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Database: PDB
Entry: 1KMS
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HEADER    OXIDOREDUCTASE                          17-DEC-01   1KMS              
TITLE     HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND 6-             
TITLE    2 ([5-QUINOLYLAMINO]METHYL)-2,4-DIAMINO-5-METHYLPYRIDO[2,3-            
TITLE    3 D]PYRIMIDINE (SRI-9439), A LIPOPHILIC ANTIFOLATE                     
COMPND    MOL_ID: 1;                                                            
COMPND   2 MOLECULE: DIHYDROFOLATE REDUCTASE;                                   
COMPND   3 CHAIN: A;                                                            
COMPND   4 SYNONYM: DHFR;                                                       
COMPND   5 EC: 1.5.1.3;                                                         
COMPND   6 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 BL21(DE3);                       
SOURCE   6 EXPRESSION_SYSTEM_TAXID: 469008;                                     
SOURCE   7 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);                                 
SOURCE   8 EXPRESSION_SYSTEM_CELLULAR_LOCATION: CYTOPLASM;                      
SOURCE   9 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;                              
SOURCE  10 EXPRESSION_SYSTEM_VECTOR: PET11A;                                    
SOURCE  11 EXPRESSION_SYSTEM_PLASMID: PDFR                                      
KEYWDS    OXIDOREDUCTASE, ANTIPARASITIC DRUGS, REDUCTASE, LIPOPHILIC            
KEYWDS   2 ANTIFOLATES                                                          
EXPDTA    X-RAY DIFFRACTION                                                     
AUTHOR    A.E.KLON,A.HEROUX,L.J.ROSS,V.PATHAK,C.A.JOHNSON,J.R.PIPER,            
AUTHOR   2 D.W.BORHANI                                                          
REVDAT   3   24-FEB-09 1KMS    1       VERSN                                    
REVDAT   2   01-APR-03 1KMS    1       JRNL                                     
REVDAT   1   10-JUL-02 1KMS    0                                                
JRNL        AUTH   A.E.KLON,A.HEROUX,L.J.ROSS,V.PATHAK,C.A.JOHNSON,             
JRNL        AUTH 2 J.R.PIPER,D.W.BORHANI                                        
JRNL        TITL   ATOMIC STRUCTURES OF HUMAN DIHYDROFOLATE REDUCTASE           
JRNL        TITL 2 COMPLEXED WITH NADPH AND TWO LIPOPHILIC                      
JRNL        TITL 3 ANTIFOLATES AT 1.09 A AND 1.05 A RESOLUTION.                 
JRNL        REF    J.MOL.BIOL.                   V. 320   677 2002              
JRNL        REFN                   ISSN 0022-2836                               
JRNL        PMID   12096917                                                     
JRNL        DOI    10.1016/S0022-2836(02)00469-2                                
REMARK   1                                                                      
REMARK   2                                                                      
REMARK   2 RESOLUTION.    1.09 ANGSTROMS.                                       
REMARK   3                                                                      
REMARK   3 REFINEMENT.                                                          
REMARK   3   PROGRAM     : SHELXL-97                                            
REMARK   3   AUTHORS     : G.M.SHELDRICK                                        
REMARK   3                                                                      
REMARK   3  DATA USED IN REFINEMENT.                                            
REMARK   3   RESOLUTION RANGE HIGH (ANGSTROMS) : 1.09                           
REMARK   3   RESOLUTION RANGE LOW  (ANGSTROMS) : 20.00                          
REMARK   3   DATA CUTOFF            (SIGMA(F)) : 0.000                          
REMARK   3   COMPLETENESS FOR RANGE        (%) : 99.6                           
REMARK   3   CROSS-VALIDATION METHOD           : THROUGHOUT                     
REMARK   3   FREE R VALUE TEST SET SELECTION   : 5% OF THE REFLECTIONS          
REMARK   3                                       WERE RANDOMLY SELECTED FOR     
REMARK   3                                       THE TEST SET.                  
REMARK   3                                                                      
REMARK   3  FIT TO DATA USED IN REFINEMENT (NO CUTOFF).                         
REMARK   3   R VALUE   (WORKING + TEST SET, NO CUTOFF) : NULL                   
REMARK   3   R VALUE          (WORKING SET, NO CUTOFF) : 0.131                  
REMARK   3   FREE R VALUE                  (NO CUTOFF) : 0.173                  
REMARK   3   FREE R VALUE TEST SET SIZE (%, NO CUTOFF) : 5.000                  
REMARK   3   FREE R VALUE TEST SET COUNT   (NO CUTOFF) : 3988                   
REMARK   3   TOTAL NUMBER OF REFLECTIONS   (NO CUTOFF) : 79411                  
REMARK   3                                                                      
REMARK   3  FIT/AGREEMENT OF MODEL FOR DATA WITH F>4SIG(F).                     
REMARK   3   R VALUE   (WORKING + TEST SET, F>4SIG(F)) : NULL                   
REMARK   3   R VALUE          (WORKING SET, F>4SIG(F)) : 0.123                  
REMARK   3   FREE R VALUE                  (F>4SIG(F)) : 0.162                  
REMARK   3   FREE R VALUE TEST SET SIZE (%, F>4SIG(F)) : 5.000                  
REMARK   3   FREE R VALUE TEST SET COUNT   (F>4SIG(F)) : 3143                   
REMARK   3   TOTAL NUMBER OF REFLECTIONS   (F>4SIG(F)) : 62954                  
REMARK   3                                                                      
REMARK   3  NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.                    
REMARK   3   PROTEIN ATOMS      : 1606                                          
REMARK   3   NUCLEIC ACID ATOMS : 0                                             
REMARK   3   HETEROGEN ATOMS    : 83                                            
REMARK   3   SOLVENT ATOMS      : 399                                           
REMARK   3                                                                      
REMARK   3  MODEL REFINEMENT.                                                   
REMARK   3   OCCUPANCY SUM OF NON-HYDROGEN ATOMS      : 1927.22                 
REMARK   3   OCCUPANCY SUM OF HYDROGEN ATOMS          : 1406.12                 
REMARK   3   NUMBER OF DISCRETELY DISORDERED RESIDUES : 66                      
REMARK   3   NUMBER OF LEAST-SQUARES PARAMETERS       : 18984                   
REMARK   3   NUMBER OF RESTRAINTS                     : 23468                   
REMARK   3                                                                      
REMARK   3  RMS DEVIATIONS FROM RESTRAINT TARGET VALUES.                        
REMARK   3   BOND LENGTHS                         (A) : 0.013                   
REMARK   3   ANGLE DISTANCES                      (A) : 0.032                   
REMARK   3   SIMILAR DISTANCES (NO TARGET VALUES) (A) : 0.000                   
REMARK   3   DISTANCES FROM RESTRAINT PLANES      (A) : 0.029                   
REMARK   3   ZERO CHIRAL VOLUMES               (A**3) : 0.076                   
REMARK   3   NON-ZERO CHIRAL VOLUMES           (A**3) : 0.086                   
REMARK   3   ANTI-BUMPING DISTANCE RESTRAINTS     (A) : 0.023                   
REMARK   3   RIGID-BOND ADP COMPONENTS         (A**2) : 0.005                   
REMARK   3   SIMILAR ADP COMPONENTS            (A**2) : 0.050                   
REMARK   3   APPROXIMATELY ISOTROPIC ADPS      (A**2) : 0.098                   
REMARK   3                                                                      
REMARK   3  BULK SOLVENT MODELING.                                              
REMARK   3   METHOD USED: MOEWS & KRETSINGER, J.MOL.BIOL.91(1973)201-228        
REMARK   3                                                                      
REMARK   3  STEREOCHEMISTRY TARGET VALUES : ENGH & HUBER                        
REMARK   3   SPECIAL CASE: NULL                                                 
REMARK   3                                                                      
REMARK   3  OTHER REFINEMENT REMARKS: REFINEMENT IN X-PLOR, ALTERNATED          
REMARK   3  WITH MANUAL REBUILDING IN O, RESULTING IN A FREE R-FACTOR OF        
REMARK   3  24.0%. SRI-9439 WAS THEN ADDED TO THE MODEL IN THE ACTIVE SITE      
REMARK   3  AND THE CIS PEPTIDE BONDS BETWEEN RESIDUES ARG-65 AND PRO-66        
REMARK   3  AND RESIDUES GLY-116 AND GLY-117 BECAME APPARENT IN 2FO-FC AND      
REMARK   3  FO-FC MAPS. REFINEMENT PROCEEDED WITH THE ADDITION OF RIDING        
REMARK   3  HYDROGEN ATOMS AND ANISOTROPIC TEMPERATURE FACTORS IN REFMAC        
REMARK   3  AND ARP, YIELDING A FREE R-FACTOR OF 19.4%. AT THIS POINT,          
REMARK   3  MOST OF THE SIDE CHAIN ALTERNATE CONFORMATIONS WERE MODELED.        
REMARK   3  ANISOTROPIC DISPLACEMENT PARAMETERS WERE REFINED IN SHELXL AND      
REMARK   3  RIDING HYDROGEN ATOMS WERE ADDED. IN THE FINAL ROUNDS OF            
REMARK   3  REFINEMENT, RESTRAINTS FOR ALL ATOMS IN SRI-9439 EXCEPT FOR         
REMARK   3  PLANARITY RESTRAINTS ON THE 5-QUINOLYLAMINO GROUP, AND ALL          
REMARK   3  NADPH ATOMS EXCEPT FOR THOSE IN THE ADENINE RING AND ADENINE        
REMARK   3  RIBOSE-2-PHOSPHATE WERE REMOVED, GIVING THE FINAL FREE R-           
REMARK   3  FACTOR (17.3%). ATTEMPTS TO RESTRAIN THE PLANARITY OF THE 5-        
REMARK   3  METHYL-5-DEAZAPTERIDINE MOIETY OF SRI-9439 RESULTED IN LARGE        
REMARK   3  DIFFERENCE ELECTRON DENSITY PEAKS FOR THE EXOCYCLIC N4 AND C5A      
REMARK   3  ATOMS, CONFIRMING THEIR OUT-OF-PLANE POSITIONS.                     
REMARK   4                                                                      
REMARK   4 1KMS COMPLIES WITH FORMAT V. 3.15, 01-DEC-08                         
REMARK 100                                                                      
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 07-JAN-02.                  
REMARK 100 THE RCSB ID CODE IS RCSB015119.                                      
REMARK 200                                                                      
REMARK 200 EXPERIMENTAL DETAILS                                                 
REMARK 200  EXPERIMENT TYPE                : X-RAY DIFFRACTION                  
REMARK 200  DATE OF DATA COLLECTION        : 25-JUN-97                          
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                       : BL7-1                              
REMARK 200  X-RAY GENERATOR MODEL          : NULL                               
REMARK 200  MONOCHROMATIC OR LAUE    (M/L) : M                                  
REMARK 200  WAVELENGTH OR RANGE        (A) : 1.08                               
REMARK 200  MONOCHROMATOR                  : SI (111)                           
REMARK 200  OPTICS                         : PT-COATED 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          : CCP4 (SCALA)                       
REMARK 200                                                                      
REMARK 200  NUMBER OF UNIQUE REFLECTIONS   : 79611                              
REMARK 200  RESOLUTION RANGE HIGH      (A) : 1.090                              
REMARK 200  RESOLUTION RANGE LOW       (A) : 20.000                             
REMARK 200  REJECTION CRITERIA  (SIGMA(I)) : 0.000                              
REMARK 200                                                                      
REMARK 200 OVERALL.                                                             
REMARK 200  COMPLETENESS FOR RANGE     (%) : 99.6                               
REMARK 200  DATA REDUNDANCY                : 3.600                              
REMARK 200  R MERGE                    (I) : 0.04700                            
REMARK 200  R SYM                      (I) : 0.04700                            
REMARK 200  <I/SIGMA(I)> FOR THE DATA SET  : 9.4000                             
REMARK 200                                                                      
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.                                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.09                     
REMARK 200  HIGHEST RESOLUTION SHELL, RANGE LOW  (A) : 1.15                     
REMARK 200  COMPLETENESS FOR SHELL     (%) : 99.1                               
REMARK 200  DATA REDUNDANCY IN SHELL       : 3.30                               
REMARK 200  R MERGE FOR SHELL          (I) : 0.42200                            
REMARK 200  R SYM FOR SHELL            (I) : 0.42200                            
REMARK 200  <I/SIGMA(I)> FOR SHELL         : 2.300                              
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: NULL                                                         
REMARK 280                                                                      
REMARK 280 CRYSTAL                                                              
REMARK 280 SOLVENT CONTENT, VS   (%): 46.00                                     
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.23                     
REMARK 280                                                                      
REMARK 280 CRYSTALLIZATION CONDITIONS: THE TERNARY COMPLEX OF DHFR WITH         
REMARK 280  NADPH AND SRI-9439 WAS FORMED BY MIXING HUMAN DHFR (20 MG/ML        
REMARK 280  IN 25 MM KPO4 (PH 7.0), 0.1 MM EDTA, AND 3 MM NAN3) WITH 60 MM      
REMARK 280  NADPH, FOLLOWED 15 MINUTES LATER BY 60 MM OF INHIBITOR IN DMSO      
REMARK 280  (FINAL CONCENTRATIONS OF 2 MM NADPH AND 2 MM INHIBITOR). THIS       
REMARK 280  COMPLEX 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         
REMARK 280  7.9-8.4), AND EQUILIBRATED WITH THE PRECIPITANT BY HANGING          
REMARK 280  DROP VAPOR DIFFUSION AT 277 K. THE CRYSTAL GREW IN ABOUT 3          
REMARK 280  WEEKS. THE CRYSTAL WAS FLASH-COOLED DIRECTLY IN LIQUID              
REMARK 280  NITROGEN AFTER HARVESTING INTO MOTHER LIQUOR CONTAINING 10%         
REMARK 280  GLYCEROL., PH 8.00, VAPOR DIFFUSION, HANGING DROP                   
REMARK 290                                                                      
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY                                            
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 21                       
REMARK 290                                                                      
REMARK 290      SYMOP   SYMMETRY                                                
REMARK 290     NNNMMM   OPERATOR                                                
REMARK 290       1555   X,Y,Z                                                   
REMARK 290       2555   -X+1/2,-Y,Z+1/2                                         
REMARK 290       3555   -X,Y+1/2,-Z+1/2                                         
REMARK 290       4555   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       20.73350            
REMARK 290   SMTRY2   2  0.000000 -1.000000  0.000000        0.00000            
REMARK 290   SMTRY3   2  0.000000  0.000000  1.000000       41.39950            
REMARK 290   SMTRY1   3 -1.000000  0.000000  0.000000        0.00000            
REMARK 290   SMTRY2   3  0.000000  1.000000  0.000000       27.63750            
REMARK 290   SMTRY3   3  0.000000  0.000000 -1.000000       41.39950            
REMARK 290   SMTRY1   4  1.000000  0.000000  0.000000       20.73350            
REMARK 290   SMTRY2   4  0.000000 -1.000000  0.000000       27.63750            
REMARK 290   SMTRY3   4  0.000000  0.000000 -1.000000        0.00000            
REMARK 290                                                                      
REMARK 290 REMARK: NULL                                                         
REMARK 300                                                                      
REMARK 300 BIOMOLECULE: 1                                                       
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM                
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN                  
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON               
REMARK 300 BURIED SURFACE AREA.                                                 
REMARK 350                                                                      
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN           
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE                
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS          
REMARK 350 GIVEN BELOW.  BOTH NON-CRYSTALLOGRAPHIC AND                          
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.                               
REMARK 350                                                                      
REMARK 350 BIOMOLECULE: 1                                                       
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC                         
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A                                     
REMARK 350   BIOMT1   1  1.000000  0.000000  0.000000        0.00000            
REMARK 350   BIOMT2   1  0.000000  1.000000  0.000000        0.00000            
REMARK 350   BIOMT3   1  0.000000  0.000000  1.000000        0.00000            
REMARK 465                                                                      
REMARK 465 MISSING RESIDUES                                                     
REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE                       
REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN               
REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)                
REMARK 465                                                                      
REMARK 465   M RES C SSSEQI                                                     
REMARK 465     VAL A     1                                                      
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     GLY A   2    N    CA   O                                         
REMARK 470     GLU A 101    CD   OE1  OE2                                       
REMARK 470     GLN A 102    NE2                                                 
REMARK 470     GLU A 143    CD   OE1  OE2                                       
REMARK 470     LYS A 173    NZ                                                  
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    LEU A   4   CA  -  CB  -  CG  ANGL. DEV. =  15.4 DEGREES          
REMARK 500    ASP A  21   CB  -  CG  -  OD1 ANGL. DEV. =   5.4 DEGREES          
REMARK 500    PHE A  31   CB  -  CG  -  CD2 ANGL. DEV. =   4.6 DEGREES          
REMARK 500    ARG A  32   NE  -  CZ  -  NH1 ANGL. DEV. =   3.4 DEGREES          
REMARK 500    ARG A  32   NE  -  CZ  -  NH2 ANGL. DEV. =  -4.1 DEGREES          
REMARK 500    MET A  37   CG  -  SD  -  CE  ANGL. DEV. =  -9.8 DEGREES          
REMARK 500    ARG A  65   NE  -  CZ  -  NH1 ANGL. DEV. =   3.5 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      -92.78   -102.11                                   
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 A 552        DISTANCE =  7.82 ANGSTROMS                       
REMARK 525    HOH A 587        DISTANCE =  5.43 ANGSTROMS                       
REMARK 525    HOH A 613        DISTANCE =  7.63 ANGSTROMS                       
REMARK 525    HOH A 628        DISTANCE =  5.20 ANGSTROMS                       
REMARK 525    HOH A 686        DISTANCE =  5.60 ANGSTROMS                       
REMARK 800                                                                      
REMARK 800 SITE                                                                 
REMARK 800 SITE_IDENTIFIER: AC1                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE SO4 A 203                 
REMARK 800 SITE_IDENTIFIER: AC2                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE SO4 A 204                 
REMARK 800 SITE_IDENTIFIER: AC3                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE LIH A 201                 
REMARK 800 SITE_IDENTIFIER: AC4                                                 
REMARK 800 EVIDENCE_CODE: SOFTWARE                                              
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NDP A 202                 
REMARK 900                                                                      
REMARK 900 RELATED ENTRIES                                                      
REMARK 900 RELATED ID: 1KMV   RELATED DB: PDB                                   
REMARK 900 HUMAN DIHYDROFOLATE REDUCTASE COMPLEXED WITH NADPH AND (Z)-          
REMARK 900 6-(2-[2,5-DIMETHOXYPHENYL]ETHEN-1-YL)-2,4-DIAMINO-5-                 
REMARK 900 METHYLPYRIDO[2,3-D]PYRIMIDINE (SRI-9662), A LIPOPHILIC               
REMARK 900 ANTIFOLATE                                                           
DBREF  1KMS A    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                                              
HET    SO4  A 203       5                                                       
HET    SO4  A 204       5                                                       
HET    LIH  A 201      25                                                       
HET    NDP  A 202      48                                                       
HETNAM     SO4 SULFATE ION                                                      
HETNAM     LIH 6-([5-QUINOLYLAMINO]METHYL)-2,4-DIAMINO-5-                       
HETNAM   2 LIH  METHYLPYRIDO[2,3-D]PYRIMIDINE                                   
HETNAM     NDP NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE                  
HETNAM   2 NDP  PHOSPHATE                                                       
HETSYN     LIH SRI-9439                                                         
FORMUL   2  SO4    2(O4 S 2-)                                                   
FORMUL   4  LIH    C18 H17 N7                                                   
FORMUL   5  NDP    C21 H30 N7 O17 P3                                            
FORMUL   6  HOH   *399(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  GLU A  101  1                                  10    
HELIX    5   5 GLY A  117  ASN A  126  1                                  10    
SHEET    1   A 8 PHE A  88  SER A  90  0                                        
SHEET    2   A 8 ILE A  71  LEU A  75  1  N  VAL A  74   O  PHE A  88           
SHEET    3   A 8 GLN A  47  GLY A  53  1  N  VAL A  50   O  ILE A  71           
SHEET    4   A 8 VAL A 109  ILE A 114  1  O  TRP A 113   N  LEU A  49           
SHEET    5   A 8 LEU A   4  VAL A  10  1  N  ASN A   5   O  ILE A 114           
SHEET    6   A 8 LEU A 131  ILE A 138  1  O  PHE A 134   N  CYS A   6           
SHEET    7   A 8 ILE A 175  LYS A 184 -1  O  LYS A 178   N  ARG A 137           
SHEET    8   A 8 TYR A 156  LEU A 158 -1  N  LYS A 157   O  GLU A 183           
SHEET    1   B 8 PHE A  88  SER A  90  0                                        
SHEET    2   B 8 ILE A  71  LEU A  75  1  N  VAL A  74   O  PHE A  88           
SHEET    3   B 8 GLN A  47  GLY A  53  1  N  VAL A  50   O  ILE A  71           
SHEET    4   B 8 VAL A 109  ILE A 114  1  O  TRP A 113   N  LEU A  49           
SHEET    5   B 8 LEU A   4  VAL A  10  1  N  ASN A   5   O  ILE A 114           
SHEET    6   B 8 LEU A 131  ILE A 138  1  O  PHE A 134   N  CYS A   6           
SHEET    7   B 8 ILE A 175  LYS A 184 -1  O  LYS A 178   N  ARG A 137           
SHEET    8   B 8 GLN A 170  GLU A 172 -1  N  GLN A 170   O  TYR A 177           
SHEET    1   C 2 GLY A  15  GLY A  17  0                                        
SHEET    2   C 2 THR A 146  PHE A 147 -1  O  THR A 146   N  GLY A  17           
CISPEP   1 ARG A   65    PRO A   66          0        -5.49                     
CISPEP   2 GLY A  116    GLY A  117          0         4.45                     
SITE     1 AC1  4 PRO A  61  GLU A  62  HOH A 500  HOH A 524                    
SITE     1 AC2  7 ARG A  28  LYS A  68  GLY A  69  HOH A 375                    
SITE     2 AC2  7 HOH A 608  HOH A 658  HOH A 695                               
SITE     1 AC3 12 ILE A   7  VAL A   8  GLU A  30  PHE A  31                    
SITE     2 AC3 12 PHE A  34  PRO A  61  VAL A 115  TYR A 121                    
SITE     3 AC3 12 NDP A 202  HOH A 302  HOH A 343  HOH A 401                    
SITE     1 AC4 38 VAL A   8  ALA A   9  ILE A  16  GLY A  17                    
SITE     2 AC4 38 LYS A  18  GLY A  20  ASP A  21  LEU A  22                    
SITE     3 AC4 38 TRP A  24  GLY A  53  LYS A  54  LYS A  55                    
SITE     4 AC4 38 THR A  56  LEU A  75  SER A  76  ARG A  77                    
SITE     5 AC4 38 GLU A  78  ARG A  91  LYS A  98  VAL A 115                    
SITE     6 AC4 38 GLY A 117  SER A 118  SER A 119  VAL A 120                    
SITE     7 AC4 38 TYR A 121  GLU A 123  THR A 146  LIH A 201                    
SITE     8 AC4 38 HOH A 317  HOH A 339  HOH A 389  HOH A 400                    
SITE     9 AC4 38 HOH A 401  HOH A 435  HOH A 581  HOH A 584                    
SITE    10 AC4 38 HOH A 643  HOH A 689                                          
CRYST1   41.467   55.275   82.799  90.00  90.00  90.00 P 21 21 21    4          
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      0.024116  0.000000  0.000000        0.00000                         
SCALE2      0.000000  0.018091  0.000000        0.00000                         
SCALE3      0.000000  0.000000  0.012077        0.00000                         
(ATOM LINES ARE NOT SHOWN.)
END                                                                             
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