GenomeNet

Database: PDB
Entry: 4KAK
LinkDB: 4KAK
Original site: 4KAK 
HEADER    OXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR 22-APR-13   4KAK              
TITLE     CRYSTAL STRUCTURE OF HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH     
TITLE    2 NADPH AND 6-ETHYL-5-[(3S)-3-[3-METHOXY-5-(PYRIDINE-4-YL)PHENYL]BUT-1-
TITLE    3 YN-1-YL]PYRIMIDINE-2,4-DIAMINE (UCP1006)                             
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: DIHYDROFOLATE REDUCTASE;                                   
COMPND   3 CHAIN: A, B;                                                         
COMPND   4 EC: 1.5.1.3;                                                         
COMPND   5 ENGINEERED: YES                                                      
SOURCE    MOL_ID: 1;                                                            
SOURCE   2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;                                   
SOURCE   3 ORGANISM_COMMON: HUMAN;                                              
SOURCE   4 ORGANISM_TAXID: 9606;                                                
SOURCE   5 STRAIN: RP11-399L5;                                                  
SOURCE   6 GENE: DHFR, HUDHFR;                                                  
SOURCE   7 EXPRESSION_SYSTEM: ESCHERICHIA COLI;                                 
SOURCE   8 EXPRESSION_SYSTEM_TAXID: 469008;                                     
SOURCE   9 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);                                 
SOURCE  10 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;                              
SOURCE  11 EXPRESSION_SYSTEM_PLASMID: PET41A(+)                                 
KEYWDS    OXIDOREDUCTASE, 5,6,7,8-TETRAHYDROFOLATE; NADP+; 7,8-DIHYDROFOLATE,   
KEYWDS   2 HYDRIDE SHIFT, OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR COMPLEX       
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    K.M.LAMB,A.C.ANDERSON                                                 
REVDAT   3   20-NOV-13 4KAK    1       HET    HETATM HETNAM REMARK              
REVDAT   2   30-OCT-13 4KAK    1       JRNL                                     
REVDAT   1   09-OCT-13 4KAK    0                                                
JRNL        AUTH   K.M.LAMB,N.G-DAYANANDAN,D.L.WRIGHT,A.C.ANDERSON              
JRNL        TITL   ELUCIDATING FEATURES THAT DRIVE THE DESIGN OF SELECTIVE      
JRNL        TITL 2 ANTIFOLATES USING CRYSTAL STRUCTURES OF HUMAN DIHYDROFOLATE  
JRNL        TITL 3 REDUCTASE.                                                   
JRNL        REF    BIOCHEMISTRY                  V.  52  7318 2013              
JRNL        REFN                   ISSN 0006-2960                               
JRNL        PMID   24053334                                                     
JRNL        DOI    10.1021/BI400852H                                            
REMARK   2                                                                      
REMARK   2 RESOLUTION.    1.80 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : PHENIX                                               
REMARK   3   AUTHORS     : PAUL ADAMS,PAVEL AFONINE,VICENT CHEN,IAN             
REMARK   3               : DAVIS,KRESHNA GOPAL,RALF GROSSE-                     
REMARK   3               : KUNSTLEVE,LI-WEI HUNG,ROBERT IMMORMINO,              
REMARK   3               : TOM IOERGER,AIRLIE MCCOY,ERIK MCKEE,NIGEL            
REMARK   3               : MORIARTY,REETAL PAI,RANDY READ,JANE                  
REMARK   3               : RICHARDSON,DAVID RICHARDSON,TOD ROMO,JIM             
REMARK   3               : SACCHETTINI,NICHOLAS SAUTER,JACOB SMITH,             
REMARK   3               : LAURENT STORONI,TOM TERWILLIGER,PETER                
REMARK   3               : ZWART                                                
REMARK   3                                                                      
REMARK   3    REFINEMENT TARGET : ENGH & HUBER                                  
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 1.80                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 32.08                          
REMARK   3   MIN(FOBS/SIGMA_FOBS)              : NULL                           
REMARK   3   COMPLETENESS FOR RANGE        (%) : 99.5                           
REMARK   3   NUMBER OF REFLECTIONS             : 36923                          
REMARK   3                                                                      
REMARK   3  FIT TO DATA USED IN REFINEMENT.                                     
REMARK   3   R VALUE     (WORKING + TEST SET) : 0.225                           
REMARK   3   R VALUE            (WORKING SET) : 0.223                           
REMARK   3   FREE R VALUE                     : 0.269                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 5.000                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 1845                            
REMARK   3                                                                      
REMARK   3  FIT TO DATA USED IN REFINEMENT (IN BINS).                           
REMARK   3   BIN  RESOLUTION RANGE  COMPL.    NWORK NFREE   RWORK  RFREE        
REMARK   3     1 32.0823 -  4.2295    0.98     2816   147  0.1716 0.1885        
REMARK   3     2  4.2295 -  3.3583    0.99     2722   160  0.1666 0.2153        
REMARK   3     3  3.3583 -  2.9341    1.00     2706   158  0.2185 0.2860        
REMARK   3     4  2.9341 -  2.6660    1.00     2692   142  0.2490 0.3038        
REMARK   3     5  2.6660 -  2.4750    1.00     2701   139  0.2503 0.3096        
REMARK   3     6  2.4750 -  2.3291    1.00     2698   149  0.2562 0.3172        
REMARK   3     7  2.3291 -  2.2125    0.99     2675   150  0.2742 0.3351        
REMARK   3     8  2.2125 -  2.1162    1.00     2712   131  0.2709 0.3076        
REMARK   3     9  2.1162 -  2.0347    1.00     2665   129  0.2737 0.3336        
REMARK   3    10  2.0347 -  1.9645    1.00     2706   122  0.3078 0.4351        
REMARK   3    11  1.9645 -  1.9031    1.00     2691   130  0.3102 0.3314        
REMARK   3    12  1.9031 -  1.8487    0.99     2655   136  0.3310 0.3792        
REMARK   3    13  1.8487 -  1.8001    1.00     2639   152  0.3318 0.3869        
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELLING.                                             
REMARK   3   METHOD USED        : FLAT BULK SOLVENT MODEL                       
REMARK   3   SOLVENT RADIUS     : 1.11                                          
REMARK   3   SHRINKAGE RADIUS   : 0.90                                          
REMARK   3   K_SOL              : NULL                                          
REMARK   3   B_SOL              : NULL                                          
REMARK   3                                                                      
REMARK   3  ERROR ESTIMATES.                                                    
REMARK   3   COORDINATE ERROR (MAXIMUM-LIKELIHOOD BASED)     : 0.270            
REMARK   3   PHASE ERROR (DEGREES, MAXIMUM-LIKELIHOOD BASED) : 30.180           
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 31.21                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 18.17                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : NULL                                                 
REMARK   3    B22 (A**2) : NULL                                                 
REMARK   3    B33 (A**2) : NULL                                                 
REMARK   3    B12 (A**2) : NULL                                                 
REMARK   3    B13 (A**2) : NULL                                                 
REMARK   3    B23 (A**2) : NULL                                                 
REMARK   3                                                                      
REMARK   3  TWINNING INFORMATION.                                               
REMARK   3   FRACTION: NULL                                                     
REMARK   3   OPERATOR: NULL                                                     
REMARK   3                                                                      
REMARK   3  DEVIATIONS FROM IDEAL VALUES.                                       
REMARK   3                 RMSD          COUNT                                  
REMARK   3   BOND      :   NULL           NULL                                  
REMARK   3   ANGLE     :   NULL           NULL                                  
REMARK   3   CHIRALITY :   NULL           NULL                                  
REMARK   3   PLANARITY :   NULL           NULL                                  
REMARK   3   DIHEDRAL  :   NULL           NULL                                  
REMARK   3                                                                      
REMARK   3  TLS DETAILS                                                         
REMARK   3   NUMBER OF TLS GROUPS  : NULL                                       
REMARK   3                                                                      
REMARK   3  NCS DETAILS                                                         
REMARK   3   NUMBER OF NCS GROUPS : NULL                                        
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: NULL                                      
REMARK   4                                                                      
REMARK   4 4KAK COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 01-MAY-13.                  
REMARK 100 THE RCSB ID CODE IS RCSB079098.                                      
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 11-JUN-11                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : 7.5                                
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : N                                  
REMARK 200  RADIATION SOURCE               : ROTATING ANODE                     
REMARK 200  BEAMLINE                       : NULL                               
REMARK 200  X-RAY GENERATOR MODEL          : RIGAKU                             
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.5418                             
REMARK 200  MONOCHROMATOR                  : NULL                               
REMARK 200  OPTICS                         : VARIMAX OPTICS                     
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : CCD                                
REMARK 200  DETECTOR MANUFACTURER          : RIGAKU RAXIS IV                    
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : STRUCTURESTUDIO                    
REMARK 200  DATA SCALING SOFTWARE          : STRUCTURESTUDIO                    
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 37016                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 1.800                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 46.820                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : 0.000                              
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 99.8                               
REMARK 200  DATA REDUNDANCY                : 3.950                              
REMARK 200  R MERGE                    (I) : 0.06100                            
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 8.3000                             
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.80                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 1.86                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : NULL                               
REMARK 200  DATA REDUNDANCY IN SHELL       : 3.88                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.49200                            
REMARK 200  R SYM FOR SHELL            (I) : 0.55400                            
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 1.000                              
REMARK 200                                                                      
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH                              
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT        
REMARK 200 SOFTWARE USED: PHASER FOR MR                                         
REMARK 200 STARTING MODEL: 2C2S                                                 
REMARK 200                                                                      
REMARK 200 REMARK: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 46.99                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.32                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1M TRIS-HCL PH 7.4, 0.2M LITHIUM       
REMARK 280  SULFATE, 30% (W/V) PEG 4000, 8% (V/V) ETHANOL, 11MM CACL2, VAPOR    
REMARK 280  DIFFUSION, HANGING DROP, TEMPERATURE 277K                           
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY                                            
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: C 2 2 21                         
REMARK 290                                                                      
REMARK 290      SYMOP   SYMMETRY                                                
REMARK 290     NNNMMM   OPERATOR                                                
REMARK 290       1555   X,Y,Z                                                   
REMARK 290       2555   -X,-Y,Z+1/2                                             
REMARK 290       3555   -X,Y,-Z+1/2                                             
REMARK 290       4555   X,-Y,-Z                                                 
REMARK 290       5555   X+1/2,Y+1/2,Z                                           
REMARK 290       6555   -X+1/2,-Y+1/2,Z+1/2                                     
REMARK 290       7555   -X+1/2,Y+1/2,-Z+1/2                                     
REMARK 290       8555   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       48.01950            
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000       48.01950            
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  1.000000  0.000000  0.000000       44.03850            
REMARK 290   SMTRY2   5  0.000000  1.000000  0.000000       46.81700            
REMARK 290   SMTRY3   5  0.000000  0.000000  1.000000        0.00000            
REMARK 290   SMTRY1   6 -1.000000  0.000000  0.000000       44.03850            
REMARK 290   SMTRY2   6  0.000000 -1.000000  0.000000       46.81700            
REMARK 290   SMTRY3   6  0.000000  0.000000  1.000000       48.01950            
REMARK 290   SMTRY1   7 -1.000000  0.000000  0.000000       44.03850            
REMARK 290   SMTRY2   7  0.000000  1.000000  0.000000       46.81700            
REMARK 290   SMTRY3   7  0.000000  0.000000 -1.000000       48.01950            
REMARK 290   SMTRY1   8  1.000000  0.000000  0.000000       44.03850            
REMARK 290   SMTRY2   8  0.000000 -1.000000  0.000000       46.81700            
REMARK 290   SMTRY3   8  0.000000  0.000000 -1.000000        0.00000            
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 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 350                                                                      
REMARK 350 BIOMOLECULE: 2                                                       
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: 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 375                                                                      
REMARK 375 SPECIAL POSITION                                                     
REMARK 375 THE FOLLOWING ATOMS ARE FOUND TO BE WITHIN 0.15 ANGSTROMS            
REMARK 375 OF A SYMMETRY RELATED ATOM AND ARE ASSUMED TO BE ON SPECIAL          
REMARK 375 POSITIONS.                                                           
REMARK 375                                                                      
REMARK 375 ATOM RES CSSEQI                                                      
REMARK 375      HOH A 405  LIES ON A SPECIAL POSITION.                          
REMARK 375      HOH A 346  LIES ON A SPECIAL POSITION.                          
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    ASP A 110      -95.71    -91.78                                   
REMARK 500    MET A 139       47.70    -89.20                                   
REMARK 500    ASP B 110      -97.78    -89.14                                   
REMARK 500    MET B 139       49.74    -89.10                                   
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                              CA A 206  CA                            
REMARK 620 N RES CSSEQI ATOM                                                    
REMARK 620 1 HOH A 381   O                                                      
REMARK 620 2 SER A   3   OG   86.5                                              
REMARK 620 3 ASN A   5   OD1  97.0 124.5                                        
REMARK 620 4 HOH A 438   O   104.7 121.7 110.8                                  
REMARK 620 N                    1     2     3                                   
REMARK 620                                                                      
REMARK 620 COORDINATION ANGLES FOR:  M RES CSSEQI METAL                         
REMARK 620                              CA B 207  CA                            
REMARK 620 N RES CSSEQI ATOM                                                    
REMARK 620 1 HOH B 388   O                                                      
REMARK 620 2 HOH A 383   O   153.2                                              
REMARK 620 3 GLU B 183   OE1 104.9  79.1                                        
REMARK 620 N                    1     2                                         
REMARK 620                                                                      
REMARK 620 COORDINATION ANGLES FOR:  M RES CSSEQI METAL                         
REMARK 620                              CA B 205  CA                            
REMARK 620 N RES CSSEQI ATOM                                                    
REMARK 620 1 HOH B 390   O                                                      
REMARK 620 2 HOH B 428   O    98.6                                              
REMARK 620 3 HOH B 438   O   122.1 109.3                                        
REMARK 620 4 ARG B  32   O   138.8  95.2  88.8                                  
REMARK 620 N                    1     2     3                                   
REMARK 620                                                                      
REMARK 620 COORDINATION ANGLES FOR:  M RES CSSEQI METAL                         
REMARK 620                              CA B 206  CA                            
REMARK 620 N RES CSSEQI ATOM                                                    
REMARK 620 1 HOH B 317   O                                                      
REMARK 620 2 HOH B 380   O   105.7                                              
REMARK 620 3 ILE B 138   O   131.1 108.6                                        
REMARK 620 N                    1     2                                         
REMARK 800                                                                      
REMARK 800 SITE                                                                 
REMARK 800 SITE_IDENTIFIER: AC1                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NDP A 201                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 06U A 202                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC3                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE EOH A 203                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC4                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE EOH A 204                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC5                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE EOH A 205                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC6                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CA A 206                  
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC7                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NDP B 201                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC8                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 06U B 202                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC9                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE EOH B 203                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: BC1                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE EOH B 204                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: BC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CA B 205                  
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: BC3                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CA B 206                  
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: BC4                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CA B 207                  
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 4KBN   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4KD7   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4KEB   RELATED DB: PDB                                   
REMARK 900 RELATED ID: 4KFJ   RELATED DB: PDB                                   
DBREF  4KAK A    1   186  UNP    P00374   DYR_HUMAN        2    187             
DBREF  4KAK B    1   186  UNP    P00374   DYR_HUMAN        2    187             
SEQRES   1 A  186  VAL GLY SER LEU ASN CYS ILE VAL ALA VAL SER GLN ASN          
SEQRES   2 A  186  MET GLY ILE GLY LYS ASN GLY ASP LEU PRO TRP PRO PRO          
SEQRES   3 A  186  LEU ARG ASN GLU PHE ARG TYR PHE GLN ARG MET THR THR          
SEQRES   4 A  186  THR SER SER VAL GLU GLY LYS GLN ASN LEU VAL ILE MET          
SEQRES   5 A  186  GLY LYS LYS THR TRP PHE SER ILE PRO GLU LYS ASN ARG          
SEQRES   6 A  186  PRO LEU LYS GLY ARG ILE ASN LEU VAL LEU SER ARG GLU          
SEQRES   7 A  186  LEU LYS GLU PRO PRO GLN GLY ALA HIS PHE LEU SER ARG          
SEQRES   8 A  186  SER LEU ASP ASP ALA LEU LYS LEU THR GLU GLN PRO GLU          
SEQRES   9 A  186  LEU ALA ASN LYS VAL ASP MET VAL TRP ILE VAL GLY GLY          
SEQRES  10 A  186  SER SER VAL TYR LYS GLU ALA MET ASN HIS PRO GLY HIS          
SEQRES  11 A  186  LEU LYS LEU PHE VAL THR ARG ILE MET GLN ASP PHE GLU          
SEQRES  12 A  186  SER ASP THR PHE PHE PRO GLU ILE ASP LEU GLU LYS TYR          
SEQRES  13 A  186  LYS LEU LEU PRO GLU TYR PRO GLY VAL LEU SER ASP VAL          
SEQRES  14 A  186  GLN GLU GLU LYS GLY ILE LYS TYR LYS PHE GLU VAL TYR          
SEQRES  15 A  186  GLU LYS ASN ASP                                              
SEQRES   1 B  186  VAL GLY SER LEU ASN CYS ILE VAL ALA VAL SER GLN ASN          
SEQRES   2 B  186  MET GLY ILE GLY LYS ASN GLY ASP LEU PRO TRP PRO PRO          
SEQRES   3 B  186  LEU ARG ASN GLU PHE ARG TYR PHE GLN ARG MET THR THR          
SEQRES   4 B  186  THR SER SER VAL GLU GLY LYS GLN ASN LEU VAL ILE MET          
SEQRES   5 B  186  GLY LYS LYS THR TRP PHE SER ILE PRO GLU LYS ASN ARG          
SEQRES   6 B  186  PRO LEU LYS GLY ARG ILE ASN LEU VAL LEU SER ARG GLU          
SEQRES   7 B  186  LEU LYS GLU PRO PRO GLN GLY ALA HIS PHE LEU SER ARG          
SEQRES   8 B  186  SER LEU ASP ASP ALA LEU LYS LEU THR GLU GLN PRO GLU          
SEQRES   9 B  186  LEU ALA ASN LYS VAL ASP MET VAL TRP ILE VAL GLY GLY          
SEQRES  10 B  186  SER SER VAL TYR LYS GLU ALA MET ASN HIS PRO GLY HIS          
SEQRES  11 B  186  LEU LYS LEU PHE VAL THR ARG ILE MET GLN ASP PHE GLU          
SEQRES  12 B  186  SER ASP THR PHE PHE PRO GLU ILE ASP LEU GLU LYS TYR          
SEQRES  13 B  186  LYS LEU LEU PRO GLU TYR PRO GLY VAL LEU SER ASP VAL          
SEQRES  14 B  186  GLN GLU GLU LYS GLY ILE LYS TYR LYS PHE GLU VAL TYR          
SEQRES  15 B  186  GLU LYS ASN ASP                                              
HET    NDP  A 201      48                                                       
HET    06U  A 202      28                                                       
HET    EOH  A 203       3                                                       
HET    EOH  A 204       3                                                       
HET    EOH  A 205       3                                                       
HET     CA  A 206       1                                                       
HET    NDP  B 201      48                                                       
HET    06U  B 202      28                                                       
HET    EOH  B 203       3                                                       
HET    EOH  B 204       3                                                       
HET     CA  B 205       1                                                       
HET     CA  B 206       1                                                       
HET     CA  B 207       1                                                       
HETNAM     NDP NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE                  
HETNAM   2 NDP  PHOSPHATE                                                       
HETNAM     06U 6-ETHYL-5-{(3R)-3-[3-METHOXY-5-(PYRIDIN-4-YL)                    
HETNAM   2 06U  PHENYL]BUT-1-YN-1-YL}PYRIMIDINE-2,4-DIAMINE                     
HETNAM     EOH ETHANOL                                                          
HETNAM      CA CALCIUM ION                                                      
FORMUL   3  NDP    2(C21 H30 N7 O17 P3)                                         
FORMUL   4  06U    2(C22 H23 N5 O)                                              
FORMUL   5  EOH    5(C2 H6 O)                                                   
FORMUL   8   CA    4(CA 2+)                                                     
FORMUL  16  HOH   *347(H2 O)                                                    
HELIX    1   1 LEU A   27  THR A   40  1                                  14    
HELIX    2   2 LYS A   54  ILE A   60  1                                   7    
HELIX    3   3 PRO A   61  ARG A   65  5                                   5    
HELIX    4   4 SER A   92  THR A  100  1                                   9    
HELIX    5   5 GLY A  117  ASN A  126  1                                  10    
HELIX    6   6 LEU B   27  THR B   40  1                                  14    
HELIX    7   7 GLY B   53  ILE B   60  1                                   8    
HELIX    8   8 PRO B   61  ARG B   65  5                                   5    
HELIX    9   9 SER B   92  THR B  100  1                                   9    
HELIX   10  10 GLY B  117  ASN B  126  1                                  10    
SHEET    1   A 8 PHE A  88  SER A  90  0                                        
SHEET    2   A 8 ILE A  71  LEU A  75  1  N  VAL A  74   O  PHE A  88           
SHEET    3   A 8 GLN A  47  GLY A  53  1  N  VAL A  50   O  ILE A  71           
SHEET    4   A 8 VAL A 109  ILE A 114  1  O  TRP A 113   N  LEU A  49           
SHEET    5   A 8 SER A   3  VAL A  10  1  N  ASN A   5   O  ILE A 114           
SHEET    6   A 8 HIS A 130  ILE A 138  1  O  PHE A 134   N  CYS A   6           
SHEET    7   A 8 ILE A 175  LYS A 184 -1  O  LYS A 178   N  ARG A 137           
SHEET    8   A 8 LYS A 157  LEU A 158 -1  N  LYS A 157   O  GLU A 183           
SHEET    1   B 8 PHE A  88  SER A  90  0                                        
SHEET    2   B 8 ILE A  71  LEU A  75  1  N  VAL A  74   O  PHE A  88           
SHEET    3   B 8 GLN A  47  GLY A  53  1  N  VAL A  50   O  ILE A  71           
SHEET    4   B 8 VAL A 109  ILE A 114  1  O  TRP A 113   N  LEU A  49           
SHEET    5   B 8 SER A   3  VAL A  10  1  N  ASN A   5   O  ILE A 114           
SHEET    6   B 8 HIS A 130  ILE A 138  1  O  PHE A 134   N  CYS A   6           
SHEET    7   B 8 ILE A 175  LYS A 184 -1  O  LYS A 178   N  ARG A 137           
SHEET    8   B 8 GLN A 170  GLU A 172 -1  N  GLN A 170   O  TYR A 177           
SHEET    1   C 2 GLY A  15  GLY A  17  0                                        
SHEET    2   C 2 THR A 146  PHE A 147 -1  O  THR A 146   N  ILE A  16           
SHEET    1   D 8 PHE B  88  SER B  90  0                                        
SHEET    2   D 8 ILE B  71  LEU B  75  1  N  VAL B  74   O  PHE B  88           
SHEET    3   D 8 GLN B  47  MET B  52  1  N  MET B  52   O  LEU B  75           
SHEET    4   D 8 VAL B 109  ILE B 114  1  O  TRP B 113   N  LEU B  49           
SHEET    5   D 8 SER B   3  VAL B  10  1  N  ASN B   5   O  ILE B 114           
SHEET    6   D 8 HIS B 130  ILE B 138  1  O  PHE B 134   N  CYS B   6           
SHEET    7   D 8 ILE B 175  LYS B 184 -1  O  TYR B 182   N  LEU B 133           
SHEET    8   D 8 LYS B 157  LEU B 158 -1  N  LYS B 157   O  GLU B 183           
SHEET    1   E 8 PHE B  88  SER B  90  0                                        
SHEET    2   E 8 ILE B  71  LEU B  75  1  N  VAL B  74   O  PHE B  88           
SHEET    3   E 8 GLN B  47  MET B  52  1  N  MET B  52   O  LEU B  75           
SHEET    4   E 8 VAL B 109  ILE B 114  1  O  TRP B 113   N  LEU B  49           
SHEET    5   E 8 SER B   3  VAL B  10  1  N  ASN B   5   O  ILE B 114           
SHEET    6   E 8 HIS B 130  ILE B 138  1  O  PHE B 134   N  CYS B   6           
SHEET    7   E 8 ILE B 175  LYS B 184 -1  O  TYR B 182   N  LEU B 133           
SHEET    8   E 8 GLN B 170  GLU B 172 -1  N  GLN B 170   O  TYR B 177           
SHEET    1   F 2 GLY B  15  GLY B  17  0                                        
SHEET    2   F 2 THR B 146  PHE B 147 -1  O  THR B 146   N  ILE B  16           
LINK        CA    CA A 206                 O   HOH A 381     1555   1555  2.47  
LINK        CA    CA B 207                 O   HOH B 388     1555   1555  2.53  
LINK         OG  SER A   3                CA    CA A 206     1555   1555  2.54  
LINK        CA    CA B 205                 O   HOH B 390     1555   1555  2.55  
LINK        CA    CA B 206                 O   HOH B 317     1555   1555  2.59  
LINK        CA    CA B 206                 O   HOH B 380     1555   1555  2.60  
LINK        CA    CA B 207                 O   HOH A 383     1555   1555  2.62  
LINK         OE1 GLU B 183                CA    CA B 207     1555   1555  2.71  
LINK         OD1 ASN A   5                CA    CA A 206     1555   1555  2.77  
LINK        CA    CA A 206                 O   HOH A 438     1555   1555  2.80  
LINK        CA    CA B 205                 O   HOH B 428     1555   1555  2.83  
LINK        CA    CA B 205                 O   HOH B 438     1555   1555  2.87  
LINK         O   ARG B  32                CA    CA B 205     1555   1555  2.92  
LINK         O   ILE B 138                CA    CA B 206     1555   1555  2.94  
CISPEP   1 ARG A   65    PRO A   66          0        -6.15                     
CISPEP   2 GLY A  116    GLY A  117          0         5.09                     
CISPEP   3 ARG B   65    PRO B   66          0        -6.45                     
CISPEP   4 GLY B  116    GLY B  117          0         2.24                     
SITE     1 AC1 29 VAL A   8  ALA A   9  ILE A  16  GLY A  17                    
SITE     2 AC1 29 GLY A  20  ASP A  21  LEU A  22  GLY A  53                    
SITE     3 AC1 29 LYS A  54  LYS A  55  THR A  56  SER A  59                    
SITE     4 AC1 29 LEU A  75  SER A  76  ARG A  77  GLU A  78                    
SITE     5 AC1 29 ARG A  91  VAL A 115  GLY A 117  SER A 118                    
SITE     6 AC1 29 SER A 119  VAL A 120  TYR A 121  GLU A 123                    
SITE     7 AC1 29 THR A 146  06U A 202  HOH A 326  HOH A 372                    
SITE     8 AC1 29 HOH A 416                                                     
SITE     1 AC2 16 ILE A   7  VAL A   8  ALA A   9  ASP A  21                    
SITE     2 AC2 16 GLU A  30  PHE A  31  PHE A  34  SER A  59                    
SITE     3 AC2 16 PRO A  61  ASN A  64  LEU A  67  VAL A 115                    
SITE     4 AC2 16 TYR A 121  THR A 136  NDP A 201  HOH A 454                    
SITE     1 AC3  5 ASP A  21  LEU A  22  TRP A  24  HOH A 380                    
SITE     2 AC3  5 GLU B 161                                                     
SITE     1 AC4  2 GLY A   2  GLU B 171                                          
SITE     1 AC5  3 GLN A  47  LYS A  68  GLY A  69                               
SITE     1 AC6  5 SER A   3  ASN A   5  LYS A 132  HOH A 381                    
SITE     2 AC6  5 HOH A 438                                                     
SITE     1 AC7 30 VAL B   8  ALA B   9  ILE B  16  GLY B  17                    
SITE     2 AC7 30 GLY B  20  ASP B  21  TRP B  24  GLY B  53                    
SITE     3 AC7 30 LYS B  54  LYS B  55  THR B  56  SER B  59                    
SITE     4 AC7 30 LEU B  75  SER B  76  ARG B  77  GLU B  78                    
SITE     5 AC7 30 ARG B  91  VAL B 115  GLY B 117  SER B 118                    
SITE     6 AC7 30 SER B 119  VAL B 120  GLU B 123  THR B 146                    
SITE     7 AC7 30 06U B 202  HOH B 309  HOH B 320  HOH B 395                    
SITE     8 AC7 30 HOH B 409  HOH B 414                                          
SITE     1 AC8 13 ILE B   7  VAL B   8  ALA B   9  ASP B  21                    
SITE     2 AC8 13 GLU B  30  PHE B  31  PHE B  34  SER B  59                    
SITE     3 AC8 13 PRO B  61  ASN B  64  VAL B 115  THR B 136                    
SITE     4 AC8 13 NDP B 201                                                     
SITE     1 AC9  3 LYS A 157  PRO B  61  GLU B  62                               
SITE     1 BC1  2 GLU A  62  LYS B 157                                          
SITE     1 BC2  4 ARG B  32  HOH B 390  HOH B 428  HOH B 438                    
SITE     1 BC3  6 VAL B  10  GLN B  12  ARG B 137  ILE B 138                    
SITE     2 BC3  6 HOH B 317  HOH B 380                                          
SITE     1 BC4  6 PRO A  25  LYS A 173  HOH A 383  TYR B 162                    
SITE     2 BC4  6 GLU B 183  HOH B 388                                          
CRYST1   88.077   93.634   96.039  90.00  90.00  90.00 C 2 2 21     16          
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      0.011354  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.010680  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.010412        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
DBGET integrated database retrieval system