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Database: PDB
Entry: 4CFN
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HEADER    CELL CYCLE                              19-NOV-13   4CFN              
TITLE     STRUCTURE-BASED DESIGN OF C8-SUBSTITUTED O6-CYCLOHEXYLMETHOXYGUANINE  
TITLE    2 CDK1 AND 2 INHIBITORS.                                               
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: CYCLIN-DEPENDENT KINASE 2;                                 
COMPND   3 CHAIN: A, C;                                                         
COMPND   4 SYNONYM: CELL DIVISION PROTEIN KINASE 2, P33 PROTEIN KINASE;         
COMPND   5 EC: 2.7.11.22, 2.7.11.23;                                            
COMPND   6 ENGINEERED: YES;                                                     
COMPND   7 OTHER_DETAILS: PHOSPHORYLATED ON RESIDUE T160;                       
COMPND   8 MOL_ID: 2;                                                           
COMPND   9 MOLECULE: CYCLIN-A2;                                                 
COMPND  10 CHAIN: B, D;                                                         
COMPND  11 FRAGMENT: CDK-ACTIVATING FRAGMENT, RESIDUES 175-432;                 
COMPND  12 SYNONYM: CYCLIN-A;                                                   
COMPND  13 ENGINEERED: YES                                                      
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606;                                                
SOURCE   5 EXPRESSION_SYSTEM: ESCHERICHIA COLI B;                               
SOURCE   6 EXPRESSION_SYSTEM_TAXID: 37762;                                      
SOURCE   7 EXPRESSION_SYSTEM_STRAIN: B834;                                      
SOURCE   8 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;                              
SOURCE   9 EXPRESSION_SYSTEM_VECTOR: PGEX-6P-1;                                 
SOURCE  10 MOL_ID: 2;                                                           
SOURCE  11 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE  12 ORGANISM_COMMON: HUMAN;                                              
SOURCE  13 ORGANISM_TAXID: 9606;                                                
SOURCE  14 EXPRESSION_SYSTEM: ESCHERICHIA COLI B;                               
SOURCE  15 EXPRESSION_SYSTEM_TAXID: 37762;                                      
SOURCE  16 EXPRESSION_SYSTEM_STRAIN: B834;                                      
SOURCE  17 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;                              
SOURCE  18 EXPRESSION_SYSTEM_VECTOR: PET21D                                     
KEYWDS    CELL CYCLE, CYCLIN DEPENDENT KINASES, STRUCTURE-BASED DRUG DESIGN,    
KEYWDS   2 CONFORMATIONAL RESTRAINT, REVERSED BINDING MODE                      
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    B.CARBAIN,D.J.PATERSON,E.ANSCOMBE,A.CAMPBELL,C.CANO,A.ECHALIER,       
AUTHOR   2 J.ENDICOTT,B.T.GOLDING,K.HAGGERTY,I.R.HARDCASTLE,P.JEWSBURY,         
AUTHOR   3 D.R.NEWELL,M.E.M.NOBLE,C.ROCHE,L.Z.WANG,R.GRIFFIN                    
REVDAT   2   12-FEB-14 4CFN    1       JRNL                                     
REVDAT   1   18-DEC-13 4CFN    0                                                
JRNL        AUTH   B.CARBAIN,D.J.PATERSON,E.ANSCOMBE,A.CAMPBELL-DEXTER,C.CANO,  
JRNL        AUTH 2 A.ECHALIER,J.ENDICOTT,B.T.GOLDING,K.HAGGERTY,I.R.HARDCASTLE, 
JRNL        AUTH 3 P.J.JEWSBURY,D.R.NEWELL,M.NOBLE,C.ROCHE,L.WANG,R.J.GRIFFIN   
JRNL        TITL   8-SUBSTITUTED O6-CYCLOHEXYLMETHYLGUANINE CDK2 INHIBITORS;    
JRNL        TITL 2 USING STRUCTURE-BASED INHIBITOR DESIGN TO OPTIMISE AN        
JRNL        TITL 3 ALTERNATIVE BINDING MODE.                                    
JRNL        REF    J.MED.CHEM.                   V.  57    56 2014              
JRNL        REFN                   ISSN 0022-2623                               
JRNL        PMID   24304238                                                     
JRNL        DOI    10.1021/JM401555V                                            
REMARK   2                                                                      
REMARK   2 RESOLUTION.    2.20 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : REFMAC 5.8.0049                                      
REMARK   3   AUTHORS     : MURSHUDOV,SKUBAK,LEBEDEV,PANNU,                      
REMARK   3                 STEINER,NICHOLLS,WINN,LONG,VAGIN                     
REMARK   3                                                                      
REMARK   3    REFINEMENT TARGET : MAXIMUM LIKELIHOOD                            
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 2.20                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 99.50                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : NONE                           
REMARK   3   COMPLETENESS FOR RANGE        (%) : 91.17                          
REMARK   3   NUMBER OF REFLECTIONS             : 65427                          
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) : 0.19932                         
REMARK   3   R VALUE            (WORKING SET) : 0.19714                         
REMARK   3   FREE R VALUE                     : 0.24087                         
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 5.0                             
REMARK   3   FREE R VALUE TEST SET COUNT      : 3463                            
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) : 2.200                        
REMARK   3   BIN RESOLUTION RANGE LOW        (A) : 2.257                        
REMARK   3   REFLECTION IN BIN     (WORKING SET) : 3914                         
REMARK   3   BIN COMPLETENESS (WORKING+TEST) (%) : 74.78                        
REMARK   3   BIN R VALUE           (WORKING SET) : 0.300                        
REMARK   3   BIN FREE R VALUE SET COUNT          : 220                          
REMARK   3   BIN FREE R VALUE                    : 0.346                        
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS            : 8896                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 82                                      
REMARK   3   SOLVENT ATOMS            : 555                                     
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : NULL                           
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 36.479                         
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : -0.11                                                
REMARK   3    B22 (A**2) : -1.82                                                
REMARK   3    B33 (A**2) : 1.93                                                 
REMARK   3    B12 (A**2) : 0.00                                                 
REMARK   3    B13 (A**2) : 0.00                                                 
REMARK   3    B23 (A**2) : 0.00                                                 
REMARK   3                                                                      
REMARK   3  ESTIMATED OVERALL COORDINATE ERROR.                                 
REMARK   3   ESU BASED ON R VALUE                            (A): 0.269         
REMARK   3   ESU BASED ON FREE R VALUE                       (A): 0.212         
REMARK   3   ESU BASED ON MAXIMUM LIKELIHOOD                 (A): 0.173         
REMARK   3   ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 14.098        
REMARK   3                                                                      
REMARK   3  CORRELATION COEFFICIENTS.                                           
REMARK   3   CORRELATION COEFFICIENT FO-FC      : 0.945                         
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : 0.915                         
REMARK   3                                                                      
REMARK   3  RMS DEVIATIONS FROM IDEAL VALUES        COUNT    RMS    WEIGHT      
REMARK   3   BOND LENGTHS REFINED ATOMS        (A):  9207 ; 0.017 ; 0.019       
REMARK   3   BOND LENGTHS OTHERS               (A):  8967 ; 0.002 ; 0.020       
REMARK   3   BOND ANGLES REFINED ATOMS   (DEGREES): 12503 ; 1.826 ; 1.983       
REMARK   3   BOND ANGLES OTHERS          (DEGREES): 20678 ; 2.492 ; 3.001       
REMARK   3   TORSION ANGLES, PERIOD 1    (DEGREES):  1104 ; 6.321 ; 5.000       
REMARK   3   TORSION ANGLES, PERIOD 2    (DEGREES):   392 ;42.020 ;23.852       
REMARK   3   TORSION ANGLES, PERIOD 3    (DEGREES):  1612 ;17.517 ;15.000       
REMARK   3   TORSION ANGLES, PERIOD 4    (DEGREES):    45 ;17.412 ;15.000       
REMARK   3   CHIRAL-CENTER RESTRAINTS       (A**3):  1411 ; 0.161 ; 0.200       
REMARK   3   GENERAL PLANES REFINED ATOMS      (A): 10091 ; 0.008 ; 0.021       
REMARK   3   GENERAL PLANES OTHERS             (A):  2058 ; 0.008 ; 0.020       
REMARK   3   NON-BONDED CONTACTS REFINED ATOMS (A):  NULL ;  NULL ;  NULL       
REMARK   3   NON-BONDED CONTACTS OTHERS        (A):  NULL ;  NULL ;  NULL       
REMARK   3   NON-BONDED TORSION REFINED ATOMS  (A):  NULL ;  NULL ;  NULL       
REMARK   3   NON-BONDED TORSION OTHERS         (A):  NULL ;  NULL ;  NULL       
REMARK   3   H-BOND (X...Y) REFINED ATOMS      (A):  NULL ;  NULL ;  NULL       
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):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY VDW OTHERS               (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY H-BOND REFINED ATOMS     (A):  NULL ;  NULL ;  NULL       
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):  4425 ; 0.611 ; 1.439       
REMARK   3   MAIN-CHAIN BOND OTHER ATOMS    (A**2):  4424 ; 0.611 ; 1.439       
REMARK   3   MAIN-CHAIN ANGLE REFINED ATOMS (A**2):  5526 ; 0.947 ; 2.155       
REMARK   3   SIDE-CHAIN BOND REFINED ATOMS  (A**2):  4782 ; 0.741 ; 1.541       
REMARK   3   SIDE-CHAIN ANGLE REFINED 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  : 4                                          
REMARK   3                                                                      
REMARK   3   TLS GROUP : 1                                                      
REMARK   3    NUMBER OF COMPONENTS GROUP : 1                                    
REMARK   3    COMPONENTS        C SSSEQI   TO  C SSSEQI                         
REMARK   3    RESIDUE RANGE :   A    -2        A   297                          
REMARK   3    ORIGIN FOR THE GROUP (A):   6.1040  40.8690  63.7250              
REMARK   3    T TENSOR                                                          
REMARK   3      T11:   0.0792 T22:   0.2018                                     
REMARK   3      T33:   0.0096 T12:   0.0047                                     
REMARK   3      T13:  -0.0185 T23:  -0.0057                                     
REMARK   3    L TENSOR                                                          
REMARK   3      L11:   1.6099 L22:   1.3072                                     
REMARK   3      L33:   1.5527 L12:   0.4361                                     
REMARK   3      L13:  -0.7919 L23:  -0.1941                                     
REMARK   3    S TENSOR                                                          
REMARK   3      S11:  -0.0157 S12:   0.1593 S13:  -0.0079                       
REMARK   3      S21:  -0.2510 S22:   0.0617 S23:   0.0782                       
REMARK   3      S31:  -0.0831 S32:  -0.1474 S33:  -0.0460                       
REMARK   3                                                                      
REMARK   3   TLS GROUP : 2                                                      
REMARK   3    NUMBER OF COMPONENTS GROUP : 1                                    
REMARK   3    COMPONENTS        C SSSEQI   TO  C SSSEQI                         
REMARK   3    RESIDUE RANGE :   B   177        B   432                          
REMARK   3    ORIGIN FOR THE GROUP (A):  21.2280  67.6290  76.5720              
REMARK   3    T TENSOR                                                          
REMARK   3      T11:   0.1066 T22:   0.1871                                     
REMARK   3      T33:   0.0190 T12:  -0.0108                                     
REMARK   3      T13:   0.0155 T23:  -0.0360                                     
REMARK   3    L TENSOR                                                          
REMARK   3      L11:   1.1173 L22:   2.3316                                     
REMARK   3      L33:   1.8009 L12:  -0.2474                                     
REMARK   3      L13:   0.3740 L23:  -0.4302                                     
REMARK   3    S TENSOR                                                          
REMARK   3      S11:  -0.0891 S12:  -0.0751 S13:   0.0711                       
REMARK   3      S21:   0.0859 S22:   0.0985 S23:  -0.1272                       
REMARK   3      S31:  -0.2459 S32:  -0.0118 S33:  -0.0094                       
REMARK   3                                                                      
REMARK   3   TLS GROUP : 3                                                      
REMARK   3    NUMBER OF COMPONENTS GROUP : 1                                    
REMARK   3    COMPONENTS        C SSSEQI   TO  C SSSEQI                         
REMARK   3    RESIDUE RANGE :   C    -2        C   294                          
REMARK   3    ORIGIN FOR THE GROUP (A):  10.4530 -11.9930 107.1030              
REMARK   3    T TENSOR                                                          
REMARK   3      T11:   0.2690 T22:   0.2928                                     
REMARK   3      T33:   0.0707 T12:   0.0274                                     
REMARK   3      T13:   0.0029 T23:   0.0743                                     
REMARK   3    L TENSOR                                                          
REMARK   3      L11:   1.8928 L22:   1.5717                                     
REMARK   3      L33:   0.8854 L12:  -0.3213                                     
REMARK   3      L13:   0.5088 L23:  -0.1318                                     
REMARK   3    S TENSOR                                                          
REMARK   3      S11:   0.0987 S12:   0.0258 S13:  -0.0971                       
REMARK   3      S21:  -0.1055 S22:  -0.1066 S23:  -0.2675                       
REMARK   3      S31:   0.0609 S32:   0.1033 S33:   0.0079                       
REMARK   3                                                                      
REMARK   3   TLS GROUP : 4                                                      
REMARK   3    NUMBER OF COMPONENTS GROUP : 1                                    
REMARK   3    COMPONENTS        C SSSEQI   TO  C SSSEQI                         
REMARK   3    RESIDUE RANGE :   D   176        D   432                          
REMARK   3    ORIGIN FOR THE GROUP (A):   7.4730  20.8320 107.9090              
REMARK   3    T TENSOR                                                          
REMARK   3      T11:   0.2754 T22:   0.2801                                     
REMARK   3      T33:   0.1387 T12:  -0.0647                                     
REMARK   3      T13:  -0.0071 T23:   0.0587                                     
REMARK   3    L TENSOR                                                          
REMARK   3      L11:   2.9420 L22:   2.5204                                     
REMARK   3      L33:   1.4075 L12:  -0.1571                                     
REMARK   3      L13:  -0.4778 L23:  -0.1786                                     
REMARK   3    S TENSOR                                                          
REMARK   3      S11:   0.0531 S12:  -0.0001 S13:   0.3695                       
REMARK   3      S21:  -0.1663 S22:  -0.1062 S23:  -0.4732                       
REMARK   3      S31:  -0.1651 S32:   0.3409 S33:   0.0531                       
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          
REMARK   3   RIDING POSITIONS.                                                  
REMARK   4                                                                      
REMARK   4 4CFN COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 19-NOV-13.                  
REMARK 100 THE PDBE ID CODE IS EBI-59013.                                       
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : NULL                               
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : NULL                               
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : ESRF                               
REMARK 200  BEAMLINE                       : ID14-2                             
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 0.934                              
REMARK 200  MONOCHROMATOR                  : NULL                               
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : CCD                                
REMARK 200  DETECTOR MANUFACTURER          : ADSC                               
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : MOSFLM                             
REMARK 200  DATA SCALING SOFTWARE          : SCALA                              
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 68917                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.20                               
REMARK 200  RESOLUTION RANGE LOW       (A) : 2.32                               
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : 0.0                                
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 92.0                               
REMARK 200  DATA REDUNDANCY                : 2.33                               
REMARK 200  R MERGE                    (I) : 0.07                               
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 10.80                              
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.20                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 2.32                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 77.4                               
REMARK 200  DATA REDUNDANCY IN SHELL       : NULL                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.42                               
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 2.10                               
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 1H1S                                       
REMARK 200                                                                      
REMARK 200 REMARK: NONE                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 57.16                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.87                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 50 MM AMMONIUM ACETATE, 10%              
REMARK 280  PEG-3350, 15 MM NACL, 100 MM HEPES, PH = 7.4, 10% DMSO              
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY                                            
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 21                       
REMARK 290                                                                      
REMARK 290      SYMOP   SYMMETRY                                                
REMARK 290     NNNMMM   OPERATOR                                                
REMARK 290       1555   X,Y,Z                                                   
REMARK 290       2555   -X+1/2,-Y,Z+1/2                                         
REMARK 290       3555   -X,Y+1/2,-Z+1/2                                         
REMARK 290       4555   X+1/2,-Y+1/2,-Z                                         
REMARK 290                                                                      
REMARK 290     WHERE NNN -> OPERATOR NUMBER                                     
REMARK 290           MMM -> TRANSLATION VECTOR                                  
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY TRANSFORMATIONS                            
REMARK 290 THE FOLLOWING TRANSFORMATIONS OPERATE ON THE ATOM/HETATM             
REMARK 290 RECORDS IN THIS ENTRY TO PRODUCE CRYSTALLOGRAPHICALLY                
REMARK 290 RELATED MOLECULES.                                                   
REMARK 290   SMTRY1   1  1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   1  0.000000  1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   1  0.000000  0.000000  1.000000        0.00000            
REMARK 290   SMTRY1   2 -1.000000  0.000000  0.000000       36.99050            
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000       73.93250            
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       67.20800            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000       73.93250            
REMARK 290   SMTRY1   4  1.000000  0.000000  0.000000       36.99050            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000       67.20800            
REMARK 290   SMTRY3   4  0.000000  0.000000 -1.000000        0.00000            
REMARK 290                                                                      
REMARK 290 REMARK: NULL                                                         
REMARK 300                                                                      
REMARK 300 BIOMOLECULE: 1, 2                                                    
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM                
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN                  
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON               
REMARK 300 BURIED SURFACE AREA.                                                 
REMARK 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 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC                    
REMARK 350 SOFTWARE USED: PISA                                                  
REMARK 350 TOTAL BURIED SURFACE AREA: 3460 ANGSTROM**2                          
REMARK 350 SURFACE AREA OF THE COMPLEX: 23220 ANGSTROM**2                       
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -19.3 KCAL/MOL                        
REMARK 350 APPLY THE FOLLOWING TO CHAINS: C, D                                  
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 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC                    
REMARK 350 SOFTWARE USED: PISA                                                  
REMARK 350 TOTAL BURIED SURFACE AREA: 3310 ANGSTROM**2                          
REMARK 350 SURFACE AREA OF THE COMPLEX: 23210 ANGSTROM**2                       
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -15.3 KCAL/MOL                        
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, 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     GLY A    -3                                                      
REMARK 465     ASP A    38                                                      
REMARK 465     THR A    39                                                      
REMARK 465     GLU A    40                                                      
REMARK 465     LEU A   298                                                      
REMARK 465     VAL B   175                                                      
REMARK 465     PRO B   176                                                      
REMARK 465     ASP B   283                                                      
REMARK 465     ASP B   284                                                      
REMARK 465     GLY C    -3                                                      
REMARK 465     HIS C   295                                                      
REMARK 465     LEU C   296                                                      
REMARK 465     ARG C   297                                                      
REMARK 465     LEU C   298                                                      
REMARK 465     VAL D   175                                                      
REMARK 465     ASP D   283                                                      
REMARK 465     ASP D   284                                                      
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   ND1B HIS A    84     O    HOH A  2044              1.76            
REMARK 500   CD2B HIS A    84     O    HOH A  2045              1.93            
REMARK 500   CE1B HIS A    84     O    HOH A  2044              0.92            
REMARK 500   CE1B HIS A    84     O    HOH A  2045              1.48            
REMARK 500   NE2B HIS A    84     O    HOH A  2044              2.17            
REMARK 500   NE2B HIS A    84     O    HOH A  2045              0.61            
REMARK 500   NE2B GLN A   131     CAR  JYM A  1298              1.90            
REMARK 500   ND1  HIS A   268     O    HOH A  2169              2.19            
REMARK 500   O    THR B   285     O    HOH B  2076              2.15            
REMARK 500   OG1  THR B   285     O    HOH B  2077              2.06            
REMARK 500   NE2  GLN B   317     O    HOH B  2005              2.14            
REMARK 500   N    THR C    41     O    HOH C  2025              1.96            
REMARK 500   CB   THR C    72     O    HOH C  2047              2.00            
REMARK 500   NE2B GLN C   131     O    HOH C  2069              1.32            
REMARK 500   NZ   LYS D   194     O    HOH D  2007              2.19            
REMARK 500   OG   SER D   209     O    HOH D  2022              2.16            
REMARK 500   N    THR D   285     O    HOH D  2053              2.05            
REMARK 500   OG1  THR D   285     O    HOH D  2052              2.14            
REMARK 500   O    GLN D   322     O    HOH D  2063              2.11            
REMARK 500   O    HOH A  2044     O    HOH A  2045              2.19            
REMARK 500   O    HOH B  2073     O    HOH B  2077              2.19            
REMARK 500   O    HOH B  2142     O    HOH B  2143              2.19            
REMARK 500   O    HOH C  2025     O    HOH C  2026              2.06            
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: CLOSE CONTACTS                                             
REMARK 500                                                                      
REMARK 500 THE FOLLOWING ATOMS THAT ARE RELATED BY CRYSTALLOGRAPHIC             
REMARK 500 SYMMETRY ARE IN CLOSE CONTACT.  AN ATOM LOCATED WITHIN 0.15          
REMARK 500 ANGSTROMS OF A SYMMETRY RELATED ATOM IS ASSUMED TO BE ON A           
REMARK 500 SPECIAL POSITION AND IS, THEREFORE, LISTED IN REMARK 375             
REMARK 500 INSTEAD OF REMARK 500.  ATOMS WITH NON-BLANK ALTERNATE               
REMARK 500 LOCATION INDICATORS ARE NOT INCLUDED IN THE CALCULATIONS.            
REMARK 500                                                                      
REMARK 500 DISTANCE CUTOFF:                                                     
REMARK 500 2.2 ANGSTROMS FOR CONTACTS NOT INVOLVING HYDROGEN ATOMS              
REMARK 500 1.6 ANGSTROMS FOR CONTACTS INVOLVING HYDROGEN ATOMS                  
REMARK 500                                                                      
REMARK 500  ATM1  RES C  SSEQI   ATM2  RES C  SSEQI  SSYMOP   DISTANCE          
REMARK 500   NH1  ARG C   217     O    HOH A  2189     2555     1.96            
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: COVALENT BOND LENGTHS                                      
REMARK 500                                                                      
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES              
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE               
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN               
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).                 
REMARK 500                                                                      
REMARK 500 STANDARD TABLE:                                                      
REMARK 500 FORMAT: (10X,I3,1X,2(A3,1X,A1,I4,A1,1X,A4,3X),1X,F6.3)               
REMARK 500                                                                      
REMARK 500 EXPECTED VALUES PROTEIN: ENGH AND HUBER, 1999                        
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996                     
REMARK 500                                                                      
REMARK 500  M RES CSSEQI ATM1   RES CSSEQI ATM2   DEVIATION                     
REMARK 500    GLU D 277   CG    GLU D 277   CD      0.101                       
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: COVALENT BOND ANGLES                                       
REMARK 500                                                                      
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES              
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE               
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN               
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).                 
REMARK 500                                                                      
REMARK 500 STANDARD TABLE:                                                      
REMARK 500 FORMAT: (10X,I3,1X,A3,1X,A1,I4,A1,3(1X,A4,2X),12X,F5.1)              
REMARK 500                                                                      
REMARK 500 EXPECTED VALUES PROTEIN: ENGH AND HUBER, 1999                        
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996                     
REMARK 500                                                                      
REMARK 500  M RES CSSEQI ATM1   ATM2   ATM3                                     
REMARK 500    ARG A 217   NE  -  CZ  -  NH1 ANGL. DEV. =   3.3 DEGREES          
REMARK 500    CYS B 327   CA  -  CB  -  SG  ANGL. DEV. = -20.5 DEGREES          
REMARK 500    CYS D 327   CB  -  CA  -  C   ANGL. DEV. =  -7.9 DEGREES          
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    ASP A 127       45.32   -154.92                                   
REMARK 500    ASP A 145       83.58     52.30                                   
REMARK 500    VAL A 164      131.35     73.87                                   
REMARK 500    SER A 181     -143.55   -146.92                                   
REMARK 500    THR A 290     -169.00   -127.58                                   
REMARK 500    LEU A 296      145.55    156.31                                   
REMARK 500    TYR B 178       -8.88     65.28                                   
REMARK 500    TRP B 372      107.98    -35.49                                   
REMARK 500    THR C  14      -55.34    -29.05                                   
REMARK 500    THR C  41       27.83   -149.46                                   
REMARK 500    ASP C 127       47.92   -153.93                                   
REMARK 500    ASP C 145       85.66     51.74                                   
REMARK 500    VAL C 164      132.90     72.89                                   
REMARK 500    SER C 181     -144.83   -149.77                                   
REMARK 500    ASP D 177      -83.17   -105.41                                   
REMARK 500    TYR D 178        1.17    -48.98                                   
REMARK 500    TRP D 372      110.53    -38.02                                   
REMARK 500    LYS D 417      -35.77    -39.54                                   
REMARK 500    ASN D 431       54.86     30.98                                   
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: NON-CIS, NON-TRANS                                         
REMARK 500                                                                      
REMARK 500 THE FOLLOWING PEPTIDE BONDS DEVIATE SIGNIFICANTLY FROM BOTH          
REMARK 500 CIS AND TRANS CONFORMATION.  CIS BONDS, IF ANY, ARE LISTED           
REMARK 500 ON CISPEP RECORDS.  TRANS IS DEFINED AS 180 +/- 30 AND               
REMARK 500 CIS IS DEFINED AS 0 +/- 30 DEGREES.                                  
REMARK 500                                 MODEL     OMEGA                      
REMARK 500 THR A   97     GLY A   98                 -147.44                    
REMARK 500 PRO A  294     HIS A  295                 -136.23                    
REMARK 500 HIS A  295     LEU A  296                  -43.72                    
REMARK 500 THR C   39     GLU C   40                  148.13                    
REMARK 500 HIS C   71     THR C   72                  145.51                    
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: CHIRAL CENTERS                                             
REMARK 500                                                                      
REMARK 500 UNEXPECTED CONFIGURATION OF THE FOLLOWING CHIRAL                     
REMARK 500 CENTER(S) USING IMPROPER CA--C--CB--N CHIRALITY                      
REMARK 500 FOR AMINO ACIDS AND C1'--O4'--N1(N9)--C2' FOR                        
REMARK 500 NUCLEIC ACIDS OR EQUIVALENT ANGLE                                    
REMARK 500 M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN                            
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE                   
REMARK 500                                                                      
REMARK 500 STANDARD TABLE:                                                      
REMARK 500 FORMAT: (10X,I3,1X,A3,1X,A1,I4,A1,6X,F5.1,6X,A1,10X,A1,3X,A16)       
REMARK 500                                                                      
REMARK 500  M RES CSSEQI    IMPROPER   EXPECTED   FOUND DETAILS                 
REMARK 500    THR C  41        24.4      L          L   OUTSIDE RANGE           
REMARK 500    THR D 285        23.6      L          L   OUTSIDE RANGE           
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 JYM A1298                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE JYM C1295                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC3                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DTT B1433                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC4                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DTT D1433                 
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 1W8C   RELATED DB: PDB                                   
REMARK 900  CO-CRYSTAL STRUCTURE OF 6-CYCLOHEXYLMETHOXY-8-ISOPROPYL             
REMARK 900  -9H-PURIN-2-YLAMINE AND MONOMERIC CDK2                              
REMARK 900 RELATED ID: 4CFM   RELATED DB: PDB                                   
REMARK 900  STRUCTURE-BASED DESIGN OF C8-SUBSTITUTED O6-                        
REMARK 900  CYCLOHEXYLMETHOXYGUANINE CDK1 AND 2 INHIBITORS.                     
REMARK 900 RELATED ID: 4CFU   RELATED DB: PDB                                   
REMARK 900  STRUCTURE-BASED DESIGN OF C8-SUBSTITUTED O6-                        
REMARK 900  CYCLOHEXYLMETHOXYGUANINE CDK1 AND 2 INHIBITORS.                     
REMARK 900 RELATED ID: 4CFV   RELATED DB: PDB                                   
REMARK 900  STRUCTURE-BASED DESIGN OF C8-SUBSTITUTED O6-                        
REMARK 900  CYCLOHEXYLMETHOXYGUANINE CDK1 AND 2 INHIBITORS.                     
REMARK 900 RELATED ID: 4CFW   RELATED DB: PDB                                   
REMARK 900  STRUCTURE-BASED DESIGN OF C8-SUBSTITUTED O6-                        
REMARK 900  CYCLOHEXYLMETHOXYGUANINE CDK1 AND 2 INHIBITORS.                     
REMARK 900 RELATED ID: 4CFX   RELATED DB: PDB                                   
REMARK 900  STRUCTURE-BASED DESIGN OF C8-SUBSTITUTED O6-                        
REMARK 900  CYCLOHEXYLMETHOXYGUANINE CDK1 AND 2 INHIBITORS.                     
REMARK 999                                                                      
REMARK 999 SEQUENCE                                                             
REMARK 999 N-TERMINAL 3C PROTEASE SITE                                          
DBREF  4CFN A    1   298  UNP    P24941   CDK2_HUMAN       1    298             
DBREF  4CFN B  175   432  UNP    P20248   CCNA2_HUMAN    175    432             
DBREF  4CFN C    1   298  UNP    P24941   CDK2_HUMAN       1    298             
DBREF  4CFN D  175   432  UNP    P20248   CCNA2_HUMAN    175    432             
SEQADV 4CFN GLY A   -3  UNP  P24941              EXPRESSION TAG                 
SEQADV 4CFN PRO A   -2  UNP  P24941              EXPRESSION TAG                 
SEQADV 4CFN GLY A   -1  UNP  P24941              EXPRESSION TAG                 
SEQADV 4CFN SER A    0  UNP  P24941              EXPRESSION TAG                 
SEQADV 4CFN GLY C   -3  UNP  P24941              EXPRESSION TAG                 
SEQADV 4CFN PRO C   -2  UNP  P24941              EXPRESSION TAG                 
SEQADV 4CFN GLY C   -1  UNP  P24941              EXPRESSION TAG                 
SEQADV 4CFN SER C    0  UNP  P24941              EXPRESSION TAG                 
SEQRES   1 A  302  GLY PRO GLY SER MET GLU ASN PHE GLN LYS VAL GLU LYS          
SEQRES   2 A  302  ILE GLY GLU GLY THR TYR GLY VAL VAL TYR LYS ALA ARG          
SEQRES   3 A  302  ASN LYS LEU THR GLY GLU VAL VAL ALA LEU LYS LYS ILE          
SEQRES   4 A  302  ARG LEU ASP THR GLU THR GLU GLY VAL PRO SER THR ALA          
SEQRES   5 A  302  ILE ARG GLU ILE SER LEU LEU LYS GLU LEU ASN HIS PRO          
SEQRES   6 A  302  ASN ILE VAL LYS LEU LEU ASP VAL ILE HIS THR GLU ASN          
SEQRES   7 A  302  LYS LEU TYR LEU VAL PHE GLU PHE LEU HIS GLN ASP LEU          
SEQRES   8 A  302  LYS LYS PHE MET ASP ALA SER ALA LEU THR GLY ILE PRO          
SEQRES   9 A  302  LEU PRO LEU ILE LYS SER TYR LEU PHE GLN LEU LEU GLN          
SEQRES  10 A  302  GLY LEU ALA PHE CYS HIS SER HIS ARG VAL LEU HIS ARG          
SEQRES  11 A  302  ASP LEU LYS PRO GLN ASN LEU LEU ILE ASN THR GLU GLY          
SEQRES  12 A  302  ALA ILE LYS LEU ALA ASP PHE GLY LEU ALA ARG ALA PHE          
SEQRES  13 A  302  GLY VAL PRO VAL ARG THR TYR TPO HIS GLU VAL VAL THR          
SEQRES  14 A  302  LEU TRP TYR ARG ALA PRO GLU ILE LEU LEU GLY CYS LYS          
SEQRES  15 A  302  TYR TYR SER THR ALA VAL ASP ILE TRP SER LEU GLY CYS          
SEQRES  16 A  302  ILE PHE ALA GLU MET VAL THR ARG ARG ALA LEU PHE PRO          
SEQRES  17 A  302  GLY ASP SER GLU ILE ASP GLN LEU PHE ARG ILE PHE ARG          
SEQRES  18 A  302  THR LEU GLY THR PRO ASP GLU VAL VAL TRP PRO GLY VAL          
SEQRES  19 A  302  THR SER MET PRO ASP TYR LYS PRO SER PHE PRO LYS TRP          
SEQRES  20 A  302  ALA ARG GLN ASP PHE SER LYS VAL VAL PRO PRO LEU ASP          
SEQRES  21 A  302  GLU ASP GLY ARG SER LEU LEU SER GLN MET LEU HIS TYR          
SEQRES  22 A  302  ASP PRO ASN LYS ARG ILE SER ALA LYS ALA ALA LEU ALA          
SEQRES  23 A  302  HIS PRO PHE PHE GLN ASP VAL THR LYS PRO VAL PRO HIS          
SEQRES  24 A  302  LEU ARG LEU                                                  
SEQRES   1 B  258  VAL PRO ASP TYR HIS GLU ASP ILE HIS THR TYR LEU ARG          
SEQRES   2 B  258  GLU MET GLU VAL LYS CYS LYS PRO LYS VAL GLY TYR MET          
SEQRES   3 B  258  LYS LYS GLN PRO ASP ILE THR ASN SER MET ARG ALA ILE          
SEQRES   4 B  258  LEU VAL ASP TRP LEU VAL GLU VAL GLY GLU GLU TYR LYS          
SEQRES   5 B  258  LEU GLN ASN GLU THR LEU HIS LEU ALA VAL ASN TYR ILE          
SEQRES   6 B  258  ASP ARG PHE LEU SER SER MET SER VAL LEU ARG GLY LYS          
SEQRES   7 B  258  LEU GLN LEU VAL GLY THR ALA ALA MET LEU LEU ALA SER          
SEQRES   8 B  258  LYS PHE GLU GLU ILE TYR PRO PRO GLU VAL ALA GLU PHE          
SEQRES   9 B  258  VAL TYR ILE THR ASP ASP THR TYR THR LYS LYS GLN VAL          
SEQRES  10 B  258  LEU ARG MET GLU HIS LEU VAL LEU LYS VAL LEU THR PHE          
SEQRES  11 B  258  ASP LEU ALA ALA PRO THR VAL ASN GLN PHE LEU THR GLN          
SEQRES  12 B  258  TYR PHE LEU HIS GLN GLN PRO ALA ASN CYS LYS VAL GLU          
SEQRES  13 B  258  SER LEU ALA MET PHE LEU GLY GLU LEU SER LEU ILE ASP          
SEQRES  14 B  258  ALA ASP PRO TYR LEU LYS TYR LEU PRO SER VAL ILE ALA          
SEQRES  15 B  258  GLY ALA ALA PHE HIS LEU ALA LEU TYR THR VAL THR GLY          
SEQRES  16 B  258  GLN SER TRP PRO GLU SER LEU ILE ARG LYS THR GLY TYR          
SEQRES  17 B  258  THR LEU GLU SER LEU LYS PRO CYS LEU MET ASP LEU HIS          
SEQRES  18 B  258  GLN THR TYR LEU LYS ALA PRO GLN HIS ALA GLN GLN SER          
SEQRES  19 B  258  ILE ARG GLU LYS TYR LYS ASN SER LYS TYR HIS GLY VAL          
SEQRES  20 B  258  SER LEU LEU ASN PRO PRO GLU THR LEU ASN LEU                  
SEQRES   1 C  302  GLY PRO GLY SER MET GLU ASN PHE GLN LYS VAL GLU LYS          
SEQRES   2 C  302  ILE GLY GLU GLY THR TYR GLY VAL VAL TYR LYS ALA ARG          
SEQRES   3 C  302  ASN LYS LEU THR GLY GLU VAL VAL ALA LEU LYS LYS ILE          
SEQRES   4 C  302  ARG LEU ASP THR GLU THR GLU GLY VAL PRO SER THR ALA          
SEQRES   5 C  302  ILE ARG GLU ILE SER LEU LEU LYS GLU LEU ASN HIS PRO          
SEQRES   6 C  302  ASN ILE VAL LYS LEU LEU ASP VAL ILE HIS THR GLU ASN          
SEQRES   7 C  302  LYS LEU TYR LEU VAL PHE GLU PHE LEU HIS GLN ASP LEU          
SEQRES   8 C  302  LYS LYS PHE MET ASP ALA SER ALA LEU THR GLY ILE PRO          
SEQRES   9 C  302  LEU PRO LEU ILE LYS SER TYR LEU PHE GLN LEU LEU GLN          
SEQRES  10 C  302  GLY LEU ALA PHE CYS HIS SER HIS ARG VAL LEU HIS ARG          
SEQRES  11 C  302  ASP LEU LYS PRO GLN ASN LEU LEU ILE ASN THR GLU GLY          
SEQRES  12 C  302  ALA ILE LYS LEU ALA ASP PHE GLY LEU ALA ARG ALA PHE          
SEQRES  13 C  302  GLY VAL PRO VAL ARG THR TYR TPO HIS GLU VAL VAL THR          
SEQRES  14 C  302  LEU TRP TYR ARG ALA PRO GLU ILE LEU LEU GLY CYS LYS          
SEQRES  15 C  302  TYR TYR SER THR ALA VAL ASP ILE TRP SER LEU GLY CYS          
SEQRES  16 C  302  ILE PHE ALA GLU MET VAL THR ARG ARG ALA LEU PHE PRO          
SEQRES  17 C  302  GLY ASP SER GLU ILE ASP GLN LEU PHE ARG ILE PHE ARG          
SEQRES  18 C  302  THR LEU GLY THR PRO ASP GLU VAL VAL TRP PRO GLY VAL          
SEQRES  19 C  302  THR SER MET PRO ASP TYR LYS PRO SER PHE PRO LYS TRP          
SEQRES  20 C  302  ALA ARG GLN ASP PHE SER LYS VAL VAL PRO PRO LEU ASP          
SEQRES  21 C  302  GLU ASP GLY ARG SER LEU LEU SER GLN MET LEU HIS TYR          
SEQRES  22 C  302  ASP PRO ASN LYS ARG ILE SER ALA LYS ALA ALA LEU ALA          
SEQRES  23 C  302  HIS PRO PHE PHE GLN ASP VAL THR LYS PRO VAL PRO HIS          
SEQRES  24 C  302  LEU ARG LEU                                                  
SEQRES   1 D  258  VAL PRO ASP TYR HIS GLU ASP ILE HIS THR TYR LEU ARG          
SEQRES   2 D  258  GLU MET GLU VAL LYS CYS LYS PRO LYS VAL GLY TYR MET          
SEQRES   3 D  258  LYS LYS GLN PRO ASP ILE THR ASN SER MET ARG ALA ILE          
SEQRES   4 D  258  LEU VAL ASP TRP LEU VAL GLU VAL GLY GLU GLU TYR LYS          
SEQRES   5 D  258  LEU GLN ASN GLU THR LEU HIS LEU ALA VAL ASN TYR ILE          
SEQRES   6 D  258  ASP ARG PHE LEU SER SER MET SER VAL LEU ARG GLY LYS          
SEQRES   7 D  258  LEU GLN LEU VAL GLY THR ALA ALA MET LEU LEU ALA SER          
SEQRES   8 D  258  LYS PHE GLU GLU ILE TYR PRO PRO GLU VAL ALA GLU PHE          
SEQRES   9 D  258  VAL TYR ILE THR ASP ASP THR TYR THR LYS LYS GLN VAL          
SEQRES  10 D  258  LEU ARG MET GLU HIS LEU VAL LEU LYS VAL LEU THR PHE          
SEQRES  11 D  258  ASP LEU ALA ALA PRO THR VAL ASN GLN PHE LEU THR GLN          
SEQRES  12 D  258  TYR PHE LEU HIS GLN GLN PRO ALA ASN CYS LYS VAL GLU          
SEQRES  13 D  258  SER LEU ALA MET PHE LEU GLY GLU LEU SER LEU ILE ASP          
SEQRES  14 D  258  ALA ASP PRO TYR LEU LYS TYR LEU PRO SER VAL ILE ALA          
SEQRES  15 D  258  GLY ALA ALA PHE HIS LEU ALA LEU TYR THR VAL THR GLY          
SEQRES  16 D  258  GLN SER TRP PRO GLU SER LEU ILE ARG LYS THR GLY TYR          
SEQRES  17 D  258  THR LEU GLU SER LEU LYS PRO CYS LEU MET ASP LEU HIS          
SEQRES  18 D  258  GLN THR TYR LEU LYS ALA PRO GLN HIS ALA GLN GLN SER          
SEQRES  19 D  258  ILE ARG GLU LYS TYR LYS ASN SER LYS TYR HIS GLY VAL          
SEQRES  20 D  258  SER LEU LEU ASN PRO PRO GLU THR LEU ASN LEU                  
MODRES 4CFN TPO A  160  THR  PHOSPHOTHREONINE                                   
MODRES 4CFN TPO C  160  THR  PHOSPHOTHREONINE                                   
HET    TPO  A 160      11                                                       
HET    TPO  C 160      11                                                       
HET    JYM  A1298      22                                                       
HET    JYM  C1295      22                                                       
HET    DTT  B1433       8                                                       
HET    DTT  D1433       8                                                       
HETNAM     JYM 6-(CYCLOHEXYLMETHOXY)-8-(TRIFLUOROMETHYL)-9H-                    
HETNAM   2 JYM  PURIN-2-AMINE                                                   
HETNAM     TPO PHOSPHOTHREONINE                                                 
HETNAM     DTT 2,3-DIHYDROXY-1,4-DITHIOBUTANE                                   
HETSYN     TPO PHOSPHONOTHREONINE                                               
HETSYN     DTT 1,4-DITHIOTHREITOL                                               
FORMUL   5  JYM    2(C13 H16 F3 N5 O)                                           
FORMUL   6  TPO    2(C4 H10 N O6 P)                                             
FORMUL   7  DTT    2(C4 H10 O2 S2)                                              
FORMUL   8  HOH   *555(H2 O)                                                    
HELIX    1   1 SER A    0  GLU A    2  5                                   3    
HELIX    2   2 PRO A   45  LEU A   58  1                                  14    
HELIX    3   3 LEU A   87  SER A   94  1                                   8    
HELIX    4   4 PRO A  100  HIS A  121  1                                  22    
HELIX    5   5 LYS A  129  GLN A  131  5                                   3    
HELIX    6   6 THR A  165  ARG A  169  5                                   5    
HELIX    7   7 ALA A  170  LEU A  175  1                                   6    
HELIX    8   8 THR A  182  ARG A  199  1                                  18    
HELIX    9   9 SER A  207  GLY A  220  1                                  14    
HELIX   10  10 GLY A  229  MET A  233  5                                   5    
HELIX   11  11 ASP A  247  VAL A  252  1                                   6    
HELIX   12  12 ASP A  256  LEU A  267  1                                  12    
HELIX   13  13 SER A  276  LEU A  281  1                                   6    
HELIX   14  14 ALA A  282  GLN A  287  5                                   6    
HELIX   15  15 TYR B  178  CYS B  193  1                                  16    
HELIX   16  16 GLY B  198  GLN B  203  1                                   6    
HELIX   17  17 THR B  207  TYR B  225  1                                  19    
HELIX   18  18 GLN B  228  SER B  244  1                                  17    
HELIX   19  19 LEU B  249  GLU B  269  1                                  21    
HELIX   20  20 GLU B  274  THR B  282  1                                   9    
HELIX   21  21 THR B  287  LEU B  302  1                                  16    
HELIX   22  22 THR B  310  LEU B  320  1                                  11    
HELIX   23  23 ASN B  326  LEU B  341  1                                  16    
HELIX   24  24 ASP B  343  LEU B  348  1                                   6    
HELIX   25  25 LEU B  351  GLY B  369  1                                  19    
HELIX   26  26 PRO B  373  GLY B  381  1                                   9    
HELIX   27  27 THR B  383  ALA B  401  1                                  19    
HELIX   28  28 PRO B  402  HIS B  404  5                                   3    
HELIX   29  29 GLN B  407  TYR B  413  1                                   7    
HELIX   30  30 LYS B  414  HIS B  419  5                                   6    
HELIX   31  31 GLY B  420  LEU B  424  5                                   5    
HELIX   32  32 SER C    0  GLU C    2  5                                   3    
HELIX   33  33 PRO C   45  LEU C   58  1                                  14    
HELIX   34  34 LEU C   87  SER C   94  1                                   8    
HELIX   35  35 PRO C  100  HIS C  121  1                                  22    
HELIX   36  36 LYS C  129  GLN C  131  5                                   3    
HELIX   37  37 THR C  165  ARG C  169  5                                   5    
HELIX   38  38 ALA C  170  LEU C  175  1                                   6    
HELIX   39  39 THR C  182  ARG C  199  1                                  18    
HELIX   40  40 SER C  207  GLY C  220  1                                  14    
HELIX   41  41 GLY C  229  MET C  233  5                                   5    
HELIX   42  42 ASP C  247  VAL C  252  1                                   6    
HELIX   43  43 ASP C  256  LEU C  267  1                                  12    
HELIX   44  44 SER C  276  ALA C  282  1                                   7    
HELIX   45  45 HIS C  283  GLN C  287  5                                   5    
HELIX   46  46 TYR D  178  CYS D  193  1                                  16    
HELIX   47  47 GLY D  198  GLN D  203  5                                   6    
HELIX   48  48 THR D  207  TYR D  225  1                                  19    
HELIX   49  49 GLN D  228  SER D  244  1                                  17    
HELIX   50  50 LEU D  249  GLU D  269  1                                  21    
HELIX   51  51 GLU D  274  THR D  282  1                                   9    
HELIX   52  52 THR D  287  LEU D  302  1                                  16    
HELIX   53  53 THR D  310  LEU D  320  1                                  11    
HELIX   54  54 ASN D  326  LEU D  341  1                                  16    
HELIX   55  55 ASP D  343  LEU D  348  1                                   6    
HELIX   56  56 LEU D  351  GLY D  369  1                                  19    
HELIX   57  57 PRO D  373  GLY D  381  1                                   9    
HELIX   58  58 THR D  383  ALA D  401  1                                  19    
HELIX   59  59 PRO D  402  HIS D  404  5                                   3    
HELIX   60  60 GLN D  407  TYR D  413  1                                   7    
HELIX   61  61 LYS D  414  HIS D  419  5                                   6    
HELIX   62  62 GLY D  420  LEU D  424  5                                   5    
SHEET    1  AA 5 PHE A   4  GLY A  11  0                                        
SHEET    2  AA 5 VAL A  17  ASN A  23 -1  O  VAL A  18   N  ILE A  10           
SHEET    3  AA 5 VAL A  29  ARG A  36 -1  O  VAL A  30   N  ALA A  21           
SHEET    4  AA 5 LYS A  75  GLU A  81 -1  O  LEU A  76   N  ILE A  35           
SHEET    5  AA 5 LEU A  66  HIS A  71 -1  N  LEU A  67   O  VAL A  79           
SHEET    1  AB 3 GLN A  85  ASP A  86  0                                        
SHEET    2  AB 3 LEU A 133  ILE A 135 -1  O  ILE A 135   N  GLN A  85           
SHEET    3  AB 3 ILE A 141  LEU A 143 -1  O  LYS A 142   N  LEU A 134           
SHEET    1  AC 2 VAL A 123  LEU A 124  0                                        
SHEET    2  AC 2 ARG A 150  ALA A 151 -1  O  ARG A 150   N  LEU A 124           
SHEET    1  CA 5 PHE C   4  GLY C  11  0                                        
SHEET    2  CA 5 VAL C  17  ASN C  23 -1  O  VAL C  18   N  ILE C  10           
SHEET    3  CA 5 VAL C  29  ARG C  36 -1  O  VAL C  30   N  ALA C  21           
SHEET    4  CA 5 LYS C  75  GLU C  81 -1  O  LEU C  76   N  ILE C  35           
SHEET    5  CA 5 LEU C  66  HIS C  71 -1  N  LEU C  67   O  VAL C  79           
SHEET    1  CB 3 GLN C  85  ASP C  86  0                                        
SHEET    2  CB 3 LEU C 133  ILE C 135 -1  O  ILE C 135   N  GLN C  85           
SHEET    3  CB 3 ILE C 141  LEU C 143 -1  O  LYS C 142   N  LEU C 134           
SHEET    1  CC 2 VAL C 123  LEU C 124  0                                        
SHEET    2  CC 2 ARG C 150  ALA C 151 -1  O  ARG C 150   N  LEU C 124           
LINK         C   TYR A 159                 N   TPO A 160     1555   1555  1.33  
LINK         C   TPO A 160                 N   HIS A 161     1555   1555  1.33  
LINK         C   TYR C 159                 N   TPO C 160     1555   1555  1.34  
LINK         C   TPO C 160                 N   HIS C 161     1555   1555  1.34  
CISPEP   1 VAL A  154    PRO A  155          0        -2.72                     
CISPEP   2 LEU A  296    ARG A  297          0       -24.70                     
CISPEP   3 GLN B  323    PRO B  324          0        -6.40                     
CISPEP   4 ASP B  345    PRO B  346          0         6.12                     
CISPEP   5 GLU C   40    THR C   41          0       -17.90                     
CISPEP   6 VAL C  154    PRO C  155          0        -1.49                     
CISPEP   7 GLN D  323    PRO D  324          0        -4.73                     
CISPEP   8 ASP D  345    PRO D  346          0        10.55                     
SITE     1 AC1 10 GLU A  12  ALA A  31  PHE A  80  LEU A  83                    
SITE     2 AC1 10 HIS A  84  GLN A  85  LEU A 134  HOH A2014                    
SITE     3 AC1 10 HOH A2041  HOH A2193                                          
SITE     1 AC2 16 GLY C  11  GLU C  12  GLY C  13  VAL C  18                    
SITE     2 AC2 16 ALA C  31  PHE C  80  LEU C  83  HIS C  84                    
SITE     3 AC2 16 GLN C  85  GLN C 131  LEU C 134  HOH C2020                    
SITE     4 AC2 16 HOH C2033  HOH C2050  HOH C2052  HOH C2123                    
SITE     1 AC3  3 TRP B 217  HOH B2031  HOH B2151                               
SITE     1 AC4  4 LEU C  96  THR C  97  TRP D 217  GLN D 254                    
CRYST1   73.981  134.416  147.865  90.00  90.00  90.00 P 21 21 21    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      0.013517  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.007440  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.006763        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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