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Database: PDB
Entry: 4DCE
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Original site: 4DCE 
HEADER    TRANSFERASE/INHIBITOR                   17-JAN-12   4DCE              
TITLE     CRYSTAL STRUCTURE OF HUMAN ANAPLASTIC LYMPHOMA KINASE IN COMPLEX WITH 
TITLE    2 A PIPERIDINE-CARBOXAMIDE INHIBITOR                                   
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: ALK TYROSINE KINASE RECEPTOR;                              
COMPND   3 CHAIN: A, B;                                                         
COMPND   4 FRAGMENT: KINASE DOMAIN, UNP RESIDUES 1078-1410;                     
COMPND   5 SYNONYM: ANAPLASTIC LYMPHOMA KINASE;                                 
COMPND   6 EC: 2.7.10.1;                                                        
COMPND   7 ENGINEERED: YES;                                                     
COMPND   8 MUTATION: YES                                                        
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606;                                                
SOURCE   5 GENE: ALK;                                                           
SOURCE   6 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA;                            
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 7108;                                       
SOURCE   8 EXPRESSION_SYSTEM_VECTOR_TYPE: VIRUS;                                
SOURCE   9 EXPRESSION_SYSTEM_PLASMID: PFASTBAC1                                 
KEYWDS    RECEPTOR TYROSINE KINASE, INHIBITOR, NPM-ALK, EML4-ALK, TRANSFERASE-  
KEYWDS   2 INHIBITOR COMPLEX                                                    
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    D.A.WHITTINGTON,L.F.EPSTEIN,H.CHEN                                    
REVDAT   3   15-NOV-17 4DCE    1       REMARK                                   
REVDAT   2   09-MAY-12 4DCE    1       JRNL                                     
REVDAT   1   08-FEB-12 4DCE    0                                                
JRNL        AUTH   M.C.BRYAN,D.A.WHITTINGTON,E.M.DOHERTY,J.R.FALSEY,A.C.CHENG,  
JRNL        AUTH 2 R.EMKEY,R.L.BRAKE,R.T.LEWIS                                  
JRNL        TITL   RAPID DEVELOPMENT OF PIPERIDINE CARBOXAMIDES AS POTENT AND   
JRNL        TITL 2 SELECTIVE ANAPLASTIC LYMPHOMA KINASE INHIBITORS.             
JRNL        REF    J.MED.CHEM.                   V.  55  1698 2012              
JRNL        REFN                   ISSN 0022-2623                               
JRNL        PMID   22263917                                                     
JRNL        DOI    10.1021/JM201565S                                            
REMARK   2                                                                      
REMARK   2 RESOLUTION.    2.03 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : REFMAC                                               
REMARK   3   AUTHORS     : MURSHUDOV,VAGIN,DODSON                               
REMARK   3                                                                      
REMARK   3    REFINEMENT TARGET : MAXIMUM LIKELIHOOD                            
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 2.03                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 38.83                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : 0.000                          
REMARK   3   COMPLETENESS FOR RANGE        (%) : 98.6                           
REMARK   3   NUMBER OF REFLECTIONS             : 39180                          
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) : 0.211                           
REMARK   3   R VALUE            (WORKING SET) : 0.208                           
REMARK   3   FREE R VALUE                     : 0.256                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 5.000                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 1972                            
REMARK   3                                                                      
REMARK   3  FIT IN THE HIGHEST RESOLUTION BIN.                                  
REMARK   3   TOTAL NUMBER OF BINS USED           : 20                           
REMARK   3   BIN RESOLUTION RANGE HIGH       (A) : 2.03                         
REMARK   3   BIN RESOLUTION RANGE LOW        (A) : 2.08                         
REMARK   3   REFLECTION IN BIN     (WORKING SET) : 2476                         
REMARK   3   BIN COMPLETENESS (WORKING+TEST) (%) : 89.21                        
REMARK   3   BIN R VALUE           (WORKING SET) : 0.2710                       
REMARK   3   BIN FREE R VALUE SET COUNT          : 154                          
REMARK   3   BIN FREE R VALUE                    : 0.3110                       
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS            : 4499                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 72                                      
REMARK   3   SOLVENT ATOMS            : 287                                     
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 31.70                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 34.41                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : -0.60000                                             
REMARK   3    B22 (A**2) : 1.79000                                              
REMARK   3    B33 (A**2) : -1.19000                                             
REMARK   3    B12 (A**2) : 0.00000                                              
REMARK   3    B13 (A**2) : -0.24000                                             
REMARK   3    B23 (A**2) : 0.00000                                              
REMARK   3                                                                      
REMARK   3  ESTIMATED OVERALL COORDINATE ERROR.                                 
REMARK   3   ESU BASED ON R VALUE                            (A): 0.226         
REMARK   3   ESU BASED ON FREE R VALUE                       (A): 0.192         
REMARK   3   ESU BASED ON MAXIMUM LIKELIHOOD                 (A): 0.143         
REMARK   3   ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 5.130         
REMARK   3                                                                      
REMARK   3 CORRELATION COEFFICIENTS.                                            
REMARK   3   CORRELATION COEFFICIENT FO-FC      : 0.947                         
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : 0.925                         
REMARK   3                                                                      
REMARK   3  RMS DEVIATIONS FROM IDEAL VALUES        COUNT    RMS    WEIGHT      
REMARK   3   BOND LENGTHS REFINED ATOMS        (A):  4686 ; 0.007 ; 0.022       
REMARK   3   BOND LENGTHS OTHERS               (A):  NULL ;  NULL ;  NULL       
REMARK   3   BOND ANGLES REFINED ATOMS   (DEGREES):  6353 ; 1.027 ; 1.993       
REMARK   3   BOND ANGLES OTHERS          (DEGREES):  NULL ;  NULL ;  NULL       
REMARK   3   TORSION ANGLES, PERIOD 1    (DEGREES):   564 ; 5.236 ; 5.000       
REMARK   3   TORSION ANGLES, PERIOD 2    (DEGREES):   203 ;35.242 ;23.990       
REMARK   3   TORSION ANGLES, PERIOD 3    (DEGREES):   781 ;13.164 ;15.000       
REMARK   3   TORSION ANGLES, PERIOD 4    (DEGREES):    30 ;16.240 ;15.000       
REMARK   3   CHIRAL-CENTER RESTRAINTS       (A**3):   688 ; 0.069 ; 0.200       
REMARK   3   GENERAL PLANES REFINED ATOMS      (A):  3562 ; 0.003 ; 0.020       
REMARK   3   GENERAL PLANES OTHERS             (A):  NULL ;  NULL ;  NULL       
REMARK   3   NON-BONDED CONTACTS REFINED ATOMS (A):  2180 ; 0.182 ; 0.200       
REMARK   3   NON-BONDED CONTACTS OTHERS        (A):  NULL ;  NULL ;  NULL       
REMARK   3   NON-BONDED TORSION REFINED ATOMS  (A):  3235 ; 0.302 ; 0.200       
REMARK   3   NON-BONDED TORSION OTHERS         (A):  NULL ;  NULL ;  NULL       
REMARK   3   H-BOND (X...Y) REFINED ATOMS      (A):   284 ; 0.119 ; 0.200       
REMARK   3   H-BOND (X...Y) OTHERS             (A):  NULL ;  NULL ;  NULL       
REMARK   3   POTENTIAL METAL-ION REFINED ATOMS (A):  NULL ;  NULL ;  NULL       
REMARK   3   POTENTIAL METAL-ION OTHERS        (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY VDW REFINED ATOMS        (A):    80 ; 0.174 ; 0.200       
REMARK   3   SYMMETRY VDW OTHERS               (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY H-BOND REFINED ATOMS     (A):    11 ; 0.126 ; 0.200       
REMARK   3   SYMMETRY H-BOND OTHERS            (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY METAL-ION REFINED ATOMS  (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY METAL-ION OTHERS         (A):  NULL ;  NULL ;  NULL       
REMARK   3                                                                      
REMARK   3  ISOTROPIC THERMAL FACTOR RESTRAINTS.     COUNT   RMS    WEIGHT      
REMARK   3   MAIN-CHAIN BOND REFINED ATOMS  (A**2):  2951 ; 0.799 ; 2.000       
REMARK   3   MAIN-CHAIN BOND OTHER ATOMS    (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   MAIN-CHAIN ANGLE REFINED ATOMS (A**2):  4639 ; 1.342 ; 3.000       
REMARK   3   MAIN-CHAIN ANGLE OTHER ATOMS   (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SIDE-CHAIN BOND REFINED ATOMS  (A**2):  1992 ; 1.315 ; 3.000       
REMARK   3   SIDE-CHAIN BOND OTHER ATOMS    (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SIDE-CHAIN ANGLE REFINED ATOMS (A**2):  1714 ; 2.197 ; 6.000       
REMARK   3   SIDE-CHAIN ANGLE OTHER ATOMS   (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   LONG RANGE B REFINED ATOMS     (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   LONG RANGE B OTHER ATOMS       (A**2):  NULL ;  NULL ;  NULL       
REMARK   3                                                                      
REMARK   3 ANISOTROPIC THERMAL FACTOR RESTRAINTS.    COUNT   RMS   WEIGHT       
REMARK   3   RIGID-BOND RESTRAINTS          (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SPHERICITY; FREE ATOMS         (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SPHERICITY; BONDED ATOMS       (A**2):  NULL ;  NULL ;  NULL       
REMARK   3                                                                      
REMARK   3  NCS RESTRAINTS STATISTICS                                           
REMARK   3   NUMBER OF DIFFERENT NCS GROUPS : NULL                              
REMARK   3                                                                      
REMARK   3  TLS DETAILS                                                         
REMARK   3   NUMBER OF TLS GROUPS  : NULL                                       
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELLING.                                             
REMARK   3   METHOD USED : MASK                                                 
REMARK   3   PARAMETERS FOR MASK CALCULATION                                    
REMARK   3   VDW PROBE RADIUS   : 1.20                                          
REMARK   3   ION PROBE RADIUS   : 0.80                                          
REMARK   3   SHRINKAGE RADIUS   : 0.80                                          
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: HYDROGENS HAVE BEEN ADDED IN THE RIDING   
REMARK   3  POSITIONS                                                           
REMARK   4                                                                      
REMARK   4 4DCE COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 23-JAN-12.                  
REMARK 100 THE DEPOSITION ID IS D_1000070153.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 14-MAR-09                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : 6.5                                
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : APS                                
REMARK 200  BEAMLINE                       : 22-ID                              
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.0000                             
REMARK 200  MONOCHROMATOR                  : SI(111)                            
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : CCD                                
REMARK 200  DETECTOR MANUFACTURER          : MARMOSAIC 300 MM CCD               
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : DENZO, HKL-2000                    
REMARK 200  DATA SCALING SOFTWARE          : SCALEPACK, HKL-2000                
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 39292                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.030                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 50.000                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : -3.000                             
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 98.5                               
REMARK 200  DATA REDUNDANCY                : 2.300                              
REMARK 200  R MERGE                    (I) : 0.04800                            
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 11.0000                            
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.03                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 2.10                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 90.3                               
REMARK 200  DATA REDUNDANCY IN SHELL       : 2.00                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.49000                            
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : NULL                               
REMARK 200                                                                      
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH                              
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT        
REMARK 200 SOFTWARE USED: EPMR                                                  
REMARK 200 STARTING MODEL: APO ALK (UNPUBLISHED)                                
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 40.91                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.08                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 27% PEG 5000 MME, 100 MM MES, 200 MM     
REMARK 280  AMMONIUM SULFATE, 5 MM DITHIOTHREITOL, PH 6.5, VAPOR DIFFUSION,     
REMARK 280  HANGING DROP, TEMPERATURE 277K                                      
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY                                            
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 1 21 1                         
REMARK 290                                                                      
REMARK 290      SYMOP   SYMMETRY                                                
REMARK 290     NNNMMM   OPERATOR                                                
REMARK 290       1555   X,Y,Z                                                   
REMARK 290       2555   -X,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       52.40950            
REMARK 290   SMTRY3   2  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 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     TYR A  1078                                                      
REMARK 465     LYS A  1079                                                      
REMARK 465     LEU A  1080                                                      
REMARK 465     SER A  1081                                                      
REMARK 465     LYS A  1082                                                      
REMARK 465     LEU A  1083                                                      
REMARK 465     ARG A  1084                                                      
REMARK 465     THR A  1085                                                      
REMARK 465     SER A  1086                                                      
REMARK 465     THR A  1087                                                      
REMARK 465     ILE A  1088                                                      
REMARK 465     MET A  1089                                                      
REMARK 465     THR A  1090                                                      
REMARK 465     ASP A  1091                                                      
REMARK 465     TYR A  1092                                                      
REMARK 465     GLY A  1125                                                      
REMARK 465     ALA A  1126                                                      
REMARK 465     PHE A  1127                                                      
REMARK 465     GLY A  1137                                                      
REMARK 465     MET A  1138                                                      
REMARK 465     PRO A  1139                                                      
REMARK 465     ASN A  1140                                                      
REMARK 465     ASP A  1141                                                      
REMARK 465     MET A  1273                                                      
REMARK 465     ALA A  1274                                                      
REMARK 465     ARG A  1275                                                      
REMARK 465     ASP A  1276                                                      
REMARK 465     ILE A  1277                                                      
REMARK 465     TYR A  1278                                                      
REMARK 465     ARG A  1279                                                      
REMARK 465     ALA A  1280                                                      
REMARK 465     SER A  1281                                                      
REMARK 465     TYR A  1282                                                      
REMARK 465     TYR A  1283                                                      
REMARK 465     ARG A  1284                                                      
REMARK 465     LYS A  1285                                                      
REMARK 465     GLY A  1286                                                      
REMARK 465     PRO A  1403                                                      
REMARK 465     LEU A  1404                                                      
REMARK 465     VAL A  1405                                                      
REMARK 465     GLU A  1406                                                      
REMARK 465     GLU A  1407                                                      
REMARK 465     GLU A  1408                                                      
REMARK 465     GLU A  1409                                                      
REMARK 465     LYS A  1410                                                      
REMARK 465     TYR B  1078                                                      
REMARK 465     LYS B  1079                                                      
REMARK 465     LEU B  1080                                                      
REMARK 465     SER B  1081                                                      
REMARK 465     LYS B  1082                                                      
REMARK 465     LEU B  1083                                                      
REMARK 465     ARG B  1084                                                      
REMARK 465     THR B  1085                                                      
REMARK 465     SER B  1086                                                      
REMARK 465     THR B  1087                                                      
REMARK 465     ILE B  1088                                                      
REMARK 465     MET B  1089                                                      
REMARK 465     THR B  1090                                                      
REMARK 465     ASP B  1091                                                      
REMARK 465     TYR B  1092                                                      
REMARK 465     ASN B  1093                                                      
REMARK 465     GLY B  1125                                                      
REMARK 465     ALA B  1126                                                      
REMARK 465     PHE B  1127                                                      
REMARK 465     GLY B  1128                                                      
REMARK 465     GLY B  1137                                                      
REMARK 465     MET B  1138                                                      
REMARK 465     PRO B  1139                                                      
REMARK 465     ASN B  1140                                                      
REMARK 465     ASP B  1141                                                      
REMARK 465     PRO B  1142                                                      
REMARK 465     MET B  1273                                                      
REMARK 465     ALA B  1274                                                      
REMARK 465     ARG B  1275                                                      
REMARK 465     ASP B  1276                                                      
REMARK 465     ILE B  1277                                                      
REMARK 465     TYR B  1278                                                      
REMARK 465     ARG B  1279                                                      
REMARK 465     ALA B  1280                                                      
REMARK 465     SER B  1281                                                      
REMARK 465     TYR B  1282                                                      
REMARK 465     TYR B  1283                                                      
REMARK 465     ARG B  1284                                                      
REMARK 465     LYS B  1285                                                      
REMARK 465     GLY B  1286                                                      
REMARK 465     GLY B  1287                                                      
REMARK 465     PRO B  1403                                                      
REMARK 465     LEU B  1404                                                      
REMARK 465     VAL B  1405                                                      
REMARK 465     GLU B  1406                                                      
REMARK 465     GLU B  1407                                                      
REMARK 465     GLU B  1408                                                      
REMARK 465     GLU B  1409                                                      
REMARK 465     LYS B  1410                                                      
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 A1248      -10.33     85.77                                   
REMARK 500    ASP A1249       56.00   -148.37                                   
REMARK 500    MET A1302      -93.70    -85.52                                   
REMARK 500    LEU B1122      -76.39   -121.62                                   
REMARK 500    ARG B1248      -14.30     83.87                                   
REMARK 500    ASP B1249       52.27   -143.54                                   
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 0JF A 1501                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 0JF B 1501                
DBREF  4DCE A 1078  1410  UNP    Q9UM73   ALK_HUMAN     1078   1410             
DBREF  4DCE B 1078  1410  UNP    Q9UM73   ALK_HUMAN     1078   1410             
SEQADV 4DCE SER A 1097  UNP  Q9UM73    CYS  1097 ENGINEERED MUTATION            
SEQADV 4DCE SER B 1097  UNP  Q9UM73    CYS  1097 ENGINEERED MUTATION            
SEQRES   1 A  333  TYR LYS LEU SER LYS LEU ARG THR SER THR ILE MET THR          
SEQRES   2 A  333  ASP TYR ASN PRO ASN TYR SER PHE ALA GLY LYS THR SER          
SEQRES   3 A  333  SER ILE SER ASP LEU LYS GLU VAL PRO ARG LYS ASN ILE          
SEQRES   4 A  333  THR LEU ILE ARG GLY LEU GLY HIS GLY ALA PHE GLY GLU          
SEQRES   5 A  333  VAL TYR GLU GLY GLN VAL SER GLY MET PRO ASN ASP PRO          
SEQRES   6 A  333  SER PRO LEU GLN VAL ALA VAL LYS THR LEU PRO GLU VAL          
SEQRES   7 A  333  CYS SER GLU GLN ASP GLU LEU ASP PHE LEU MET GLU ALA          
SEQRES   8 A  333  LEU ILE ILE SER LYS PHE ASN HIS GLN ASN ILE VAL ARG          
SEQRES   9 A  333  CYS ILE GLY VAL SER LEU GLN SER LEU PRO ARG PHE ILE          
SEQRES  10 A  333  LEU LEU GLU LEU MET ALA GLY GLY ASP LEU LYS SER PHE          
SEQRES  11 A  333  LEU ARG GLU THR ARG PRO ARG PRO SER GLN PRO SER SER          
SEQRES  12 A  333  LEU ALA MET LEU ASP LEU LEU HIS VAL ALA ARG ASP ILE          
SEQRES  13 A  333  ALA CYS GLY CYS GLN TYR LEU GLU GLU ASN HIS PHE ILE          
SEQRES  14 A  333  HIS ARG ASP ILE ALA ALA ARG ASN CYS LEU LEU THR CYS          
SEQRES  15 A  333  PRO GLY PRO GLY ARG VAL ALA LYS ILE GLY ASP PHE GLY          
SEQRES  16 A  333  MET ALA ARG ASP ILE TYR ARG ALA SER TYR TYR ARG LYS          
SEQRES  17 A  333  GLY GLY CYS ALA MET LEU PRO VAL LYS TRP MET PRO PRO          
SEQRES  18 A  333  GLU ALA PHE MET GLU GLY ILE PHE THR SER LYS THR ASP          
SEQRES  19 A  333  THR TRP SER PHE GLY VAL LEU LEU TRP GLU ILE PHE SER          
SEQRES  20 A  333  LEU GLY TYR MET PRO TYR PRO SER LYS SER ASN GLN GLU          
SEQRES  21 A  333  VAL LEU GLU PHE VAL THR SER GLY GLY ARG MET ASP PRO          
SEQRES  22 A  333  PRO LYS ASN CYS PRO GLY PRO VAL TYR ARG ILE MET THR          
SEQRES  23 A  333  GLN CYS TRP GLN HIS GLN PRO GLU ASP ARG PRO ASN PHE          
SEQRES  24 A  333  ALA ILE ILE LEU GLU ARG ILE GLU TYR CYS THR GLN ASP          
SEQRES  25 A  333  PRO ASP VAL ILE ASN THR ALA LEU PRO ILE GLU TYR GLY          
SEQRES  26 A  333  PRO LEU VAL GLU GLU GLU GLU LYS                              
SEQRES   1 B  333  TYR LYS LEU SER LYS LEU ARG THR SER THR ILE MET THR          
SEQRES   2 B  333  ASP TYR ASN PRO ASN TYR SER PHE ALA GLY LYS THR SER          
SEQRES   3 B  333  SER ILE SER ASP LEU LYS GLU VAL PRO ARG LYS ASN ILE          
SEQRES   4 B  333  THR LEU ILE ARG GLY LEU GLY HIS GLY ALA PHE GLY GLU          
SEQRES   5 B  333  VAL TYR GLU GLY GLN VAL SER GLY MET PRO ASN ASP PRO          
SEQRES   6 B  333  SER PRO LEU GLN VAL ALA VAL LYS THR LEU PRO GLU VAL          
SEQRES   7 B  333  CYS SER GLU GLN ASP GLU LEU ASP PHE LEU MET GLU ALA          
SEQRES   8 B  333  LEU ILE ILE SER LYS PHE ASN HIS GLN ASN ILE VAL ARG          
SEQRES   9 B  333  CYS ILE GLY VAL SER LEU GLN SER LEU PRO ARG PHE ILE          
SEQRES  10 B  333  LEU LEU GLU LEU MET ALA GLY GLY ASP LEU LYS SER PHE          
SEQRES  11 B  333  LEU ARG GLU THR ARG PRO ARG PRO SER GLN PRO SER SER          
SEQRES  12 B  333  LEU ALA MET LEU ASP LEU LEU HIS VAL ALA ARG ASP ILE          
SEQRES  13 B  333  ALA CYS GLY CYS GLN TYR LEU GLU GLU ASN HIS PHE ILE          
SEQRES  14 B  333  HIS ARG ASP ILE ALA ALA ARG ASN CYS LEU LEU THR CYS          
SEQRES  15 B  333  PRO GLY PRO GLY ARG VAL ALA LYS ILE GLY ASP PHE GLY          
SEQRES  16 B  333  MET ALA ARG ASP ILE TYR ARG ALA SER TYR TYR ARG LYS          
SEQRES  17 B  333  GLY GLY CYS ALA MET LEU PRO VAL LYS TRP MET PRO PRO          
SEQRES  18 B  333  GLU ALA PHE MET GLU GLY ILE PHE THR SER LYS THR ASP          
SEQRES  19 B  333  THR TRP SER PHE GLY VAL LEU LEU TRP GLU ILE PHE SER          
SEQRES  20 B  333  LEU GLY TYR MET PRO TYR PRO SER LYS SER ASN GLN GLU          
SEQRES  21 B  333  VAL LEU GLU PHE VAL THR SER GLY GLY ARG MET ASP PRO          
SEQRES  22 B  333  PRO LYS ASN CYS PRO GLY PRO VAL TYR ARG ILE MET THR          
SEQRES  23 B  333  GLN CYS TRP GLN HIS GLN PRO GLU ASP ARG PRO ASN PHE          
SEQRES  24 B  333  ALA ILE ILE LEU GLU ARG ILE GLU TYR CYS THR GLN ASP          
SEQRES  25 B  333  PRO ASP VAL ILE ASN THR ALA LEU PRO ILE GLU TYR GLY          
SEQRES  26 B  333  PRO LEU VAL GLU GLU GLU GLU LYS                              
HET    0JF  A1501      36                                                       
HET    0JF  B1501      36                                                       
HETNAM     0JF (3S)-N-(4-METHYLBENZYL)-1-{2-[(3,4,5-TRIMETHOXYPHENYL)           
HETNAM   2 0JF  AMINO]PYRIMIDIN-4-YL}PIPERIDINE-3-CARBOXAMIDE                   
FORMUL   3  0JF    2(C27 H33 N5 O4)                                             
FORMUL   5  HOH   *287(H2 O)                                                    
HELIX    1   1 SER A 1104  LEU A 1108  5                                   5    
HELIX    2   2 PRO A 1112  LYS A 1114  5                                   3    
HELIX    3   3 SER A 1157  PHE A 1174  1                                  18    
HELIX    4   4 LEU A 1204  THR A 1211  1                                   8    
HELIX    5   5 ALA A 1222  ASN A 1243  1                                  22    
HELIX    6   6 ALA A 1251  ARG A 1253  5                                   3    
HELIX    7   7 PRO A 1292  MET A 1296  5                                   5    
HELIX    8   8 PRO A 1297  MET A 1302  1                                   6    
HELIX    9   9 THR A 1307  SER A 1324  1                                  18    
HELIX   10  10 SER A 1334  SER A 1344  1                                  11    
HELIX   11  11 PRO A 1355  TRP A 1366  1                                  12    
HELIX   12  12 GLN A 1369  ARG A 1373  5                                   5    
HELIX   13  13 ASN A 1375  GLN A 1388  1                                  14    
HELIX   14  14 ASP A 1389  ASN A 1394  1                                   6    
HELIX   15  15 SER B 1106  LEU B 1108  5                                   3    
HELIX   16  16 PRO B 1112  LYS B 1114  5                                   3    
HELIX   17  17 SER B 1157  PHE B 1174  1                                  18    
HELIX   18  18 LEU B 1204  ARG B 1212  1                                   9    
HELIX   19  19 ALA B 1222  ASN B 1243  1                                  22    
HELIX   20  20 ALA B 1251  ARG B 1253  5                                   3    
HELIX   21  21 PRO B 1292  MET B 1296  5                                   5    
HELIX   22  22 PRO B 1297  GLY B 1304  1                                   8    
HELIX   23  23 THR B 1307  SER B 1324  1                                  18    
HELIX   24  24 SER B 1334  SER B 1344  1                                  11    
HELIX   25  25 PRO B 1355  TRP B 1366  1                                  12    
HELIX   26  26 GLN B 1369  ARG B 1373  5                                   5    
HELIX   27  27 ASN B 1375  ASP B 1389  1                                  15    
HELIX   28  28 ASP B 1389  ASN B 1394  1                                   6    
SHEET    1   A 2 TYR A1096  PHE A1098  0                                        
SHEET    2   A 2 LYS A1101  SER A1103 -1  O  SER A1103   N  TYR A1096           
SHEET    1   B 5 ILE A1116  GLY A1123  0                                        
SHEET    2   B 5 VAL A1130  VAL A1135 -1  O  GLU A1132   N  ARG A1120           
SHEET    3   B 5 LEU A1145  THR A1151 -1  O  VAL A1147   N  GLY A1133           
SHEET    4   B 5 PHE A1193  GLU A1197 -1  O  LEU A1196   N  ALA A1148           
SHEET    5   B 5 CYS A1182  SER A1186 -1  N  GLY A1184   O  LEU A1195           
SHEET    1   C 3 GLY A1202  ASP A1203  0                                        
SHEET    2   C 3 CYS A1255  LEU A1257 -1  O  LEU A1257   N  GLY A1202           
SHEET    3   C 3 ALA A1266  ILE A1268 -1  O  LYS A1267   N  LEU A1256           
SHEET    1   D 2 ASN B1095  PHE B1098  0                                        
SHEET    2   D 2 LYS B1101  SER B1104 -1  O  SER B1103   N  TYR B1096           
SHEET    1   E 5 ILE B1116  GLY B1121  0                                        
SHEET    2   E 5 VAL B1130  VAL B1135 -1  O  GLU B1132   N  ARG B1120           
SHEET    3   E 5 LEU B1145  THR B1151 -1  O  VAL B1149   N  TYR B1131           
SHEET    4   E 5 PHE B1193  GLU B1197 -1  O  LEU B1196   N  ALA B1148           
SHEET    5   E 5 CYS B1182  SER B1186 -1  N  GLY B1184   O  LEU B1195           
SHEET    1   F 3 GLY B1202  ASP B1203  0                                        
SHEET    2   F 3 CYS B1255  LEU B1257 -1  O  LEU B1257   N  GLY B1202           
SHEET    3   F 3 ALA B1266  ILE B1268 -1  O  LYS B1267   N  LEU B1256           
CISPEP   1 LEU A 1190    PRO A 1191          0        -1.29                     
CISPEP   2 LEU B 1190    PRO B 1191          0        -2.32                     
SITE     1 AC1 15 LEU A1122  ALA A1148  LYS A1150  GLU A1167                    
SITE     2 AC1 15 ILE A1171  ILE A1179  VAL A1180  GLU A1197                    
SITE     3 AC1 15 MET A1199  ALA A1200  GLY A1202  LEU A1256                    
SITE     4 AC1 15 GLY A1269  ASP A1270  PHE A1271                               
SITE     1 AC2 16 LEU B1122  VAL B1130  ALA B1148  LYS B1150                    
SITE     2 AC2 16 ILE B1171  LEU B1196  GLU B1197  MET B1199                    
SITE     3 AC2 16 ALA B1200  GLY B1202  ASP B1203  LEU B1256                    
SITE     4 AC2 16 GLY B1269  ASP B1270  PHE B1271  HOH B1673                    
CRYST1   51.612  104.819   57.817  90.00  90.15  90.00 P 1 21 1      4          
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      0.019375  0.000000  0.000049        0.00000                         
SCALE2      0.000000  0.009540  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.017296        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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