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Database: PDB
Entry: 4WAF
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HEADER    TRANSFERASE/TRANSFERASE INHIBITOR       29-AUG-14   4WAF              
TITLE     CRYSTAL STRUCTURE OF A NOVEL TETRAHYDROPYRAZOLO[1,5-A]PYRAZINE IN AN  
TITLE    2 ENGINEERED PI3K ALPHA                                                
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC   
COMPND   3 SUBUNIT ALPHA ISOFORM;                                               
COMPND   4 CHAIN: A;                                                            
COMPND   5 SYNONYM: PTDINS-3-KINASE SUBUNIT ALPHA,PHOSPHATIDYLINOSITOL 4,5-     
COMPND   6 BISPHOSPHATE 3-KINASE 110 KDA CATALYTIC SUBUNIT ALPHA,P110ALPHA,     
COMPND   7 PHOSPHOINOSITIDE-3-KINASE CATALYTIC ALPHA POLYPEPTIDE,               
COMPND   8 SERINE/THREONINE PROTEIN KINASE PIK3CA;                              
COMPND   9 EC: 2.7.1.153,2.7.11.1;                                              
COMPND  10 ENGINEERED: YES;                                                     
COMPND  11 MUTATION: YES;                                                       
COMPND  12 MOL_ID: 2;                                                           
COMPND  13 MOLECULE: PHOSPHATIDYLINOSITOL 3-KINASE REGULATORY SUBUNIT ALPHA;    
COMPND  14 CHAIN: B;                                                            
COMPND  15 FRAGMENT: UNP RESIDUES 2-317;                                        
COMPND  16 SYNONYM: PTDINS-3-KINASE REGULATORY SUBUNIT ALPHA,                   
COMPND  17 PHOSPHATIDYLINOSITOL 3-KINASE 85 KDA REGULATORY SUBUNIT ALPHA,PTDINS-
COMPND  18 3-KINASE REGULATORY SUBUNIT P85-ALPHA;                               
COMPND  19 ENGINEERED: YES;                                                     
COMPND  20 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: PIK3CA;                                                        
SOURCE   6 EXPRESSION_SYSTEM: TRICHOPLUSIA NI;                                  
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 7111;                                       
SOURCE   8 EXPRESSION_SYSTEM_CELL_LINE: TN5;                                    
SOURCE   9 EXPRESSION_SYSTEM_VECTOR_TYPE: BACULOVIRUS;                          
SOURCE  10 MOL_ID: 2;                                                           
SOURCE  11 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE  12 ORGANISM_COMMON: HUMAN;                                              
SOURCE  13 ORGANISM_TAXID: 9606;                                                
SOURCE  14 GENE: PIK3R1, GRB1;                                                  
SOURCE  15 EXPRESSION_SYSTEM: TRICHOPLUSIA NI;                                  
SOURCE  16 EXPRESSION_SYSTEM_TAXID: 7111;                                       
SOURCE  17 EXPRESSION_SYSTEM_CELL_LINE: TN5;                                    
SOURCE  18 EXPRESSION_SYSTEM_VECTOR_TYPE: BACULOVIRUS                           
KEYWDS    PI3K, CHIMERA, LIPID KINASE, TRANSFERASE-TRANSFERASE INHIBITOR        
KEYWDS   2 COMPLEX                                                              
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    M.S.KNAPP,R.A.ELLING                                                  
REVDAT   2   28-JAN-15 4WAF    1       JRNL                                     
REVDAT   1   31-DEC-14 4WAF    0                                                
JRNL        AUTH   P.A.BARSANTI,R.J.AVERSA,X.JIN,Y.PAN,Y.LU,R.ELLING,R.JAIN,    
JRNL        AUTH 2 M.KNAPP,J.LAN,X.LIN,P.RUDEWICZ,J.SIM,L.TARICANI,G.THOMAS,    
JRNL        AUTH 3 L.XIAO,Q.YUE                                                 
JRNL        TITL   STRUCTURE-BASED DRUG DESIGN OF NOVEL POTENT AND SELECTIVE    
JRNL        TITL 2 TETRAHYDROPYRAZOLO[1,5-A]PYRAZINES AS ATR INHIBITORS.        
JRNL        REF    ACS MED.CHEM.LETT.            V.   6    37 2015              
JRNL        REFN                   ISSN 1948-5875                               
JRNL        PMID   25589927                                                     
JRNL        DOI    10.1021/ML500353P                                            
REMARK   2                                                                      
REMARK   2 RESOLUTION.    2.39 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : BUSTER 2.11.5                                        
REMARK   3   AUTHORS     : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,              
REMARK   3               : PACIOREK,ROVERSI,SHARFF,SMART,VONRHEIN,              
REMARK   3               : WOMACK,MATTHEWS,TEN EYCK,TRONRUD                     
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 2.39                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 48.65                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : 0.000                          
REMARK   3   COMPLETENESS FOR RANGE        (%) : 100.0                          
REMARK   3   NUMBER OF REFLECTIONS             : 56611                          
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)  : 0.202                          
REMARK   3   R VALUE            (WORKING SET)  : 0.199                          
REMARK   3   FREE R VALUE                      : 0.247                          
REMARK   3   FREE R VALUE TEST SET SIZE   (%)  : 5.050                          
REMARK   3   FREE R VALUE TEST SET COUNT       : 3010                           
REMARK   3   ESTIMATED ERROR OF FREE R VALUE   : NULL                           
REMARK   3                                                                      
REMARK   3  FIT IN THE HIGHEST RESOLUTION BIN.                                  
REMARK   3   TOTAL NUMBER OF BINS USED               : 20                       
REMARK   3   BIN RESOLUTION RANGE HIGH   (ANGSTROMS) : 2.39                     
REMARK   3   BIN RESOLUTION RANGE LOW    (ANGSTROMS) : 2.45                     
REMARK   3   BIN COMPLETENESS (WORKING+TEST)     (%) : 99.97                    
REMARK   3   REFLECTIONS IN BIN (WORKING + TEST SET) : 4350                     
REMARK   3   BIN R VALUE        (WORKING + TEST SET) : 0.2437                   
REMARK   3   REFLECTIONS IN BIN        (WORKING SET) : 4122                     
REMARK   3   BIN R VALUE               (WORKING SET) : 0.2423                   
REMARK   3   BIN FREE R VALUE                        : 0.2699                   
REMARK   3   BIN FREE R VALUE TEST SET SIZE      (%) : 5.24                     
REMARK   3   BIN FREE R VALUE TEST SET COUNT         : 228                      
REMARK   3   ESTIMATED ERROR OF BIN FREE R VALUE     : NULL                     
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS            : 10042                                   
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 31                                      
REMARK   3   SOLVENT ATOMS            : 288                                     
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 63.64                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 65.66                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : 1.28080                                              
REMARK   3    B22 (A**2) : 6.73520                                              
REMARK   3    B33 (A**2) : -8.01600                                             
REMARK   3    B12 (A**2) : 0.00000                                              
REMARK   3    B13 (A**2) : 0.00000                                              
REMARK   3    B23 (A**2) : 0.00000                                              
REMARK   3                                                                      
REMARK   3  ESTIMATED COORDINATE ERROR.                                         
REMARK   3   ESD FROM LUZZATI PLOT                    (A) : NULL                
REMARK   3   DPI (BLOW EQ-10) BASED ON R VALUE        (A) : 0.360               
REMARK   3   DPI (BLOW EQ-9) BASED ON FREE R VALUE    (A) : 0.243               
REMARK   3   DPI (CRUICKSHANK) BASED ON R VALUE       (A) : 0.360               
REMARK   3   DPI (CRUICKSHANK) BASED ON FREE R VALUE  (A) : 0.246               
REMARK   3                                                                      
REMARK   3   REFERENCES: BLOW, D. (2002) ACTA CRYST D58, 792-797                
REMARK   3               CRUICKSHANK, D.W.J. (1999) ACTA CRYST D55, 583-601     
REMARK   3                                                                      
REMARK   3 CORRELATION COEFFICIENTS.                                            
REMARK   3   CORRELATION COEFFICIENT FO-FC      : 0.945                         
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : 0.914                         
REMARK   3                                                                      
REMARK   3   NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15                    
REMARK   3   TERM                          COUNT    WEIGHT   FUNCTION.          
REMARK   3    BOND LENGTHS              : 10315  ; 2.000  ; HARMONIC            
REMARK   3    BOND ANGLES               : 13984  ; 2.000  ; HARMONIC            
REMARK   3    TORSION ANGLES            : 3605   ; 2.000  ; SINUSOIDAL          
REMARK   3    TRIGONAL CARBON PLANES    : 275    ; 2.000  ; HARMONIC            
REMARK   3    GENERAL PLANES            : 1505   ; 5.000  ; HARMONIC            
REMARK   3    ISOTROPIC THERMAL FACTORS : 10315  ; 20.000 ; HARMONIC            
REMARK   3    BAD NON-BONDED CONTACTS   : NULL   ; NULL   ; NULL                
REMARK   3    IMPROPER TORSIONS         : NULL   ; NULL   ; NULL                
REMARK   3    PSEUDOROTATION ANGLES     : NULL   ; NULL   ; NULL                
REMARK   3    CHIRAL IMPROPER TORSION   : 1356   ; 5.000  ; SEMIHARMONIC        
REMARK   3    SUM OF OCCUPANCIES        : 3      ; 1.000  ; HARMONIC            
REMARK   3    UTILITY DISTANCES         : NULL   ; NULL   ; NULL                
REMARK   3    UTILITY ANGLES            : NULL   ; NULL   ; NULL                
REMARK   3    UTILITY TORSION           : NULL   ; NULL   ; NULL                
REMARK   3    IDEAL-DIST CONTACT TERM   : 11695  ; 4.000  ; SEMIHARMONIC        
REMARK   3                                                                      
REMARK   3   RMS DEVIATIONS FROM IDEAL VALUES.                                  
REMARK   3    BOND LENGTHS                       (A) : 0.009                    
REMARK   3    BOND ANGLES                  (DEGREES) : 1.04                     
REMARK   3    PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 2.51                     
REMARK   3    OTHER TORSION ANGLES         (DEGREES) : 18.27                    
REMARK   3                                                                      
REMARK   3  TLS DETAILS                                                         
REMARK   3   NUMBER OF TLS GROUPS  : 2                                          
REMARK   3                                                                      
REMARK   3   TLS GROUP : 1                                                      
REMARK   3    SELECTION: { A|* }                                                
REMARK   3    ORIGIN FOR THE GROUP (A):   -9.4545   27.3944  -26.7296           
REMARK   3    T TENSOR                                                          
REMARK   3     T11:    0.0000 T22:    0.0000                                    
REMARK   3     T33:    0.0000 T12:    0.0000                                    
REMARK   3     T13:    0.0000 T23:    0.0000                                    
REMARK   3    L TENSOR                                                          
REMARK   3     L11:    0.0000 L22:    0.0000                                    
REMARK   3     L33:    0.0000 L12:    0.0000                                    
REMARK   3     L13:    0.0000 L23:    0.0000                                    
REMARK   3    S TENSOR                                                          
REMARK   3     S11:    0.0000 S12:    0.0000 S13:    0.0000                     
REMARK   3     S21:    0.0000 S22:    0.0000 S23:    0.0000                     
REMARK   3     S31:    0.0000 S32:    0.0000 S33:    0.0000                     
REMARK   3                                                                      
REMARK   3   TLS GROUP : 2                                                      
REMARK   3    SELECTION: { B|* }                                                
REMARK   3    ORIGIN FOR THE GROUP (A):  -13.7185   15.5186  -48.4079           
REMARK   3    T TENSOR                                                          
REMARK   3     T11:    0.0000 T22:    0.0000                                    
REMARK   3     T33:    0.0000 T12:    0.0000                                    
REMARK   3     T13:    0.0000 T23:    0.0000                                    
REMARK   3    L TENSOR                                                          
REMARK   3     L11:    0.0000 L22:    0.0000                                    
REMARK   3     L33:    0.0000 L12:    0.0000                                    
REMARK   3     L13:    0.0000 L23:    0.0000                                    
REMARK   3    S TENSOR                                                          
REMARK   3     S11:    0.0000 S12:    0.0000 S13:    0.0000                     
REMARK   3     S21:    0.0000 S22:    0.0000 S23:    0.0000                     
REMARK   3     S31:    0.0000 S32:    0.0000 S33:    0.0000                     
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: NULL                                      
REMARK   4                                                                      
REMARK   4 4WAF COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 29-AUG-14.                  
REMARK 100 THE DEPOSITION ID IS D_1000203392.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 22-AUG-11                          
REMARK 200  TEMPERATURE           (KELVIN) : 103.15                             
REMARK 200  PH                             : NULL                               
REMARK 200  NUMBER OF CRYSTALS USED        : NULL                               
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : APS                                
REMARK 200  BEAMLINE                       : 17-ID                              
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.0                                
REMARK 200  MONOCHROMATOR                  : SI(111) DOUBLE-CRYSTAL             
REMARK 200                                   MONOCHROMATOR                      
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : PIXEL                              
REMARK 200  DETECTOR MANUFACTURER          : DECTRIS PILATUS 6M                 
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : NULL                               
REMARK 200  DATA SCALING SOFTWARE          : NULL                               
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 59769                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.389                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 48.650                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : NULL                               
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 100.0                              
REMARK 200  DATA REDUNDANCY                : 6.700                              
REMARK 200  R MERGE                    (I) : 0.06800                            
REMARK 200  R SYM                      (I) : 0.06300                            
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 19.4000                            
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.39                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 2.45                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : NULL                               
REMARK 200  DATA REDUNDANCY IN SHELL       : 6.70                               
REMARK 200  R MERGE FOR SHELL          (I) : NULL                               
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 2.100                              
REMARK 200                                                                      
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH                              
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT        
REMARK 200 SOFTWARE USED: NULL                                                  
REMARK 200 STARTING MODEL: PDB ENTRY 4JPS                                       
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 45.70                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.27                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 12% PEG 3350, 120MM POTASSIUM            
REMARK 280  THIOCYANATE, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 303.15K     
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       52.24150            
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000       66.75350            
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       53.26250            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000       66.75350            
REMARK 290   SMTRY1   4  1.000000  0.000000  0.000000       52.24150            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000       53.26250            
REMARK 290   SMTRY3   4  0.000000  0.000000 -1.000000        0.00000            
REMARK 290                                                                      
REMARK 290 REMARK: NULL                                                         
REMARK 300                                                                      
REMARK 300 BIOMOLECULE: 1                                                       
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM                
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN                  
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON               
REMARK 300 BURIED SURFACE AREA.                                                 
REMARK 350                                                                      
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN           
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE                
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS          
REMARK 350 GIVEN BELOW.  BOTH NON-CRYSTALLOGRAPHIC AND                          
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.                               
REMARK 350                                                                      
REMARK 350 BIOMOLECULE: 1                                                       
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: DIMERIC                           
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC                    
REMARK 350 SOFTWARE USED: PISA                                                  
REMARK 350 TOTAL BURIED SURFACE AREA: 6770 ANGSTROM**2                          
REMARK 350 SURFACE AREA OF THE COMPLEX: 53890 ANGSTROM**2                       
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -22.0 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     SER A   231                                                      
REMARK 465     LYS A   232                                                      
REMARK 465     LYS A   233                                                      
REMARK 465     THR A   313                                                      
REMARK 465     ALA A   314                                                      
REMARK 465     THR A   315                                                      
REMARK 465     PRO A   316                                                      
REMARK 465     TYR A   317                                                      
REMARK 465     MET A   318                                                      
REMARK 465     ASN A   319                                                      
REMARK 465     GLY A   320                                                      
REMARK 465     GLU A   321                                                      
REMARK 465     THR A   322                                                      
REMARK 465     SER A   501                                                      
REMARK 465     ARG A   502                                                      
REMARK 465     GLU A   503                                                      
REMARK 465     ALA A   504                                                      
REMARK 465     GLY A   505                                                      
REMARK 465     PHE A   506                                                      
REMARK 465     SER A   507                                                      
REMARK 465     TYR A   508                                                      
REMARK 465     SER A   509                                                      
REMARK 465     HIS A   510                                                      
REMARK 465     ALA A   511                                                      
REMARK 465     GLY A   512                                                      
REMARK 465     LEU A   513                                                      
REMARK 465     SER A   514                                                      
REMARK 465     ASN A   515                                                      
REMARK 465     ARG A   516                                                      
REMARK 465     LEU A   517                                                      
REMARK 465     ALA A   518                                                      
REMARK 465     ARG A   519                                                      
REMARK 465     ASP A   520                                                      
REMARK 465     ASN A   521                                                      
REMARK 465     GLU A   522                                                      
REMARK 465     LEU A   523                                                      
REMARK 465     GLY A   865                                                      
REMARK 465     LEU A   866                                                      
REMARK 465     LYS A   867                                                      
REMARK 465     GLY A   868                                                      
REMARK 465     ALA A   869                                                      
REMARK 465     LEU A   870                                                      
REMARK 465     GLN A   871                                                      
REMARK 465     ILE A  1062                                                      
REMARK 465     LYS A  1063                                                      
REMARK 465     GLN A  1064                                                      
REMARK 465     HIS A  1065                                                      
REMARK 465     ALA A  1066                                                      
REMARK 465     LEU A  1067                                                      
REMARK 465     ASN A  1068                                                      
REMARK 465     HIS A  1069                                                      
REMARK 465     HIS A  1070                                                      
REMARK 465     HIS A  1071                                                      
REMARK 465     HIS A  1072                                                      
REMARK 465     HIS A  1073                                                      
REMARK 465     HIS A  1074                                                      
REMARK 465     MET B   295                                                      
REMARK 465     GLU B   296                                                      
REMARK 465     TYR B   297                                                      
REMARK 465     MET B   298                                                      
REMARK 465     PRO B   299                                                      
REMARK 465     MET B   300                                                      
REMARK 465     GLU B   301                                                      
REMARK 465     HIS B   302                                                      
REMARK 465     ASN B   303                                                      
REMARK 465     LEU B   304                                                      
REMARK 465     GLN B   305                                                      
REMARK 465     TYR B   306                                                      
REMARK 465     LEU B   307                                                      
REMARK 465     PRO B   308                                                      
REMARK 465     PRO B   309                                                      
REMARK 465     LYS B   310                                                      
REMARK 465     PRO B   311                                                      
REMARK 465     PRO B   312                                                      
REMARK 465     LYS B   313                                                      
REMARK 465     PRO B   314                                                      
REMARK 465     THR B   315                                                      
REMARK 465     THR B   316                                                      
REMARK 465     VAL B   317                                                      
REMARK 465     ALA B   318                                                      
REMARK 465     ASN B   319                                                      
REMARK 465     ASN B   320                                                      
REMARK 465     GLY B   321                                                      
REMARK 465     MET B   322                                                      
REMARK 465     ASN B   323                                                      
REMARK 465     ASN B   324                                                      
REMARK 465     LYS B   363                                                      
REMARK 465     MET B   364                                                      
REMARK 465     HIS B   365                                                      
REMARK 465     GLY B   366                                                      
REMARK 465     HIS B   385                                                      
REMARK 465     ARG B   386                                                      
REMARK 465     ASP B   387                                                      
REMARK 465     GLY B   388                                                      
REMARK 465     LYS B   389                                                      
REMARK 465     TYR B   390                                                      
REMARK 465     GLY B   391                                                      
REMARK 465     SER B   412                                                      
REMARK 465     TYR B   416                                                      
REMARK 465     ASN B   417                                                      
REMARK 465     PRO B   418                                                      
REMARK 465     LYS B   419                                                      
REMARK 465     TYR B   431                                                      
REMARK 465     LYS B   592                                                      
REMARK 465     LYS B   593                                                      
REMARK 465     LEU B   594                                                      
REMARK 465     ASN B   595                                                      
REMARK 465     GLU B   596                                                      
REMARK 465     TRP B   597                                                      
REMARK 465     LEU B   598                                                      
REMARK 465     GLY B   599                                                      
REMARK 465     ASN B   600                                                      
REMARK 465     GLU B   601                                                      
REMARK 465     ASN B   602                                                      
REMARK 465     THR B   603                                                      
REMARK 465     GLU B   604                                                      
REMARK 465     ASP B   605                                                      
REMARK 465     GLN B   606                                                      
REMARK 465     TYR B   607                                                      
REMARK 465     SER B   608                                                      
REMARK 465     LEU B   609                                                      
REMARK 465     VAL B   610                                                      
REMARK 465     GLU B   611                                                      
REMARK 465     ASP B   612                                                      
REMARK 465     ASP B   613                                                      
REMARK 465     GLU B   614                                                      
REMARK 465     ASP B   615                                                      
REMARK 465     LEU B   616                                                      
REMARK 465     PRO B   617                                                      
REMARK 470                                                                      
REMARK 470 MISSING ATOM                                                         
REMARK 470 THE FOLLOWING RESIDUES HAVE MISSING ATOMS (M=MODEL NUMBER;           
REMARK 470 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;          
REMARK 470 I=INSERTION CODE):                                                   
REMARK 470   M RES CSSEQI  ATOMS                                                
REMARK 470     GLU A 109    CG   CD   OE1  OE2                                  
REMARK 470     MET A 130    CG   SD   CE                                        
REMARK 470     LYS A 132    CG   CD   CE   NZ                                   
REMARK 470     LYS A 148    CG   CD   CE   NZ                                   
REMARK 470     GLU A 176    CG   CD   OE1  OE2                                  
REMARK 470     LYS A 179    CG   CD   CE   NZ                                   
REMARK 470     LYS A 187    CG   CD   CE   NZ                                   
REMARK 470     ASN A 201    CG   OD1  ND2                                       
REMARK 470     GLN A 205    CG   CD   OE1  NE2                                  
REMARK 470     GLU A 218    CG   CD   OE1  OE2                                  
REMARK 470     LEU A 234    CG   CD1  CD2                                       
REMARK 470     SER A 235    OG                                                  
REMARK 470     SER A 236    OG                                                  
REMARK 470     GLN A 238    CG   CD   OE1  NE2                                  
REMARK 470     LYS A 240    CG   CD   CE   NZ                                   
REMARK 470     LEU A 241    CG   CD1  CD2                                       
REMARK 470     VAL A 243    CG1  CG2                                            
REMARK 470     GLU A 245    CG   CD   OE1  OE2                                  
REMARK 470     TYR A 246    CG   CD1  CD2  CE1  CE2  CZ   OH                    
REMARK 470     GLN A 247    CG   CD   OE1  NE2                                  
REMARK 470     LYS A 249    CG   CD   CE   NZ                                   
REMARK 470     LYS A 264    CG   CD   CE   NZ                                   
REMARK 470     ARG A 281    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     GLU A 291    CG   CD   OE1  OE2                                  
REMARK 470     MET A 299    CG   SD   CE                                        
REMARK 470     SER A 306    OG                                                  
REMARK 470     ARG A 309    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     ARG A 349    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     LYS A 353    CG   CD   CE   NZ                                   
REMARK 470     GLU A 365    CG   CD   OE1  OE2                                  
REMARK 470     LYS A 413    CG   CD   CE   NZ                                   
REMARK 470     LYS A 416    CG   CD   CE   NZ                                   
REMARK 470     TRP A 498    CG   CD1  CD2  NE1  CE2  CE3  CZ2                   
REMARK 470     TRP A 498    CZ3  CH2                                            
REMARK 470     ARG A 524    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     LYS A 528    CG   CD   CE   NZ                                   
REMARK 470     GLU A 529    CG   CD   OE1  OE2                                  
REMARK 470     LYS A 532    CG   CD   CE   NZ                                   
REMARK 470     LYS A 573    CG   CD   CE   NZ                                   
REMARK 470     LYS A 588    CG   CD   CE   NZ                                   
REMARK 470     MET A 697    CG   SD   CE                                        
REMARK 470     LYS A 729    CG   CD   CE   NZ                                   
REMARK 470     LYS A 733    CG   CD   CE   NZ                                   
REMARK 470     ARG A 740    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     ARG A 770    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     ARG A 777    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     LYS A 863    CG   CD   CE   NZ                                   
REMARK 470     PHE A 872    CG   CD1  CD2  CE1  CE2  CZ                         
REMARK 470     LYS A 882    CG   CD   CE   NZ                                   
REMARK 470     LYS A 886    CG   CD   CE   NZ                                   
REMARK 470     GLU A 888    CG   CD   OE1  OE2                                  
REMARK 470     LYS A 942    CG   CD   CE   NZ                                   
REMARK 470     TYR A 947    CG   CD1  CD2  CE1  CE2  CZ   OH                    
REMARK 470     ARG A 949    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     LYS A 973    CD   CE   NZ                                        
REMARK 470     ARG A 975    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     GLU A 982    CG   CD   OE1  OE2                                  
REMARK 470     LYS A1054    CG   CD   CE   NZ                                   
REMARK 470     MET A1055    CG   SD   CE                                        
REMARK 470     ASP A1056    CG   OD1  OD2                                       
REMARK 470     TRP A1057    CG   CD1  CD2  NE1  CE2  CE3  CZ2                   
REMARK 470     TRP A1057    CZ3  CH2                                            
REMARK 470     HIS A1060    CG   ND1  CD2  CE1  NE2                             
REMARK 470     THR A1061    OG1  CG2                                            
REMARK 470     ASN B 325    CG   OD1  ND2                                       
REMARK 470     MET B 326    CG   SD   CE                                        
REMARK 470     SER B 327    OG                                                  
REMARK 470     GLU B 345    CG   CD   OE1  OE2                                  
REMARK 470     LYS B 374    CG   CD   CE   NZ                                   
REMARK 470     PHE B 398    CG   CD1  CD2  CE1  CE2  CZ                         
REMARK 470     VAL B 401    CG1  CG2                                            
REMARK 470     GLU B 403    CG   CD   OE1  OE2                                  
REMARK 470     LEU B 404    CG   CD1  CD2                                       
REMARK 470     GLU B 411    CG   CD   OE1  OE2                                  
REMARK 470     LEU B 413    CG   CD1  CD2                                       
REMARK 470     GLN B 415    CG   CD   OE1  NE2                                  
REMARK 470     LEU B 420    CG   CD1  CD2                                       
REMARK 470     ASP B 421    CG   OD1  OD2                                       
REMARK 470     VAL B 422    CG1  CG2                                            
REMARK 470     LYS B 423    CG   CD   CE   NZ                                   
REMARK 470     LEU B 424    CG   CD1  CD2                                       
REMARK 470     TYR B 426    CG   CD1  CD2  CE1  CE2  CZ   OH                    
REMARK 470     GLN B 432    CG   CD   OE1  NE2                                  
REMARK 470     GLN B 433    CG   CD   OE1  NE2                                  
REMARK 470     ASP B 434    CG   OD1  OD2                                       
REMARK 470     GLN B 435    CG   CD   OE1  NE2                                  
REMARK 470     VAL B 436    CG1  CG2                                            
REMARK 470     LYS B 438    CG   CD   CE   NZ                                   
REMARK 470     GLU B 468    CG   CD   OE1  OE2                                  
REMARK 470     LYS B 511    CG   CD   CE   NZ                                   
REMARK 470     LYS B 513    CG   CD   CE   NZ                                   
REMARK 470     ARG B 514    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     GLU B 515    CG   CD   OE1  OE2                                  
REMARK 470     GLU B 518    CG   CD   OE1  OE2                                  
REMARK 470     LYS B 519    CG   CD   CE   NZ                                   
REMARK 470     GLU B 520    CD   OE1  OE2                                       
REMARK 470     LYS B 530    CG   CD   CE   NZ                                   
REMARK 470     LYS B 550    CG   CD   CE   NZ                                   
REMARK 470     LYS B 551    CG   CD   CE   NZ                                   
REMARK 470     GLN B 572    CG   CD   OE1  NE2                                  
REMARK 470     LYS B 587    CG   CD   CE   NZ                                   
REMARK 470     ARG B 590    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     GLN B 591    CG   CD   OE1  NE2                                  
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    ASN A 157       59.72   -113.06                                   
REMARK 500    ASN A 201      -14.70     66.53                                   
REMARK 500    ASN A 202       80.26     54.15                                   
REMARK 500    ASP A 258       48.73    -89.25                                   
REMARK 500    PHE A 261       68.42   -105.70                                   
REMARK 500    LEU A 339      -74.73    -85.76                                   
REMARK 500    ASN A 380       74.71   -118.73                                   
REMARK 500    GLU A 469       46.04    -98.85                                   
REMARK 500    LEU A 601        0.86    -69.06                                   
REMARK 500    GLN A 721      -83.08   -108.24                                   
REMARK 500    LEU A 793      -59.65   -126.18                                   
REMARK 500    PHE A 794      127.23   -176.55                                   
REMARK 500    ASP A 933       74.30     47.20                                   
REMARK 500    LEU A 938     -154.52     52.77                                   
REMARK 500    HIS A1060       84.53    -65.24                                   
REMARK 500    LEU B 328      -91.31   -130.04                                   
REMARK 500    LEU B 425      -84.81   -112.86                                   
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 3K6 A 1101                
DBREF  4WAF A    2  1068  UNP    P42336   PK3CA_HUMAN      2   1068             
DBREF  4WAF B  302   617  UNP    P27986   P85A_HUMAN       2    317             
SEQADV 4WAF LYS A  232  UNP  P42336    MET   232 ENGINEERED MUTATION            
SEQADV 4WAF LYS A  233  UNP  P42336    LEU   233 ENGINEERED MUTATION            
SEQADV 4WAF MET A  800  UNP  P42336    ILE   800 ENGINEERED MUTATION            
SEQADV 4WAF VAL A  930  UNP  P42336    PHE   930 ENGINEERED MUTATION            
SEQADV 4WAF HIS A 1069  UNP  P42336              EXPRESSION TAG                 
SEQADV 4WAF HIS A 1070  UNP  P42336              EXPRESSION TAG                 
SEQADV 4WAF HIS A 1071  UNP  P42336              EXPRESSION TAG                 
SEQADV 4WAF HIS A 1072  UNP  P42336              EXPRESSION TAG                 
SEQADV 4WAF HIS A 1073  UNP  P42336              EXPRESSION TAG                 
SEQADV 4WAF HIS A 1074  UNP  P42336              EXPRESSION TAG                 
SEQADV 4WAF MET B  295  UNP  P27986              INITIATING METHIONINE          
SEQADV 4WAF GLU B  296  UNP  P27986              EXPRESSION TAG                 
SEQADV 4WAF TYR B  297  UNP  P27986              EXPRESSION TAG                 
SEQADV 4WAF MET B  298  UNP  P27986              EXPRESSION TAG                 
SEQADV 4WAF PRO B  299  UNP  P27986              EXPRESSION TAG                 
SEQADV 4WAF MET B  300  UNP  P27986              EXPRESSION TAG                 
SEQADV 4WAF GLU B  301  UNP  P27986              EXPRESSION TAG                 
SEQADV 4WAF TYR B  306  UNP  P27986    THR     6 ENGINEERED MUTATION            
SEQRES   1 A 1073  PRO PRO ARG PRO SER SER GLY GLU LEU TRP GLY ILE HIS          
SEQRES   2 A 1073  LEU MET PRO PRO ARG ILE LEU VAL GLU CYS LEU LEU PRO          
SEQRES   3 A 1073  ASN GLY MET ILE VAL THR LEU GLU CYS LEU ARG GLU ALA          
SEQRES   4 A 1073  THR LEU ILE THR ILE LYS HIS GLU LEU PHE LYS GLU ALA          
SEQRES   5 A 1073  ARG LYS TYR PRO LEU HIS GLN LEU LEU GLN ASP GLU SER          
SEQRES   6 A 1073  SER TYR ILE PHE VAL SER VAL THR GLN GLU ALA GLU ARG          
SEQRES   7 A 1073  GLU GLU PHE PHE ASP GLU THR ARG ARG LEU CYS ASP LEU          
SEQRES   8 A 1073  ARG LEU PHE GLN PRO PHE LEU LYS VAL ILE GLU PRO VAL          
SEQRES   9 A 1073  GLY ASN ARG GLU GLU LYS ILE LEU ASN ARG GLU ILE GLY          
SEQRES  10 A 1073  PHE ALA ILE GLY MET PRO VAL CYS GLU PHE ASP MET VAL          
SEQRES  11 A 1073  LYS ASP PRO GLU VAL GLN ASP PHE ARG ARG ASN ILE LEU          
SEQRES  12 A 1073  ASN VAL CYS LYS GLU ALA VAL ASP LEU ARG ASP LEU ASN          
SEQRES  13 A 1073  SER PRO HIS SER ARG ALA MET TYR VAL TYR PRO PRO ASN          
SEQRES  14 A 1073  VAL GLU SER SER PRO GLU LEU PRO LYS HIS ILE TYR ASN          
SEQRES  15 A 1073  LYS LEU ASP LYS GLY GLN ILE ILE VAL VAL ILE TRP VAL          
SEQRES  16 A 1073  ILE VAL SER PRO ASN ASN ASP LYS GLN LYS TYR THR LEU          
SEQRES  17 A 1073  LYS ILE ASN HIS ASP CYS VAL PRO GLU GLN VAL ILE ALA          
SEQRES  18 A 1073  GLU ALA ILE ARG LYS LYS THR ARG SER LYS LYS LEU SER          
SEQRES  19 A 1073  SER GLU GLN LEU LYS LEU CYS VAL LEU GLU TYR GLN GLY          
SEQRES  20 A 1073  LYS TYR ILE LEU LYS VAL CYS GLY CYS ASP GLU TYR PHE          
SEQRES  21 A 1073  LEU GLU LYS TYR PRO LEU SER GLN TYR LYS TYR ILE ARG          
SEQRES  22 A 1073  SER CYS ILE MET LEU GLY ARG MET PRO ASN LEU MET LEU          
SEQRES  23 A 1073  MET ALA LYS GLU SER LEU TYR SER GLN LEU PRO MET ASP          
SEQRES  24 A 1073  CYS PHE THR MET PRO SER TYR SER ARG ARG ILE SER THR          
SEQRES  25 A 1073  ALA THR PRO TYR MET ASN GLY GLU THR SER THR LYS SER          
SEQRES  26 A 1073  LEU TRP VAL ILE ASN SER ALA LEU ARG ILE LYS ILE LEU          
SEQRES  27 A 1073  CYS ALA THR TYR VAL ASN VAL ASN ILE ARG ASP ILE ASP          
SEQRES  28 A 1073  LYS ILE TYR VAL ARG THR GLY ILE TYR HIS GLY GLY GLU          
SEQRES  29 A 1073  PRO LEU CYS ASP ASN VAL ASN THR GLN ARG VAL PRO CYS          
SEQRES  30 A 1073  SER ASN PRO ARG TRP ASN GLU TRP LEU ASN TYR ASP ILE          
SEQRES  31 A 1073  TYR ILE PRO ASP LEU PRO ARG ALA ALA ARG LEU CYS LEU          
SEQRES  32 A 1073  SER ILE CYS SER VAL LYS GLY ARG LYS GLY ALA LYS GLU          
SEQRES  33 A 1073  GLU HIS CYS PRO LEU ALA TRP GLY ASN ILE ASN LEU PHE          
SEQRES  34 A 1073  ASP TYR THR ASP THR LEU VAL SER GLY LYS MET ALA LEU          
SEQRES  35 A 1073  ASN LEU TRP PRO VAL PRO HIS GLY LEU GLU ASP LEU LEU          
SEQRES  36 A 1073  ASN PRO ILE GLY VAL THR GLY SER ASN PRO ASN LYS GLU          
SEQRES  37 A 1073  THR PRO CYS LEU GLU LEU GLU PHE ASP TRP PHE SER SER          
SEQRES  38 A 1073  VAL VAL LYS PHE PRO ASP MET SER VAL ILE GLU GLU HIS          
SEQRES  39 A 1073  ALA ASN TRP SER VAL SER ARG GLU ALA GLY PHE SER TYR          
SEQRES  40 A 1073  SER HIS ALA GLY LEU SER ASN ARG LEU ALA ARG ASP ASN          
SEQRES  41 A 1073  GLU LEU ARG GLU ASN ASP LYS GLU GLN LEU LYS ALA ILE          
SEQRES  42 A 1073  SER THR ARG ASP PRO LEU SER GLU ILE THR GLU GLN GLU          
SEQRES  43 A 1073  LYS ASP PHE LEU TRP SER HIS ARG HIS TYR CYS VAL THR          
SEQRES  44 A 1073  ILE PRO GLU ILE LEU PRO LYS LEU LEU LEU SER VAL LYS          
SEQRES  45 A 1073  TRP ASN SER ARG ASP GLU VAL ALA GLN MET TYR CYS LEU          
SEQRES  46 A 1073  VAL LYS ASP TRP PRO PRO ILE LYS PRO GLU GLN ALA MET          
SEQRES  47 A 1073  GLU LEU LEU ASP CYS ASN TYR PRO ASP PRO MET VAL ARG          
SEQRES  48 A 1073  GLY PHE ALA VAL ARG CYS LEU GLU LYS TYR LEU THR ASP          
SEQRES  49 A 1073  ASP LYS LEU SER GLN TYR LEU ILE GLN LEU VAL GLN VAL          
SEQRES  50 A 1073  LEU LYS TYR GLU GLN TYR LEU ASP ASN LEU LEU VAL ARG          
SEQRES  51 A 1073  PHE LEU LEU LYS LYS ALA LEU THR ASN GLN ARG ILE GLY          
SEQRES  52 A 1073  HIS PHE PHE PHE TRP HIS LEU LYS SER GLU MET HIS ASN          
SEQRES  53 A 1073  LYS THR VAL SER GLN ARG PHE GLY LEU LEU LEU GLU SER          
SEQRES  54 A 1073  TYR CYS ARG ALA CYS GLY MET TYR LEU LYS HIS LEU ASN          
SEQRES  55 A 1073  ARG GLN VAL GLU ALA MET GLU LYS LEU ILE ASN LEU THR          
SEQRES  56 A 1073  ASP ILE LEU LYS GLN GLU LYS LYS ASP GLU THR GLN LYS          
SEQRES  57 A 1073  VAL GLN MET LYS PHE LEU VAL GLU GLN MET ARG ARG PRO          
SEQRES  58 A 1073  ASP PHE MET ASP ALA LEU GLN GLY PHE LEU SER PRO LEU          
SEQRES  59 A 1073  ASN PRO ALA HIS GLN LEU GLY ASN LEU ARG LEU GLU GLU          
SEQRES  60 A 1073  CYS ARG ILE MET SER SER ALA LYS ARG PRO LEU TRP LEU          
SEQRES  61 A 1073  ASN TRP GLU ASN PRO ASP ILE MET SER GLU LEU LEU PHE          
SEQRES  62 A 1073  GLN ASN ASN GLU ILE MET PHE LYS ASN GLY ASP ASP LEU          
SEQRES  63 A 1073  ARG GLN ASP MET LEU THR LEU GLN ILE ILE ARG ILE MET          
SEQRES  64 A 1073  GLU ASN ILE TRP GLN ASN GLN GLY LEU ASP LEU ARG MET          
SEQRES  65 A 1073  LEU PRO TYR GLY CYS LEU SER ILE GLY ASP CYS VAL GLY          
SEQRES  66 A 1073  LEU ILE GLU VAL VAL ARG ASN SER HIS THR ILE MET GLN          
SEQRES  67 A 1073  ILE GLN CYS LYS GLY GLY LEU LYS GLY ALA LEU GLN PHE          
SEQRES  68 A 1073  ASN SER HIS THR LEU HIS GLN TRP LEU LYS ASP LYS ASN          
SEQRES  69 A 1073  LYS GLY GLU ILE TYR ASP ALA ALA ILE ASP LEU PHE THR          
SEQRES  70 A 1073  ARG SER CYS ALA GLY TYR CYS VAL ALA THR PHE ILE LEU          
SEQRES  71 A 1073  GLY ILE GLY ASP ARG HIS ASN SER ASN ILE MET VAL LYS          
SEQRES  72 A 1073  ASP ASP GLY GLN LEU VAL HIS ILE ASP PHE GLY HIS PHE          
SEQRES  73 A 1073  LEU ASP HIS LYS LYS LYS LYS PHE GLY TYR LYS ARG GLU          
SEQRES  74 A 1073  ARG VAL PRO PHE VAL LEU THR GLN ASP PHE LEU ILE VAL          
SEQRES  75 A 1073  ILE SER LYS GLY ALA GLN GLU CYS THR LYS THR ARG GLU          
SEQRES  76 A 1073  PHE GLU ARG PHE GLN GLU MET CYS TYR LYS ALA TYR LEU          
SEQRES  77 A 1073  ALA ILE ARG GLN HIS ALA ASN LEU PHE ILE ASN LEU PHE          
SEQRES  78 A 1073  SER MET MET LEU GLY SER GLY MET PRO GLU LEU GLN SER          
SEQRES  79 A 1073  PHE ASP ASP ILE ALA TYR ILE ARG LYS THR LEU ALA LEU          
SEQRES  80 A 1073  ASP LYS THR GLU GLN GLU ALA LEU GLU TYR PHE MET LYS          
SEQRES  81 A 1073  GLN MET ASN ASP ALA HIS HIS GLY GLY TRP THR THR LYS          
SEQRES  82 A 1073  MET ASP TRP ILE PHE HIS THR ILE LYS GLN HIS ALA LEU          
SEQRES  83 A 1073  ASN HIS HIS HIS HIS HIS HIS                                  
SEQRES   1 B  323  MET GLU TYR MET PRO MET GLU HIS ASN LEU GLN TYR LEU          
SEQRES   2 B  323  PRO PRO LYS PRO PRO LYS PRO THR THR VAL ALA ASN ASN          
SEQRES   3 B  323  GLY MET ASN ASN ASN MET SER LEU GLN ASP ALA GLU TRP          
SEQRES   4 B  323  TYR TRP GLY ASP ILE SER ARG GLU GLU VAL ASN GLU LYS          
SEQRES   5 B  323  LEU ARG ASP THR ALA ASP GLY THR PHE LEU VAL ARG ASP          
SEQRES   6 B  323  ALA SER THR LYS MET HIS GLY ASP TYR THR LEU THR LEU          
SEQRES   7 B  323  ARG LYS GLY GLY ASN ASN LYS LEU ILE LYS ILE PHE HIS          
SEQRES   8 B  323  ARG ASP GLY LYS TYR GLY PHE SER ASP PRO LEU THR PHE          
SEQRES   9 B  323  SER SER VAL VAL GLU LEU ILE ASN HIS TYR ARG ASN GLU          
SEQRES  10 B  323  SER LEU ALA GLN TYR ASN PRO LYS LEU ASP VAL LYS LEU          
SEQRES  11 B  323  LEU TYR PRO VAL SER LYS TYR GLN GLN ASP GLN VAL VAL          
SEQRES  12 B  323  LYS GLU ASP ASN ILE GLU ALA VAL GLY LYS LYS LEU HIS          
SEQRES  13 B  323  GLU TYR ASN THR GLN PHE GLN GLU LYS SER ARG GLU TYR          
SEQRES  14 B  323  ASP ARG LEU TYR GLU GLU TYR THR ARG THR SER GLN GLU          
SEQRES  15 B  323  ILE GLN MET LYS ARG THR ALA ILE GLU ALA PHE ASN GLU          
SEQRES  16 B  323  THR ILE LYS ILE PHE GLU GLU GLN CYS GLN THR GLN GLU          
SEQRES  17 B  323  ARG TYR SER LYS GLU TYR ILE GLU LYS PHE LYS ARG GLU          
SEQRES  18 B  323  GLY ASN GLU LYS GLU ILE GLN ARG ILE MET HIS ASN TYR          
SEQRES  19 B  323  ASP LYS LEU LYS SER ARG ILE SER GLU ILE ILE ASP SER          
SEQRES  20 B  323  ARG ARG ARG LEU GLU GLU ASP LEU LYS LYS GLN ALA ALA          
SEQRES  21 B  323  GLU TYR ARG GLU ILE ASP LYS ARG MET ASN SER ILE LYS          
SEQRES  22 B  323  PRO ASP LEU ILE GLN LEU ARG LYS THR ARG ASP GLN TYR          
SEQRES  23 B  323  LEU MET TRP LEU THR GLN LYS GLY VAL ARG GLN LYS LYS          
SEQRES  24 B  323  LEU ASN GLU TRP LEU GLY ASN GLU ASN THR GLU ASP GLN          
SEQRES  25 B  323  TYR SER LEU VAL GLU ASP ASP GLU ASP LEU PRO                  
HET    3K6  A1101      31                                                       
HETNAM     3K6 N,N-DIMETHYL-4-[(6R)-6-METHYL-5-(1H-PYRROLO[2,3-                 
HETNAM   2 3K6  B]PYRIDIN-4-YL)-4,5,6,7-TETRAHYDROPYRAZOLO[1,5-                 
HETNAM   3 3K6  A]PYRAZIN-3-YL]BENZENESULFONAMIDE                               
FORMUL   3  3K6    C22 H24 N6 O2 S                                              
FORMUL   4  HOH   *288(H2 O)                                                    
HELIX    1 AA1 THR A   41  ALA A   53  1                                  13    
HELIX    2 AA2 ARG A   54  TYR A   56  5                                   3    
HELIX    3 AA3 LEU A   58  LEU A   62  5                                   5    
HELIX    4 AA4 ASP A   64  TYR A   68  5                                   5    
HELIX    5 AA5 ARG A   88  LEU A   92  5                                   5    
HELIX    6 AA6 ASN A  107  GLY A  122  1                                  16    
HELIX    7 AA7 VAL A  125  VAL A  131  1                                   7    
HELIX    8 AA8 ASP A  133  ILE A  143  1                                  11    
HELIX    9 AA9 ILE A  143  ASP A  155  1                                  13    
HELIX   10 AB1 PRO A  159  TYR A  167  1                                   9    
HELIX   11 AB2 PRO A  178  ASN A  183  1                                   6    
HELIX   12 AB3 VAL A  216  LYS A  227  1                                  12    
HELIX   13 AB4 SER A  236  VAL A  243  1                                   8    
HELIX   14 AB5 PRO A  266  GLN A  269  5                                   4    
HELIX   15 AB6 TYR A  270  GLY A  280  1                                  11    
HELIX   16 AB7 LYS A  290  SER A  295  1                                   6    
HELIX   17 AB8 PRO A  305  ARG A  310  1                                   6    
HELIX   18 AB9 TRP A  328  ILE A  330  5                                   3    
HELIX   19 AC1 PRO A  394  LEU A  396  5                                   3    
HELIX   20 AC2 ASP A  488  VAL A  500  1                                  13    
HELIX   21 AC3 GLU A  525  ARG A  537  1                                  13    
HELIX   22 AC4 THR A  544  HIS A  554  1                                  11    
HELIX   23 AC5 TYR A  557  GLU A  563  5                                   7    
HELIX   24 AC6 ILE A  564  VAL A  572  1                                   9    
HELIX   25 AC7 SER A  576  ASP A  589  1                                  14    
HELIX   26 AC8 LYS A  594  MET A  599  1                                   6    
HELIX   27 AC9 GLU A  600  ASP A  603  5                                   4    
HELIX   28 AD1 ASP A  608  LEU A  623  1                                  16    
HELIX   29 AD2 THR A  624  VAL A  638  1                                  15    
HELIX   30 AD3 LEU A  639  GLU A  642  5                                   4    
HELIX   31 AD4 ASN A  647  LEU A  658  1                                  12    
HELIX   32 AD5 ASN A  660  SER A  673  1                                  14    
HELIX   33 AD6 VAL A  680  CYS A  695  1                                  16    
HELIX   34 AD7 MET A  697  GLN A  721  1                                  25    
HELIX   35 AD8 THR A  727  ARG A  740  1                                  14    
HELIX   36 AD9 ARG A  741  GLN A  749  1                                   9    
HELIX   37 AE1 ARG A  765  CYS A  769  5                                   5    
HELIX   38 AE2 MET A  789  LEU A  793  5                                   5    
HELIX   39 AE3 LEU A  807  GLN A  827  1                                  21    
HELIX   40 AE4 ILE A  857  GLY A  864  1                                   8    
HELIX   41 AE5 HIS A  875  ASN A  885  1                                  11    
HELIX   42 AE6 LYS A  886  GLU A  888  5                                   3    
HELIX   43 AE7 ILE A  889  GLY A  912  1                                  24    
HELIX   44 AE8 THR A  957  SER A  965  1                                   9    
HELIX   45 AE9 THR A  974  HIS A  994  1                                  21    
HELIX   46 AF1 HIS A  994  MET A 1005  1                                  12    
HELIX   47 AF2 SER A 1015  LEU A 1026  1                                  12    
HELIX   48 AF3 THR A 1031  HIS A 1048  1                                  18    
HELIX   49 AF4 SER B  339  ARG B  348  1                                  10    
HELIX   50 AF5 SER B  400  GLU B  411  1                                  12    
HELIX   51 AF6 GLN B  433  VAL B  437  1                                   5    
HELIX   52 AF7 ASN B  441  GLU B  515  1                                  75    
HELIX   53 AF8 ASN B  517  GLY B  588  1                                  72    
SHEET    1 AA1 5 ILE A  31  LEU A  37  0                                        
SHEET    2 AA1 5 ARG A  19  LEU A  25 -1  N  CYS A  24   O  VAL A  32           
SHEET    3 AA1 5 PHE A  98  ILE A 102  1  O  LEU A  99   N  LEU A  25           
SHEET    4 AA1 5 ILE A  69  VAL A  73 -1  N  VAL A  71   O  LYS A 100           
SHEET    5 AA1 5 ARG A  79  PHE A  82 -1  O  PHE A  82   N  PHE A  70           
SHEET    1 AA2 5 ASP A 203  ASN A 212  0                                        
SHEET    2 AA2 5 GLN A 189  VAL A 198 -1  N  ILE A 190   O  ILE A 211           
SHEET    3 AA2 5 ASN A 284  ALA A 289  1  O  LEU A 287   N  TRP A 195           
SHEET    4 AA2 5 TYR A 250  VAL A 254 -1  N  LYS A 253   O  MET A 286           
SHEET    5 AA2 5 TYR A 260  PHE A 261 -1  O  PHE A 261   N  LEU A 252           
SHEET    1 AA3 2 THR A 324  SER A 326  0                                        
SHEET    2 AA3 2 VAL A 483  LYS A 485  1  O  LYS A 485   N  LYS A 325           
SHEET    1 AA4 4 ARG A 382  TYR A 392  0                                        
SHEET    2 AA4 4 ALA A 333  ALA A 341 -1  N  LEU A 339   O  TRP A 383           
SHEET    3 AA4 4 CYS A 472  PHE A 477 -1  O  GLU A 474   N  CYS A 340           
SHEET    4 AA4 4 GLY A 439  ASN A 444 -1  N  LEU A 443   O  LEU A 473           
SHEET    1 AA5 3 GLU A 365  PRO A 366  0                                        
SHEET    2 AA5 3 LYS A 353  HIS A 362 -1  N  HIS A 362   O  GLU A 365           
SHEET    3 AA5 3 VAL A 371  ASN A 372 -1  O  VAL A 371   N  THR A 358           
SHEET    1 AA6 4 GLU A 365  PRO A 366  0                                        
SHEET    2 AA6 4 LYS A 353  HIS A 362 -1  N  HIS A 362   O  GLU A 365           
SHEET    3 AA6 4 ARG A 401  LYS A 413 -1  O  CYS A 407   N  TYR A 355           
SHEET    4 AA6 4 LYS A 416  ASN A 428 -1  O  LEU A 422   N  ILE A 406           
SHEET    1 AA7 2 PHE A 751  LEU A 752  0                                        
SHEET    2 AA7 2 GLN A 760  LEU A 761 -1  O  LEU A 761   N  PHE A 751           
SHEET    1 AA8 5 ARG A 770  ILE A 771  0                                        
SHEET    2 AA8 5 LEU A 779  GLU A 784 -1  O  TRP A 780   N  ARG A 770           
SHEET    3 AA8 5 ASN A 796  ASN A 803 -1  O  ASN A 797   N  TRP A 783           
SHEET    4 AA8 5 VAL A 845  GLU A 849 -1  O  ILE A 848   N  MET A 800           
SHEET    5 AA8 5 CYS A 838  GLY A 842 -1  N  LEU A 839   O  LEU A 847           
SHEET    1 AA9 3 SER A 854  THR A 856  0                                        
SHEET    2 AA9 3 ILE A 921  LYS A 924 -1  O  VAL A 923   N  HIS A 855           
SHEET    3 AA9 3 LEU A 929  HIS A 931 -1  O  VAL A 930   N  MET A 922           
SHEET    1 AB1 4 TYR B 334  GLY B 336  0                                        
SHEET    2 AB1 4 PHE B 355  ASP B 359  1  O  VAL B 357   N  TRP B 335           
SHEET    3 AB1 4 TYR B 368  LYS B 374 -1  O  THR B 369   N  ARG B 358           
SHEET    4 AB1 4 ASN B 377  ILE B 383 -1  O  ILE B 381   N  LEU B 370           
CISPEP   1 SER A  158    PRO A  159          0         6.03                     
CISPEP   2 SER A  199    PRO A  200          0        -0.21                     
SITE     1 AC1 13 TRP A 780  MET A 800  LYS A 802  ASP A 810                    
SITE     2 AC1 13 TYR A 836  ILE A 848  GLU A 849  VAL A 850                    
SITE     3 AC1 13 VAL A 851  SER A 854  GLN A 859  MET A 922                    
SITE     4 AC1 13 ASP A 933                                                     
CRYST1  104.483  106.525  133.507  90.00  90.00  90.00 P 21 21 21    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      0.009571  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.009387  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.007490        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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