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Database: PDB
Entry: 1TTV
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Original site: 1TTV 
HEADER    LIGASE                                  23-JUN-04   1TTV              
TITLE     NMR STRUCTURE OF A COMPLEX BETWEEN MDM2 AND A SMALL                   
TITLE    2 MOLECULE INHIBITOR                                                   
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: UBIQUITIN-PROTEIN LIGASE E3 MDM2;                          
COMPND   3 CHAIN: A;                                                            
COMPND   4 FRAGMENT: RESIUDES 13-119;                                           
COMPND   5 SYNONYM: P53-BINDING PROTEIN MDM2, DOUBLE MINUTE 2 PROTEIN,          
COMPND   6 XDM2;                                                                
COMPND   7 EC: 6.3.2.-;                                                         
COMPND   8 ENGINEERED: YES;                                                     
COMPND   9 MUTATION: YES                                                        
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: XENOPUS LAEVIS;                                 
SOURCE   3 ORGANISM_COMMON: AFRICAN CLAWED FROG;                                
SOURCE   4 ORGANISM_TAXID: 8355;                                                
SOURCE   5 GENE: MDM2;                                                          
SOURCE   6 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21;                            
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, PROTEIN-PROTEIN INTERACTION, LIGASE                             
EXPDTA    SOLUTION NMR                                                          
NUMMDL    18                                                                    
AUTHOR    D.C.FRY,S.D.EMERSON,S.PALME,B.T.VU,C.M.LIU,F.PODLASKI                 
REVDAT   2   24-FEB-09 1TTV    1       VERSN                                    
REVDAT   1   04-JAN-05 1TTV    0                                                
JRNL        AUTH   D.C.FRY,S.D.EMERSON,S.PALME,B.T.VU,C.M.LIU,                  
JRNL        AUTH 2 F.PODLASKI                                                   
JRNL        TITL   NMR STRUCTURE OF A COMPLEX BETWEEN MDM2 AND A                
JRNL        TITL 2 SMALL MOLECULE INHIBITOR.                                    
JRNL        REF    J.BIOMOL.NMR                  V.  30   163 2004              
JRNL        REFN                   ISSN 0925-2738                               
JRNL        PMID   15557803                                                     
JRNL        DOI    10.1023/B:JNMR.0000048856.84603.9B                           
REMARK   1                                                                      
REMARK   2                                                                      
REMARK   2 RESOLUTION. NOT APPLICABLE.                                          
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : CNX 2000.1                                           
REMARK   3   AUTHORS     : BRUNGER ET AL.                                       
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: STRUCTURE CALCULATIONS UTILIZED 1169      
REMARK   3  NOE-BASED DISTANCE CONSTRAINTS, OF WHICH 54 WERE                    
REMARK   3  INTERMOLECULAR; 176 DIHEDRAL ANGLE CONSTRAINTS; AND 48              
REMARK   3  HYDROGEN BOND CONSTRAINTS. THE PIPERAZINYL MOIETY OF THE            
REMARK   3  INHIBITOR GAVE NO NOES, HENCE THE POSITIONS OF ITS ATOMS ARE        
REMARK   3  NOT KNOWN AND THE STEREOCHEMISTRY IS NOT RIGOROUSLY                 
REMARK   3  ESTABLISHED.                                                        
REMARK   4                                                                      
REMARK   4 1TTV COMPLIES WITH FORMAT V. 3.15, 01-DEC-08                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 25-JUN-04.                  
REMARK 100 THE RCSB ID CODE IS RCSB022895.                                      
REMARK 210                                                                      
REMARK 210 EXPERIMENTAL DETAILS                                                 
REMARK 210  EXPERIMENT TYPE                : NMR                                
REMARK 210  TEMPERATURE           (KELVIN) : 293                                
REMARK 210  PH                             : 7.0                                
REMARK 210  IONIC STRENGTH                 : 50MM D13-MES; 150MM KCL; 50MM      
REMARK 210                                   D10-DTT; 1.5MM NAN3                
REMARK 210  PRESSURE                       : AMBIENT                            
REMARK 210  SAMPLE CONTENTS                : 0.6MM 13C/15N-MDM2; 3.5MM          
REMARK 210                                   INHIBITOR; 50MM D13-MES; 150MM     
REMARK 210                                   KCL; 50MM D10-DTT; 1.5MM NAN3      
REMARK 210                                                                      
REMARK 210  NMR EXPERIMENTS CONDUCTED      : 3D_15N-SEPARATED_NOESY, 3D_        
REMARK 210                                   13C-SEPARATED_NOESY, 2D 13C/       
REMARK 210                                   15N-FILTERED NOESY                 
REMARK 210  SPECTROMETER FIELD STRENGTH    : 600 MHZ                            
REMARK 210  SPECTROMETER MODEL             : INOVA                              
REMARK 210  SPECTROMETER MANUFACTURER      : VARIAN                             
REMARK 210                                                                      
REMARK 210  STRUCTURE DETERMINATION.                                            
REMARK 210   SOFTWARE USED                 : FELIX 2000, NMRVIEW 5.0.3,         
REMARK 210                                   CNX 2000.1                         
REMARK 210   METHOD USED                   : SIMULATED ANNEALING                
REMARK 210                                                                      
REMARK 210 CONFORMERS, NUMBER CALCULATED   : 42                                 
REMARK 210 CONFORMERS, NUMBER SUBMITTED    : 18                                 
REMARK 210 CONFORMERS, SELECTION CRITERIA  : STRUCTURES WITH ACCEPTABLE         
REMARK 210                                   COVALENT GEOMETRY,STRUCTURES       
REMARK 210                                   WITH THE LEAST RESTRAINT           
REMARK 210                                   VIOLATIONS                         
REMARK 210                                                                      
REMARK 210 BEST REPRESENTATIVE CONFORMER IN THIS ENSEMBLE : 4                   
REMARK 210                                                                      
REMARK 210 REMARK: NULL                                                         
REMARK 215                                                                      
REMARK 215 NMR STUDY                                                            
REMARK 215 THE COORDINATES IN THIS ENTRY WERE GENERATED FROM SOLUTION           
REMARK 215 NMR DATA.  PROTEIN DATA BANK CONVENTIONS REQUIRE THAT                
REMARK 215 CRYST1 AND SCALE RECORDS BE INCLUDED, BUT THE VALUES ON              
REMARK 215 THESE RECORDS ARE MEANINGLESS.                                       
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  1 SER A  16      -74.65   -173.05                                   
REMARK 500  1 THR A  17      -58.95   -165.12                                   
REMARK 500  1 ASP A  19       26.99   -158.29                                   
REMARK 500  1 LYS A  41      179.85    -51.77                                   
REMARK 500  1 GLN A  61       63.16     71.87                                   
REMARK 500  1 LYS A  66      -78.52    -46.49                                   
REMARK 500  1 GLU A  86      129.57    179.35                                   
REMARK 500  2 ILE A  15      -42.96   -148.22                                   
REMARK 500  2 SER A  16      -66.23     70.08                                   
REMARK 500  2 GLU A  21     -166.12   -106.85                                   
REMARK 500  2 GLN A  61       62.18     69.77                                   
REMARK 500  2 ASN A 102       32.23    -96.12                                   
REMARK 500  2 GLU A 110      163.88     60.83                                   
REMARK 500  3 SER A  16      -75.06   -166.72                                   
REMARK 500  3 THR A  17      -67.47   -163.60                                   
REMARK 500  3 GLU A  21     -163.37   -117.39                                   
REMARK 500  3 THR A  27      158.94    -48.65                                   
REMARK 500  3 LYS A  41      177.52    -52.19                                   
REMARK 500  3 GLN A  61       60.25     72.01                                   
REMARK 500  3 ASN A 102       37.96    -95.63                                   
REMARK 500  3 VAL A 104      -82.83    -53.35                                   
REMARK 500  4 ILE A  15      -77.05     64.57                                   
REMARK 500  4 SER A  16      -80.66     61.52                                   
REMARK 500  4 ASP A  19      135.28     63.83                                   
REMARK 500  4 GLU A  21      -81.75   -145.38                                   
REMARK 500  4 THR A  27      162.07    -49.20                                   
REMARK 500  4 LYS A  41      176.15    -49.15                                   
REMARK 500  4 GLN A  61       69.19     69.67                                   
REMARK 500  4 ASN A 102       43.32    -96.67                                   
REMARK 500  5 ILE A  15      -68.24     68.64                                   
REMARK 500  5 SER A  16     -179.68     57.10                                   
REMARK 500  5 THR A  17      167.96     60.12                                   
REMARK 500  5 GLN A  40      -58.16   -125.47                                   
REMARK 500  5 GLN A  61       60.98     75.08                                   
REMARK 500  5 ASN A 102       37.39    -95.92                                   
REMARK 500  5 VAL A 104      -81.87    -52.01                                   
REMARK 500  6 HIS A  14       94.37    -68.43                                   
REMARK 500  6 THR A  17      -73.60     65.61                                   
REMARK 500  6 GLN A  61       67.51     67.56                                   
REMARK 500  6 ASN A 102       33.23    -97.24                                   
REMARK 500  6 ASN A 107      100.52    -57.64                                   
REMARK 500  6 GLU A 110      162.31    173.38                                   
REMARK 500  7 ILE A  15      164.14     58.82                                   
REMARK 500  7 THR A  17      -78.12     64.09                                   
REMARK 500  7 ASP A  19      -79.86   -178.68                                   
REMARK 500  7 LYS A  41      179.25    -54.35                                   
REMARK 500  7 MET A  46      -33.16    -39.17                                   
REMARK 500  7 GLN A  61       65.17     68.74                                   
REMARK 500  7 ASN A 107      101.86    -58.02                                   
REMARK 500  7 PHE A 116       30.84    -98.54                                   
REMARK 500  8 SER A  16     -169.48    178.62                                   
REMARK 500  8 LYS A  41      179.36    -56.12                                   
REMARK 500  8 GLN A  61       68.17     68.29                                   
REMARK 500  8 VAL A 104      -90.68    -48.12                                   
REMARK 500  9 SER A  16      -78.30     64.98                                   
REMARK 500  9 ASP A  19      -65.53   -125.73                                   
REMARK 500  9 GLN A  40      -68.94   -120.40                                   
REMARK 500  9 LYS A  41      175.59    -50.56                                   
REMARK 500  9 GLN A  61       55.45     73.78                                   
REMARK 500  9 ASN A 102       32.76    -99.42                                   
REMARK 500 10 THR A  17     -169.34     56.72                                   
REMARK 500 10 ASP A  19       28.44   -155.84                                   
REMARK 500 10 LYS A  41      179.87    -58.05                                   
REMARK 500 10 VAL A  49      -70.00    -52.07                                   
REMARK 500 10 GLN A  61       65.84     70.00                                   
REMARK 500 10 ASN A 102       34.92    -96.28                                   
REMARK 500 10 VAL A 104      -99.11    -53.88                                   
REMARK 500 10 GLU A 110       91.88     43.09                                   
REMARK 500 11 SER A  16      -66.41   -165.01                                   
REMARK 500 11 THR A  17      -75.12   -150.81                                   
REMARK 500 11 LYS A  41      179.86    -54.17                                   
REMARK 500 11 GLN A  61       63.74     71.13                                   
REMARK 500 11 VAL A 104      -70.18    -56.14                                   
REMARK 500 12 THR A  17      -67.19     68.89                                   
REMARK 500 12 ASP A  19       28.87   -158.19                                   
REMARK 500 12 GLU A  21     -148.78   -107.11                                   
REMARK 500 12 GLN A  40      -73.08   -114.71                                   
REMARK 500 12 LYS A  41      175.20    -48.59                                   
REMARK 500 12 GLN A  61       65.84     71.08                                   
REMARK 500 12 ASN A 102       31.66    -94.76                                   
REMARK 500 12 GLU A 110     -179.39   -170.87                                   
REMARK 500 13 ILE A  15      163.99     60.30                                   
REMARK 500 13 SER A  16      -71.96    -84.89                                   
REMARK 500 13 THR A  17      -53.62   -161.77                                   
REMARK 500 13 GLU A  21     -171.79     56.49                                   
REMARK 500 13 THR A  27      159.55    -49.12                                   
REMARK 500 13 GLN A  61       64.21     70.45                                   
REMARK 500 13 ASN A 102       30.97    -92.93                                   
REMARK 500 14 SER A  16       93.63     47.62                                   
REMARK 500 14 THR A  17     -164.64     63.92                                   
REMARK 500 14 SER A  18      109.12    -54.69                                   
REMARK 500 14 GLU A  21      171.70     56.73                                   
REMARK 500 14 LYS A  41      179.79    -55.93                                   
REMARK 500 14 GLN A  61       66.24     69.81                                   
REMARK 500 14 ASN A 102       37.43    -92.91                                   
REMARK 500 14 VAL A 104      -84.71    -52.32                                   
REMARK 500 14 GLU A 110      137.25     63.64                                   
REMARK 500 15 THR A  17      -72.26     66.30                                   
REMARK 500 15 GLN A  40      -70.24   -114.75                                   
REMARK 500 15 LYS A  41      175.61    -49.04                                   
REMARK 500 15 GLN A  61       63.09     69.88                                   
REMARK 500 16 SER A  16       66.71   -118.48                                   
REMARK 500 16 ASP A  19      133.78     63.85                                   
REMARK 500 16 LYS A  41      179.63    -53.94                                   
REMARK 500 16 GLN A  61       65.49     70.16                                   
REMARK 500 16 ASN A 102       31.34    -99.25                                   
REMARK 500 16 GLU A 110       82.95   -155.85                                   
REMARK 500 17 SER A  16      -66.94     69.43                                   
REMARK 500 17 THR A  17      -45.38   -159.23                                   
REMARK 500 17 GLU A  21       30.80   -153.19                                   
REMARK 500 17 GLN A  61       62.90     71.53                                   
REMARK 500 17 MET A  98      -70.94    -59.39                                   
REMARK 500 17 LYS A 109       91.98    -61.65                                   
REMARK 500 18 ILE A  15     -162.59     55.23                                   
REMARK 500 18 SER A  16       88.12     75.47                                   
REMARK 500 18 GLU A  21      -59.27   -155.35                                   
REMARK 500 18 THR A  27      156.70    -46.12                                   
REMARK 500 18 GLN A  61       59.37     73.32                                   
REMARK 500 18 GLU A  86      125.41    176.22                                   
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 600                                                                      
REMARK 600 HETEROGEN                                                            
REMARK 600                                                                      
REMARK 600 AUTHOR NOTED THAT THE PIPERIZINYL MOIETY PRODUCED NO NOES,           
REMARK 600 SO THE POSITIONS OF ITS ATOMS COULD NOT BE DETERMINED                
REMARK 600 EXPERIMENTALLY AND ARE NOT INCLUDED IN THE COORDINATES.              
REMARK 610                                                                      
REMARK 610 MISSING HETEROATOM                                                   
REMARK 610 THE FOLLOWING RESIDUES HAVE MISSING ATOMS (M=MODEL NUMBER;           
REMARK 610 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;          
REMARK 610 I=INSERTION CODE):                                                   
REMARK 610   M RES C SSEQI                                                      
REMARK 610   1 IMY A  120                                                       
REMARK 610   2 IMY A  120                                                       
REMARK 610   3 IMY A  120                                                       
REMARK 610   4 IMY A  120                                                       
REMARK 610   5 IMY A  120                                                       
REMARK 610   6 IMY A  120                                                       
REMARK 610   7 IMY A  120                                                       
REMARK 610   8 IMY A  120                                                       
REMARK 610   9 IMY A  120                                                       
REMARK 610  10 IMY A  120                                                       
REMARK 610  11 IMY A  120                                                       
REMARK 610  12 IMY A  120                                                       
REMARK 610  13 IMY A  120                                                       
REMARK 610  14 IMY A  120                                                       
REMARK 610  15 IMY A  120                                                       
REMARK 610  16 IMY A  120                                                       
REMARK 610  17 IMY A  120                                                       
REMARK 610  18 IMY A  120                                                       
REMARK 800                                                                      
REMARK 800 SITE                                                                 
REMARK 800 SITE_IDENTIFIER: AC1                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE IMY A 120                 
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 1YCQ   RELATED DB: PDB                                   
REMARK 900 X-RAY STRUCTURE OF MDM2 WITH A P53 PEPTIDE BY KUSSIE ET AL.          
REMARK 900 RELATED ID: 1RV1   RELATED DB: PDB                                   
REMARK 900 X-RAY STRUCTURE OF MDM2 WITH AN IMIDAZOLINE INHIBITOR BY             
REMARK 900 LUKACS, KAMMLOTT, AND GRAVES                                         
DBREF  1TTV A   13   119  UNP    P56273   MDM2_XENLA      13    119             
SEQADV 1TTV LEU A   50  UNP  P56273    ILE    50 ENGINEERED                     
SEQADV 1TTV HIS A   92  UNP  P56273    PRO    92 ENGINEERED                     
SEQADV 1TTV ILE A   95  UNP  P56273    LEU    95 ENGINEERED                     
SEQRES   1 A  107  ASN HIS ILE SER THR SER ASP GLN GLU LYS LEU VAL GLN          
SEQRES   2 A  107  PRO THR PRO LEU LEU LEU SER LEU LEU LYS SER ALA GLY          
SEQRES   3 A  107  ALA GLN LYS GLU THR PHE THR MET LYS GLU VAL LEU TYR          
SEQRES   4 A  107  HIS LEU GLY GLN TYR ILE MET ALA LYS GLN LEU TYR ASP          
SEQRES   5 A  107  GLU LYS GLN GLN HIS ILE VAL HIS CYS SER ASN ASP PRO          
SEQRES   6 A  107  LEU GLY GLU LEU PHE GLY VAL GLN GLU PHE SER VAL LYS          
SEQRES   7 A  107  GLU HIS ARG ARG ILE TYR ALA MET ILE SER ARG ASN LEU          
SEQRES   8 A  107  VAL SER ALA ASN VAL LYS GLU SER SER GLU ASP ILE PHE          
SEQRES   9 A  107  GLY ASN VAL                                                  
HET    IMY  A 120      54                                                       
HETNAM     IMY 1-{[4,5-BIS(4-CHLOROPHENYL)-2-(2-ISOPROPOXY-4-                   
HETNAM   2 IMY  METHOXYPHENYL)-4,5-DIHYDRO-1H-IMIDAZOL-1-                       
HETNAM   3 IMY  YL]CARBONYL}PIPERAZINE                                          
HETSYN     IMY CIS-[4,5-BIS-(4-CHLOROPHENYL)-2-(2-ISOPROPOXY-4-                 
HETSYN   2 IMY  METHOXYPHENYL)-4,5-DIHYD ROIMIDAZOL-1-YL]-PIPERAZIN-1-          
HETSYN   3 IMY  YL-METHANONE                                                    
FORMUL   2  IMY    C30 H32 CL2 N4 O3                                            
HELIX    1   1 THR A   27  ALA A   37  1                                  11    
HELIX    2   2 THR A   45  GLN A   61  1                                  17    
HELIX    3   3 ASP A   76  GLY A   83  1                                   8    
HELIX    4   4 GLU A   91  ARG A  101  1                                  11    
SHEET    1   A 2 VAL A  24  PRO A  26  0                                        
SHEET    2   A 2 LEU A 103  ALA A 106 -1  O  SER A 105   N  GLN A  25           
SHEET    1   B 2 ILE A  70  VAL A  71  0                                        
SHEET    2   B 2 PHE A  87  SER A  88 -1  O  PHE A  87   N  VAL A  71           
SITE     1 AC1  8 LEU A  50  LEU A  53  GLY A  54  ILE A  57                    
SITE     2 AC1  8 GLN A  68  HIS A  69  VAL A  89  HIS A  92                    
CRYST1    1.000    1.000    1.000  90.00  90.00  90.00 P 1           1          
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      1.000000  0.000000  0.000000        0.00000                         
SCALE2      0.000000  1.000000  0.000000        0.00000                         
SCALE3      0.000000  0.000000  1.000000        0.00000                         
MODEL        1                                                                  
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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