HEADER CHAPERONE 20-MAR-07 2UWD
TITLE INHIBITION OF THE HSP90 MOLECULAR CHAPERONE IN VITRO AND IN VIVO BY
TITLE 2 NOVEL, SYNTHETIC, POTENT RESORCINYLIC PYRAZOLE, ISOXAZOLE AMIDE
TITLE 3 ANALOGS
COMPND MOL_ID: 1;
COMPND 2 MOLECULE: HEAT SHOCK PROTEIN HSP 90-ALPHA;
COMPND 3 CHAIN: A;
COMPND 4 SYNONYM: HEAT SHOCK PROTEIN HSP90-ALPHA, HSP 86, RENAL CARCINOMA
COMPND 5 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 ORGAN: SKIN;
SOURCE 6 TISSUE: MELANOMA;
SOURCE 7 EXPRESSION_SYSTEM: ESCHERICHIA COLI;
SOURCE 8 EXPRESSION_SYSTEM_TAXID: 562
KEYWDS CHAPERONE, HEAT SHOCK, ATP-BINDING, PHOSPHORYLATION, NUCLEOTIDE-
KEYWDS 2 BINDING
EXPDTA X-RAY DIFFRACTION
AUTHOR S.Y.SHARP,C.PRODROMOU,K.BOXALL,M.V.POWERS,J.L.HOLMES,G.BOX,
AUTHOR 2 T.P.MATTHEWS,K.M.CHEUNG,A.KALUSA,K.JAMES,A.HAYES,A.HARDCASTLE,
AUTHOR 3 B.DYMOCK,P.A.BROUGH,X.BARRIL,J.E.CANSFIELD,L.M.WRIGHT,A.SURGENOR,
AUTHOR 4 N.FOLOPPE,W.AHERNE,L.PEARL,K.JONES,E.MCDONALD,F.RAYNAUD,S.ECCLES,
AUTHOR 5 M.DRYSDALE,P.WORKMAN
REVDAT 4 13-DEC-23 2UWD 1 LINK
REVDAT 3 28-FEB-18 2UWD 1 JRNL
REVDAT 2 24-FEB-09 2UWD 1 VERSN
REVDAT 1 24-APR-07 2UWD 0
JRNL AUTH S.Y.SHARP,C.PRODROMOU,K.BOXALL,M.V.POWERS,J.L.HOLMES,G.BOX,
JRNL AUTH 2 T.P.MATTHEWS,K.M.CHEUNG,A.KALUSA,K.JAMES,A.HAYES,
JRNL AUTH 3 A.HARDCASTLE,B.DYMOCK,P.A.BROUGH,X.BARRIL,J.E.CANSFIELD,
JRNL AUTH 4 L.WRIGHT,A.SURGENOR,N.FOLOPPE,R.E.HUBBARD,W.AHERNE,L.PEARL,
JRNL AUTH 5 K.JONES,E.MCDONALD,F.RAYNAUD,S.ECCLES,M.DRYSDALE,P.WORKMAN
JRNL TITL INHIBITION OF THE HEAT SHOCK PROTEIN 90 MOLECULAR CHAPERONE
JRNL TITL 2 IN VITRO AND IN VIVO BY NOVEL, SYNTHETIC, POTENT
JRNL TITL 3 RESORCINYLIC PYRAZOLE/ISOXAZOLE AMIDE ANALOGUES.
JRNL REF MOL. CANCER THER. V. 6 1198 2007
JRNL REFN ISSN 1535-7163
JRNL PMID 17431102
JRNL DOI 10.1158/1535-7163.MCT-07-0149
REMARK 2
REMARK 2 RESOLUTION. 1.90 ANGSTROMS.
REMARK 3
REMARK 3 REFINEMENT.
REMARK 3 PROGRAM : REFMAC 5.2.0019
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) : 65.94
REMARK 3 DATA CUTOFF (SIGMA(F)) : NULL
REMARK 3 COMPLETENESS FOR RANGE (%) : 88.5
REMARK 3 NUMBER OF REFLECTIONS : 19470
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) : 0.201
REMARK 3 FREE R VALUE : 0.259
REMARK 3 FREE R VALUE TEST SET SIZE (%) : 5.100
REMARK 3 FREE R VALUE TEST SET COUNT : 1048
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) : 813
REMARK 3 BIN COMPLETENESS (WORKING+TEST) (%) : NULL
REMARK 3 BIN R VALUE (WORKING SET) : 0.3910
REMARK 3 BIN FREE R VALUE SET COUNT : 39
REMARK 3 BIN FREE R VALUE : 0.4140
REMARK 3
REMARK 3 NUMBER OF NON-HYDROGEN ATOMS USED IN REFINEMENT.
REMARK 3 PROTEIN ATOMS : 1625
REMARK 3 NUCLEIC ACID ATOMS : 0
REMARK 3 HETEROGEN ATOMS : 34
REMARK 3 SOLVENT ATOMS : 308
REMARK 3
REMARK 3 B VALUES.
REMARK 3 FROM WILSON PLOT (A**2) : NULL
REMARK 3 MEAN B VALUE (OVERALL, A**2) : 28.09
REMARK 3 OVERALL ANISOTROPIC B VALUE.
REMARK 3 B11 (A**2) : -0.23000
REMARK 3 B22 (A**2) : 0.70000
REMARK 3 B33 (A**2) : -0.47000
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): 0.167
REMARK 3 ESU BASED ON FREE R VALUE (A): 0.166
REMARK 3 ESU BASED ON MAXIMUM LIKELIHOOD (A): 0.099
REMARK 3 ESU FOR B VALUES BASED ON MAXIMUM LIKELIHOOD (A**2): 3.269
REMARK 3
REMARK 3 CORRELATION COEFFICIENTS.
REMARK 3 CORRELATION COEFFICIENT FO-FC : 0.951
REMARK 3 CORRELATION COEFFICIENT FO-FC FREE : 0.921
REMARK 3
REMARK 3 RMS DEVIATIONS FROM IDEAL VALUES COUNT RMS WEIGHT
REMARK 3 BOND LENGTHS REFINED ATOMS (A): 1691 ; 0.016 ; 0.022
REMARK 3 BOND LENGTHS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 BOND ANGLES REFINED ATOMS (DEGREES): 2286 ; 1.462 ; 1.985
REMARK 3 BOND ANGLES OTHERS (DEGREES): NULL ; NULL ; NULL
REMARK 3 TORSION ANGLES, PERIOD 1 (DEGREES): 209 ; 6.301 ; 5.000
REMARK 3 TORSION ANGLES, PERIOD 2 (DEGREES): 73 ;37.120 ;25.068
REMARK 3 TORSION ANGLES, PERIOD 3 (DEGREES): 305 ;14.097 ;15.000
REMARK 3 TORSION ANGLES, PERIOD 4 (DEGREES): 7 ;18.504 ;15.000
REMARK 3 CHIRAL-CENTER RESTRAINTS (A**3): 259 ; 0.099 ; 0.200
REMARK 3 GENERAL PLANES REFINED ATOMS (A): 1254 ; 0.006 ; 0.020
REMARK 3 GENERAL PLANES OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED CONTACTS REFINED ATOMS (A): 829 ; 0.196 ; 0.200
REMARK 3 NON-BONDED CONTACTS OTHERS (A): NULL ; NULL ; NULL
REMARK 3 NON-BONDED TORSION REFINED ATOMS (A): 1152 ; 0.295 ; 0.200
REMARK 3 NON-BONDED TORSION OTHERS (A): NULL ; NULL ; NULL
REMARK 3 H-BOND (X...Y) REFINED ATOMS (A): 254 ; 0.155 ; 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): 44 ; 0.186 ; 0.200
REMARK 3 SYMMETRY VDW OTHERS (A): NULL ; NULL ; NULL
REMARK 3 SYMMETRY H-BOND REFINED ATOMS (A): 28 ; 0.239 ; 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): 1071 ; 0.958 ; 1.500
REMARK 3 MAIN-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 MAIN-CHAIN ANGLE REFINED ATOMS (A**2): 1667 ; 1.443 ; 2.000
REMARK 3 MAIN-CHAIN ANGLE OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN BOND REFINED ATOMS (A**2): 716 ; 2.319 ; 3.000
REMARK 3 SIDE-CHAIN BOND OTHER ATOMS (A**2): NULL ; NULL ; NULL
REMARK 3 SIDE-CHAIN ANGLE REFINED ATOMS (A**2): 618 ; 3.341 ; 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 : 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 2UWD COMPLIES WITH FORMAT V. 3.30, 13-JUL-11
REMARK 100
REMARK 100 THIS ENTRY HAS BEEN PROCESSED BY PDBE ON 20-MAR-07.
REMARK 100 THE DEPOSITION ID IS D_1290031976.
REMARK 200
REMARK 200 EXPERIMENTAL DETAILS
REMARK 200 EXPERIMENT TYPE : X-RAY DIFFRACTION
REMARK 200 DATE OF DATA COLLECTION : 11-SEP-03
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 : CU FILTER
REMARK 200 OPTICS : OSMIC BLUE MIRRORS
REMARK 200
REMARK 200 DETECTOR TYPE : IMAGE PLATE
REMARK 200 DETECTOR MANUFACTURER : RIGAKU IMAGE PLATE
REMARK 200 INTENSITY-INTEGRATION SOFTWARE : D*TREK
REMARK 200 DATA SCALING SOFTWARE : D*TREK
REMARK 200
REMARK 200 NUMBER OF UNIQUE REFLECTIONS : 23194
REMARK 200 RESOLUTION RANGE HIGH (A) : 1.900
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 (%) : 99.1
REMARK 200 DATA REDUNDANCY : 3.200
REMARK 200 R MERGE (I) : 0.06000
REMARK 200 R SYM (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR THE DATA SET : 8.0000
REMARK 200
REMARK 200 IN THE HIGHEST RESOLUTION SHELL.
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE HIGH (A) : 1.90
REMARK 200 HIGHEST RESOLUTION SHELL, RANGE LOW (A) : 2.12
REMARK 200 COMPLETENESS FOR SHELL (%) : 89.0
REMARK 200 DATA REDUNDANCY IN SHELL : 2.70
REMARK 200 R MERGE FOR SHELL (I) : 0.30000
REMARK 200 R SYM FOR SHELL (I) : NULL
REMARK 200 <I/SIGMA(I)> FOR SHELL : 3.300
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 (%): 58.00
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: 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 32.64850
REMARK 290 SMTRY2 5 0.000000 1.000000 0.000000 44.34150
REMARK 290 SMTRY3 5 0.000000 0.000000 1.000000 49.85050
REMARK 290 SMTRY1 6 -1.000000 0.000000 0.000000 32.64850
REMARK 290 SMTRY2 6 0.000000 -1.000000 0.000000 44.34150
REMARK 290 SMTRY3 6 0.000000 0.000000 1.000000 49.85050
REMARK 290 SMTRY1 7 -1.000000 0.000000 0.000000 32.64850
REMARK 290 SMTRY2 7 0.000000 1.000000 0.000000 44.34150
REMARK 290 SMTRY3 7 0.000000 0.000000 -1.000000 49.85050
REMARK 290 SMTRY1 8 1.000000 0.000000 0.000000 32.64850
REMARK 290 SMTRY2 8 0.000000 -1.000000 0.000000 44.34150
REMARK 290 SMTRY3 8 0.000000 0.000000 -1.000000 49.85050
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: 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 65.29700
REMARK 350 BIOMT2 2 0.000000 -1.000000 0.000000 0.00000
REMARK 350 BIOMT3 2 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 1
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 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 GLU A 16 CG CD OE1 OE2
REMARK 470 GLN A 123 CG CD OE1 NE2
REMARK 470 GLU A 192 CD OE1 OE2
REMARK 470 LYS A 224 CA C O CB CG CD CE
REMARK 470 LYS A 224 NZ
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 O3 SO4 A 1227 O HOH A 2300 2.06
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 ALA A 124 42.10 -102.73
REMARK 500 ALA A 166 -140.17 64.16
REMARK 500 GLU A 178 108.65 -23.87
REMARK 500 ARG A 182 134.42 -171.98
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 A2081 DISTANCE = 8.90 ANGSTROMS
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 MG A1226 MG
REMARK 620 N RES CSSEQI ATOM
REMARK 620 1 SER A 113 OG
REMARK 620 2 HOH A2100 O 102.6
REMARK 620 3 HOH A2175 O 137.0 105.6
REMARK 620 N 1 2
REMARK 800
REMARK 800 SITE
REMARK 800 SITE_IDENTIFIER: AC1
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE MG A1225
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC2
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE MG A1226
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC3
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE SO4 A1227
REMARK 800
REMARK 800 SITE_IDENTIFIER: AC4
REMARK 800 EVIDENCE_CODE: SOFTWARE
REMARK 800 SITE_DESCRIPTION: BINDING SITE FOR RESIDUE 2GG A1228
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 900 RELATED ID: 2BT0 RELATED DB: PDB
REMARK 900 NOVEL, POTENT SMALL MOLECULE INHIBITORS OF THE MOLECULAR CHAPERONE
REMARK 900 HSP90 DISCOVERED THROUGH STRUCTURE-BASED DESIGN
REMARK 900 RELATED ID: 2BUG RELATED DB: PDB
REMARK 900 SOLUTION STRUCTURE OF THE TPR DOMAIN FROM PROTEIN PHOSPHATASE 5 IN
REMARK 900 COMPLEX WITH HSP90 DERIVED PEPTIDE
REMARK 900 RELATED ID: 2BYH RELATED DB: PDB
REMARK 900 3-(5-CHLORO-2,4-DIHYDROXYPHENYL)-PYRAZOLE- 4-CARBOXAMIDES AS
REMARK 900 INHIBITORS OF THE HSP90 MOLECULAR CHAPERONE
REMARK 900 RELATED ID: 2BYI RELATED DB: PDB
REMARK 900 3-(5-CHLORO-2,4-DIHYDROXYPHENYL)-PYRAZOLE- 4-CARBOXAMIDES AS
REMARK 900 INHIBITORS OF THE HSP90 MOLECULAR CHAPERONE
REMARK 900 RELATED ID: 2BZ5 RELATED DB: PDB
REMARK 900 STRUCTURE-BASED DISCOVERY OF A NEW CLASS OF HSP90 INHIBITORS
REMARK 900 RELATED ID: 2C2L RELATED DB: PDB
REMARK 900 CRYSTAL STRUCTURE OF THE CHIP U-BOX E3 UBIQUITIN LIGASE
REMARK 900 RELATED ID: 2CCS RELATED DB: PDB
REMARK 900 HUMAN HSP90 WITH 4-CHLORO-6-(4-PIPERAZIN- 1-YL-1H-PYRAZOL-3-YL)-
REMARK 900 BENZENE-1,2-DIOL
REMARK 900 RELATED ID: 2CCT RELATED DB: PDB
REMARK 900 HUMAN HSP90 WITH 5-(5-CHLORO-2,4- DIHYDROXY-PHENYL)-4-PIPERAZIN-1-
REMARK 900 YL-2H- PYRAZOLE-3-CARBOXYLIC ACID ETHYLAMIDE
REMARK 900 RELATED ID: 2CCU RELATED DB: PDB
REMARK 900 HUMAN HSP90 WITH 4-CHLORO-6-(4-(4-(4- METHANESULPHONYL-BENZYL)-
REMARK 900 PIERAZIN-1-YL)-1H- PYRAZOL-3-YL)-BENZENE-1,3-DIOL
REMARK 900 RELATED ID: 2CDD RELATED DB: PDB
REMARK 900 HUMAN HSP90 WITH 4-(4-(2,3-DIHYDRO- BENZOL(1,4)DIOXIN-6-YL)-5-
REMARK 900 METHYL-1H- PYRAZOL-3-YL)-6-ETHYL-BENZENE-1,3-DIOL
REMARK 900 RELATED ID: 2FWY RELATED DB: PDB
REMARK 900 STRUCTURE OF HUMAN HSP90-ALPHA BOUND TO THE POTENT WATERSOLUBLE
REMARK 900 INHIBITOR PU-H64
REMARK 900 RELATED ID: 2FWZ RELATED DB: PDB
REMARK 900 STRUCTURE OF HUMAN HSP90-ALPHA BOUND TO THE POTENT WATERSOLUBLE
REMARK 900 INHIBITOR PU-H71
DBREF 2UWD A 1 1 PDB 2UWD 2UWD 1 1
DBREF 2UWD A 2 236 UNP P07900 HS90A_HUMAN 1 235
SEQRES 1 A 236 MET PRO GLU GLU THR GLN THR GLN ASP GLN PRO MET GLU
SEQRES 2 A 236 GLU GLU GLU VAL GLU THR PHE ALA PHE GLN ALA GLU ILE
SEQRES 3 A 236 ALA GLN LEU MET SER LEU ILE ILE ASN THR PHE TYR SER
SEQRES 4 A 236 ASN LYS GLU ILE PHE LEU ARG GLU LEU ILE SER ASN SER
SEQRES 5 A 236 SER ASP ALA LEU ASP LYS ILE ARG TYR GLU SER LEU THR
SEQRES 6 A 236 ASP PRO SER LYS LEU ASP SER GLY LYS GLU LEU HIS ILE
SEQRES 7 A 236 ASN LEU ILE PRO ASN LYS GLN ASP ARG THR LEU THR ILE
SEQRES 8 A 236 VAL ASP THR GLY ILE GLY MET THR LYS ALA ASP LEU ILE
SEQRES 9 A 236 ASN ASN LEU GLY THR ILE ALA LYS SER GLY THR LYS ALA
SEQRES 10 A 236 PHE MET GLU ALA LEU GLN ALA GLY ALA ASP ILE SER MET
SEQRES 11 A 236 ILE GLY GLN PHE GLY VAL GLY PHE TYR SER ALA TYR LEU
SEQRES 12 A 236 VAL ALA GLU LYS VAL THR VAL ILE THR LYS HIS ASN ASP
SEQRES 13 A 236 ASP GLU GLN TYR ALA TRP GLU SER SER ALA GLY GLY SER
SEQRES 14 A 236 PHE THR VAL ARG THR ASP THR GLY GLU PRO MET GLY ARG
SEQRES 15 A 236 GLY THR LYS VAL ILE LEU HIS LEU LYS GLU ASP GLN THR
SEQRES 16 A 236 GLU TYR LEU GLU GLU ARG ARG ILE LYS GLU ILE VAL LYS
SEQRES 17 A 236 LYS HIS SER GLN PHE ILE GLY TYR PRO ILE THR LEU PHE
SEQRES 18 A 236 VAL GLU LYS GLU ARG ASP LYS GLU VAL SER ASP ASP GLU
SEQRES 19 A 236 ALA GLU
HET MG A1225 1
HET MG A1226 1
HET SO4 A1227 5
HET 2GG A1228 27
HETNAM MG MAGNESIUM ION
HETNAM SO4 SULFATE ION
HETNAM 2GG 5-(5-CHLORO-2,4-DIHYDROXYPHENYL)-N-ETHYL-4-(4-
HETNAM 2 2GG METHOXYPHENYL)ISOXAZOLE-3-CARBOXAMIDE
FORMUL 2 MG 2(MG 2+)
FORMUL 4 SO4 O4 S 2-
FORMUL 5 2GG C19 H17 CL N2 O5
FORMUL 6 HOH *308(H2 O)
HELIX 1 1 GLN A 23 THR A 36 1 14
HELIX 2 2 GLU A 42 LEU A 64 1 23
HELIX 3 3 ASP A 66 ASP A 71 5 6
HELIX 4 4 THR A 99 ASN A 105 1 7
HELIX 5 5 ASN A 106 THR A 109 5 4
HELIX 6 6 ILE A 110 ALA A 124 1 15
HELIX 7 7 ASP A 127 GLY A 135 5 9
HELIX 8 8 VAL A 136 LEU A 143 5 8
HELIX 9 9 GLU A 192 LEU A 198 5 7
HELIX 10 10 GLU A 199 SER A 211 1 13
SHEET 1 AA 8 VAL A 17 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
LINK OG SER A 113 MG MG A1226 1555 1555 2.97
LINK MG MG A1226 O HOH A2100 1555 2655 3.03
LINK MG MG A1226 O HOH A2175 1555 1555 3.01
SITE 1 AC1 3 ASP A 86 ARG A 87 HIS A 189
SITE 1 AC2 5 ARG A 60 ILE A 110 SER A 113 HOH A2100
SITE 2 AC2 5 HOH A2175
SITE 1 AC3 3 ASP A 54 HOH A2300 HOH A2304
SITE 1 AC4 19 LEU A 48 ASN A 51 SER A 52 ALA A 55
SITE 2 AC4 19 LYS A 58 ASP A 93 ILE A 96 GLY A 97
SITE 3 AC4 19 MET A 98 ASP A 102 LEU A 107 GLY A 108
SITE 4 AC4 19 PHE A 138 THR A 184 VAL A 186 HOH A2157
SITE 5 AC4 19 HOH A2173 HOH A2305 HOH A2308
CRYST1 65.297 88.683 99.701 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 0.015315 0.000000 0.000000 0.00000
SCALE2 0.000000 0.011276 0.000000 0.00000
SCALE3 0.000000 0.000000 0.010030 0.00000
(ATOM LINES ARE NOT SHOWN.)
END
