[English] 日本語
Yorodumi
- PDB-3wha: Hsp90 alpha N-terminal domain in complex with a tricyclic inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3wha
TitleHsp90 alpha N-terminal domain in complex with a tricyclic inhibitor
ComponentsHeat shock protein HSP 90-alphaHeat shock response
KeywordsChaperone/chaperone Inhibitor / Chaperone / Chaperone-chaperone Inhibitor complex
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-WHA / Heat shock protein HSP 90-alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.3 Å
AuthorsFukami, T.A. / Ono, N.
CitationJournal: Bioorg.Med.Chem. / Year: 2014
Title: Design and synthesis of 2-amino-6-(1H,3H-benzo[de]isochromen-6-yl)-1,3,5-triazines as novel Hsp90 inhibitors
Authors: Suda, A. / Kawasaki, K. / Komiyama, S. / Isshiki, Y. / Yoon, D.-O. / Kim, S.-J. / Na, Y.-J. / Hasegawa, K. / Fukami, T.A. / Sato, S. / Miura, T. / Ono, N. / Yamazaki, T. / Saitoh, R. / ...Authors: Suda, A. / Kawasaki, K. / Komiyama, S. / Isshiki, Y. / Yoon, D.-O. / Kim, S.-J. / Na, Y.-J. / Hasegawa, K. / Fukami, T.A. / Sato, S. / Miura, T. / Ono, N. / Yamazaki, T. / Saitoh, R. / Shimma, N. / Shiratori, Y. / Tsukuda, T.
History
DepositionAug 23, 2013Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jan 29, 2014Provider: repository / Type: Initial release
Revision 1.1Nov 8, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / 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 / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_symmetry / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_symmetry / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_symmetry / _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
hetero molecules


Theoretical massNumber of molelcules
Total (without water)52,5246
Polymers51,5762
Non-polymers9484
Water11,458636
1
A: Heat shock protein HSP 90-alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)26,2963
Polymers25,7881
Non-polymers5082
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)26,2283
Polymers25,7881
Non-polymers4402
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
A: Heat shock protein HSP 90-alpha
hetero molecules

A: Heat shock protein HSP 90-alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)52,5926
Polymers51,5762
Non-polymers1,0164
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_454-x-1,y,-z-11
Buried area1510 Å2
ΔGint-9 kcal/mol
Surface area19700 Å2
MethodPISA
4
B: Heat shock protein HSP 90-alpha
hetero molecules

B: Heat shock protein HSP 90-alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)52,4566
Polymers51,5762
Non-polymers8804
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation2_554-x,y,-z-11
Buried area1710 Å2
ΔGint-11 kcal/mol
Surface area19400 Å2
MethodPISA
Unit cell
Length a, b, c (Å)107.170, 98.920, 64.240
Angle α, β, γ (deg.)90.000, 124.550, 90.000
Int Tables number5
Space group name H-MC121
Components on special symmetry positions
IDModelComponents
11B-302-

MG

-
Components

#1: Protein Heat shock protein HSP 90-alpha / Heat shock response / Heat shock 86 kDa / HSP 86 / HSP86 / Renal carcinoma antigen NY-REN-38


Mass: 25787.965 Da / Num. of mol.: 2 / Fragment: UNP residues 9-236
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HSP90AA1 / Plasmid: pT7-7 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)CP / References: UniProt: P07900
#2: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#3: Chemical ChemComp-WHA / 4-{[4-amino-6-(5-chloro-1H,3H-benzo[de]isochromen-6-yl)-1,3,5-triazin-2-yl]sulfanyl}butanamide


Mass: 415.897 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C19H18ClN5O2S
#4: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mg
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 636 / 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: 2.7 Å3/Da / Density % sol: 54.5 %
Crystal growTemperature: 278 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 22%(w/v) PEG 3350, 0.2M MgCl2, 0.1M Na-MES, pH 6.5, vapor diffusion, sitting drop, temperature 278K

-
Data collection

DiffractionMean temperature: 100 K / Ambient temp details: NATIVE
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Jul 22, 2010 / Details: mirrors
RadiationMonochromator: double crystal / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 1.3→44.134 Å / Num. all: 133172 / Num. obs: 133172 / % possible obs: 98.7 % / Redundancy: 3.3 % / Rmerge(I) obs: 0.044 / Rsym value: 0.044 / Net I/σ(I): 14.5
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) allNum. measured allNum. unique all% possible all
1.3-1.333.290.332.2432305981198.64
1.33-1.373.310.292.6232027967799.43
1.37-1.413.250.233.2530455937299.36
1.41-1.453.070.193.9827954911499.49
1.45-1.53.390.164.7629992885499.36
1.5-1.553.370.136.0228851855399.13
1.55-1.613.360.17.3827480817698.97
1.61-1.683.320.098.4626218788698.67
1.68-1.753.140.089.4423603752498.31
1.75-1.843.150.0611.1522723720498.04
1.84-1.943.350.0512.8122746679797.55
1.94-2.063.310.0514.1621356644697.47
2.06-2.23.260.0415.9219770606997.74
2.2-2.373.150.0415.4617752563697.72
2.37-2.62.950.0415.9315490524298.25
2.6-2.913.470.0316.6716405473298.52
2.91-3.363.50.0316.5214797423099.28
3.36-4.113.40.0317.212132357299.1
4.11-5.813.250.0318.998974275798.37
5.81-44.133.660.0314.85561152097.14

-
Phasing

PhasingMethod: molecular replacement
Phasing MRRfactor: 39.45
Highest resolutionLowest resolution
Rotation2.5 Å28.4 Å
Translation2.5 Å28.4 Å

-
Processing

Software
NameVersionClassificationNB
SCALA3.3.16data scaling
PHASER2.1.4phasing
BUSTER-TNTrefinement
PDB_EXTRACT3.11data extraction
XDSdata reduction
BUSTER2.11.2refinement
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3B28

3b28


Resolution: 1.3→44.13 Å / Cor.coef. Fo:Fc: 0.9513 / Cor.coef. Fo:Fc free: 0.9465 / Occupancy max: 1 / Occupancy min: 0.5 / SU R Cruickshank DPI: 0.045 / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.2003 6705 5.03 %RANDOM
Rwork0.1842 ---
obs0.185 133171 98.64 %-
Displacement parametersBiso max: 71.7 Å2 / Biso mean: 16.8126 Å2 / Biso min: 6.79 Å2
Baniso -1Baniso -2Baniso -3
1--0.8715 Å20 Å2-1.0619 Å2
2--1.602 Å20 Å2
3----0.7305 Å2
Refine analyzeLuzzati coordinate error obs: 0.145 Å
Refinement stepCycle: LAST / Resolution: 1.3→44.13 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3280 0 63 636 3979
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1255SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes91HARMONIC2
X-RAY DIFFRACTIONt_gen_planes494HARMONIC5
X-RAY DIFFRACTIONt_it3463HARMONIC20
X-RAY DIFFRACTIONt_nbd0SEMIHARMONIC5
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion464SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact4596SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d3463HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg4675HARMONIC21.09
X-RAY DIFFRACTIONt_omega_torsion4.08
X-RAY DIFFRACTIONt_other_torsion13.96
LS refinement shellResolution: 1.3→1.33 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.238 502 5.12 %
Rwork0.2141 9298 -
all0.2153 9800 -
obs--98.64 %

+
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