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Database: PDB
Entry: 6OVC
LinkDB: 6OVC
Original site: 6OVC 
HEADER    APOPTOSIS/INHIBITOR                     07-MAY-19   6OVC              
TITLE     HMCL1 INHIBITOR COMPLEX                                               
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: INDUCED MYELOID LEUKEMIA CELL DIFFERENTIATION PROTEIN MCL- 
COMPND   3 1;                                                                   
COMPND   4 CHAIN: A;                                                            
COMPND   5 SYNONYM: BCL-2-LIKE PROTEIN 3,BCL2-L-3,BCL-2-RELATED PROTEIN         
COMPND   6 EAT/MCL1,MCL1/EAT;                                                   
COMPND   7 ENGINEERED: YES                                                      
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606;                                                
SOURCE   5 GENE: MCL1, BCL2L3;                                                  
SOURCE   6 EXPRESSION_SYSTEM: ESCHERICHIA COLI K-12;                            
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 83333                                       
KEYWDS    INHIBITOR, MCL1 SMALL MOLECULE COMPLEX, APOPTOSIS, APOPTOSIS-         
KEYWDS   2 INHIBITOR COMPLEX                                                    
EXPDTA    SOLUTION NMR                                                          
AUTHOR    L.POPPE                                                               
REVDAT   1   22-MAY-19 6OVC    0                                                
JRNL        AUTH   S.CAENEPEEL,S.P.BROWN,B.BELMONTES,G.MOODY,K.S.KEEGAN,D.CHUI, 
JRNL        AUTH 2 D.A.WHITTINGTON,X.HUANG,L.POPPE,A.C.CHENG,M.CARDOZO,J.HOUZE, 
JRNL        AUTH 3 Y.LI,B.LUCAS,N.A.PARAS,X.WANG,J.P.TAYGERLY,M.VIMOLRATANA,    
JRNL        AUTH 4 M.ZANCANELLA,L.ZHU,E.CAJULIS,T.OSGOOD,J.SUN,L.DAMON,         
JRNL        AUTH 5 R.K.EGAN,P.GRENINGER,J.D.MCCLANAGHAN,J.GONG,D.MOUJALLED,     
JRNL        AUTH 6 G.POMILIO,P.BELTRAN,C.H.BENES,A.W.ROBERTS,D.C.HUANG,A.WEI,   
JRNL        AUTH 7 J.CANON,A.COXON,P.E.HUGHES                                   
JRNL        TITL   AMG 176, A SELECTIVE MCL1 INHIBITOR, IS EFFECTIVE IN         
JRNL        TITL 2 HEMATOLOGIC CANCER MODELS ALONE AND IN COMBINATION WITH      
JRNL        TITL 3 ESTABLISHED THERAPIES.                                       
JRNL        REF    CANCER DISCOV                 V.   8  1582 2018              
JRNL        REFN                   ESSN 2159-8290                               
JRNL        PMID   30254093                                                     
JRNL        DOI    10.1158/2159-8290.CD-18-0387                                 
REMARK   2                                                                      
REMARK   2 RESOLUTION. NOT APPLICABLE.                                          
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : MOE                                                  
REMARK   3   AUTHORS     : CCG                                                  
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: THE AUTHOR STATES THAT THE SMALL          
REMARK   3  MOLECULE - PROTEIN COMPLEX WAS OBTAINED BY LIGAND-PROTEIN NOE       
REMARK   3  CONSTRAINTS DOCKING OF A SMALL MOLECULE TO A PREVIOUSLY OBTAINED    
REMARK   3  NMR STRUCTURE OF THE APO FORM (PDB ENTRY 2MHS).                     
REMARK   4                                                                      
REMARK   4 6OVC COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 08-MAY-19.                  
REMARK 100 THE DEPOSITION ID IS D_1000241297.                                   
REMARK 210                                                                      
REMARK 210 EXPERIMENTAL DETAILS                                                 
REMARK 210  EXPERIMENT TYPE                : NMR                                
REMARK 210  TEMPERATURE           (KELVIN) : 298; 310                           
REMARK 210  PH                             : 7.4; 7.4                           
REMARK 210  IONIC STRENGTH                 : 50; 50                             
REMARK 210  PRESSURE                       : 1 ATM; 1 ATM                       
REMARK 210  SAMPLE CONTENTS                : 0.5 MM [U-99% 13C; U-99% 15N]      
REMARK 210                                   HUMAN MCL1 PROTEIN, 0.5 MM SMALL   
REMARK 210                                   MOLECULE, 20 MM SODIUM PHOSPHATE,  
REMARK 210                                   50 MM SODIUM CHLORIDE, 90% H2O/    
REMARK 210                                   10% D2O; 0.5 MM [U-99% 13C; U-99%  
REMARK 210                                   15N] HMCL1 PROTEIN, 0.25 MG/L      
REMARK 210                                   SMALL MOLECULE, 90% H2O/10% D2O    
REMARK 210                                                                      
REMARK 210  NMR EXPERIMENTS CONDUCTED      : 2D X-FILTERED NOESY; 2D X          
REMARK 210                                   FILTERED NOESY-HSQC; 2D HSQC-      
REMARK 210                                   NOESY                              
REMARK 210  SPECTROMETER FIELD STRENGTH    : 800 MHZ                            
REMARK 210  SPECTROMETER MODEL             : AVANCE                             
REMARK 210  SPECTROMETER MANUFACTURER      : BRUKER                             
REMARK 210                                                                      
REMARK 210  STRUCTURE DETERMINATION.                                            
REMARK 210   SOFTWARE USED                 : TOPSPIN 3.0, MATLAB                
REMARK 210   METHOD USED                   : SIMULATED ANNEALING                
REMARK 210                                                                      
REMARK 210 CONFORMERS, NUMBER CALCULATED   : 1                                  
REMARK 210 CONFORMERS, NUMBER SUBMITTED    : 1                                  
REMARK 210 CONFORMERS, SELECTION CRITERIA  : STRUCTURES WITH THE LOWEST         
REMARK 210                                   ENERGY                             
REMARK 210                                                                      
REMARK 210 BEST REPRESENTATIVE CONFORMER IN THIS ENSEMBLE : 1                   
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 300                                                                      
REMARK 300 BIOMOLECULE: 1                                                       
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 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    ASP A  26      143.99     64.70                                   
REMARK 500    ARG A  32     -119.37     52.95                                   
REMARK 500    LEU A  63      -21.78   -140.53                                   
REMARK 500    PHE A  85      -81.87    -85.84                                   
REMARK 500    SER A  86     -103.17     53.25                                   
REMARK 500    VAL A  89      128.50     61.87                                   
REMARK 500    TRP A  92       -5.29     63.77                                   
REMARK 500    GLU A 115      -25.94   -145.15                                   
REMARK 500    PHE A 150      -69.58   -129.30                                   
REMARK 500    ASP A 154       35.67    -87.74                                   
REMARK 500    HIS A 159     -166.00     49.89                                   
REMARK 500    HIS A 160       87.09     61.40                                   
REMARK 500    HIS A 163      -91.10     56.27                                   
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 N8J A 201                 
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 2MHS   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 30610   RELATED DB: BMRB                                 
REMARK 900 HMCL1 INHIBITOR COMPLEX                                              
DBREF  6OVC A    2   158  UNP    Q07820   MCL1_HUMAN     171    327             
SEQADV 6OVC MET A    1  UNP  Q07820              INITIATING METHIONINE          
SEQADV 6OVC SER A  117  UNP  Q07820    CYS   286 CONFLICT                       
SEQADV 6OVC HIS A  159  UNP  Q07820              EXPRESSION TAG                 
SEQADV 6OVC HIS A  160  UNP  Q07820              EXPRESSION TAG                 
SEQADV 6OVC HIS A  161  UNP  Q07820              EXPRESSION TAG                 
SEQADV 6OVC HIS A  162  UNP  Q07820              EXPRESSION TAG                 
SEQADV 6OVC HIS A  163  UNP  Q07820              EXPRESSION TAG                 
SEQADV 6OVC HIS A  164  UNP  Q07820              EXPRESSION TAG                 
SEQRES   1 A  164  MET GLU ASP GLU LEU TYR ARG GLN SER LEU GLU ILE ILE          
SEQRES   2 A  164  SER ARG TYR LEU ARG GLU GLN ALA THR GLY ALA LYS ASP          
SEQRES   3 A  164  THR LYS PRO MET GLY ARG SER GLY ALA THR SER ARG LYS          
SEQRES   4 A  164  ALA LEU GLU THR LEU ARG ARG VAL GLY ASP GLY VAL GLN          
SEQRES   5 A  164  ARG ASN HIS GLU THR ALA PHE GLN GLY MET LEU ARG LYS          
SEQRES   6 A  164  LEU ASP ILE LYS ASN GLU ASP ASP VAL LYS SER LEU SER          
SEQRES   7 A  164  ARG VAL MET ILE HIS VAL PHE SER ASP GLY VAL THR ASN          
SEQRES   8 A  164  TRP GLY ARG ILE VAL THR LEU ILE SER PHE GLY ALA PHE          
SEQRES   9 A  164  VAL ALA LYS HIS LEU LYS THR ILE ASN GLN GLU SER SER          
SEQRES  10 A  164  ILE GLU PRO LEU ALA GLU SER ILE THR ASP VAL LEU VAL          
SEQRES  11 A  164  ARG THR LYS ARG ASP TRP LEU VAL LYS GLN ARG GLY TRP          
SEQRES  12 A  164  ASP GLY PHE VAL GLU PHE PHE HIS VAL GLU ASP LEU GLU          
SEQRES  13 A  164  GLY GLY HIS HIS HIS HIS HIS HIS                              
HET    N8J  A 201      61                                                       
HETNAM     N8J (2S)-N-(BENZYLSULFONYL)-4-(CYCLOBUTYLMETHYL)-2-(2,4-             
HETNAM   2 N8J  DICHLOROPHENYL)-3,4-DIHYDRO-2H-1,4-BENZOXAZINE-6-               
HETNAM   3 N8J  CARBOXAMIDE                                                     
FORMUL   2  N8J    C27 H26 CL2 N2 O4 S                                          
HELIX    1 AA1 LEU A    5  THR A   22  1                                  18    
HELIX    2 AA2 GLY A   34  GLY A   48  1                                  15    
HELIX    3 AA3 HIS A   55  GLY A   61  1                                   7    
HELIX    4 AA4 GLU A   71  SER A   76  1                                   6    
HELIX    5 AA5 LEU A   77  ARG A   79  5                                   3    
HELIX    6 AA6 VAL A   80  SER A   86  1                                   7    
HELIX    7 AA7 ILE A   95  ILE A  112  1                                  18    
HELIX    8 AA8 ILE A  118  LYS A  133  1                                  16    
HELIX    9 AA9 ASP A  135  ARG A  141  1                                   7    
HELIX   10 AB1 ARG A  141  HIS A  151  1                                  11    
HELIX   11 AB2 GLU A  153  GLY A  157  5                                   5    
SITE     1 AC1  8 HIS A  55  MET A  62  LEU A  66  VAL A  84                    
SITE     2 AC1  8 ARG A  94  THR A  97  LEU A  98  PHE A 101                    
CRYST1    1.000    1.000    1.000  90.00  90.00  90.00 P 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                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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