HEADER OXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR 14-JUL-10 3NXU
TITLE CRYSTAL STRUCTURE OF HUMAN CYTOCHROME P4503A4 BOUND TO AN INHIBITOR
TITLE 2 RITONAVIR
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: CYTOCHROME P450 3A4;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: UNP RESIDUES 1-2 AND 25-503;
COMPND 5 SYNONYM: QUININE 3-MONOOXYGENASE, CYPIIIA4, NIFEDIPINE OXIDASE,
COMPND 6 CYTOCHROME P450 3A3, CYPIIIA3, CYTOCHROME P450 HLP,
COMPND 7 TAUROCHENODEOXYCHOLATE 6-ALPHA-HYDROXYLASE, CYTOCHROME P450 NF-25,
COMPND 8 CYTOCHROME P450-PCN1, ALBENDAZOLE MONOOXYGENASE, ALBENDAZOLE
COMPND 9 SULFOXIDASE;
COMPND 10 EC: 1.14.13.67, 1.14.13.97, 1.14.13.32;
COMPND 11 ENGINEERED: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 GENE: CYP3A3, CYP3A4;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 469008;
SOURCE 8 EXPRESSION_SYSTEM_STRAIN: BL21(DE3)
KEYWDS ALPHA BETA PROTEIN, CYTOCHROME P450 FOLD, HEMOPROTEIN, MONOOXYGENASE,
KEYWDS 2 CYTOCHROME P450 REDUCTASE, ENDOPLASMIC RETICULUM, OXIDOREDUCTASE-
KEYWDS 3 OXIDOREDUCTASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR I.F.SEVRIOUKOVA,T.L.POULOS
REVDAT 6 06-SEP-23 3NXU 1 REMARK SEQADV LINK
REVDAT 5 08-NOV-17 3NXU 1 REMARK
REVDAT 4 22-DEC-10 3NXU 1 HEADER KEYWDS REMARK
REVDAT 3 10-NOV-10 3NXU 1 JRNL
REVDAT 2 27-OCT-10 3NXU 1 JRNL
REVDAT 1 20-OCT-10 3NXU 0
JRNL AUTH I.F.SEVRIOUKOVA,T.L.POULOS
JRNL TITL STRUCTURE AND MECHANISM OF THE COMPLEX BETWEEN CYTOCHROME
JRNL TITL 2 P4503A4 AND RITONAVIR.
JRNL REF PROC.NATL.ACAD.SCI.USA V. 107 18422 2010
JRNL REFN ISSN 0027-8424
JRNL PMID 20937904
JRNL DOI 10.1073/PNAS.1010693107
REMARK 2
REMARK 2 RESOLUTION. 2.00 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : CNS
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) : 2.00
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 40.40
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) (%) : 97.4
REMARK 3 NUMBER OF REFLECTIONS : 76649
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) : 0.232
REMARK 3 FREE R VALUE : 0.262
REMARK 3 FREE R VALUE TEST SET SIZE (%) : NULL
REMARK 3 FREE R VALUE TEST SET COUNT : 3889
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : NULL
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) : 2.00
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.13
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 97.00
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : NULL
REMARK 3 BIN R VALUE (WORKING SET) : 0.3090
REMARK 3 BIN FREE R VALUE : 0.3460
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : NULL
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 618
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : 0.014
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 7356
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 210
REMARK 3 SOLVENT ATOMS : 389
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 34.80
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 44.30
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 9.80000
REMARK 3 B22 (A**2) : 0.00000
REMARK 3 B33 (A**2) : 0.00000
REMARK 3 B12 (A**2) : -7.90000
REMARK 3 B13 (A**2) : -1.89000
REMARK 3 B23 (A**2) : -5.44000
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : 0.30
REMARK 3 ESD FROM SIGMAA (A) : 0.28
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) : 0.34
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 1.400
REMARK 3 BOND ANGLES (DEGREES) : NULL
REMARK 3 DIHEDRAL ANGLES (DEGREES) : 21.80
REMARK 3 IMPROPER ANGLES (DEGREES) : 1.350
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 : NULL
REMARK 3 KSOL : NULL
REMARK 3 BSOL : NULL
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 3NXU COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 27-JUL-10.
REMARK 100 THE DEPOSITION ID IS D_1000060414.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : NULL
REMARK 200 TEMPERATURE (KELVIN) : 103
REMARK 200 PH : 6.0
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : Y
REMARK 200 RADIATION SOURCE : SSRL
REMARK 200 BEAMLINE : BL11-1
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1
REMARK 200 MONOCHROMATOR : YALE MIRRORS
REMARK 200 OPTICS : MIRRORS
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : MARMOSAIC 325 MM CCD
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : MOSFLM
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 76811
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.000
REMARK 200 RESOLUTION RANGE LOW (A) : 77.380
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 2.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 98.0
REMARK 200 DATA REDUNDANCY : 3.700
REMARK 200 R MERGE (I) : 0.06400
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 10.8000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.00
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.05
REMARK 200 COMPLETENESS FOR SHELL (%) : 97.4
REMARK 200 DATA REDUNDANCY IN SHELL : 3.80
REMARK 200 R MERGE FOR SHELL (I) : 0.35000
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 4.600
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: PHASER
REMARK 200 STARTING MODEL: 1TQN
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 53.80
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.66
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 100 MM SODIUM MALONATE PH 6.0, 12 %
REMARK 280 POLYETHYLENE GLYCOL 3350, MICROBATCH UNDER OIL, TEMPERATURE 293K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: C 1 2 1
REMARK 290
REMARK 290 SYMOP SYMMETRY
REMARK 290 NNNMMM OPERATOR
REMARK 290 1555 X,Y,Z
REMARK 290 2555 -X,Y,-Z
REMARK 290 3555 X+1/2,Y+1/2,Z
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 0.00000
REMARK 290 SMTRY2 2 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 3 1.000000 0.000000 0.000000 81.06150
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 47.34500
REMARK 290 SMTRY3 3 0.000000 0.000000 1.000000 0.00000
REMARK 290 SMTRY1 4 -1.000000 0.000000 0.000000 81.06150
REMARK 290 SMTRY2 4 0.000000 1.000000 0.000000 47.34500
REMARK 290 SMTRY3 4 0.000000 0.000000 -1.000000 0.00000
REMARK 290
REMARK 290 REMARK: NULL
REMARK 300
REMARK 300 BIOMOLECULE: 1, 2
REMARK 300 SEE REMARK 350 FOR THE AUTHOR PROVIDED AND/OR PROGRAM
REMARK 300 GENERATED ASSEMBLY INFORMATION FOR THE STRUCTURE IN
REMARK 300 THIS ENTRY. THE REMARK MAY ALSO PROVIDE INFORMATION ON
REMARK 300 BURIED SURFACE AREA.
REMARK 350
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS
REMARK 350 GIVEN BELOW. BOTH NON-CRYSTALLOGRAPHIC AND
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.
REMARK 350
REMARK 350 BIOMOLECULE: 1
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A
REMARK 350 BIOMT1 1 1.000000 0.000000 0.000000 0.00000
REMARK 350 BIOMT2 1 0.000000 1.000000 0.000000 0.00000
REMARK 350 BIOMT3 1 0.000000 0.000000 1.000000 0.00000
REMARK 350
REMARK 350 BIOMOLECULE: 2
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: MONOMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: MONOMERIC
REMARK 350 SOFTWARE USED: PISA
REMARK 350 APPLY THE FOLLOWING TO CHAINS: B
REMARK 350 BIOMT1 1 1.000000 0.000000 0.000000 0.00000
REMARK 350 BIOMT2 1 0.000000 1.000000 0.000000 0.00000
REMARK 350 BIOMT3 1 0.000000 0.000000 1.000000 0.00000
REMARK 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 23
REMARK 465 ALA A 24
REMARK 465 TYR A 25
REMARK 465 GLY A 26
REMARK 465 THR A 27
REMARK 465 HIS A 28
REMARK 465 GLN A 265
REMARK 465 LYS A 266
REMARK 465 HIS A 267
REMARK 465 SER A 281
REMARK 465 LYS A 282
REMARK 465 GLU A 283
REMARK 465 THR A 284
REMARK 465 GLU A 285
REMARK 465 SER A 286
REMARK 465 HIS A 287
REMARK 465 LYS A 288
REMARK 465 ASP A 497
REMARK 465 GLY A 498
REMARK 465 THR A 499
REMARK 465 VAL A 500
REMARK 465 SER A 501
REMARK 465 GLY A 502
REMARK 465 ALA A 503
REMARK 465 HIS A 504
REMARK 465 HIS A 505
REMARK 465 HIS A 506
REMARK 465 HIS A 507
REMARK 465 MET B 23
REMARK 465 ALA B 24
REMARK 465 TYR B 25
REMARK 465 GLY B 26
REMARK 465 THR B 27
REMARK 465 HIS B 28
REMARK 465 GLN B 265
REMARK 465 LYS B 266
REMARK 465 HIS B 267
REMARK 465 SER B 281
REMARK 465 LYS B 282
REMARK 465 GLU B 283
REMARK 465 THR B 284
REMARK 465 GLU B 285
REMARK 465 SER B 286
REMARK 465 HIS B 287
REMARK 465 LYS B 288
REMARK 465 ASP B 497
REMARK 465 GLY B 498
REMARK 465 THR B 499
REMARK 465 VAL B 500
REMARK 465 SER B 501
REMARK 465 GLY B 502
REMARK 465 ALA B 503
REMARK 465 HIS B 504
REMARK 465 HIS B 505
REMARK 465 HIS B 506
REMARK 465 HIS B 507
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 NH2 ARG A 375 O1A HEM A 508 2.17
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 HIS A 30 3.31 -63.21
REMARK 500 PHE A 46 -48.52 66.52
REMARK 500 VAL A 101 -34.48 -136.83
REMARK 500 PHE A 102 61.26 -111.97
REMARK 500 ASP A 123 -126.15 42.07
REMARK 500 ARG A 212 68.10 -113.15
REMARK 500 TYR A 307 -63.07 -92.20
REMARK 500 MET A 353 90.77 -67.56
REMARK 500 LYS A 379 147.45 -178.51
REMARK 500 PRO A 405 32.26 -64.06
REMARK 500 ASN A 462 -32.88 -141.01
REMARK 500 HIS B 30 7.58 -69.45
REMARK 500 PHE B 46 -57.91 68.80
REMARK 500 VAL B 95 -66.69 -105.11
REMARK 500 PHE B 102 61.76 -105.88
REMARK 500 ASP B 123 -126.98 40.97
REMARK 500 PHE B 137 50.13 -112.31
REMARK 500 ASP B 194 54.46 35.99
REMARK 500 GLN B 279 1.92 -64.17
REMARK 500 ASN B 341 54.33 35.30
REMARK 500 MET B 353 93.79 -66.90
REMARK 500 LYS B 424 -40.56 -27.31
REMARK 500 GLN B 461 32.54 -90.38
REMARK 500 ASN B 462 -20.37 -159.16
REMARK 500 LEU B 483 107.40 -50.15
REMARK 500
REMARK 500 REMARK: NULL
REMARK 620
REMARK 620 METAL COORDINATION
REMARK 620 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 620 SSEQ=SEQUENCE NUMBER; I=INSERTION CODE):
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 HEM A 508 FE
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 CYS A 442 SG
REMARK 620 2 HEM A 508 NA 98.6
REMARK 620 3 HEM A 508 NB 86.1 89.0
REMARK 620 4 HEM A 508 NC 85.2 176.2 91.2
REMARK 620 5 HEM A 508 ND 94.2 90.8 179.7 89.0
REMARK 620 6 RIT A 600 N5 174.0 87.0 91.9 89.3 87.9
REMARK 620 N 1 2 3 4 5
REMARK 620
REMARK 620 COORDINATION ANGLES FOR: M RES CSSEQI METAL
REMARK 620 HEM B 508 FE
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 CYS B 442 SG
REMARK 620 2 HEM B 508 NA 94.5
REMARK 620 3 HEM B 508 NB 85.2 89.3
REMARK 620 4 HEM B 508 NC 85.1 179.6 90.8
REMARK 620 5 HEM B 508 ND 94.2 90.8 179.4 89.1
REMARK 620 6 RIT B 600 N5 167.1 97.7 98.9 82.6 81.6
REMARK 620 N 1 2 3 4 5
REMARK 630
REMARK 630 MOLECULE TYPE: PEPTIDE-LIKE INHIBITOR
REMARK 630 MOLECULE NAME: RITONAVIR
REMARK 630 (M=MODEL NUMBER; RES=RESIDUE NAME; C=CHAIN IDENTIFIER;
REMARK 630 SSSEQ=SEQUENCE NUMBER; I=INSERTION CODE.)
REMARK 630
REMARK 630 M RES C SSSEQI
REMARK 630 RIT A 600
REMARK 630 RIT B 600
REMARK 630 SOURCE: NULL
REMARK 630 TAXONOMY: NULL
REMARK 630 SUBCOMP: 013 015 VAL 019
REMARK 630 DETAILS: NULL
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DMS A 700
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DMS A 701
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DMS A 702
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DMS A 703
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC5
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE HEM A 508
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC6
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE RIT A 600
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC7
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DMS B 704
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC8
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE DMS B 705
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC9
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE HEM B 508
REMARK 800
REMARK 800 SITE_IDENTIFIER: BC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE RIT B 600
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 1TQN RELATED DB: PDB
REMARK 900 HUMAN CYTOCHROME P4503A4
REMARK 900 RELATED ID: 2V0M RELATED DB: PDB
REMARK 900 HUMAN CYTOCHROME P4503A4 BOUND TO KETOCONAZOLE
REMARK 900 RELATED ID: 2J0D RELATED DB: PDB
REMARK 900 HUMAN CYTOCHROME P4503A4 BOUND TO ERYTHROMYCIN
REMARK 900 RELATED ID: 1W0F RELATED DB: PDB
REMARK 900 HUMAN CYTOCHROME P4503A4 BOUND TO PROGESTERONE
REMARK 900 RELATED ID: 1W0G RELATED DB: PDB
REMARK 900 HUMAN CYTOCHROME P4503A4 BOUND TO METYRAPONE
REMARK 900 RELATED ID: 1W0E RELATED DB: PDB
REMARK 900 HUMAN CYTOCHROME P4503A4
REMARK 999
REMARK 999 THIS PROTEIN CONSISTS OF UNP RESIDUES 1-2 AND 25-503. DUE TO A
REMARK 999 DELETION OF UNP RESIDUES 3-24, RESIDUES 23-24 (MET ALA) IN 3NXU
REMARK 999 CORRESPONDING TO UNP RESIDUE 1-2.
DBREF 3NXU A 25 503 UNP P08684 CP3A4_HUMAN 25 503
DBREF 3NXU B 25 503 UNP P08684 CP3A4_HUMAN 25 503
SEQADV 3NXU MET A 23 UNP P08684 SEE REMARK 999
SEQADV 3NXU ALA A 24 UNP P08684 SEE REMARK 999
SEQADV 3NXU HIS A 504 UNP P08684 EXPRESSION TAG
SEQADV 3NXU HIS A 505 UNP P08684 EXPRESSION TAG
SEQADV 3NXU HIS A 506 UNP P08684 EXPRESSION TAG
SEQADV 3NXU HIS A 507 UNP P08684 EXPRESSION TAG
SEQADV 3NXU MET B 23 UNP P08684 SEE REMARK 999
SEQADV 3NXU ALA B 24 UNP P08684 SEE REMARK 999
SEQADV 3NXU HIS B 504 UNP P08684 EXPRESSION TAG
SEQADV 3NXU HIS B 505 UNP P08684 EXPRESSION TAG
SEQADV 3NXU HIS B 506 UNP P08684 EXPRESSION TAG
SEQADV 3NXU HIS B 507 UNP P08684 EXPRESSION TAG
SEQRES 1 A 485 MET ALA TYR GLY THR HIS SER HIS GLY LEU PHE LYS LYS
SEQRES 2 A 485 LEU GLY ILE PRO GLY PRO THR PRO LEU PRO PHE LEU GLY
SEQRES 3 A 485 ASN ILE LEU SER TYR HIS LYS GLY PHE CYS MET PHE ASP
SEQRES 4 A 485 MET GLU CYS HIS LYS LYS TYR GLY LYS VAL TRP GLY PHE
SEQRES 5 A 485 TYR ASP GLY GLN GLN PRO VAL LEU ALA ILE THR ASP PRO
SEQRES 6 A 485 ASP MET ILE LYS THR VAL LEU VAL LYS GLU CYS TYR SER
SEQRES 7 A 485 VAL PHE THR ASN ARG ARG PRO PHE GLY PRO VAL GLY PHE
SEQRES 8 A 485 MET LYS SER ALA ILE SER ILE ALA GLU ASP GLU GLU TRP
SEQRES 9 A 485 LYS ARG LEU ARG SER LEU LEU SER PRO THR PHE THR SER
SEQRES 10 A 485 GLY LYS LEU LYS GLU MET VAL PRO ILE ILE ALA GLN TYR
SEQRES 11 A 485 GLY ASP VAL LEU VAL ARG ASN LEU ARG ARG GLU ALA GLU
SEQRES 12 A 485 THR GLY LYS PRO VAL THR LEU LYS ASP VAL PHE GLY ALA
SEQRES 13 A 485 TYR SER MET ASP VAL ILE THR SER THR SER PHE GLY VAL
SEQRES 14 A 485 ASN ILE ASP SER LEU ASN ASN PRO GLN ASP PRO PHE VAL
SEQRES 15 A 485 GLU ASN THR LYS LYS LEU LEU ARG PHE ASP PHE LEU ASP
SEQRES 16 A 485 PRO PHE PHE LEU SER ILE THR VAL PHE PRO PHE LEU ILE
SEQRES 17 A 485 PRO ILE LEU GLU VAL LEU ASN ILE CYS VAL PHE PRO ARG
SEQRES 18 A 485 GLU VAL THR ASN PHE LEU ARG LYS SER VAL LYS ARG MET
SEQRES 19 A 485 LYS GLU SER ARG LEU GLU ASP THR GLN LYS HIS ARG VAL
SEQRES 20 A 485 ASP PHE LEU GLN LEU MET ILE ASP SER GLN ASN SER LYS
SEQRES 21 A 485 GLU THR GLU SER HIS LYS ALA LEU SER ASP LEU GLU LEU
SEQRES 22 A 485 VAL ALA GLN SER ILE ILE PHE ILE PHE ALA GLY TYR GLU
SEQRES 23 A 485 THR THR SER SER VAL LEU SER PHE ILE MET TYR GLU LEU
SEQRES 24 A 485 ALA THR HIS PRO ASP VAL GLN GLN LYS LEU GLN GLU GLU
SEQRES 25 A 485 ILE ASP ALA VAL LEU PRO ASN LYS ALA PRO PRO THR TYR
SEQRES 26 A 485 ASP THR VAL LEU GLN MET GLU TYR LEU ASP MET VAL VAL
SEQRES 27 A 485 ASN GLU THR LEU ARG LEU PHE PRO ILE ALA MET ARG LEU
SEQRES 28 A 485 GLU ARG VAL CYS LYS LYS ASP VAL GLU ILE ASN GLY MET
SEQRES 29 A 485 PHE ILE PRO LYS GLY VAL VAL VAL MET ILE PRO SER TYR
SEQRES 30 A 485 ALA LEU HIS ARG ASP PRO LYS TYR TRP THR GLU PRO GLU
SEQRES 31 A 485 LYS PHE LEU PRO GLU ARG PHE SER LYS LYS ASN LYS ASP
SEQRES 32 A 485 ASN ILE ASP PRO TYR ILE TYR THR PRO PHE GLY SER GLY
SEQRES 33 A 485 PRO ARG ASN CYS ILE GLY MET ARG PHE ALA LEU MET ASN
SEQRES 34 A 485 MET LYS LEU ALA LEU ILE ARG VAL LEU GLN ASN PHE SER
SEQRES 35 A 485 PHE LYS PRO CYS LYS GLU THR GLN ILE PRO LEU LYS LEU
SEQRES 36 A 485 SER LEU GLY GLY LEU LEU GLN PRO GLU LYS PRO VAL VAL
SEQRES 37 A 485 LEU LYS VAL GLU SER ARG ASP GLY THR VAL SER GLY ALA
SEQRES 38 A 485 HIS HIS HIS HIS
SEQRES 1 B 485 MET ALA TYR GLY THR HIS SER HIS GLY LEU PHE LYS LYS
SEQRES 2 B 485 LEU GLY ILE PRO GLY PRO THR PRO LEU PRO PHE LEU GLY
SEQRES 3 B 485 ASN ILE LEU SER TYR HIS LYS GLY PHE CYS MET PHE ASP
SEQRES 4 B 485 MET GLU CYS HIS LYS LYS TYR GLY LYS VAL TRP GLY PHE
SEQRES 5 B 485 TYR ASP GLY GLN GLN PRO VAL LEU ALA ILE THR ASP PRO
SEQRES 6 B 485 ASP MET ILE LYS THR VAL LEU VAL LYS GLU CYS TYR SER
SEQRES 7 B 485 VAL PHE THR ASN ARG ARG PRO PHE GLY PRO VAL GLY PHE
SEQRES 8 B 485 MET LYS SER ALA ILE SER ILE ALA GLU ASP GLU GLU TRP
SEQRES 9 B 485 LYS ARG LEU ARG SER LEU LEU SER PRO THR PHE THR SER
SEQRES 10 B 485 GLY LYS LEU LYS GLU MET VAL PRO ILE ILE ALA GLN TYR
SEQRES 11 B 485 GLY ASP VAL LEU VAL ARG ASN LEU ARG ARG GLU ALA GLU
SEQRES 12 B 485 THR GLY LYS PRO VAL THR LEU LYS ASP VAL PHE GLY ALA
SEQRES 13 B 485 TYR SER MET ASP VAL ILE THR SER THR SER PHE GLY VAL
SEQRES 14 B 485 ASN ILE ASP SER LEU ASN ASN PRO GLN ASP PRO PHE VAL
SEQRES 15 B 485 GLU ASN THR LYS LYS LEU LEU ARG PHE ASP PHE LEU ASP
SEQRES 16 B 485 PRO PHE PHE LEU SER ILE THR VAL PHE PRO PHE LEU ILE
SEQRES 17 B 485 PRO ILE LEU GLU VAL LEU ASN ILE CYS VAL PHE PRO ARG
SEQRES 18 B 485 GLU VAL THR ASN PHE LEU ARG LYS SER VAL LYS ARG MET
SEQRES 19 B 485 LYS GLU SER ARG LEU GLU ASP THR GLN LYS HIS ARG VAL
SEQRES 20 B 485 ASP PHE LEU GLN LEU MET ILE ASP SER GLN ASN SER LYS
SEQRES 21 B 485 GLU THR GLU SER HIS LYS ALA LEU SER ASP LEU GLU LEU
SEQRES 22 B 485 VAL ALA GLN SER ILE ILE PHE ILE PHE ALA GLY TYR GLU
SEQRES 23 B 485 THR THR SER SER VAL LEU SER PHE ILE MET TYR GLU LEU
SEQRES 24 B 485 ALA THR HIS PRO ASP VAL GLN GLN LYS LEU GLN GLU GLU
SEQRES 25 B 485 ILE ASP ALA VAL LEU PRO ASN LYS ALA PRO PRO THR TYR
SEQRES 26 B 485 ASP THR VAL LEU GLN MET GLU TYR LEU ASP MET VAL VAL
SEQRES 27 B 485 ASN GLU THR LEU ARG LEU PHE PRO ILE ALA MET ARG LEU
SEQRES 28 B 485 GLU ARG VAL CYS LYS LYS ASP VAL GLU ILE ASN GLY MET
SEQRES 29 B 485 PHE ILE PRO LYS GLY VAL VAL VAL MET ILE PRO SER TYR
SEQRES 30 B 485 ALA LEU HIS ARG ASP PRO LYS TYR TRP THR GLU PRO GLU
SEQRES 31 B 485 LYS PHE LEU PRO GLU ARG PHE SER LYS LYS ASN LYS ASP
SEQRES 32 B 485 ASN ILE ASP PRO TYR ILE TYR THR PRO PHE GLY SER GLY
SEQRES 33 B 485 PRO ARG ASN CYS ILE GLY MET ARG PHE ALA LEU MET ASN
SEQRES 34 B 485 MET LYS LEU ALA LEU ILE ARG VAL LEU GLN ASN PHE SER
SEQRES 35 B 485 PHE LYS PRO CYS LYS GLU THR GLN ILE PRO LEU LYS LEU
SEQRES 36 B 485 SER LEU GLY GLY LEU LEU GLN PRO GLU LYS PRO VAL VAL
SEQRES 37 B 485 LEU LYS VAL GLU SER ARG ASP GLY THR VAL SER GLY ALA
SEQRES 38 B 485 HIS HIS HIS HIS
HET DMS A 700 4
HET DMS A 701 4
HET DMS A 702 4
HET DMS A 703 4
HET HEM A 508 43
HET RIT A 600 50
HET DMS B 704 4
HET DMS B 705 4
HET HEM B 508 43
HET RIT B 600 50
HETNAM DMS DIMETHYL SULFOXIDE
HETNAM HEM PROTOPORPHYRIN IX CONTAINING FE
HETNAM RIT RITONAVIR
HETSYN HEM HEME
HETSYN RIT A-84538
FORMUL 3 DMS 6(C2 H6 O S)
FORMUL 7 HEM 2(C34 H32 FE N4 O4)
FORMUL 8 RIT 2(C37 H48 N6 O5 S2)
FORMUL 13 HOH *389(H2 O)
HELIX 1 1 GLY A 31 GLY A 37 1 7
HELIX 2 2 ASN A 49 LYS A 55 5 7
HELIX 3 3 GLY A 56 GLY A 69 1 14
HELIX 4 4 ASP A 86 VAL A 95 1 10
HELIX 5 5 VAL A 111 ALA A 117 5 7
HELIX 6 6 GLU A 122 SER A 134 1 13
HELIX 7 7 PRO A 135 PHE A 137 5 3
HELIX 8 8 THR A 138 GLY A 167 1 30
HELIX 9 9 LEU A 172 GLY A 190 1 19
HELIX 10 10 ASP A 194 ASN A 198 5 5
HELIX 11 11 ASP A 201 LYS A 208 1 8
HELIX 12 12 ASP A 217 PHE A 226 1 10
HELIX 13 13 PHE A 228 LEU A 236 1 9
HELIX 14 14 PRO A 242 ASP A 263 1 22
HELIX 15 15 ASP A 270 ASN A 280 1 11
HELIX 16 16 SER A 291 THR A 323 1 33
HELIX 17 17 HIS A 324 LEU A 339 1 16
HELIX 18 18 THR A 346 MET A 353 1 8
HELIX 19 19 MET A 353 PHE A 367 1 15
HELIX 20 20 PRO A 397 ARG A 403 1 7
HELIX 21 21 LEU A 415 PHE A 419 5 5
HELIX 22 22 SER A 420 ASP A 425 1 6
HELIX 23 23 GLY A 444 GLN A 461 1 18
HELIX 24 24 GLY B 31 GLY B 37 1 7
HELIX 25 25 ASN B 49 LYS B 55 5 7
HELIX 26 26 GLY B 56 GLY B 69 1 14
HELIX 27 27 ASP B 86 VAL B 95 1 10
HELIX 28 28 VAL B 111 ALA B 117 5 7
HELIX 29 29 GLU B 122 SER B 134 1 13
HELIX 30 30 PRO B 135 PHE B 137 5 3
HELIX 31 31 THR B 138 GLY B 167 1 30
HELIX 32 32 LEU B 172 GLY B 190 1 19
HELIX 33 33 ASP B 194 ASN B 198 5 5
HELIX 34 34 ASP B 201 LYS B 208 1 8
HELIX 35 35 ASP B 217 PHE B 226 1 10
HELIX 36 36 PHE B 228 LEU B 236 1 9
HELIX 37 37 PRO B 242 LEU B 261 1 20
HELIX 38 38 ASP B 270 GLN B 279 1 10
HELIX 39 39 SER B 291 THR B 323 1 33
HELIX 40 40 HIS B 324 LEU B 339 1 16
HELIX 41 41 PRO B 340 ALA B 343 5 4
HELIX 42 42 THR B 346 MET B 353 1 8
HELIX 43 43 MET B 353 PHE B 367 1 15
HELIX 44 44 PRO B 397 HIS B 402 1 6
HELIX 45 45 LEU B 415 PHE B 419 5 5
HELIX 46 46 SER B 420 ASP B 425 1 6
HELIX 47 47 GLY B 444 GLN B 461 1 18
SHEET 1 A 4 VAL A 71 ASP A 76 0
SHEET 2 A 4 GLN A 79 ILE A 84 -1 O ALA A 83 N TRP A 72
SHEET 3 A 4 VAL A 393 ILE A 396 1 O MET A 395 N LEU A 82
SHEET 4 A 4 LEU A 373 VAL A 376 -1 N LEU A 373 O ILE A 396
SHEET 1 B 3 VAL A 170 THR A 171 0
SHEET 2 B 3 VAL A 490 SER A 495 -1 O LEU A 491 N VAL A 170
SHEET 3 B 3 PHE A 463 LYS A 466 -1 N LYS A 466 O LYS A 492
SHEET 1 C 2 VAL A 381 ILE A 383 0
SHEET 2 C 2 MET A 386 ILE A 388 -1 O ILE A 388 N VAL A 381
SHEET 1 D 4 VAL B 71 ASP B 76 0
SHEET 2 D 4 GLN B 79 ILE B 84 -1 O VAL B 81 N PHE B 74
SHEET 3 D 4 VAL B 393 ILE B 396 1 O MET B 395 N LEU B 82
SHEET 4 D 4 LEU B 373 VAL B 376 -1 N LEU B 373 O ILE B 396
SHEET 1 E 3 VAL B 170 THR B 171 0
SHEET 2 E 3 VAL B 490 SER B 495 -1 O LEU B 491 N VAL B 170
SHEET 3 E 3 PHE B 463 PRO B 467 -1 N LYS B 466 O LYS B 492
SHEET 1 F 2 VAL B 381 ILE B 383 0
SHEET 2 F 2 MET B 386 ILE B 388 -1 O ILE B 388 N VAL B 381
LINK SG CYS A 442 FE HEM A 508 1555 1555 2.28
LINK FE HEM A 508 N5 RIT A 600 1555 1555 2.23
LINK SG CYS B 442 FE HEM B 508 1555 1555 2.26
LINK FE HEM B 508 N5 RIT B 600 1555 1555 2.29
CISPEP 1 ILE A 473 PRO A 474 0 0.39
CISPEP 2 ILE B 473 PRO B 474 0 0.19
SITE 1 AC1 7 GLY A 56 PHE A 57 CYS A 58 MET A 371
SITE 2 AC1 7 SER A 478 LEU A 479 GLY A 480
SITE 1 AC2 5 PHE A 226 PRO A 227 PHE A 228 PRO B 231
SITE 2 AC2 5 HOH B 670
SITE 1 AC3 4 ILE A 50 TYR A 53 PHE A 215 LEU A 216
SITE 1 AC4 4 CYS A 239 VAL A 240 ARG A 243 HOH A 630
SITE 1 AC5 22 HOH A 11 ARG A 105 ILE A 118 TRP A 126
SITE 2 AC5 22 ARG A 130 PHE A 302 ALA A 305 THR A 309
SITE 3 AC5 22 ILE A 369 ALA A 370 ARG A 375 PRO A 434
SITE 4 AC5 22 PHE A 435 GLY A 436 SER A 437 ARG A 440
SITE 5 AC5 22 ASN A 441 CYS A 442 ILE A 443 GLY A 444
SITE 6 AC5 22 MET A 452 RIT A 600
SITE 1 AC6 20 HOH A 1 PHE A 108 SER A 119 ILE A 120
SITE 2 AC6 20 LEU A 210 LEU A 211 PHE A 215 PHE A 241
SITE 3 AC6 20 ILE A 301 PHE A 304 ALA A 305 THR A 309
SITE 4 AC6 20 ILE A 369 ALA A 370 ARG A 372 GLU A 374
SITE 5 AC6 20 GLY A 481 HEM A 508 HOH A 511 HOH A 628
SITE 1 AC7 8 GLY B 56 PHE B 57 CYS B 58 MET B 371
SITE 2 AC7 8 LEU B 477 SER B 478 LEU B 479 GLY B 480
SITE 1 AC8 2 PHE B 219 CYS B 239
SITE 1 AC9 21 ARG B 105 ILE B 118 SER B 119 TRP B 126
SITE 2 AC9 21 ARG B 130 PHE B 302 ALA B 305 VAL B 313
SITE 3 AC9 21 ILE B 369 ALA B 370 ARG B 375 PRO B 434
SITE 4 AC9 21 PHE B 435 GLY B 436 ARG B 440 ASN B 441
SITE 5 AC9 21 CYS B 442 ILE B 443 MET B 452 HOH B 546
SITE 6 AC9 21 RIT B 600
SITE 1 BC1 22 HOH B 6 PHE B 108 SER B 119 ILE B 120
SITE 2 BC1 22 LEU B 210 LEU B 211 PHE B 213 PHE B 215
SITE 3 BC1 22 PHE B 241 ILE B 301 PHE B 304 ALA B 305
SITE 4 BC1 22 THR B 309 ARG B 372 GLU B 374 GLY B 481
SITE 5 BC1 22 HEM B 508 HOH B 521 HOH B 522 HOH B 546
SITE 6 BC1 22 HOH B 650 HOH B 656
CRYST1 162.123 94.690 93.130 90.00 124.25 90.00 C 1 2 1 8
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 0.006168 0.000000 0.004200 0.00000
SCALE2 0.000000 0.010561 0.000000 0.00000
SCALE3 0.000000 0.000000 0.012990 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
