HEADER OXIDOREDUCTASE/TRANSFERASE 13-AUG-09 3INV
TITLE TRYPANOSOMA CRUZI DIHYDROFOLATE REDUCTASE-THYMIDYLATE SYNTHASE
TITLE 2 COMPLEXED WITH NADPH, DUMP AND C-448 ANTIFOLATE
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: BIFUNCTIONAL DIHYDROFOLATE REDUCTASE-THYMIDYLATE SYNTHASE;
COMPND 3 CHAIN: A, B;
COMPND 4 SYNONYM: DHFR-TS, DIHYDROFOLATE REDUCTASE, THYMIDYLATE SYNTHASE;
COMPND 5 EC: 1.5.1.3, 2.1.1.45;
COMPND 6 ENGINEERED: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: TRYPANOSOMA CRUZI;
SOURCE 3 ORGANISM_TAXID: 5693;
SOURCE 4 STRAIN: Y;
SOURCE 5 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 6 EXPRESSION_SYSTEM_TAXID: 469008;
SOURCE 7 EXPRESSION_SYSTEM_STRAIN: BL21(DE3) PLYSS;
SOURCE 8 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 9 EXPRESSION_SYSTEM_PLASMID: PET11C
KEYWDS DHFR-TS ANTIFOLATE COMPLEX, METHYLTRANSFERASE, MULTIFUNCTIONAL
KEYWDS 2 ENZYME, NADP, NUCLEOTIDE BIOSYNTHESIS, ONE-CARBON METABOLISM,
KEYWDS 3 OXIDOREDUCTASE, TRANSFERASE, OXIDOREDUCTASE-TRANSFERASE COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR P.CHITNUMSUB,J.YUVANIYAMA,Y.YUTHAVONG
REVDAT 6 03-APR-24 3INV 1 REMARK
REVDAT 5 21-FEB-24 3INV 1 REMARK
REVDAT 4 24-JAN-18 3INV 1 JRNL
REVDAT 3 01-NOV-17 3INV 1 REMARK
REVDAT 2 02-MAR-11 3INV 1 HETSYN
REVDAT 1 28-JUL-10 3INV 0
JRNL AUTH P.CHITNUMSUB,J.YUVANIYAMA,T.VILAIVAN,J.VANICHTANANKUL,
JRNL AUTH 2 S.KAMCHONWONGPAISAN,Y.YUTHAVONG
JRNL TITL STRUCTURAL BASIS OF ANTIFOLATE INHIBITION OF TRYPANOSOMA
JRNL TITL 2 CRUZI DIHYDROFOLATE REDUCTASE-THYMIDYLATE SYNTHASE
JRNL REF TO BE PUBLISHED
JRNL REFN
REMARK 2
REMARK 2 RESOLUTION. 2.37 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNS 1.2
REMARK 3 AUTHORS : BRUNGER,ADAMS,CLORE,DELANO,GROS,GROSSE-
REMARK 3 : KUNSTLEVE,JIANG,KUSZEWSKI,NILGES,PANNU,
REMARK 3 : READ,RICE,SIMONSON,WARREN
REMARK 3
REMARK 3 REFINEMENT TARGET : ENGH & HUBER
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.37
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 46.94
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : NULL
REMARK 3 DATA CUTOFF LOW (ABS(F)) : NULL
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : 91.5
REMARK 3 NUMBER OF REFLECTIONS : 40392
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 SET) : 0.189
REMARK 3 FREE R VALUE : 0.243
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.000
REMARK 3 FREE R VALUE TEST SET COUNT : 2036
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : 0.005
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : NULL
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 2.37
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.48
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 85.50
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 4385
REMARK 3 BIN R VALUE (WORKING SET) : 0.2180
REMARK 3 BIN FREE R VALUE : 0.3100
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 5.20
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 241
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : 0.020
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 8180
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 212
REMARK 3 SOLVENT ATOMS : 315
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 23.40
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 30.20
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.54000
REMARK 3 B22 (A**2) : 5.12000
REMARK 3 B33 (A**2) : -5.66000
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 COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.25
REMARK 3 ESD FROM SIGMAA (A) : 0.20
REMARK 3 LOW RESOLUTION CUTOFF (A) : 5.00
REMARK 3
REMARK 3 CROSS-VALIDATED ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM C-V LUZZATI PLOT (A) : 0.35
REMARK 3 ESD FROM C-V SIGMAA (A) : 0.31
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.008
REMARK 3 BOND ANGLES (DEGREES) : 1.600
REMARK 3 DIHEDRAL ANGLES (DEGREES) : NULL
REMARK 3 IMPROPER ANGLES (DEGREES) : NULL
REMARK 3
REMARK 3 ISOTROPIC THERMAL MODEL : OVERALL
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. RMS SIGMA
REMARK 3 MAIN-CHAIN BOND (A**2) : NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE (A**2) : NULL ; NULL
REMARK 3 SIDE-CHAIN BOND (A**2) : NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE (A**2) : NULL ; NULL
REMARK 3
REMARK 3 BULK SOLVENT MODELING.
REMARK 3 METHOD USED : CNS BULK SOLVENT MODEL USED
REMARK 3 KSOL : 0.35
REMARK 3 BSOL : 29.97
REMARK 3
REMARK 3 NCS MODEL : NULL
REMARK 3
REMARK 3 NCS RESTRAINTS. RMS SIGMA/WEIGHT
REMARK 3 GROUP 1 POSITIONAL (A) : NULL ; NULL
REMARK 3 GROUP 1 B-FACTOR (A**2) : NULL ; NULL
REMARK 3
REMARK 3 PARAMETER FILE 1 : NULL
REMARK 3 TOPOLOGY FILE 1 : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 3INV COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 17-AUG-09.
REMARK 100 THE DEPOSITION ID IS D_1000054643.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 21-NOV-05
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : 5.6
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : SPRING-8
REMARK 200 BEAMLINE : BL38B1
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.1
REMARK 200 MONOCHROMATOR : MIRROR
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : IMAGE PLATE
REMARK 200 DETECTOR MANUFACTURER : RIGAKU RAXIS
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : DENZO, HKL-2000
REMARK 200 DATA SCALING SOFTWARE : SCALEPACK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 40406
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.370
REMARK 200 RESOLUTION RANGE LOW (A) : 46.940
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 91.5
REMARK 200 DATA REDUNDANCY : 2.800
REMARK 200 R MERGE (I) : 0.06100
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 22.7000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.37
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.45
REMARK 200 COMPLETENESS FOR SHELL (%) : 84.7
REMARK 200 DATA REDUNDANCY IN SHELL : 2.50
REMARK 200 R MERGE FOR SHELL (I) : 0.12300
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : NULL
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: AMORE
REMARK 200 STARTING MODEL: LEISHMANIA MAJOR DHFR-TS
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 46.23
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.29
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PEG4000, NH4OAC, PH 5.6, MICROBATCH,
REMARK 280 TEMPERATURE 297K
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 83.91200
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 83.91200
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 46.94050
REMARK 290 SMTRY2 5 0.000000 1.000000 0.000000 68.45000
REMARK 290 SMTRY3 5 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 6 -1.000000 0.000000 0.000000 46.94050
REMARK 290 SMTRY2 6 0.000000 -1.000000 0.000000 68.45000
REMARK 290 SMTRY3 6 0.000000 0.000000 1.000000 83.91200
REMARK 290 SMTRY1 7 -1.000000 0.000000 0.000000 46.94050
REMARK 290 SMTRY2 7 0.000000 1.000000 0.000000 68.45000
REMARK 290 SMTRY3 7 0.000000 0.000000 -1.000000 83.91200
REMARK 290 SMTRY1 8 1.000000 0.000000 0.000000 46.94050
REMARK 290 SMTRY2 8 0.000000 -1.000000 0.000000 68.45000
REMARK 290 SMTRY3 8 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: DIMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 TOTAL BURIED SURFACE AREA: 9180 ANGSTROM**2
REMARK 350 SURFACE AREA OF THE COMPLEX: 41650 ANGSTROM**2
REMARK 350 CHANGE IN SOLVENT FREE ENERGY: -30.0 KCAL/MOL
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, 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 465
REMARK 465 MISSING RESIDUES
REMARK 465 THE FOLLOWING RESIDUES WERE NOT LOCATED IN THE
REMARK 465 EXPERIMENT. (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN
REMARK 465 IDENTIFIER; SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)
REMARK 465
REMARK 465 M RES C SSSEQI
REMARK 465 MET A 1
REMARK 465 SER A 516
REMARK 465 MET A 517
REMARK 465 LYS A 518
REMARK 465 MET A 519
REMARK 465 ALA A 520
REMARK 465 VAL A 521
REMARK 465 MET B 1
REMARK 465 SER B 2
REMARK 465 SER B 516
REMARK 465 MET B 517
REMARK 465 LYS B 518
REMARK 465 MET B 519
REMARK 465 ALA B 520
REMARK 465 VAL B 521
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 PHE A 266 NH2 ARG B 271 2.19
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: TORSION ANGLES
REMARK 500
REMARK 500 TORSION ANGLES OUTSIDE THE EXPECTED RAMACHANDRAN REGIONS:
REMARK 500 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 500 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE).
REMARK 500
REMARK 500 STANDARD TABLE:
REMARK 500 FORMAT:(10X,I3,1X,A3,1X,A1,I4,A1,4X,F7.2,3X,F7.2)
REMARK 500
REMARK 500 EXPECTED VALUES: GJ KLEYWEGT AND TA JONES (1996). PHI/PSI-
REMARK 500 CHOLOGY: RAMACHANDRAN REVISITED. STRUCTURE 4, 1395 - 1400
REMARK 500
REMARK 500 M RES CSSEQI PSI PHI
REMARK 500 LYS A 70 94.88 -164.43
REMARK 500 SER A 100 141.73 -174.89
REMARK 500 PRO A 113 -76.43 -48.31
REMARK 500 SER A 186 58.56 -148.19
REMARK 500 ARG A 192 127.74 -171.59
REMARK 500 LYS A 285 109.87 -168.59
REMARK 500 LEU A 331 59.02 -95.05
REMARK 500 MET A 337 -0.02 79.19
REMARK 500 TYR A 343 -101.92 17.99
REMARK 500 THR A 355 -68.67 -125.16
REMARK 500 CYS A 403 -62.69 -95.11
REMARK 500 PRO B 9 -168.87 -74.79
REMARK 500 GLU B 31 -2.92 -55.52
REMARK 500 PRO B 42 23.70 -69.30
REMARK 500 PRO B 66 154.38 -46.46
REMARK 500 GLU B 116 20.37 -79.63
REMARK 500 ALA B 202 -19.73 78.04
REMARK 500 ARG B 257 -8.32 -55.31
REMARK 500 ASN B 277 -3.99 69.41
REMARK 500 THR B 304 -3.74 -140.67
REMARK 500 TYR B 343 -99.89 17.81
REMARK 500 HIS B 349 48.55 -143.85
REMARK 500 THR B 355 -64.73 -121.76
REMARK 500
REMARK 500 REMARK: NULL
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE C50 A 601
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NDP A 602
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE UMP A 603
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE GOL A 701
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE GOL A 705
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE C50 B 601
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC7
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE NDP B 602
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC8
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE UMP B 603
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC9
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE GOL B 702
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE GOL B 703
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE GOL B 704
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 3CL9 RELATED DB: PDB
REMARK 900 THE SAME PROTEIN COMPLEXED WITH MTX
REMARK 900 RELATED ID: 3HBB RELATED DB: PDB
REMARK 900 THE SAME PROTEIN COMPLEXED WITH TMQ
REMARK 900 RELATED ID: 2H2Q RELATED DB: PDB
REMARK 900 THE SAME PROTEIN IN FOLATE-FREE STATE
REMARK 900 RELATED ID: 3CLB RELATED DB: PDB
REMARK 900 THE SAME PROTEIN COMPLEXED WITH TMQ
REMARK 900 RELATED ID: 3IRM RELATED DB: PDB
REMARK 900 TCDHFR-TS PROTEIN IN COMPLEX WITH CYCLOGUANIL
REMARK 900 RELATED ID: 3IRN RELATED DB: PDB
REMARK 900 TCDHFR-TS PROTEIN IN COMPLEX WITH NADPH AND CYCLOGUANIL
REMARK 900 RELATED ID: 3IRO RELATED DB: PDB
REMARK 900 TCDHFR-TS PROTEIN IN COMPLEX WITH NADPH NADPH AND Q-8 ANTIFOLATE
DBREF 3INV A 1 521 UNP Q27793 DRTS_TRYCR 1 521
DBREF 3INV B 1 521 UNP Q27793 DRTS_TRYCR 1 521
SEQRES 1 A 521 MET SER LEU PHE LYS ILE ARG MET PRO GLU THR VAL ALA
SEQRES 2 A 521 GLU GLY THR ARG LEU ALA LEU ARG ALA PHE SER LEU VAL
SEQRES 3 A 521 VAL ALA VAL ASP GLU HIS GLY GLY ILE GLY ASP GLY ARG
SEQRES 4 A 521 SER ILE PRO TRP ASN VAL PRO GLU ASP MET LYS PHE PHE
SEQRES 5 A 521 ARG ASP LEU THR THR LYS LEU ARG GLY LYS ASN VAL LYS
SEQRES 6 A 521 PRO SER PRO ALA LYS ARG ASN ALA VAL VAL MET GLY ARG
SEQRES 7 A 521 LYS THR TRP ASP SER ILE PRO PRO LYS PHE ARG PRO LEU
SEQRES 8 A 521 PRO GLY ARG LEU ASN VAL VAL LEU SER SER THR LEU THR
SEQRES 9 A 521 THR GLN HIS LEU LEU ASP GLY LEU PRO ASP GLU GLU LYS
SEQRES 10 A 521 ARG ASN LEU HIS ALA ASP SER ILE VAL ALA VAL ASN GLY
SEQRES 11 A 521 GLY LEU GLU GLN ALA LEU ARG LEU LEU ALA SER PRO ASN
SEQRES 12 A 521 TYR THR PRO SER ILE GLU THR VAL TYR CYS ILE GLY GLY
SEQRES 13 A 521 GLY SER VAL TYR ALA GLU ALA LEU ARG PRO PRO CYS VAL
SEQRES 14 A 521 HIS LEU LEU GLN ALA ILE TYR ARG THR THR ILE ARG ALA
SEQRES 15 A 521 SER GLU SER SER CYS SER VAL PHE PHE ARG VAL PRO GLU
SEQRES 16 A 521 SER GLY THR GLU ALA ALA ALA GLY ILE GLU TRP GLN ARG
SEQRES 17 A 521 GLU THR ILE SER GLU GLU LEU THR SER ALA ASN GLY ASN
SEQRES 18 A 521 GLU THR LYS TYR TYR PHE GLU LYS LEU ILE PRO ARG ASN
SEQRES 19 A 521 ARG GLU GLU GLU GLN TYR LEU SER LEU VAL ASP ARG ILE
SEQRES 20 A 521 ILE ARG GLU GLY ASN VAL LYS HIS ASP ARG THR GLY VAL
SEQRES 21 A 521 GLY THR LEU SER ILE PHE GLY ALA GLN MET ARG PHE SER
SEQRES 22 A 521 LEU ARG ASN ASN ARG LEU PRO LEU LEU THR THR LYS ARG
SEQRES 23 A 521 VAL PHE TRP ARG GLY VAL CYS GLU GLU LEU LEU TRP PHE
SEQRES 24 A 521 LEU ARG GLY GLU THR TYR ALA LYS LYS LEU SER ASP LYS
SEQRES 25 A 521 GLY VAL HIS ILE TRP ASP ASP ASN GLY SER ARG ALA PHE
SEQRES 26 A 521 LEU ASP SER ARG GLY LEU THR GLU TYR GLU GLU MET ASP
SEQRES 27 A 521 LEU GLY PRO VAL TYR GLY PHE GLN TRP ARG HIS PHE GLY
SEQRES 28 A 521 ALA ALA TYR THR HIS HIS ASP ALA ASN TYR ASP GLY GLN
SEQRES 29 A 521 GLY VAL ASP GLN ILE LYS ALA ILE VAL GLU THR LEU LYS
SEQRES 30 A 521 THR ASN PRO ASP ASP ARG ARG MET LEU PHE THR ALA TRP
SEQRES 31 A 521 ASN PRO SER ALA LEU PRO ARG MET ALA LEU PRO PRO CYS
SEQRES 32 A 521 HIS LEU LEU ALA GLN PHE TYR VAL SER ASN GLY GLU LEU
SEQRES 33 A 521 SER CYS MET LEU TYR GLN ARG SER CYS ASP MET GLY LEU
SEQRES 34 A 521 GLY VAL PRO PHE ASN ILE ALA SER TYR ALA LEU LEU THR
SEQRES 35 A 521 ILE LEU ILE ALA LYS ALA THR GLY LEU ARG PRO GLY GLU
SEQRES 36 A 521 LEU VAL HIS THR LEU GLY ASP ALA HIS VAL TYR SER ASN
SEQRES 37 A 521 HIS VAL GLU PRO CYS ASN GLU GLN LEU LYS ARG VAL PRO
SEQRES 38 A 521 ARG ALA PHE PRO TYR LEU VAL PHE ARG ARG GLU ARG GLU
SEQRES 39 A 521 PHE LEU GLU ASP TYR GLU GLU GLY ASP MET GLU VAL ILE
SEQRES 40 A 521 ASP TYR ALA PRO TYR PRO PRO ILE SER MET LYS MET ALA
SEQRES 41 A 521 VAL
SEQRES 1 B 521 MET SER LEU PHE LYS ILE ARG MET PRO GLU THR VAL ALA
SEQRES 2 B 521 GLU GLY THR ARG LEU ALA LEU ARG ALA PHE SER LEU VAL
SEQRES 3 B 521 VAL ALA VAL ASP GLU HIS GLY GLY ILE GLY ASP GLY ARG
SEQRES 4 B 521 SER ILE PRO TRP ASN VAL PRO GLU ASP MET LYS PHE PHE
SEQRES 5 B 521 ARG ASP LEU THR THR LYS LEU ARG GLY LYS ASN VAL LYS
SEQRES 6 B 521 PRO SER PRO ALA LYS ARG ASN ALA VAL VAL MET GLY ARG
SEQRES 7 B 521 LYS THR TRP ASP SER ILE PRO PRO LYS PHE ARG PRO LEU
SEQRES 8 B 521 PRO GLY ARG LEU ASN VAL VAL LEU SER SER THR LEU THR
SEQRES 9 B 521 THR GLN HIS LEU LEU ASP GLY LEU PRO ASP GLU GLU LYS
SEQRES 10 B 521 ARG ASN LEU HIS ALA ASP SER ILE VAL ALA VAL ASN GLY
SEQRES 11 B 521 GLY LEU GLU GLN ALA LEU ARG LEU LEU ALA SER PRO ASN
SEQRES 12 B 521 TYR THR PRO SER ILE GLU THR VAL TYR CYS ILE GLY GLY
SEQRES 13 B 521 GLY SER VAL TYR ALA GLU ALA LEU ARG PRO PRO CYS VAL
SEQRES 14 B 521 HIS LEU LEU GLN ALA ILE TYR ARG THR THR ILE ARG ALA
SEQRES 15 B 521 SER GLU SER SER CYS SER VAL PHE PHE ARG VAL PRO GLU
SEQRES 16 B 521 SER GLY THR GLU ALA ALA ALA GLY ILE GLU TRP GLN ARG
SEQRES 17 B 521 GLU THR ILE SER GLU GLU LEU THR SER ALA ASN GLY ASN
SEQRES 18 B 521 GLU THR LYS TYR TYR PHE GLU LYS LEU ILE PRO ARG ASN
SEQRES 19 B 521 ARG GLU GLU GLU GLN TYR LEU SER LEU VAL ASP ARG ILE
SEQRES 20 B 521 ILE ARG GLU GLY ASN VAL LYS HIS ASP ARG THR GLY VAL
SEQRES 21 B 521 GLY THR LEU SER ILE PHE GLY ALA GLN MET ARG PHE SER
SEQRES 22 B 521 LEU ARG ASN ASN ARG LEU PRO LEU LEU THR THR LYS ARG
SEQRES 23 B 521 VAL PHE TRP ARG GLY VAL CYS GLU GLU LEU LEU TRP PHE
SEQRES 24 B 521 LEU ARG GLY GLU THR TYR ALA LYS LYS LEU SER ASP LYS
SEQRES 25 B 521 GLY VAL HIS ILE TRP ASP ASP ASN GLY SER ARG ALA PHE
SEQRES 26 B 521 LEU ASP SER ARG GLY LEU THR GLU TYR GLU GLU MET ASP
SEQRES 27 B 521 LEU GLY PRO VAL TYR GLY PHE GLN TRP ARG HIS PHE GLY
SEQRES 28 B 521 ALA ALA TYR THR HIS HIS ASP ALA ASN TYR ASP GLY GLN
SEQRES 29 B 521 GLY VAL ASP GLN ILE LYS ALA ILE VAL GLU THR LEU LYS
SEQRES 30 B 521 THR ASN PRO ASP ASP ARG ARG MET LEU PHE THR ALA TRP
SEQRES 31 B 521 ASN PRO SER ALA LEU PRO ARG MET ALA LEU PRO PRO CYS
SEQRES 32 B 521 HIS LEU LEU ALA GLN PHE TYR VAL SER ASN GLY GLU LEU
SEQRES 33 B 521 SER CYS MET LEU TYR GLN ARG SER CYS ASP MET GLY LEU
SEQRES 34 B 521 GLY VAL PRO PHE ASN ILE ALA SER TYR ALA LEU LEU THR
SEQRES 35 B 521 ILE LEU ILE ALA LYS ALA THR GLY LEU ARG PRO GLY GLU
SEQRES 36 B 521 LEU VAL HIS THR LEU GLY ASP ALA HIS VAL TYR SER ASN
SEQRES 37 B 521 HIS VAL GLU PRO CYS ASN GLU GLN LEU LYS ARG VAL PRO
SEQRES 38 B 521 ARG ALA PHE PRO TYR LEU VAL PHE ARG ARG GLU ARG GLU
SEQRES 39 B 521 PHE LEU GLU ASP TYR GLU GLU GLY ASP MET GLU VAL ILE
SEQRES 40 B 521 ASP TYR ALA PRO TYR PRO PRO ILE SER MET LYS MET ALA
SEQRES 41 B 521 VAL
HET C50 A 601 23
HET NDP A 602 48
HET UMP A 603 20
HET GOL A 701 6
HET GOL A 705 6
HET C50 B 601 23
HET NDP B 602 48
HET UMP B 603 20
HET GOL B 702 6
HET GOL B 703 6
HET GOL B 704 6
HETNAM C50 1-[3-(2,3-DICHLOROPHENOXY)PROPOXY]-6,6-DIMETHYL-1,6-
HETNAM 2 C50 DIHYDRO-1,3,5-TRIAZINE-2,4-DIAMINE
HETNAM NDP NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE
HETNAM 2 NDP PHOSPHATE
HETNAM UMP 2'-DEOXYURIDINE 5'-MONOPHOSPHATE
HETNAM GOL GLYCEROL
HETSYN UMP DUMP
HETSYN GOL GLYCERIN; PROPANE-1,2,3-TRIOL
FORMUL 3 C50 2(C14 H19 CL2 N5 O2)
FORMUL 4 NDP 2(C21 H30 N7 O17 P3)
FORMUL 5 UMP 2(C9 H13 N2 O8 P)
FORMUL 6 GOL 5(C3 H8 O3)
FORMUL 14 HOH *315(H2 O)
HELIX 1 1 VAL A 45 LYS A 58 1 14
HELIX 2 2 ARG A 78 ILE A 84 1 7
HELIX 3 3 PRO A 85 ARG A 89 5 5
HELIX 4 4 THR A 104 GLY A 111 1 8
HELIX 5 5 ASP A 114 HIS A 121 1 8
HELIX 6 6 GLY A 131 ALA A 140 1 10
HELIX 7 7 GLY A 156 LEU A 164 1 9
HELIX 8 8 PRO A 167 HIS A 170 5 4
HELIX 9 9 THR A 198 ALA A 202 5 5
HELIX 10 10 ASN A 234 GLY A 251 1 18
HELIX 11 11 ARG A 275 ARG A 278 5 4
HELIX 12 12 PHE A 288 ARG A 301 1 14
HELIX 13 13 ALA A 306 ASP A 311 1 6
HELIX 14 14 TRP A 317 SER A 322 1 6
HELIX 15 15 SER A 322 ARG A 329 1 8
HELIX 16 16 VAL A 342 PHE A 350 1 9
HELIX 17 17 ASP A 367 ASN A 379 1 13
HELIX 18 18 ALA A 394 MET A 398 5 5
HELIX 19 19 GLY A 430 THR A 449 1 20
HELIX 20 20 HIS A 469 LEU A 477 1 9
HELIX 21 21 PHE A 495 TYR A 499 5 5
HELIX 22 22 GLU A 500 GLY A 502 5 3
HELIX 23 23 ALA B 13 ARG B 17 5 5
HELIX 24 24 VAL B 45 LYS B 58 1 14
HELIX 25 25 ARG B 78 ILE B 84 1 7
HELIX 26 26 PRO B 85 ARG B 89 5 5
HELIX 27 27 THR B 104 GLY B 111 1 8
HELIX 28 28 LEU B 120 ASP B 123 5 4
HELIX 29 29 GLY B 131 SER B 141 1 11
HELIX 30 30 GLY B 156 LEU B 164 1 9
HELIX 31 31 PRO B 167 HIS B 170 5 4
HELIX 32 32 THR B 198 ALA B 202 5 5
HELIX 33 33 ASN B 234 GLY B 251 1 18
HELIX 34 34 ARG B 275 ARG B 278 5 4
HELIX 35 35 PHE B 288 ARG B 301 1 14
HELIX 36 36 ALA B 306 ASP B 311 1 6
HELIX 37 37 SER B 322 ARG B 329 1 8
HELIX 38 38 VAL B 342 PHE B 350 1 9
HELIX 39 39 ASP B 367 ASN B 379 1 13
HELIX 40 40 ALA B 394 MET B 398 5 5
HELIX 41 41 GLY B 430 ALA B 448 1 19
HELIX 42 42 HIS B 469 LEU B 477 1 9
HELIX 43 43 PHE B 495 TYR B 499 5 5
HELIX 44 44 GLU B 500 GLY B 502 5 3
SHEET 1 A 8 ILE A 125 VAL A 128 0
SHEET 2 A 8 ARG A 94 LEU A 99 1 N VAL A 98 O VAL A 128
SHEET 3 A 8 ARG A 71 GLY A 77 1 N VAL A 74 O VAL A 97
SHEET 4 A 8 ILE A 148 CYS A 153 1 O TYR A 152 N VAL A 75
SHEET 5 A 8 PHE A 23 ASP A 30 1 N SER A 24 O VAL A 151
SHEET 6 A 8 LEU A 172 ARG A 181 1 O TYR A 176 N LEU A 25
SHEET 7 A 8 LYS A 224 PRO A 232 -1 O LEU A 230 N ILE A 175
SHEET 8 A 8 TRP A 206 ILE A 211 -1 N GLN A 207 O ILE A 231
SHEET 1 B 8 ILE A 125 VAL A 128 0
SHEET 2 B 8 ARG A 94 LEU A 99 1 N VAL A 98 O VAL A 128
SHEET 3 B 8 ARG A 71 GLY A 77 1 N VAL A 74 O VAL A 97
SHEET 4 B 8 ILE A 148 CYS A 153 1 O TYR A 152 N VAL A 75
SHEET 5 B 8 PHE A 23 ASP A 30 1 N SER A 24 O VAL A 151
SHEET 6 B 8 LEU A 172 ARG A 181 1 O TYR A 176 N LEU A 25
SHEET 7 B 8 LYS A 224 PRO A 232 -1 O LEU A 230 N ILE A 175
SHEET 8 B 8 LEU A 215 THR A 216 -1 N LEU A 215 O TYR A 225
SHEET 1 C 2 GLY A 34 GLY A 36 0
SHEET 2 C 2 VAL A 189 PHE A 190 -1 O VAL A 189 N ILE A 35
SHEET 1 D 6 ASN A 252 HIS A 255 0
SHEET 2 D 6 GLY A 261 SER A 273 -1 O THR A 262 N LYS A 254
SHEET 3 D 6 ARG A 452 TYR A 466 -1 O HIS A 458 N MET A 270
SHEET 4 D 6 GLU A 415 ASP A 426 1 N CYS A 418 O VAL A 457
SHEET 5 D 6 HIS A 404 SER A 412 -1 N TYR A 410 O SER A 417
SHEET 6 D 6 LEU A 386 THR A 388 -1 N PHE A 387 O ALA A 407
SHEET 1 E 2 TYR A 486 PHE A 489 0
SHEET 2 E 2 MET A 504 ILE A 507 -1 O GLU A 505 N VAL A 488
SHEET 1 F 8 ILE B 125 VAL B 128 0
SHEET 2 F 8 ARG B 94 LEU B 99 1 N VAL B 98 O VAL B 128
SHEET 3 F 8 ARG B 71 GLY B 77 1 N VAL B 74 O LEU B 95
SHEET 4 F 8 ILE B 148 CYS B 153 1 O TYR B 152 N VAL B 75
SHEET 5 F 8 PHE B 23 ASP B 30 1 N SER B 24 O VAL B 151
SHEET 6 F 8 LEU B 172 ARG B 181 1 O ILE B 180 N VAL B 29
SHEET 7 F 8 LYS B 224 PRO B 232 -1 O TYR B 226 N THR B 179
SHEET 8 F 8 TRP B 206 ILE B 211 -1 N GLU B 209 O LYS B 229
SHEET 1 G 8 ILE B 125 VAL B 128 0
SHEET 2 G 8 ARG B 94 LEU B 99 1 N VAL B 98 O VAL B 128
SHEET 3 G 8 ARG B 71 GLY B 77 1 N VAL B 74 O LEU B 95
SHEET 4 G 8 ILE B 148 CYS B 153 1 O TYR B 152 N VAL B 75
SHEET 5 G 8 PHE B 23 ASP B 30 1 N SER B 24 O VAL B 151
SHEET 6 G 8 LEU B 172 ARG B 181 1 O ILE B 180 N VAL B 29
SHEET 7 G 8 LYS B 224 PRO B 232 -1 O TYR B 226 N THR B 179
SHEET 8 G 8 LEU B 215 THR B 216 -1 N LEU B 215 O TYR B 225
SHEET 1 H 2 GLY B 34 GLY B 36 0
SHEET 2 H 2 VAL B 189 PHE B 190 -1 O VAL B 189 N ILE B 35
SHEET 1 I 6 ASN B 252 HIS B 255 0
SHEET 2 I 6 GLY B 261 SER B 273 -1 O SER B 264 N ASN B 252
SHEET 3 I 6 ARG B 452 TYR B 466 -1 O LEU B 460 N ALA B 268
SHEET 4 I 6 GLU B 415 ASP B 426 1 N CYS B 425 O ASP B 462
SHEET 5 I 6 HIS B 404 SER B 412 -1 N TYR B 410 O SER B 417
SHEET 6 I 6 LEU B 386 THR B 388 -1 N PHE B 387 O ALA B 407
SHEET 1 J 2 TYR B 486 PHE B 489 0
SHEET 2 J 2 MET B 504 ILE B 507 -1 O ILE B 507 N TYR B 486
CISPEP 1 ARG A 89 PRO A 90 0 -0.25
CISPEP 2 THR A 145 PRO A 146 0 1.14
CISPEP 3 PRO A 166 PRO A 167 0 0.16
CISPEP 4 ARG B 89 PRO B 90 0 -0.29
CISPEP 5 THR B 145 PRO B 146 0 0.11
CISPEP 6 PRO B 166 PRO B 167 0 0.06
SITE 1 AC1 11 VAL A 26 VAL A 27 ILE A 41 ASP A 48
SITE 2 AC1 11 MET A 49 PHE A 52 THR A 80 PHE A 88
SITE 3 AC1 11 ILE A 154 TYR A 160 NDP A 602
SITE 1 AC2 29 VAL A 27 ALA A 28 ILE A 35 GLY A 36
SITE 2 AC2 29 ASP A 37 GLY A 38 ARG A 39 SER A 40
SITE 3 AC2 29 ILE A 41 GLY A 77 ARG A 78 LYS A 79
SITE 4 AC2 29 THR A 80 LEU A 99 SER A 100 SER A 101
SITE 5 AC2 29 THR A 102 GLY A 130 GLY A 131 ILE A 154
SITE 6 AC2 29 GLY A 155 GLY A 156 GLY A 157 SER A 158
SITE 7 AC2 29 VAL A 159 TYR A 160 C50 A 601 HOH A1073
SITE 8 AC2 29 HOH A1156
SITE 1 AC3 18 ARG A 257 CYS A 403 HIS A 404 GLN A 422
SITE 2 AC3 18 ARG A 423 SER A 424 CYS A 425 ASP A 426
SITE 3 AC3 18 GLY A 430 ASN A 434 HIS A 464 TYR A 466
SITE 4 AC3 18 GOL A 701 GOL A 705 HOH A1036 HOH A1160
SITE 5 AC3 18 ARG B 383 ARG B 384
SITE 1 AC4 4 LEU A 429 PHE A 433 UMP A 603 GOL A 705
SITE 1 AC5 7 GLU A 295 TYR A 343 HIS A 404 PHE A 433
SITE 2 AC5 7 UMP A 603 GOL A 701 HOH A1197
SITE 1 AC6 12 VAL B 26 VAL B 27 ILE B 41 ASP B 48
SITE 2 AC6 12 PHE B 52 ILE B 84 PRO B 85 PHE B 88
SITE 3 AC6 12 ILE B 154 TYR B 160 THR B 178 NDP B 602
SITE 1 AC7 26 ALA B 28 ILE B 35 ASP B 37 GLY B 38
SITE 2 AC7 26 ARG B 39 SER B 40 ILE B 41 GLY B 77
SITE 3 AC7 26 ARG B 78 LYS B 79 THR B 80 LEU B 99
SITE 4 AC7 26 SER B 100 SER B 101 THR B 102 GLY B 130
SITE 5 AC7 26 GLY B 131 ILE B 154 GLY B 155 GLY B 156
SITE 6 AC7 26 GLY B 157 SER B 158 VAL B 159 TYR B 160
SITE 7 AC7 26 C50 B 601 HOH B1274
SITE 1 AC8 16 ARG A 383 ARG A 384 CYS B 403 HIS B 404
SITE 2 AC8 16 GLN B 422 ARG B 423 SER B 424 ASP B 426
SITE 3 AC8 16 GLY B 430 ASN B 434 HIS B 464 TYR B 466
SITE 4 AC8 16 GOL B 703 GOL B 704 HOH B1146 HOH B1218
SITE 1 AC9 5 GLY A 267 GLN B 239 GLN B 269 ARG B 271
SITE 2 AC9 5 HOH B1031
SITE 1 BC1 3 GLY B 430 UMP B 603 GOL B 704
SITE 1 BC2 8 GLU B 295 ILE B 316 TYR B 343 HIS B 404
SITE 2 BC2 8 UMP B 603 GOL B 703 HOH B1067 HOH B1111
CRYST1 93.881 136.900 167.824 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 0.010652 0.000000 0.000000 0.00000
SCALE2 0.000000 0.007305 0.000000 0.00000
SCALE3 0.000000 0.000000 0.005959 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
