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Database: PDB
Entry: 5IU2
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HEADER    TRANSFERASE                             17-MAR-16   5IU2              
TITLE     DISCOVERY OF IMIDAZOQUINOLINES AS A NOVEL CLASS OF POTENT, SELECTIVE  
TITLE    2 AND IN VIVO EFFICACIOUS COT KINASE INHIBITORS                        
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 8;          
COMPND   3 CHAIN: A, B;                                                         
COMPND   4 SYNONYM: CANCER OSAKA THYROID ONCOGENE,PROTO-ONCOGENE C-COT,         
COMPND   5 SERINE/THREONINE-PROTEIN KINASE COT,TUMOR PROGRESSION LOCUS 2,TPL-2; 
COMPND   6 EC: 2.7.11.25                                                        
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606                                                 
KEYWDS    COT, TPL-2, MAP3K8, KINASE, INHIBITOR, COMPLEX, TRANSFERASE           
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    S.GUTMANN,A.HINNIGER                                                  
REVDAT   2   07-SEP-16 5IU2    1       JRNL                                     
REVDAT   1   24-AUG-16 5IU2    0                                                
SPRSDE     24-AUG-16 5IU2      4Y83 4Y85                                        
JRNL        AUTH   R.GLATTHAR,A.STOJANOVIC,T.TROXLER,H.MATTES,H.MOBITZ,         
JRNL        AUTH 2 R.BEERLI,J.BLANZ,E.GASSMANN,P.DRUCKES,G.FENDRICH,S.GUTMANN,  
JRNL        AUTH 3 G.MARTINY-BARON,F.SPENCE,J.HORNFELD,J.E.PEEL,H.SPARRER       
JRNL        TITL   DISCOVERY OF IMIDAZOQUINOLINES AS A NOVEL CLASS OF POTENT,   
JRNL        TITL 2 SELECTIVE, AND IN VIVO EFFICACIOUS CANCER OSAKA THYROID      
JRNL        TITL 3 (COT) KINASE INHIBITORS.                                     
JRNL        REF    J.MED.CHEM.                   V.  59  7544 2016              
JRNL        REFN                   ISSN 0022-2623                               
JRNL        PMID   27502541                                                     
JRNL        DOI    10.1021/ACS.JMEDCHEM.6B00598                                 
REMARK   2                                                                      
REMARK   2 RESOLUTION.    2.70 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) : 2.70                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 58.01                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : 0.000                          
REMARK   3   COMPLETENESS FOR RANGE        (%) : 99.8                           
REMARK   3   NUMBER OF REFLECTIONS             : 20361                          
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)  : 0.234                          
REMARK   3   R VALUE            (WORKING SET)  : 0.233                          
REMARK   3   FREE R VALUE                      : 0.258                          
REMARK   3   FREE R VALUE TEST SET SIZE   (%)  : 5.000                          
REMARK   3   FREE R VALUE TEST SET COUNT       : 1019                           
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               : 10                       
REMARK   3   BIN RESOLUTION RANGE HIGH   (ANGSTROMS) : 2.70                     
REMARK   3   BIN RESOLUTION RANGE LOW    (ANGSTROMS) : 2.85                     
REMARK   3   BIN COMPLETENESS (WORKING+TEST)     (%) : 99.81                    
REMARK   3   REFLECTIONS IN BIN (WORKING + TEST SET) : 2936                     
REMARK   3   BIN R VALUE        (WORKING + TEST SET) : 0.2998                   
REMARK   3   REFLECTIONS IN BIN        (WORKING SET) : 2789                     
REMARK   3   BIN R VALUE               (WORKING SET) : 0.2965                   
REMARK   3   BIN FREE R VALUE                        : 0.3598                   
REMARK   3   BIN FREE R VALUE TEST SET SIZE      (%) : 5.01                     
REMARK   3   BIN FREE R VALUE TEST SET COUNT         : 147                      
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            : 4769                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 74                                      
REMARK   3   SOLVENT ATOMS            : 150                                     
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 50.76                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 29.06                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : -4.06000                                             
REMARK   3    B22 (A**2) : 1.22620                                              
REMARK   3    B33 (A**2) : 2.83380                                              
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) : 0.429               
REMARK   3   DPI (BLOW EQ-10) BASED ON R VALUE        (A) : NULL                
REMARK   3   DPI (BLOW EQ-9) BASED ON FREE R VALUE    (A) : 0.344               
REMARK   3   DPI (CRUICKSHANK) BASED ON R VALUE       (A) : NULL                
REMARK   3   DPI (CRUICKSHANK) BASED ON FREE R VALUE  (A) : 0.344               
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      : 0.890                         
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : 0.851                         
REMARK   3                                                                      
REMARK   3   NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15                    
REMARK   3   TERM                          COUNT    WEIGHT   FUNCTION.          
REMARK   3    BOND LENGTHS              : 4980   ; 2.000  ; HARMONIC            
REMARK   3    BOND ANGLES               : 6784   ; 2.000  ; HARMONIC            
REMARK   3    TORSION ANGLES            : 1625   ; 2.000  ; SINUSOIDAL          
REMARK   3    TRIGONAL CARBON PLANES    : 92     ; 2.000  ; HARMONIC            
REMARK   3    GENERAL PLANES            : 728    ; 5.000  ; HARMONIC            
REMARK   3    ISOTROPIC THERMAL FACTORS : 4980   ; 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   : 655    ; 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   : 5642   ; 4.000  ; SEMIHARMONIC        
REMARK   3                                                                      
REMARK   3   RMS DEVIATIONS FROM IDEAL VALUES.                                  
REMARK   3    BOND LENGTHS                       (A) : 0.008                    
REMARK   3    BOND ANGLES                  (DEGREES) : 0.98                     
REMARK   3    PEPTIDE OMEGA TORSION ANGLES (DEGREES) : 2.37                     
REMARK   3    OTHER TORSION ANGLES         (DEGREES) : 17.99                    
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):  -14.4225   17.2603   -6.6568           
REMARK   3    T TENSOR                                                          
REMARK   3     T11:   -0.1306 T22:   -0.0750                                    
REMARK   3     T33:   -0.0317 T12:   -0.0144                                    
REMARK   3     T13:    0.0275 T23:    0.0734                                    
REMARK   3    L TENSOR                                                          
REMARK   3     L11:    0.4391 L22:    1.4279                                    
REMARK   3     L33:    0.3266 L12:   -0.1672                                    
REMARK   3     L13:    0.0258 L23:    0.3918                                    
REMARK   3    S TENSOR                                                          
REMARK   3     S11:    0.0293 S12:   -0.0612 S13:    0.0302                     
REMARK   3     S21:   -0.1315 S22:   -0.0004 S23:   -0.1273                     
REMARK   3     S31:   -0.0601 S32:   -0.0454 S33:   -0.0289                     
REMARK   3                                                                      
REMARK   3   TLS GROUP : 2                                                      
REMARK   3    SELECTION: { B|* }                                                
REMARK   3    ORIGIN FOR THE GROUP (A):  -43.4190    0.6358  -18.5099           
REMARK   3    T TENSOR                                                          
REMARK   3     T11:   -0.1716 T22:   -0.0309                                    
REMARK   3     T33:   -0.0602 T12:    0.0241                                    
REMARK   3     T13:   -0.0018 T23:    0.0022                                    
REMARK   3    L TENSOR                                                          
REMARK   3     L11:    0.2032 L22:    0.1924                                    
REMARK   3     L33:    0.9980 L12:    0.0091                                    
REMARK   3     L13:   -0.0428 L23:    0.4532                                    
REMARK   3    S TENSOR                                                          
REMARK   3     S11:   -0.0051 S12:    0.1091 S13:    0.0430                     
REMARK   3     S21:   -0.0593 S22:   -0.0596 S23:    0.0313                     
REMARK   3     S31:   -0.0963 S32:   -0.0758 S33:    0.0647                     
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: NULL                                      
REMARK   4                                                                      
REMARK   4 5IU2 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 17-MAR-16.                  
REMARK 100 THE DEPOSITION ID IS D_1000219427.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 21-NOV-10                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : NULL                               
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : SLS                                
REMARK 200  BEAMLINE                       : X10SA                              
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.0000                             
REMARK 200  MONOCHROMATOR                  : NULL                               
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : PIXEL                              
REMARK 200  DETECTOR MANUFACTURER          : DECTRIS PILATUS 6M                 
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : XDS                                
REMARK 200  DATA SCALING SOFTWARE          : XSCALE                             
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 20386                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.700                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 71.660                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : NULL                               
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 99.9                               
REMARK 200  DATA REDUNDANCY                : 6.530                              
REMARK 200  R MERGE                    (I) : NULL                               
REMARK 200  R SYM                      (I) : 0.12900                            
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 12.5300                            
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) : 2.81                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : NULL                               
REMARK 200  DATA REDUNDANCY IN SHELL       : NULL                               
REMARK 200  R MERGE FOR SHELL          (I) : NULL                               
REMARK 200  R SYM FOR SHELL            (I) : 0.49200                            
REMARK 200  <I/SIGMA(I)> FOR SHELL         : NULL                               
REMARK 200                                                                      
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH                              
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT        
REMARK 200 SOFTWARE USED: PHASER                                                
REMARK 200 STARTING MODEL: 4Y85                                                 
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 48.30                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.38                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1 M BIS-TRIS PH 7, 1.7 M AMMONIUM      
REMARK 280  SULFATE, 0.01 M PROLINE. PROTEIN SOLUTION (COT:COMPOUND 1:1) WAS    
REMARK 280  MIXED WITH AN EQUAL VOLUME (1 UL) OF RESERVOIR SOLUTION.            
REMARK 280  EQUILIBRATION WAS DONE OVER 500 UL RESERVOIR SOLUTION., VAPOR       
REMARK 280  DIFFUSION, HANGING DROP, TEMPERATURE 298K                           
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY                                            
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 2 21 21                        
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,Y+1/2,-Z+1/2                                         
REMARK 290       4555   -X,-Y+1/2,Z+1/2                                         
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        0.00000            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       43.71500            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000       62.56000            
REMARK 290   SMTRY1   4 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000       43.71500            
REMARK 290   SMTRY3   4  0.000000  0.000000  1.000000       62.56000            
REMARK 290                                                                      
REMARK 290 REMARK: NULL                                                         
REMARK 300                                                                      
REMARK 300 BIOMOLECULE: 1, 2                                                    
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM                
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN                  
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON               
REMARK 300 BURIED SURFACE AREA.                                                 
REMARK 350                                                                      
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN           
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE                
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS          
REMARK 350 GIVEN BELOW.  BOTH NON-CRYSTALLOGRAPHIC AND                          
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.                               
REMARK 350                                                                      
REMARK 350 BIOMOLECULE: 1                                                       
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC                         
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 350                                                                      
REMARK 350 BIOMOLECULE: 2                                                       
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC                         
REMARK 350 APPLY THE FOLLOWING TO CHAINS: B                                     
REMARK 350   BIOMT1   1  1.000000  0.000000  0.000000        0.00000            
REMARK 350   BIOMT2   1  0.000000  1.000000  0.000000        0.00000            
REMARK 350   BIOMT3   1  0.000000  0.000000  1.000000        0.00000            
REMARK 465                                                                      
REMARK 465 MISSING RESIDUES                                                     
REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE                       
REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN               
REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)                
REMARK 465                                                                      
REMARK 465   M RES C SSSEQI                                                     
REMARK 465     GLY A    64                                                      
REMARK 465     PRO A    65                                                      
REMARK 465     SER A    66                                                      
REMARK 465     GLY A    67                                                      
REMARK 465     GLN A    68                                                      
REMARK 465     GLU A    69                                                      
REMARK 465     VAL A    70                                                      
REMARK 465     PRO A    71                                                      
REMARK 465     TRP A    72                                                      
REMARK 465     THR A    94                                                      
REMARK 465     ALA A    95                                                      
REMARK 465     LYS A    96                                                      
REMARK 465     HIS A    97                                                      
REMARK 465     ILE A   139                                                      
REMARK 465     PRO A   390                                                      
REMARK 465     PRO A   391                                                      
REMARK 465     ARG A   392                                                      
REMARK 465     GLU A   393                                                      
REMARK 465     ASP A   394                                                      
REMARK 465     GLN A   395                                                      
REMARK 465     GLY B    64                                                      
REMARK 465     PRO B    65                                                      
REMARK 465     SER B    66                                                      
REMARK 465     GLY B    67                                                      
REMARK 465     GLN B    68                                                      
REMARK 465     GLU B    69                                                      
REMARK 465     VAL B    70                                                      
REMARK 465     PRO B    71                                                      
REMARK 465     TRP B    72                                                      
REMARK 465     THR B    94                                                      
REMARK 465     ALA B    95                                                      
REMARK 465     LYS B    96                                                      
REMARK 465     ILE B   139                                                      
REMARK 465     PRO B   390                                                      
REMARK 465     PRO B   391                                                      
REMARK 465     ARG B   392                                                      
REMARK 465     GLU B   393                                                      
REMARK 465     ASP B   394                                                      
REMARK 465     GLN B   395                                                      
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     LEU A  73    CG   CD1  CD2                                       
REMARK 470     ARG A  77    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     GLU A  82    CG   CD   OE1  OE2                                  
REMARK 470     ASN A  89    CG   OD1  ND2                                       
REMARK 470     PHE A  98    CG   CD1  CD2  CE1  CE2  CZ                         
REMARK 470     GLN A 101    CG   CD   OE1  NE2                                  
REMARK 470     ARG A 102    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     GLN A 104    CG   CD   OE1  NE2                                  
REMARK 470     SER A 125    OG                                                  
REMARK 470     SER A 141    OG                                                  
REMARK 470     ASP A 142    CG   OD1  OD2                                       
REMARK 470     LYS A 151    CG   CD   CE   NZ                                   
REMARK 470     LYS A 159    CG   CD   CE   NZ                                   
REMARK 470     LYS A 175    CG   CD   CE   NZ                                   
REMARK 470     PRO A 176    CG   CD                                             
REMARK 470     GLU A 201    CG   CD   OE1  OE2                                  
REMARK 470     LYS A 248    CD   CE   NZ                                        
REMARK 470     SER A 263    OG                                                  
REMARK 470     LYS A 285    CG   CD   CE   NZ                                   
REMARK 470     ASP A 286    CG   OD1  OD2                                       
REMARK 470     ARG A 288    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     ARG A 302    CD   NE   CZ   NH1  NH2                             
REMARK 470     THR A 322    CG2                                                 
REMARK 470     LYS A 345    CG   CD   CE   NZ                                   
REMARK 470     ASP A 352    CG   OD1  OD2                                       
REMARK 470     ASP A 355    CG   OD1  OD2                                       
REMARK 470     ASP A 356    CG   OD1  OD2                                       
REMARK 470     LYS A 384    CG   CD   CE   NZ                                   
REMARK 470     GLU A 386    CG   CD   OE1  OE2                                  
REMARK 470     LEU B  73    CG   CD1  CD2                                       
REMARK 470     ARG B  77    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     GLU B  82    CG   CD   OE1  OE2                                  
REMARK 470     SER B  92    OG                                                  
REMARK 470     ASN B  93    CG   OD1  ND2                                       
REMARK 470     HIS B  97    CG   ND1  CD2  CE1  NE2                             
REMARK 470     PHE B  98    CG   CD1  CD2  CE1  CE2  CZ                         
REMARK 470     GLN B 101    CG   CD   OE1  NE2                                  
REMARK 470     ARG B 102    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     GLN B 104    CG   CD   OE1  NE2                                  
REMARK 470     SER B 125    OG                                                  
REMARK 470     LYS B 133    CG   CD   CE   NZ                                   
REMARK 470     SER B 141    OG                                                  
REMARK 470     ASP B 142    CG   OD1  OD2                                       
REMARK 470     ILE B 144    CG1  CG2  CD1                                       
REMARK 470     LYS B 151    CG   CD   CE   NZ                                   
REMARK 470     LYS B 159    CG   CD   CE   NZ                                   
REMARK 470     LYS B 175    CG   CD   CE   NZ                                   
REMARK 470     PRO B 176    CG   CD                                             
REMARK 470     ARG B 186    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     GLU B 201    CG   CD   OE1  OE2                                  
REMARK 470     LYS B 248    CD   CE   NZ                                        
REMARK 470     SER B 263    OG                                                  
REMARK 470     LYS B 285    CG   CD   CE   NZ                                   
REMARK 470     ARG B 288    NE   CZ   NH1  NH2                                  
REMARK 470     ARG B 302    CG   CD   NE   CZ   NH1  NH2                        
REMARK 470     THR B 322    CG2                                                 
REMARK 470     LYS B 345    CG   CD   CE   NZ                                   
REMARK 470     ASP B 355    CG   OD1  OD2                                       
REMARK 470     ASP B 356    CG   OD1  OD2                                       
REMARK 470     GLU B 363    CG   CD   OE1  OE2                                  
REMARK 470     GLU B 386    CG   CD   OE1  OE2                                  
REMARK 470     ASN B 389    CG   OD1  ND2                                       
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    HIS A 252       -5.73     71.95                                   
REMARK 500    ASP A 253       57.06   -143.74                                   
REMARK 500    ASP A 270       91.75     58.81                                   
REMARK 500    SER A 338       39.18   -144.07                                   
REMARK 500    ASP A 356       66.80   -103.31                                   
REMARK 500    HIS B 252       -5.78     71.78                                   
REMARK 500    ASP B 253       56.94   -143.61                                   
REMARK 500    ASP B 270       91.68     58.50                                   
REMARK 500    SER B 338       39.75   -143.31                                   
REMARK 500    ASP B 356       65.98   -101.88                                   
REMARK 500    GLU B 370      123.54    -39.30                                   
REMARK 500    LEU B 388       51.38    -96.89                                   
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: MAIN CHAIN PLANARITY                                       
REMARK 500                                                                      
REMARK 500 THE FOLLOWING RESIDUES HAVE A PSEUDO PLANARITY                       
REMARK 500 TORSION ANGLE, C(I) - CA(I) - N(I+1) - O(I), GREATER                 
REMARK 500 10.0 DEGREES. (M=MODEL NUMBER; RES=RESIDUE NAME;                     
REMARK 500 C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;                            
REMARK 500 I=INSERTION CODE).                                                   
REMARK 500                                                                      
REMARK 500  M RES CSSEQI        ANGLE                                           
REMARK 500    LYS B 175        -10.14                                           
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 6DA A 401                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: binding site for residue 6DA B 401                 
DBREF  5IU2 A   66   395  UNP    P41279   M3K8_HUMAN      66    395             
DBREF  5IU2 B   66   395  UNP    P41279   M3K8_HUMAN      66    395             
SEQADV 5IU2 GLY A   64  UNP  P41279              EXPRESSION TAG                 
SEQADV 5IU2 PRO A   65  UNP  P41279              EXPRESSION TAG                 
SEQADV 5IU2 GLY B   64  UNP  P41279              EXPRESSION TAG                 
SEQADV 5IU2 PRO B   65  UNP  P41279              EXPRESSION TAG                 
SEQRES   1 A  332  GLY PRO SER GLY GLN GLU VAL PRO TRP LEU SER SER VAL          
SEQRES   2 A  332  ARG TYR GLY THR VAL GLU ASP LEU LEU ALA PHE ALA ASN          
SEQRES   3 A  332  HIS ILE SER ASN THR ALA LYS HIS PHE TYR GLY GLN ARG          
SEQRES   4 A  332  PRO GLN GLU SER GLY ILE LEU LEU ASN MET VAL ILE THR          
SEQRES   5 A  332  PRO GLN ASN GLY ARG TYR GLN ILE ASP SER ASP VAL LEU          
SEQRES   6 A  332  LEU ILE PRO TRP LYS LEU THR TYR ARG ASN ILE GLY SER          
SEQRES   7 A  332  ASP PHE ILE PRO ARG GLY ALA PHE GLY LYS VAL TYR LEU          
SEQRES   8 A  332  ALA GLN ASP ILE LYS THR LYS LYS ARG MET ALA CYS LYS          
SEQRES   9 A  332  LEU ILE PRO VAL ASP GLN PHE LYS PRO SER ASP VAL GLU          
SEQRES  10 A  332  ILE GLN ALA CYS PHE ARG HIS GLU ASN ILE ALA GLU LEU          
SEQRES  11 A  332  TYR GLY ALA VAL LEU TRP GLY GLU THR VAL HIS LEU PHE          
SEQRES  12 A  332  MET GLU ALA GLY GLU GLY GLY SER VAL LEU GLU LYS LEU          
SEQRES  13 A  332  GLU SER CYS GLY PRO MET ARG GLU PHE GLU ILE ILE TRP          
SEQRES  14 A  332  VAL THR LYS HIS VAL LEU LYS GLY LEU ASP PHE LEU HIS          
SEQRES  15 A  332  SER LYS LYS VAL ILE HIS HIS ASP ILE LYS PRO SER ASN          
SEQRES  16 A  332  ILE VAL PHE MET SER THR LYS ALA VAL LEU VAL ASP PHE          
SEQRES  17 A  332  GLY LEU SER VAL GLN MET THR GLU ASP VAL TYR PHE PRO          
SEQRES  18 A  332  LYS ASP LEU ARG GLY THR GLU ILE TYR MET SER PRO GLU          
SEQRES  19 A  332  VAL ILE LEU CYS ARG GLY HIS SER THR LYS ALA ASP ILE          
SEQRES  20 A  332  TYR SER LEU GLY ALA THR LEU ILE HIS MET GLN THR GLY          
SEQRES  21 A  332  THR PRO PRO TRP VAL LYS ARG TYR PRO ARG SER ALA TYR          
SEQRES  22 A  332  PRO SER TYR LEU TYR ILE ILE HIS LYS GLN ALA PRO PRO          
SEQRES  23 A  332  LEU GLU ASP ILE ALA ASP ASP CYS SER PRO GLY MET ARG          
SEQRES  24 A  332  GLU LEU ILE GLU ALA SER LEU GLU ARG ASN PRO ASN HIS          
SEQRES  25 A  332  ARG PRO ARG ALA ALA ASP LEU LEU LYS HIS GLU ALA LEU          
SEQRES  26 A  332  ASN PRO PRO ARG GLU ASP GLN                                  
SEQRES   1 B  332  GLY PRO SER GLY GLN GLU VAL PRO TRP LEU SER SER VAL          
SEQRES   2 B  332  ARG TYR GLY THR VAL GLU ASP LEU LEU ALA PHE ALA ASN          
SEQRES   3 B  332  HIS ILE SER ASN THR ALA LYS HIS PHE TYR GLY GLN ARG          
SEQRES   4 B  332  PRO GLN GLU SER GLY ILE LEU LEU ASN MET VAL ILE THR          
SEQRES   5 B  332  PRO GLN ASN GLY ARG TYR GLN ILE ASP SER ASP VAL LEU          
SEQRES   6 B  332  LEU ILE PRO TRP LYS LEU THR TYR ARG ASN ILE GLY SER          
SEQRES   7 B  332  ASP PHE ILE PRO ARG GLY ALA PHE GLY LYS VAL TYR LEU          
SEQRES   8 B  332  ALA GLN ASP ILE LYS THR LYS LYS ARG MET ALA CYS LYS          
SEQRES   9 B  332  LEU ILE PRO VAL ASP GLN PHE LYS PRO SER ASP VAL GLU          
SEQRES  10 B  332  ILE GLN ALA CYS PHE ARG HIS GLU ASN ILE ALA GLU LEU          
SEQRES  11 B  332  TYR GLY ALA VAL LEU TRP GLY GLU THR VAL HIS LEU PHE          
SEQRES  12 B  332  MET GLU ALA GLY GLU GLY GLY SER VAL LEU GLU LYS LEU          
SEQRES  13 B  332  GLU SER CYS GLY PRO MET ARG GLU PHE GLU ILE ILE TRP          
SEQRES  14 B  332  VAL THR LYS HIS VAL LEU LYS GLY LEU ASP PHE LEU HIS          
SEQRES  15 B  332  SER LYS LYS VAL ILE HIS HIS ASP ILE LYS PRO SER ASN          
SEQRES  16 B  332  ILE VAL PHE MET SER THR LYS ALA VAL LEU VAL ASP PHE          
SEQRES  17 B  332  GLY LEU SER VAL GLN MET THR GLU ASP VAL TYR PHE PRO          
SEQRES  18 B  332  LYS ASP LEU ARG GLY THR GLU ILE TYR MET SER PRO GLU          
SEQRES  19 B  332  VAL ILE LEU CYS ARG GLY HIS SER THR LYS ALA ASP ILE          
SEQRES  20 B  332  TYR SER LEU GLY ALA THR LEU ILE HIS MET GLN THR GLY          
SEQRES  21 B  332  THR PRO PRO TRP VAL LYS ARG TYR PRO ARG SER ALA TYR          
SEQRES  22 B  332  PRO SER TYR LEU TYR ILE ILE HIS LYS GLN ALA PRO PRO          
SEQRES  23 B  332  LEU GLU ASP ILE ALA ASP ASP CYS SER PRO GLY MET ARG          
SEQRES  24 B  332  GLU LEU ILE GLU ALA SER LEU GLU ARG ASN PRO ASN HIS          
SEQRES  25 B  332  ARG PRO ARG ALA ALA ASP LEU LEU LYS HIS GLU ALA LEU          
SEQRES  26 B  332  ASN PRO PRO ARG GLU ASP GLN                                  
HET    6DA  A 401      37                                                       
HET    6DA  B 401      37                                                       
HETNAM     6DA N-[2-(MORPHOLIN-4-YL)ETHYL]-6-(8-PHENYL-1H-IMIDAZO[4,5-          
HETNAM   2 6DA  C][1,7]NAPHTHYRIDIN-1-YL)-1,3-BENZOTHIAZOL-2-AMINE              
FORMUL   3  6DA    2(C28 H25 N7 O S)                                            
FORMUL   5  HOH   *150(H2 O)                                                    
HELIX    1 AA1 THR A   80  SER A   92  1                                  13    
HELIX    2 AA2 GLN A  122  ASP A  126  1                                   5    
HELIX    3 AA3 PRO A  176  PHE A  185  1                                  10    
HELIX    4 AA4 SER A  214  GLY A  223  1                                  10    
HELIX    5 AA5 ARG A  226  LYS A  247  1                                  22    
HELIX    6 AA6 LYS A  255  SER A  257  5                                   3    
HELIX    7 AA7 THR A  290  MET A  294  5                                   5    
HELIX    8 AA8 SER A  295  CYS A  301  1                                   7    
HELIX    9 AA9 THR A  306  GLY A  323  1                                  18    
HELIX   10 AB1 SER A  338  ALA A  347  1                                  10    
HELIX   11 AB2 SER A  358  LEU A  369  1                                  12    
HELIX   12 AB3 ASN A  372  ARG A  376  5                                   5    
HELIX   13 AB4 ARG A  378  LYS A  384  1                                   7    
HELIX   14 AB5 THR B   80  SER B   92  1                                  13    
HELIX   15 AB6 GLN B  122  ASP B  126  1                                   5    
HELIX   16 AB7 PRO B  176  PHE B  185  1                                  10    
HELIX   17 AB8 SER B  214  GLY B  223  1                                  10    
HELIX   18 AB9 ARG B  226  LYS B  247  1                                  22    
HELIX   19 AC1 LYS B  255  SER B  257  5                                   3    
HELIX   20 AC2 THR B  290  MET B  294  5                                   5    
HELIX   21 AC3 SER B  295  CYS B  301  1                                   7    
HELIX   22 AC4 THR B  306  GLY B  323  1                                  18    
HELIX   23 AC5 SER B  338  ALA B  347  1                                  10    
HELIX   24 AC6 SER B  358  LEU B  369  1                                  12    
HELIX   25 AC7 ASN B  372  ARG B  376  5                                   5    
HELIX   26 AC8 ARG B  378  LYS B  384  1                                   7    
SHEET    1 AA1 7 VAL A  76  TYR A  78  0                                        
SHEET    2 AA1 7 GLU A 105  LEU A 109  1  O  GLY A 107   N  ARG A  77           
SHEET    3 AA1 7 LEU A 193  TRP A 199 -1  O  LEU A 198   N  SER A 106           
SHEET    4 AA1 7 THR A 202  MET A 207 -1  O  HIS A 204   N  VAL A 197           
SHEET    5 AA1 7 ARG A 163  PRO A 170 -1  N  ILE A 169   O  VAL A 203           
SHEET    6 AA1 7 LYS A 151  ASP A 157 -1  N  LYS A 151   O  LEU A 168           
SHEET    7 AA1 7 VAL A 127  PRO A 131 -1  N  ILE A 130   O  LEU A 154           
SHEET    1 AA2 2 VAL A 249  ILE A 250  0                                        
SHEET    2 AA2 2 VAL A 275  GLN A 276 -1  O  VAL A 275   N  ILE A 250           
SHEET    1 AA3 2 ILE A 259  PHE A 261  0                                        
SHEET    2 AA3 2 ALA A 266  LEU A 268 -1  O  VAL A 267   N  VAL A 260           
SHEET    1 AA4 7 VAL B  76  TYR B  78  0                                        
SHEET    2 AA4 7 GLU B 105  LEU B 109  1  O  GLY B 107   N  ARG B  77           
SHEET    3 AA4 7 LEU B 193  TRP B 199 -1  O  LEU B 198   N  SER B 106           
SHEET    4 AA4 7 THR B 202  MET B 207 -1  O  HIS B 204   N  VAL B 197           
SHEET    5 AA4 7 ARG B 163  PRO B 170 -1  N  ILE B 169   O  VAL B 203           
SHEET    6 AA4 7 LYS B 151  ASP B 157 -1  N  TYR B 153   O  CYS B 166           
SHEET    7 AA4 7 VAL B 127  PRO B 131 -1  N  ILE B 130   O  LEU B 154           
SHEET    1 AA5 2 VAL B 249  ILE B 250  0                                        
SHEET    2 AA5 2 VAL B 275  GLN B 276 -1  O  VAL B 275   N  ILE B 250           
SHEET    1 AA6 2 ILE B 259  PHE B 261  0                                        
SHEET    2 AA6 2 ALA B 266  LEU B 268 -1  O  VAL B 267   N  VAL B 260           
CISPEP   1 ALA A  347    PRO A  348          0         5.93                     
CISPEP   2 ALA B  347    PRO B  348          0         2.44                     
SITE     1 AC1 22 TRP A 132  LEU A 134  PHE A 149  GLY A 150                    
SITE     2 AC1 22 VAL A 152  ALA A 165  LYS A 167  MET A 207                    
SITE     3 AC1 22 GLU A 208  GLY A 210  GLY A 213  SER A 214                    
SITE     4 AC1 22 GLU A 217  SER A 257  ASN A 258  VAL A 260                    
SITE     5 AC1 22 VAL A 269  ASP A 270  HOH A 502  HOH A 539                    
SITE     6 AC1 22 HOH A 542  HOH A 556                                          
SITE     1 AC2 22 TRP B 132  LEU B 134  PHE B 149  GLY B 150                    
SITE     2 AC2 22 VAL B 152  ALA B 165  LYS B 167  MET B 207                    
SITE     3 AC2 22 GLU B 208  ALA B 209  GLY B 210  GLY B 213                    
SITE     4 AC2 22 SER B 214  GLU B 217  SER B 257  ASN B 258                    
SITE     5 AC2 22 VAL B 260  VAL B 269  ASP B 270  HOH B 506                    
SITE     6 AC2 22 HOH B 508  HOH B 534                                          
CRYST1   65.480   87.430  125.120  90.00  90.00  90.00 P 2 21 21     8          
ORIGX1      1.000000  0.000000  0.000000        0.00000                         
ORIGX2      0.000000  1.000000  0.000000        0.00000                         
ORIGX3      0.000000  0.000000  1.000000        0.00000                         
SCALE1      0.015272  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.011438  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.007992        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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