[English] 日本語
Yorodumi
- PDB-3bm9: Discovery of Benzisoxazoles as Potent Inhibitors of Chaperone Hsp90 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3bm9
TitleDiscovery of Benzisoxazoles as Potent Inhibitors of Chaperone Hsp90
ComponentsHeat shock protein HSP 90-alpha
KeywordsCHAPERONE / ATP binding domain / Alternative splicing / ATP-binding / Cytoplasm / Nucleotide-binding / Phosphoprotein / Stress response
Function / homology
Function and homology information


sperm mitochondrial sheath / sulfonylurea receptor binding / dATP binding / CTP binding / positive regulation of protein polymerization / Scavenging by Class F Receptors / vRNP Assembly / UTP binding / chaperone-mediated autophagy / sperm plasma membrane ...sperm mitochondrial sheath / sulfonylurea receptor binding / dATP binding / CTP binding / positive regulation of protein polymerization / Scavenging by Class F Receptors / vRNP Assembly / UTP binding / chaperone-mediated autophagy / sperm plasma membrane / Respiratory syncytial virus genome replication / Rho GDP-dissociation inhibitor binding / telomerase holoenzyme complex assembly / mitochondrial transport / Drug-mediated inhibition of ERBB2 signaling / Resistance of ERBB2 KD mutants to trastuzumab / Resistance of ERBB2 KD mutants to sapitinib / Resistance of ERBB2 KD mutants to tesevatinib / Resistance of ERBB2 KD mutants to neratinib / Resistance of ERBB2 KD mutants to osimertinib / Resistance of ERBB2 KD mutants to afatinib / Resistance of ERBB2 KD mutants to AEE788 / Resistance of ERBB2 KD mutants to lapatinib / Drug resistance in ERBB2 TMD/JMD mutants / Uptake and function of diphtheria toxin / protein import into mitochondrial matrix / TPR domain binding / dendritic growth cone / PIWI-interacting RNA (piRNA) biogenesis / Assembly and release of respiratory syncytial virus (RSV) virions / non-chaperonin molecular chaperone ATPase / protein unfolding / Sema3A PAK dependent Axon repulsion / regulation of protein ubiquitination / positive regulation of cell size / HSF1-dependent transactivation / protein folding chaperone complex / enzyme-substrate adaptor activity / response to unfolded protein / regulation of protein-containing complex assembly / HSF1 activation / Attenuation phase / neurofibrillary tangle assembly / chaperone-mediated protein complex assembly / RHOBTB2 GTPase cycle / regulation of postsynaptic membrane neurotransmitter receptor levels / axonal growth cone / telomere maintenance via telomerase / skeletal muscle contraction / positive regulation of lamellipodium assembly / nitric oxide metabolic process / response to salt stress / positive regulation of defense response to virus by host / DNA polymerase binding / eNOS activation / positive regulation of telomere maintenance via telomerase / Signaling by ERBB2 / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / cardiac muscle cell apoptotic process / endocytic vesicle lumen / positive regulation of cardiac muscle contraction / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / Recruitment of NuMA to mitotic centrosomes / Anchoring of the basal body to the plasma membrane / activation of innate immune response / lysosomal lumen / ESR-mediated signaling / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / positive regulation of interferon-beta production / Constitutive Signaling by Overexpressed ERBB2 / protein tyrosine kinase binding / response to cold / AURKA Activation by TPX2 / nitric-oxide synthase regulator activity / VEGFR2 mediated vascular permeability / response to cocaine / ATP-dependent protein folding chaperone / brush border membrane / Signaling by ERBB2 TMD/JMD mutants / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / positive regulation of protein import into nucleus / DDX58/IFIH1-mediated induction of interferon-alpha/beta / cellular response to virus / Regulation of actin dynamics for phagocytic cup formation / response to estrogen / Regulation of necroptotic cell death / VEGFA-VEGFR2 Pathway / extracellular matrix / tau protein binding / Downregulation of ERBB2 signaling / neuron migration / histone deacetylase binding / Chaperone Mediated Autophagy / disordered domain specific binding / positive regulation of nitric oxide biosynthetic process / Aggrephagy
Similarity search - Function
Heat shock protein Hsp90, conserved site / Heat shock hsp90 proteins family signature. / Histidine kinase-like ATPase, C-terminal domain / HSP90, C-terminal domain / Heat shock protein Hsp90, N-terminal / Heat Shock Protein 90 / Heat shock protein Hsp90 family / Hsp90 protein / Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase / Histidine kinase/HSP90-like ATPase ...Heat shock protein Hsp90, conserved site / Heat shock hsp90 proteins family signature. / Histidine kinase-like ATPase, C-terminal domain / HSP90, C-terminal domain / Heat shock protein Hsp90, N-terminal / Heat Shock Protein 90 / Heat shock protein Hsp90 family / Hsp90 protein / Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase / Histidine kinase/HSP90-like ATPase / Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase / Histidine kinase-like ATPases / Histidine kinase/HSP90-like ATPase superfamily / Ribosomal protein S5 domain 2-type fold / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-BXZ / Heat shock protein HSP 90-alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 1.6 Å
AuthorsGopalsamy, A. / Shi, M. / Vogan, E.M. / Golas, J. / Jacob, J. / Johnson, J. / Lee, F. / Nilakantan, R. / Peterson, R. / Svenson, K. ...Gopalsamy, A. / Shi, M. / Vogan, E.M. / Golas, J. / Jacob, J. / Johnson, J. / Lee, F. / Nilakantan, R. / Peterson, R. / Svenson, K. / Tam, M.S. / Wen, Y. / Chopra, R. / Ellingboe, J. / Arndt, K. / Boschelli, F.
CitationJournal: J.Med.Chem. / Year: 2008
Title: Discovery of benzisoxazoles as potent inhibitors of chaperone heat shock protein 90.
Authors: Gopalsamy, A. / Shi, M. / Golas, J. / Vogan, E. / Jacob, J. / Johnson, M. / Lee, F. / Nilakantan, R. / Petersen, R. / Svenson, K. / Chopra, R. / Tam, M.S. / Wen, Y. / Ellingboe, J. / Arndt, K. / Boschelli, F.
History
DepositionDec 12, 2007Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 8, 2008Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Feb 21, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Remark 40MOLPROBITY STRUCTURE VALIDATION PROGRAMS: MOLPROBITY (KING, REDUCE, AND PROBE) AUTHORS : I.W. ...MOLPROBITY STRUCTURE VALIDATION PROGRAMS: MOLPROBITY (KING, REDUCE, AND PROBE) AUTHORS : I.W.DAVIS,V.B.CHEN, : R.M.IMMORMINO,J.J.HEADD,W.B.ARENDALL,J.M.WORD AUTHORS : I.W.DAVIS,A.LEAVER-FAY,V.B.CHEN,J.N.BLOCK, : G.J.KAPRAL,X.WANG,L.W.MURRAY,W.B.ARENDALL, : J.SNOEYINK,J.S.RICHARDSON,D.C.RICHARDSON REFERENCE : MOLPROBITY: ALL-ATOM CONTACTS AND STRUCTURE : VALIDATION FOR PROTEINS AND NUCLEIC ACIDS : NUCLEIC ACIDS RESEARCH. 2007;35:W375-83.

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Heat shock protein HSP 90-alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)25,7352
Polymers25,4131
Non-polymers3221
Water6,395355
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)66.089, 89.033, 100.172
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number23
Space group name H-MI222
Components on special symmetry positions
IDModelComponents
11A-367-

HOH

-
Components

#1: Protein Heat shock protein HSP 90-alpha / HSP 86 / Renal carcinoma antigen NY-REN-38


Mass: 25412.568 Da / Num. of mol.: 1 / Fragment: N-terminal domain, UNP RESIDUES 10-236
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HSP90AA1, HSP90A, HSPC1, HSPCA / Plasmid: pET28A / Production host: Escherichia coli (E. coli) / Strain (production host): BL21DE3 / References: UniProt: P07900
#2: Chemical ChemComp-BXZ / 4-bromo-6-(6-hydroxy-1,2-benzisoxazol-3-yl)benzene-1,3-diol


Mass: 322.111 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C13H8BrNO4
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 355 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.9 Å3/Da / Density % sol: 57.58 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7.5
Details: 20% PEG3350, 0.2M MAGNESIUM ACETATE, PH 7.5, TEMPERATURE 277K; FROZEN BY 1-STEP TRANSFER TO 25% GLYCEROL, 15% PEG3350, 0.15M MAGNESIUM ACETATE, VAPOR DIFFUSION, HANGING DROP

-
Data collection

DiffractionMean temperature: 93 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU FR-E+ SUPERBRIGHT / Wavelength: 1.5418 Å
DetectorType: RIGAKU SATURN 92 / Detector: CCD / Date: Dec 12, 2007 / Details: mirrors
RadiationMonochromator: Osmic mirrors / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 1.6→34.65 Å / Num. all: 39219 / Num. obs: 36317 / % possible obs: 92.6 % / Observed criterion σ(F): 0 / Observed criterion σ(I): 1 / Redundancy: 9.2 % / Biso Wilson estimate: 14.785 Å2 / Rsym value: 0.055 / Net I/σ(I): 26.4
Reflection shellResolution: 1.6→1.64 Å / Redundancy: 1.6 % / Mean I/σ(I) obs: 3.3 / Num. unique all: 2592 / Rsym value: 0.208 / % possible all: 59.8

-
Processing

Software
NameVersionClassification
PHENIX(phenix.refine)refinement
StructureStudiodata collection
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 1.6→34.65 Å / SU ML: 0.15 / Isotropic thermal model: isotropic / Cross valid method: THROUGHOUT / σ(F): -3 / Phase error: 18 / Stereochemistry target values: Engh & Huber
Details: LIGAND BXZ OCCUPANCY WAS REFINED AS A SINGLE GROUP TO 0.85. FOLLOWING THIS REFINEMENT, THE OCCUPANCY OF THE BROMINE ATOM WAS ADJUSTED TO 0.70 BASED ON RESIDUAL MAPS. RESIDUES 155 to 157 SHOW ...Details: LIGAND BXZ OCCUPANCY WAS REFINED AS A SINGLE GROUP TO 0.85. FOLLOWING THIS REFINEMENT, THE OCCUPANCY OF THE BROMINE ATOM WAS ADJUSTED TO 0.70 BASED ON RESIDUAL MAPS. RESIDUES 155 to 157 SHOW TWO (MAINCHAIN) CONFORMATIONS, BUT ONLY THE MAJOR CONFORMATION WAS MODELED
RfactorNum. reflection% reflectionSelection details
Rfree0.1861 1744 5.03 %Random
Rwork0.1635 ---
all0.1646 39211 --
obs0.1646 36282 92.4 %-
Displacement parametersBiso mean: 20.11 Å2
Baniso -1Baniso -2Baniso -3
1--2.2099 Å20 Å20 Å2
2--1.2539 Å20 Å2
3---0.9561 Å2
Refinement stepCycle: LAST / Resolution: 1.6→34.65 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1662 0 19 355 2036
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONf_bond_d0.004
X-RAY DIFFRACTIONf_angle_d0.924
X-RAY DIFFRACTIONf_dihedral_angle_d15.044
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 12

Resolution (Å)Rfactor RfreeNum. reflection Rfree% reflection Rfree (%)Rfactor RworkNum. reflection Rwork% reflection obs (%)Num. reflection obs
1.6-1.64830.194794.5560.1782165554
1.6483-1.70150.2396960.1806722232
1.7015-1.76240.211300.1759802462
1.7624-1.83290.22761240.1717842572
1.8329-1.91630.17291390.16872700
1.9163-2.01740.19361690.1658942895
2.0174-2.14370.16971580.1572983013
2.1437-2.30920.18311560.1522983019
2.3092-2.54150.17271770.1661983011
2.5415-2.90910.19491680.1678983051
2.9091-3.66460.17641720.1564993112
3.6646-34.650.18011760.1538993236

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more