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Database: PDB
Entry: 3V01
LinkDB: 3V01
Original site: 3V01 
HEADER    TRANSFERASE/INHIBITOR                   07-DEC-11   3V01              
TITLE     DISCOVERY OF NOVEL ALLOSTERIC MEK INHIBITORS POSSESSING CLASSICAL AND 
TITLE    2 NON-CLASSICAL BIDENTATE SER212 INTERACTIONS.                         
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 1;
COMPND   3 CHAIN: A;                                                            
COMPND   4 FRAGMENT: UNP RESIDUES 62-393;                                       
COMPND   5 SYNONYM: MAP KINASE KINASE 1, MAPKK 1, MKK1, ERK ACTIVATOR KINASE 1, 
COMPND   6 MAPK/ERK KINASE 1, MEK 1;                                            
COMPND   7 EC: 2.7.12.2;                                                        
COMPND   8 ENGINEERED: YES                                                      
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606;                                                
SOURCE   5 GENE: MAP2K1, MEK1, PRKMK1;                                          
SOURCE   6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;                                 
SOURCE   7 EXPRESSION_SYSTEM_TAXID: 562;                                        
SOURCE   8 EXPRESSION_SYSTEM_STRAIN: ROSETTA 2;                                 
SOURCE   9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;                              
SOURCE  10 EXPRESSION_SYSTEM_PLASMID: PET24B                                    
KEYWDS    KINASE, TRANSFERASE-INHIBITOR COMPLEX                                 
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    R.HEALD,P.JACKSON,P.SAVY,M.JONES,E.GANCIA,B.BURTON,R.NEWMAN,J.BOGGS,  
AUTHOR   2 E.CHAN,J.CHAN,E.CHOO,M.MERCHANT,M.ULTSCH,C.WIESMANN,M.BELVIN,S.PRICE 
REVDAT   3   13-SEP-23 3V01    1       REMARK SEQADV LINK                       
REVDAT   2   18-JUL-12 3V01    1       JRNL                                     
REVDAT   1   09-MAY-12 3V01    0                                                
JRNL        AUTH   R.A.HEALD,P.JACKSON,P.SAVY,M.JONES,E.GANCIA,B.BURTON,        
JRNL        AUTH 2 R.NEWMAN,J.BOGGS,E.CHAN,J.CHAN,E.CHOO,M.MERCHANT,P.RUDEWICZ, 
JRNL        AUTH 3 M.ULTSCH,C.WIESMANN,Q.YUE,M.BELVIN,S.PRICE                   
JRNL        TITL   DISCOVERY OF NOVEL ALLOSTERIC MITOGEN-ACTIVATED PROTEIN      
JRNL        TITL 2 KINASE KINASE (MEK) 1,2 INHIBITORS POSSESSING BIDENTATE      
JRNL        TITL 3 SER212 INTERACTIONS.                                         
JRNL        REF    J.MED.CHEM.                   V.  55  4594 2012              
JRNL        REFN                   ISSN 0022-2623                               
JRNL        PMID   22506516                                                     
JRNL        DOI    10.1021/JM2017094                                            
REMARK   2                                                                      
REMARK   2 RESOLUTION.    2.71 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : REFMAC 5.2.0005                                      
REMARK   3   AUTHORS     : MURSHUDOV,SKUBAK,LEBEDEV,PANNU,STEINER,              
REMARK   3               : NICHOLLS,WINN,LONG,VAGIN                             
REMARK   3                                                                      
REMARK   3    REFINEMENT TARGET : MAXIMUM LIKELIHOOD                            
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 2.71                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 20.00                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : 2.000                          
REMARK   3   COMPLETENESS FOR RANGE        (%) : 99.7                           
REMARK   3   NUMBER OF REFLECTIONS             : 12675                          
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) : 0.189                           
REMARK   3   R VALUE            (WORKING SET) : 0.187                           
REMARK   3   FREE R VALUE                     : 0.240                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 4.800                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 640                             
REMARK   3                                                                      
REMARK   3  FIT IN THE HIGHEST RESOLUTION BIN.                                  
REMARK   3   TOTAL NUMBER OF BINS USED           : 25                           
REMARK   3   BIN RESOLUTION RANGE HIGH       (A) : 2.71                         
REMARK   3   BIN RESOLUTION RANGE LOW        (A) : 2.76                         
REMARK   3   REFLECTION IN BIN     (WORKING SET) : 705                          
REMARK   3   BIN COMPLETENESS (WORKING+TEST) (%) : 98.26                        
REMARK   3   BIN R VALUE           (WORKING SET) : 0.2850                       
REMARK   3   BIN FREE R VALUE SET COUNT          : 27                           
REMARK   3   BIN FREE R VALUE                    : 0.2920                       
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS            : 2261                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 59                                      
REMARK   3   SOLVENT ATOMS            : 0                                       
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 71.66                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 85.63                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : 2.30000                                              
REMARK   3    B22 (A**2) : 2.30000                                              
REMARK   3    B33 (A**2) : -3.45000                                             
REMARK   3    B12 (A**2) : 1.15000                                              
REMARK   3    B13 (A**2) : 0.00000                                              
REMARK   3    B23 (A**2) : 0.00000                                              
REMARK   3                                                                      
REMARK   3  ESTIMATED OVERALL COORDINATE ERROR.                                 
REMARK   3   ESU BASED ON R VALUE                            (A): 0.425         
REMARK   3   ESU BASED ON FREE R VALUE                       (A): 0.282         
REMARK   3   ESU BASED ON MAXIMUM LIKELIHOOD                 (A): 0.213         
REMARK   3   ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 23.079        
REMARK   3                                                                      
REMARK   3 CORRELATION COEFFICIENTS.                                            
REMARK   3   CORRELATION COEFFICIENT FO-FC      : 0.961                         
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : 0.920                         
REMARK   3                                                                      
REMARK   3  RMS DEVIATIONS FROM IDEAL VALUES        COUNT    RMS    WEIGHT      
REMARK   3   BOND LENGTHS REFINED ATOMS        (A):  2369 ; 0.013 ; 0.022       
REMARK   3   BOND LENGTHS OTHERS               (A):  2174 ; 0.002 ; 0.020       
REMARK   3   BOND ANGLES REFINED ATOMS   (DEGREES):  3200 ; 1.628 ; 2.012       
REMARK   3   BOND ANGLES OTHERS          (DEGREES):  5083 ; 0.794 ; 3.000       
REMARK   3   TORSION ANGLES, PERIOD 1    (DEGREES):   286 ; 5.746 ; 5.000       
REMARK   3   TORSION ANGLES, PERIOD 2    (DEGREES):    97 ;33.976 ;24.433       
REMARK   3   TORSION ANGLES, PERIOD 3    (DEGREES):   425 ;16.008 ;15.000       
REMARK   3   TORSION ANGLES, PERIOD 4    (DEGREES):    12 ;17.346 ;15.000       
REMARK   3   CHIRAL-CENTER RESTRAINTS       (A**3):   349 ; 0.079 ; 0.200       
REMARK   3   GENERAL PLANES REFINED ATOMS      (A):  2553 ; 0.004 ; 0.020       
REMARK   3   GENERAL PLANES OTHERS             (A):   448 ; 0.001 ; 0.020       
REMARK   3   NON-BONDED CONTACTS REFINED ATOMS (A):   500 ; 0.216 ; 0.200       
REMARK   3   NON-BONDED CONTACTS OTHERS        (A):  2119 ; 0.172 ; 0.200       
REMARK   3   NON-BONDED TORSION REFINED ATOMS  (A):  1148 ; 0.185 ; 0.200       
REMARK   3   NON-BONDED TORSION OTHERS         (A):  1404 ; 0.086 ; 0.200       
REMARK   3   H-BOND (X...Y) REFINED ATOMS      (A):    45 ; 0.148 ; 0.200       
REMARK   3   H-BOND (X...Y) OTHERS             (A):  NULL ;  NULL ;  NULL       
REMARK   3   POTENTIAL METAL-ION REFINED ATOMS (A):     2 ; 0.054 ; 0.200       
REMARK   3   POTENTIAL METAL-ION OTHERS        (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY VDW REFINED ATOMS        (A):     7 ; 0.103 ; 0.200       
REMARK   3   SYMMETRY VDW OTHERS               (A):    30 ; 0.155 ; 0.200       
REMARK   3   SYMMETRY H-BOND REFINED ATOMS     (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY H-BOND OTHERS            (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY METAL-ION REFINED ATOMS  (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY METAL-ION OTHERS         (A):  NULL ;  NULL ;  NULL       
REMARK   3                                                                      
REMARK   3  ISOTROPIC THERMAL FACTOR RESTRAINTS.     COUNT   RMS    WEIGHT      
REMARK   3   MAIN-CHAIN BOND REFINED ATOMS  (A**2):  1450 ; 3.559 ; 2.500       
REMARK   3   MAIN-CHAIN BOND OTHER ATOMS    (A**2):   586 ; 0.695 ; 2.500       
REMARK   3   MAIN-CHAIN ANGLE REFINED ATOMS (A**2):  2318 ; 5.414 ; 5.000       
REMARK   3   MAIN-CHAIN ANGLE OTHER ATOMS   (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SIDE-CHAIN BOND REFINED ATOMS  (A**2):  1024 ; 3.548 ; 2.500       
REMARK   3   SIDE-CHAIN BOND OTHER ATOMS    (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SIDE-CHAIN ANGLE REFINED ATOMS (A**2):   882 ; 5.638 ; 5.000       
REMARK   3   SIDE-CHAIN ANGLE OTHER ATOMS   (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   LONG RANGE B REFINED ATOMS     (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   LONG RANGE B OTHER ATOMS       (A**2):  NULL ;  NULL ;  NULL       
REMARK   3                                                                      
REMARK   3 ANISOTROPIC THERMAL FACTOR RESTRAINTS.    COUNT   RMS   WEIGHT       
REMARK   3   RIGID-BOND RESTRAINTS          (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SPHERICITY; FREE ATOMS         (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SPHERICITY; BONDED ATOMS       (A**2):  NULL ;  NULL ;  NULL       
REMARK   3                                                                      
REMARK   3  NCS RESTRAINTS STATISTICS                                           
REMARK   3   NUMBER OF DIFFERENT NCS GROUPS : NULL                              
REMARK   3                                                                      
REMARK   3  TLS DETAILS                                                         
REMARK   3   NUMBER OF TLS GROUPS  : 1                                          
REMARK   3                                                                      
REMARK   3   TLS GROUP : 1                                                      
REMARK   3    NUMBER OF COMPONENTS GROUP : 2                                    
REMARK   3    COMPONENTS        C SSSEQI   TO  C SSSEQI                         
REMARK   3    RESIDUE RANGE :   A   501        A   503                          
REMARK   3    RESIDUE RANGE :   A    61        A   382                          
REMARK   3    ORIGIN FOR THE GROUP (A):  30.1506  21.2187  -9.1333              
REMARK   3    T TENSOR                                                          
REMARK   3      T11:   0.0051 T22:  -0.2240                                     
REMARK   3      T33:   0.0058 T12:   0.1440                                     
REMARK   3      T13:  -0.0016 T23:  -0.0090                                     
REMARK   3    L TENSOR                                                          
REMARK   3      L11:   1.5250 L22:   1.1634                                     
REMARK   3      L33:   5.5379 L12:   0.2058                                     
REMARK   3      L13:  -0.8587 L23:   0.5917                                     
REMARK   3    S TENSOR                                                          
REMARK   3      S11:  -0.2105 S12:   0.2005 S13:  -0.4247                       
REMARK   3      S21:  -0.1336 S22:   0.0549 S23:   0.2577                       
REMARK   3      S31:  -0.2677 S32:  -0.2238 S33:   0.1555                       
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELLING.                                             
REMARK   3   METHOD USED : MASK                                                 
REMARK   3   PARAMETERS FOR MASK CALCULATION                                    
REMARK   3   VDW PROBE RADIUS   : 1.40                                          
REMARK   3   ION PROBE RADIUS   : 0.80                                          
REMARK   3   SHRINKAGE RADIUS   : 0.80                                          
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: HYDROGENS HAVE BEEN ADDED IN THE RIDING   
REMARK   3  POSITIONS                                                           
REMARK   4                                                                      
REMARK   4 3V01 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 11-JAN-12.                  
REMARK 100 THE DEPOSITION ID IS D_1000069423.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 09-JUN-06                          
REMARK 200  TEMPERATURE           (KELVIN) : 200                                
REMARK 200  PH                             : 7.2                                
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : ALS                                
REMARK 200  BEAMLINE                       : 5.0.2                              
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.0                                
REMARK 200  MONOCHROMATOR                  : SI 111 CHANNEL                     
REMARK 200  OPTICS                         : NULL                               
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : CCD                                
REMARK 200  DETECTOR MANUFACTURER          : ADSC QUANTUM 315                   
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : HKL-2000                           
REMARK 200  DATA SCALING SOFTWARE          : SCALEPACK                          
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 13330                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 2.700                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 50.000                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : 3.000                              
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 99.7                               
REMARK 200  DATA REDUNDANCY                : 4.800                              
REMARK 200  R MERGE                    (I) : NULL                               
REMARK 200  R SYM                      (I) : 0.05700                            
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 24.2300                            
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : NULL                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : NULL                     
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) : NULL                               
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: AMORE                                                 
REMARK 200 STARTING MODEL: PDB ENTRY 1S9J                                       
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 62.54                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 3.28                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 16-20% W/V PEG8K, 0.1M HEPES, 250MM      
REMARK 280  NH4H2PO4, 1MM TCEP, PH 7.2, VAPOR DIFFUSION, HANGING DROP,          
REMARK 280  TEMPERATURE 286K                                                    
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY                                            
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 62                             
REMARK 290                                                                      
REMARK 290      SYMOP   SYMMETRY                                                
REMARK 290     NNNMMM   OPERATOR                                                
REMARK 290       1555   X,Y,Z                                                   
REMARK 290       2555   -Y,X-Y,Z+2/3                                            
REMARK 290       3555   -X+Y,-X,Z+1/3                                           
REMARK 290       4555   -X,-Y,Z                                                 
REMARK 290       5555   Y,-X+Y,Z+2/3                                            
REMARK 290       6555   X-Y,X,Z+1/3                                             
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 -0.500000 -0.866025  0.000000        0.00000            
REMARK 290   SMTRY2   2  0.866025 -0.500000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000       86.34733            
REMARK 290   SMTRY1   3 -0.500000  0.866025  0.000000        0.00000            
REMARK 290   SMTRY2   3 -0.866025 -0.500000  0.000000        0.00000            
REMARK 290   SMTRY3   3  0.000000  0.000000  1.000000       43.17367            
REMARK 290   SMTRY1   4 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   4  0.000000  0.000000  1.000000        0.00000            
REMARK 290   SMTRY1   5  0.500000  0.866025  0.000000        0.00000            
REMARK 290   SMTRY2   5 -0.866025  0.500000  0.000000        0.00000            
REMARK 290   SMTRY3   5  0.000000  0.000000  1.000000       86.34733            
REMARK 290   SMTRY1   6  0.500000 -0.866025  0.000000        0.00000            
REMARK 290   SMTRY2   6  0.866025  0.500000  0.000000        0.00000            
REMARK 290   SMTRY3   6  0.000000  0.000000  1.000000       43.17367            
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     ASN A   221                                                      
REMARK 465     SER A   222                                                      
REMARK 465     PHE A   223                                                      
REMARK 465     GLY A   276                                                      
REMARK 465     CYS A   277                                                      
REMARK 465     GLN A   278                                                      
REMARK 465     VAL A   279                                                      
REMARK 465     GLU A   280                                                      
REMARK 465     GLY A   281                                                      
REMARK 465     ASP A   282                                                      
REMARK 465     ALA A   283                                                      
REMARK 465     ALA A   284                                                      
REMARK 465     GLU A   285                                                      
REMARK 465     THR A   286                                                      
REMARK 465     PRO A   287                                                      
REMARK 465     PRO A   288                                                      
REMARK 465     ARG A   289                                                      
REMARK 465     PRO A   290                                                      
REMARK 465     ARG A   291                                                      
REMARK 465     THR A   292                                                      
REMARK 465     PRO A   293                                                      
REMARK 465     GLY A   294                                                      
REMARK 465     ARG A   295                                                      
REMARK 465     PRO A   296                                                      
REMARK 465     LEU A   297                                                      
REMARK 465     SER A   298                                                      
REMARK 465     SER A   299                                                      
REMARK 465     TYR A   300                                                      
REMARK 465     GLY A   301                                                      
REMARK 465     MET A   302                                                      
REMARK 465     ASP A   303                                                      
REMARK 465     SER A   304                                                      
REMARK 465     ARG A   305                                                      
REMARK 465     GLN A   383                                                      
REMARK 465     PRO A   384                                                      
REMARK 465     SER A   385                                                      
REMARK 465     THR A   386                                                      
REMARK 465     PRO A   387                                                      
REMARK 465     THR A   388                                                      
REMARK 465     HIS A   389                                                      
REMARK 465     ALA A   390                                                      
REMARK 465     ALA A   391                                                      
REMARK 465     GLY A   392                                                      
REMARK 465     VAL A   393                                                      
REMARK 465     LEU A   394                                                      
REMARK 465     GLU A   395                                                      
REMARK 465     HIS A   396                                                      
REMARK 465     HIS A   397                                                      
REMARK 465     HIS A   398                                                      
REMARK 465     HIS A   399                                                      
REMARK 465     HIS A   400                                                      
REMARK 465     HIS A   401                                                      
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: COVALENT BOND LENGTHS                                      
REMARK 500                                                                      
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES              
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE               
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN               
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).                 
REMARK 500                                                                      
REMARK 500 STANDARD TABLE:                                                      
REMARK 500 FORMAT: (10X,I3,1X,2(A3,1X,A1,I4,A1,1X,A4,3X),1X,F6.3)               
REMARK 500                                                                      
REMARK 500 EXPECTED VALUES PROTEIN: ENGH AND HUBER, 1999                        
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996                     
REMARK 500                                                                      
REMARK 500  M RES CSSEQI ATM1   RES CSSEQI ATM2   DEVIATION                     
REMARK 500    LYS A 362   C     LYS A 362   O       0.145                       
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: TORSION ANGLES                                             
REMARK 500                                                                      
REMARK 500 TORSION ANGLES OUTSIDE THE EXPECTED RAMACHANDRAN REGIONS:            
REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;               
REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).                             
REMARK 500                                                                      
REMARK 500 STANDARD TABLE:                                                      
REMARK 500 FORMAT:(10X,I3,1X,A3,1X,A1,I4,A1,4X,F7.2,3X,F7.2)                    
REMARK 500                                                                      
REMARK 500 EXPECTED VALUES: GJ KLEYWEGT AND TA JONES (1996). PHI/PSI-           
REMARK 500 CHOLOGY: RAMACHANDRAN REVISITED. STRUCTURE 4, 1395 - 1400            
REMARK 500                                                                      
REMARK 500  M RES CSSEQI        PSI       PHI                                   
REMARK 500    ILE A  71      -63.34    -94.60                                   
REMARK 500    ASN A  78       53.29     18.07                                   
REMARK 500    GLU A 102       90.66    -66.98                                   
REMARK 500    SER A 135      -91.27   -102.31                                   
REMARK 500    ARG A 189       -7.02     88.60                                   
REMARK 500    ASP A 190       55.41   -156.50                                   
REMARK 500    SER A 241     -142.70   -173.22                                   
REMARK 500    GLU A 367      151.82    -46.01                                   
REMARK 500    LEU A 381      -75.47   -126.06                                   
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 620                                                                      
REMARK 620 METAL COORDINATION                                                   
REMARK 620 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;               
REMARK 620 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE):                             
REMARK 620                                                                      
REMARK 620 COORDINATION ANGLES FOR:  M RES CSSEQI METAL                         
REMARK 620                              MG A 503  MG                            
REMARK 620 N RES CSSEQI ATOM                                                    
REMARK 620 1 ASN A 195   OD1                                                    
REMARK 620 2 ASP A 208   OD2  81.3                                              
REMARK 620 3 ATP A 502   O1B  85.5 161.1                                        
REMARK 620 4 ATP A 502   O2A 152.0  87.4  98.2                                  
REMARK 620 N                    1     2     3                                   
REMARK 800                                                                      
REMARK 800 SITE                                                                 
REMARK 800 SITE_IDENTIFIER: AC1                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 3V0 A 501                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE ATP A 502                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC3                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE MG A 503                  
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 3V04   RELATED DB: PDB                                   
DBREF  3V01 A   62   393  UNP    Q02750   MP2K1_HUMAN     62    393             
SEQADV 3V01 MET A   61  UNP  Q02750              EXPRESSION TAG                 
SEQADV 3V01 LEU A  394  UNP  Q02750              EXPRESSION TAG                 
SEQADV 3V01 GLU A  395  UNP  Q02750              EXPRESSION TAG                 
SEQADV 3V01 HIS A  396  UNP  Q02750              EXPRESSION TAG                 
SEQADV 3V01 HIS A  397  UNP  Q02750              EXPRESSION TAG                 
SEQADV 3V01 HIS A  398  UNP  Q02750              EXPRESSION TAG                 
SEQADV 3V01 HIS A  399  UNP  Q02750              EXPRESSION TAG                 
SEQADV 3V01 HIS A  400  UNP  Q02750              EXPRESSION TAG                 
SEQADV 3V01 HIS A  401  UNP  Q02750              EXPRESSION TAG                 
SEQRES   1 A  341  MET GLU LEU LYS ASP ASP ASP PHE GLU LYS ILE SER GLU          
SEQRES   2 A  341  LEU GLY ALA GLY ASN GLY GLY VAL VAL PHE LYS VAL SER          
SEQRES   3 A  341  HIS LYS PRO SER GLY LEU VAL MET ALA ARG LYS LEU ILE          
SEQRES   4 A  341  HIS LEU GLU ILE LYS PRO ALA ILE ARG ASN GLN ILE ILE          
SEQRES   5 A  341  ARG GLU LEU GLN VAL LEU HIS GLU CYS ASN SER PRO TYR          
SEQRES   6 A  341  ILE VAL GLY PHE TYR GLY ALA PHE TYR SER ASP GLY GLU          
SEQRES   7 A  341  ILE SER ILE CYS MET GLU HIS MET ASP GLY GLY SER LEU          
SEQRES   8 A  341  ASP GLN VAL LEU LYS LYS ALA GLY ARG ILE PRO GLU GLN          
SEQRES   9 A  341  ILE LEU GLY LYS VAL SER ILE ALA VAL ILE LYS GLY LEU          
SEQRES  10 A  341  THR TYR LEU ARG GLU LYS HIS LYS ILE MET HIS ARG ASP          
SEQRES  11 A  341  VAL LYS PRO SER ASN ILE LEU VAL ASN SER ARG GLY GLU          
SEQRES  12 A  341  ILE LYS LEU CYS ASP PHE GLY VAL SER GLY GLN LEU ILE          
SEQRES  13 A  341  ASP SER MET ALA ASN SER PHE VAL GLY THR ARG SER TYR          
SEQRES  14 A  341  MET SER PRO GLU ARG LEU GLN GLY THR HIS TYR SER VAL          
SEQRES  15 A  341  GLN SER ASP ILE TRP SER MET GLY LEU SER LEU VAL GLU          
SEQRES  16 A  341  MET ALA VAL GLY ARG TYR PRO ILE PRO PRO PRO ASP ALA          
SEQRES  17 A  341  LYS GLU LEU GLU LEU MET PHE GLY CYS GLN VAL GLU GLY          
SEQRES  18 A  341  ASP ALA ALA GLU THR PRO PRO ARG PRO ARG THR PRO GLY          
SEQRES  19 A  341  ARG PRO LEU SER SER TYR GLY MET ASP SER ARG PRO PRO          
SEQRES  20 A  341  MET ALA ILE PHE GLU LEU LEU ASP TYR ILE VAL ASN GLU          
SEQRES  21 A  341  PRO PRO PRO LYS LEU PRO SER GLY VAL PHE SER LEU GLU          
SEQRES  22 A  341  PHE GLN ASP PHE VAL ASN LYS CYS LEU ILE LYS ASN PRO          
SEQRES  23 A  341  ALA GLU ARG ALA ASP LEU LYS GLN LEU MET VAL HIS ALA          
SEQRES  24 A  341  PHE ILE LYS ARG SER ASP ALA GLU GLU VAL ASP PHE ALA          
SEQRES  25 A  341  GLY TRP LEU CYS SER THR ILE GLY LEU ASN GLN PRO SER          
SEQRES  26 A  341  THR PRO THR HIS ALA ALA GLY VAL LEU GLU HIS HIS HIS          
SEQRES  27 A  341  HIS HIS HIS                                                  
HET    3V0  A 501      27                                                       
HET    ATP  A 502      31                                                       
HET     MG  A 503       1                                                       
HETNAM     3V0 N-{[(2R)-2,3-DIHYDROXYPROPYL]OXY}-3-[(2-FLUORO-4-                
HETNAM   2 3V0  IODOPHENYL)AMINO]FURO[3,2-C]PYRIDINE-2-CARBOXAMIDE              
HETNAM     ATP ADENOSINE-5'-TRIPHOSPHATE                                        
HETNAM      MG MAGNESIUM ION                                                    
FORMUL   2  3V0    C17 H15 F I N3 O5                                            
FORMUL   3  ATP    C10 H16 N5 O13 P3                                            
FORMUL   4   MG    MG 2+                                                        
HELIX    1   1 LYS A   64  ASP A   66  5                                   3    
HELIX    2   2 ALA A  106  GLN A  116  1                                  11    
HELIX    3   3 VAL A  117  CYS A  121  5                                   5    
HELIX    4   4 SER A  150  GLY A  159  1                                  10    
HELIX    5   5 PRO A  162  LYS A  185  1                                  24    
HELIX    6   6 LYS A  192  SER A  194  5                                   3    
HELIX    7   7 SER A  212  ALA A  220  1                                   9    
HELIX    8   8 SER A  231  GLY A  237  1                                   7    
HELIX    9   9 VAL A  242  GLY A  259  1                                  18    
HELIX   10  10 ASP A  267  PHE A  275  1                                   9    
HELIX   11  11 ALA A  309  GLU A  320  1                                  12    
HELIX   12  12 SER A  331  LEU A  342  1                                  12    
HELIX   13  13 ASP A  351  VAL A  357  1                                   7    
HELIX   14  14 HIS A  358  GLU A  367  1                                  10    
HELIX   15  15 ASP A  370  GLY A  380  1                                  11    
SHEET    1   A 5 PHE A  68  ALA A  76  0                                        
SHEET    2   A 5 VAL A  81  HIS A  87 -1  O  LYS A  84   N  ILE A  71           
SHEET    3   A 5 VAL A  93  HIS A 100 -1  O  ARG A  96   N  PHE A  83           
SHEET    4   A 5 GLU A 138  GLU A 144 -1  O  MET A 143   N  ALA A  95           
SHEET    5   A 5 PHE A 129  TYR A 134 -1  N  PHE A 133   O  SER A 140           
SHEET    1   B 2 ILE A 196  VAL A 198  0                                        
SHEET    2   B 2 ILE A 204  LEU A 206 -1  O  LYS A 205   N  LEU A 197           
LINK         OD1 ASN A 195                MG    MG A 503     1555   1555  2.23  
LINK         OD2 ASP A 208                MG    MG A 503     1555   1555  1.99  
LINK         O1B ATP A 502                MG    MG A 503     1555   1555  1.91  
LINK         O2A ATP A 502                MG    MG A 503     1555   1555  2.01  
CISPEP   1 ILE A  263    PRO A  264          0         2.19                     
SITE     1 AC1 14 GLY A  77  ASN A  78  GLY A  80  LYS A  97                    
SITE     2 AC1 14 VAL A 127  ILE A 141  ASP A 208  PHE A 209                    
SITE     3 AC1 14 GLY A 210  VAL A 211  SER A 212  LEU A 215                    
SITE     4 AC1 14 MET A 219  ATP A 502                                          
SITE     1 AC2 18 ALA A  76  GLY A  77  ASN A  78  GLY A  80                    
SITE     2 AC2 18 VAL A  82  ALA A  95  LYS A  97  MET A 143                    
SITE     3 AC2 18 GLU A 144  MET A 146  SER A 150  GLN A 153                    
SITE     4 AC2 18 LYS A 192  SER A 194  ASN A 195  ASP A 208                    
SITE     5 AC2 18 3V0 A 501   MG A 503                                          
SITE     1 AC3  4 LYS A  97  ASN A 195  ASP A 208  ATP A 502                    
CRYST1   81.619   81.619  129.521  90.00  90.00 120.00 P 62          6          
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      0.012252  0.007074  0.000000        0.00000                         
SCALE2      0.000000  0.014147  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.007721        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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