[English] 日本語
Yorodumi
- PDB-6c42: Estrogen Receptor Alpha Ligand Binding Domain in Complex with OP1156 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6c42
TitleEstrogen Receptor Alpha Ligand Binding Domain in Complex with OP1156
ComponentsEstrogen receptor
Keywordstrascription/transcription inhibitor / Estrogen Receptor Alpha / Antiestrogen / Selective Estrogen Receptor Degrader / Endocrine Therapy / Steroid Receptor / Nuclear Hormone Receptor / Breast Cancer / Acquired Antiestrogen Resistance / TRANSCRIPTION / trascription-transcription inhibitor complex
Function / homology
Function and homology information


regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / regulation of branching involved in prostate gland morphogenesis / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / nuclear estrogen receptor activity / epithelial cell proliferation involved in mammary gland duct elongation ...regulation of epithelial cell apoptotic process / antral ovarian follicle growth / G protein-coupled estrogen receptor activity / regulation of branching involved in prostate gland morphogenesis / RUNX1 regulates transcription of genes involved in WNT signaling / RUNX1 regulates estrogen receptor mediated transcription / regulation of toll-like receptor signaling pathway / prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis / nuclear estrogen receptor activity / epithelial cell proliferation involved in mammary gland duct elongation / epithelial cell development / prostate epithelial cord elongation / negative regulation of smooth muscle cell apoptotic process / mammary gland branching involved in pregnancy / uterus development / vagina development / TFIIB-class transcription factor binding / androgen metabolic process / steroid hormone receptor signaling pathway / mammary gland alveolus development / estrogen receptor signaling pathway / 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 / protein localization to chromatin / 14-3-3 protein binding / TBP-class protein binding / nitric-oxide synthase regulator activity / steroid 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 / SUMOylation of intracellular receptors / euchromatin / negative regulation of DNA-binding transcription factor activity / beta-catenin binding / transcription coactivator binding / positive regulation of DNA-binding transcription factor activity / Nuclear Receptor transcription pathway / response to estrogen / Regulation of RUNX2 expression and activity / Constitutive Signaling by Aberrant PI3K in Cancer / nuclear receptor activity / male gonad development / positive regulation of nitric oxide biosynthetic process / sequence-specific double-stranded DNA binding / positive regulation of fibroblast proliferation / Ovarian tumor domain proteases / PIP3 activates AKT signaling / response to estradiol / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / ATPase binding / regulation of inflammatory response / fibroblast proliferation / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / 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 / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / 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 / enzyme binding / negative regulation of transcription by RNA polymerase II / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / zinc ion binding / nucleoplasm / identical protein binding / membrane / nucleus / plasma membrane / cytoplasm / cytosol
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 / Nuclear hormones receptors DNA-binding region signature. ...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-85M / Estrogen receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.997 Å
AuthorsFanning, S.W. / Hodges-Gallager, L. / Myles, D.C. / Sun, R. / Fowler, C.E. / Green, B.D. / Harmon, C.L. / Greene, G.L. / Kushner, P.J.
Funding support United States, 2items
OrganizationGrant numberCountry
Susan G. Komen FoundationPDF14301382 United States
Ludwig Fund for Metastasis Research United States
CitationJournal: Nat Commun / Year: 2018
Title: Specific stereochemistry of OP-1074 disrupts estrogen receptor alpha helix 12 and confers pure antiestrogenic activity.
Authors: Fanning, S.W. / Hodges-Gallagher, L. / Myles, D.C. / Sun, R. / Fowler, C.E. / Plant, I.N. / Green, B.D. / Harmon, C.L. / Greene, G.L. / Kushner, P.J.
History
DepositionJan 11, 2018Deposition site: RCSB / Processing site: RCSB
SupersessionFeb 14, 2018ID: 5UF9
Revision 1.0Feb 14, 2018Provider: repository / Type: Initial release
Revision 1.1Feb 27, 2019Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _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 1.2Oct 4, 2023Group: Advisory / Data collection ...Advisory / 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 / pdbx_unobs_or_zero_occ_atoms / struct_ref_seq_dif
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ref_seq_dif.details

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Estrogen receptor
B: Estrogen receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)57,6024
Polymers56,7102
Non-polymers8912
Water7,746430
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: homology
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2710 Å2
ΔGint-8 kcal/mol
Surface area19630 Å2
MethodPISA
Unit cell
Length a, b, c (Å)102.805, 58.016, 87.854
Angle α, β, γ (deg.)90.00, 103.01, 90.00
Int Tables number5
Space group name H-MC121

-
Components

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


Mass: 28355.207 Da / Num. of mol.: 2 / Mutation: C381S, C417S, C530S, L536S
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-85M / (2R,3S,4R)-3-(4-hydroxyphenyl)-4-methyl-2-{4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}-3,4-dihydro-2H-1-benzopyran-7-ol


Mass: 445.550 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C28H31NO4 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 430 / 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: 2.25 Å3/Da / Density % sol: 45.35 %
Crystal growTemperature: 298.15 K / Method: vapor diffusion, hanging drop / Details: 15% PEG 3,350, HEPES pH 6.5, 200 mM MgCl2

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 19-BM / Wavelength: 0.97 Å
DetectorType: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Jun 15, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97 Å / Relative weight: 1
ReflectionResolution: 1.997→20 Å / Num. obs: 34199 / % possible obs: 99.6 % / Redundancy: 3.7 % / Net I/σ(I): 1.82
Reflection shellResolution: 2→2.03 Å

-
Processing

Software
NameVersionClassification
PHENIX1.9_1692refinement
HKL-3000data reduction
HKL-3000data scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4XI3

4xi3


Resolution: 1.997→19.761 Å / SU ML: 0.25 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 26.86
RfactorNum. reflection% reflection
Rfree0.2684 1685 5.04 %
Rwork0.2283 --
obs0.2304 33450 97.32 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 1.997→19.761 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3519 0 66 430 4015
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0023669
X-RAY DIFFRACTIONf_angle_d0.5554974
X-RAY DIFFRACTIONf_dihedral_angle_d12.9581304
X-RAY DIFFRACTIONf_chiral_restr0.024591
X-RAY DIFFRACTIONf_plane_restr0.001616
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.9975-2.05620.28861380.28872651X-RAY DIFFRACTION99
2.0562-2.12250.30131510.27282695X-RAY DIFFRACTION100
2.1225-2.19830.3351480.28822608X-RAY DIFFRACTION96
2.1983-2.28610.5905920.49142176X-RAY DIFFRACTION79
2.2861-2.390.39491370.28752551X-RAY DIFFRACTION95
2.39-2.51580.27711550.23332686X-RAY DIFFRACTION100
2.5158-2.67310.29361490.22762719X-RAY DIFFRACTION100
2.6731-2.87890.27461360.22652700X-RAY DIFFRACTION100
2.8789-3.16750.25461340.21612737X-RAY DIFFRACTION100
3.1675-3.62340.23631360.2132745X-RAY DIFFRACTION100
3.6234-4.55590.2311580.17952708X-RAY DIFFRACTION99
4.5559-19.76190.20161510.18362789X-RAY DIFFRACTION100
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
13.7044.2154-1.55484.8008-1.95267.4289-0.49850.44011.137-0.02450.38480.2119-1.08310.0342-0.00830.4739-0.0209-0.02980.2550.04890.35578.1015-5.434218.9308
23.1210.1948-0.9236.087-0.96281.70720.03030.1416-0.060.20680.0720.73770.185-0.3584-0.10260.23990.029-0.00120.314-0.05630.2794-12.2008-24.143130.7489
34.79152.3831-3.61471.4856-2.14463.476-0.02060.59350.1540.040.21070.1124-0.1855-0.4541-0.15590.19550.0497-0.01680.2534-0.01480.2011-2.4369-21.847117.4998
42.1614-0.1788-1.73751.2129-0.11743.9101-0.22940.182-0.19470.10370.0328-0.050.2626-0.03370.19540.14080.0264-0.02330.1506-0.01140.19063.9122-24.599618.8719
54.1211-1.15191.21181.9342-0.13526.04160.0271-0.3791-0.28890.00020.09180.38570.2131-0.176-0.07950.18970.00550.00510.26260.03950.1659-2.8651-28.156237.1783
66.92645.0102-0.25076.93120.6812.4009-0.0095-0.6504-0.32130.017-0.1746-0.15330.0880.02230.15840.2460.0865-0.02370.27650.03460.1797.4141-27.262435.3249
71.05860.44040.63653.024-0.16627.51780.05560.32840.032-0.34140.0838-0.201-0.09970.14910.04880.18420.0295-0.0220.24520.030.261310.9741-18.814519.6901
83.09370.76981.07244.52762.84437.509-0.00030.23630.1558-0.30190.3142-0.3917-0.2780.2919-0.26140.18940.03760.00160.21380.05730.220117.4164-13.087915.2648
92.79190.1102-0.87421.9981-0.65611.3186-0.08480.4214-0.286-0.05750.11020.03590.1952-0.17590.04140.2440.06880.04520.2945-0.03090.22017.2464-26.882120.6394
106.1053-0.21742.88183.70930.27093.666-0.0708-0.19530.55151.0179-0.1413-1.5257-0.40750.4214-0.03930.4179-0.0638-0.02370.3442-0.01310.602339.8407-23.539632.1973
112.84490.07340.07283.91790.14252.75330.02160.3328-0.3158-0.4665-0.0254-0.13570.22290.113-0.03480.23850.09190.03290.30350.04420.280833.6113-46.101521.5105
122.0595-0.4770.52612.71190.91642.93940.10460.15510.1818-0.0868-0.0956-0.1014-0.08750.0280.09220.16380.07780.00970.17050.0360.222628.709-37.042725.0021
137.93840.3514-2.70960.2452-0.53691.64060.19861.19420.10430.0064-0.22670.1030.6255-0.29690.01570.63430.2539-0.02050.6321-0.09860.324324.2249-46.27676.5782
143.51311.19670.3464.31340.16192.88150.06490.40840.0646-1.0673-0.13010.03970.0468-0.2112-0.09690.43930.1512-0.01960.45470.0790.277123.4066-33.805110.5756
151.70810.05761.24435.2645-0.14321.4737-0.0432-0.13490.4119-0.00340.0532-0.26240.10560.06220.10230.2170.0594-0.00160.32590.02410.323429.3383-23.104528.1363
161.76211.35140.04865.6876-0.00991.09410.11160.15680.0186-0.1685-0.14020.1122-0.00490.0230.02960.2170.0873-0.00640.26510.00260.218820.3208-29.255119.6931
176.6992-1.91260.66054.7553-3.46492.71190.2860.2043-0.5299-0.0764-0.23530.13640.25950.3652-0.07850.29940.08090.07590.34630.03590.244825.7635-47.886634.554
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 311 through 321 )
2X-RAY DIFFRACTION2chain 'A' and (resid 322 through 341 )
3X-RAY DIFFRACTION3chain 'A' and (resid 342 through 371 )
4X-RAY DIFFRACTION4chain 'A' and (resid 372 through 395 )
5X-RAY DIFFRACTION5chain 'A' and (resid 396 through 420 )
6X-RAY DIFFRACTION6chain 'A' and (resid 421 through 438 )
7X-RAY DIFFRACTION7chain 'A' and (resid 439 through 465 )
8X-RAY DIFFRACTION8chain 'A' and (resid 466 through 496 )
9X-RAY DIFFRACTION9chain 'A' and (resid 497 through 548 )
10X-RAY DIFFRACTION10chain 'B' and (resid 306 through 321 )
11X-RAY DIFFRACTION11chain 'B' and (resid 322 through 363 )
12X-RAY DIFFRACTION12chain 'B' and (resid 364 through 407 )
13X-RAY DIFFRACTION13chain 'B' and (resid 408 through 420 )
14X-RAY DIFFRACTION14chain 'B' and (resid 421 through 438 )
15X-RAY DIFFRACTION15chain 'B' and (resid 439 through 496 )
16X-RAY DIFFRACTION16chain 'B' and (resid 497 through 528 )
17X-RAY DIFFRACTION17chain 'B' and (resid 529 through 547 )

+
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://pdbjlvh1.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