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Database: PDB
Entry: 5KE0
LinkDB: 5KE0
Original site: 5KE0 
HEADER    TRANSFERASE/TRANSFERASE INHIBITOR       09-JUN-16   5KE0              
TITLE     DISCOVERY OF 1-1H-PYRAZOLO 4,3-C PYRIDINE-6-YL UREA INHIBITORS OF     
TITLE    2 EXTRACELLULAR SIGNAL REGULATED KINASE ERK FOR THE TREATMENT OF       
TITLE    3 CANCERS                                                              
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: MITOGEN-ACTIVATED PROTEIN KINASE 1;                        
COMPND   3 CHAIN: A;                                                            
COMPND   4 SYNONYM: MAPK 1,ERT1,EXTRACELLULAR SIGNAL-REGULATED KINASE 2,ERK-2,  
COMPND   5 MAP KINASE ISOFORM P42,P42-MAPK,MITOGEN-ACTIVATED PROTEIN KINASE 2,  
COMPND   6 MAPK 2;                                                              
COMPND   7 EC: 2.7.11.24;                                                       
COMPND   8 ENGINEERED: YES                                                      
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: RATTUS NORVEGICUS;                              
SOURCE   3 ORGANISM_COMMON: RAT;                                                
SOURCE   4 ORGANISM_TAXID: 10116;                                               
SOURCE   5 GENE: MAPK1, ERK2, MAPK, PRKM1;                                      
SOURCE   6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;                                 
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 469008;                                     
SOURCE   8 EXPRESSION_SYSTEM_STRAIN: BL21(DE3)                                  
KEYWDS    TRANSFERASE, SERINE/THREONINE-PROTEIN KINASE, MAP KINASE,             
KEYWDS   2 TRANSFERASE-TRANSFERASE INHIBITOR COMPLEX                            
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    A.HRUZA,J.LIM                                                         
REVDAT   3   22-NOV-17 5KE0    1       JRNL   REMARK                            
REVDAT   2   27-JUL-16 5KE0    1       JRNL                                     
REVDAT   1   06-JUL-16 5KE0    0                                                
JRNL        AUTH   J.LIM,E.H.KELLEY,J.L.METHOT,H.ZHOU,A.PETROCCHI,H.CHEN,       
JRNL        AUTH 2 S.E.HILL,M.C.HINTON,A.HRUZA,J.O.JUNG,J.K.MACLEAN,M.MANSUETO, 
JRNL        AUTH 3 G.N.NAUMOV,U.PHILIPPAR,S.RAUT,P.SPACCIAPOLI,D.SUN,           
JRNL        AUTH 4 P.SILIPHAIVANH                                               
JRNL        TITL   DISCOVERY OF 1-(1H-PYRAZOLO[4,3-C]PYRIDIN-6-YL)UREA          
JRNL        TITL 2 INHIBITORS OF EXTRACELLULAR SIGNAL-REGULATED KINASE (ERK)    
JRNL        TITL 3 FOR THE TREATMENT OF CANCERS.                                
JRNL        REF    J.MED.CHEM.                   V.  59  6501 2016              
JRNL        REFN                   ISSN 0022-2623                               
JRNL        PMID   27329786                                                     
JRNL        DOI    10.1021/ACS.JMEDCHEM.6B00708                                 
REMARK   2                                                                      
REMARK   2 RESOLUTION.    1.68 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : BUSTER 2.11.6                                        
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) : 1.68                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 16.93                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : 0.000                          
REMARK   3   COMPLETENESS FOR RANGE        (%) : 99.6                           
REMARK   3   NUMBER OF REFLECTIONS             : 47210                          
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)  : 0.169                          
REMARK   3   R VALUE            (WORKING SET)  : 0.168                          
REMARK   3   FREE R VALUE                      : 0.191                          
REMARK   3   FREE R VALUE TEST SET SIZE   (%)  : 5.010                          
REMARK   3   FREE R VALUE TEST SET COUNT       : 2367                           
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) : 1.68                     
REMARK   3   BIN RESOLUTION RANGE LOW    (ANGSTROMS) : 1.72                     
REMARK   3   BIN COMPLETENESS (WORKING+TEST)     (%) : 98.66                    
REMARK   3   REFLECTIONS IN BIN (WORKING + TEST SET) : 3424                     
REMARK   3   BIN R VALUE        (WORKING + TEST SET) : 0.1876                   
REMARK   3   REFLECTIONS IN BIN        (WORKING SET) : 3258                     
REMARK   3   BIN R VALUE               (WORKING SET) : 0.1867                   
REMARK   3   BIN FREE R VALUE                        : 0.2049                   
REMARK   3   BIN FREE R VALUE TEST SET SIZE      (%) : 4.85                     
REMARK   3   BIN FREE R VALUE TEST SET COUNT         : 166                      
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            : 2780                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 52                                      
REMARK   3   SOLVENT ATOMS            : 269                                     
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 24.37                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 29.68                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : -2.70570                                             
REMARK   3    B22 (A**2) : 0.35000                                              
REMARK   3    B33 (A**2) : 2.35570                                              
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) : 0.188               
REMARK   3   DPI (BLOW EQ-10) BASED ON R VALUE        (A) : 0.088               
REMARK   3   DPI (BLOW EQ-9) BASED ON FREE R VALUE    (A) : 0.084               
REMARK   3   DPI (CRUICKSHANK) BASED ON R VALUE       (A) : 0.103               
REMARK   3   DPI (CRUICKSHANK) BASED ON FREE R VALUE  (A) : 0.082               
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      : 0.955                         
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : 0.951                         
REMARK   3                                                                      
REMARK   3   NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15                    
REMARK   3   TERM                          COUNT    WEIGHT   FUNCTION.          
REMARK   3    BOND LENGTHS              : 5744   ; 2.000  ; HARMONIC            
REMARK   3    BOND ANGLES               : 10382  ; 2.000  ; HARMONIC            
REMARK   3    TORSION ANGLES            : 1267   ; 2.000  ; SINUSOIDAL          
REMARK   3    TRIGONAL CARBON PLANES    : 74     ; 2.000  ; HARMONIC            
REMARK   3    GENERAL PLANES            : 864    ; 5.000  ; HARMONIC            
REMARK   3    ISOTROPIC THERMAL FACTORS : 5744   ; 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   : 370    ; 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   : 6479   ; 4.000  ; SEMIHARMONIC        
REMARK   3                                                                      
REMARK   3   RMS DEVIATIONS FROM IDEAL VALUES.                                  
REMARK   3    BOND LENGTHS                       (A) : 0.010                    
REMARK   3    BOND ANGLES                  (DEGREES) : 1.01                     
REMARK   3    PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 3.66                     
REMARK   3    OTHER TORSION ANGLES         (DEGREES) : 14.21                    
REMARK   3                                                                      
REMARK   3  TLS DETAILS                                                         
REMARK   3   NUMBER OF TLS GROUPS  : 1                                          
REMARK   3                                                                      
REMARK   3   TLS GROUP : 1                                                      
REMARK   3    SELECTION: { A|* }                                                
REMARK   3    ORIGIN FOR THE GROUP (A):   53.1969   19.5008   19.3800           
REMARK   3    T TENSOR                                                          
REMARK   3     T11:   -0.0231 T22:   -0.0631                                    
REMARK   3     T33:   -0.0789 T12:    0.0015                                    
REMARK   3     T13:   -0.0030 T23:    0.0029                                    
REMARK   3    L TENSOR                                                          
REMARK   3     L11:    0.8927 L22:    0.6669                                    
REMARK   3     L33:    1.0382 L12:   -0.3153                                    
REMARK   3     L13:   -0.5239 L23:    0.0418                                    
REMARK   3    S TENSOR                                                          
REMARK   3     S11:    0.0221 S12:    0.0827 S13:   -0.0667                     
REMARK   3     S21:   -0.0378 S22:   -0.0460 S23:    0.0735                     
REMARK   3     S31:   -0.0195 S32:   -0.0364 S33:    0.0239                     
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: NULL                                      
REMARK   4                                                                      
REMARK   4 5KE0 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 13-JUN-16.                  
REMARK 100 THE DEPOSITION ID IS D_1000222081.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 22-JUL-11                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : 6.4                                
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : APS                                
REMARK 200  BEAMLINE                       : 17-ID                              
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.00000                            
REMARK 200  MONOCHROMATOR                  : NULL                               
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : PIXEL                              
REMARK 200  DETECTOR MANUFACTURER          : DECTRIS PILATUS3 6M                
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : XDS (VERSION DECEMBER 6 2010)      
REMARK 200  DATA SCALING SOFTWARE          : SCALA                              
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 47325                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 1.680                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 62.920                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : NULL                               
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 99.8                               
REMARK 200  DATA REDUNDANCY                : 6.300                              
REMARK 200  R MERGE                    (I) : 0.06700                            
REMARK 200  R SYM                      (I) : 0.06700                            
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 16.7000                            
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.68                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 1.69                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 100.0                              
REMARK 200  DATA REDUNDANCY IN SHELL       : 6.70                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.63500                            
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 2.600                              
REMARK 200                                                                      
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH                              
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: NULL                         
REMARK 200 SOFTWARE USED: MOLREP                                                
REMARK 200 STARTING MODEL: NULL                                                 
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 52.43                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.59                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1M MES, PH 6.4, 2.0M AMMONIUM          
REMARK 280  SULFATE, 5% PEG 400, 0.5% DMSO, 1% GLYEROL, 0.0005M OLOMOUCINE.     
REMARK 280  10 DAY SOAK WITH NEW COMPOUND AT 500 MICROMOLAR CONCENTRATION,      
REMARK 280  VAPOR DIFFUSION, HANGING DROP, TEMPERATURE 277K                     
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY                                            
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 2                        
REMARK 290                                                                      
REMARK 290      SYMOP   SYMMETRY                                                
REMARK 290     NNNMMM   OPERATOR                                                
REMARK 290       1555   X,Y,Z                                                   
REMARK 290       2555   -X,-Y,Z                                                 
REMARK 290       3555   -X+1/2,Y+1/2,-Z                                         
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        0.00000            
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000        0.00000            
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000       35.55250            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       45.66700            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000        0.00000            
REMARK 290   SMTRY1   4  1.000000  0.000000  0.000000       35.55250            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000       45.66700            
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 TOTAL BURIED SURFACE AREA: 940 ANGSTROM**2                           
REMARK 350 SURFACE AREA OF THE COMPLEX: 16000 ANGSTROM**2                       
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -68.0 KCAL/MOL                        
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     MET A    -7                                                      
REMARK 465     ALA A    -6                                                      
REMARK 465     HIS A    -5                                                      
REMARK 465     HIS A    -4                                                      
REMARK 465     HIS A    -3                                                      
REMARK 465     HIS A    -2                                                      
REMARK 465     HIS A    -1                                                      
REMARK 465     HIS A     0                                                      
REMARK 465     MET A     1                                                      
REMARK 465     ALA A     2                                                      
REMARK 465     ALA A     3                                                      
REMARK 465     ALA A     4                                                      
REMARK 465     ALA A     5                                                      
REMARK 465     ALA A     6                                                      
REMARK 465     ALA A     7                                                      
REMARK 465     GLY A     8                                                      
REMARK 465     PRO A     9                                                      
REMARK 465     GLU A    10                                                      
REMARK 465     MET A    11                                                      
REMARK 465     VAL A    12                                                      
REMARK 465     ARG A    13                                                      
REMARK 465     GLY A    14                                                      
REMARK 465     GLN A    15                                                      
REMARK 465     TYR A   356                                                      
REMARK 465     ARG A   357                                                      
REMARK 465     SER A   358                                                      
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    ILE A  29      -58.19   -127.26                                   
REMARK 500    ASP A 147       41.88   -150.34                                   
REMARK 500    ASP A 165       80.56     69.35                                   
REMARK 500    ASN A 199       12.76   -163.15                                   
REMARK 500    ILE A 254      -66.60     76.91                                   
REMARK 500    LEU A 292       43.85    -97.84                                   
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 6S9 A 401                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 402                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC3                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 403                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC4                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 404                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC5                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 405                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC6                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue SO4 A 406                 
DBREF  5KE0 A    1   358  UNP    P63086   MK01_RAT         1    358             
SEQADV 5KE0 MET A   -7  UNP  P63086              INITIATING METHIONINE          
SEQADV 5KE0 ALA A   -6  UNP  P63086              EXPRESSION TAG                 
SEQADV 5KE0 HIS A   -5  UNP  P63086              EXPRESSION TAG                 
SEQADV 5KE0 HIS A   -4  UNP  P63086              EXPRESSION TAG                 
SEQADV 5KE0 HIS A   -3  UNP  P63086              EXPRESSION TAG                 
SEQADV 5KE0 HIS A   -2  UNP  P63086              EXPRESSION TAG                 
SEQADV 5KE0 HIS A   -1  UNP  P63086              EXPRESSION TAG                 
SEQADV 5KE0 HIS A    0  UNP  P63086              EXPRESSION TAG                 
SEQRES   1 A  366  MET ALA HIS HIS HIS HIS HIS HIS MET ALA ALA ALA ALA          
SEQRES   2 A  366  ALA ALA GLY PRO GLU MET VAL ARG GLY GLN VAL PHE ASP          
SEQRES   3 A  366  VAL GLY PRO ARG TYR THR ASN LEU SER TYR ILE GLY GLU          
SEQRES   4 A  366  GLY ALA TYR GLY MET VAL CYS SER ALA TYR ASP ASN LEU          
SEQRES   5 A  366  ASN LYS VAL ARG VAL ALA ILE LYS LYS ILE SER PRO PHE          
SEQRES   6 A  366  GLU HIS GLN THR TYR CYS GLN ARG THR LEU ARG GLU ILE          
SEQRES   7 A  366  LYS ILE LEU LEU ARG PHE ARG HIS GLU ASN ILE ILE GLY          
SEQRES   8 A  366  ILE ASN ASP ILE ILE ARG ALA PRO THR ILE GLU GLN MET          
SEQRES   9 A  366  LYS ASP VAL TYR ILE VAL GLN ASP LEU MET GLU THR ASP          
SEQRES  10 A  366  LEU TYR LYS LEU LEU LYS THR GLN HIS LEU SER ASN ASP          
SEQRES  11 A  366  HIS ILE CYS TYR PHE LEU TYR GLN ILE LEU ARG GLY LEU          
SEQRES  12 A  366  LYS TYR ILE HIS SER ALA ASN VAL LEU HIS ARG ASP LEU          
SEQRES  13 A  366  LYS PRO SER ASN LEU LEU LEU ASN THR THR CYS ASP LEU          
SEQRES  14 A  366  LYS ILE CYS ASP PHE GLY LEU ALA ARG VAL ALA ASP PRO          
SEQRES  15 A  366  ASP HIS ASP HIS THR GLY PHE LEU THR GLU TYR VAL ALA          
SEQRES  16 A  366  THR ARG TRP TYR ARG ALA PRO GLU ILE MET LEU ASN SER          
SEQRES  17 A  366  LYS GLY TYR THR LYS SER ILE ASP ILE TRP SER VAL GLY          
SEQRES  18 A  366  CYS ILE LEU ALA GLU MET LEU SER ASN ARG PRO ILE PHE          
SEQRES  19 A  366  PRO GLY LYS HIS TYR LEU ASP GLN LEU ASN HIS ILE LEU          
SEQRES  20 A  366  GLY ILE LEU GLY SER PRO SER GLN GLU ASP LEU ASN CYS          
SEQRES  21 A  366  ILE ILE ASN LEU LYS ALA ARG ASN TYR LEU LEU SER LEU          
SEQRES  22 A  366  PRO HIS LYS ASN LYS VAL PRO TRP ASN ARG LEU PHE PRO          
SEQRES  23 A  366  ASN ALA ASP SER LYS ALA LEU ASP LEU LEU ASP LYS MET          
SEQRES  24 A  366  LEU THR PHE ASN PRO HIS LYS ARG ILE GLU VAL GLU GLN          
SEQRES  25 A  366  ALA LEU ALA HIS PRO TYR LEU GLU GLN TYR TYR ASP PRO          
SEQRES  26 A  366  SER ASP GLU PRO ILE ALA GLU ALA PRO PHE LYS PHE ASP          
SEQRES  27 A  366  MET GLU LEU ASP ASP LEU PRO LYS GLU LYS LEU LYS GLU          
SEQRES  28 A  366  LEU ILE PHE GLU GLU THR ALA ARG PHE GLN PRO GLY TYR          
SEQRES  29 A  366  ARG SER                                                      
HET    6S9  A 401      45                                                       
HET    SO4  A 402       5                                                       
HET    SO4  A 403       5                                                       
HET    SO4  A 404       5                                                       
HET    SO4  A 405       5                                                       
HET    SO4  A 406       5                                                       
HETNAM     6S9 1-[3-(2-METHYLPYRIDIN-4-YL)-1~{H}-PYRAZOLO[4,3-                  
HETNAM   2 6S9  C]PYRIDIN-6-YL]-3-(PHENYLMETHYL)UREA                            
HETNAM     SO4 SULFATE ION                                                      
FORMUL   2  6S9    C20 H18 N6 O                                                 
FORMUL   3  SO4    5(O4 S 2-)                                                   
FORMUL   8  HOH   *269(H2 O)                                                    
HELIX    1 AA1 HIS A   59  PHE A   76  1                                  18    
HELIX    2 AA2 LEU A  110  GLN A  117  1                                   8    
HELIX    3 AA3 SER A  120  ALA A  141  1                                  22    
HELIX    4 AA4 LYS A  149  SER A  151  5                                   3    
HELIX    5 AA5 ASP A  173  ASP A  177  5                                   5    
HELIX    6 AA6 THR A  188  ARG A  192  5                                   5    
HELIX    7 AA7 ALA A  193  MET A  197  5                                   5    
HELIX    8 AA8 LYS A  205  ASN A  222  1                                  18    
HELIX    9 AA9 HIS A  230  GLY A  243  1                                  14    
HELIX   10 AB1 SER A  246  CYS A  252  1                                   7    
HELIX   11 AB2 ASN A  255  LEU A  265  1                                  11    
HELIX   12 AB3 PRO A  272  PHE A  277  1                                   6    
HELIX   13 AB4 ASP A  281  LEU A  292  1                                  12    
HELIX   14 AB5 GLU A  301  ALA A  307  1                                   7    
HELIX   15 AB6 HIS A  308  GLU A  312  5                                   5    
HELIX   16 AB7 ASP A  316  GLU A  320  5                                   5    
HELIX   17 AB8 PRO A  337  THR A  349  1                                  13    
HELIX   18 AB9 ALA A  350  GLN A  353  5                                   4    
SHEET    1 AA1 5 TYR A  23  GLU A  31  0                                        
SHEET    2 AA1 5 GLY A  35  ASP A  42 -1  O  TYR A  41   N  THR A  24           
SHEET    3 AA1 5 VAL A  47  ILE A  54 -1  O  VAL A  49   N  ALA A  40           
SHEET    4 AA1 5 VAL A  99  ASP A 104 -1  O  ILE A 101   N  LYS A  52           
SHEET    5 AA1 5 ASP A  86  ILE A  88 -1  N  ASP A  86   O  VAL A 102           
SHEET    1 AA2 3 THR A 108  ASP A 109  0                                        
SHEET    2 AA2 3 LEU A 153  LEU A 155 -1  O  LEU A 155   N  THR A 108           
SHEET    3 AA2 3 LEU A 161  ILE A 163 -1  O  LYS A 162   N  LEU A 154           
SHEET    1 AA3 2 VAL A 143  LEU A 144  0                                        
SHEET    2 AA3 2 ARG A 170  VAL A 171 -1  O  ARG A 170   N  LEU A 144           
CISPEP   1 GLY A   20    PRO A   21          0        -3.03                     
SITE     1 AC1 14 GLY A  32  GLY A  35  VAL A  37  ALA A  50                    
SITE     2 AC1 14 LYS A  52  GLN A 103  ASP A 104  LEU A 105                    
SITE     3 AC1 14 MET A 106  GLU A 107  LYS A 112  LEU A 154                    
SITE     4 AC1 14 ASP A 165  HOH A 594                                          
SITE     1 AC2  7 ARG A  68  ARG A 170  VAL A 171  ASP A 330                    
SITE     2 AC2  7 MET A 331  HOH A 538  HOH A 564                               
SITE     1 AC3  6 ARG A  75  PRO A 326  PHE A 327  LYS A 328                    
SITE     2 AC3  6 PHE A 329  HOH A 652                                          
SITE     1 AC4  6 ARG A  65  ARG A 146  ARG A 170  VAL A 186                    
SITE     2 AC4  6 TYR A 203  HOH A 508                                          
SITE     1 AC5  5 ARG A 189  ARG A 192  TYR A 231  HOH A 576                    
SITE     2 AC5  5 HOH A 639                                                     
SITE     1 AC6  9 ASN A 121  GLY A 180  LYS A 257  HOH A 524                    
SITE     2 AC6  9 HOH A 527  HOH A 545  HOH A 579  HOH A 695                    
SITE     3 AC6  9 HOH A 696                                                     
CRYST1   71.105   91.334   62.917  90.00  90.00  90.00 P 21 21 2     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      0.014064  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.010949  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.015894        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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