HEADER OXIDOREDUCTASE/OXIDOREDUCTASE INHIBITOR 24-AUG-11 3TJS
TITLE CRYSTAL STRUCTURE OF THE COMPLEX BETWEEN HUMAN CYTOCHROME P450 3A4 AND
TITLE 2 DESTHIAZOLYLMETHYLOXYCARBONYL RITONAVIR
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: CYTOCHROME P450 3A4;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: SEE REMARK 999;
COMPND 5 SYNONYM: ALBENDAZOLE MONOOXYGENASE, ALBENDAZOLE SULFOXIDASE,
COMPND 6 CYPIIIA3, CYPIIIA4, CYTOCHROME P450 3A3, CYTOCHROME P450 HLP,
COMPND 7 CYTOCHROME P450 NF-25, CYTOCHROME P450-PCN1, NIFEDIPINE OXIDASE,
COMPND 8 QUININE 3-MONOOXYGENASE, TAUROCHENODEOXYCHOLATE 6-ALPHA-HYDROXYLASE;
COMPND 9 EC: 1.14.13.32;
COMPND 10 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: CYP3A4, CYP3A3;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI BL21(DE3);
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 469008;
SOURCE 8 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID;
SOURCE 9 EXPRESSION_SYSTEM_PLASMID: PCWORI
KEYWDS MONOOXYGENASE, CYTOCHROME P450, ENDOPLASMIC RETICULUM,
KEYWDS 2 OXIDOREDUCTASE-OXIDOREDUCTASE INHIBITOR COMPLEX
EXPDTA X-RAY DIFFRACTION
AUTHOR I.F.SEVRIOUKOVA,T.L.POULOS
REVDAT 6 13-SEP-23 3TJS 1 REMARK LINK
REVDAT 5 08-NOV-17 3TJS 1 REMARK
REVDAT 4 28-JUN-17 3TJS 1 SOURCE DBREF SEQADV
REVDAT 3 11-APR-12 3TJS 1 JRNL
REVDAT 2 04-APR-12 3TJS 1 JRNL
REVDAT 1 07-MAR-12 3TJS 0
JRNL AUTH I.F.SEVRIOUKOVA,T.L.POULOS
JRNL TITL INTERACTION OF HUMAN CYTOCHROME P4503A4 WITH RITONAVIR
JRNL TITL 2 ANALOGS.
JRNL REF ARCH.BIOCHEM.BIOPHYS. V. 520 108 2012
JRNL REFN ISSN 0003-9861
JRNL PMID 22410611
JRNL DOI 10.1016/J.ABB.2012.02.018
REMARK 2
REMARK 2 RESOLUTION. 2.25 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.5.0109
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) : 2.25
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 38.40
REMARK 3 DATA CUTOFF (SIGMA(F)) : NULL
REMARK 3 COMPLETENESS FOR RANGE (%) : 98.5
REMARK 3 NUMBER OF REFLECTIONS : 21981
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) : 0.231
REMARK 3 R VALUE (WORKING SET) : 0.228
REMARK 3 FREE R VALUE : 0.297
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.100
REMARK 3 FREE R VALUE TEST SET COUNT : 1177
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) : 2.25
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 2.31
REMARK 3 REFLECTION IN BIN (WORKING SET) : 1593
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 99.71
REMARK 3 BIN R VALUE (WORKING SET) : 0.2940
REMARK 3 BIN FREE R VALUE SET COUNT : 108
REMARK 3 BIN FREE R VALUE : 0.3430
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 3609
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 84
REMARK 3 SOLVENT ATOMS : 50
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 39.70
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 57.72
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 4.00000
REMARK 3 B22 (A**2) : -1.49000
REMARK 3 B33 (A**2) : -2.50000
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): 0.385
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.283
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.200
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 17.877
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.938
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.904
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 3797 ; 0.020 ; 0.022
REMARK 3 BOND LENGTHS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 5149 ; 1.955 ; 2.035
REMARK 3 BOND ANGLES OTHERS (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 447 ; 7.371 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 156 ;37.980 ;23.782
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 681 ;20.261 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 22 ;24.317 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 569 ; 0.137 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 2821 ; 0.012 ; 0.021
REMARK 3 GENERAL PLANES OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) OTHERS (A): NULL ; NULL ; NULL
REMARK 3 POTENTIAL METAL-ION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 POTENTIAL METAL-ION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY VDW REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY VDW OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): NULL ; NULL ; NULL
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): 2255 ; 0.941 ; 1.500
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 3689 ; 1.698 ; 2.000
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 1542 ; 2.769 ; 3.000
REMARK 3 SIDE-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): 1459 ; 4.277 ; 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 29 A 496
REMARK 3 ORIGIN FOR THE GROUP (A): 19.9406 -23.9069 -12.3464
REMARK 3 T TENSOR
REMARK 3 T11: 0.0249 T22: 0.1306
REMARK 3 T33: 0.0980 T12: -0.0231
REMARK 3 T13: 0.0055 T23: -0.0362
REMARK 3 L TENSOR
REMARK 3 L11: 0.5513 L22: 3.0346
REMARK 3 L33: 1.3037 L12: -0.4900
REMARK 3 L13: -0.0804 L23: 0.2282
REMARK 3 S TENSOR
REMARK 3 S11: -0.0487 S12: -0.0065 S13: -0.0656
REMARK 3 S21: 0.2020 S22: 0.0181 S23: 0.0957
REMARK 3 S31: 0.1260 S32: -0.1706 S33: 0.0307
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 : A 601 A 650
REMARK 3 ORIGIN FOR THE GROUP (A): 22.6508 -18.2402 -17.3137
REMARK 3 T TENSOR
REMARK 3 T11: 0.0289 T22: 0.2333
REMARK 3 T33: 0.1751 T12: -0.0349
REMARK 3 T13: 0.0031 T23: 0.0293
REMARK 3 L TENSOR
REMARK 3 L11: 0.8071 L22: 2.4136
REMARK 3 L33: 0.4639 L12: -0.7220
REMARK 3 L13: 0.1997 L23: 0.6081
REMARK 3 S TENSOR
REMARK 3 S11: 0.0802 S12: 0.1051 S13: 0.0437
REMARK 3 S21: 0.0264 S22: -0.0142 S23: -0.0594
REMARK 3 S31: 0.0932 S32: -0.0397 S33: -0.0660
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : 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:
REMARK 3 HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
REMARK 3 U VALUES : RESIDUAL ONLY
REMARK 4
REMARK 4 3TJS COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 26-AUG-11.
REMARK 100 THE DEPOSITION ID IS D_1000067564.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 21-NOV-10
REMARK 200 TEMPERATURE (KELVIN) : 83
REMARK 200 PH : 6.4
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) : 1.0
REMARK 200 MONOCHROMATOR : SIDE SCATTERING I-BEAM BENT
REMARK 200 SINGLE CRYSTAL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : CCD
REMARK 200 DETECTOR MANUFACTURER : ADSC QUANTUM 315R
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : MOSFLM
REMARK 200 DATA SCALING SOFTWARE : SCALA
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 23181
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.250
REMARK 200 RESOLUTION RANGE LOW (A) : 49.300
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : NULL
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 98.8
REMARK 200 DATA REDUNDANCY : 6.500
REMARK 200 R MERGE (I) : 0.07400
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 11.0000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 2.25
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.37
REMARK 200 COMPLETENESS FOR SHELL (%) : 99.7
REMARK 200 DATA REDUNDANCY IN SHELL : 6.30
REMARK 200 R MERGE FOR SHELL (I) : 0.43400
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 3.200
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: PDB ENTRY 3NXU
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 43.81
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.19
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 10% PEG3350, 80 MM MALONATE, PH 6.4,
REMARK 280 MICROBATCH UNDER OIL, TEMPERATURE 293K
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: I 2 2 2
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,Y,-Z
REMARK 290 4555 X,-Y,-Z
REMARK 290 5555 X+1/2,Y+1/2,Z+1/2
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+1/2
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 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 0.00000
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 0.00000
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 39.39500
REMARK 290 SMTRY2 5 0.000000 1.000000 0.000000 49.30000
REMARK 290 SMTRY3 5 0.000000 0.000000 1.000000 62.53500
REMARK 290 SMTRY1 6 -1.000000 0.000000 0.000000 39.39500
REMARK 290 SMTRY2 6 0.000000 -1.000000 0.000000 49.30000
REMARK 290 SMTRY3 6 0.000000 0.000000 1.000000 62.53500
REMARK 290 SMTRY1 7 -1.000000 0.000000 0.000000 39.39500
REMARK 290 SMTRY2 7 0.000000 1.000000 0.000000 49.30000
REMARK 290 SMTRY3 7 0.000000 0.000000 -1.000000 62.53500
REMARK 290 SMTRY1 8 1.000000 0.000000 0.000000 39.39500
REMARK 290 SMTRY2 8 0.000000 -1.000000 0.000000 49.30000
REMARK 290 SMTRY3 8 0.000000 0.000000 -1.000000 62.53500
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 MET A 21
REMARK 465 ALA A 22
REMARK 465 TYR A 23
REMARK 465 LEU A 24
REMARK 465 TYR A 25
REMARK 465 GLY A 26
REMARK 465 THR A 27
REMARK 465 HIS A 28
REMARK 465 ARG A 212
REMARK 465 PHE A 213
REMARK 465 ASP A 214
REMARK 465 PHE A 215
REMARK 465 LEU A 216
REMARK 465 ASP A 217
REMARK 465 PRO A 218
REMARK 465 ASP A 263
REMARK 465 THR A 264
REMARK 465 GLN A 265
REMARK 465 LYS A 266
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 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 OE2 GLU A 354 O HOH A 642 2.11
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 GLU A 262 CG GLU A 262 CD 0.096
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 A 375 CG - CD - NE ANGL. DEV. = -16.9 DEGREES
REMARK 500 ARG A 375 NE - CZ - NH1 ANGL. DEV. = 5.5 DEGREES
REMARK 500 ARG A 375 NE - CZ - NH2 ANGL. DEV. = -8.6 DEGREES
REMARK 500 ARG A 440 CG - CD - NE ANGL. DEV. = -14.3 DEGREES
REMARK 500 ARG A 440 CD - NE - CZ ANGL. DEV. = 11.5 DEGREES
REMARK 500 ARG A 440 NE - CZ - NH1 ANGL. DEV. = -6.3 DEGREES
REMARK 500 ARG A 440 NE - CZ - NH2 ANGL. DEV. = 5.0 DEGREES
REMARK 500 PRO A 474 C - N - CD ANGL. DEV. = -21.0 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 HIS A 30 3.46 -68.98
REMARK 500 PHE A 46 -54.59 73.24
REMARK 500 VAL A 95 -71.04 -109.91
REMARK 500 ASP A 123 -115.43 41.85
REMARK 500 ASP A 201 116.52 -36.13
REMARK 500 PHE A 228 0.42 -63.47
REMARK 500 ARG A 268 -64.25 68.14
REMARK 500 VAL A 269 15.32 108.20
REMARK 500 ASP A 270 175.35 -56.80
REMARK 500 PHE A 271 -34.37 -32.56
REMARK 500 GLN A 279 -3.80 -59.88
REMARK 500 LEU A 339 76.52 -115.15
REMARK 500 MET A 371 -23.65 75.20
REMARK 500 LYS A 424 -18.38 -41.91
REMARK 500 ASN A 441 -178.93 -66.90
REMARK 500 PRO A 474 98.76 23.02
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: NON-CIS, NON-TRANS
REMARK 500
REMARK 500 THE FOLLOWING PEPTIDE BONDS DEVIATE SIGNIFICANTLY FROM BOTH
REMARK 500 CIS AND TRANS CONFORMATION. CIS BONDS, IF ANY, ARE LISTED
REMARK 500 ON CISPEP RECORDS. TRANS IS DEFINED AS 180 +/- 30 AND
REMARK 500 CIS IS DEFINED AS 0 +/- 30 DEGREES.
REMARK 500 MODEL OMEGA
REMARK 500 HIS A 267 ARG A 268 146.62
REMARK 500 ILE A 473 PRO A 474 -112.10
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: MAIN CHAIN PLANARITY
REMARK 500
REMARK 500 THE FOLLOWING RESIDUES HAVE A PSEUDO PLANARITY
REMARK 500 TORSION ANGLE, C(I) - CA(I) - N(I+1) - O(I), GREATER
REMARK 500 10.0 DEGREES. (M=MODEL NUMBER; RES=RESIDUE NAME;
REMARK 500 C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;
REMARK 500 I=INSERTION CODE).
REMARK 500
REMARK 500 M RES CSSEQI ANGLE
REMARK 500 VAL A 269 12.21
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 90.9
REMARK 620 3 HEM A 508 NB 88.1 86.1
REMARK 620 4 HEM A 508 NC 91.1 178.0 94.3
REMARK 620 5 HEM A 508 ND 95.0 91.6 176.1 87.9
REMARK 620 6 D0R A 600 N11 170.5 97.2 87.5 80.9 89.7
REMARK 620 N 1 2 3 4 5
REMARK 630
REMARK 630 MOLECULE TYPE: PEPTIDE-LIKE ANTIVIRAL
REMARK 630 MOLECULE NAME: N-[(2S,4S,5S)-5-AMINO-4-HYDROXY-1,6-DIPHENYLHEXAN-2-
REMARK 630 YL]-N~2~-(METHYL{[2-(PROPAN-2-YL)-1,3-THIAZOL-4-YL]METHYL}
REMARK 630 CARBAMOYL)-L-VALINAMIDE
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 D0R A 600
REMARK 630 SOURCE: NULL
REMARK 630 TAXONOMY: NULL
REMARK 630 SUBCOMP: 019 VAL 015
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 HEM A 508
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE D0R A 600
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 3NXU RELATED DB: PDB
REMARK 900 CRYSTALLOGRAPHIC COMPLEX BETWEEN CYTOCHROME P450 3A4 AND RITONAVIR
REMARK 999
REMARK 999 SEQUENCE
REMARK 999 UNP RESIDUES 3-22 ARE DELETED.
DBREF 3TJS A 23 503 UNP P08684 CP3A4_HUMAN 23 503
SEQADV 3TJS MET A 21 UNP P08684 EXPRESSION TAG
SEQADV 3TJS ALA A 22 UNP P08684 EXPRESSION TAG
SEQADV 3TJS HIS A 504 UNP P08684 EXPRESSION TAG
SEQADV 3TJS HIS A 505 UNP P08684 EXPRESSION TAG
SEQADV 3TJS HIS A 506 UNP P08684 EXPRESSION TAG
SEQADV 3TJS HIS A 507 UNP P08684 EXPRESSION TAG
SEQRES 1 A 487 MET ALA TYR LEU TYR GLY THR HIS SER HIS GLY LEU PHE
SEQRES 2 A 487 LYS LYS LEU GLY ILE PRO GLY PRO THR PRO LEU PRO PHE
SEQRES 3 A 487 LEU GLY ASN ILE LEU SER TYR HIS LYS GLY PHE CYS MET
SEQRES 4 A 487 PHE ASP MET GLU CYS HIS LYS LYS TYR GLY LYS VAL TRP
SEQRES 5 A 487 GLY PHE TYR ASP GLY GLN GLN PRO VAL LEU ALA ILE THR
SEQRES 6 A 487 ASP PRO ASP MET ILE LYS THR VAL LEU VAL LYS GLU CYS
SEQRES 7 A 487 TYR SER VAL PHE THR ASN ARG ARG PRO PHE GLY PRO VAL
SEQRES 8 A 487 GLY PHE MET LYS SER ALA ILE SER ILE ALA GLU ASP GLU
SEQRES 9 A 487 GLU TRP LYS ARG LEU ARG SER LEU LEU SER PRO THR PHE
SEQRES 10 A 487 THR SER GLY LYS LEU LYS GLU MET VAL PRO ILE ILE ALA
SEQRES 11 A 487 GLN TYR GLY ASP VAL LEU VAL ARG ASN LEU ARG ARG GLU
SEQRES 12 A 487 ALA GLU THR GLY LYS PRO VAL THR LEU LYS ASP VAL PHE
SEQRES 13 A 487 GLY ALA TYR SER MET ASP VAL ILE THR SER THR SER PHE
SEQRES 14 A 487 GLY VAL ASN ILE ASP SER LEU ASN ASN PRO GLN ASP PRO
SEQRES 15 A 487 PHE VAL GLU ASN THR LYS LYS LEU LEU ARG PHE ASP PHE
SEQRES 16 A 487 LEU ASP PRO PHE PHE LEU SER ILE THR VAL PHE PRO PHE
SEQRES 17 A 487 LEU ILE PRO ILE LEU GLU VAL LEU ASN ILE CYS VAL PHE
SEQRES 18 A 487 PRO ARG GLU VAL THR ASN PHE LEU ARG LYS SER VAL LYS
SEQRES 19 A 487 ARG MET LYS GLU SER ARG LEU GLU ASP THR GLN LYS HIS
SEQRES 20 A 487 ARG VAL ASP PHE LEU GLN LEU MET ILE ASP SER GLN ASN
SEQRES 21 A 487 SER LYS GLU THR GLU SER HIS LYS ALA LEU SER ASP LEU
SEQRES 22 A 487 GLU LEU VAL ALA GLN SER ILE ILE PHE ILE PHE ALA GLY
SEQRES 23 A 487 TYR GLU THR THR SER SER VAL LEU SER PHE ILE MET TYR
SEQRES 24 A 487 GLU LEU ALA THR HIS PRO ASP VAL GLN GLN LYS LEU GLN
SEQRES 25 A 487 GLU GLU ILE ASP ALA VAL LEU PRO ASN LYS ALA PRO PRO
SEQRES 26 A 487 THR TYR ASP THR VAL LEU GLN MET GLU TYR LEU ASP MET
SEQRES 27 A 487 VAL VAL ASN GLU THR LEU ARG LEU PHE PRO ILE ALA MET
SEQRES 28 A 487 ARG LEU GLU ARG VAL CYS LYS LYS ASP VAL GLU ILE ASN
SEQRES 29 A 487 GLY MET PHE ILE PRO LYS GLY VAL VAL VAL MET ILE PRO
SEQRES 30 A 487 SER TYR ALA LEU HIS ARG ASP PRO LYS TYR TRP THR GLU
SEQRES 31 A 487 PRO GLU LYS PHE LEU PRO GLU ARG PHE SER LYS LYS ASN
SEQRES 32 A 487 LYS ASP ASN ILE ASP PRO TYR ILE TYR THR PRO PHE GLY
SEQRES 33 A 487 SER GLY PRO ARG ASN CYS ILE GLY MET ARG PHE ALA LEU
SEQRES 34 A 487 MET ASN MET LYS LEU ALA LEU ILE ARG VAL LEU GLN ASN
SEQRES 35 A 487 PHE SER PHE LYS PRO CYS LYS GLU THR GLN ILE PRO LEU
SEQRES 36 A 487 LYS LEU SER LEU GLY GLY LEU LEU GLN PRO GLU LYS PRO
SEQRES 37 A 487 VAL VAL LEU LYS VAL GLU SER ARG ASP GLY THR VAL SER
SEQRES 38 A 487 GLY ALA HIS HIS HIS HIS
HET HEM A 508 43
HET D0R A 600 41
HETNAM HEM PROTOPORPHYRIN IX CONTAINING FE
HETNAM D0R N-[(2S,4S,5S)-5-AMINO-4-HYDROXY-1,6-DIPHENYLHEXAN-2-
HETNAM 2 D0R YL]-N~2~-(METHYL{[2-(PROPAN-2-YL)-1,3-THIAZOL-4-
HETNAM 3 D0R YL]METHYL}CARBAMOYL)-L-VALINAMIDE
HETSYN HEM HEME
HETSYN D0R DESTHIAZOLYLMETHYLOXYCARBONYL RITONAVIR
FORMUL 2 HEM C34 H32 FE N4 O4
FORMUL 3 D0R C32 H45 N5 O3 S
FORMUL 4 HOH *50(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 LEU A 210 1 10
HELIX 12 12 PHE A 220 VAL A 225 1 6
HELIX 13 13 PHE A 226 ILE A 230 5 5
HELIX 14 14 PRO A 231 LEU A 236 1 6
HELIX 15 15 PRO A 242 GLU A 262 1 21
HELIX 16 16 ASP A 270 GLN A 279 1 10
HELIX 17 17 SER A 291 THR A 323 1 33
HELIX 18 18 HIS A 324 LEU A 339 1 16
HELIX 19 19 PRO A 340 ALA A 343 5 4
HELIX 20 20 THR A 346 GLN A 352 1 7
HELIX 21 21 MET A 353 PHE A 367 1 15
HELIX 22 22 PRO A 397 ARG A 403 1 7
HELIX 23 23 LEU A 415 SER A 420 5 6
HELIX 24 24 SER A 437 ASN A 441 5 5
HELIX 25 25 GLY A 444 ASN A 462 1 19
SHEET 1 A 4 VAL A 71 ASP A 76 0
SHEET 2 A 4 GLN A 79 ILE A 84 -1 O VAL A 81 N PHE A 74
SHEET 3 A 4 VAL A 393 ILE A 396 1 O VAL A 393 N LEU A 82
SHEET 4 A 4 LEU A 373 VAL A 376 -1 N ARG A 375 O VAL A 394
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 SER A 464 O GLU A 494
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
LINK SG CYS A 442 FE HEM A 508 1555 1555 2.25
LINK FE HEM A 508 N11 D0R A 600 1555 1555 2.11
SITE 1 AC1 21 ARG A 105 ILE A 118 SER A 119 TRP A 126
SITE 2 AC1 21 ARG A 130 ALA A 305 GLY A 306 THR A 309
SITE 3 AC1 21 ALA A 370 ARG A 375 PRO A 434 PHE A 435
SITE 4 AC1 21 GLY A 436 SER A 437 ARG A 440 ASN A 441
SITE 5 AC1 21 CYS A 442 ILE A 443 ALA A 448 D0R A 600
SITE 6 AC1 21 HOH A 624
SITE 1 AC2 8 SER A 119 LEU A 210 PHE A 304 ALA A 305
SITE 2 AC2 8 ILE A 369 ALA A 370 GLY A 481 HEM A 508
CRYST1 78.790 98.600 125.070 90.00 90.00 90.00 I 2 2 2 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 0.012692 0.000000 0.000000 0.00000
SCALE2 0.000000 0.010142 0.000000 0.00000
SCALE3 0.000000 0.000000 0.007996 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
