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Database: PDB
Entry: 4JPS
LinkDB: 4JPS
Original site: 4JPS 
HEADER    TRANSFERASE/TRANSFERASE INHIBITOR       19-MAR-13   4JPS              
TITLE     CO-CRYSTAL STRUCTURES OF THE LIPID KINASE PI3K ALPHA WITH PAN AND     
TITLE    2 ISOFORM SELECTIVE INHIBITORS                                         
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: PI3-KINASE SUBUNIT ALPHA, PI3K-ALPHA, PI3KALPHA, PTDINS-3-  
COMPND   6 KINASE SUBUNIT ALPHA, PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE 
COMPND   7 110 KDA CATALYTIC SUBUNIT ALPHA, PTDINS-3-KINASE SUBUNIT P110-ALPHA, 
COMPND   8 P110ALPHA, PHOSPHOINOSITIDE-3-KINASE CATALYTIC ALPHA POLYPEPTIDE,    
COMPND   9 SERINE/THREONINE PROTEIN KINASE PIK3CA;                              
COMPND  10 EC: 2.7.1.153, 2.7.11.1;                                             
COMPND  11 ENGINEERED: YES;                                                     
COMPND  12 MUTATION: YES;                                                       
COMPND  13 MOL_ID: 2;                                                           
COMPND  14 MOLECULE: PHOSPHATIDYLINOSITOL 3-KINASE REGULATORY SUBUNIT ALPHA;    
COMPND  15 CHAIN: B;                                                            
COMPND  16 SYNONYM: PI3-KINASE REGULATORY SUBUNIT ALPHA, PI3K REGULATORY SUBUNIT
COMPND  17 ALPHA, PTDINS-3-KINASE REGULATORY SUBUNIT ALPHA, PHOSPHATIDYLINOSITOL
COMPND  18 3-KINASE 85 KDA REGULATORY SUBUNIT ALPHA, PI3-KINASE SUBUNIT P85-    
COMPND  19 ALPHA, PTDINS-3-KINASE REGULATORY SUBUNIT P85-ALPHA;                 
COMPND  20 ENGINEERED: YES                                                      
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606;                                                
SOURCE   5 GENE: PIK3CA;                                                        
SOURCE   6 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA;                            
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 7108;                                       
SOURCE   8 EXPRESSION_SYSTEM_STRAIN: SF9;                                       
SOURCE   9 MOL_ID: 2;                                                           
SOURCE  10 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE  11 ORGANISM_COMMON: HUMAN;                                              
SOURCE  12 ORGANISM_TAXID: 9606;                                                
SOURCE  13 GENE: GRB1, PIK3R1;                                                  
SOURCE  14 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA;                            
SOURCE  15 EXPRESSION_SYSTEM_TAXID: 7108;                                       
SOURCE  16 EXPRESSION_SYSTEM_STRAIN: SF9                                        
KEYWDS    CLASS I PHOSPHATIDYLINOSITOL 3-KINASES, P85 ALPHA, TRANSFERASE-       
KEYWDS   2 TRANSFERASE INHIBITOR COMPLEX                                        
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    M.S.KNAPP,R.A.ELLING                                                  
REVDAT   2   15-NOV-17 4JPS    1       REMARK                                   
REVDAT   1   02-APR-14 4JPS    0                                                
JRNL        AUTH   P.FURET,V.GUAGNANO,R.A.FAIRHURST,P.IMBACH-WEESE,I.BRUCE,     
JRNL        AUTH 2 M.KNAPP,C.FRITSCH,F.BLASCO,J.BLANZ,R.AICHHOLZ,J.HAMON,       
JRNL        AUTH 3 D.FABBRO,G.CARAVATTI                                         
JRNL        TITL   DISCOVERY OF NVP-BYL719 A POTENT AND SELECTIVE               
JRNL        TITL 2 PHOSPHATIDYLINOSITOL-3 KINASE ALPHA INHIBITOR SELECTED FOR   
JRNL        TITL 3 CLINICAL EVALUATION.                                         
JRNL        REF    BIOORG.MED.CHEM.LETT.         V.  23  3741 2013              
JRNL        REFN                   ISSN 0960-894X                               
JRNL        PMID   23726034                                                     
JRNL        DOI    10.1016/J.BMCL.2013.05.007                                   
REMARK   2                                                                      
REMARK   2 RESOLUTION.    2.20 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : BUSTER-TNT                                           
REMARK   3   AUTHORS     : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,              
REMARK   3               : PACIOREK,ROVERSI,SMART,VONRHEIN,WOMACK,              
REMARK   3               : MATTHEWS,TEN EYCK,TRONRUD                            
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 2.20                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 50.00                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : 0.000                          
REMARK   3   COMPLETENESS FOR RANGE        (%) : 96.6                           
REMARK   3   NUMBER OF REFLECTIONS             : 73703                          
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)  : 0.206                          
REMARK   3   R VALUE            (WORKING SET)  : 0.205                          
REMARK   3   FREE R VALUE                      : 0.228                          
REMARK   3   FREE R VALUE TEST SET SIZE   (%)  : 4.970                          
REMARK   3   FREE R VALUE TEST SET COUNT       : 3662                           
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) : 2.20                     
REMARK   3   BIN RESOLUTION RANGE LOW    (ANGSTROMS) : 2.26                     
REMARK   3   BIN COMPLETENESS (WORKING+TEST)     (%) : 96.56                    
REMARK   3   REFLECTIONS IN BIN (WORKING + TEST SET) : 5476                     
REMARK   3   BIN R VALUE        (WORKING + TEST SET) : 0.2276                   
REMARK   3   REFLECTIONS IN BIN        (WORKING SET) : 5221                     
REMARK   3   BIN R VALUE               (WORKING SET) : 0.2273                   
REMARK   3   BIN FREE R VALUE                        : 0.2338                   
REMARK   3   BIN FREE R VALUE TEST SET SIZE      (%) : 4.66                     
REMARK   3   BIN FREE R VALUE TEST SET COUNT         : 255                      
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            : 9937                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 33                                      
REMARK   3   SOLVENT ATOMS            : 506                                     
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 47.56                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 52.75                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : 1.82430                                              
REMARK   3    B22 (A**2) : 3.29450                                              
REMARK   3    B33 (A**2) : -5.11880                                             
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) : NULL                
REMARK   3   DPI (BLOW EQ-9) BASED ON FREE R VALUE    (A) : NULL                
REMARK   3   DPI (CRUICKSHANK) BASED ON R VALUE       (A) : 0.255               
REMARK   3   DPI (CRUICKSHANK) BASED ON FREE R VALUE  (A) : NULL                
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      : 0.943                         
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : 0.936                         
REMARK   3                                                                      
REMARK   3   NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15                    
REMARK   3   TERM                          COUNT    WEIGHT   FUNCTION.          
REMARK   3    BOND LENGTHS              : 10243  ; 2.000  ; HARMONIC            
REMARK   3    BOND ANGLES               : 13858  ; 2.000  ; HARMONIC            
REMARK   3    TORSION ANGLES            : 3673   ; 2.000  ; SINUSOIDAL          
REMARK   3    TRIGONAL CARBON PLANES    : 286    ; 2.000  ; HARMONIC            
REMARK   3    GENERAL PLANES            : 1474   ; 5.000  ; HARMONIC            
REMARK   3    ISOTROPIC THERMAL FACTORS : 10243  ; 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   : 1312   ; 5.000  ; SEMIHARMONIC        
REMARK   3    SUM OF OCCUPANCIES        : 5      ; 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   : 12011  ; 4.000  ; SEMIHARMONIC        
REMARK   3                                                                      
REMARK   3   RMS DEVIATIONS FROM IDEAL VALUES.                                  
REMARK   3    BOND LENGTHS                       (A) : 0.008                    
REMARK   3    BOND ANGLES                  (DEGREES) : 0.99                     
REMARK   3    PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 2.85                     
REMARK   3    OTHER TORSION ANGLES         (DEGREES) : 17.29                    
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):   -9.4061  -26.8159   27.3466           
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):  -10.5723  -15.5751   48.3630           
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 4JPS COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 22-MAR-13.                  
REMARK 100 THE DEPOSITION ID IS D_1000078350.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 13-OCT-11                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : 7.5                                
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : ALS                                
REMARK 200  BEAMLINE                       : 5.0.2                              
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                  : DOUBLE-CRYSTAL, SI(111) LIQUID     
REMARK 200                                   N2 COOLED                          
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : CCD                                
REMARK 200  DETECTOR MANUFACTURER          : ADSC QUANTUM 315R                  
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : XSCALE                             
REMARK 200  DATA SCALING SOFTWARE          : SCALA 3.3.20, XSCALE               
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 98307                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.000                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 133.667                            
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : 1.000                              
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 97.4                               
REMARK 200  DATA REDUNDANCY                : 4.900                              
REMARK 200  R MERGE                    (I) : NULL                               
REMARK 200  R SYM                      (I) : 0.05300                            
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 15.3000                            
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.00                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 2.11                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 98.7                               
REMARK 200  DATA REDUNDANCY IN SHELL       : 4.90                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.01000                            
REMARK 200  R SYM FOR SHELL            (I) : 1.02600                            
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 0.800                              
REMARK 200                                                                      
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH                              
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT        
REMARK 200 SOFTWARE USED: RIGID BODY                                            
REMARK 200 STARTING MODEL: NULL                                                 
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 46.97                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.32                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 12% PEG 3350, 120MM KSCN, 6UL PROTEIN    
REMARK 280  TO 4UL WELL WITH STREAK SEEDING AT 18C , PH 7.5, VAPOR DIFFUSION,   
REMARK 280  HANGING DROP, TEMPERATURE 303K                                      
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       52.43250            
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000       66.83350            
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       53.09750            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000       66.83350            
REMARK 290   SMTRY1   4  1.000000  0.000000  0.000000       52.43250            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000       53.09750            
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: 6640 ANGSTROM**2                          
REMARK 350 SURFACE AREA OF THE COMPLEX: 53480 ANGSTROM**2                       
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -19.0 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     MET A     1                                                      
REMARK 465     LYS A   228                                                      
REMARK 465     THR A   229                                                      
REMARK 465     ARG A   230                                                      
REMARK 465     SER A   231                                                      
REMARK 465     LYS A   232                                                      
REMARK 465     LYS A   233                                                      
REMARK 465     LEU A   234                                                      
REMARK 465     SER A   235                                                      
REMARK 465     SER A   236                                                      
REMARK 465     GLU A   237                                                      
REMARK 465     GLN A   238                                                      
REMARK 465     LEU A   239                                                      
REMARK 465     LYS A   240                                                      
REMARK 465     LEU A   241                                                      
REMARK 465     CYS A   242                                                      
REMARK 465     VAL A   243                                                      
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   323                                                      
REMARK 465     TRP A   498                                                      
REMARK 465     SER A   499                                                      
REMARK 465     VAL A   500                                                      
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     ARG A   524                                                      
REMARK 465     GLY A   864                                                      
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   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     ASN B   325                                                      
REMARK 465     MET B   326                                                      
REMARK 465     SER B   327                                                      
REMARK 465     LEU B   328                                                      
REMARK 465     GLN B   329                                                      
REMARK 465     ASP B   330                                                      
REMARK 465     ALA B   331                                                      
REMARK 465     MET B   364                                                      
REMARK 465     HIS B   365                                                      
REMARK 465     GLY B   366                                                      
REMARK 465     ASP B   387                                                      
REMARK 465     GLY B   388                                                      
REMARK 465     LYS B   389                                                      
REMARK 465     TYR B   390                                                      
REMARK 465     SER B   399                                                      
REMARK 465     SER B   400                                                      
REMARK 465     VAL B   401                                                      
REMARK 465     VAL B   402                                                      
REMARK 465     GLU B   403                                                      
REMARK 465     LEU B   404                                                      
REMARK 465     ILE B   405                                                      
REMARK 465     ASN B   406                                                      
REMARK 465     HIS B   407                                                      
REMARK 465     TYR B   408                                                      
REMARK 465     ARG B   409                                                      
REMARK 465     ASN B   410                                                      
REMARK 465     GLU B   411                                                      
REMARK 465     SER B   412                                                      
REMARK 465     LEU B   413                                                      
REMARK 465     ALA B   414                                                      
REMARK 465     GLN B   415                                                      
REMARK 465     TYR B   416                                                      
REMARK 465     ASN B   417                                                      
REMARK 465     PRO B   418                                                      
REMARK 465     LYS B   419                                                      
REMARK 465     LEU B   420                                                      
REMARK 465     ASP B   421                                                      
REMARK 465     VAL B   422                                                      
REMARK 465     TYR B   431                                                      
REMARK 465     GLN B   432                                                      
REMARK 465     GLN B   433                                                      
REMARK 465     LYS B   593                                                      
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     MET A 130    CG   SD   CE                                        
REMARK 470     LYS A 132    CG   CD   CE   NZ                                   
REMARK 470     LYS A 179    CG   CD   CE   NZ                                   
REMARK 470     LYS A 187    CG   CD   CE   NZ                                   
REMARK 470     LYS A 204    CG   CD   CE   NZ                                   
REMARK 470     LEU A 244    CG   CD1  CD2                                       
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     MET A 299    CG   SD   CE                                        
REMARK 470     LYS A 416    CG   CD   CE   NZ                                   
REMARK 470     TRP A 479    CG   CD1  CD2  NE1  CE2  CE3  CZ2                   
REMARK 470     TRP A 479    CZ3  CH2                                            
REMARK 470     GLU A 525    CG   CD   OE1  OE2                                  
REMARK 470     LYS A 528    CG   CD   CE   NZ                                   
REMARK 470     LYS A 532    CG   CD   CE   NZ                                   
REMARK 470     LYS A 594    CG   CD   CE   NZ                                   
REMARK 470     MET A 697    CG   SD   CE                                        
REMARK 470     LYS A 700    CG   CD   CE   NZ                                   
REMARK 470     LYS A 948    CG   CD   CE   NZ                                   
REMARK 470     LYS A 973    CG   CD   CE   NZ                                   
REMARK 470     ARG A 975    CG   CD   NE   CZ   NH1  NH2                        
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     ILE A1058    CG1  CG2  CD1                                       
REMARK 470     PHE A1059    CG   CD1  CD2  CE1  CE2  CZ                         
REMARK 470     HIS A1060    CG   ND1  CD2  CE1  NE2                             
REMARK 470     GLU B 345    CG   CD   OE1  OE2                                  
REMARK 470     LYS B 363    CG   CD   CE   NZ                                   
REMARK 470     LEU B 370    CG   CD1  CD2                                       
REMARK 470     ARG B 386    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     TYR B 426    CG   CD1  CD2  CE1  CE2  CZ   OH                    
REMARK 470     LYS B 430    CG   CD   CE   NZ                                   
REMARK 470     LYS B 438    CG   CD   CE   NZ                                   
REMARK 470     LYS B 506    CG   CD   CE   NZ                                   
REMARK 470     LYS B 511    CG   CD   CE   NZ                                   
REMARK 470     LYS B 513    CG   CD   CE   NZ                                   
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     MET B 582    CG   SD   CE                                        
REMARK 470     LYS B 587    CG   CD   CE   NZ                                   
REMARK 470     LYS B 592    CG   CD   CE   NZ                                   
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    THR B 362   C   -  N   -  CA  ANGL. DEV. =  15.5 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    PHE A 261       65.31   -105.67                                   
REMARK 500    LEU A 339      -76.71    -87.38                                   
REMARK 500    GLU A 469       47.23    -95.77                                   
REMARK 500    SER A 481       13.01     59.55                                   
REMARK 500    HIS A 495      -82.44     65.38                                   
REMARK 500    GLN A 721      -78.41   -111.67                                   
REMARK 500    PHE A 794      141.10   -171.94                                   
REMARK 500    ASP A 933       71.09     49.69                                   
REMARK 500    LEU A 938     -152.04     56.82                                   
REMARK 500    MET A1055      125.44     77.65                                   
REMARK 500    SER B 361        4.36    -58.40                                   
REMARK 500    THR B 362       86.86    121.13                                   
REMARK 500    GLN B 591      146.49     77.25                                   
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 SCN A 1101                
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 1LT A 1102                
DBREF  4JPS A    1  1068  UNP    P42336   PK3CA_HUMAN      1   1068             
DBREF  4JPS B  307   593  UNP    P27986   P85A_HUMAN     307    593             
SEQADV 4JPS LYS A  232  UNP  P42336    MET   232 ENGINEERED MUTATION            
SEQADV 4JPS LYS A  233  UNP  P42336    LEU   233 ENGINEERED MUTATION            
SEQADV 4JPS HIS A 1069  UNP  P42336              EXPRESSION TAG                 
SEQADV 4JPS HIS A 1070  UNP  P42336              EXPRESSION TAG                 
SEQADV 4JPS HIS A 1071  UNP  P42336              EXPRESSION TAG                 
SEQADV 4JPS HIS A 1072  UNP  P42336              EXPRESSION TAG                 
SEQADV 4JPS HIS A 1073  UNP  P42336              EXPRESSION TAG                 
SEQADV 4JPS HIS A 1074  UNP  P42336              EXPRESSION TAG                 
SEQADV 4JPS MET B  301  UNP  P27986              EXPRESSION TAG                 
SEQADV 4JPS HIS B  302  UNP  P27986              EXPRESSION TAG                 
SEQADV 4JPS ASN B  303  UNP  P27986              EXPRESSION TAG                 
SEQADV 4JPS LEU B  304  UNP  P27986              EXPRESSION TAG                 
SEQADV 4JPS GLN B  305  UNP  P27986              EXPRESSION TAG                 
SEQADV 4JPS TYR B  306  UNP  P27986              EXPRESSION TAG                 
SEQRES   1 A 1074  MET PRO PRO ARG PRO SER SER GLY GLU LEU TRP GLY ILE          
SEQRES   2 A 1074  HIS LEU MET PRO PRO ARG ILE LEU VAL GLU CYS LEU LEU          
SEQRES   3 A 1074  PRO ASN GLY MET ILE VAL THR LEU GLU CYS LEU ARG GLU          
SEQRES   4 A 1074  ALA THR LEU ILE THR ILE LYS HIS GLU LEU PHE LYS GLU          
SEQRES   5 A 1074  ALA ARG LYS TYR PRO LEU HIS GLN LEU LEU GLN ASP GLU          
SEQRES   6 A 1074  SER SER TYR ILE PHE VAL SER VAL THR GLN GLU ALA GLU          
SEQRES   7 A 1074  ARG GLU GLU PHE PHE ASP GLU THR ARG ARG LEU CYS ASP          
SEQRES   8 A 1074  LEU ARG LEU PHE GLN PRO PHE LEU LYS VAL ILE GLU PRO          
SEQRES   9 A 1074  VAL GLY ASN ARG GLU GLU LYS ILE LEU ASN ARG GLU ILE          
SEQRES  10 A 1074  GLY PHE ALA ILE GLY MET PRO VAL CYS GLU PHE ASP MET          
SEQRES  11 A 1074  VAL LYS ASP PRO GLU VAL GLN ASP PHE ARG ARG ASN ILE          
SEQRES  12 A 1074  LEU ASN VAL CYS LYS GLU ALA VAL ASP LEU ARG ASP LEU          
SEQRES  13 A 1074  ASN SER PRO HIS SER ARG ALA MET TYR VAL TYR PRO PRO          
SEQRES  14 A 1074  ASN VAL GLU SER SER PRO GLU LEU PRO LYS HIS ILE TYR          
SEQRES  15 A 1074  ASN LYS LEU ASP LYS GLY GLN ILE ILE VAL VAL ILE TRP          
SEQRES  16 A 1074  VAL ILE VAL SER PRO ASN ASN ASP LYS GLN LYS TYR THR          
SEQRES  17 A 1074  LEU LYS ILE ASN HIS ASP CYS VAL PRO GLU GLN VAL ILE          
SEQRES  18 A 1074  ALA GLU ALA ILE ARG LYS LYS THR ARG SER LYS LYS LEU          
SEQRES  19 A 1074  SER SER GLU GLN LEU LYS LEU CYS VAL LEU GLU TYR GLN          
SEQRES  20 A 1074  GLY LYS TYR ILE LEU LYS VAL CYS GLY CYS ASP GLU TYR          
SEQRES  21 A 1074  PHE LEU GLU LYS TYR PRO LEU SER GLN TYR LYS TYR ILE          
SEQRES  22 A 1074  ARG SER CYS ILE MET LEU GLY ARG MET PRO ASN LEU MET          
SEQRES  23 A 1074  LEU MET ALA LYS GLU SER LEU TYR SER GLN LEU PRO MET          
SEQRES  24 A 1074  ASP CYS PHE THR MET PRO SER TYR SER ARG ARG ILE SER          
SEQRES  25 A 1074  THR ALA THR PRO TYR MET ASN GLY GLU THR SER THR LYS          
SEQRES  26 A 1074  SER LEU TRP VAL ILE ASN SER ALA LEU ARG ILE LYS ILE          
SEQRES  27 A 1074  LEU CYS ALA THR TYR VAL ASN VAL ASN ILE ARG ASP ILE          
SEQRES  28 A 1074  ASP LYS ILE TYR VAL ARG THR GLY ILE TYR HIS GLY GLY          
SEQRES  29 A 1074  GLU PRO LEU CYS ASP ASN VAL ASN THR GLN ARG VAL PRO          
SEQRES  30 A 1074  CYS SER ASN PRO ARG TRP ASN GLU TRP LEU ASN TYR ASP          
SEQRES  31 A 1074  ILE TYR ILE PRO ASP LEU PRO ARG ALA ALA ARG LEU CYS          
SEQRES  32 A 1074  LEU SER ILE CYS SER VAL LYS GLY ARG LYS GLY ALA LYS          
SEQRES  33 A 1074  GLU GLU HIS CYS PRO LEU ALA TRP GLY ASN ILE ASN LEU          
SEQRES  34 A 1074  PHE ASP TYR THR ASP THR LEU VAL SER GLY LYS MET ALA          
SEQRES  35 A 1074  LEU ASN LEU TRP PRO VAL PRO HIS GLY LEU GLU ASP LEU          
SEQRES  36 A 1074  LEU ASN PRO ILE GLY VAL THR GLY SER ASN PRO ASN LYS          
SEQRES  37 A 1074  GLU THR PRO CYS LEU GLU LEU GLU PHE ASP TRP PHE SER          
SEQRES  38 A 1074  SER VAL VAL LYS PHE PRO ASP MET SER VAL ILE GLU GLU          
SEQRES  39 A 1074  HIS ALA ASN TRP SER VAL SER ARG GLU ALA GLY PHE SER          
SEQRES  40 A 1074  TYR SER HIS ALA GLY LEU SER ASN ARG LEU ALA ARG ASP          
SEQRES  41 A 1074  ASN GLU LEU ARG GLU ASN ASP LYS GLU GLN LEU LYS ALA          
SEQRES  42 A 1074  ILE SER THR ARG ASP PRO LEU SER GLU ILE THR GLU GLN          
SEQRES  43 A 1074  GLU LYS ASP PHE LEU TRP SER HIS ARG HIS TYR CYS VAL          
SEQRES  44 A 1074  THR ILE PRO GLU ILE LEU PRO LYS LEU LEU LEU SER VAL          
SEQRES  45 A 1074  LYS TRP ASN SER ARG ASP GLU VAL ALA GLN MET TYR CYS          
SEQRES  46 A 1074  LEU VAL LYS ASP TRP PRO PRO ILE LYS PRO GLU GLN ALA          
SEQRES  47 A 1074  MET GLU LEU LEU ASP CYS ASN TYR PRO ASP PRO MET VAL          
SEQRES  48 A 1074  ARG GLY PHE ALA VAL ARG CYS LEU GLU LYS TYR LEU THR          
SEQRES  49 A 1074  ASP ASP LYS LEU SER GLN TYR LEU ILE GLN LEU VAL GLN          
SEQRES  50 A 1074  VAL LEU LYS TYR GLU GLN TYR LEU ASP ASN LEU LEU VAL          
SEQRES  51 A 1074  ARG PHE LEU LEU LYS LYS ALA LEU THR ASN GLN ARG ILE          
SEQRES  52 A 1074  GLY HIS PHE PHE PHE TRP HIS LEU LYS SER GLU MET HIS          
SEQRES  53 A 1074  ASN LYS THR VAL SER GLN ARG PHE GLY LEU LEU LEU GLU          
SEQRES  54 A 1074  SER TYR CYS ARG ALA CYS GLY MET TYR LEU LYS HIS LEU          
SEQRES  55 A 1074  ASN ARG GLN VAL GLU ALA MET GLU LYS LEU ILE ASN LEU          
SEQRES  56 A 1074  THR ASP ILE LEU LYS GLN GLU LYS LYS ASP GLU THR GLN          
SEQRES  57 A 1074  LYS VAL GLN MET LYS PHE LEU VAL GLU GLN MET ARG ARG          
SEQRES  58 A 1074  PRO ASP PHE MET ASP ALA LEU GLN GLY PHE LEU SER PRO          
SEQRES  59 A 1074  LEU ASN PRO ALA HIS GLN LEU GLY ASN LEU ARG LEU GLU          
SEQRES  60 A 1074  GLU CYS ARG ILE MET SER SER ALA LYS ARG PRO LEU TRP          
SEQRES  61 A 1074  LEU ASN TRP GLU ASN PRO ASP ILE MET SER GLU LEU LEU          
SEQRES  62 A 1074  PHE GLN ASN ASN GLU ILE ILE PHE LYS ASN GLY ASP ASP          
SEQRES  63 A 1074  LEU ARG GLN ASP MET LEU THR LEU GLN ILE ILE ARG ILE          
SEQRES  64 A 1074  MET GLU ASN ILE TRP GLN ASN GLN GLY LEU ASP LEU ARG          
SEQRES  65 A 1074  MET LEU PRO TYR GLY CYS LEU SER ILE GLY ASP CYS VAL          
SEQRES  66 A 1074  GLY LEU ILE GLU VAL VAL ARG ASN SER HIS THR ILE MET          
SEQRES  67 A 1074  GLN ILE GLN CYS LYS GLY GLY LEU LYS GLY ALA LEU GLN          
SEQRES  68 A 1074  PHE ASN SER HIS THR LEU HIS GLN TRP LEU LYS ASP LYS          
SEQRES  69 A 1074  ASN LYS GLY GLU ILE TYR ASP ALA ALA ILE ASP LEU PHE          
SEQRES  70 A 1074  THR ARG SER CYS ALA GLY TYR CYS VAL ALA THR PHE ILE          
SEQRES  71 A 1074  LEU GLY ILE GLY ASP ARG HIS ASN SER ASN ILE MET VAL          
SEQRES  72 A 1074  LYS ASP ASP GLY GLN LEU PHE HIS ILE ASP PHE GLY HIS          
SEQRES  73 A 1074  PHE LEU ASP HIS LYS LYS LYS LYS PHE GLY TYR LYS ARG          
SEQRES  74 A 1074  GLU ARG VAL PRO PHE VAL LEU THR GLN ASP PHE LEU ILE          
SEQRES  75 A 1074  VAL ILE SER LYS GLY ALA GLN GLU CYS THR LYS THR ARG          
SEQRES  76 A 1074  GLU PHE GLU ARG PHE GLN GLU MET CYS TYR LYS ALA TYR          
SEQRES  77 A 1074  LEU ALA ILE ARG GLN HIS ALA ASN LEU PHE ILE ASN LEU          
SEQRES  78 A 1074  PHE SER MET MET LEU GLY SER GLY MET PRO GLU LEU GLN          
SEQRES  79 A 1074  SER PHE ASP ASP ILE ALA TYR ILE ARG LYS THR LEU ALA          
SEQRES  80 A 1074  LEU ASP LYS THR GLU GLN GLU ALA LEU GLU TYR PHE MET          
SEQRES  81 A 1074  LYS GLN MET ASN ASP ALA HIS HIS GLY GLY TRP THR THR          
SEQRES  82 A 1074  LYS MET ASP TRP ILE PHE HIS THR ILE LYS GLN HIS ALA          
SEQRES  83 A 1074  LEU ASN HIS HIS HIS HIS HIS HIS                              
SEQRES   1 B  293  MET HIS ASN LEU GLN TYR LEU PRO PRO LYS PRO PRO LYS          
SEQRES   2 B  293  PRO THR THR VAL ALA ASN ASN GLY MET ASN ASN ASN MET          
SEQRES   3 B  293  SER LEU GLN ASP ALA GLU TRP TYR TRP GLY ASP ILE SER          
SEQRES   4 B  293  ARG GLU GLU VAL ASN GLU LYS LEU ARG ASP THR ALA ASP          
SEQRES   5 B  293  GLY THR PHE LEU VAL ARG ASP ALA SER THR LYS MET HIS          
SEQRES   6 B  293  GLY ASP TYR THR LEU THR LEU ARG LYS GLY GLY ASN ASN          
SEQRES   7 B  293  LYS LEU ILE LYS ILE PHE HIS ARG ASP GLY LYS TYR GLY          
SEQRES   8 B  293  PHE SER ASP PRO LEU THR PHE SER SER VAL VAL GLU LEU          
SEQRES   9 B  293  ILE ASN HIS TYR ARG ASN GLU SER LEU ALA GLN TYR ASN          
SEQRES  10 B  293  PRO LYS LEU ASP VAL LYS LEU LEU TYR PRO VAL SER LYS          
SEQRES  11 B  293  TYR GLN GLN ASP GLN VAL VAL LYS GLU ASP ASN ILE GLU          
SEQRES  12 B  293  ALA VAL GLY LYS LYS LEU HIS GLU TYR ASN THR GLN PHE          
SEQRES  13 B  293  GLN GLU LYS SER ARG GLU TYR ASP ARG LEU TYR GLU GLU          
SEQRES  14 B  293  TYR THR ARG THR SER GLN GLU ILE GLN MET LYS ARG THR          
SEQRES  15 B  293  ALA ILE GLU ALA PHE ASN GLU THR ILE LYS ILE PHE GLU          
SEQRES  16 B  293  GLU GLN CYS GLN THR GLN GLU ARG TYR SER LYS GLU TYR          
SEQRES  17 B  293  ILE GLU LYS PHE LYS ARG GLU GLY ASN GLU LYS GLU ILE          
SEQRES  18 B  293  GLN ARG ILE MET HIS ASN TYR ASP LYS LEU LYS SER ARG          
SEQRES  19 B  293  ILE SER GLU ILE ILE ASP SER ARG ARG ARG LEU GLU GLU          
SEQRES  20 B  293  ASP LEU LYS LYS GLN ALA ALA GLU TYR ARG GLU ILE ASP          
SEQRES  21 B  293  LYS ARG MET ASN SER ILE LYS PRO ASP LEU ILE GLN LEU          
SEQRES  22 B  293  ARG LYS THR ARG ASP GLN TYR LEU MET TRP LEU THR GLN          
SEQRES  23 B  293  LYS GLY VAL ARG GLN LYS LYS                                  
HET    SCN  A1101       3                                                       
HET    1LT  A1102      30                                                       
HETNAM     SCN THIOCYANATE ION                                                  
HETNAM     1LT (2S)-N~1~-{4-METHYL-5-[2-(1,1,1-TRIFLUORO-2-                     
HETNAM   2 1LT  METHYLPROPAN-2-YL)PYRIDIN-4-YL]-1,3-THIAZOL-2-                  
HETNAM   3 1LT  YL}PYRROLIDINE-1,2-DICARBOXAMIDE                                
FORMUL   3  SCN    C N S 1-                                                     
FORMUL   4  1LT    C19 H22 F3 N5 O2 S                                           
FORMUL   5  HOH   *506(H2 O)                                                    
HELIX    1   1 THR A   41  ALA A   53  1                                  13    
HELIX    2   2 ARG A   54  TYR A   56  5                                   3    
HELIX    3   3 LEU A   58  LEU A   62  5                                   5    
HELIX    4   4 ASP A   64  TYR A   68  5                                   5    
HELIX    5   5 ARG A   88  LEU A   92  5                                   5    
HELIX    6   6 ASN A  107  GLY A  122  1                                  16    
HELIX    7   7 VAL A  125  VAL A  131  1                                   7    
HELIX    8   8 ASP A  133  ILE A  143  1                                  11    
HELIX    9   9 ILE A  143  LEU A  156  1                                  14    
HELIX   10  10 PRO A  159  TYR A  167  1                                   9    
HELIX   11  11 PRO A  178  ASN A  183  1                                   6    
HELIX   12  12 VAL A  216  LYS A  227  1                                  12    
HELIX   13  13 GLU A  245  GLY A  248  5                                   4    
HELIX   14  14 PRO A  266  GLN A  269  5                                   4    
HELIX   15  15 TYR A  270  GLY A  280  1                                  11    
HELIX   16  16 LYS A  290  SER A  295  1                                   6    
HELIX   17  17 PRO A  305  ARG A  310  5                                   6    
HELIX   18  18 TRP A  328  ILE A  330  5                                   3    
HELIX   19  19 PRO A  394  LEU A  396  5                                   3    
HELIX   20  20 ASP A  488  GLU A  493  1                                   6    
HELIX   21  21 ASN A  526  ARG A  537  1                                  12    
HELIX   22  22 THR A  544  HIS A  554  1                                  11    
HELIX   23  23 TYR A  557  GLU A  563  5                                   7    
HELIX   24  24 ILE A  564  VAL A  572  1                                   9    
HELIX   25  25 SER A  576  TRP A  590  1                                  15    
HELIX   26  26 LYS A  594  MET A  599  1                                   6    
HELIX   27  27 GLU A  600  ASP A  603  5                                   4    
HELIX   28  28 ASP A  608  LEU A  623  1                                  16    
HELIX   29  29 THR A  624  LEU A  639  1                                  16    
HELIX   30  30 LYS A  640  GLU A  642  5                                   3    
HELIX   31  31 ASN A  647  LEU A  658  1                                  12    
HELIX   32  32 ASN A  660  SER A  673  1                                  14    
HELIX   33  33 VAL A  680  CYS A  695  1                                  16    
HELIX   34  34 MET A  697  GLN A  721  1                                  25    
HELIX   35  35 THR A  727  ARG A  740  1                                  14    
HELIX   36  36 ARG A  741  GLN A  749  1                                   9    
HELIX   37  37 ARG A  765  CYS A  769  5                                   5    
HELIX   38  38 MET A  789  LEU A  793  5                                   5    
HELIX   39  39 LEU A  807  ASN A  826  1                                  20    
HELIX   40  40 ILE A  857  CYS A  862  1                                   6    
HELIX   41  41 HIS A  875  ASN A  885  1                                  11    
HELIX   42  42 LYS A  886  GLU A  888  5                                   3    
HELIX   43  43 ILE A  889  GLY A  912  1                                  24    
HELIX   44  44 LYS A  941  GLY A  946  1                                   6    
HELIX   45  45 THR A  957  SER A  965  1                                   9    
HELIX   46  46 THR A  974  HIS A  994  1                                  21    
HELIX   47  47 HIS A  994  MET A 1004  1                                  11    
HELIX   48  48 SER A 1015  LEU A 1026  1                                  12    
HELIX   49  49 THR A 1031  HIS A 1048  1                                  18    
HELIX   50  50 SER B  339  ARG B  348  1                                  10    
HELIX   51  51 ASN B  441  GLY B  516  1                                  76    
HELIX   52  52 ASN B  517  GLY B  588  1                                  72    
SHEET    1   A 5 ILE A  31  LEU A  37  0                                        
SHEET    2   A 5 ARG A  19  LEU A  25 -1  N  ILE A  20   O  CYS A  36           
SHEET    3   A 5 PHE A  98  ILE A 102  1  O  VAL A 101   N  LEU A  25           
SHEET    4   A 5 ILE A  69  VAL A  73 -1  N  VAL A  71   O  LYS A 100           
SHEET    5   A 5 ARG A  79  PHE A  82 -1  O  PHE A  82   N  PHE A  70           
SHEET    1   B 4 ASP A 203  ASN A 212  0                                        
SHEET    2   B 4 GLN A 189  VAL A 198 -1  N  VAL A 192   O  LEU A 209           
SHEET    3   B 4 ASN A 284  ALA A 289  1  O  LEU A 287   N  TRP A 195           
SHEET    4   B 4 TYR A 250  VAL A 254 -1  N  LYS A 253   O  MET A 286           
SHEET    1   C 2 LYS A 325  SER A 326  0                                        
SHEET    2   C 2 VAL A 484  LYS A 485  1  O  LYS A 485   N  LYS A 325           
SHEET    1   D 4 ARG A 382  TYR A 392  0                                        
SHEET    2   D 4 ALA A 333  ALA A 341 -1  N  LEU A 334   O  TYR A 389           
SHEET    3   D 4 CYS A 472  PHE A 477 -1  O  GLU A 474   N  CYS A 340           
SHEET    4   D 4 GLY A 439  ASN A 444 -1  N  MET A 441   O  LEU A 475           
SHEET    1   E 3 GLU A 365  PRO A 366  0                                        
SHEET    2   E 3 LYS A 353  HIS A 362 -1  N  HIS A 362   O  GLU A 365           
SHEET    3   E 3 VAL A 371  ASN A 372 -1  O  VAL A 371   N  THR A 358           
SHEET    1   F 4 GLU A 365  PRO A 366  0                                        
SHEET    2   F 4 LYS A 353  HIS A 362 -1  N  HIS A 362   O  GLU A 365           
SHEET    3   F 4 ARG A 401  LYS A 413 -1  O  ARG A 401   N  TYR A 361           
SHEET    4   F 4 LYS A 416  ASN A 428 -1  O  LEU A 422   N  ILE A 406           
SHEET    1   G 2 PHE A 751  SER A 753  0                                        
SHEET    2   G 2 ASN A 756  LEU A 761 -1  O  LEU A 761   N  PHE A 751           
SHEET    1   H 5 ARG A 770  ILE A 771  0                                        
SHEET    2   H 5 LEU A 779  GLU A 784 -1  O  TRP A 780   N  ARG A 770           
SHEET    3   H 5 ASN A 796  ASN A 803 -1  O  PHE A 801   N  LEU A 779           
SHEET    4   H 5 VAL A 845  GLU A 849 -1  O  ILE A 848   N  ILE A 800           
SHEET    5   H 5 CYS A 838  GLY A 842 -1  N  LEU A 839   O  LEU A 847           
SHEET    1   I 3 SER A 854  THR A 856  0                                        
SHEET    2   I 3 ILE A 921  LYS A 924 -1  O  VAL A 923   N  HIS A 855           
SHEET    3   I 3 LEU A 929  HIS A 931 -1  O  PHE A 930   N  MET A 922           
SHEET    1   J 4 ASN B 377  ILE B 383  0                                        
SHEET    2   J 4 TYR B 368  LYS B 374 -1  N  LYS B 374   O  ASN B 377           
SHEET    3   J 4 THR B 354  ASP B 359 -1  N  THR B 354   O  ARG B 373           
SHEET    4   J 4 TYR B 426  PRO B 427  1  O  TYR B 426   N  PHE B 355           
CISPEP   1 SER A  158    PRO A  159          0        -2.50                     
CISPEP   2 SER A  199    PRO A  200          0         5.44                     
SITE     1 AC1  4 ARG A 979  GLU A 982  LYS A 986  HOH A1625                    
SITE     1 AC2 14 TRP A 780  ILE A 800  LYS A 802  TYR A 836                    
SITE     2 AC2 14 ILE A 848  GLU A 849  VAL A 851  SER A 854                    
SITE     3 AC2 14 HIS A 855  GLN A 859  MET A 922  ILE A 932                    
SITE     4 AC2 14 HOH A1219  HOH A1606                                          
CRYST1  104.865  106.195  133.667  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      0.009536  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.009417  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.007481        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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