HEADER CHAPERONE 21-JUN-10 2XHR
TITLE STRUCTURE OF HSP90 WITH SMALL MOLECULE INHIBITOR BOUND
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: HEAT SHOCK PROTEIN HSP 90-ALPHA;
COMPND 3 CHAIN: A;
COMPND 4 FRAGMENT: N-TERMINAL DOMAIN (9-236);
COMPND 5 SYNONYM: HSP 86, RENAL CARCINOMA ANTIGEN NY-REN-38;
COMPND 6 ENGINEERED: YES
SOURCE MOL_ID: 1;
SOURCE 2 ORGANISM_SCIENTIFIC: HOMO SAPIENS;
SOURCE 3 ORGANISM_COMMON: HUMAN;
SOURCE 4 ORGANISM_TAXID: 9606;
SOURCE 5 GENE: HSP90, HSP90A, HSP90AA1, HSPC1, HSPCA;
SOURCE 6 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 7 EXPRESSION_SYSTEM_TAXID: 469008;
SOURCE 8 EXPRESSION_SYSTEM_STRAIN: BL21(DE3)
KEYWDS CHAPERONE, ATP BINDING DOMAIN, N-TERMINAL DOMAIN, STRESS RESPONSE
EXPDTA X-RAY DIFFRACTION
AUTHOR C.W.MURRAY,M.G.CARR,O.CALLAGHAN,G.CHESSARI,M.CONGREVE,S.COWAN,
AUTHOR 2 J.E.COYLE,R.DOWNHAM,E.FIGUEROA,M.FREDERICKSON,B.GRAHAM,R.MCMENAMIN,
AUTHOR 3 M.A.OBRIEN,S.PATEL,T.R.PHILLIPS,G.WILLIAMS,A.J.WOODHEAD,
AUTHOR 4 A.J.A.WOOLFORD
REVDAT 1 01-SEP-10 2XHR 0
JRNL AUTH C.W.MURRAY,M.G.CARR,O.CALLAGHAN,G.CHESSARI,M.CONGREVE,
JRNL AUTH 2 S.COWAN,J.E.COYLE,R.DOWNHAM,E.FIGUEROA,M.FREDERICKSON,
JRNL AUTH 3 B.GRAHAM,R.MCMENAMIN,M.A.O'BRIEN,S.PATEL,T.R.PHILLIPS,
JRNL AUTH 4 G.WILLIAMS,A.J.WOODHEAD,A.J.A.WOOLFORD
JRNL TITL FRAGMENT-BASED DRUG DISCOVERY APPLIED TO HSP90. DISCOVERY
JRNL TITL 2 OF TWO LEAD SERIES WITH HIGH LIGAND EFFICIENCY.
JRNL REF J.MED.CHEM. V. 53 5942 2010
JRNL REFN ISSN 0022-2623
JRNL PMID 20718493
JRNL DOI 10.1021/JM100059D
REMARK 2
REMARK 2 RESOLUTION. 2.20 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : BUSTER-TNT 2.5.1
REMARK 3 AUTHORS : BRICOGNE,BLANC,BRANDL,FLENSBURG,KELLER,
REMARK 3 : PACIOREK,ROVERSI,SMART,VONRHEIN,WOMACK,
REMARK 3 : MATTHEWS,TEN EYCK,TRONRUD
REMARK 3
REMARK 3 DATA USED IN REFINEMENT.
REMARK 3 RESOLUTION RANGE HIGH (ANGSTROMS) : 2.20
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 36.20
REMARK 3 DATA CUTOFF (SIGMA(F)) : 0.0
REMARK 3 COMPLETENESS FOR RANGE (%) : 98.97
REMARK 3 NUMBER OF REFLECTIONS : 15070
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) : 0.2532
REMARK 3 R VALUE (WORKING SET) : 0.2506
REMARK 3 FREE R VALUE : 0.3036
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.0
REMARK 3 FREE R VALUE TEST SET COUNT : 754
REMARK 3
REMARK 3 FIT IN THE HIGHEST RESOLUTION BIN.
REMARK 3 TOTAL NUMBER OF BINS USED : 9
REMARK 3 BIN RESOLUTION RANGE HIGH (ANGSTROMS) : 2.20
REMARK 3 BIN RESOLUTION RANGE LOW (ANGSTROMS) : 2.33
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : 98.97
REMARK 3 REFLECTIONS IN BIN (WORKING + TEST SET) : 2378
REMARK 3 BIN R VALUE (WORKING + TEST SET) : 0.2737
REMARK 3 REFLECTIONS IN BIN (WORKING SET) : 2252
REMARK 3 BIN R VALUE (WORKING SET) : 0.2717
REMARK 3 BIN FREE R VALUE : 0.3127
REMARK 3 BIN FREE R VALUE TEST SET SIZE (%) : 5.30
REMARK 3 BIN FREE R VALUE TEST SET COUNT : 126
REMARK 3 ESTIMATED ERROR OF FREE R VALUE : NULL
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 1635
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 25
REMARK 3 SOLVENT ATOMS : 78
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : 52.394
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 51.83
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 7.76473219
REMARK 3 B22 (A**2) : -9.19235508
REMARK 3 B33 (A**2) : 1.42762289
REMARK 3 B12 (A**2) : 0.00000000
REMARK 3 B13 (A**2) : 0.00000000
REMARK 3 B23 (A**2) : 0.00000000
REMARK 3
REMARK 3 ESTIMATED COORDINATE ERROR.
REMARK 3 ESD FROM LUZZATI PLOT (A) : NULL
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : NULL
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : NULL
REMARK 3
REMARK 3 NUMBER OF GEOMETRIC FUNCTION TERMS DEFINED : 15
REMARK 3 TERM COUNT WEIGHT FUNCTION.
REMARK 3 BOND LENGTHS : NULL ; NULL ; NULL
REMARK 3 BOND ANGLES : NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES : NULL ; NULL ; NULL
REMARK 3 TRIGONAL CARBON PLANES : NULL ; NULL ; NULL
REMARK 3 GENERAL PLANES : NULL ; NULL ; NULL
REMARK 3 ISOTROPIC THERMAL FACTORS : NULL ; NULL ; NULL
REMARK 3 BAD NON-BONDED CONTACTS : NULL ; NULL ; NULL
REMARK 3 IMPROPER TORSIONS : NULL ; NULL ; NULL
REMARK 3 PSEUDOROTATION ANGLES : NULL ; NULL ; NULL
REMARK 3 CHIRAL IMPROPER TORSION : NULL ; NULL ; NULL
REMARK 3 SUM OF OCCUPANCIES : NULL ; NULL ; NULL
REMARK 3 UTILITY DISTANCES : NULL ; NULL ; NULL
REMARK 3 UTILITY ANGLES : NULL ; NULL ; NULL
REMARK 3 UTILITY TORSION : NULL ; NULL ; NULL
REMARK 3 IDEAL-DIST CONTACT TERM : NULL ; NULL ; NULL
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES.
REMARK 3 BOND LENGTHS (A) : NULL
REMARK 3 BOND ANGLES (DEGREES) : NULL
REMARK 3 PEPTIDE OMEGA TORSION ANGLES (DEGREES) : NULL
REMARK 3 OTHER TORSION ANGLES (DEGREES) : NULL
REMARK 3
REMARK 3 TLS DETAILS
REMARK 3 NUMBER OF TLS GROUPS : NULL
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES RMS WEIGHT COUNT
REMARK 3 BOND LENGTHS (A) : 0.011 ; 2.00 ; 1688
REMARK 3 BOND ANGLES (DEGREES) : 1.367 ; 2.00 ; 2272
REMARK 3 TORSION ANGLES (DEGREES) : 19.138 ; 2.00 ; 345
REMARK 3 TRIGONAL CARBON PLANES (A) : NULL ; NULL ; NULL
REMARK 3 GENERAL PLANES (A) : NULL ; NULL ; NULL
REMARK 3 ISOTROPIC THERMAL FACTORS (A**2) : NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS (A) : NULL ; NULL ; NULL
REMARK 3
REMARK 3 INCORRECT CHIRAL-CENTERS (COUNT) : NULL
REMARK 3
REMARK 3 OTHER REFINEMENT REMARKS: NULL
REMARK 4
REMARK 4 2XHR COMPLIES WITH FORMAT V. 3.20, 01-DEC-08
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 21-JUN-10.
REMARK 100 THE PDBE ID CODE IS EBI-44317.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : NULL
REMARK 200 TEMPERATURE (KELVIN) : 100
REMARK 200 PH : NULL
REMARK 200 NUMBER OF CRYSTALS USED : NULL
REMARK 200
REMARK 200 SYNCHROTRON (Y/N) : N
REMARK 200 RADIATION SOURCE : ROTATING ANODE
REMARK 200 BEAMLINE : NULL
REMARK 200 X-RAY GENERATOR MODEL : NULL
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.54718
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : NULL
REMARK 200
REMARK 200 DETECTOR TYPE : NULL
REMARK 200 DETECTOR MANUFACTURER : NULL
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : NULL
REMARK 200 DATA SCALING SOFTWARE : NULL
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 15199
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.20
REMARK 200 RESOLUTION RANGE LOW (A) : 36.19
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 0.0
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.2
REMARK 200 DATA REDUNDANCY : 2.5
REMARK 200 R MERGE (I) : 0.10
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) : NULL
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : NULL
REMARK 200 COMPLETENESS FOR SHELL (%) : NULL
REMARK 200 DATA REDUNDANCY IN SHELL : NULL
REMARK 200 R MERGE FOR SHELL (I) : NULL
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: OTHER
REMARK 200 SOFTWARE USED: NULL
REMARK 200 STARTING MODEL: NONE
REMARK 200
REMARK 200 REMARK: NONE
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 52.82
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.61
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: NULL
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 32.82600
REMARK 290 SMTRY2 5 0.000000 1.000000 0.000000 44.77950
REMARK 290 SMTRY3 5 0.000000 0.000000 1.000000 49.59050
REMARK 290 SMTRY1 6 -1.000000 0.000000 0.000000 32.82600
REMARK 290 SMTRY2 6 0.000000 -1.000000 0.000000 44.77950
REMARK 290 SMTRY3 6 0.000000 0.000000 1.000000 49.59050
REMARK 290 SMTRY1 7 -1.000000 0.000000 0.000000 32.82600
REMARK 290 SMTRY2 7 0.000000 1.000000 0.000000 44.77950
REMARK 290 SMTRY3 7 0.000000 0.000000 -1.000000 49.59050
REMARK 290 SMTRY1 8 1.000000 0.000000 0.000000 32.82600
REMARK 290 SMTRY2 8 0.000000 -1.000000 0.000000 44.77950
REMARK 290 SMTRY3 8 0.000000 0.000000 -1.000000 49.59050
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 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 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 -12
REMARK 465 GLY A -11
REMARK 465 SER A -10
REMARK 465 SER A -9
REMARK 465 HIS A -8
REMARK 465 HIS A -7
REMARK 465 HIS A -6
REMARK 465 HIS A -5
REMARK 465 HIS A -4
REMARK 465 HIS A -3
REMARK 465 SER A -2
REMARK 465 SER A -1
REMARK 465 GLY A 0
REMARK 465 LEU A 1
REMARK 465 VAL A 2
REMARK 465 PRO A 3
REMARK 465 ARG A 4
REMARK 465 GLY A 5
REMARK 465 SER A 6
REMARK 465 HIS A 7
REMARK 465 MET A 8
REMARK 465 ASP A 9
REMARK 465 GLN A 10
REMARK 465 PRO A 11
REMARK 465 MET A 12
REMARK 465 GLU A 13
REMARK 465 GLU A 14
REMARK 465 GLU A 15
REMARK 465 GLU A 16
REMARK 465 GLU A 225
REMARK 465 ARG A 226
REMARK 465 ASP A 227
REMARK 465 LYS A 228
REMARK 465 GLU A 229
REMARK 465 VAL A 230
REMARK 465 SER A 231
REMARK 465 ASP A 232
REMARK 465 ASP A 233
REMARK 465 GLU A 234
REMARK 465 ALA A 235
REMARK 465 GLU A 236
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 PRO A 67 C - N - CD ANGL. DEV. = -22.3 DEGREES
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 GLU A 62 -10.26 -47.93
REMARK 500 THR A 65 41.76 -90.66
REMARK 500 ASP A 66 103.18 153.40
REMARK 500 ASN A 106 -81.70 -50.15
REMARK 500 THR A 109 -50.85 -132.14
REMARK 500 ALA A 124 17.64 173.58
REMARK 500 ALA A 166 -145.69 67.70
REMARK 500 ARG A 182 129.95 -172.50
REMARK 500 PHE A 213 62.91 -110.05
REMARK 500
REMARK 500 REMARK: NULL
REMARK 500
REMARK 500 GEOMETRY AND STEREOCHEMISTRY
REMARK 500 SUBTOPIC: CHIRAL CENTERS
REMARK 500
REMARK 500 UNEXPECTED CONFIGURATION OF THE FOLLOWING CHIRAL
REMARK 500 CENTER(S) USING IMPROPER CA--C--CB--N CHIRALITY
REMARK 500 FOR AMINO ACIDS AND C1'--O4'--N1(N9)--C2' FOR
REMARK 500 NUCLEIC ACIDS OR EQUIVALENT ANGLE
REMARK 500 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,A1,6X,F5.1,6X,A1,10X,A1,3X,A16)
REMARK 500
REMARK 500 M RES CSSEQI IMPROPER EXPECTED FOUND DETAILS
REMARK 500 ILE A 110 22.4 L L OUTSIDE RANGE
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 C0P A1001
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 2CDD RELATED DB: PDB
REMARK 900 HUMAN HSP90 WITH 4-(4-(2,3-DIHYDRO-
REMARK 900 BENZOL(1,4)DIOXIN-6-YL)-5-METHYL-1H-
REMARK 900 PYRAZOL-3-YL)-6-ETHYL-BENZENE-1,3-DIOL
REMARK 900 RELATED ID: 1YES RELATED DB: PDB
REMARK 900 HUMAN HSP90 GELDANAMYCIN-BINDING DOMAIN, "OPEN
REMARK 900 " CONFORMATION
REMARK 900 RELATED ID: 1UY9 RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 8-BENZO[1,3]
REMARK 900 DIOXOL-,5-YLMETHYL-9-BUTYL-9H-PURIN-6-
REMARK 900 YLAMINE
REMARK 900 RELATED ID: 1BYQ RELATED DB: PDB
REMARK 900 HSP90 N-TERMINAL DOMAIN BOUND TO ADP-MG
REMARK 900 RELATED ID: 2BSM RELATED DB: PDB
REMARK 900 NOVEL, POTENT SMALL MOLECULE INHIBITORS OF
REMARK 900 THE MOLECULAR CHAPERONE HSP90 DISCOVERED
REMARK 900 THROUGH STRUCTURE-BASED DESIGN
REMARK 900 RELATED ID: 1OSF RELATED DB: PDB
REMARK 900 HUMAN HSP90 IN COMPLEX WITH 17-DESMETHOXY-
REMARK 900 17-N,N-DIMETHYLAMINOETHYLAMINO-GELDANAMYCIN
REMARK 900 RELATED ID: 2WI3 RELATED DB: PDB
REMARK 900 ORALLY ACTIVE 2-AMINO THIENOPYRIMIDINE
REMARK 900 INHIBITORS OF THE HSP90 CHAPERONE
REMARK 900 RELATED ID: 1UY8 RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 9-BUTYL-8-(3-
REMARK 900 TRIMETHOXY-BENZYL)-9H-PURIN-6YLAMINE
REMARK 900 RELATED ID: 2BUG RELATED DB: PDB
REMARK 900 SOLUTION STRUCTURE OF THE TPR DOMAIN FROM
REMARK 900 PROTEIN PHOSPHATASE 5 IN COMPLEX WITH HSP90
REMARK 900 DERIVED PEPTIDE
REMARK 900 RELATED ID: 2WI4 RELATED DB: PDB
REMARK 900 ORALLY ACTIVE 2-AMINO THIENOPYRIMIDINE
REMARK 900 INHIBITORS OF THE HSP90 CHAPERONE
REMARK 900 RELATED ID: 2UWD RELATED DB: PDB
REMARK 900 INHIBITION OF THE HSP90 MOLECULAR CHAPERONE
REMARK 900 IN VITRO AND IN VIVO BY NOVEL, SYNTHETIC
REMARK 900 , POTENT RESORCINYLIC PYRAZOLE, ISOXAZOLE AMIDE
REMARK 900 ANALOGS
REMARK 900 RELATED ID: 2WI7 RELATED DB: PDB
REMARK 900 ORALLY ACTIVE 2-AMINO THIENOPYRIMIDINE
REMARK 900 INHIBITORS OF THE HSP90 CHAPERONE
REMARK 900 RELATED ID: 2BT0 RELATED DB: PDB
REMARK 900 NOVEL, POTENT SMALL MOLECULE INHIBITORS OF
REMARK 900 THE MOLECULAR CHAPERONE HSP90 DISCOVERED
REMARK 900 THROUGH STRUCTURE-BASED DESIGN
REMARK 900 RELATED ID: 1YER RELATED DB: PDB
REMARK 900 HUMAN HSP90 GELDANAMYCIN-BINDING DOMAIN, "
REMARK 900 CLOSED" CONFORMATION
REMARK 900 RELATED ID: 2XDU RELATED DB: PDB
REMARK 900 STRUCTRE OF HSP90 WITH SMALL MOLECULE
REMARK 900 INHIBITOR BOUND
REMARK 900 RELATED ID: 1UYG RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 8-(2,5-DIMETHOXY-
REMARK 900 BENZYL)-2-FLUORO-9H-PURIN-6-YLAMINE
REMARK 900 RELATED ID: 2BZ5 RELATED DB: PDB
REMARK 900 STRUCTURE-BASED DISCOVERY OF A NEW CLASS
REMARK 900 OF HSP90 INHIBITORS
REMARK 900 RELATED ID: 2CCU RELATED DB: PDB
REMARK 900 HUMAN HSP90 WITH 4-CHLORO-6-(4-(4-(4-
REMARK 900 METHANESULPHONYL-BENZYL)-PIERAZIN-1-YL)-1H-
REMARK 900 PYRAZOL-3-YL)-BENZENE-1,3-DIOL
REMARK 900 RELATED ID: 2XDS RELATED DB: PDB
REMARK 900 STRUCTRE OF HSP90 WITH SMALL MOLECULE
REMARK 900 INHIBITOR BOUND
REMARK 900 RELATED ID: 2XDX RELATED DB: PDB
REMARK 900 STRUCTRE OF HSP90 WITH SMALL MOLECULE
REMARK 900 INHIBITOR BOUND
REMARK 900 RELATED ID: 2CCS RELATED DB: PDB
REMARK 900 HUMAN HSP90 WITH 4-CHLORO-6-(4-PIPERAZIN-
REMARK 900 1-YL-1H-PYRAZOL-3-YL)-BENZENE-1,2-DIOL
REMARK 900 RELATED ID: 1UYF RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 8-(2-CHLORO-3,4,
REMARK 900 5-TRIMETHOXY-BENZYL)-2-FLUORO-9-PENT-4-
REMARK 900 YLNYL-9H-PURIN-6-YLAMINE
REMARK 900 RELATED ID: 1YC3 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF HUMAN HSP90ALPHA
REMARK 900 COMPLEXED WITHDIHYDROXYPHENYLPYRAZOLES
REMARK 900 RELATED ID: 1UYI RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 8-(2,5-DIMETHOXY-
REMARK 900 BENZYL)-2-FLUORO-9-PENT-9H-PURIN-6-
REMARK 900 YLAMINE
REMARK 900 RELATED ID: 1UYD RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 9-BUTYL-8-(2-
REMARK 900 CHLORO-3,4,5-TRIMETHOXY-BENZYL)-9H-PURIN-
REMARK 900 6-YLAMINE
REMARK 900 RELATED ID: 2BYI RELATED DB: PDB
REMARK 900 3-(5-CHLORO-2,4-DIHYDROXYPHENYL)-PYRAZOLE-
REMARK 900 4-CARBOXAMIDES AS INHIBITORS OF THE HSP90
REMARK 900 MOLECULAR CHAPERONE
REMARK 900 RELATED ID: 2XDL RELATED DB: PDB
REMARK 900 STRUCTURE OF HSP90 WITH SMALL MOLECULE
REMARK 900 INHIBITOR BOUND
REMARK 900 RELATED ID: 2WI2 RELATED DB: PDB
REMARK 900 ORALLY ACTIVE 2-AMINO THIENOPYRIMIDINE
REMARK 900 INHIBITORS OF THE HSP90 CHAPERONE
REMARK 900 RELATED ID: 2VCI RELATED DB: PDB
REMARK 900 4,5 DIARYL ISOXAZOLE HSP90 CHAPERONE
REMARK 900 INHIBITORS: POTENTIAL THERAPEUTIC AGENTS FOR
REMARK 900 THE TREATMENT OF CANCER
REMARK 900 RELATED ID: 1UY6 RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 9-BUTYL-8-(3,4,
REMARK 900 5-TRIMETHOXY-BENZYL)-9H-PURIN-6-YLAMINE
REMARK 900 RELATED ID: 2WI1 RELATED DB: PDB
REMARK 900 ORALLY ACTIVE 2-AMINO THIENOPYRIMIDINE
REMARK 900 INHIBITORS OF THE HSP90 CHAPERONE
REMARK 900 RELATED ID: 2VCJ RELATED DB: PDB
REMARK 900 4,5 DIARYL ISOXAZOLE HSP90 CHAPERONE
REMARK 900 INHIBITORS: POTENTIAL THERAPEUTIC AGENTS FOR
REMARK 900 THE TREATMENT OF CANCER
REMARK 900 RELATED ID: 1YC4 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF HUMAN HSP90ALPHA
REMARK 900 COMPLEXED WITHDIHYDROXYPHENYLPYRAZOLES
REMARK 900 RELATED ID: 2C2L RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF THE CHIP U-BOX E3
REMARK 900 UBIQUITIN LIGASE
REMARK 900 RELATED ID: 2FWZ RELATED DB: PDB
REMARK 900 STRUCTURE OF HUMAN HSP90-ALPHA BOUND TO
REMARK 900 THE POTENT WATERSOLUBLE INHIBITOR PU-H71
REMARK 900 RELATED ID: 2XDK RELATED DB: PDB
REMARK 900 STRUCTURE OF HSP90 WITH SMALL MOLECULE
REMARK 900 INHIBITOR BOUND
REMARK 900 RELATED ID: 1UYH RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 9-BUTYL-8-(2,5-
REMARK 900 DIMETHOXY-BENZYL)-2-FLUORO-9H-PURIN-6-
REMARK 900 YLAMINE
REMARK 900 RELATED ID: 1UYK RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 8-BENZO[1,3]
REMARK 900 DIOXOL-,5-YLMETHYL-9-BUTYL-2-FLUORO-9H-
REMARK 900 PURIN-6-YLAMINE
REMARK 900 RELATED ID: 2CCT RELATED DB: PDB
REMARK 900 HUMAN HSP90 WITH 5-(5-CHLORO-2,4-
REMARK 900 DIHYDROXY-PHENYL)-4-PIPERAZIN-1-YL-2H-
REMARK 900 PYRAZOLE-3-CARBOXYLIC ACID ETHYLAMIDE
REMARK 900 RELATED ID: 2FWY RELATED DB: PDB
REMARK 900 STRUCTURE OF HUMAN HSP90-ALPHA BOUND TO
REMARK 900 THE POTENT WATERSOLUBLE INHIBITOR PU-H64
REMARK 900 RELATED ID: 1UYL RELATED DB: PDB
REMARK 900 STRUCTURE-ACTIVITY RELATIONSHIPS IN PURINE-
REMARK 900 BASED INHIBITOR BINDING TO HSP90 ISOFORMS
REMARK 900 RELATED ID: 1UYE RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 8-(2-CHLORO-3,4,
REMARK 900 5-TRIMETHOXY-BENZYL)-9-PENT-4-YLNYL-9H-
REMARK 900 PURIN-6-YLAMINE
REMARK 900 RELATED ID: 2WI6 RELATED DB: PDB
REMARK 900 ORALLY ACTIVE 2-AMINO THIENOPYRIMIDINE
REMARK 900 INHIBITORS OF THE HSP90 CHAPERONE
REMARK 900 RELATED ID: 2XAB RELATED DB: PDB
REMARK 900 STRUCTURE OF HSP90 WITH AN INHIBITOR BOUND
REMARK 900 RELATED ID: 1YC1 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURES OF HUMAN HSP90ALPHA
REMARK 900 COMPLEXED WITHDIHYDROXYPHENYLPYRAZOLES
REMARK 900 RELATED ID: 2XHT RELATED DB: PDB
REMARK 900 STRUCTRE OF HSP90 WITH SMALL MOLECULE
REMARK 900 INHIBITOR BOUND
REMARK 900 RELATED ID: 1UYC RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 9-BUTYL-8-(2,5-
REMARK 900 DIMETHOXY-BENZYL)-9H-PURIN-6-YLAMINE
REMARK 900 RELATED ID: 1UY7 RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 9-BUTYL-8-(4-
REMARK 900 METHOXY-BENZYL)-9H-PURIN-6-YLAMINE
REMARK 900 RELATED ID: 1YET RELATED DB: PDB
REMARK 900 GELDANAMYCIN BOUND TO THE HSP90 GELDANAMYCIN-
REMARK 900 BINDING DOMAIN
REMARK 900 RELATED ID: 2JJC RELATED DB: PDB
REMARK 900 HSP90 ALPHA ATPASE DOMAIN WITH BOUND SMALL
REMARK 900 MOLECULE FRAGMENT
REMARK 900 RELATED ID: 2BYH RELATED DB: PDB
REMARK 900 3-(5-CHLORO-2,4-DIHYDROXYPHENYL)-PYRAZOLE-
REMARK 900 4-CARBOXAMIDES AS INHIBITORS OF THE HSP90
REMARK 900 MOLECULAR CHAPERONE
REMARK 900 RELATED ID: 2WI5 RELATED DB: PDB
REMARK 900 ORALLY ACTIVE 2-AMINO THIENOPYRIMIDINE
REMARK 900 INHIBITORS OF THE HSP90 CHAPERONE
DBREF 2XHR A 9 236 UNP P07900 HS90A_HUMAN 9 236
SEQADV 2XHR MET A -12 UNP P07900 EXPRESSION TAG
SEQADV 2XHR GLY A -11 UNP P07900 EXPRESSION TAG
SEQADV 2XHR SER A -10 UNP P07900 EXPRESSION TAG
SEQADV 2XHR SER A -9 UNP P07900 EXPRESSION TAG
SEQADV 2XHR HIS A -8 UNP P07900 EXPRESSION TAG
SEQADV 2XHR HIS A -7 UNP P07900 EXPRESSION TAG
SEQADV 2XHR HIS A -6 UNP P07900 EXPRESSION TAG
SEQADV 2XHR HIS A -5 UNP P07900 EXPRESSION TAG
SEQADV 2XHR HIS A -4 UNP P07900 EXPRESSION TAG
SEQADV 2XHR HIS A -3 UNP P07900 EXPRESSION TAG
SEQADV 2XHR SER A -2 UNP P07900 EXPRESSION TAG
SEQADV 2XHR SER A -1 UNP P07900 EXPRESSION TAG
SEQADV 2XHR GLY A 0 UNP P07900 EXPRESSION TAG
SEQADV 2XHR LEU A 1 UNP P07900 EXPRESSION TAG
SEQADV 2XHR VAL A 2 UNP P07900 EXPRESSION TAG
SEQADV 2XHR PRO A 3 UNP P07900 EXPRESSION TAG
SEQADV 2XHR ARG A 4 UNP P07900 EXPRESSION TAG
SEQADV 2XHR GLY A 5 UNP P07900 EXPRESSION TAG
SEQADV 2XHR SER A 6 UNP P07900 EXPRESSION TAG
SEQADV 2XHR HIS A 7 UNP P07900 EXPRESSION TAG
SEQADV 2XHR MET A 8 UNP P07900 EXPRESSION TAG
SEQRES 1 A 249 MET GLY SER SER HIS HIS HIS HIS HIS HIS SER SER GLY
SEQRES 2 A 249 LEU VAL PRO ARG GLY SER HIS MET ASP GLN PRO MET GLU
SEQRES 3 A 249 GLU GLU GLU VAL GLU THR PHE ALA PHE GLN ALA GLU ILE
SEQRES 4 A 249 ALA GLN LEU MET SER LEU ILE ILE ASN THR PHE TYR SER
SEQRES 5 A 249 ASN LYS GLU ILE PHE LEU ARG GLU LEU ILE SER ASN SER
SEQRES 6 A 249 SER ASP ALA LEU ASP LYS ILE ARG TYR GLU SER LEU THR
SEQRES 7 A 249 ASP PRO SER LYS LEU ASP SER GLY LYS GLU LEU HIS ILE
SEQRES 8 A 249 ASN LEU ILE PRO ASN LYS GLN ASP ARG THR LEU THR ILE
SEQRES 9 A 249 VAL ASP THR GLY ILE GLY MET THR LYS ALA ASP LEU ILE
SEQRES 10 A 249 ASN ASN LEU GLY THR ILE ALA LYS SER GLY THR LYS ALA
SEQRES 11 A 249 PHE MET GLU ALA LEU GLN ALA GLY ALA ASP ILE SER MET
SEQRES 12 A 249 ILE GLY GLN PHE GLY VAL GLY PHE TYR SER ALA TYR LEU
SEQRES 13 A 249 VAL ALA GLU LYS VAL THR VAL ILE THR LYS HIS ASN ASP
SEQRES 14 A 249 ASP GLU GLN TYR ALA TRP GLU SER SER ALA GLY GLY SER
SEQRES 15 A 249 PHE THR VAL ARG THR ASP THR GLY GLU PRO MET GLY ARG
SEQRES 16 A 249 GLY THR LYS VAL ILE LEU HIS LEU LYS GLU ASP GLN THR
SEQRES 17 A 249 GLU TYR LEU GLU GLU ARG ARG ILE LYS GLU ILE VAL LYS
SEQRES 18 A 249 LYS HIS SER GLN PHE ILE GLY TYR PRO ILE THR LEU PHE
SEQRES 19 A 249 VAL GLU LYS GLU ARG ASP LYS GLU VAL SER ASP ASP GLU
SEQRES 20 A 249 ALA GLU
HET C0P A1001 42
HETNAM C0P 4-CHLORO-6-[2,4-DICHLORO-5-(2-MORPHOLIN-4-
HETNAM 2 C0P YLETHOXY)PHENYL]PYRIMIDIN-2-AMINE
FORMUL 2 C0P C16 H17 CL3 N4 O2
FORMUL 3 HOH *78(H2 O)
HELIX 1 1 GLN A 23 THR A 36 1 14
HELIX 2 2 GLU A 42 GLU A 62 1 21
HELIX 3 3 ASP A 66 GLY A 73 5 8
HELIX 4 4 THR A 99 THR A 109 1 11
HELIX 5 5 ALA A 111 GLN A 123 1 13
HELIX 6 6 ASP A 127 GLY A 135 5 9
HELIX 7 7 VAL A 136 LEU A 143 5 8
HELIX 8 8 GLU A 192 LEU A 198 5 7
HELIX 9 9 GLU A 199 SER A 211 1 13
SHEET 1 AA 8 GLU A 18 ALA A 21 0
SHEET 2 AA 8 SER A 169 THR A 174 -1 O PHE A 170 N PHE A 20
SHEET 3 AA 8 TYR A 160 SER A 164 -1 O ALA A 161 N ARG A 173
SHEET 4 AA 8 ALA A 145 LYS A 153 -1 O VAL A 148 N SER A 164
SHEET 5 AA 8 GLY A 183 LEU A 190 -1 O GLY A 183 N LYS A 153
SHEET 6 AA 8 THR A 88 ASP A 93 -1 O LEU A 89 N LEU A 188
SHEET 7 AA 8 ILE A 78 ASN A 83 -1 O ASN A 79 N VAL A 92
SHEET 8 AA 8 ILE A 218 LEU A 220 1 O THR A 219 N LEU A 80
SITE 1 AC1 14 SER A 52 ALA A 55 ASP A 93 GLY A 97
SITE 2 AC1 14 MET A 98 ASN A 106 LEU A 107 ILE A 110
SITE 3 AC1 14 GLY A 135 PHE A 138 THR A 184 HOH A2013
SITE 4 AC1 14 HOH A2058 HOH A2078
CRYST1 65.652 89.559 99.181 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 0.015232 0.000000 0.000000 0.00000
SCALE2 0.000000 0.011166 0.000000 0.00000
SCALE3 0.000000 0.000000 0.010083 0.00000
(ATOM LINES ARE NOT SHOWN.)
END