GenomeNet

Database: PDB
Entry: 2C2T
LinkDB: 2C2T
Original site: 2C2T 
HEADER    OXIDOREDUCTASE                          30-SEP-05   2C2T              
TITLE     HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND 2,4-DIAMINO-5- 
TITLE    2 ((7,8-DICARBAUNDECABORAN-7-YL)METHYL)-6-METHYLPYRIMIDINE, A NOVEL    
TITLE    3 BORON CONTAINING, NONCLASSICAL ANTIFOLATE                            
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, LIPOPHILIC ANTIFOLATES, NADP, ONE- CARBON   
KEYWDS   2 METABOLISM, OXIDOREDUCTASE, REDUCTASE                                
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    A.K.W.LEUNG,R.C.REYNOLDS,J.M.RIORDAN,D.W.BORHANI                      
REVDAT   7   08-MAY-19 2C2T    1       REMARK                                   
REVDAT   6   06-MAR-19 2C2T    1       REMARK                                   
REVDAT   5   24-FEB-09 2C2T    1       VERSN                                    
REVDAT   4   17-JUL-07 2C2T    1       JRNL                                     
REVDAT   3   26-JUN-07 2C2T    1       JRNL                                     
REVDAT   2   08-MAY-07 2C2T    1       HETATM ANISOU CONECT                     
REVDAT   1   10-APR-07 2C2T    0                                                
JRNL        AUTH   R.C.REYNOLDS,S.R.CAMPBELL,R.G.FAIRCHILD,R.L.KISLIUK,         
JRNL        AUTH 2 P.L.MICCA,S.F.QUEENER,J.M.RIORDAN,W.D.SEDWICK,W.R.WAUD,      
JRNL        AUTH 3 A.K.W.LEUNG,R.W.DIXON,W.J.SULING,D.W.BORHANI                 
JRNL        TITL   NOVEL BORON-CONTAINING, NONCLASSICAL ANTIFOLATES: SYNTHESIS  
JRNL        TITL 2 AND PRELIMINARY BIOLOGICAL AND STRUCTURAL EVALUATION.        
JRNL        REF    J.MED.CHEM.                   V.  50  3283 2007              
JRNL        REFN                   ISSN 0022-2623                               
JRNL        PMID   17569517                                                     
JRNL        DOI    10.1021/JM0701977                                            
REMARK   2                                                                      
REMARK   2 RESOLUTION.    1.50 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) : 1.50                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 20.00                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : NULL                           
REMARK   3   COMPLETENESS FOR RANGE        (%) : 98.1                           
REMARK   3   NUMBER OF REFLECTIONS             : 59389                          
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) : 0.160                           
REMARK   3   R VALUE            (WORKING SET) : 0.158                           
REMARK   3   FREE R VALUE                     : 0.213                           
REMARK   3   FREE R VALUE TEST SET SIZE   (%) : 5.100                           
REMARK   3   FREE R VALUE TEST SET COUNT      : 3168                            
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) : 1.50                         
REMARK   3   BIN RESOLUTION RANGE LOW        (A) : 1.54                         
REMARK   3   REFLECTION IN BIN     (WORKING SET) : 3938                         
REMARK   3   BIN COMPLETENESS (WORKING+TEST) (%) : 89.87                        
REMARK   3   BIN R VALUE           (WORKING SET) : 0.2020                       
REMARK   3   BIN FREE R VALUE SET COUNT          : 205                          
REMARK   3   BIN FREE R VALUE                    : 0.3020                       
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS            : 3004                                    
REMARK   3   NUCLEIC ACID ATOMS       : 0                                       
REMARK   3   HETEROGEN ATOMS          : 186                                     
REMARK   3   SOLVENT ATOMS            : 607                                     
REMARK   3                                                                      
REMARK   3  B VALUES.                                                           
REMARK   3   FROM WILSON PLOT           (A**2) : 19.00                          
REMARK   3   MEAN B VALUE      (OVERALL, A**2) : 17.53                          
REMARK   3   OVERALL ANISOTROPIC B VALUE.                                       
REMARK   3    B11 (A**2) : -0.19000                                             
REMARK   3    B22 (A**2) : 0.52000                                              
REMARK   3    B33 (A**2) : -0.33000                                             
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): 0.096         
REMARK   3   ESU BASED ON FREE R VALUE                       (A): 0.083         
REMARK   3   ESU BASED ON MAXIMUM LIKELIHOOD                 (A): 0.058         
REMARK   3   ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 3.466         
REMARK   3                                                                      
REMARK   3 CORRELATION COEFFICIENTS.                                            
REMARK   3   CORRELATION COEFFICIENT FO-FC      : 0.972                         
REMARK   3   CORRELATION COEFFICIENT FO-FC FREE : 0.953                         
REMARK   3                                                                      
REMARK   3  RMS DEVIATIONS FROM IDEAL VALUES        COUNT    RMS    WEIGHT      
REMARK   3   BOND LENGTHS REFINED ATOMS        (A):  3403 ; 0.012 ; 0.022       
REMARK   3   BOND LENGTHS OTHERS               (A):  2354 ; 0.002 ; 0.020       
REMARK   3   BOND ANGLES REFINED ATOMS   (DEGREES):  4879 ; 1.451 ; 2.016       
REMARK   3   BOND ANGLES OTHERS          (DEGREES):  5864 ; 1.202 ; 2.967       
REMARK   3   TORSION ANGLES, PERIOD 1    (DEGREES):   378 ; 5.892 ; 5.000       
REMARK   3   TORSION ANGLES, PERIOD 2    (DEGREES):   145 ;39.148 ;25.310       
REMARK   3   TORSION ANGLES, PERIOD 3    (DEGREES):   597 ;12.361 ;15.000       
REMARK   3   TORSION ANGLES, PERIOD 4    (DEGREES):    13 ;12.057 ;15.000       
REMARK   3   CHIRAL-CENTER RESTRAINTS       (A**3):   494 ; 0.090 ; 0.200       
REMARK   3   GENERAL PLANES REFINED ATOMS      (A):  3517 ; 0.006 ; 0.020       
REMARK   3   GENERAL PLANES OTHERS             (A):   588 ; 0.001 ; 0.020       
REMARK   3   NON-BONDED CONTACTS REFINED ATOMS (A):   515 ; 0.201 ; 0.200       
REMARK   3   NON-BONDED CONTACTS OTHERS        (A):  2293 ; 0.194 ; 0.200       
REMARK   3   NON-BONDED TORSION REFINED ATOMS  (A):  1499 ; 0.176 ; 0.200       
REMARK   3   NON-BONDED TORSION OTHERS         (A):  1668 ; 0.084 ; 0.200       
REMARK   3   H-BOND (X...Y) REFINED ATOMS      (A):   368 ; 0.141 ; 0.200       
REMARK   3   H-BOND (X...Y) OTHERS             (A):     1 ; 0.003 ; 0.200       
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):    14 ; 0.144 ; 0.200       
REMARK   3   SYMMETRY VDW OTHERS               (A):    65 ; 0.180 ; 0.200       
REMARK   3   SYMMETRY H-BOND REFINED ATOMS     (A):    61 ; 0.204 ; 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):  2484 ; 1.413 ; 1.500       
REMARK   3   MAIN-CHAIN BOND OTHER ATOMS    (A**2):   751 ; 0.557 ; 1.500       
REMARK   3   MAIN-CHAIN ANGLE REFINED ATOMS (A**2):  3146 ; 1.684 ; 2.000       
REMARK   3   MAIN-CHAIN ANGLE OTHER ATOMS   (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SIDE-CHAIN BOND REFINED ATOMS  (A**2):  1745 ; 2.642 ; 3.000       
REMARK   3   SIDE-CHAIN BOND OTHER ATOMS    (A**2):  NULL ;  NULL ;  NULL       
REMARK   3   SIDE-CHAIN ANGLE REFINED ATOMS (A**2):  1473 ; 3.438 ; 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 : 1                                    
REMARK   3    COMPONENTS        C SSSEQI   TO  C SSSEQI                         
REMARK   3    RESIDUE RANGE :   A     1        A   300                          
REMARK   3    ORIGIN FOR THE GROUP (A):   0.4730  23.8260  -1.1920              
REMARK   3    T TENSOR                                                          
REMARK   3      T11:  -0.0372 T22:  -0.0433                                     
REMARK   3      T33:  -0.0130 T12:  -0.0189                                     
REMARK   3      T13:  -0.0070 T23:   0.0102                                     
REMARK   3    L TENSOR                                                          
REMARK   3      L11:   1.0381 L22:   0.6196                                     
REMARK   3      L33:   0.8420 L12:   0.1600                                     
REMARK   3      L13:   0.1488 L23:   0.2707                                     
REMARK   3    S TENSOR                                                          
REMARK   3      S11:  -0.0182 S12:  -0.0446 S13:  -0.0465                       
REMARK   3      S21:   0.0824 S22:   0.0013 S23:  -0.0016                       
REMARK   3      S31:   0.0889 S32:  -0.0625 S33:   0.0169                       
REMARK   3                                                                      
REMARK   3   TLS GROUP : 2                                                      
REMARK   3    NUMBER OF COMPONENTS GROUP : 1                                    
REMARK   3    COMPONENTS        C SSSEQI   TO  C SSSEQI                         
REMARK   3    RESIDUE RANGE :   B     1        B   300                          
REMARK   3    ORIGIN FOR THE GROUP (A):  21.0690  45.4130  22.7240              
REMARK   3    T TENSOR                                                          
REMARK   3      T11:  -0.0178 T22:  -0.0171                                     
REMARK   3      T33:  -0.0351 T12:   0.0663                                     
REMARK   3      T13:  -0.0101 T23:  -0.0238                                     
REMARK   3    L TENSOR                                                          
REMARK   3      L11:   0.8996 L22:   0.9927                                     
REMARK   3      L33:   1.2146 L12:  -0.1986                                     
REMARK   3      L13:   0.1000 L23:   0.4537                                     
REMARK   3    S TENSOR                                                          
REMARK   3      S11:  -0.1266 S12:  -0.1883 S13:   0.0915                       
REMARK   3      S21:   0.1138 S22:   0.0773 S23:  -0.0166                       
REMARK   3      S31:  -0.0093 S32:  -0.0842 S33:   0.0493                       
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   : 1.40                                          
REMARK   3   ION PROBE RADIUS   : 0.80                                          
REMARK   3   SHRINKAGE RADIUS   : 0.80                                          
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: HYDROGENS HAVE BEEN ADDED IN THE RIDING   
REMARK   3  POSITIONS                                                           
REMARK   4                                                                      
REMARK   4 2C2T COMPLIES WITH FORMAT V. 3.30, 13-JUL-11                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 30-SEP-05.                  
REMARK 100 THE DEPOSITION ID IS D_1290025832.                                   
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 03-MAR-99                          
REMARK 200  TEMPERATURE           (KELVIN) : 100.0                              
REMARK 200  PH                             : 8.00                               
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) : 0.78300                            
REMARK 200  MONOCHROMATOR                  : SI (111)                           
REMARK 200  OPTICS                         : MIRROR                             
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   : 62594                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 1.500                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 35.000                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : 0.000                              
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 98.4                               
REMARK 200  DATA REDUNDANCY                : 2.900                              
REMARK 200  R MERGE                    (I) : 0.06000                            
REMARK 200  R SYM                      (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 8.4000                             
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.50                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 1.54                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 90.1                               
REMARK 200  DATA REDUNDANCY IN SHELL       : 2.10                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.45000                            
REMARK 200  R SYM FOR SHELL            (I) : NULL                               
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 1.700                              
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 STRUCTURE                     
REMARK 200                                                                      
REMARK 200 REMARK: INTENSITIES WERE CONVERTED TO STRUCTURE FACTORS USING CCP4   
REMARK 200  PROGRAM TRUNCATE.                                                   
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 46.70                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.30                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: THE TERNARY COMPLEX OF DHFR WITH NADPH   
REMARK 280  AND 39B WAS FORMED BY MIXING HUMAN DHFR (20 MG/ML IN 25 MM KPO4     
REMARK 280  (PH 7.0), 0.1 MM EDTA, AND 3 MM NAN3) WITH 60 MM NADPH, FOLLOWED    
REMARK 280  15 MINUTES LATER BY 60 MM OF INHIBITOR IN DMSO (FINAL               
REMARK 280  CONCENTRATIONS OF 2 MM NADPH AND 2 MM INHIBITOR). THIS COMPLEX      
REMARK 280  SOLUTION WAS MIXED WITH AN EQUAL VOLUME OF PRECIPITANT              
REMARK 280  CONTAINING 24-33% PEG 4000, 0.2 M LI2SO4, 0.1 M TRIS CL (PH 7.9-    
REMARK 280  8.4), 5% GLYCEROL, AND EQUILIBRATED WITH THE PRECIPITANT BY         
REMARK 280  HANGING DROP VAPOR DIFFUSION AT 277 K. THE CRYSTAL GREW IN ABOUT    
REMARK 280  3 WEEKS. THE CRYSTAL WAS FLASH-COOLED DIRECTLY IN LIQUID            
REMARK 280  NITROGEN AFTER HARVESTING INTO MOTHER LIQUOR CONTAINING 10%         
REMARK 280  GLYCEROL. NOTE THAT THE INHIBITOR IS ACTUALLY A RACEMIC MIXTURE     
REMARK 280  OF 39B AND ITS ENANTIOMER, HERE CALLED 39E. IT IS THE RACEMATE      
REMARK 280  THAT IS BOUND IN THE CRYSTAL, REPRESENTED IN THE COORDINATES AS     
REMARK 280  A 1:1 STATISTICALLY-DISORDERED MIXTURE OF 39B AND 39E., PH 8.00,    
REMARK 280  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       48.01600            
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       48.01600            
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       43.81400            
REMARK 290   SMTRY2   5  0.000000  1.000000  0.000000       47.17700            
REMARK 290   SMTRY3   5  0.000000  0.000000  1.000000        0.00000            
REMARK 290   SMTRY1   6 -1.000000  0.000000  0.000000       43.81400            
REMARK 290   SMTRY2   6  0.000000 -1.000000  0.000000       47.17700            
REMARK 290   SMTRY3   6  0.000000  0.000000  1.000000       48.01600            
REMARK 290   SMTRY1   7 -1.000000  0.000000  0.000000       43.81400            
REMARK 290   SMTRY2   7  0.000000  1.000000  0.000000       47.17700            
REMARK 290   SMTRY3   7  0.000000  0.000000 -1.000000       48.01600            
REMARK 290   SMTRY1   8  1.000000  0.000000  0.000000       43.81400            
REMARK 290   SMTRY2   8  0.000000 -1.000000  0.000000       47.17700            
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: PQS                                                   
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: PQS                                                   
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 B2303  LIES ON A SPECIAL POSITION.                          
REMARK 480                                                                      
REMARK 480 ZERO OCCUPANCY ATOM                                                  
REMARK 480 THE FOLLOWING RESIDUES HAVE ATOMS MODELED WITH ZERO                  
REMARK 480 OCCUPANCY. THE LOCATION AND PROPERTIES OF THESE ATOMS                
REMARK 480 MAY NOT BE RELIABLE. (M=MODEL NUMBER; RES=RESIDUE NAME;              
REMARK 480 C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE):         
REMARK 480   M RES C SSEQI ATOMS                                                
REMARK 480     ARG A   28   NE   CZ   NH1  NH2                                  
REMARK 480     LYS A   80   CG   CD   CE   NZ                                   
REMARK 480     ARG A   91   NE   CZ   NH1  NH2                                  
REMARK 480     LYS A  108   CD   CE   NZ                                        
REMARK 480     ARG B   28   NE   CZ   NH1  NH2                                  
REMARK 480     GLU B   44   CG   CD   OE1  OE2                                  
REMARK 480     LYS B   63   CG   CD   CE   NZ                                   
REMARK 480     GLU B   78   CD   OE1  OE2                                       
REMARK 480     ARG B   91   CD   NE   CZ   NH1  NH2                             
REMARK 480     GLU B  150   CG   CD   OE1  OE2                                  
REMARK 480     GLU B  161   CD   OE1  OE2                                       
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   O    HOH A  2131     O    HOH A  2261              2.17            
REMARK 500   O    HOH B  2123     O    HOH B  2239              2.18            
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: CLOSE CONTACTS                                             
REMARK 500                                                                      
REMARK 500 THE FOLLOWING ATOMS THAT ARE RELATED BY CRYSTALLOGRAPHIC             
REMARK 500 SYMMETRY ARE IN CLOSE CONTACT.  AN ATOM LOCATED WITHIN 0.15          
REMARK 500 ANGSTROMS OF A SYMMETRY RELATED ATOM IS ASSUMED TO BE ON A           
REMARK 500 SPECIAL POSITION AND IS, THEREFORE, LISTED IN REMARK 375             
REMARK 500 INSTEAD OF REMARK 500.  ATOMS WITH NON-BLANK ALTERNATE               
REMARK 500 LOCATION INDICATORS ARE NOT INCLUDED IN THE CALCULATIONS.            
REMARK 500                                                                      
REMARK 500 DISTANCE CUTOFF:                                                     
REMARK 500 2.2 ANGSTROMS FOR CONTACTS NOT INVOLVING HYDROGEN ATOMS              
REMARK 500 1.6 ANGSTROMS FOR CONTACTS INVOLVING HYDROGEN ATOMS                  
REMARK 500                                                                      
REMARK 500  ATM1  RES C  SSEQI   ATM2  RES C  SSEQI  SSYMOP   DISTANCE          
REMARK 500   O    GLU A    78     CD   LYS A    80     3555     1.79            
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: COVALENT BOND LENGTHS                                      
REMARK 500                                                                      
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES              
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE               
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN               
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).                 
REMARK 500                                                                      
REMARK 500 STANDARD TABLE:                                                      
REMARK 500 FORMAT: (10X,I3,1X,2(A3,1X,A1,I4,A1,1X,A4,3X),1X,F6.3)               
REMARK 500                                                                      
REMARK 500 EXPECTED VALUES PROTEIN: ENGH AND HUBER, 1999                        
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996                     
REMARK 500                                                                      
REMARK 500  M RES CSSEQI ATM1   RES CSSEQI ATM2   DEVIATION                     
REMARK 500    ARG A  28   CD    ARG A  28   NE     -0.271                       
REMARK 500    LYS A  80   CB    LYS A  80   CG     -0.437                       
REMARK 500    ARG A  91   CD    ARG A  91   NE     -0.323                       
REMARK 500    ARG B  28   CD    ARG B  28   NE     -0.419                       
REMARK 500    GLU B  44   CB    GLU B  44   CG      0.916                       
REMARK 500    LYS B  63   CB    LYS B  63   CG     -0.481                       
REMARK 500    GLU B  78   CG    GLU B  78   CD      0.127                       
REMARK 500    GLU B 150   CB    GLU B 150   CG     -0.447                       
REMARK 500    GLU B 161   CG    GLU B 161   CD     -0.184                       
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: COVALENT BOND ANGLES                                       
REMARK 500                                                                      
REMARK 500 THE STEREOCHEMICAL PARAMETERS OF THE FOLLOWING RESIDUES              
REMARK 500 HAVE VALUES WHICH DEVIATE FROM EXPECTED VALUES BY MORE               
REMARK 500 THAN 6*RMSD (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN               
REMARK 500 IDENTIFIER; SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).                 
REMARK 500                                                                      
REMARK 500 STANDARD TABLE:                                                      
REMARK 500 FORMAT: (10X,I3,1X,A3,1X,A1,I4,A1,3(1X,A4,2X),12X,F5.1)              
REMARK 500                                                                      
REMARK 500 EXPECTED VALUES PROTEIN: ENGH AND HUBER, 1999                        
REMARK 500 EXPECTED VALUES NUCLEIC ACID: CLOWNEY ET AL 1996                     
REMARK 500                                                                      
REMARK 500  M RES CSSEQI ATM1   ATM2   ATM3                                     
REMARK 500    ARG B  28   CG  -  CD  -  NE  ANGL. DEV. =  37.6 DEGREES          
REMARK 500    ARG B  28   CD  -  NE  -  CZ  ANGL. DEV. =  24.7 DEGREES          
REMARK 500    GLU B  44   CA  -  CB  -  CG  ANGL. DEV. = -16.2 DEGREES          
REMARK 500    LYS B  63   CA  -  CB  -  CG  ANGL. DEV. =  19.3 DEGREES          
REMARK 500    GLU B 150   CA  -  CB  -  CG  ANGL. DEV. =  23.7 DEGREES          
REMARK 500    GLU B 150   CB  -  CG  -  CD  ANGL. DEV. =  53.8 DEGREES          
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    ASP A 110      -98.04    -97.85                                   
REMARK 500    ASP B 110      -93.57    -98.97                                   
REMARK 500    MET B 139       41.46    -86.73                                   
REMARK 500                                                                      
REMARK 500 REMARK: NULL                                                         
REMARK 500                                                                      
REMARK 500 GEOMETRY AND STEREOCHEMISTRY                                         
REMARK 500 SUBTOPIC: PLANAR GROUPS                                              
REMARK 500                                                                      
REMARK 500 PLANAR GROUPS IN THE FOLLOWING RESIDUES HAVE A TOTAL                 
REMARK 500 RMS DISTANCE OF ALL ATOMS FROM THE BEST-FIT PLANE                    
REMARK 500 BY MORE THAN AN EXPECTED VALUE OF 6*RMSD, WITH AN                    
REMARK 500 RMSD 0.02 ANGSTROMS, OR AT LEAST ONE ATOM HAS                        
REMARK 500 AN RMSD GREATER THAN THIS VALUE                                      
REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;               
REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).                             
REMARK 500                                                                      
REMARK 500  M RES CSSEQI        RMS     TYPE                                    
REMARK 500    ARG A  91         0.08    SIDE CHAIN                              
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 A2015        DISTANCE =  6.67 ANGSTROMS                       
REMARK 525    HOH A2033        DISTANCE =  5.86 ANGSTROMS                       
REMARK 525    HOH A2040        DISTANCE =  6.76 ANGSTROMS                       
REMARK 525    HOH A2043        DISTANCE =  6.64 ANGSTROMS                       
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 A1187                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 39B A1188                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC3                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 39E A1189                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC4                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NDP B1187                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC5                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 39B B1188                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC6                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 39E B1189                 
REMARK 800                                                                      
REMARK 800 SITE_IDENTIFIER: AC7                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE GOL B1190                 
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
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               
REMARK 900 RELATED ID: 1DHF   RELATED DB: PDB                                   
REMARK 900 DIHYDROFOLATE REDUCTASE (DHFR) COMPLEX WITH FOLATE                   
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: 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: 1DRF   RELATED DB: PDB                                   
REMARK 900 DIHYDROFOLATE REDUCTASE COMPLEX WITH FOLATE                          
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: 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: 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: 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: 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: 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: 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: 1OHJ   RELATED DB: PDB                                   
REMARK 900 HUMAN DIHYDROFOLATE REDUCTASE, MONOCLINIC (P21 ) CRYSTAL FORM        
REMARK 900 RELATED ID: 1OHK   RELATED DB: PDB                                   
REMARK 900 HUMAN DIHYDROFOLATE REDUCTASE, ORTHORHOMBIC (P21 21 21) CRYSTAL FORM 
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: 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: 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: 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: 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: 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: 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: 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: 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: 2DHF   RELATED DB: PDB                                   
REMARK 900 DIHYDROFOLATE REDUCTASE (DHFR) COMPLEX WITH 5 -DEAZAFOLATE           
DBREF  2C2T A    1   186  UNP    P00374   DYR_HUMAN        1    186             
DBREF  2C2T B    1   186  UNP    P00374   DYR_HUMAN        1    186             
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  A1187      48                                                       
HET    39B  A1188      21                                                       
HET    39E  A1189      21                                                       
HET    NDP  B1187      48                                                       
HET    39B  B1188      21                                                       
HET    39E  B1189      21                                                       
HET    GOL  B1190       6                                                       
HETNAM     NDP NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE                  
HETNAM   2 NDP  PHOSPHATE                                                       
HETNAM     39B (S)-2,4-DIAMINO-5-((7,8-DICARBAUNDECABORAN-7-YL)                 
HETNAM   2 39B  METHYL)-6-METHYLPYRIMIDINE                                      
HETNAM     39E (R)-2,4-DIAMINO-5-((7,8-DICARBAUNDECABORAN-7-YL)                 
HETNAM   2 39E  METHYL)-6-METHYLPYRIMIDINE                                      
HETNAM     GOL GLYCEROL                                                         
HETSYN     GOL GLYCERIN; PROPANE-1,2,3-TRIOL                                    
FORMUL   3  NDP    2(C21 H30 N7 O17 P3)                                         
FORMUL   4  39B    2(C8 H20 B9 N4)                                              
FORMUL   5  39E    2(C8 H20 B9 N4)                                              
FORMUL   9  GOL    C3 H8 O3                                                     
FORMUL  10  HOH   *607(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  HIS A  127  1                                  11    
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  SER A  11  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 8 PHE A  88  SER A  90  0                                        
SHEET    2  AB 8 ILE A  71  LEU A  75  1  O  ASN A  72   N  PHE A  88           
SHEET    3  AB 8 GLN A  47  GLY A  53  1  O  ASN A  48   N  ILE A  71           
SHEET    4  AB 8 VAL A 109  ILE A 114  1  N  ASP A 110   O  GLN A  47           
SHEET    5  AB 8 SER A   3  SER A  11  1  O  ASN A   5   N  ILE A 114           
SHEET    6  AB 8 HIS A 130  ILE A 138  1  O  HIS A 130   N  LEU A   4           
SHEET    7  AB 8 ILE A 175  LYS A 184 -1  O  LYS A 178   N  ARG A 137           
SHEET    8  AB 8 GLN A 170  GLU A 172 -1  O  GLN A 170   N  TYR A 177           
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 ILE B  71  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  VAL B  10  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 8 PHE B  88  SER B  90  0                                        
SHEET    2  BB 8 ILE B  71  LEU B  75  1  O  ASN B  72   N  PHE B  88           
SHEET    3  BB 8 GLN B  47  GLY B  53  1  O  ASN B  48   N  ILE B  71           
SHEET    4  BB 8 VAL B 109  ILE B 114  1  N  ASP B 110   O  GLN B  47           
SHEET    5  BB 8 SER B   3  VAL B  10  1  O  ASN B   5   N  ILE B 114           
SHEET    6  BB 8 HIS B 130  ILE B 138  1  O  HIS B 130   N  LEU B   4           
SHEET    7  BB 8 ILE B 175  LYS B 184 -1  O  LYS B 178   N  ARG B 137           
SHEET    8  BB 8 GLN B 170  GLU B 172 -1  O  GLN B 170   N  TYR B 177           
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           
CISPEP   1 ARG A   65    PRO A   66          0        -8.69                     
CISPEP   2 GLY A  116    GLY A  117          0         6.06                     
CISPEP   3 ARG B   65    PRO B   66          0        -8.73                     
CISPEP   4 GLY B  116    GLY B  117          0         5.63                     
SITE     1 AC1 37 VAL A   8  ALA A   9  ILE A  16  GLY A  17                    
SITE     2 AC1 37 GLY A  20  ASP A  21  LEU A  22  GLY A  53                    
SITE     3 AC1 37 LYS A  54  LYS A  55  THR A  56  LEU A  75                    
SITE     4 AC1 37 SER A  76  ARG A  77  GLU A  78  ARG A  91                    
SITE     5 AC1 37 VAL A 115  GLY A 117  SER A 118  SER A 119                    
SITE     6 AC1 37 VAL A 120  TYR A 121  GLU A 123  THR A 146                    
SITE     7 AC1 37 39B A1188  39E A1189  HOH A2204  HOH A2223                    
SITE     8 AC1 37 HOH A2289  HOH A2290  HOH A2291  HOH A2292                    
SITE     9 AC1 37 HOH A2293  HOH A2294  HOH A2295  HOH A2296                    
SITE    10 AC1 37 HOH A2297                                                     
SITE     1 AC2  8 ILE A   7  VAL A   8  LEU A  22  GLU A  30                    
SITE     2 AC2  8 PHE A  34  VAL A 115  TYR A 121  NDP A1187                    
SITE     1 AC3  8 ILE A   7  VAL A   8  LEU A  22  GLU A  30                    
SITE     2 AC3  8 PHE A  34  VAL A 115  TYR A 121  NDP A1187                    
SITE     1 AC4 33 VAL B   8  ALA B   9  ILE B  16  GLY B  17                    
SITE     2 AC4 33 GLY B  20  ASP B  21  LEU B  22  GLY B  53                    
SITE     3 AC4 33 LYS B  54  LYS B  55  THR B  56  LEU B  75                    
SITE     4 AC4 33 SER B  76  ARG B  77  GLU B  78  ARG B  91                    
SITE     5 AC4 33 VAL B 115  GLY B 117  SER B 118  SER B 119                    
SITE     6 AC4 33 VAL B 120  TYR B 121  GLU B 123  THR B 146                    
SITE     7 AC4 33 39B B1188  39E B1189  HOH B2130  HOH B2203                    
SITE     8 AC4 33 HOH B2209  HOH B2231  HOH B2305  HOH B2306                    
SITE     9 AC4 33 HOH B2308                                                     
SITE     1 AC5  7 ILE B   7  VAL B   8  GLU B  30  PHE B  34                    
SITE     2 AC5  7 VAL B 115  TYR B 121  NDP B1187                               
SITE     1 AC6  7 ILE B   7  VAL B   8  GLU B  30  PHE B  34                    
SITE     2 AC6  7 VAL B 115  TYR B 121  NDP B1187                               
SITE     1 AC7  7 LEU B 166  ASP B 168  VAL B 169  HOH B2268                    
SITE     2 AC7  7 HOH B2275  HOH B2309  HOH B2310                               
CRYST1   87.628   94.354   96.032  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      0.011412  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.010598  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.010413        0.00000                         
MTRIX1   1 -0.075211  0.995712 -0.053853       -2.64408    1                    
MTRIX2   1 -0.994412 -0.078906 -0.070138       47.66513    1                    
MTRIX3   1 -0.074087  0.048277  0.996082       22.69347    1                    
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
DBGET integrated database retrieval system