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Database: PDB
Entry: 4RIO
LinkDB: 4RIO
Original site: 4RIO 
HEADER    TRANSFERASE/INHIBITOR                   07-OCT-14   4RIO              
TITLE     CRYSTAL STRUCTURE OF JAK3 KINASE DOMAIN IN COMPLEX WITH A             
TITLE    2 PYRROLOPYRIDAZINE CARBOXAMIDE INHIBITOR                              
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: TYROSINE-PROTEIN KINASE JAK3;                              
COMPND   3 CHAIN: A;                                                            
COMPND   4 FRAGMENT: KINASE DOMAIN (UNP RESIDUES 810-1100);                     
COMPND   5 SYNONYM: JANUS KINASE 3, JAK-3, LEUKOCYTE JANUS KINASE, L-JAK;       
COMPND   6 EC: 2.7.10.2;                                                        
COMPND   7 ENGINEERED: YES;                                                     
COMPND   8 MUTATION: YES                                                        
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606;                                                
SOURCE   5 GENE: JAK3;                                                          
SOURCE   6 EXPRESSION_SYSTEM: SPODOPTERA FRUGIPERDA;                            
SOURCE   7 EXPRESSION_SYSTEM_COMMON: FALL ARMYWORM;                             
SOURCE   8 EXPRESSION_SYSTEM_TAXID: 7108;                                       
SOURCE   9 EXPRESSION_SYSTEM_VECTOR_TYPE: BACULOVIRUS TRANSFER VECTOR           
KEYWDS    TRANSFERASE, TRANSFERASE-INHIBITOR COMPLEX                            
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    J.S.SACK                                                              
REVDAT   1   24-DEC-14 4RIO    0                                                
JRNL        AUTH   J.J.DUAN,Z.LU,B.JIANG,B.V.YANG,L.M.DOWEYKO,D.S.NIRSCHL,      
JRNL        AUTH 2 L.E.HAQUE,S.LIN,G.BROWN,J.HYNES,J.S.TOKARSKI,J.S.SACK,       
JRNL        AUTH 3 J.KHAN,J.S.LIPPY,R.F.ZHANG,S.PITT,G.SHEN,W.J.PITTS,          
JRNL        AUTH 4 P.H.CARTER,J.C.BARRISH,S.G.NADLER,L.M.SALTER-CID,M.MCKINNON, 
JRNL        AUTH 5 A.FURA,G.L.SCHIEVEN,S.T.WROBLESKI                            
JRNL        TITL   DISCOVERY OF PYRROLO[1,2-B]PYRIDAZINE-3-CARBOXAMIDES AS      
JRNL        TITL 2 JANUS KINASE (JAK) INHIBITORS.                               
JRNL        REF    BIOORG.MED.CHEM.LETT.         V.  24  5721 2014              
JRNL        REFN                   ISSN 0960-894X                               
JRNL        PMID   25453808                                                     
JRNL        DOI    10.1016/J.BMCL.2014.10.061                                   
REMARK   2                                                                      
REMARK   2 RESOLUTION.    2.69 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) : 2.69                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 41.83                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : 0.000                          
REMARK   3   COMPLETENESS FOR RANGE        (%) : 99.7                           
REMARK   3   NUMBER OF REFLECTIONS             : 9202                           
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)  : 0.218                          
REMARK   3   R VALUE            (WORKING SET)  : 0.215                          
REMARK   3   FREE R VALUE                      : 0.281                          
REMARK   3   FREE R VALUE TEST SET SIZE   (%)  : 5.040                          
REMARK   3   FREE R VALUE TEST SET COUNT       : 464                            
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               : 5                        
REMARK   3   BIN RESOLUTION RANGE HIGH   (ANGSTROMS) : 2.69                     
REMARK   3   BIN RESOLUTION RANGE LOW    (ANGSTROMS) : 3.01                     
REMARK   3   BIN COMPLETENESS (WORKING+TEST)     (%) : 99.65                    
REMARK   3   REFLECTIONS IN BIN (WORKING + TEST SET) : 2533                     
REMARK   3   BIN R VALUE        (WORKING + TEST SET) : 0.2205                   
REMARK   3   REFLECTIONS IN BIN        (WORKING SET) : 2398                     
REMARK   3   BIN R VALUE               (WORKING SET) : 0.2152                   
REMARK   3   BIN FREE R VALUE                        : 0.3143                   
REMARK   3   BIN FREE R VALUE TEST SET SIZE      (%) : 5.33                     
REMARK   3   BIN FREE R VALUE TEST SET COUNT         : 135                      
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            : 2206                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 20                                      
REMARK   3   SOLVENT ATOMS            : 22                                      
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 64.08                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 55.28                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : -17.33030                                            
REMARK   3    B22 (A**2) : 21.00980                                             
REMARK   3    B33 (A**2) : -3.67960                                             
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) : 0.338               
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) : 1.905               
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      : 0.892                         
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : 0.860                         
REMARK   3                                                                      
REMARK   3   NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15                    
REMARK   3   TERM                          COUNT    WEIGHT   FUNCTION.          
REMARK   3    BOND LENGTHS              : 2281   ; 2.000  ; HARMONIC            
REMARK   3    BOND ANGLES               : 3100   ; 2.000  ; HARMONIC            
REMARK   3    TORSION ANGLES            : 769    ; 2.000  ; SINUSOIDAL          
REMARK   3    TRIGONAL CARBON PLANES    : 50     ; 2.000  ; HARMONIC            
REMARK   3    GENERAL PLANES            : 349    ; 5.000  ; HARMONIC            
REMARK   3    ISOTROPIC THERMAL FACTORS : 2281   ; 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   : 282    ; 5.000  ; SEMIHARMONIC        
REMARK   3    SUM OF OCCUPANCIES        : NULL   ; NULL   ; NULL                
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   : 2625   ; 4.000  ; SEMIHARMONIC        
REMARK   3                                                                      
REMARK   3   RMS DEVIATIONS FROM IDEAL VALUES.                                  
REMARK   3    BOND LENGTHS                       (A) : 0.010                    
REMARK   3    BOND ANGLES                  (DEGREES) : 1.13                     
REMARK   3    PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 2.97                     
REMARK   3    OTHER TORSION ANGLES         (DEGREES) : 19.71                    
REMARK   3                                                                      
REMARK   3  TLS DETAILS                                                         
REMARK   3   NUMBER OF TLS GROUPS  : NULL                                       
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: NULL                                      
REMARK   4                                                                      
REMARK   4 4RIO COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 09-OCT-14.                  
REMARK 100 THE RCSB ID CODE IS RCSB087393.                                      
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 02-APR-10                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : 5.8                                
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : CLSI                               
REMARK 200  BEAMLINE                       : 08ID-1                             
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 0.980                              
REMARK 200  MONOCHROMATOR                  : NULL                               
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : CCD                                
REMARK 200  DETECTOR MANUFACTURER          : RAYONIX MX-300                     
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : HKL2000 (DENZO)                    
REMARK 200  DATA SCALING SOFTWARE          : HKL2000 (SCALEPACK)                
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 9255                               
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.700                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 50.000                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : 0.000                              
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 99.6                               
REMARK 200  DATA REDUNDANCY                : 5.900                              
REMARK 200  R MERGE                    (I) : 0.17900                            
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 9.9000                             
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.70                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 2.80                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 98.9                               
REMARK 200  DATA REDUNDANCY IN SHELL       : 5.90                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.61100                            
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 2.700                              
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: NULL                                                 
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 48.15                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.37                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 30% PEG-3350, 200MM MAGNESIUM CHLORIDE   
REMARK 280  100MM BIS-TRIS PH 5.8, VAPOR DIFFUSION, HANGING DROP, TEMPERATURE   
REMARK 280  293K                                                                
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       23.77000            
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000       43.99000            
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       37.72000            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000       43.99000            
REMARK 290   SMTRY1   4  1.000000  0.000000  0.000000       23.77000            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000       37.72000            
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: MONOMERIC                         
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC                  
REMARK 350 SOFTWARE USED: PISA                                                  
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A                                     
REMARK 350   BIOMT1   1  1.000000  0.000000  0.000000        0.00000            
REMARK 350   BIOMT2   1  0.000000  1.000000  0.000000        0.00000            
REMARK 350   BIOMT3   1  0.000000  0.000000  1.000000        0.00000            
REMARK 465                                                                      
REMARK 465 MISSING RESIDUES                                                     
REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE                       
REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN               
REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)                
REMARK 465                                                                      
REMARK 465   M RES C SSSEQI                                                     
REMARK 465     GLY A   808                                                      
REMARK 465     PRO A   809                                                      
REMARK 465     ALA A   810                                                      
REMARK 465     SER A   811                                                      
REMARK 465     GLN A   812                                                      
REMARK 465     ASP A   813                                                      
REMARK 465     PRO A   814                                                      
REMARK 465     SER A  1100                                                      
REMARK 470                                                                      
REMARK 470 MISSING ATOM                                                         
REMARK 470 THE FOLLOWING RESIDUES HAVE MISSING ATOMS (M=MODEL NUMBER;           
REMARK 470 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;          
REMARK 470 I=INSERTION CODE):                                                   
REMARK 470   M RES CSSEQI  ATOMS                                                
REMARK 470     LYS A 823    CG   CD   CE   NZ                                   
REMARK 470     LYS A 830    CG   CD   CE   NZ                                   
REMARK 470     PHE A 833    CG   CD1  CD2  CE1  CE2  CZ                         
REMARK 470     HIS A 859    CG   ND1  CD2  CE1  NE2                             
REMARK 470     ARG A 866    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     ARG A 870    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     ARG A 895    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     ARG A 984    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     GLU A 985    CG   CD   OE1  OE2                                  
REMARK 470     LYS A1026    CG   CD   CE   NZ                                   
REMARK 470     ARG A1036    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     ARG A1049    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     GLU A1052    CG   CD   OE1  OE2                                  
REMARK 470     GLU A1055    CG   CD   OE1  OE2                                  
REMARK 470     GLN A1083    CG   CD   OE1  NE2                                  
REMARK 470     MET A1097    CG   SD   CE                                        
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 833       -7.22     80.88                                   
REMARK 500    ASP A 842       78.66   -115.18                                   
REMARK 500    PRO A 862       95.68    -20.70                                   
REMARK 500    ASP A 863      -43.76    177.62                                   
REMARK 500    LEU A 898      140.15     73.63                                   
REMARK 500    ASP A 949       34.36   -143.34                                   
REMARK 500    ASP A 967       82.00     60.58                                   
REMARK 500    GLU A 985      -97.13    -21.14                                   
REMARK 500    PRO A 986     -159.56    -95.54                                   
REMARK 500    TYR A1023       35.02     39.68                                   
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 3QX A 4000                
DBREF  4RIO A  810  1100  UNP    P52333   JAK3_HUMAN     810   1100             
SEQADV 4RIO GLY A  808  UNP  P52333              EXPRESSION TAG                 
SEQADV 4RIO PRO A  809  UNP  P52333              EXPRESSION TAG                 
SEQADV 4RIO SER A  811  UNP  P52333    CYS   811 ENGINEERED MUTATION            
SEQADV 4RIO SER A 1040  UNP  P52333    CYS  1040 ENGINEERED MUTATION            
SEQADV 4RIO SER A 1048  UNP  P52333    CYS  1048 ENGINEERED MUTATION            
SEQRES   1 A  293  GLY PRO ALA SER GLN ASP PRO THR ILE PHE GLU GLU ARG          
SEQRES   2 A  293  HIS LEU LYS TYR ILE SER GLN LEU GLY LYS GLY ASN PHE          
SEQRES   3 A  293  GLY SER VAL GLU LEU CYS ARG TYR ASP PRO LEU GLY ASP          
SEQRES   4 A  293  ASN THR GLY ALA LEU VAL ALA VAL LYS GLN LEU GLN HIS          
SEQRES   5 A  293  SER GLY PRO ASP GLN GLN ARG ASP PHE GLN ARG GLU ILE          
SEQRES   6 A  293  GLN ILE LEU LYS ALA LEU HIS SER ASP PHE ILE VAL LYS          
SEQRES   7 A  293  TYR ARG GLY VAL SER TYR GLY PRO GLY ARG GLN SER LEU          
SEQRES   8 A  293  ARG LEU VAL MET GLU TYR LEU PRO SER GLY CYS LEU ARG          
SEQRES   9 A  293  ASP PHE LEU GLN ARG HIS ARG ALA ARG LEU ASP ALA SER          
SEQRES  10 A  293  ARG LEU LEU LEU TYR SER SER GLN ILE CYS LYS GLY MET          
SEQRES  11 A  293  GLU TYR LEU GLY SER ARG ARG CYS VAL HIS ARG ASP LEU          
SEQRES  12 A  293  ALA ALA ARG ASN ILE LEU VAL GLU SER GLU ALA HIS VAL          
SEQRES  13 A  293  LYS ILE ALA ASP PHE GLY LEU ALA LYS LEU LEU PRO LEU          
SEQRES  14 A  293  ASP LYS ASP TYR TYR VAL VAL ARG GLU PRO GLY GLN SER          
SEQRES  15 A  293  PRO ILE PHE TRP TYR ALA PRO GLU SER LEU SER ASP ASN          
SEQRES  16 A  293  ILE PHE SER ARG GLN SER ASP VAL TRP SER PHE GLY VAL          
SEQRES  17 A  293  VAL LEU TYR GLU LEU PHE THR TYR CYS ASP LYS SER CYS          
SEQRES  18 A  293  SER PRO SER ALA GLU PHE LEU ARG MET MET GLY SER GLU          
SEQRES  19 A  293  ARG ASP VAL PRO ALA LEU SER ARG LEU LEU GLU LEU LEU          
SEQRES  20 A  293  GLU GLU GLY GLN ARG LEU PRO ALA PRO PRO ALA CYS PRO          
SEQRES  21 A  293  ALA GLU VAL HIS GLU LEU MET LYS LEU CYS TRP ALA PRO          
SEQRES  22 A  293  SER PRO GLN ASP ARG PRO SER PHE SER ALA LEU GLY PRO          
SEQRES  23 A  293  GLN LEU ASP MET LEU TRP SER                                  
HET    3QX  A4000      20                                                       
HETNAM     3QX 4-{[(1R,2S)-2-FLUORO-2-                                          
HETNAM   2 3QX  METHYLCYCLOPENTYL]AMINO}PYRROLO[1,2-B]PYRIDAZINE-3-             
HETNAM   3 3QX  CARBOXAMIDE                                                     
FORMUL   2  3QX    C14 H17 F N4 O                                               
FORMUL   3  HOH   *22(H2 O)                                                     
HELIX    1   1 ASP A  863  ALA A  877  1                                  15    
HELIX    2   2 CYS A  909  HIS A  917  1                                   9    
HELIX    3   3 ARG A  918  LEU A  921  5                                   4    
HELIX    4   4 ASP A  922  ARG A  943  1                                  22    
HELIX    5   5 ALA A  951  ARG A  953  5                                   3    
HELIX    6   6 PRO A  990  TYR A  994  5                                   5    
HELIX    7   7 ALA A  995  ASN A 1002  1                                   8    
HELIX    8   8 ARG A 1006  THR A 1022  1                                  17    
HELIX    9   9 SER A 1029  GLY A 1039  1                                  11    
HELIX   10  10 PRO A 1045  GLU A 1056  1                                  12    
HELIX   11  11 PRO A 1067  TRP A 1078  1                                  12    
HELIX   12  12 SER A 1081  ARG A 1085  5                                   5    
HELIX   13  13 SER A 1087  TRP A 1099  1                                  13    
SHEET    1   A 6 ILE A 816  GLU A 818  0                                        
SHEET    2   A 6 TYR A 886  TYR A 891  1  O  TYR A 891   N  PHE A 817           
SHEET    3   A 6 LEU A 900  GLU A 903 -1  O  VAL A 901   N  ARG A 887           
SHEET    4   A 6 ALA A 850  LEU A 857 -1  N  ALA A 853   O  MET A 902           
SHEET    5   A 6 GLY A 834  TYR A 841 -1  N  CYS A 839   O  VAL A 852           
SHEET    6   A 6 LEU A 822  GLY A 829 -1  N  ILE A 825   O  LEU A 838           
SHEET    1   B 2 CYS A 945  VAL A 946  0                                        
SHEET    2   B 2 LYS A 972  LEU A 973 -1  O  LYS A 972   N  VAL A 946           
SHEET    1   C 2 ILE A 955  SER A 959  0                                        
SHEET    2   C 2 HIS A 962  ILE A 965 -1  O  LYS A 964   N  LEU A 956           
SHEET    1   D 2 TYR A 980  VAL A 982  0                                        
SHEET    2   D 2 ILE A1003  SER A1005 -1  O  PHE A1004   N  TYR A 981           
CISPEP   1 GLY A  894    ARG A  895          0         0.77                     
CISPEP   2 GLN A  896    SER A  897          0        -2.47                     
CISPEP   3 GLU A  985    PRO A  986          0         7.42                     
SITE     1 AC1  9 ALA A 853  VAL A 884  MET A 902  GLU A 903                    
SITE     2 AC1  9 TYR A 904  LEU A 905  GLY A 908  LEU A 956                    
SITE     3 AC1  9 HOH A4113                                                     
CRYST1   47.540   75.440   87.980  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      0.021035  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.013256  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.011366        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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