HEADER TRANSCRIPTION REGULATION, RECEPTOR 31-MAR-05 1Z95
TITLE CRYSTAL STRUCTURE OF THE ANDROGEN RECEPTOR LIGAND-BINDING DOMAIN W741L
TITLE 2 MUTANT COMPLEX WITH R-BICALUTAMIDE
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: ANDROGEN RECEPTOR;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: LIGAND BINDING DOMAIN;
COMPND 5 SYNONYM: DIHYDROTESTOSTERONE RECEPTOR;
COMPND 6 ENGINEERED: YES;
COMPND 7 MUTATION: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 6 EXPRESSION_SYSTEM_TAXID: 562;
SOURCE 7 EXPRESSION_SYSTEM_VECTOR_TYPE: PLASMID
KEYWDS STEROID HORMONES; RECEPTORS; CELLULAR PROLIFERATION; CELLULAR
KEYWDS 2 DIFFERENTIATION, TRANSCRIPTION REGULATION, RECEPTOR
EXPDTA X-RAY DIFFRACTION
AUTHOR C.E.BOHL,W.GAO,D.D.MILLER,C.E.BELL,J.T.DALTON
REVDAT 4 23-AUG-23 1Z95 1 REMARK
REVDAT 3 20-OCT-21 1Z95 1 REMARK SEQADV
REVDAT 2 24-FEB-09 1Z95 1 VERSN
REVDAT 1 19-APR-05 1Z95 0
JRNL AUTH C.E.BOHL,W.GAO,D.D.MILLER,C.E.BELL,J.T.DALTON
JRNL TITL STRUCTURAL BASIS FOR ANTAGONISM AND RESISTANCE OF
JRNL TITL 2 BICALUTAMIDE IN PROSTATE CANCER.
JRNL REF PROC.NATL.ACAD.SCI.USA V. 102 6201 2005
JRNL REFN ISSN 0027-8424
JRNL PMID 15833816
JRNL DOI 10.1073/PNAS.0500381102
REMARK 2
REMARK 2 RESOLUTION. 1.80 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) : 1.80
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 24.46
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.000
REMARK 3 DATA CUTOFF HIGH (ABS(F)) : 903043.690
REMARK 3 DATA CUTOFF LOW (ABS(F)) : 0.0000
REMARK 3 COMPLETENESS (WORKING+TEST) (%) : 95.4
REMARK 3 NUMBER OF REFLECTIONS : 24657
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) : 0.223
REMARK 3 FREE R VALUE : 0.256
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 9.900
REMARK 3 FREE R VALUE TEST SET COUNT : 2446
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 : 6
REMARK 3 BIN RESOLUTION RANGE HIGH (A) : 1.80
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 1.91
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 77.00
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 2942
REMARK 3 BIN R VALUE (WORKING SET) : 0.3350
REMARK 3 BIN FREE R VALUE : 0.3720
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 9.40
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 306
REMARK 3 ESTIMATED ERROR OF BIN FREE R VALUE : 0.021
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 1946
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 34
REMARK 3 SOLVENT ATOMS : 134
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 28.80
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 31.20
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 2.81000
REMARK 3 B22 (A**2) : -5.44000
REMARK 3 B33 (A**2) : 2.63000
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) : 0.24
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) : 0.28
REMARK 3 ESD FROM C-V SIGMAA (A) : 0.32
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : 0.006
REMARK 3 BOND ANGLES (DEGREES) : 1.100
REMARK 3 DIHEDRAL ANGLES (DEGREES) : 18.70
REMARK 3 IMPROPER ANGLES (DEGREES) : 0.780
REMARK 3
REMARK 3 ISOTROPIC THERMAL MODEL : RESTRAINED
REMARK 3
REMARK 3 ISOTROPIC THERMAL FACTOR RESTRAINTS. RMS SIGMA
REMARK 3 MAIN-CHAIN BOND (A**2) : 1.270 ; 1.500
REMARK 3 MAIN-CHAIN ANGLE (A**2) : 1.900 ; 2.000
REMARK 3 SIDE-CHAIN BOND (A**2) : 2.350 ; 2.000
REMARK 3 SIDE-CHAIN ANGLE (A**2) : 3.310 ; 2.500
REMARK 3
REMARK 3 BULK SOLVENT MODELING.
REMARK 3 METHOD USED : FLAT MODEL
REMARK 3 KSOL : 0.35
REMARK 3 BSOL : 43.18
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 : PROTEIN_REP.PARAM
REMARK 3 PARAMETER FILE 2 : SO4.PARAM
REMARK 3 PARAMETER FILE 3 : BIC.PARAM
REMARK 3 PARAMETER FILE 4 : WATER_REP.PARAM
REMARK 3 PARAMETER FILE 5 : NULL
REMARK 3 TOPOLOGY FILE 1 : PROTEIN.TOP
REMARK 3 TOPOLOGY FILE 2 : SO4.TOP
REMARK 3 TOPOLOGY FILE 3 : BIC.TOP
REMARK 3 TOPOLOGY FILE 4 : NULL
REMARK 3 TOPOLOGY FILE 5 : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 1Z95 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY RCSB ON 07-APR-05.
REMARK 100 THE DEPOSITION ID IS D_1000032454.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 02-NOV-04
REMARK 200 TEMPERATURE (KELVIN) : 95
REMARK 200 PH : 7.5
REMARK 200 NUMBER OF CRYSTALS USED : 1
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : N
REMARK 200 RADIATION SOURCE : ROTATING ANODE
REMARK 200 BEAMLINE : NULL
REMARK 200 X-RAY GENERATOR MODEL : RIGAKU RU300
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.5418
REMARK 200 MONOCHROMATOR : MIRRORS
REMARK 200 OPTICS : MIRRORS
REMARK 200
REMARK 200 DETECTOR TYPE : IMAGE PLATE
REMARK 200 DETECTOR MANUFACTURER : RIGAKU RAXIS IV
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : D*TREK, CRYSTALCLEAR
REMARK 200 (MSC/RIGAKU)
REMARK 200 DATA SCALING SOFTWARE : D*TREK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 24747
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.800
REMARK 200 RESOLUTION RANGE LOW (A) : 24.500
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 95.7
REMARK 200 DATA REDUNDANCY : NULL
REMARK 200 R MERGE (I) : 0.04100
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : NULL
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.80
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 1.86
REMARK 200 COMPLETENESS FOR SHELL (%) : 72.7
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : 0.04100
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: CNS
REMARK 200 STARTING MODEL: 1I37
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 45.00
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.29
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: 0.1 M HEPES, 0.75 M LITHIUM SULFATE,
REMARK 280 PH 7.5, VAPOR DIFFUSION, SITTING DROP, TEMPERATURE 295K
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 28.24500
REMARK 290 SMTRY2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 290 SMTRY3 2 0.000000 0.000000 1.000000 36.08000
REMARK 290 SMTRY1 3 -1.000000 0.000000 0.000000 0.00000
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 33.23500
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 36.08000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 28.24500
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 33.23500
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 CYS A 844
REMARK 465 LYS A 845
REMARK 465 ARG A 846
REMARK 465 LYS A 847
REMARK 465 ASN A 848
REMARK 465 PRO A 849
REMARK 465 THR A 850
REMARK 465 SER A 851
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 ASN A 756 -66.39 -93.83
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 SO4 A 402
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 198 A 501
DBREF 1Z95 A 672 917 UNP P10275 ANDR_HUMAN 671 916
SEQADV 1Z95 LEU A 741 UNP P10275 TRP 740 ENGINEERED MUTATION
SEQRES 1 A 246 ILE PHE LEU ASN VAL LEU GLU ALA ILE GLU PRO GLY VAL
SEQRES 2 A 246 VAL CYS ALA GLY HIS ASP ASN ASN GLN PRO ASP SER PHE
SEQRES 3 A 246 ALA ALA LEU LEU SER SER LEU ASN GLU LEU GLY GLU ARG
SEQRES 4 A 246 GLN LEU VAL HIS VAL VAL LYS TRP ALA LYS ALA LEU PRO
SEQRES 5 A 246 GLY PHE ARG ASN LEU HIS VAL ASP ASP GLN MET ALA VAL
SEQRES 6 A 246 ILE GLN TYR SER LEU MET GLY LEU MET VAL PHE ALA MET
SEQRES 7 A 246 GLY TRP ARG SER PHE THR ASN VAL ASN SER ARG MET LEU
SEQRES 8 A 246 TYR PHE ALA PRO ASP LEU VAL PHE ASN GLU TYR ARG MET
SEQRES 9 A 246 HIS LYS SER ARG MET TYR SER GLN CYS VAL ARG MET ARG
SEQRES 10 A 246 HIS LEU SER GLN GLU PHE GLY TRP LEU GLN ILE THR PRO
SEQRES 11 A 246 GLN GLU PHE LEU CYS MET LYS ALA LEU LEU LEU PHE SER
SEQRES 12 A 246 ILE ILE PRO VAL ASP GLY LEU LYS ASN GLN LYS PHE PHE
SEQRES 13 A 246 ASP GLU LEU ARG MET ASN TYR ILE LYS GLU LEU ASP ARG
SEQRES 14 A 246 ILE ILE ALA CYS LYS ARG LYS ASN PRO THR SER CYS SER
SEQRES 15 A 246 ARG ARG PHE TYR GLN LEU THR LYS LEU LEU ASP SER VAL
SEQRES 16 A 246 GLN PRO ILE ALA ARG GLU LEU HIS GLN PHE THR PHE ASP
SEQRES 17 A 246 LEU LEU ILE LYS SER HIS MET VAL SER VAL ASP PHE PRO
SEQRES 18 A 246 GLU MET MET ALA GLU ILE ILE SER VAL GLN VAL PRO LYS
SEQRES 19 A 246 ILE LEU SER GLY LYS VAL LYS PRO ILE TYR PHE HIS
HET SO4 A 402 5
HET 198 A 501 29
HETNAM SO4 SULFATE ION
HETNAM 198 R-BICALUTAMIDE
HETSYN 198 (2R)-N-[4-CYANO-3-(TRIFLUOROMETHYL)PHENYL]-3-[(4-
HETSYN 2 198 FLUOROPHENYL)SULFONYL]-2-HYDROXY-2-METHYLPROPANAMIDE
FORMUL 2 SO4 O4 S 2-
FORMUL 3 198 C18 H14 F4 N2 O4 S
FORMUL 4 HOH *134(H2 O)
HELIX 1 1 ILE A 672 GLU A 681 1 10
HELIX 2 2 SER A 696 ALA A 721 1 26
HELIX 3 3 GLY A 724 LEU A 728 5 5
HELIX 4 4 HIS A 729 VAL A 757 1 29
HELIX 5 5 ASN A 771 SER A 778 1 8
HELIX 6 6 MET A 780 LEU A 797 1 18
HELIX 7 7 THR A 800 PHE A 813 1 14
HELIX 8 8 ASN A 823 ALA A 843 1 21
HELIX 9 9 CYS A 852 LYS A 883 1 32
HELIX 10 10 PRO A 892 GLN A 902 1 11
HELIX 11 11 GLN A 902 SER A 908 1 7
SHEET 1 A 2 LEU A 762 ALA A 765 0
SHEET 2 A 2 LEU A 768 PHE A 770 -1 O PHE A 770 N LEU A 762
SHEET 1 B 2 ILE A 815 PRO A 817 0
SHEET 2 B 2 VAL A 911 PRO A 913 -1 O LYS A 912 N ILE A 816
SITE 1 AC1 6 HOH A 161 SER A 696 PHE A 697 LYS A 777
SITE 2 AC1 6 ARG A 779 SER A 853
SITE 1 AC2 17 HOH A 101 HOH A 108 LEU A 704 ASN A 705
SITE 2 AC2 17 LEU A 707 GLY A 708 GLN A 711 MET A 742
SITE 3 AC2 17 MET A 745 VAL A 746 MET A 749 ARG A 752
SITE 4 AC2 17 PHE A 764 LEU A 873 THR A 877 MET A 895
SITE 5 AC2 17 ILE A 899
CRYST1 56.490 66.470 72.160 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 0.017702 0.000000 0.000000 0.00000
SCALE2 0.000000 0.015044 0.000000 0.00000
SCALE3 0.000000 0.000000 0.013858 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
