[English] 日本語
Yorodumi
- PDB-5h22: Hsp90 alpha N-terminal domain in complex with an inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5h22
TitleHsp90 alpha N-terminal domain in complex with an inhibitor
ComponentsHsp90aa1 protein
KeywordsCHAPERONE/INHIBITOR / HSP90 / inhibitor / CHAPERONE-INHIBITOR complex
Function / homology
Function and homology information


Drug-mediated inhibition of ERBB2 signaling / ESR-mediated signaling / DDX58/IFIH1-mediated induction of interferon-alpha/beta / HSF1-dependent transactivation / Signaling by ERBB2 / HSF1 activation / RHOBTB2 GTPase cycle / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / eNOS activation / Sema3A PAK dependent Axon repulsion ...Drug-mediated inhibition of ERBB2 signaling / ESR-mediated signaling / DDX58/IFIH1-mediated induction of interferon-alpha/beta / HSF1-dependent transactivation / Signaling by ERBB2 / HSF1 activation / RHOBTB2 GTPase cycle / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / eNOS activation / Sema3A PAK dependent Axon repulsion / Attenuation phase / positive regulation of cytotoxic T cell differentiation / VEGFR2 mediated vascular permeability / Downregulation of ERBB2 signaling / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / Regulation of necroptotic cell death / Extra-nuclear estrogen signaling / The role of GTSE1 in G2/M progression after G2 checkpoint / Regulation of actin dynamics for phagocytic cup formation / Loss of Nlp from mitotic centrosomes / Recruitment of mitotic centrosome proteins and complexes / Loss of proteins required for interphase microtubule organization from the centrosome / Anchoring of the basal body to the plasma membrane / Estrogen-dependent gene expression / Recruitment of NuMA to mitotic centrosomes / AURKA Activation by TPX2 / Regulation of PLK1 Activity at G2/M Transition / VEGFA-VEGFR2 Pathway / sperm plasma membrane / sperm mitochondrial sheath / sulfonylurea receptor binding / CTP binding / positive regulation of protein polymerization / UTP binding / dATP binding / telomerase holoenzyme complex assembly / Rho GDP-dissociation inhibitor binding / positive regulation of cell size / dendritic growth cone / protein import into mitochondrial matrix / TPR domain binding / non-chaperonin molecular chaperone ATPase / regulation of protein ubiquitination / response to salt stress / protein folding chaperone complex / response to unfolded protein / cardiac muscle cell apoptotic process / enzyme-substrate adaptor activity / chaperone-mediated protein complex assembly / axonal growth cone / neurofibrillary tangle assembly / positive regulation of lamellipodium assembly / regulation of postsynaptic membrane neurotransmitter receptor levels / sperm flagellum / response to cold / nitric oxide biosynthetic process / positive regulation of defense response to virus by host / skeletal muscle contraction / DNA polymerase binding / Neutrophil degranulation / positive regulation of cardiac muscle contraction / activation of innate immune response / protein folding chaperone / positive regulation of interferon-beta production / protein tyrosine kinase binding / nitric-oxide synthase regulator activity / ATP-dependent protein folding chaperone / brush border membrane / response to cocaine / cellular response to virus / positive regulation of protein import into nucleus / myelin sheath / neuron migration / protein refolding / response to estrogen / tau protein binding / histone deacetylase binding / positive regulation of nitric oxide biosynthetic process / disordered domain specific binding / positive regulation of protein catabolic process / : / melanosome / regulation of protein localization / cellular response to heat / response to heat / protein folding / GTPase binding / scaffold protein binding / protein phosphatase binding / extracellular matrix / basolateral plasma membrane / regulation of apoptotic process / transmembrane transporter binding / protein stabilization / apical plasma membrane / response to xenobiotic stimulus / response to antibiotic / ubiquitin protein ligase binding / mRNA binding / neuronal cell body
Similarity search - Function
Heat shock protein Hsp90, conserved site / Heat shock hsp90 proteins family signature. / Histidine kinase-like ATPase, C-terminal domain / Heat Shock Protein 90 / HSP90, C-terminal domain / Heat shock protein Hsp90, N-terminal / Heat shock protein Hsp90 family / Hsp90 protein / Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase / Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase ...Heat shock protein Hsp90, conserved site / Heat shock hsp90 proteins family signature. / Histidine kinase-like ATPase, C-terminal domain / Heat Shock Protein 90 / HSP90, C-terminal domain / Heat shock protein Hsp90, N-terminal / Heat shock protein Hsp90 family / Hsp90 protein / Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase / Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase / Histidine kinase-like ATPases / Histidine kinase/HSP90-like ATPase / Histidine kinase/HSP90-like ATPase superfamily / Ribosomal protein S5 domain 2-type fold / 2-Layer Sandwich / Alpha Beta
Similarity search - Domain/homology
Chem-7FT / Hsp90aa1 protein / Heat shock protein HSP 90-alpha
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.499 Å
AuthorsKim, E.E. / Shin, S.C. / Keum, G.C.
Funding support Korea, Republic Of, 1items
OrganizationGrant numberCountry
NRF 20110021713 Korea, Republic Of
CitationJournal: Bioorg. Med. Chem. Lett. / Year: 2017
Title: Synthesis and in vitro antiproliferative activity of C5-benzyl substituted 2-amino-pyrrolo[2,3-d]pyrimidines as potent Hsp90 inhibitors.
Authors: Lee, J.H. / Shin, S.C. / Seo, S.H. / Seo, Y.H. / Jeong, N. / Kim, C.W. / Kim, E.E. / Keum, G.
History
DepositionOct 13, 2016Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Oct 11, 2017Provider: repository / Type: Initial release
Revision 1.1Apr 24, 2019Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Nov 8, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Hsp90aa1 protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)24,5172
Polymers24,1091
Non-polymers4081
Water4,756264
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area0 Å2
ΔGint0 kcal/mol
Surface area10480 Å2
MethodPISA
Unit cell
Length a, b, c (Å)66.787, 90.581, 98.943
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number23
Space group name H-MI222

-
Components

#1: Protein Hsp90aa1 protein / Heat shock protein HSP 90-alpha


Mass: 24109.275 Da / Num. of mol.: 1 / Fragment: UNP residues 10-224
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Hsp90aa1
Production host: Escherichia coli-Pichia pastoris shuttle vector pPpARG4 (others)
References: UniProt: A0PJ91, UniProt: P07901*PLUS
#2: Chemical ChemComp-7FT / 4-chloranyl-7-[(4-methoxy-3,5-dimethyl-pyridin-2-yl)methyl]-5-(phenylmethyl)pyrrolo[2,3-d]pyrimidin-2-amine


Mass: 407.896 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Formula: C22H22ClN5O
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 264 / 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: 3.2 Å3/Da / Density % sol: 61.59 %
Crystal growTemperature: 295 K / Method: vapor diffusion, sitting drop / pH: 8.5 / Details: 1.0M ammonium Sulfate, 0.1M Tris-HCl (pH8.5)

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: PAL/PLS / Beamline: 5C (4A) / Wavelength: 0.97951 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: Sep 27, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97951 Å / Relative weight: 1
ReflectionResolution: 1.499→50 Å / Num. obs: 48302 / % possible obs: 99.2 % / Redundancy: 7.6 % / Rmerge(I) obs: 0.076 / Net I/σ(I): 27.5
Reflection shellResolution: 1.5→1.55 Å / Rmerge(I) obs: 0.34

-
Processing

Software
NameVersionClassification
PHENIX(1.10.1_2155: ???)refinement
PDB_EXTRACT3.2data extraction
HKL-2000data processing
HKL-2000data scaling
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1UY6

1uy6


Resolution: 1.499→29.87 Å / SU ML: 0.14 / Cross valid method: FREE R-VALUE / σ(F): 1.5 / Phase error: 19.32
RfactorNum. reflection% reflection
Rfree0.2077 2000 4.17 %
Rwork0.1941 --
obs0.1947 47908 99.01 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 1.499→29.87 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1672 0 0 264 1936
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0051701
X-RAY DIFFRACTIONf_angle_d0.8282296
X-RAY DIFFRACTIONf_dihedral_angle_d21.377625
X-RAY DIFFRACTIONf_chiral_restr0.078259
X-RAY DIFFRACTIONf_plane_restr0.004290
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.4992-1.53670.28331350.2643100X-RAY DIFFRACTION96
1.5367-1.57820.23771410.2333239X-RAY DIFFRACTION99
1.5782-1.62470.26481430.22143266X-RAY DIFFRACTION99
1.6247-1.67710.22271410.20593247X-RAY DIFFRACTION99
1.6771-1.7370.19951420.19633254X-RAY DIFFRACTION99
1.737-1.80660.20341420.19493267X-RAY DIFFRACTION99
1.8066-1.88880.21661420.18993258X-RAY DIFFRACTION99
1.8888-1.98830.21661430.18123280X-RAY DIFFRACTION100
1.9883-2.11290.20311440.18793307X-RAY DIFFRACTION100
2.1129-2.2760.18631440.18773322X-RAY DIFFRACTION100
2.276-2.50490.21561440.1953304X-RAY DIFFRACTION100
2.5049-2.86710.22491450.21463321X-RAY DIFFRACTION100
2.8671-3.61130.21091470.1893370X-RAY DIFFRACTION100
3.6113-29.87620.18471470.18143373X-RAY DIFFRACTION97

+
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