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Database: PDB
Entry: 2W3B
LinkDB: 2W3B
Original site: 2W3B 
HEADER    OXIDOREDUCTASE                          11-NOV-08   2W3B              
TITLE     HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND A LIPOPHILIC   
TITLE    2 ANTIFOLATE SELECTIVE FOR MYCOBACTERIUM AVIUM DHFR, 6-((2,5-          
TITLE    3 DIETHOXYPHENYL)AMINOMETHYL)-2,4-DIAMINO-5-METHYLPYRIDO(2,3-D)        
TITLE    4 PYRIMIDINE (SRI-8686)                                                
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 EXPRESSION_SYSTEM: ESCHERICHIA COLI;                                 
SOURCE   6 EXPRESSION_SYSTEM_TAXID: 469008;                                     
SOURCE   7 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);                                 
SOURCE   8 EXPRESSION_SYSTEM_VECTOR: PET11A;                                    
SOURCE   9 EXPRESSION_SYSTEM_PLASMID: PDFR                                      
KEYWDS    NONCLASSICAL ANTIFOLATES, ONE-CARBON METABOLISM, LIPOPHILIC           
KEYWDS   2 ANTIFOLATES, NADP, REDUCTASE, OXIDOREDUCTASE                         
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    A.K.W.LEUNG,R.C.REYNOLDS,D.W.BORHANI                                  
REVDAT   3   08-MAY-19 2W3B    1       REMARK                                   
REVDAT   2   06-MAR-19 2W3B    1       REMARK                                   
REVDAT   1   17-NOV-09 2W3B    0                                                
JRNL        AUTH   A.K.W.LEUNG,L.J.ROSS,S.ZYWNO-VAN GINKEL,R.C.REYNOLDS,        
JRNL        AUTH 2 L.E.SEITZ,V.PATHAK,W.W.BARROW,E.L.WHITE,W.J.SULING,          
JRNL        AUTH 3 J.R.PIPER,D.W.BORHANI                                        
JRNL        TITL   STRUCTURAL BASIS FOR SELECTIVE INHIBITION OF MYCOBACTERIUM   
JRNL        TITL 2 AVIUM DIHYDROFOLATE REDUCTASE BY A LIPOPHILIC ANTIFOLATE     
JRNL        REF    TO BE PUBLISHED                                              
JRNL        REFN                                                                
REMARK   2                                                                      
REMARK   2 RESOLUTION.    1.27 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : REFMAC 5.2.0019                                      
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) : 1.27                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 14.95                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : NULL                           
REMARK   3   COMPLETENESS FOR RANGE        (%) : 99.8                           
REMARK   3   NUMBER OF REFLECTIONS             : 98560                          
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) : 0.172                           
REMARK   3   R VALUE            (WORKING SET) : 0.171                           
REMARK   3   FREE R VALUE                     : 0.203                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 5.100                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 5251                            
REMARK   3                                                                      
REMARK   3  FIT IN THE HIGHEST RESOLUTION BIN.                                  
REMARK   3   TOTAL NUMBER OF BINS USED           : 20                           
REMARK   3   BIN RESOLUTION RANGE HIGH       (A) : 1.27                         
REMARK   3   BIN RESOLUTION RANGE LOW        (A) : 1.30                         
REMARK   3   REFLECTION IN BIN     (WORKING SET) : 7090                         
REMARK   3   BIN COMPLETENESS (WORKING+TEST) (%) : NULL                         
REMARK   3   BIN R VALUE           (WORKING SET) : 0.2600                       
REMARK   3   BIN FREE R VALUE SET COUNT          : 407                          
REMARK   3   BIN FREE R VALUE                    : 0.2950                       
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS            : 2917                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 216                                     
REMARK   3   SOLVENT ATOMS            : 573                                     
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 16.10                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 16.01                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : -0.23000                                             
REMARK   3    B22 (A**2) : 0.46000                                              
REMARK   3    B33 (A**2) : -0.24000                                             
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 OVERALL COORDINATE ERROR.                                 
REMARK   3   ESU BASED ON R VALUE                            (A): 0.054         
REMARK   3   ESU BASED ON FREE R VALUE                       (A): 0.052         
REMARK   3   ESU BASED ON MAXIMUM LIKELIHOOD                 (A): 0.037         
REMARK   3   ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 1.906         
REMARK   3                                                                      
REMARK   3 CORRELATION COEFFICIENTS.                                            
REMARK   3   CORRELATION COEFFICIENT FO-FC      : 0.973                         
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : 0.963                         
REMARK   3                                                                      
REMARK   3  RMS DEVIATIONS FROM IDEAL VALUES        COUNT    RMS    WEIGHT      
REMARK   3   BOND LENGTHS REFINED ATOMS        (A):  3374 ; 0.012 ; 0.022       
REMARK   3   BOND LENGTHS OTHERS               (A):  2317 ; 0.005 ; 0.020       
REMARK   3   BOND ANGLES REFINED ATOMS   (DEGREES):  4618 ; 1.648 ; 2.050       
REMARK   3   BOND ANGLES OTHERS          (DEGREES):  5648 ; 1.228 ; 3.000       
REMARK   3   TORSION ANGLES, PERIOD 1    (DEGREES):   405 ; 6.151 ; 5.000       
REMARK   3   TORSION ANGLES, PERIOD 2    (DEGREES):   130 ;36.887 ;24.923       
REMARK   3   TORSION ANGLES, PERIOD 3    (DEGREES):   559 ;11.058 ;15.000       
REMARK   3   TORSION ANGLES, PERIOD 4    (DEGREES):    12 ;10.274 ;15.000       
REMARK   3   CHIRAL-CENTER RESTRAINTS       (A**3):   482 ; 0.096 ; 0.200       
REMARK   3   GENERAL PLANES REFINED ATOMS      (A):  3699 ; 0.007 ; 0.020       
REMARK   3   GENERAL PLANES OTHERS             (A):   619 ; 0.002 ; 0.020       
REMARK   3   NON-BONDED CONTACTS REFINED ATOMS (A):   595 ; 0.225 ; 0.200       
REMARK   3   NON-BONDED CONTACTS OTHERS        (A):  2413 ; 0.205 ; 0.200       
REMARK   3   NON-BONDED TORSION REFINED ATOMS  (A):  1602 ; 0.183 ; 0.200       
REMARK   3   NON-BONDED TORSION OTHERS         (A):  1627 ; 0.085 ; 0.200       
REMARK   3   H-BOND (X...Y) REFINED ATOMS      (A):   346 ; 0.149 ; 0.200       
REMARK   3   H-BOND (X...Y) OTHERS             (A):  NULL ;  NULL ;  NULL       
REMARK   3   POTENTIAL METAL-ION REFINED ATOMS (A):  NULL ;  NULL ;  NULL       
REMARK   3   POTENTIAL METAL-ION OTHERS        (A):  NULL ;  NULL ;  NULL       
REMARK   3   SYMMETRY VDW REFINED ATOMS        (A):    11 ; 0.231 ; 0.200       
REMARK   3   SYMMETRY VDW OTHERS               (A):    56 ; 0.253 ; 0.200       
REMARK   3   SYMMETRY H-BOND REFINED ATOMS     (A):    77 ; 0.143 ; 0.200       
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):  1974 ; 1.275 ; 1.500       
REMARK   3   MAIN-CHAIN BOND OTHER ATOMS    (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   MAIN-CHAIN ANGLE REFINED ATOMS (A**2):  3233 ; 1.950 ; 2.000       
REMARK   3   MAIN-CHAIN ANGLE OTHER ATOMS   (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SIDE-CHAIN BOND REFINED ATOMS  (A**2):  1432 ; 2.768 ; 3.000       
REMARK   3   SIDE-CHAIN BOND OTHER ATOMS    (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SIDE-CHAIN ANGLE REFINED ATOMS (A**2):  1385 ; 3.718 ; 4.500       
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  : 2                                          
REMARK   3                                                                      
REMARK   3   TLS GROUP : 1                                                      
REMARK   3    NUMBER OF COMPONENTS GROUP : 4                                    
REMARK   3    COMPONENTS        C SSSEQI   TO  C SSSEQI                         
REMARK   3    RESIDUE RANGE :   A     1        A   185                          
REMARK   3    RESIDUE RANGE :   A   201        A   201                          
REMARK   3    RESIDUE RANGE :   A   301        A   301                          
REMARK   3    RESIDUE RANGE :   A   401        A   401                          
REMARK   3    ORIGIN FOR THE GROUP (A):   0.6120  23.9080  -1.1710              
REMARK   3    T TENSOR                                                          
REMARK   3      T11:  -0.0388 T22:  -0.0334                                     
REMARK   3      T33:  -0.0318 T12:  -0.0161                                     
REMARK   3      T13:  -0.0101 T23:   0.0005                                     
REMARK   3    L TENSOR                                                          
REMARK   3      L11:   1.1050 L22:   0.8013                                     
REMARK   3      L33:   0.9024 L12:   0.1095                                     
REMARK   3      L13:  -0.0592 L23:   0.1211                                     
REMARK   3    S TENSOR                                                          
REMARK   3      S11:  -0.0038 S12:  -0.0632 S13:  -0.0420                       
REMARK   3      S21:   0.0910 S22:  -0.0200 S23:  -0.0174                       
REMARK   3      S31:   0.0546 S32:  -0.0127 S33:   0.0238                       
REMARK   3                                                                      
REMARK   3   TLS GROUP : 2                                                      
REMARK   3    NUMBER OF COMPONENTS GROUP : 4                                    
REMARK   3    COMPONENTS        C SSSEQI   TO  C SSSEQI                         
REMARK   3    RESIDUE RANGE :   B     1        B   186                          
REMARK   3    RESIDUE RANGE :   B   201        B   201                          
REMARK   3    RESIDUE RANGE :   B   301        B   301                          
REMARK   3    RESIDUE RANGE :   B   401        B   401                          
REMARK   3    ORIGIN FOR THE GROUP (A):  20.9470  45.2080  22.6730              
REMARK   3    T TENSOR                                                          
REMARK   3      T11:  -0.0066 T22:  -0.0334                                     
REMARK   3      T33:  -0.0693 T12:   0.0594                                     
REMARK   3      T13:  -0.0036 T23:  -0.0251                                     
REMARK   3    L TENSOR                                                          
REMARK   3      L11:   1.2455 L22:   1.3847                                     
REMARK   3      L33:   1.7082 L12:  -0.2111                                     
REMARK   3      L13:   0.0155 L23:   0.1525                                     
REMARK   3    S TENSOR                                                          
REMARK   3      S11:  -0.1546 S12:  -0.2329 S13:   0.0679                       
REMARK   3      S21:   0.1145 S22:   0.0608 S23:  -0.0567                       
REMARK   3      S31:   0.0384 S32:  -0.0904 S33:   0.0938                       
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELLING.                                             
REMARK   3   METHOD USED : BABINET MODEL WITH MASK                              
REMARK   3   PARAMETERS FOR MASK CALCULATION                                    
REMARK   3   VDW PROBE RADIUS   : 1.20                                          
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 2W3B COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 11-NOV-08.                  
REMARK 100 THE DEPOSITION ID IS D_1290038071.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 18-JAN-00                          
REMARK 200  TEMPERATURE           (KELVIN) : 100                                
REMARK 200  PH                             : 8.75                               
REMARK 200  NUMBER OF CRYSTALS USED        : 1                                  
REMARK 200                                                                      
REMARK 200  SYNCHROTRON              (Y/N) : Y                                  
REMARK 200  RADIATION SOURCE               : SSRL                               
REMARK 200  BEAMLINE                       : BL9-1                              
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 0.785                              
REMARK 200  MONOCHROMATOR                  : SI                                 
REMARK 200  OPTICS                         : MIRRORS                            
REMARK 200                                                                      
REMARK 200  DETECTOR TYPE                  : IMAGE PLATE                        
REMARK 200  DETECTOR MANUFACTURER          : MARRESEARCH                        
REMARK 200  INTENSITY-INTEGRATION SOFTWARE : MOSFLM                             
REMARK 200  DATA SCALING SOFTWARE          : SCALA                              
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 109188                             
REMARK 200  RESOLUTION RANGE HIGH      (A) : 1.250                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 15.000                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : -10.000                            
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 98.9                               
REMARK 200  DATA REDUNDANCY                : 3.400                              
REMARK 200  R MERGE                    (I) : 0.05000                            
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 10.1000                            
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.25                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 1.28                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 88.0                               
REMARK 200  DATA REDUNDANCY IN SHELL       : 2.80                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.71000                            
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 1.400                              
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: UNPUBLISHED HUMAN DHFR FOLATE COMPLEX                
REMARK 200                                                                      
REMARK 200 REMARK: NONE                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 46.61                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.30                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: HUMAN DHFR/FOLATE COMPLEX WAS MIXED      
REMARK 280  WITH NADPH AND 6-((2,5-DIETHOXYPHENYL)AMINOMETHYL)-2, 4-DIAMINO-    
REMARK 280  5-METHYLPYRIDO(2,3-D)PYRIMIDINE (SRI-8686) (BOTH 2 MM FINAL).       
REMARK 280  CRYSTALS WERE GROWN BY HANGING DROP VAPOR DIFFUSION AT 277 K BY     
REMARK 280  MIXING EQUAL VOLUMES OF PROTEIN/NADPH/SRI-8686 WITH RESERVOIR       
REMARK 280  (24% PEG 4000, 200 MM LI2SO4, 100 MM TRIS.HCL, PH 8.75).            
REMARK 280  TRUNCATED TRIANGULAR CRYSTALS APPEARED SLOWLY, IN ABOUT A MONTH.    
REMARK 280  THE CRYSTAL WAS CRYOPROTECTED WITH 15% GLYCEROL AND FLASH-COOLED    
REMARK 280  IN LIQUID N2., VAPOR DIFFUSION, HANGING DROP                        
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       47.71950            
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       47.71950            
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       43.86250            
REMARK 290   SMTRY2   5  0.000000  1.000000  0.000000       47.19350            
REMARK 290   SMTRY3   5  0.000000  0.000000  1.000000        0.00000            
REMARK 290   SMTRY1   6 -1.000000  0.000000  0.000000       43.86250            
REMARK 290   SMTRY2   6  0.000000 -1.000000  0.000000       47.19350            
REMARK 290   SMTRY3   6  0.000000  0.000000  1.000000       47.71950            
REMARK 290   SMTRY1   7 -1.000000  0.000000  0.000000       43.86250            
REMARK 290   SMTRY2   7  0.000000  1.000000  0.000000       47.19350            
REMARK 290   SMTRY3   7  0.000000  0.000000 -1.000000       47.71950            
REMARK 290   SMTRY1   8  1.000000  0.000000  0.000000       43.86250            
REMARK 290   SMTRY2   8  0.000000 -1.000000  0.000000       47.19350            
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 B2263  LIES ON A SPECIAL POSITION.                          
REMARK 465                                                                      
REMARK 465 MISSING RESIDUES                                                     
REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE                       
REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN               
REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)                
REMARK 465                                                                      
REMARK 465   M RES C SSSEQI                                                     
REMARK 465     MET A     0                                                      
REMARK 465     ASP A   186                                                      
REMARK 465     MET B     0                                                      
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     GLN A  84    CD   OE1  NE2                                       
REMARK 470     ARG A  91    CD   NE   CZ   NH1  NH2                             
REMARK 470     LYS A  98    CG   CD   CE   NZ                                   
REMARK 470     GLU A 101    CD   OE1  OE2                                       
REMARK 470     LYS A 108    CD   CE   NZ                                        
REMARK 470     GLU A 150    CG   CD   OE1  OE2                                  
REMARK 470     LYS A 157    CD   CE   NZ                                        
REMARK 470     ARG B  28    CD   NE   CZ   NH1  NH2                             
REMARK 470     ARG B  32    NE   CZ   NH1  NH2                                  
REMARK 470     GLU B  44    CG   CD   OE1  OE2                                  
REMARK 470     LYS B  63    CD   CE   NZ                                        
REMARK 470     LYS B  68    CE   NZ                                             
REMARK 470     ARG B  77    NE   CZ   NH1  NH2                                  
REMARK 470     GLU B  78    CD   OE1  OE2                                       
REMARK 470     GLU B  81    CD   OE1  OE2                                       
REMARK 470     GLN B  84    CD   OE1  NE2                                       
REMARK 470     GLU B 123    CD   OE1  OE2                                       
REMARK 470     GLU B 150    CG   CD   OE1  OE2                                  
REMARK 470     LYS B 155    CE   NZ                                             
REMARK 470     LYS B 157    CD   CE   NZ                                        
REMARK 470     GLU B 161    CD   OE1  OE2                                       
REMARK 470     ASP B 186    C    O    CB   CG   OD1  OD2                        
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: CLOSE CONTACTS IN SAME ASYMMETRIC UNIT                     
REMARK 500                                                                      
REMARK 500 THE FOLLOWING ATOMS ARE IN CLOSE CONTACT.                            
REMARK 500                                                                      
REMARK 500  ATM1  RES C  SSEQI   ATM2  RES C  SSEQI           DISTANCE          
REMARK 500   NZ   LYS B   132     OH   TYR B   162              2.00            
REMARK 500   O    LEU A    79     O    HOH A  2160              2.09            
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    LYS A  80     -103.17    116.66                                   
REMARK 500    ASP A 110      -96.19    -94.84                                   
REMARK 500    MET A 139       48.71    -89.48                                   
REMARK 500    MET A 139       48.71    -85.78                                   
REMARK 500    ASP B 110      -94.58    -94.32                                   
REMARK 500    MET B 139       41.26    -86.79                                   
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 525                                                                      
REMARK 525 SOLVENT                                                              
REMARK 525                                                                      
REMARK 525 THE SOLVENT MOLECULES HAVE CHAIN IDENTIFIERS THAT                    
REMARK 525 INDICATE THE POLYMER CHAIN WITH WHICH THEY ARE MOST                  
REMARK 525 CLOSELY ASSOCIATED. THE REMARK LISTS ALL THE SOLVENT                 
REMARK 525 MOLECULES WHICH ARE MORE THAN 5A AWAY FROM THE                       
REMARK 525 NEAREST POLYMER CHAIN (M = MODEL NUMBER;                             
REMARK 525 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE                  
REMARK 525 NUMBER; I=INSERTION CODE):                                           
REMARK 525                                                                      
REMARK 525  M RES CSSEQI                                                        
REMARK 525    HOH A2010        DISTANCE =  6.44 ANGSTROMS                       
REMARK 525    HOH A2024        DISTANCE =  6.29 ANGSTROMS                       
REMARK 525    HOH A2184        DISTANCE =  7.13 ANGSTROMS                       
REMARK 525    HOH B2009        DISTANCE =  6.61 ANGSTROMS                       
REMARK 525    HOH B2116        DISTANCE =  6.19 ANGSTROMS                       
REMARK 525    HOH B2217        DISTANCE =  8.33 ANGSTROMS                       
REMARK 600                                                                      
REMARK 600 HETEROGEN                                                            
REMARK 600                                                                      
REMARK 600 6-((2,5-DIETHOXYPHENYL)AMINOMETHYL)-2,                               
REMARK 600  4-DIAMINO-5-METHYLPYRIDO(2,3-D)PYRIMIDINE (VG9): SRI-8686           
REMARK 600 FOLIC ACID (FOL): FOLATE                                             
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                               K A 501   K                            
REMARK 620 N RES CSSEQI ATOM                                                    
REMARK 620 1 VAL A  43   O                                                      
REMARK 620 2 SER A  41   O   112.7                                              
REMARK 620 3 SER A  41   OG   81.0  65.0                                        
REMARK 620 4 LYS A  46   O    81.9 147.5  90.5                                  
REMARK 620 5 HOH A2111   O   157.1  84.1  93.2  75.9                            
REMARK 620 N                    1     2     3     4                             
REMARK 620                                                                      
REMARK 620 COORDINATION ANGLES FOR:  M RES CSSEQI METAL                         
REMARK 620                               K B 501   K                            
REMARK 620 N RES CSSEQI ATOM                                                    
REMARK 620 1 VAL B  43   O                                                      
REMARK 620 2 LYS B  46   O    81.0                                              
REMARK 620 3 HOH B2078   O    94.4 175.2                                        
REMARK 620 4 HOH B2089   O   150.1  78.9 104.9                                  
REMARK 620 5 SER B  41   OG   65.0  77.5  99.4  89.1                            
REMARK 620 N                    1     2     3     4                             
REMARK 700                                                                      
REMARK 700 SHEET                                                                
REMARK 700 THE SHEET STRUCTURE OF THIS MOLECULE IS BIFURCATED. IN               
REMARK 700 ORDER TO REPRESENT THIS FEATURE IN THE SHEET RECORDS BELOW,          
REMARK 700 TWO SHEETS ARE DEFINED.                                              
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 VG9 A 301                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC3                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE FOL A 401                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC4                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE K A 501                   
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC5                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NDP B 201                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC6                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE VG9 B 301                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC7                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE FOL B 401                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC8                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE K B 501                   
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 2W3A   RELATED DB: PDB                                   
REMARK 900 HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND TRIMETHOPRIM  
REMARK 900 RELATED ID: 2C2S   RELATED DB: PDB                                   
REMARK 900 HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND 2,4-DIAMINO-  
REMARK 900 5-(1-O- CARBORANYLMETHYL)-6-METHYLPYRIMIDINE, A NOVEL BORON          
REMARK 900 CONTANING, NONCLASSICAL ANTIFOLATE                                   
REMARK 900 RELATED ID: 2W3M   RELATED DB: PDB                                   
REMARK 900 HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND FOLATE        
REMARK 900 RELATED ID: 1DHF   RELATED DB: PDB                                   
REMARK 900 DIHYDROFOLATE REDUCTASE (DHFR) COMPLEX WITH FOLATE                   
REMARK 900 RELATED ID: 2DHF   RELATED DB: PDB                                   
REMARK 900 DIHYDROFOLATE REDUCTASE (DHFR) COMPLEX WITH 5 -DEAZAFOLATE           
REMARK 900 RELATED ID: 1S3W   RELATED DB: PDB                                   
REMARK 900 STRUCTURE DETERMINATION OF TETRAHYDROQUINAZOLINEANTIFOALTES IN       
REMARK 900 COMPLEX WITH HUMAN AND PNEUMOCYSTIS CARINIIDIHYDROFOLATE REDUCTASE:  
REMARK 900 CORRELATIONS OF ENZYMESELECTIVITY AND STEREOCHEMISTRY                
REMARK 900 RELATED ID: 1S3V   RELATED DB: PDB                                   
REMARK 900 STRUCTURE DETERMINATION OF TETRAHYDROQUINAZOLINEANTIFOLATES IN       
REMARK 900 COMPLEX WITH HUMAN AND PNEUMOCYSTIS CARINIIDIHYDROFOLATE REDUCTASE:  
REMARK 900 CORRELATIONS OF ENZYMESELECTIVITY AND STEREOCHEMISTRY                
REMARK 900 RELATED ID: 1PD8   RELATED DB: PDB                                   
REMARK 900 ANALYSIS OF THREE CRYSTAL STRUCTURE DETERMINATIONS OF A 5-METHYL-6-  
REMARK 900 N- METHYLANILINO PYRIDOPYRIMIDINE ANTIFOLATECOMPLEX WITH HUMAN       
REMARK 900 DIHYDROFOLATE REDUCTASE                                              
REMARK 900 RELATED ID: 1DLS   RELATED DB: PDB                                   
REMARK 900 DIHYDROFOLATE REDUCTASE (DHFR) MUTANT WITH LEU 22 REPLACED BY TYR    
REMARK 900 (L22Y) COMPLEXED WITH NADPH AND METHOTREXATE                         
REMARK 900 RELATED ID: 1DLR   RELATED DB: PDB                                   
REMARK 900 DIHYDROFOLATE REDUCTASE (DHFR) MUTANT WITH LEU 22 REPLACED BY PHE    
REMARK 900 (L22F) COMPLEXED WITH NADPH AND PIRITREXIM (PTX)                     
REMARK 900 RELATED ID: 1U72   RELATED DB: PDB                                   
REMARK 900 UNDERSTANDING THE ROLE OF LEU22 VARIANTS IN METHOTREXATERESISTANCE:  
REMARK 900 COMPARISON OF WILD- TYPE AND LEU22ARG VARIANTMOUSE AND HUMAN         
REMARK 900 DIHYDRFOLATE REDUCTASE TERNARY CRYSTALCOMPLEXES WITH METHOTREXATE    
REMARK 900 AND NADPH                                                            
REMARK 900 RELATED ID: 1OHK   RELATED DB: PDB                                   
REMARK 900 HUMAN DIHYDROFOLATE REDUCTASE, ORTHORHOMBIC (P21 21 21) CRYSTAL FORM 
REMARK 900 RELATED ID: 1YHO   RELATED DB: PDB                                   
REMARK 900 SOLUTION STRUCTURE OF HUMAN DIHYDROFOLATE REDUCTASECOMPLEXED WITH    
REMARK 900 TRIMETHOPRIM AND NADPH , 25 STRUCTURES                               
REMARK 900 RELATED ID: 2C2T   RELATED DB: PDB                                   
REMARK 900 HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND 2,4-DIAMINO-  
REMARK 900 5-((7,8- DICARBAUNDECABORAN-7-YL)METHYL)-6- METHYLPYRIMIDINE, A      
REMARK 900 NOVEL BORON CONTANING, NONCLASSICAL ANTIFOLATE                       
REMARK 900 RELATED ID: 1OHJ   RELATED DB: PDB                                   
REMARK 900 HUMAN DIHYDROFOLATE REDUCTASE, MONOCLINIC (P21 ) CRYSTAL FORM        
REMARK 900 RELATED ID: 1PD9   RELATED DB: PDB                                   
REMARK 900 ANALYSIS OF THREE CRYSTAL STRUCTURE DETERMINATIONS OF A 5-METHYL-6-  
REMARK 900 N- METHYLANILINO PYRIDOPYRIMIDINE ANTIFOLATECOMPLEX WITH HUMAN       
REMARK 900 DIHYDROFOLATE REDUCTASE                                              
REMARK 900 RELATED ID: 1KMV   RELATED DB: PDB                                   
REMARK 900 HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND (Z)-6-(2-[2,  
REMARK 900 5-DIMETHOXYPHENYL] ETHEN-1-YL)-2,4-DIAMINO-5-METHYLPYRIDO[2 ,3-D]    
REMARK 900 PYRIMIDINE (SRI-9662), A LIPOPHILICANTIFOLATE                        
REMARK 900 RELATED ID: 1HFR   RELATED DB: PDB                                   
REMARK 900 COMPARISON OF TERNARY CRYSTAL COMPLEXES OF HUMAN DIHYDROFOLATE       
REMARK 900 REDUCTASE WITH NADPH AND A CLASSICAL ANTITUMOR FUROPYRIMDINE         
REMARK 900 RELATED ID: 1MVT   RELATED DB: PDB                                   
REMARK 900 ANALYSIS OF TWO POLYMORPHIC FORMS OF A PYRIDO[2,3-D]PYRIMIDINE N9-   
REMARK 900 C10 REVERSE- BRIDGE ANTIFOLATE BINARYCOMPLEX WITH HUMAN              
REMARK 900 DIHYDROFOLATE REDUCTASE                                              
REMARK 900 RELATED ID: 1U71   RELATED DB: PDB                                   
REMARK 900 UNDERSTANDING THE ROLE OF LEU22 VARIANTS IN METHOTREXATERESISTANCE:  
REMARK 900 COMPARISON OF WILD- TYPE AND LEU22ARG VARIANTMOUSE AND HUMAN         
REMARK 900 DIHYDROFOLATE REDUCTASE TERNARY CRYSTALCOMPLEXES WITH METHOTREXATE   
REMARK 900 AND NADPH                                                            
REMARK 900 RELATED ID: 1KMS   RELATED DB: PDB                                   
REMARK 900 HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND 6-([5-        
REMARK 900 QUINOLYLAMINO]METHYL)-2,4 -DIAMINO-5-METHYLPYRIDO[2,3-D]PYRIMIDINE   
REMARK 900 ( SRI-9439), A LIPOPHILIC ANTIFOLATE                                 
REMARK 900 RELATED ID: 1PDB   RELATED DB: PDB                                   
REMARK 900 ANALYSIS OF THREE CRYSTAL STRUCTURE DETERMINATIONS OF A 5-METHYL-6-  
REMARK 900 N- METHYLANILINO PYRIDOPYRIMIDINE ANTIFOLATECOMPLEX WITH HUMAN       
REMARK 900 DIHYDROFOLATE REDUCTASE                                              
REMARK 900 RELATED ID: 1HFQ   RELATED DB: PDB                                   
REMARK 900 COMPARISON OF TERNARY CRYSTAL COMPLEXES OF HUMAN DIHYDROFOLATE       
REMARK 900 REDUCTASE WITH NADPH AND A CLASSICAL ANTITUMOR FUROPYRIMDINE         
REMARK 900 RELATED ID: 1MVS   RELATED DB: PDB                                   
REMARK 900 ANALYSIS OF TWO POLYMORPHIC FORMS OF A PYRIDO[2,3-D]PYRIMIDINE N9-   
REMARK 900 C10 REVERSE- BRIDGE ANTIFOLATE BINARYCOMPLEX WITH HUMAN              
REMARK 900 DIHYDROFOLATE REDUCTASE                                              
REMARK 900 RELATED ID: 1DRF   RELATED DB: PDB                                   
REMARK 900 DIHYDROFOLATE REDUCTASE COMPLEX WITH FOLATE                          
REMARK 900 RELATED ID: 1S3U   RELATED DB: PDB                                   
REMARK 900 STRUCTURE DETERMINATION OF TETRAHYDROQUINAZOLINEANTIFOLATES IN       
REMARK 900 COMPLEX WITH HUMAN AND PNEUMOCYSTIS CARINIIDIHYDROFOLATE REDUCTASE:  
REMARK 900 CORRELATIONS OF ENZYMESELECTIVITY AND STEREOCHEMISTRY                
REMARK 900 RELATED ID: 1HFP   RELATED DB: PDB                                   
REMARK 900 COMPARISON OF TERNARY CRYSTAL COMPLEXES OF HUMAN DIHYDROFOLATE       
REMARK 900 REDUCTASE WITH NADPH AND A CLASSICAL ANTITUMOR FUROPYRIMDINE         
REMARK 900 RELATED ID: 1BOZ   RELATED DB: PDB                                   
REMARK 900 STRUCTURE-BASED DESIGN AND SYNTHESIS OF LIPOPHILIC 2,4- DIAMINO-6-   
REMARK 900 SUBSTITUTED QUINAZOLINES AND THEIR EVALUATION AS INHIBITORS OF       
REMARK 900 DIHYDROFOLATE REDUCTASE AND POTENTIAL ANTITUMOR AGENTS               
DBREF  2W3B A    0   186  UNP    P00374   DYR_HUMAN        1    187             
DBREF  2W3B B    0   186  UNP    P00374   DYR_HUMAN        1    187             
SEQRES   1 A  187  MET VAL GLY SER LEU ASN CYS ILE VAL ALA VAL SER GLN          
SEQRES   2 A  187  ASN MET GLY ILE GLY LYS ASN GLY ASP LEU PRO TRP PRO          
SEQRES   3 A  187  PRO LEU ARG ASN GLU PHE ARG TYR PHE GLN ARG MET THR          
SEQRES   4 A  187  THR THR SER SER VAL GLU GLY LYS GLN ASN LEU VAL ILE          
SEQRES   5 A  187  MET GLY LYS LYS THR TRP PHE SER ILE PRO GLU LYS ASN          
SEQRES   6 A  187  ARG PRO LEU LYS GLY ARG ILE ASN LEU VAL LEU SER ARG          
SEQRES   7 A  187  GLU LEU LYS GLU PRO PRO GLN GLY ALA HIS PHE LEU SER          
SEQRES   8 A  187  ARG SER LEU ASP ASP ALA LEU LYS LEU THR GLU GLN PRO          
SEQRES   9 A  187  GLU LEU ALA ASN LYS VAL ASP MET VAL TRP ILE VAL GLY          
SEQRES  10 A  187  GLY SER SER VAL TYR LYS GLU ALA MET ASN HIS PRO GLY          
SEQRES  11 A  187  HIS LEU LYS LEU PHE VAL THR ARG ILE MET GLN ASP PHE          
SEQRES  12 A  187  GLU SER ASP THR PHE PHE PRO GLU ILE ASP LEU GLU LYS          
SEQRES  13 A  187  TYR LYS LEU LEU PRO GLU TYR PRO GLY VAL LEU SER ASP          
SEQRES  14 A  187  VAL GLN GLU GLU LYS GLY ILE LYS TYR LYS PHE GLU VAL          
SEQRES  15 A  187  TYR GLU LYS ASN ASP                                          
SEQRES   1 B  187  MET VAL GLY SER LEU ASN CYS ILE VAL ALA VAL SER GLN          
SEQRES   2 B  187  ASN MET GLY ILE GLY LYS ASN GLY ASP LEU PRO TRP PRO          
SEQRES   3 B  187  PRO LEU ARG ASN GLU PHE ARG TYR PHE GLN ARG MET THR          
SEQRES   4 B  187  THR THR SER SER VAL GLU GLY LYS GLN ASN LEU VAL ILE          
SEQRES   5 B  187  MET GLY LYS LYS THR TRP PHE SER ILE PRO GLU LYS ASN          
SEQRES   6 B  187  ARG PRO LEU LYS GLY ARG ILE ASN LEU VAL LEU SER ARG          
SEQRES   7 B  187  GLU LEU LYS GLU PRO PRO GLN GLY ALA HIS PHE LEU SER          
SEQRES   8 B  187  ARG SER LEU ASP ASP ALA LEU LYS LEU THR GLU GLN PRO          
SEQRES   9 B  187  GLU LEU ALA ASN LYS VAL ASP MET VAL TRP ILE VAL GLY          
SEQRES  10 B  187  GLY SER SER VAL TYR LYS GLU ALA MET ASN HIS PRO GLY          
SEQRES  11 B  187  HIS LEU LYS LEU PHE VAL THR ARG ILE MET GLN ASP PHE          
SEQRES  12 B  187  GLU SER ASP THR PHE PHE PRO GLU ILE ASP LEU GLU LYS          
SEQRES  13 B  187  TYR LYS LEU LEU PRO GLU TYR PRO GLY VAL LEU SER ASP          
SEQRES  14 B  187  VAL GLN GLU GLU LYS GLY ILE LYS TYR LYS PHE GLU VAL          
SEQRES  15 B  187  TYR GLU LYS ASN ASP                                          
HET    NDP  A 201      48                                                       
HET    VG9  A 301      27                                                       
HET    FOL  A 401      32                                                       
HET      K  A 501       1                                                       
HET    NDP  B 201      48                                                       
HET    VG9  B 301      27                                                       
HET    FOL  B 401      32                                                       
HET      K  B 501       1                                                       
HETNAM     NDP NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE                  
HETNAM   2 NDP  PHOSPHATE                                                       
HETNAM     VG9 6-{[(2,5-DIETHOXYPHENYL)AMINO]METHYL}-5-METHYLPYRIDO[2,          
HETNAM   2 VG9  3-D]PYRIMIDINE-2,4-DIAMINE                                      
HETNAM     FOL FOLIC ACID                                                       
HETNAM       K POTASSIUM ION                                                    
FORMUL   3  NDP    2(C21 H30 N7 O17 P3)                                         
FORMUL   4  VG9    2(C19 H24 N6 O2)                                             
FORMUL   5  FOL    2(C19 H19 N7 O6)                                             
FORMUL   6    K    2(K 1+)                                                      
FORMUL  11  HOH   *573(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 LYS B   54  ILE B   60  1                                   7    
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  AA 8 PHE A  88  SER A  90  0                                        
SHEET    2  AA 8 ILE A  71  LEU A  75  1  O  ASN A  72   N  PHE A  88           
SHEET    3  AA 8 GLN A  47  GLY A  53  1  O  ASN A  48   N  ILE A  71           
SHEET    4  AA 8 VAL A 109  ILE A 114  1  N  ASP A 110   O  GLN A  47           
SHEET    5  AA 8 SER A   3  VAL A  10  1  O  ASN A   5   N  ILE A 114           
SHEET    6  AA 8 HIS A 130  ILE A 138  1  O  HIS A 130   N  LEU A   4           
SHEET    7  AA 8 ILE A 175  LYS A 184 -1  O  LYS A 178   N  ARG A 137           
SHEET    8  AA 8 LYS A 157  LEU A 158 -1  O  LYS A 157   N  GLU A 183           
SHEET    1  AB 7 PHE A  88  SER A  90  0                                        
SHEET    2  AB 7 ILE A  71  LEU A  75  1  O  ASN A  72   N  PHE A  88           
SHEET    3  AB 7 GLN A  47  GLY A  53  1  O  ASN A  48   N  ILE A  71           
SHEET    4  AB 7 VAL A 109  ILE A 114  1  N  ASP A 110   O  GLN A  47           
SHEET    5  AB 7 SER A   3  VAL A  10  1  O  ASN A   5   N  ILE A 114           
SHEET    6  AB 7 HIS A 130  ILE A 138  1  O  HIS A 130   N  LEU A   4           
SHEET    7  AB 7 ILE A 175  LYS A 184 -1  O  LYS A 178   N  ARG A 137           
SHEET    1  AC 2 GLY A  15  GLY A  17  0                                        
SHEET    2  AC 2 THR A 146  PHE A 147 -1  O  THR A 146   N  ILE A  16           
SHEET    1  BA 8 PHE B  88  SER B  90  0                                        
SHEET    2  BA 8 ARG B  70  LEU B  75  1  O  ASN B  72   N  PHE B  88           
SHEET    3  BA 8 GLN B  47  GLY B  53  1  O  ASN B  48   N  ILE B  71           
SHEET    4  BA 8 VAL B 109  ILE B 114  1  N  ASP B 110   O  GLN B  47           
SHEET    5  BA 8 SER B   3  SER B  11  1  O  ASN B   5   N  ILE B 114           
SHEET    6  BA 8 HIS B 130  ILE B 138  1  O  HIS B 130   N  LEU B   4           
SHEET    7  BA 8 ILE B 175  LYS B 184 -1  O  LYS B 178   N  ARG B 137           
SHEET    8  BA 8 LYS B 157  LEU B 158 -1  O  LYS B 157   N  GLU B 183           
SHEET    1  BB 7 PHE B  88  SER B  90  0                                        
SHEET    2  BB 7 ARG B  70  LEU B  75  1  O  ASN B  72   N  PHE B  88           
SHEET    3  BB 7 GLN B  47  GLY B  53  1  O  ASN B  48   N  ILE B  71           
SHEET    4  BB 7 VAL B 109  ILE B 114  1  N  ASP B 110   O  GLN B  47           
SHEET    5  BB 7 SER B   3  SER B  11  1  O  ASN B   5   N  ILE B 114           
SHEET    6  BB 7 HIS B 130  ILE B 138  1  O  HIS B 130   N  LEU B   4           
SHEET    7  BB 7 ILE B 175  LYS B 184 -1  O  LYS B 178   N  ARG B 137           
SHEET    1  BC 2 GLY B  15  GLY B  17  0                                        
SHEET    2  BC 2 THR B 146  PHE B 147 -1  O  THR B 146   N  ILE B  16           
LINK         K     K A 501                 O   VAL A  43     1555   1555  2.74  
LINK         K     K A 501                 O   SER A  41     1555   1555  2.84  
LINK         K     K A 501                 OG  SER A  41     1555   1555  3.16  
LINK         K     K A 501                 O   LYS A  46     1555   1555  2.71  
LINK         K     K A 501                 O   HOH A2111     1555   1555  2.95  
LINK         K     K B 501                 O   VAL B  43     1555   1555  2.81  
LINK         K     K B 501                 O   LYS B  46     1555   1555  2.59  
LINK         K     K B 501                 O   HOH B2078     1555   1555  2.93  
LINK         K     K B 501                 O   HOH B2089     1555   1555  2.77  
LINK         K     K B 501                 OG  SER B  41     1555   1555  3.08  
CISPEP   1 ARG A   65    PRO A   66          0        -7.22                     
CISPEP   2 LEU A   79    LYS A   80          0         3.48                     
CISPEP   3 GLY A  116    GLY A  117          0         4.19                     
CISPEP   4 ARG B   65    PRO B   66          0        -7.69                     
CISPEP   5 GLY B  116    GLY B  117          0         5.60                     
SITE     1 AC1 35 VAL A   8  ALA A   9  ILE A  16  GLY A  17                    
SITE     2 AC1 35 LYS A  18  GLY A  20  ASP A  21  LEU A  22                    
SITE     3 AC1 35 GLY A  53  LYS A  54  LYS A  55  THR A  56                    
SITE     4 AC1 35 LEU A  75  SER A  76  ARG A  77  GLU A  78                    
SITE     5 AC1 35 ARG A  91  VAL A 115  GLY A 117  SER A 118                    
SITE     6 AC1 35 SER A 119  VAL A 120  TYR A 121  THR A 146                    
SITE     7 AC1 35 VG9 A 301  FOL A 401  HOH A2134  HOH A2209                    
SITE     8 AC1 35 HOH A2234  HOH A2300  HOH A2302  HOH A2303                    
SITE     9 AC1 35 HOH A2304  HOH A2305  HOH A2306                               
SITE     1 AC2 16 ILE A   7  VAL A   8  ALA A   9  ASP A  21                    
SITE     2 AC2 16 LEU A  22  GLU A  30  PHE A  31  PHE A  34                    
SITE     3 AC2 16 GLN A  35  SER A  59  PRO A  61  ASN A  64                    
SITE     4 AC2 16 VAL A 115  TYR A 121  NDP A 201  HOH A2305                    
SITE     1 AC3 19 ILE A   7  VAL A   8  ALA A   9  GLU A  30                    
SITE     2 AC3 19 PHE A  31  ARG A  32  PHE A  34  GLN A  35                    
SITE     3 AC3 19 ILE A  60  ASN A  64  LEU A  67  ARG A  70                    
SITE     4 AC3 19 VAL A 115  THR A 136  NDP A 201  HOH A2305                    
SITE     5 AC3 19 HOH A2308  HOH A2309  HOH A2310                               
SITE     1 AC4  4 SER A  41  VAL A  43  LYS A  46  HOH A2111                    
SITE     1 AC5 30 VAL B   8  ALA B   9  ILE B  16  GLY B  17                    
SITE     2 AC5 30 ASP B  21  LEU B  22  GLY B  53  LYS B  54                    
SITE     3 AC5 30 LYS B  55  THR B  56  SER B  59  LEU B  75                    
SITE     4 AC5 30 SER B  76  ARG B  77  GLU B  78  ARG B  91                    
SITE     5 AC5 30 VAL B 115  GLY B 117  SER B 118  SER B 119                    
SITE     6 AC5 30 VAL B 120  TYR B 121  THR B 146  VG9 B 301                    
SITE     7 AC5 30 FOL B 401  HOH B2159  HOH B2186  HOH B2264                    
SITE     8 AC5 30 HOH B2265  HOH B2266                                          
SITE     1 AC6 16 ILE B   7  VAL B   8  ALA B   9  GLU B  30                    
SITE     2 AC6 16 PHE B  31  PHE B  34  PRO B  61  LEU B  67                    
SITE     3 AC6 16 ARG B  70  VAL B 115  TYR B 121  NDP B 201                    
SITE     4 AC6 16 HOH B2012  HOH B2038  HOH B2264  HOH B2267                    
SITE     1 AC7 18 ILE B   7  VAL B   8  ALA B   9  GLU B  30                    
SITE     2 AC7 18 PHE B  31  ARG B  32  PHE B  34  GLN B  35                    
SITE     3 AC7 18 ILE B  60  ASN B  64  LEU B  67  ARG B  70                    
SITE     4 AC7 18 VAL B 115  THR B 136  NDP B 201  HOH B2047                    
SITE     5 AC7 18 HOH B2264  HOH B2268                                          
SITE     1 AC8  5 SER B  41  VAL B  43  LYS B  46  HOH B2078                    
SITE     2 AC8  5 HOH B2089                                                     
CRYST1   87.725   94.387   95.439  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      0.011399  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.010595  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.010478        0.00000                         
MTRIX1   1 -0.074950  0.996292 -0.042240       -2.61422    1                    
MTRIX2   1 -0.994802 -0.077632 -0.065899       47.67767    1                    
MTRIX3   1 -0.068934  0.037081  0.996932       22.85954    1                    
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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