[English] 日本語
Yorodumi
- PDB-6chw: Estrogen Receptor Alpha Y537S covalently bound to antagonist H3B-5942. -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6chw
TitleEstrogen Receptor Alpha Y537S covalently bound to antagonist H3B-5942.
ComponentsEstrogen receptor
Keywordsnuclear protein/antagonist / Nuclear hormone receptor / covalent antagonist / activating mutation / breast cancer / NUCLEAR PROTEIN / nuclear protein-antagonist complex
Function / homology
Function and homology information


regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / regulation of branching involved in prostate gland morphogenesis / prostate epithelial cord elongation / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway / nuclear estrogen receptor activity ...regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / regulation of branching involved in prostate gland morphogenesis / prostate epithelial cord elongation / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway / nuclear estrogen receptor activity / epithelial cell proliferation involved in mammary gland duct elongation / epithelial cell development / vagina development / mammary gland branching involved in pregnancy / negative regulation of smooth muscle cell apoptotic process / uterus development / TFIIB-class transcription factor binding / androgen metabolic process / steroid hormone receptor signaling pathway / mammary gland alveolus development / cellular response to estrogen stimulus / estrogen response element binding / nuclear receptor-mediated steroid hormone signaling pathway / negative regulation of canonical NF-kappaB signal transduction / Nuclear signaling by ERBB4 / RNA polymerase II preinitiation complex assembly / 14-3-3 protein binding / protein localization to chromatin / estrogen receptor signaling pathway / steroid binding / nitric-oxide synthase regulator activity / TBP-class protein binding / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / ESR-mediated signaling / transcription corepressor binding / negative regulation of miRNA transcription / positive regulation of nitric-oxide synthase activity / cellular response to estradiol stimulus / transcription coregulator binding / stem cell differentiation / nuclear estrogen receptor binding / positive regulation of DNA-binding transcription factor activity / SUMOylation of intracellular receptors / euchromatin / negative regulation of DNA-binding transcription factor activity / transcription coactivator binding / beta-catenin binding / Nuclear Receptor transcription pathway / response to estrogen / Constitutive Signaling by Aberrant PI3K in Cancer / male gonad development / nuclear receptor activity / Regulation of RUNX2 expression and activity / positive regulation of fibroblast proliferation / sequence-specific double-stranded DNA binding / positive regulation of nitric oxide biosynthetic process / Ovarian tumor domain proteases / PIP3 activates AKT signaling / response to estradiol / phospholipase C-activating G protein-coupled receptor signaling pathway / ATPase binding / regulation of inflammatory response / positive regulation of cytosolic calcium ion concentration / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / fibroblast proliferation / DNA-binding transcription activator activity, RNA polymerase II-specific / Estrogen-dependent gene expression / transcription regulator complex / Extra-nuclear estrogen signaling / calmodulin binding / DNA-binding transcription factor activity, RNA polymerase II-specific / chromatin remodeling / DNA-binding transcription factor activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of gene expression / chromatin binding / regulation of DNA-templated transcription / chromatin / regulation of transcription by RNA polymerase II / protein kinase binding / positive regulation of DNA-templated transcription / Golgi apparatus / negative regulation of transcription by RNA polymerase II / enzyme binding / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / zinc ion binding / nucleoplasm / identical protein binding / membrane / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Estrogen receptor / Oestrogen-type nuclear receptor final C-terminal domain / : / Oestrogen receptor / Oestrogen-type nuclear receptor final C-terminal / Estrogen receptor/oestrogen-related receptor / : / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormone receptor ...Estrogen receptor / Oestrogen-type nuclear receptor final C-terminal domain / : / Oestrogen receptor / Oestrogen-type nuclear receptor final C-terminal / Estrogen receptor/oestrogen-related receptor / : / Retinoid X Receptor / Retinoid X Receptor / Nuclear hormone receptor / Nuclear hormones receptors DNA-binding region signature. / Zinc finger, nuclear hormone receptor-type / Zinc finger, C4 type (two domains) / Nuclear hormone receptors DNA-binding domain profile. / c4 zinc finger in nuclear hormone receptors / Nuclear hormone receptor, ligand-binding domain / Nuclear hormone receptor-like domain superfamily / Ligand-binding domain of nuclear hormone receptor / Nuclear receptor (NR) ligand-binding (LBD) domain profile. / Ligand binding domain of hormone receptors / Zinc finger, NHR/GATA-type / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-F3D / Estrogen receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 1.89 Å
AuthorsLarsen, N.A.
CitationJournal: Cancer Discov / Year: 2018
Title: Discovery of Selective Estrogen Receptor Covalent Antagonists for the Treatment of ER alphaWTand ER alphaMUTBreast Cancer.
Authors: Puyang, X. / Furman, C. / Zheng, G.Z. / Wu, Z.J. / Banka, D. / Aithal, K. / Agoulnik, S. / Bolduc, D.M. / Buonamici, S. / Caleb, B. / Das, S. / Eckley, S. / Fekkes, P. / Hao, M.H. / Hart, A. ...Authors: Puyang, X. / Furman, C. / Zheng, G.Z. / Wu, Z.J. / Banka, D. / Aithal, K. / Agoulnik, S. / Bolduc, D.M. / Buonamici, S. / Caleb, B. / Das, S. / Eckley, S. / Fekkes, P. / Hao, M.H. / Hart, A. / Houtman, R. / Irwin, S. / Joshi, J.J. / Karr, C. / Kim, A. / Kumar, N. / Kumar, P. / Kuznetsov, G. / Lai, W.G. / Larsen, N. / Mackenzie, C. / Martin, L.A. / Melchers, D. / Moriarty, A. / Nguyen, T.V. / Norris, J. / O'Shea, M. / Pancholi, S. / Prajapati, S. / Rajagopalan, S. / Reynolds, D.J. / Rimkunas, V. / Rioux, N. / Ribas, R. / Siu, A. / Sivakumar, S. / Subramanian, V. / Thomas, M. / Vaillancourt, F.H. / Wang, J. / Wardell, S. / Wick, M.J. / Yao, S. / Yu, L. / Warmuth, M. / Smith, P.G. / Zhu, P. / Korpal, M.
History
DepositionFeb 23, 2018Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 21, 2018Provider: repository / Type: Initial release
Revision 1.1Jul 25, 2018Group: Data collection / Database references / Derived calculations
Category: citation / citation_author / pdbx_struct_special_symmetry
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Aug 29, 2018Group: Data collection / Database references / Category: citation / citation_author / Item: _citation.title / _citation_author.name
Revision 1.3Sep 12, 2018Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.4Feb 26, 2020Group: Derived calculations / Category: pdbx_struct_oper_list
Item: _pdbx_struct_oper_list.matrix[1][1] / _pdbx_struct_oper_list.matrix[1][2] ..._pdbx_struct_oper_list.matrix[1][1] / _pdbx_struct_oper_list.matrix[1][2] / _pdbx_struct_oper_list.matrix[2][1] / _pdbx_struct_oper_list.matrix[2][2] / _pdbx_struct_oper_list.name / _pdbx_struct_oper_list.symmetry_operation / _pdbx_struct_oper_list.vector[1] / _pdbx_struct_oper_list.vector[2] / _pdbx_struct_oper_list.vector[3]
Revision 1.5Oct 23, 2024Group: Data collection / Database references / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Estrogen receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)28,7976
Polymers28,0361
Non-polymers7615
Water2,702150
1
A: Estrogen receptor
hetero molecules

A: Estrogen receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)57,59412
Polymers56,0722
Non-polymers1,52210
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation10_665-y+1,-x+1,-z+1/61
Unit cell
Length a, b, c (Å)58.735, 58.735, 274.814
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number179
Space group name H-MP6522
Components on special symmetry positions
IDModelComponents
11A-760-

HOH

21A-809-

HOH

-
Components

#1: Protein Estrogen receptor / ER / ER-alpha / Estradiol receptor / Nuclear receptor subfamily 3 group A member 1


Mass: 28035.957 Da / Num. of mol.: 1 / Mutation: C381S, C417S, Y537S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ESR1, ESR, NR3A1 / Production host: Escherichia coli (E. coli) / References: UniProt: P03372
#2: Chemical ChemComp-F3D / 4-[(2-{4-[(1E)-1-(1H-indazol-5-yl)-2-phenylbut-1-en-1-yl]phenoxy}ethyl)amino]-N,N-dimethylbutanamide


Mass: 496.643 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C31H36N4O2
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C2H6O2
#4: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 150 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.44 Å3/Da / Density % sol: 49.6 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 6-12% PEG 3350, 50-150 mM MgCL2, 0.1 M imidazole pH 7.1

-
Data collection

DiffractionMean temperature: 120 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 21-ID-F / Wavelength: 0.9787 Å
DetectorType: RAYONIX MX225-HS / Detector: CCD / Date: Oct 25, 2014
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9787 Å / Relative weight: 1
ReflectionResolution: 1.75→50 Å / Num. obs: 29591 / % possible obs: 100 % / Redundancy: 15.4 % / Rmerge(I) obs: 0.085 / Rpim(I) all: 0.023 / Rrim(I) all: 0.088 / Χ2: 1.038 / Net I/σ(I): 8.6 / Num. measured all: 456399
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. unique obsCC1/2Rpim(I) allRrim(I) allΧ2% possible all
1.75-1.8115.90.88828550.9040.2290.9171.024100
1.81-1.8915.90.59228880.9610.1530.6121.07100
1.89-1.9715.90.40128650.9790.1030.4141.062100
1.97-2.0715.90.26828860.9890.0690.2771.033100
2.07-2.215.90.17629100.9950.0450.1821.014100
2.2-2.3815.80.12829040.9970.0330.1321.027100
2.38-2.6115.70.10429470.9960.0270.1081.027100
2.61-2.9915.30.129860.9960.0270.1041.051100
2.99-3.7714.60.08230370.9970.0220.0851.061100
3.77-5013.60.06133130.9970.0170.0631.01399.7

-
Processing

Software
NameVersionClassification
REFMAC5.8.0158refinement
SCALEPACKdata scaling
PDB_EXTRACT3.24data extraction
HKL-3000data reduction
MOLREPphasing
RefinementResolution: 1.89→44.47 Å / Cor.coef. Fo:Fc: 0.956 / Cor.coef. Fo:Fc free: 0.918 / SU B: 3.362 / SU ML: 0.101 / Cross valid method: THROUGHOUT / ESU R: 0.152 / ESU R Free: 0.154 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.25694 1216 5.1 %RANDOM
Rwork0.19954 ---
obs0.20239 22475 99.97 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso mean: 37.582 Å2
Baniso -1Baniso -2Baniso -3
1--0 Å2-0 Å2-0 Å2
2---0 Å20 Å2
3---0 Å2
Refinement stepCycle: 1 / Resolution: 1.89→44.47 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1956 0 53 150 2159
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0190.0192061
X-RAY DIFFRACTIONr_bond_other_d0.0050.021997
X-RAY DIFFRACTIONr_angle_refined_deg2.0432.0022781
X-RAY DIFFRACTIONr_angle_other_deg1.2633.0054624
X-RAY DIFFRACTIONr_dihedral_angle_1_deg7.0265251
X-RAY DIFFRACTIONr_dihedral_angle_2_deg38.78724.09683
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.13215383
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.4221511
X-RAY DIFFRACTIONr_chiral_restr0.1450.2322
X-RAY DIFFRACTIONr_gen_planes_refined0.0110.022212
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02394
X-RAY DIFFRACTIONr_nbd_refined
X-RAY DIFFRACTIONr_nbd_other
X-RAY DIFFRACTIONr_nbtor_refined
X-RAY DIFFRACTIONr_nbtor_other
X-RAY DIFFRACTIONr_xyhbond_nbd_refined
X-RAY DIFFRACTIONr_xyhbond_nbd_other
X-RAY DIFFRACTIONr_metal_ion_refined
X-RAY DIFFRACTIONr_metal_ion_other
X-RAY DIFFRACTIONr_symmetry_vdw_refined
X-RAY DIFFRACTIONr_symmetry_vdw_other
X-RAY DIFFRACTIONr_symmetry_hbond_refined
X-RAY DIFFRACTIONr_symmetry_hbond_other
X-RAY DIFFRACTIONr_symmetry_metal_ion_refined
X-RAY DIFFRACTIONr_symmetry_metal_ion_other
X-RAY DIFFRACTIONr_mcbond_it3.5863.542992
X-RAY DIFFRACTIONr_mcbond_other3.5823.538991
X-RAY DIFFRACTIONr_mcangle_it5.0195.2871241
X-RAY DIFFRACTIONr_mcangle_other5.0185.2921242
X-RAY DIFFRACTIONr_scbond_it4.8384.0081068
X-RAY DIFFRACTIONr_scbond_other4.8374.0091069
X-RAY DIFFRACTIONr_scangle_it
X-RAY DIFFRACTIONr_scangle_other6.7295.8031539
X-RAY DIFFRACTIONr_long_range_B_refined9.52243.9132437
X-RAY DIFFRACTIONr_long_range_B_other9.52143.9242438
X-RAY DIFFRACTIONr_rigid_bond_restr
X-RAY DIFFRACTIONr_sphericity_free
X-RAY DIFFRACTIONr_sphericity_bonded
LS refinement shellResolution: 1.89→1.939 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.381 79 -
Rwork0.24 1601 -
obs--100 %

+
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