GenomeNet

Database: PDB
Entry: 4JSC
LinkDB: 4JSC
Original site: 4JSC 
HEADER    LIGASE/LIGASE INHIBITOR                 22-MAR-13   4JSC              
TITLE     THE 2.5A CRYSTAL STRUCTURE OF HUMANIZED XENOPUS MDM2 WITH RO5316533 - 
TITLE    2 A PYRROLIDINE MDM2 INHIBITOR                                         
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: E3 UBIQUITIN-PROTEIN LIGASE MDM2;                          
COMPND   3 CHAIN: A, B;                                                         
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    PYRROLIDINE, LIGASE-ANTAGONIST COMPLEX, E3 UBIQUITIN LIGASE, P53,     
KEYWDS   2 NUCLEUS, LIGASE-LIGASE INHIBITOR COMPLEX                             
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    C.A.JANSON,C.LUKACS,B.GRAVES                                          
REVDAT   2   05-FEB-14 4JSC    1       JRNL                                     
REVDAT   1   24-JUL-13 4JSC    0                                                
JRNL        AUTH   Q.DING,Z.ZHANG,J.J.LIU,N.JIANG,J.ZHANG,T.M.ROSS,X.J.CHU,     
JRNL        AUTH 2 D.BARTKOVITZ,F.PODLASKI,C.JANSON,C.TOVAR,Z.M.FILIPOVIC,      
JRNL        AUTH 3 B.HIGGINS,K.GLENN,K.PACKMAN,L.T.VASSILEV,B.GRAVES            
JRNL        TITL   DISCOVERY OF RG7388, A POTENT AND SELECTIVE P53-MDM2         
JRNL        TITL 2 INHIBITOR IN CLINICAL DEVELOPMENT.                           
JRNL        REF    J.MED.CHEM.                   V.  56  5979 2013              
JRNL        REFN                   ISSN 0022-2623                               
JRNL        PMID   23808545                                                     
JRNL        DOI    10.1021/JM400487C                                            
REMARK   1                                                                      
REMARK   1 REFERENCE 1                                                          
REMARK   1  AUTH   C.TOVAR,B.GRAVES,K.PACKMAN,Z.FILIPOVIC,B.H.XIA,C.TARDELL,    
REMARK   1  AUTH 2 R.GARRIDO,E.LEE,K.KOLINSKY,K.H.TO,M.LINN,F.PODLASKI,         
REMARK   1  AUTH 3 P.WOVKULICH,B.VU,L.T.VASSILEV                                
REMARK   1  TITL   MDM2 SMALL-MOLECULE ANTAGONIST RG7112 ACTIVATES P53          
REMARK   1  TITL 2 SIGNALING AND REGRESSES HUMAN TUMORS IN PRECLINICAL CANCER   
REMARK   1  TITL 3 MODELS.                                                      
REMARK   1  REF    CANCER RES.                   V.  73  2587 2013              
REMARK   1  REFN                   ISSN 0008-5472                               
REMARK   1  PMID   23400593                                                     
REMARK   1  DOI    10.1158/0008-5472.CAN-12-2807                                
REMARK   2                                                                      
REMARK   2 RESOLUTION.    2.50 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) : 2.50                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 35.81                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : 0.000                          
REMARK   3   DATA CUTOFF HIGH         (ABS(F)) : 713583.850                     
REMARK   3   DATA CUTOFF LOW          (ABS(F)) : 0.0000                         
REMARK   3   COMPLETENESS (WORKING+TEST)   (%) : 99.9                           
REMARK   3   NUMBER OF REFLECTIONS             : 7443                           
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) : 0.316                           
REMARK   3   R VALUE            (WORKING SET) : 0.312                           
REMARK   3   FREE R VALUE                     : 0.370                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 5.300                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 393                             
REMARK   3   ESTIMATED ERROR OF FREE R VALUE  : 0.019                           
REMARK   3                                                                      
REMARK   3  FIT/AGREEMENT OF MODEL WITH ALL DATA.                               
REMARK   3   R VALUE     (WORKING + TEST SET, NO CUTOFF) : 0.3160               
REMARK   3   R VALUE            (WORKING SET, NO CUTOFF) : 0.3120               
REMARK   3   FREE R VALUE                    (NO CUTOFF) : 0.370                
REMARK   3   FREE R VALUE TEST SET SIZE   (%, NO CUTOFF) : 5.300                
REMARK   3   FREE R VALUE TEST SET COUNT     (NO CUTOFF) : 393                  
REMARK   3   ESTIMATED ERROR OF FREE R VALUE (NO CUTOFF) : 0.0190               
REMARK   3   TOTAL NUMBER OF REFLECTIONS     (NO CUTOFF) : 7443                 
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) : 2.50                         
REMARK   3   BIN RESOLUTION RANGE LOW        (A) : 2.66                         
REMARK   3   BIN COMPLETENESS (WORKING+TEST) (%) : 100.00                       
REMARK   3   REFLECTIONS IN BIN    (WORKING SET) : 1178                         
REMARK   3   BIN R VALUE           (WORKING SET) : 0.4040                       
REMARK   3   BIN FREE R VALUE                    : 0.5140                       
REMARK   3   BIN FREE R VALUE TEST SET SIZE  (%) : 5.20                         
REMARK   3   BIN FREE R VALUE TEST SET COUNT     : 64                           
REMARK   3   ESTIMATED ERROR OF BIN FREE R VALUE : 0.064                        
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS            : 1348                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 74                                      
REMARK   3   SOLVENT ATOMS            : 52                                      
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 37.80                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 42.00                          
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) : 0.54                            
REMARK   3   ESD FROM SIGMAA              (A) : 0.44                            
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) : 0.69                            
REMARK   3   ESD FROM C-V SIGMAA          (A) : 0.56                            
REMARK   3                                                                      
REMARK   3  RMS DEVIATIONS FROM IDEAL VALUES.                                   
REMARK   3   BOND LENGTHS                 (A) : 0.008                           
REMARK   3   BOND ANGLES            (DEGREES) : 1.200                           
REMARK   3   DIHEDRAL ANGLES        (DEGREES) : 24.400                          
REMARK   3   IMPROPER ANGLES        (DEGREES) : 0.870                           
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) : 1.570 ; 1.500                
REMARK   3   MAIN-CHAIN ANGLE             (A**2) : 2.650 ; 2.000                
REMARK   3   SIDE-CHAIN BOND              (A**2) : 1.990 ; 2.000                
REMARK   3   SIDE-CHAIN ANGLE             (A**2) : 3.000 ; 2.500                
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELING.                                              
REMARK   3   METHOD USED : FLAT MODEL                                           
REMARK   3   KSOL        : 0.38                                                 
REMARK   3   BSOL        : 45.88                                                
REMARK   3                                                                      
REMARK   3  NCS MODEL : NONE                                                    
REMARK   3                                                                      
REMARK   3  NCS RESTRAINTS.                         RMS   SIGMA/WEIGHT          
REMARK   3   GROUP  1  POSITIONAL            (A) : NULL  ; NULL                 
REMARK   3   GROUP  1  B-FACTOR           (A**2) : NULL  ; 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  : RO5316533.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   : RO5316533.TPX                                  
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: NULL                                      
REMARK   4                                                                      
REMARK   4 4JSC COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 16-APR-13.                  
REMARK 100 THE RCSB ID CODE IS RCSB078442.                                      
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 10-DEC-08                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : 6.0                                
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : N                                  
REMARK 200  RADIATION SOURCE               : ROTATING ANODE                     
REMARK 200  BEAMLINE                       : NULL                               
REMARK 200  X-RAY GENERATOR MODEL          : RIGAKU MICROMAX-007                
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.5418                             
REMARK 200  MONOCHROMATOR                  : MIRRORS                            
REMARK 200  OPTICS                         : MIRRORS                            
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : IMAGE PLATE                        
REMARK 200  DETECTOR MANUFACTURER          : RIGAKU RAXIS HTC                   
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : CRYSTALCLEAR                       
REMARK 200  DATA SCALING SOFTWARE          : D*TREK                             
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 8382                               
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.400                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 35.810                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : 0.000                              
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 99.9                               
REMARK 200  DATA REDUNDANCY                : 3.560                              
REMARK 200  R MERGE                    (I) : 0.12100                            
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 5.9000                             
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.40                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 2.49                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 100.0                              
REMARK 200  DATA REDUNDANCY IN SHELL       : 3.61                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.42900                            
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 1.800                              
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   (%): 54.67                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.71                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 50% SATURATED AMMONIUM SULFATE, 0.1M     
REMARK 280  BIS-TRIS, PH 6.0, 5% PEG 550MME, 5MM DTT, VAPOR DIFFUSION,          
REMARK 280  HANGING DROP, TEMPERATURE 278K                                      
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY                                            
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: C 1 2 1                          
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       37.74500            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       36.86000            
REMARK 290   SMTRY3   3  0.000000  0.000000  1.000000        0.00000            
REMARK 290   SMTRY1   4 -1.000000  0.000000  0.000000       37.74500            
REMARK 290   SMTRY2   4  0.000000  1.000000  0.000000       36.86000            
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                                                    
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 300 REMARK: FULL-LENGTH PROTEIN IS A DIMER, FORMED THROUGH CONTACTS IN   
REMARK 300 THE C-TERMINAL DOMAINS, BUT THE N-TERMINAL FRAGMENT IS A MONOMER ON  
REMARK 300 ITS OWN                                                              
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 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC                  
REMARK 350 SOFTWARE USED: PISA                                                  
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 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC                  
REMARK 350 SOFTWARE USED: PISA                                                  
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 465                                                                      
REMARK 465 MISSING RESIDUES                                                     
REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE                       
REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN               
REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)                
REMARK 465                                                                      
REMARK 465   M RES C SSSEQI                                                     
REMARK 465     MET A    20                                                      
REMARK 465     GLU A    21                                                      
REMARK 465     SER A   105                                                      
REMARK 465     MET B    20                                                      
REMARK 465     GLU B    21                                                      
REMARK 465     SER B   105                                                      
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    LEU A  29      -71.76    -55.83                                   
REMARK 500    GLN A  67      -94.78    -37.44                                   
REMARK 500    GLN A  68       33.87   -157.09                                   
REMARK 500    GLU A  91       63.01   -101.60                                   
REMARK 500    THR B  27      152.11    -46.55                                   
REMARK 500    GLN B  61       34.48     73.64                                   
REMARK 500    GLN B  67      -73.58    -62.59                                   
REMARK 500    GLN B  68       13.12   -155.13                                   
REMARK 500    VAL B  89        2.64    -64.35                                   
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 1OY A 201                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 1OY B 201                 
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 4JRG   RELATED DB: PDB                                   
REMARK 900 SAME PROTEIN WITH A CLOSELY RELATED PYRROLIDINE INHIBITOR            
REMARK 900 RELATED ID: 4IPF   RELATED DB: PDB                                   
REMARK 900 SAME PROTEIN WITH A NUTLIN INHIBITOR - RG7112                        
DBREF  4JSC A   21   105  UNP    P56273   MDM2_XENLA      21    105             
DBREF  4JSC B   21   105  UNP    P56273   MDM2_XENLA      21    105             
SEQADV 4JSC MET A   20  UNP  P56273              INITIATING METHIONINE          
SEQADV 4JSC LEU A   50  UNP  P56273    ILE    50 ENGINEERED MUTATION            
SEQADV 4JSC HIS A   92  UNP  P56273    PRO    92 ENGINEERED MUTATION            
SEQADV 4JSC ILE A   95  UNP  P56273    LEU    95 ENGINEERED MUTATION            
SEQADV 4JSC MET B   20  UNP  P56273              INITIATING METHIONINE          
SEQADV 4JSC LEU B   50  UNP  P56273    ILE    50 ENGINEERED MUTATION            
SEQADV 4JSC HIS B   92  UNP  P56273    PRO    92 ENGINEERED MUTATION            
SEQADV 4JSC ILE B   95  UNP  P56273    LEU    95 ENGINEERED MUTATION            
SEQRES   1 A   86  MET GLU LYS LEU VAL GLN PRO THR PRO LEU LEU LEU SER          
SEQRES   2 A   86  LEU LEU LYS SER ALA GLY ALA GLN LYS GLU THR PHE THR          
SEQRES   3 A   86  MET LYS GLU VAL LEU TYR HIS LEU GLY GLN TYR ILE MET          
SEQRES   4 A   86  ALA LYS GLN LEU TYR ASP GLU LYS GLN GLN HIS ILE VAL          
SEQRES   5 A   86  HIS CYS SER ASN ASP PRO LEU GLY GLU LEU PHE GLY VAL          
SEQRES   6 A   86  GLN GLU PHE SER VAL LYS GLU HIS ARG ARG ILE TYR ALA          
SEQRES   7 A   86  MET ILE SER ARG ASN LEU VAL SER                              
SEQRES   1 B   86  MET GLU LYS LEU VAL GLN PRO THR PRO LEU LEU LEU SER          
SEQRES   2 B   86  LEU LEU LYS SER ALA GLY ALA GLN LYS GLU THR PHE THR          
SEQRES   3 B   86  MET LYS GLU VAL LEU TYR HIS LEU GLY GLN TYR ILE MET          
SEQRES   4 B   86  ALA LYS GLN LEU TYR ASP GLU LYS GLN GLN HIS ILE VAL          
SEQRES   5 B   86  HIS CYS SER ASN ASP PRO LEU GLY GLU LEU PHE GLY VAL          
SEQRES   6 B   86  GLN GLU PHE SER VAL LYS GLU HIS ARG ARG ILE TYR ALA          
SEQRES   7 B   86  MET ILE SER ARG ASN LEU VAL SER                              
HET    1OY  A 201      37                                                       
HET    1OY  B 201      37                                                       
HETNAM     1OY (3S,4R,5S)-3-(3-CHLORO-2-FLUOROPHENYL)-4-(4-CHLORO-2-            
HETNAM   2 1OY  FLUOROPHENYL)-4-CYANO-N-[(3S)-3,4-DIHYDROXYBUTYL]-5-            
HETNAM   3 1OY  (2,2-DIMETHYLPROPYL)-D-PROLINAMIDE                              
FORMUL   3  1OY    2(C27 H31 CL2 F2 N3 O3)                                      
FORMUL   5  HOH   *52(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  PHE A   82  1                                   7    
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 THR B   45  GLN B   61  1                                  17    
HELIX    7   7 ASP B   64  HIS B   69  1                                   6    
HELIX    8   8 ASP B   76  PHE B   82  1                                   7    
HELIX    9   9 GLU B   91  ARG B  101  1                                  11    
SHEET    1   A 2 ILE A  70  HIS A  72  0                                        
SHEET    2   A 2 GLU A  86  SER A  88 -1  O  PHE A  87   N  VAL A  71           
SHEET    1   B 2 ILE B  70  HIS B  72  0                                        
SHEET    2   B 2 GLU B  86  SER B  88 -1  O  PHE B  87   N  VAL B  71           
SITE     1 AC1 11 LEU A  50  LEU A  53  GLY A  54  MET A  58                    
SITE     2 AC1 11 HIS A  69  VAL A  89  LYS A  90  HIS A  92                    
SITE     3 AC1 11 ILE A  95  TYR A  96  GLU B  86                               
SITE     1 AC2  9 GLU A  86  LEU B  50  HIS B  69  PHE B  82                    
SITE     2 AC2  9 VAL B  89  LYS B  90  HIS B  92  ILE B  95                    
SITE     3 AC2  9 TYR B  96                                                     
CRYST1   75.490   73.720   40.968  90.00 108.44  90.00 C 1 2 1       8          
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      0.013247  0.000000  0.004416        0.00000                         
SCALE2      0.000000  0.013565  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.025730        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
DBGET integrated database retrieval system