HEADER CHAPERONE 24-MAY-05 2BT0
TITLE NOVEL, POTENT SMALL MOLECULE INHIBITORS OF THE MOLECULAR CHAPERONE
TITLE 2 HSP90 DISCOVERED THROUGH STRUCTURE-BASED DESIGN
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: HEAT SHOCK PROTEIN HSP90-ALPHA;
COMPND 3 CHAIN: A, B;
COMPND 4 FRAGMENT: N-TERMINAL DOMAIN, RESIDUES 1-235;
COMPND 5 SYNONYM: HSP 86;
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 ORGAN: SKIN;
SOURCE 6 TISSUE: MELANOMA;
SOURCE 7 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 8 EXPRESSION_SYSTEM_TAXID: 469008;
SOURCE 9 EXPRESSION_SYSTEM_STRAIN: BL21(DE3);
SOURCE 10 EXPRESSION_SYSTEM_PLASMID: PET19
KEYWDS ATP-BINDING, CHAPERONE, HEAT SHOCK, PHOSPHORYLATION
EXPDTA X-RAY DIFFRACTION
AUTHOR B.W.DYMOCK,X.BARRIL,P.A.BROUGH,J.E.CANSFIELD,A.MASSEY,E.MCDONALD,
AUTHOR 2 R.E.HUBBARD,A.SURGENOR,S.D.ROUGHLEY,P.WEBB,P.WORKMAN,L.WRIGHT,
AUTHOR 3 M.J.DRYSDALE
REVDAT 5 13-DEC-23 2BT0 1 REMARK
REVDAT 4 28-FEB-18 2BT0 1 JRNL
REVDAT 3 24-FEB-09 2BT0 1 VERSN
REVDAT 2 29-JUN-05 2BT0 1 JRNL
REVDAT 1 02-JUN-05 2BT0 0
JRNL AUTH B.W.DYMOCK,X.BARRIL,P.A.BROUGH,J.E.CANSFIELD,A.MASSEY,
JRNL AUTH 2 E.MCDONALD,R.E.HUBBARD,A.SURGENOR,S.D.ROUGHLEY,P.WEBB,
JRNL AUTH 3 P.WORKMAN,L.WRIGHT,M.J.DRYSDALE
JRNL TITL NOVEL, POTENT SMALL-MOLECULE INHIBITORS OF THE MOLECULAR
JRNL TITL 2 CHAPERONE HSP90 DISCOVERED THROUGH STRUCTURE-BASED DESIGN.
JRNL REF J. MED. CHEM. V. 48 4212 2005
JRNL REFN ISSN 0022-2623
JRNL PMID 15974572
JRNL DOI 10.1021/JM050355Z
REMARK 2
REMARK 2 RESOLUTION. 1.90 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.1.24
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) : 1.90
REMARK 3 RESOLUTION RANGE LOW (ANGSTROMS) : 30.00
REMARK 3 DATA CUTOFF (SIGMA(F)) : NULL
REMARK 3 COMPLETENESS FOR RANGE (%) : 95.3
REMARK 3 NUMBER OF REFLECTIONS : 40741
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) : 0.204
REMARK 3 R VALUE (WORKING SET) : 0.202
REMARK 3 FREE R VALUE : 0.244
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.100
REMARK 3 FREE R VALUE TEST SET COUNT : 2170
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) : 1.90
REMARK 3 BIN RESOLUTION RANGE LOW (A) : 1.95
REMARK 3 REFLECTION IN BIN (WORKING SET) : 2158
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : NULL
REMARK 3 BIN R VALUE (WORKING SET) : 0.3190
REMARK 3 BIN FREE R VALUE SET COUNT : 109
REMARK 3 BIN FREE R VALUE : 0.3520
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 3272
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 52
REMARK 3 SOLVENT ATOMS : 487
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 18.63
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : 0.39000
REMARK 3 B22 (A**2) : 0.30000
REMARK 3 B33 (A**2) : -0.69000
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): 0.154
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.147
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.121
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 4.498
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.948
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.929
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 3407 ; 0.011 ; 0.022
REMARK 3 BOND LENGTHS OTHERS (A): 3050 ; 0.002 ; 0.020
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 4597 ; 1.279 ; 1.941
REMARK 3 BOND ANGLES OTHERS (DEGREES): 7136 ; 1.381 ; 2.999
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 414 ; 6.187 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): NULL ; NULL ; NULL
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 517 ; 0.076 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 3747 ; 0.005 ; 0.020
REMARK 3 GENERAL PLANES OTHERS (A): 648 ; 0.002 ; 0.020
REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A): 728 ; 0.191 ; 0.200
REMARK 3 NON-BONDED CONTACTS OTHERS (A): 3773 ; 0.237 ; 0.200
REMARK 3 NON-BONDED TORSION REFINED ATOMS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION OTHERS (A): 2030 ; 0.084 ; 0.200
REMARK 3 H-BOND (X...Y) REFINED ATOMS (A): 364 ; 0.152 ; 0.200
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): 10 ; 0.126 ; 0.200
REMARK 3 SYMMETRY VDW OTHERS (A): 49 ; 0.292 ; 0.200
REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): 19 ; 0.205 ; 0.200
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): 2058 ; 0.620 ; 1.500
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 3332 ; 1.150 ; 2.000
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 1349 ; 1.707 ; 3.000
REMARK 3 SIDE-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): 1265 ; 2.895 ; 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 : NULL
REMARK 3
REMARK 3 BULK SOLVENT MODELLING.
REMARK 3 METHOD USED : BABINET MODEL WITH 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: HYDROGENS HAVE BEEN ADDED IN THE RIDING
REMARK 3 POSITIONS.
REMARK 4
REMARK 4 2BT0 COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 24-MAY-05.
REMARK 100 THE DEPOSITION ID IS D_1290024221.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 04-AUG-04
REMARK 200 TEMPERATURE (KELVIN) : 100.0
REMARK 200 PH : 6.50
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 RUH3R
REMARK 200 MONOCHROMATIC OR LAUE (M/L) : M
REMARK 200 WAVELENGTH OR RANGE (A) : 1.5418
REMARK 200 MONOCHROMATOR : NULL
REMARK 200 OPTICS : OSMIC BLUE MIRRORS
REMARK 200
REMARK 200 DETECTOR TYPE : IMAGE PLATE
REMARK 200 DETECTOR MANUFACTURER : MARRESEARCH
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : D*TREK
REMARK 200 DATA SCALING SOFTWARE : D*TREK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 19136
REMARK 200 RESOLUTION RANGE HIGH (A) : 2.000
REMARK 200 RESOLUTION RANGE LOW (A) : 30.000
REMARK 200 REJECTION CRITERIA (SIGMA(I)) : 2.000
REMARK 200
REMARK 200 OVERALL.
REMARK 200 COMPLETENESS FOR RANGE (%) : 99.0
REMARK 200 DATA REDUNDANCY : 3.420
REMARK 200 R MERGE (I) : 0.08000
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 10.6000
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) : 2.07
REMARK 200 COMPLETENESS FOR SHELL (%) : 93.0
REMARK 200 DATA REDUNDANCY IN SHELL : 2.44
REMARK 200 R MERGE FOR SHELL (I) : 0.30000
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 3.400
REMARK 200
REMARK 200 DIFFRACTION PROTOCOL: SINGLE WAVELENGTH
REMARK 200 METHOD USED TO DETERMINE THE STRUCTURE: MOLECULAR REPLACEMENT
REMARK 200 SOFTWARE USED: AMORE
REMARK 200 STARTING MODEL: PDB ENTRY 1UY6
REMARK 200
REMARK 200 REMARK: NULL
REMARK 280
REMARK 280 CRYSTAL
REMARK 280 SOLVENT CONTENT, VS (%): 57.50
REMARK 280 MATTHEWS COEFFICIENT, VM (ANGSTROMS**3/DA): 2.90
REMARK 280
REMARK 280 CRYSTALLIZATION CONDITIONS: PH 6.50
REMARK 290
REMARK 290 CRYSTALLOGRAPHIC SYMMETRY
REMARK 290 SYMMETRY OPERATORS FOR SPACE GROUP: P 21 21 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+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 32.09400
REMARK 290 SMTRY2 3 0.000000 1.000000 0.000000 44.25400
REMARK 290 SMTRY3 3 0.000000 0.000000 -1.000000 0.00000
REMARK 290 SMTRY1 4 1.000000 0.000000 0.000000 32.09400
REMARK 290 SMTRY2 4 0.000000 -1.000000 0.000000 44.25400
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: DIMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC
REMARK 350 SOFTWARE USED: PQS
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 BIOMT1 2 -1.000000 0.000000 0.000000 0.00000
REMARK 350 BIOMT2 2 0.000000 -1.000000 0.000000 -88.50800
REMARK 350 BIOMT3 2 0.000000 0.000000 1.000000 0.00000
REMARK 350
REMARK 350 BIOMOLECULE: 2
REMARK 350 AUTHOR DETERMINED BIOLOGICAL UNIT: DIMERIC
REMARK 350 SOFTWARE DETERMINED QUATERNARY STRUCTURE: DIMERIC
REMARK 350 SOFTWARE USED: PQS
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 350 BIOMT1 2 -1.000000 0.000000 0.000000 0.00000
REMARK 350 BIOMT2 2 0.000000 -1.000000 0.000000 -88.50800
REMARK 350 BIOMT3 2 0.000000 0.000000 1.000000 0.00000
REMARK 400
REMARK 400 COMPOUND
REMARK 400 FUNCTION: ATPASE ACTIVITY
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 PRO A 2
REMARK 465 GLU A 3
REMARK 465 GLU A 4
REMARK 465 THR A 5
REMARK 465 GLN A 6
REMARK 465 THR A 7
REMARK 465 GLN 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 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 465 PRO B 2
REMARK 465 GLU B 3
REMARK 465 GLU B 4
REMARK 465 THR B 5
REMARK 465 GLN B 6
REMARK 465 THR B 7
REMARK 465 GLN B 8
REMARK 465 ASP B 9
REMARK 465 GLN B 10
REMARK 465 PRO B 11
REMARK 465 MET B 12
REMARK 465 GLU B 13
REMARK 465 GLU B 14
REMARK 465 GLU B 15
REMARK 465 GLU B 225
REMARK 465 ARG B 226
REMARK 465 ASP B 227
REMARK 465 LYS B 228
REMARK 465 GLU B 229
REMARK 465 VAL B 230
REMARK 465 SER B 231
REMARK 465 ASP B 232
REMARK 465 ASP B 233
REMARK 465 GLU B 234
REMARK 465 ALA B 235
REMARK 465 GLU B 236
REMARK 470
REMARK 470 MISSING ATOM
REMARK 470 THE FOLLOWING RESIDUES HAVE MISSING ATOMS (M=MODEL NUMBER;
REMARK 470 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE NUMBER;
REMARK 470 I=INSERTION CODE):
REMARK 470 M RES CSSEQI ATOMS
REMARK 470 LYS A 224 CA C O CB CG CD CE
REMARK 470 LYS A 224 NZ
REMARK 470 LYS B 224 CA C O CB CG CD CE
REMARK 470 LYS B 224 NZ
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 TYR A 38 109.33 -162.82
REMARK 500 ILE A 110 58.17 -93.49
REMARK 500 ALA A 166 -138.06 55.80
REMARK 500 TYR B 38 104.94 -163.92
REMARK 500 ALA B 111 -124.38 56.59
REMARK 500 ALA B 166 -143.89 64.98
REMARK 500 ARG B 182 136.38 -173.03
REMARK 500
REMARK 500 REMARK: NULL
REMARK 525
REMARK 525 SOLVENT
REMARK 525
REMARK 525 THE SOLVENT MOLECULES HAVE CHAIN IDENTIFIERS THAT
REMARK 525 INDICATE THE POLYMER CHAIN WITH WHICH THEY ARE MOST
REMARK 525 CLOSELY ASSOCIATED. THE REMARK LISTS ALL THE SOLVENT
REMARK 525 MOLECULES WHICH ARE MORE THAN 5A AWAY FROM THE
REMARK 525 NEAREST POLYMER CHAIN (M = MODEL NUMBER;
REMARK 525 RES=RESIDUE NAME; C=CHAIN IDENTIFIER; SSEQ=SEQUENCE
REMARK 525 NUMBER; I=INSERTION CODE):
REMARK 525
REMARK 525 M RES CSSEQI
REMARK 525 HOH B2043 DISTANCE = 6.40 ANGSTROMS
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CT5 A1224
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE CT5 B1224
REMARK 900
REMARK 900 RELATED ENTRIES
REMARK 900 RELATED ID: 1BYQ RELATED DB: PDB
REMARK 900 HSP90 N-TERMINAL DOMAIN BOUND TO ADP-MG
REMARK 900 RELATED ID: 1OSF RELATED DB: PDB
REMARK 900 HUMAN HSP90 IN COMPLEX WITH 17-DESMETHOXY- 17-N,N-
REMARK 900 DIMETHYLAMINOETHYLAMINO-GELDANAMYCIN
REMARK 900 RELATED ID: 1UY6 RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 9-BUTYL-8- (3,4,5-TRIMETHOXY-BENZYL)-9H-
REMARK 900 PURIN-6-YLAMINE
REMARK 900 RELATED ID: 1UY7 RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 9-BUTYL-8- (4-METHOXY-BENZYL)-9H-PURIN-6-
REMARK 900 YLAMINE
REMARK 900 RELATED ID: 1UY8 RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 9-BUTYL-8- (3-TRIMETHOXY-BENZYL)-9H-PURIN-
REMARK 900 6YLAMINE
REMARK 900 RELATED ID: 1UY9 RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 8-BENZO[1,3] DIOXOL-,5-YLMETHYL-9-BUTYL-9H-
REMARK 900 PURIN-6- YLAMINE
REMARK 900 RELATED ID: 1UYC RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 9-BUTYL-8- (2,5-DIMETHOXY-BENZYL)-9H-PURIN-6-
REMARK 900 YLAMINE
REMARK 900 RELATED ID: 1UYD RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 9-BUTYL-8- (2-CHLORO-3,4,5-TRIMETHOXY-BENZYL)
REMARK 900 -9H-PURIN- 6-YLAMINE
REMARK 900 RELATED ID: 1UYE RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 8-(2-CHLORO-3,4, 5-TRIMETHOXY-BENZYL)-9-PENT-
REMARK 900 4-YLNYL-9H- PURIN-6-YLAMINE
REMARK 900 RELATED ID: 1UYF RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 8-(2-CHLORO-3,4, 5-TRIMETHOXY-BENZYL)-2-
REMARK 900 FLUORO-9-PENT-4- YLNYL-9H-PURIN-6-YLAMINE
REMARK 900 RELATED ID: 1UYG RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 8-(2,5-DIMETHOXY- BENZYL)-2-FLUORO-9H-PURIN-
REMARK 900 6-YLAMINE
REMARK 900 RELATED ID: 1UYH RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 9-BUTYL-8- (2,5-DIMETHOXY-BENZYL)-2-FLUORO-
REMARK 900 9H-PURIN-6- YLAMINE
REMARK 900 RELATED ID: 1UYI RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 8-(2,5-DIMETHOXY- BENZYL)-2-FLUORO-9-PENT-9H-
REMARK 900 PURIN-6- YLAMINE
REMARK 900 RELATED ID: 1UYK RELATED DB: PDB
REMARK 900 HUMAN HSP90-ALPHA WITH 8-BENZO[1,3] DIOXOL-,5-YLMETHYL-9-BUTYL-2-
REMARK 900 FLUORO-9H- PURIN-6-YLAMINE
REMARK 900 RELATED ID: 1UYL RELATED DB: PDB
REMARK 900 STRUCTURE-ACTIVITY RELATIONSHIPS IN PURINE- BASED INHIBITOR BINDING
REMARK 900 TO HSP90 ISOFORMS
REMARK 900 RELATED ID: 1YC1 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURES OF HUMAN HSP90ALPHA COMPLEXED
REMARK 900 WITHDIHYDROXYPHENYLPYRAZOLES
REMARK 900 RELATED ID: 1YC3 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF HUMAN HSP90ALPHA COMPLEXED
REMARK 900 WITHDIHYDROXYPHENYLPYRAZOLES
REMARK 900 RELATED ID: 1YC4 RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF HUMAN HSP90ALPHA COMPLEXED
REMARK 900 WITHDIHYDROXYPHENYLPYRAZOLES
REMARK 900 RELATED ID: 1YER RELATED DB: PDB
REMARK 900 HUMAN HSP90 GELDANAMYCIN-BINDING DOMAIN, "CLOSED" CONFORMATION
REMARK 900 RELATED ID: 1YES RELATED DB: PDB
REMARK 900 HUMAN HSP90 GELDANAMYCIN-BINDING DOMAIN, "OPEN" CONFORMATION
REMARK 900 RELATED ID: 1YET RELATED DB: PDB
REMARK 900 GELDANAMYCIN BOUND TO THE HSP90 GELDANAMYCIN- BINDING DOMAIN
REMARK 900 RELATED ID: 2BSM RELATED DB: PDB
REMARK 900 NOVEL, POTENT SMALL MOLECULE INHIBITORS OF THE MOLECULAR CHAPERONE
REMARK 900 HSP90 DISCOVERED THROUGH STRUCTURE-BASED DESIGN
REMARK 999
REMARK 999 SEQUENCE
REMARK 999 THE CONFLICT IS ALSO MENTIONED IN UNP
DBREF 2BT0 A 2 236 UNP P07900 HS90A_HUMAN 1 235
DBREF 2BT0 B 2 236 UNP P07900 HS90A_HUMAN 1 235
SEQADV 2BT0 SER A 63 UNP P07900 THR 62 CONFLICT
SEQADV 2BT0 SER B 63 UNP P07900 THR 62 CONFLICT
SEQRES 1 A 235 PRO GLU GLU THR GLN THR GLN ASP GLN PRO MET GLU GLU
SEQRES 2 A 235 GLU GLU VAL GLU THR PHE ALA PHE GLN ALA GLU ILE ALA
SEQRES 3 A 235 GLN LEU MET SER LEU ILE ILE ASN THR PHE TYR SER ASN
SEQRES 4 A 235 LYS GLU ILE PHE LEU ARG GLU LEU ILE SER ASN SER SER
SEQRES 5 A 235 ASP ALA LEU ASP LYS ILE ARG TYR GLU SER LEU THR ASP
SEQRES 6 A 235 PRO SER LYS LEU ASP SER GLY LYS GLU LEU HIS ILE ASN
SEQRES 7 A 235 LEU ILE PRO ASN LYS GLN ASP ARG THR LEU THR ILE VAL
SEQRES 8 A 235 ASP THR GLY ILE GLY MET THR LYS ALA ASP LEU ILE ASN
SEQRES 9 A 235 ASN LEU GLY THR ILE ALA LYS SER GLY THR LYS ALA PHE
SEQRES 10 A 235 MET GLU ALA LEU GLN ALA GLY ALA ASP ILE SER MET ILE
SEQRES 11 A 235 GLY GLN PHE GLY VAL GLY PHE TYR SER ALA TYR LEU VAL
SEQRES 12 A 235 ALA GLU LYS VAL THR VAL ILE THR LYS HIS ASN ASP ASP
SEQRES 13 A 235 GLU GLN TYR ALA TRP GLU SER SER ALA GLY GLY SER PHE
SEQRES 14 A 235 THR VAL ARG THR ASP THR GLY GLU PRO MET GLY ARG GLY
SEQRES 15 A 235 THR LYS VAL ILE LEU HIS LEU LYS GLU ASP GLN THR GLU
SEQRES 16 A 235 TYR LEU GLU GLU ARG ARG ILE LYS GLU ILE VAL LYS LYS
SEQRES 17 A 235 HIS SER GLN PHE ILE GLY TYR PRO ILE THR LEU PHE VAL
SEQRES 18 A 235 GLU LYS GLU ARG ASP LYS GLU VAL SER ASP ASP GLU ALA
SEQRES 19 A 235 GLU
SEQRES 1 B 235 PRO GLU GLU THR GLN THR GLN ASP GLN PRO MET GLU GLU
SEQRES 2 B 235 GLU GLU VAL GLU THR PHE ALA PHE GLN ALA GLU ILE ALA
SEQRES 3 B 235 GLN LEU MET SER LEU ILE ILE ASN THR PHE TYR SER ASN
SEQRES 4 B 235 LYS GLU ILE PHE LEU ARG GLU LEU ILE SER ASN SER SER
SEQRES 5 B 235 ASP ALA LEU ASP LYS ILE ARG TYR GLU SER LEU THR ASP
SEQRES 6 B 235 PRO SER LYS LEU ASP SER GLY LYS GLU LEU HIS ILE ASN
SEQRES 7 B 235 LEU ILE PRO ASN LYS GLN ASP ARG THR LEU THR ILE VAL
SEQRES 8 B 235 ASP THR GLY ILE GLY MET THR LYS ALA ASP LEU ILE ASN
SEQRES 9 B 235 ASN LEU GLY THR ILE ALA LYS SER GLY THR LYS ALA PHE
SEQRES 10 B 235 MET GLU ALA LEU GLN ALA GLY ALA ASP ILE SER MET ILE
SEQRES 11 B 235 GLY GLN PHE GLY VAL GLY PHE TYR SER ALA TYR LEU VAL
SEQRES 12 B 235 ALA GLU LYS VAL THR VAL ILE THR LYS HIS ASN ASP ASP
SEQRES 13 B 235 GLU GLN TYR ALA TRP GLU SER SER ALA GLY GLY SER PHE
SEQRES 14 B 235 THR VAL ARG THR ASP THR GLY GLU PRO MET GLY ARG GLY
SEQRES 15 B 235 THR LYS VAL ILE LEU HIS LEU LYS GLU ASP GLN THR GLU
SEQRES 16 B 235 TYR LEU GLU GLU ARG ARG ILE LYS GLU ILE VAL LYS LYS
SEQRES 17 B 235 HIS SER GLN PHE ILE GLY TYR PRO ILE THR LEU PHE VAL
SEQRES 18 B 235 GLU LYS GLU ARG ASP LYS GLU VAL SER ASP ASP GLU ALA
SEQRES 19 B 235 GLU
HET CT5 A1224 26
HET CT5 B1224 26
HETNAM CT5 4-[4-(2,3-DIHYDRO-1,4-BENZODIOXIN-6-YL)-3-METHYL-1H-
HETNAM 2 CT5 PYRAZOL-5-YL]-6-ETHYLBENZENE-1,3-DIOL
FORMUL 3 CT5 2(C20 H20 N2 O4)
FORMUL 5 HOH *487(H2 O)
HELIX 1 1 GLN A 23 THR A 36 1 14
HELIX 2 2 ASN A 40 GLU A 42 5 3
HELIX 3 3 ILE A 43 LEU A 64 1 22
HELIX 4 4 ASP A 66 ASP A 71 5 6
HELIX 5 5 THR A 99 ASN A 105 1 7
HELIX 6 6 ASN A 106 THR A 109 5 4
HELIX 7 7 ILE A 110 ALA A 124 1 15
HELIX 8 8 ASP A 127 GLY A 135 5 9
HELIX 9 9 VAL A 136 LEU A 143 5 8
HELIX 10 10 GLU A 192 LEU A 198 5 7
HELIX 11 11 GLU A 199 SER A 211 1 13
HELIX 12 12 GLN B 23 THR B 36 1 14
HELIX 13 13 GLU B 42 ASP B 66 1 25
HELIX 14 14 PRO B 67 ASP B 71 5 5
HELIX 15 15 THR B 99 THR B 109 1 11
HELIX 16 16 GLY B 114 ALA B 124 1 11
HELIX 17 17 ASP B 127 GLY B 135 5 9
HELIX 18 18 VAL B 136 LEU B 143 5 8
HELIX 19 19 GLU B 192 LEU B 198 5 7
HELIX 20 20 GLU B 199 SER B 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
SHEET 1 BA 8 GLU B 18 ALA B 21 0
SHEET 2 BA 8 SER B 169 THR B 174 -1 O PHE B 170 N PHE B 20
SHEET 3 BA 8 TYR B 160 SER B 164 -1 O ALA B 161 N ARG B 173
SHEET 4 BA 8 ALA B 145 LYS B 153 -1 O VAL B 148 N SER B 164
SHEET 5 BA 8 GLY B 183 LEU B 190 -1 O GLY B 183 N LYS B 153
SHEET 6 BA 8 THR B 88 ASP B 93 -1 O LEU B 89 N LEU B 188
SHEET 7 BA 8 ILE B 78 ASN B 83 -1 O ASN B 79 N VAL B 92
SHEET 8 BA 8 ILE B 218 LEU B 220 1 O THR B 219 N LEU B 80
SITE 1 AC1 15 ASN A 51 SER A 52 ASP A 54 ALA A 55
SITE 2 AC1 15 LYS A 58 ASP A 93 ILE A 96 GLY A 97
SITE 3 AC1 15 LEU A 107 GLY A 108 PHE A 138 THR A 184
SITE 4 AC1 15 VAL A 186 HOH A2120 HOH A2240
SITE 1 AC2 16 ASN B 51 SER B 52 ALA B 55 ASP B 93
SITE 2 AC2 16 ILE B 96 GLY B 97 MET B 98 ASN B 106
SITE 3 AC2 16 LEU B 107 PHE B 138 THR B 184 VAL B 186
SITE 4 AC2 16 HOH B2073 HOH B2129 HOH B2132 HOH B2247
CRYST1 64.188 88.508 98.549 90.00 90.00 90.00 P 21 21 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 0.015579 0.000000 0.000000 0.00000
SCALE2 0.000000 0.011298 0.000000 0.00000
SCALE3 0.000000 0.000000 0.010147 0.00000
(ATOM LINES ARE NOT SHOWN.)
END