[English] 日本語
Yorodumi
- PDB-3k99: HSP90 N-terminal domain in complex with 4-(1,3-dihydro-2H-isoindo... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3k99
TitleHSP90 N-terminal domain in complex with 4-(1,3-dihydro-2H-isoindol-2-ylcarbonyl)benzene-1,3-diol
ComponentsHeat shock protein HSP 90-alphaHeat shock response
KeywordsCHAPERONE / HSP90 / N-terminal domain / ATP binding domain / inhibition / Acetylation / Alternative splicing / ATP-binding / Cytoplasm / Nucleotide-binding / Phosphoprotein / Stress response
Function / homology
Function and homology information


sperm mitochondrial sheath / dATP binding / Scavenging by Class F Receptors / sulfonylurea receptor binding / CTP binding / positive regulation of protein polymerization / vRNP Assembly / UTP binding / sperm plasma membrane / positive regulation of tau-protein kinase activity ...sperm mitochondrial sheath / dATP binding / Scavenging by Class F Receptors / sulfonylurea receptor binding / CTP binding / positive regulation of protein polymerization / vRNP Assembly / UTP binding / sperm plasma membrane / positive regulation of tau-protein kinase activity / protein insertion into mitochondrial outer membrane / telomerase holoenzyme complex assembly / chaperone-mediated autophagy / Rho GDP-dissociation inhibitor binding / Uptake and function of diphtheria toxin / 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 / PIWI-interacting RNA (piRNA) biogenesis / TPR domain binding / non-chaperonin molecular chaperone ATPase / regulation of postsynaptic membrane neurotransmitter receptor levels / dendritic growth cone / Sema3A PAK dependent Axon repulsion / regulation of protein ubiquitination / positive regulation of cell size / skeletal muscle contraction / protein unfolding / regulation of protein-containing complex assembly / HSF1-dependent transactivation / telomere maintenance via telomerase / response to unfolded protein / HSF1 activation / chaperone-mediated protein complex assembly / Attenuation phase / RHOBTB2 GTPase cycle / DNA polymerase binding / positive regulation of lamellipodium assembly / axonal growth cone / eNOS activation / endocytic vesicle lumen / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / positive regulation of cardiac muscle contraction / positive regulation of defense response to virus by host / Signaling by ERBB2 / Recruitment of mitotic centrosome proteins and complexes / cardiac muscle cell apoptotic process / response to salt stress / positive regulation of telomerase activity / Recruitment of NuMA to mitotic centrosomes / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / protein tyrosine kinase binding / Anchoring of the basal body to the plasma membrane / positive regulation of interferon-beta production / activation of innate immune response / response to cold / nitric-oxide synthase regulator activity / lysosomal lumen / Constitutive Signaling by Overexpressed ERBB2 / ESR-mediated signaling / AURKA Activation by TPX2 / response to cocaine / VEGFR2 mediated vascular permeability / brush border membrane / ATP-dependent protein folding chaperone / Signaling by ERBB2 TMD/JMD mutants / neuron migration / tau protein binding / DDX58/IFIH1-mediated induction of interferon-alpha/beta / Constitutive Signaling by EGFRvIII / Signaling by ERBB2 ECD mutants / Signaling by ERBB2 KD Mutants / Regulation of necroptotic cell death / Regulation of actin dynamics for phagocytic cup formation / Downregulation of ERBB2 signaling / cellular response to virus / VEGFA-VEGFR2 Pathway / Aggrephagy / Chaperone Mediated Autophagy / positive regulation of protein import into nucleus / response to estrogen / histone deacetylase binding / positive regulation of protein catabolic process / The role of GTSE1 in G2/M progression after G2 checkpoint / positive regulation of nitric oxide biosynthetic process / regulation of protein localization / disordered domain specific binding / Regulation of PLK1 Activity at G2/M Transition / melanosome / unfolded protein binding
Similarity search - Function
Heat shock protein Hsp90, conserved site / Heat shock hsp90 proteins family signature. / 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-like ATPase, C-terminal domain / Heat Shock Protein 90 / Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase ...Heat shock protein Hsp90, conserved site / Heat shock hsp90 proteins family signature. / 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-like ATPase, C-terminal domain / Heat Shock Protein 90 / 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-PFT / Heat shock protein HSP 90-alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
AuthorsGajiwala, K.S. / Davies II, J.F.
CitationJournal: J.Med.Chem. / Year: 2010
Title: Dihydroxyphenylisoindoline amides as orally bioavailable inhibitors of the heat shock protein 90 (hsp90) molecular chaperone.
Authors: Kung, P.P. / Huang, B. / Zhang, G. / Zhou, J.Z. / Wang, J. / Digits, J.A. / Skaptason, J. / Yamazaki, S. / Neul, D. / Zientek, M. / Elleraas, J. / Mehta, P. / Yin, M.J. / Hickey, M.J. / ...Authors: Kung, P.P. / Huang, B. / Zhang, G. / Zhou, J.Z. / Wang, J. / Digits, J.A. / Skaptason, J. / Yamazaki, S. / Neul, D. / Zientek, M. / Elleraas, J. / Mehta, P. / Yin, M.J. / Hickey, M.J. / Gajiwala, K.S. / Rodgers, C. / Davies, J.F. / Gehring, M.R.
History
DepositionOct 15, 2009Deposition site: RCSB / Processing site: RCSB
Revision 1.0Feb 9, 2010Provider: 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

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)106,6688
Polymers105,6474
Non-polymers1,0214
Water7,008389
1
A: Heat shock protein HSP 90-alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)26,6672
Polymers26,4121
Non-polymers2551
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Heat shock protein HSP 90-alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)26,6672
Polymers26,4121
Non-polymers2551
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
C: Heat shock protein HSP 90-alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)26,6672
Polymers26,4121
Non-polymers2551
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
4
D: Heat shock protein HSP 90-alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)26,6672
Polymers26,4121
Non-polymers2551
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
5
A: Heat shock protein HSP 90-alpha
hetero molecules

C: Heat shock protein HSP 90-alpha
hetero molecules

B: Heat shock protein HSP 90-alpha
D: Heat shock protein HSP 90-alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)106,6688
Polymers105,6474
Non-polymers1,0214
Water724
TypeNameSymmetry operationNumber
crystal symmetry operation3_745-x+2,y-1/2,-z+1/21
crystal symmetry operation3_645-x+1,y-1/2,-z+1/21
identity operation1_555x,y,z1
Buried area5840 Å2
ΔGint-31 kcal/mol
Surface area38870 Å2
MethodPISA
Unit cell
Length a, b, c (Å)46.773, 82.958, 219.325
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

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


Mass: 26411.730 Da / Num. of mol.: 4 / Fragment: N-terminal domain (UNP residues 9-225)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HSP90AA1, HSP90A, HSPC1, HSPCA / Production host: Escherichia coli (E. coli) / References: UniProt: P07900
#2: Chemical
ChemComp-PFT / 4-(1,3-dihydro-2H-isoindol-2-ylcarbonyl)benzene-1,3-diol


Mass: 255.269 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C15H13NO3
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 389 / 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: 2.01 Å3/Da / Density % sol: 38.92 %
Crystal growTemperature: 295 K / Method: vapor diffusion, hanging drop / pH: 4.2
Details: 16% ethylene glycol, 0.1 M phosphate-citrate, pH 4.2, 30 mM TCEP, VAPOR DIFFUSION, HANGING DROP, temperature 295K

-
Data collection

DiffractionMean temperature: 98 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU RU200 / Wavelength: 1.5418 Å
DetectorType: MAR scanner 345 mm plate / Detector: IMAGE PLATE / Date: Jul 17, 2005 / Details: Mirrors
RadiationMonochromator: Mirrors / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.5418 Å / Relative weight: 1
ReflectionResolution: 2.1→20 Å / Num. all: 52918 / Num. obs: 50822 / % possible obs: 99.8 % / Observed criterion σ(F): 1 / Observed criterion σ(I): 1 / Redundancy: 4.4 % / Biso Wilson estimate: 18.1 Å2 / Rmerge(I) obs: 0.079 / Rsym value: 0.079 / Net I/σ(I): 17.4
Reflection shellResolution: 2.1→2.17 Å / Redundancy: 4.2 % / Rmerge(I) obs: 0.424 / Mean I/σ(I) obs: 2.9 / Num. unique all: 5008 / Rsym value: 0.424 / % possible all: 99.6

-
Processing

Software
NameClassification
MAR345dtbdata collection
CNXrefinement
HKL-2000data reduction
SCALEPACKdata scaling
CNXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.1→19.95 Å / Rfactor Rfree error: 0.005 / Data cutoff high absF: 318081.09 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 0 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.245 2449 5 %RANDOM
Rwork0.204 ---
obs0.206 48679 95.5 %-
all-50748 --
Solvent computationSolvent model: FLAT MODEL / Bsol: 45.0616 Å2 / ksol: 0.367746 e/Å3
Displacement parametersBiso mean: 29.3 Å2
Baniso -1Baniso -2Baniso -3
1-5.53 Å20 Å20 Å2
2---3.5 Å20 Å2
3----2.02 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.3 Å0.24 Å
Luzzati d res low-5 Å
Luzzati sigma a0.21 Å0.16 Å
Refinement stepCycle: LAST / Resolution: 2.1→19.95 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6838 0 76 389 7303
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_bond_d0.005
X-RAY DIFFRACTIONc_angle_deg0.8
X-RAY DIFFRACTIONc_dihedral_angle_d21
X-RAY DIFFRACTIONc_improper_angle_d0.58
X-RAY DIFFRACTIONc_mcbond_it1.321.5
X-RAY DIFFRACTIONc_mcangle_it2.012
X-RAY DIFFRACTIONc_scbond_it2.152
X-RAY DIFFRACTIONc_scangle_it3.142.5
LS refinement shellResolution: 2.1→2.23 Å / Rfactor Rfree error: 0.015 / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.283 354 4.7 %
Rwork0.233 7238 -
obs--90.4 %
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1protein_rep.pprotein.top
X-RAY DIFFRACTION2dna-rna_rep.pdna-rna.top
X-RAY DIFFRACTION3water_rep.parwater.top
X-RAY DIFFRACTION4ion.paramion.top
X-RAY DIFFRACTION5pfi.parampfi.top

+
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