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Database: PDB
Entry: 5AMN
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HEADER    TRANSFERASE                             11-MAR-15   5AMN              
TITLE     THE DISCOVERY OF 2-SUBSTITUTED PHENOL QUINAZOLINES AS POTENT AND      
TITLE    2 SELECTIVE RET KINASE INHIBITORS                                      
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: PROTO-ONCOGENE TYROSINE-PROTEIN KINASE RECEPTOR RET;       
COMPND   3 CHAIN: A;                                                            
COMPND   4 FRAGMENT: KINASE DOMAIN, RESIDUES 705-826,841-1012;                  
COMPND   5 SYNONYM: CADHERIN FAMILY MEMBER 12, PROTO-ONCOGENE C-RET;            
COMPND   6 EC: 2.7.10.1;                                                        
COMPND   7 ENGINEERED: YES;                                                     
COMPND   8 OTHER_DETAILS: PHOSPHORYLATION AT Y900 AND Y905                      
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606;                                                
SOURCE   5 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA;                            
SOURCE   6 EXPRESSION_SYSTEM_COMMON: FALL ARMYWORM;                             
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 7108;                                       
SOURCE   8 EXPRESSION_SYSTEM_CELL_LINE: SF9;                                    
SOURCE   9 EXPRESSION_SYSTEM_VECTOR_TYPE: BACULOVIRUS                           
KEYWDS    TRANSFERASE, RET, ONCOGENE, RECEPTOR TYROSINE KINASE, CHEMICAL        
KEYWDS   2 INHIBITOR, CANCER                                                    
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    R.NEWTON,K.BOWLER,E.M.BURNS,P.CHAPMAN,E.FAIRWEATHER,S.FRITZL,         
AUTHOR   2 K.GOLDBERG,N.M.HAMILTON,S.V.HOLT,G.V.HOPKINS,S.D.JONES,A.M.JORDAN,   
AUTHOR   3 A.LYONS,N.Q.MCDONALD,L.A.MAGUIRE,D.P.MOULD,A.G.PURKISS,H.F.SMALL,    
AUTHOR   4 A.STOWELL,G.J.THOMSON,I.D.WADDELL,B.WASZKOWYCZ,A.J.WATSON,           
AUTHOR   5 D.J.OGILVIE                                                          
REVDAT   3   28-FEB-18 5AMN    1       JRNL                                     
REVDAT   2   02-MAR-16 5AMN    1       JRNL                                     
REVDAT   1   17-FEB-16 5AMN    0                                                
JRNL        AUTH   R.NEWTON,K.A.BOWLER,E.M.BURNS,P.J.CHAPMAN,E.E.FAIRWEATHER,   
JRNL        AUTH 2 S.J.R.FRITZL,K.M.GOLDBERG,N.M.HAMILTON,S.V.HOLT,G.V.HOPKINS, 
JRNL        AUTH 3 S.D.JONES,A.M.JORDAN,A.J.LYONS,H.NIKKI MARCH,N.Q.MCDONALD,   
JRNL        AUTH 4 L.A.MAGUIRE,D.P.MOULD,A.G.PURKISS,H.F.SMALL,A.I.J.STOWELL,   
JRNL        AUTH 5 G.J.THOMSON,I.D.WADDELL,B.WASZKOWYCZ,A.J.WATSON,D.J.OGILVIE  
JRNL        TITL   THE DISCOVERY OF 2-SUBSTITUTED PHENOL QUINAZOLINES AS POTENT 
JRNL        TITL 2 RET KINASE INHIBITORS WITH IMPROVED KDR SELECTIVITY.         
JRNL        REF    EUR J MED CHEM                V. 112    20 2016              
JRNL        REFN                   ISSN 1768-3254                               
JRNL        PMID   26874741                                                     
JRNL        DOI    10.1016/J.EJMECH.2016.01.039                                 
REMARK   2                                                                      
REMARK   2 RESOLUTION.    2.57 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : PHENIX (PHENIX.REFINE)                               
REMARK   3   AUTHORS     : PAUL ADAMS,PAVEL AFONINE,VINCENT CHEN,IAN            
REMARK   3               : DAVIS,KRESHNA GOPAL,RALF GROSSE-KUNSTLEVE,           
REMARK   3               : LI-WEI HUNG,ROBERT IMMORMINO,TOM IOERGER,            
REMARK   3               : AIRLIE MCCOY,ERIK MCKEE,NIGEL MORIARTY,              
REMARK   3               : REETAL PAI,RANDY READ,JANE RICHARDSON,               
REMARK   3               : DAVID RICHARDSON,TOD ROMO,JIM SACCHETTINI,           
REMARK   3               : NICHOLAS SAUTER,JACOB SMITH,LAURENT                  
REMARK   3               : STORONI,TOM TERWILLIGER,PETER ZWART                  
REMARK   3                                                                      
REMARK   3    REFINEMENT TARGET : ML                                            
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 2.57                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 60.71                          
REMARK   3   MIN(FOBS/SIGMA_FOBS)              : 1.360                          
REMARK   3   COMPLETENESS FOR RANGE        (%) : 99.9                           
REMARK   3   NUMBER OF REFLECTIONS             : 10852                          
REMARK   3                                                                      
REMARK   3  FIT TO DATA USED IN REFINEMENT.                                     
REMARK   3   R VALUE     (WORKING + TEST SET) : 0.186                           
REMARK   3   R VALUE            (WORKING SET) : 0.183                           
REMARK   3   FREE R VALUE                     : 0.237                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 5.100                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 551                             
REMARK   3                                                                      
REMARK   3  FIT TO DATA USED IN REFINEMENT (IN BINS).                           
REMARK   3   BIN  RESOLUTION RANGE  COMPL.    NWORK NFREE   RWORK  RFREE        
REMARK   3     1 60.7269 -  4.0793    1.00     2751   151  0.1677 0.1982        
REMARK   3     2  4.0793 -  3.2379    1.00     2563   118  0.1704 0.2169        
REMARK   3     3  3.2379 -  2.8286    1.00     2496   152  0.2113 0.2973        
REMARK   3     4  2.8286 -  2.5700    1.00     2491   130  0.2225 0.3185        
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELLING.                                             
REMARK   3   METHOD USED        : FLAT BULK SOLVENT MODEL                       
REMARK   3   SOLVENT RADIUS     : 1.11                                          
REMARK   3   SHRINKAGE RADIUS   : 0.90                                          
REMARK   3   K_SOL              : NULL                                          
REMARK   3   B_SOL              : NULL                                          
REMARK   3                                                                      
REMARK   3  ERROR ESTIMATES.                                                    
REMARK   3   COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED)     : 0.260            
REMARK   3   PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 23.100           
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 36.66                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 35.69                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : NULL                                                 
REMARK   3    B22 (A**2) : NULL                                                 
REMARK   3    B33 (A**2) : NULL                                                 
REMARK   3    B12 (A**2) : NULL                                                 
REMARK   3    B13 (A**2) : NULL                                                 
REMARK   3    B23 (A**2) : NULL                                                 
REMARK   3                                                                      
REMARK   3  TWINNING INFORMATION.                                               
REMARK   3   FRACTION: NULL                                                     
REMARK   3   OPERATOR: NULL                                                     
REMARK   3                                                                      
REMARK   3  DEVIATIONS FROM IDEAL VALUES.                                       
REMARK   3                 RMSD          COUNT                                  
REMARK   3   BOND      :  0.003           2308                                  
REMARK   3   ANGLE     :  0.621           3119                                  
REMARK   3   CHIRALITY :  0.025            342                                  
REMARK   3   PLANARITY :  0.002            390                                  
REMARK   3   DIHEDRAL  : 12.878            859                                  
REMARK   3                                                                      
REMARK   3  TLS DETAILS                                                         
REMARK   3   NUMBER OF TLS GROUPS  : 3                                          
REMARK   3   TLS GROUP : 1                                                      
REMARK   3    SELECTION: CHAIN 'A' AND (RESID 700 THROUGH 710)                  
REMARK   3    ORIGIN FOR THE GROUP (A):  54.8606 -21.5725  -3.9999              
REMARK   3    T TENSOR                                                          
REMARK   3      T11:   0.4366 T22:   0.3900                                     
REMARK   3      T33:   0.3321 T12:   0.0671                                     
REMARK   3      T13:  -0.0217 T23:   0.0292                                     
REMARK   3    L TENSOR                                                          
REMARK   3      L11:   6.2400 L22:   7.8593                                     
REMARK   3      L33:   2.5756 L12:   5.6644                                     
REMARK   3      L13:   2.5482 L23:   4.3554                                     
REMARK   3    S TENSOR                                                          
REMARK   3      S11:   0.1989 S12:   0.7414 S13:   1.2697                       
REMARK   3      S21:  -0.5955 S22:  -0.8246 S23:   0.8231                       
REMARK   3      S31:  -0.8957 S32:  -0.9015 S33:   0.6306                       
REMARK   3   TLS GROUP : 2                                                      
REMARK   3    SELECTION: CHAIN 'A' AND (RESID 714 THROUGH 819)                  
REMARK   3    ORIGIN FOR THE GROUP (A):  67.4777  -9.9551   6.9729              
REMARK   3    T TENSOR                                                          
REMARK   3      T11:   0.2148 T22:   0.2225                                     
REMARK   3      T33:   0.3035 T12:   0.0310                                     
REMARK   3      T13:   0.0323 T23:   0.0142                                     
REMARK   3    L TENSOR                                                          
REMARK   3      L11:   0.5821 L22:   3.8175                                     
REMARK   3      L33:   2.1703 L12:   0.7874                                     
REMARK   3      L13:   0.3066 L23:   0.5636                                     
REMARK   3    S TENSOR                                                          
REMARK   3      S11:  -0.0552 S12:   0.0634 S13:  -0.0188                       
REMARK   3      S21:  -0.0276 S22:   0.0117 S23:   0.1845                       
REMARK   3      S31:  -0.0558 S32:  -0.0364 S33:   0.0480                       
REMARK   3   TLS GROUP : 3                                                      
REMARK   3    SELECTION: CHAIN 'A' AND (RESID 846 THROUGH 1009 )                
REMARK   3    ORIGIN FOR THE GROUP (A):  73.9033 -28.5118  20.5889              
REMARK   3    T TENSOR                                                          
REMARK   3      T11:   0.2513 T22:   0.2266                                     
REMARK   3      T33:   0.2103 T12:  -0.0218                                     
REMARK   3      T13:  -0.0012 T23:   0.0196                                     
REMARK   3    L TENSOR                                                          
REMARK   3      L11:   1.9141 L22:   4.1403                                     
REMARK   3      L33:   2.0075 L12:  -0.6544                                     
REMARK   3      L13:   0.1291 L23:   0.3679                                     
REMARK   3    S TENSOR                                                          
REMARK   3      S11:  -0.0586 S12:  -0.1379 S13:  -0.0659                       
REMARK   3      S21:   0.3148 S22:  -0.0079 S23:  -0.0433                       
REMARK   3      S31:   0.1007 S32:  -0.0337 S33:   0.0606                       
REMARK   3                                                                      
REMARK   3  NCS DETAILS                                                         
REMARK   3   NUMBER OF NCS GROUPS : NULL                                        
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: NULL                                      
REMARK   4                                                                      
REMARK   4 5AMN COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 11-MAR-15.                  
REMARK 100 THE DEPOSITION ID IS D_1290063177.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 23-APR-14                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : 4.4                                
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : DIAMOND                            
REMARK 200  BEAMLINE                       : I03                                
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 0.97630                            
REMARK 200  MONOCHROMATOR                  : DOUBLE CRYSTAL SILICON             
REMARK 200  OPTICS                         : MIRRORS                            
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : PIXEL                              
REMARK 200  DETECTOR MANUFACTURER          : DECTRIS PILATUS 6M                 
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : XDS                                
REMARK 200  DATA SCALING SOFTWARE          : AIMLESS                            
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 10852                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.570                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 60.730                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : 1.000                              
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 99.9                               
REMARK 200  DATA REDUNDANCY                : 13.60                              
REMARK 200  R MERGE                    (I) : 0.20000                            
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 11.4000                            
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.57                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 2.64                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 100.0                              
REMARK 200  DATA REDUNDANCY IN SHELL       : 14.50                              
REMARK 200  R MERGE FOR SHELL          (I) : 0.90000                            
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 3.300                              
REMARK 200                                                                      
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH                              
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT        
REMARK 200 SOFTWARE USED: PHASER                                                
REMARK 200 STARTING MODEL: PDB ENTRY 3TXO                                       
REMARK 200                                                                      
REMARK 200 REMARK: MOLECULAR REPLACEMENT USED N- AND C-LOBES SEPARATELY.        
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 46.70                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.31                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 3.4M SODIUM FORMATE 0.1M SODIUM          
REMARK 280  ACETATE PH 4.4                                                      
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY                                            
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 43 21 2                        
REMARK 290                                                                      
REMARK 290      SYMOP   SYMMETRY                                                
REMARK 290     NNNMMM   OPERATOR                                                
REMARK 290       1555   X,Y,Z                                                   
REMARK 290       2555   -X,-Y,Z+1/2                                             
REMARK 290       3555   -Y+1/2,X+1/2,Z+3/4                                      
REMARK 290       4555   Y+1/2,-X+1/2,Z+1/4                                      
REMARK 290       5555   -X+1/2,Y+1/2,-Z+3/4                                     
REMARK 290       6555   X+1/2,-Y+1/2,-Z+1/4                                     
REMARK 290       7555   Y,X,-Z                                                  
REMARK 290       8555   -Y,-X,-Z+1/2                                            
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      121.42000            
REMARK 290   SMTRY1   3  0.000000 -1.000000  0.000000       25.28500            
REMARK 290   SMTRY2   3  1.000000  0.000000  0.000000       25.28500            
REMARK 290   SMTRY3   3  0.000000  0.000000  1.000000      182.13000            
REMARK 290   SMTRY1   4  0.000000  1.000000  0.000000       25.28500            
REMARK 290   SMTRY2   4 -1.000000  0.000000  0.000000       25.28500            
REMARK 290   SMTRY3   4  0.000000  0.000000  1.000000       60.71000            
REMARK 290   SMTRY1   5 -1.000000  0.000000  0.000000       25.28500            
REMARK 290   SMTRY2   5  0.000000  1.000000  0.000000       25.28500            
REMARK 290   SMTRY3   5  0.000000  0.000000 -1.000000      182.13000            
REMARK 290   SMTRY1   6  1.000000  0.000000  0.000000       25.28500            
REMARK 290   SMTRY2   6  0.000000 -1.000000  0.000000       25.28500            
REMARK 290   SMTRY3   6  0.000000  0.000000 -1.000000       60.71000            
REMARK 290   SMTRY1   7  0.000000  1.000000  0.000000        0.00000            
REMARK 290   SMTRY2   7  1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY3   7  0.000000  0.000000 -1.000000        0.00000            
REMARK 290   SMTRY1   8  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY2   8 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY3   8  0.000000  0.000000 -1.000000      121.42000            
REMARK 290                                                                      
REMARK 290 REMARK: NULL                                                         
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: DIMERIC                           
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC                    
REMARK 350 SOFTWARE USED: PISA                                                  
REMARK 350 TOTAL BURIED SURFACE AREA: 6870 ANGSTROM**2                          
REMARK 350 SURFACE AREA OF THE COMPLEX: 24620 ANGSTROM**2                       
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -17.6 KCAL/MOL                        
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   BIOMT1   2  0.000000  1.000000  0.000000      101.14000            
REMARK 350   BIOMT2   2  1.000000  0.000000  0.000000     -101.14000            
REMARK 350   BIOMT3   2  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     LEU A   712                                                      
REMARK 465     GLU A   713                                                      
REMARK 465     GLY A   823                                                      
REMARK 465     PRO A   824                                                      
REMARK 465     GLY A   825                                                      
REMARK 465     TYR A   826                                                      
REMARK 465     PRO A   841                                                      
REMARK 465     ASP A   842                                                      
REMARK 465     LYS A  1011                                                      
REMARK 465     ARG A  1012                                                      
REMARK 470                                                                      
REMARK 470 MISSING ATOM                                                         
REMARK 470 THE FOLLOWING RESIDUES HAVE MISSING ATOMS (M=MODEL NUMBER;           
REMARK 470 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;          
REMARK 470 I=INSERTION CODE):                                                   
REMARK 470   M RES CSSEQI  ATOMS                                                
REMARK 470     LYS A 710    CG   CD   CE   NZ                                   
REMARK 470     ILE A 711    CG1  CG2  CD1                                       
REMARK 470     ASP A 714    CG   OD1  OD2                                       
REMARK 470     LYS A 716    NZ                                                  
REMARK 470     LYS A 722    CG   CD   CE   NZ                                   
REMARK 470     LYS A 747    CG   CD   CE   NZ                                   
REMARK 470     GLU A 762    CG   CD   OE1  OE2                                  
REMARK 470     LYS A 780    CD   CE   NZ                                        
REMARK 470     ASN A 783    CG   OD1  ND2                                       
REMARK 470     LYS A 789    CD   CE   NZ                                        
REMARK 470     GLN A 796    CG   CD   OE1  NE2                                  
REMARK 470     GLU A 818    CD   OE1  OE2                                       
REMARK 470     SER A 819    OG                                                  
REMARK 470     LYS A 821    CG   CD   CE   NZ                                   
REMARK 470     VAL A 822    CG1                                                 
REMARK 470     GLU A 843    CG   CD   OE1  OE2                                  
REMARK 470     ARG A 844    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     GLU A 867    CG   CD   OE1  OE2                                  
REMARK 470     GLU A 884    CD   OE1  OE2                                       
REMARK 470     LYS A 887    CE   NZ                                             
REMARK 470     GLU A 901    CG   CD   OE1  OE2                                  
REMARK 470     GLU A 902    CG   CD   OE1  OE2                                  
REMARK 470     LYS A 965    CE   NZ                                             
REMARK 470     ASP A 974    CG   OD1  OD2                                       
REMARK 470     GLU A 978    CG   CD   OE1  OE2                                  
REMARK 470     GLU A 979    CG   CD   OE1  OE2                                  
REMARK 470     ARG A 982    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     GLN A 986    OE1  NE2                                            
REMARK 470     LYS A 989    CE   NZ                                             
REMARK 470     GLU A 991    CG   CD   OE1  OE2                                  
REMARK 470     LYS A 994    CD   CE   NZ                                        
REMARK 470     LYS A1003    CG   CD   CE   NZ                                   
REMARK 470     LYS A1007    CG   CD   CE   NZ                                   
REMARK 470     VAL A1010    CG1  CG2                                            
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: CLOSE CONTACTS IN SAME ASYMMETRIC UNIT                     
REMARK 500                                                                      
REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT.                            
REMARK 500                                                                      
REMARK 500  ATM1  RES C  SSEQI   ATM2  RES C  SSEQI           DISTANCE          
REMARK 500   OE1  GLU A   805     O    HOH A  3019              2.13            
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
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    ARG A 820       51.84   -101.41                                   
REMARK 500    ARG A 873       -6.64     77.05                                   
REMARK 500    ASP A 874       43.78   -143.60                                   
REMARK 500    ASP A 892       78.55     56.50                                   
REMARK 500    ASN A 975       63.16   -108.86                                   
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 600                                                                      
REMARK 600 HETEROGEN                                                            
REMARK 600                                                                      
REMARK 600 PHOSPHOTYROSINE (PTR): PHOSPHORYLATION OF TYROSINE RESIDUES          
REMARK 600 FORMIC ACID (FMT): PRESENT AS FORMATE.                               
REMARK 800                                                                      
REMARK 800 SITE                                                                 
REMARK 800 SITE_IDENTIFIER: AC1                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE FMT A 2011                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE FMT A 2012                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC3                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE FMT A 2013                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC4                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE FMT A 2014                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC5                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE FMT A 2015                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC6                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE FMT A 2016                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC7                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE FMT A 2017                
REMARK 999                                                                      
REMARK 999 SEQUENCE                                                             
REMARK 999 RESIDUES 827-840 HAVE BEEN DELETED FROM THE CONSTRUCT                
DBREF  5AMN A  705   826  UNP    P07949   RET_HUMAN      705    826             
DBREF  5AMN A  841  1012  UNP    P07949   RET_HUMAN      841   1012             
SEQADV 5AMN GLY A  700  UNP  P07949              EXPRESSION TAG                 
SEQADV 5AMN PRO A  701  UNP  P07949              EXPRESSION TAG                 
SEQADV 5AMN LEU A  702  UNP  P07949              EXPRESSION TAG                 
SEQADV 5AMN SER A  703  UNP  P07949              EXPRESSION TAG                 
SEQADV 5AMN LEU A  704  UNP  P07949              EXPRESSION TAG                 
SEQRES   1 A  299  GLY PRO LEU SER LEU SER VAL ASP ALA PHE LYS ILE LEU          
SEQRES   2 A  299  GLU ASP PRO LYS TRP GLU PHE PRO ARG LYS ASN LEU VAL          
SEQRES   3 A  299  LEU GLY LYS THR LEU GLY GLU GLY GLU PHE GLY LYS VAL          
SEQRES   4 A  299  VAL LYS ALA THR ALA PHE HIS LEU LYS GLY ARG ALA GLY          
SEQRES   5 A  299  TYR THR THR VAL ALA VAL LYS MET LEU LYS GLU ASN ALA          
SEQRES   6 A  299  SER PRO SER GLU LEU ARG ASP LEU LEU SER GLU PHE ASN          
SEQRES   7 A  299  VAL LEU LYS GLN VAL ASN HIS PRO HIS VAL ILE LYS LEU          
SEQRES   8 A  299  TYR GLY ALA CYS SER GLN ASP GLY PRO LEU LEU LEU ILE          
SEQRES   9 A  299  VAL GLU TYR ALA LYS TYR GLY SER LEU ARG GLY PHE LEU          
SEQRES  10 A  299  ARG GLU SER ARG LYS VAL GLY PRO GLY TYR PRO ASP GLU          
SEQRES  11 A  299  ARG ALA LEU THR MET GLY ASP LEU ILE SER PHE ALA TRP          
SEQRES  12 A  299  GLN ILE SER GLN GLY MET GLN TYR LEU ALA GLU MET LYS          
SEQRES  13 A  299  LEU VAL HIS ARG ASP LEU ALA ALA ARG ASN ILE LEU VAL          
SEQRES  14 A  299  ALA GLU GLY ARG LYS MET LYS ILE SER ASP PHE GLY LEU          
SEQRES  15 A  299  SER ARG ASP VAL PTR GLU GLU ASP SER PTR VAL LYS ARG          
SEQRES  16 A  299  SER GLN GLY ARG ILE PRO VAL LYS TRP MET ALA ILE GLU          
SEQRES  17 A  299  SER LEU PHE ASP HIS ILE TYR THR THR GLN SER ASP VAL          
SEQRES  18 A  299  TRP SER PHE GLY VAL LEU LEU TRP GLU ILE VAL THR LEU          
SEQRES  19 A  299  GLY GLY ASN PRO TYR PRO GLY ILE PRO PRO GLU ARG LEU          
SEQRES  20 A  299  PHE ASN LEU LEU LYS THR GLY HIS ARG MET GLU ARG PRO          
SEQRES  21 A  299  ASP ASN CYS SER GLU GLU MET TYR ARG LEU MET LEU GLN          
SEQRES  22 A  299  CYS TRP LYS GLN GLU PRO ASP LYS ARG PRO VAL PHE ALA          
SEQRES  23 A  299  ASP ILE SER LYS ASP LEU GLU LYS MET MET VAL LYS ARG          
MODRES 5AMN PTR A  900  TYR  O-PHOSPHOTYROSINE                                  
MODRES 5AMN PTR A  905  TYR  O-PHOSPHOTYROSINE                                  
HET    PTR  A 900      16                                                       
HET    PTR  A 905      16                                                       
HET    DTQ  A2018      37                                                       
HET    FMT  A2011       5                                                       
HET    FMT  A2012       5                                                       
HET    FMT  A2013       5                                                       
HET    FMT  A2014       5                                                       
HET    FMT  A2015       5                                                       
HET    FMT  A2016       5                                                       
HET    FMT  A2017       5                                                       
HETNAM     PTR O-PHOSPHOTYROSINE                                                
HETNAM     DTQ 4-[3-HYDROXYANILINO]-6,7-DIMETHOXYQUINAZOLINE                    
HETNAM     FMT FORMIC ACID                                                      
HETSYN     PTR PHOSPHONOTYROSINE                                                
FORMUL   1  PTR    2(C9 H12 N O6 P)                                             
FORMUL   2  DTQ    C16 H15 N3 O3                                                
FORMUL   3  FMT    7(C H2 O2)                                                   
FORMUL  10  HOH   *48(H2 O)                                                     
HELIX    1   1 GLY A  700  ILE A  711  1                                  12    
HELIX    2   2 ASP A  714  TRP A  717  5                                   4    
HELIX    3   3 PRO A  720  LYS A  722  5                                   3    
HELIX    4   4 SER A  765  LYS A  780  1                                  16    
HELIX    5   5 SER A  811  SER A  819  1                                   9    
HELIX    6   6 THR A  847  GLU A  867  1                                  21    
HELIX    7   7 ALA A  876  ARG A  878  5                                   3    
HELIX    8   8 PRO A  914  MET A  918  5                                   5    
HELIX    9   9 ALA A  919  HIS A  926  1                                   8    
HELIX   10  10 THR A  929  THR A  946  1                                  18    
HELIX   11  11 PRO A  956  GLU A  958  5                                   3    
HELIX   12  12 ARG A  959  THR A  966  1                                   8    
HELIX   13  13 SER A  977  TRP A  988  1                                  12    
HELIX   14  14 GLU A  991  ARG A  995  5                                   5    
HELIX   15  15 VAL A  997  MET A 1009  1                                  13    
SHEET    1  AA 5 LEU A 724  GLU A 732  0                                        
SHEET    2  AA 5 GLY A 736  PHE A 744 -1  O  VAL A 738   N  LEU A 730           
SHEET    3  AA 5 TYR A 752  LEU A 760 -1  O  THR A 753   N  ALA A 743           
SHEET    4  AA 5 LEU A 801  GLU A 805 -1  O  LEU A 802   N  LYS A 758           
SHEET    5  AA 5 LEU A 790  CYS A 794 -1  N  TYR A 791   O  ILE A 803           
SHEET    1  AB 2 LEU A 870  VAL A 871  0                                        
SHEET    2  AB 2 ARG A 897  ASP A 898 -1  O  ARG A 897   N  VAL A 871           
SHEET    1  AC 2 ILE A 880  ALA A 883  0                                        
SHEET    2  AC 2 LYS A 887  ILE A 890 -1  O  LYS A 887   N  ALA A 883           
SHEET    1  AD 2 PTR A 905  VAL A 906  0                                        
SHEET    2  AD 2 ILE A 927  TYR A 928 -1  O  TYR A 928   N  PTR A 905           
LINK         C   VAL A 899                 N   PTR A 900     1555   1555  1.33  
LINK         C   PTR A 900                 N   GLU A 901     1555   1555  1.33  
LINK         C   SER A 904                 N   PTR A 905     1555   1555  1.33  
LINK         C   PTR A 905                 N   VAL A 906     1555   1555  1.33  
SITE     1 AC1  8 GLY A 700  PRO A 701  LEU A 702  SER A 703                    
SITE     2 AC1  8 GLN A 910  LEU A 923  PHE A 924  HIS A 926                    
SITE     1 AC2  5 ARG A 873  LEU A 895  LYS A 907  GLY A 911                    
SITE     2 AC2  5 ARG A 912                                                     
SITE     1 AC3  4 ASP A 707  LYS A 728  LYS A 740  TYR A 806                    
SITE     1 AC4  1 HOH A3039                                                     
SITE     1 AC5  4 ALA A 866  VAL A 997  PHE A 998  ALA A 999                    
SITE     1 AC6  1 LYS A 747                                                     
SITE     1 AC7  3 THR A 754  PHE A 924  HOH A3009                               
CRYST1   50.570   50.570  242.840  90.00  90.00  90.00 P 43 21 2     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      0.019775  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.019775  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.004118        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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