B 91 ARG B 101 1 11
HELIX 9 9 THR C 27 ALA C 37 1 11
HELIX 10 10 THR C 45 GLN C 61 1 17
HELIX 11 11 ASP C 76 GLY C 83 1 8
HELIX 12 12 GLU C 91 ARG C 101 1 11
SHEET 1 A 2 GLN A 25 PRO A 26 0
SHEET 2 A 2 LEU A 103 SER A 105 -1 O VAL A 104 N GLN A 25
SHEET 1 B 3 TYR A 63 ASP A 64 0
SHEET 2 B 3 ILE A 70 HIS A 72 -1 O ILE A 70 N ASP A 64
SHEET 3 B 3 GLU A 86 SER A 88 -1 O PHE A 87 N VAL A 71
SHEET 1 C 2 LEU B 23 VAL B 24 0
SHEET 2 C 2 PHE B 44 THR B 45 -1 O PHE B 44 N VAL B 24
SHEET 1 D 2 ILE B 70 HIS B 72 0
SHEET 2 D 2 GLU B 86 SER B 88 -1 O PHE B 87 N VAL B 71
SHEET 1 E 2 ILE C 70 HIS C 72 0
SHEET 2 E 2 GLU C 86 SER C 88 -1 O PHE C 87 N VAL C 71
SITE 1 AC1 12 LEU A 50 HIS A 69 PHE A 82 VAL A 89
SITE 2 AC1 12 LYS A 90 HIS A 92 ILE A 95 TYR A 96
SITE 3 AC1 12 HOH A 314 LYS C 90 20W C 201 HOH C 308
SITE 1 AC2 8 HIS A 92 TYR A 96 HOH A 306 HOH A 317
SITE 2 AC2 8 LYS C 90 GLU C 91 HIS C 92 ARG C 93
SITE 1 AC3 8 LYS A 90 GLU A 91 HIS A 92 ARG A 93
SITE 2 AC3 8 HOH A 307 HOH A 315 HIS C 92 TYR C 96
SITE 1 AC4 6 PRO A 28 LEU A 29 PRO B 28 LEU B 29
SITE 2 AC4 6 PRO C 28 LEU C 29
SITE 1 AC5 10 LEU B 50 MET B 58 TYR B 63 GLU B 65
SITE 2 AC5 10 GLN B 68 VAL B 89 LYS B 90 HIS B 92
SITE 3 AC5 10 ILE B 95 TYR B 96
SITE 1 AC6 10 20W A 201 HOH A 314 LEU C 50 MET C 58
SITE 2 AC6 10 HIS C 69 VAL C 89 LYS C 90 HIS C 92
SITE 3 AC6 10 TYR C 96 HOH C 311
CRYST1 88.742 132.093 35.797 90.00 90.00 90.00 P 21 21 2 12
ORIGX1 1.000000 0.000000 0.000000 0.00000
ORIGX2 0.000000 1.000000 0.000000 0.00000
ORIGX3 0.000000 0.000000 1.000000 0.00000
SCALE1 0.011269 0.000000 0.000000 0.00000
SCALE2 0.000000 0.007570 0.000000 0.00000
SCALE3 0.000000 0.000000 0.027935 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
